Romanian Journal of Ophthalmology · Avram Elena 95 Insights in the treatment of congenital...

Romanian Journal of Ophthalmology

EDITOR-IN-CHIEF Mihail Zemba, M.D., Ph.D. Bucharest, Romania

E-mail: [email protected]

ASSOCIATE EDITOR Ovidiu Musat, M.D., Ph.D. Bucharest, Romania


EXECUTIVE EDITOR Prof. Victor Lorin Purcarea, Ph.D. Bucharest, Romania


ASSISTANT EDITORS Horia Stanca, M.D., Ph.D. Bucharest, Romania

E-mail: [email protected] Daniel Branisteanu, M.D., Ph.D. Iasi, Romania


INTERNATIONAL EDITORIAL ADVISORY BOARD Prof. Khaled al Rakhawy, M.D., Ph.D. Cairo, Egipt Daniel Baron M.D., Ph.D. Nantes, France Prof. Zsolt Biro M.D., Ph.D. Pecs, Hungary Prof. Derald Brackmann M.D., Ph.D. Los Angeles, USA Thierry Chazalon M.D., Ph.D. Nantes, France Prof. Gabriel Coscas M.D., Ph.D. Paris, France Prof. J.J. De Laey M.D., Ph.D. Gent, Belgium Prof. Fabian Hoehn M.D., Ph.D. Pforzheim, Germany

Prof. Christian Paul Jonescu-Cuypers M.D., Ph.D. Berlin, Germany Prof. Slobodanka Latinovic M.D., Ph.D. Novi Sad, Serbia Prof. Dan Milea M.D., Ph.D. Angers, France Gabor Rado M.D., Ph.D. Budapest, Hungary Prof.Gabor Scharioth M.D., Ph.D. Recklinghausen, Germany Prof. Wolfgang Schrader M.D., Ph.D. Wuerzburg, Germany Prof. Fankhauser Franz M.D., Ph.D. Bern, Switzerland

NATIONAL EDITORIAL ADVISORY BOARD Assoc.Prof. Florian Balta, M.D., Ph.D. Bucharest, Romania Prof. Dorin Chiselita M.D., Ph.D. Iasi, Romania Assoc. Prof. Mircea Filip M.D., Ph.D. Bucharest, Romania Prof. Mihnea Munteanu M.D., Ph.D. Timisoara, Romania Daniela Selaru M.D., Ph.D. Bucharest, Romania

Assoc.Prof. Cristina Stan M.D., Ph.D. Cluj Napoca, Romania Prof. Adriana Stanila M.D., Ph.D. Sibiu, Romania Cornel Stefan M.D., Ph.D. Bucharest, Romania Calin Tataru M.D.,Ph.D. Bucharest, Romania Prof.Dr. Cristina Vladutiu M.D., Ph.D. Cluj Napoca, Romania

NATIONAL EDITORIAL BOARD Gheorghe Anghel M.D., Ph.D. Bucharest, Romania Eugen Bendelic M.D., Ph.D. Chisinau, Republic of Moldova Camelia Bogdanici M.D., Ph.D. Iasi, Romania Daniel Branisteanu M.D., Ph.D. Iasi, Romania Marian Burcea M.D., Ph.D. Bucharest, Romania Catalina Corbu M.D., Ph.D. Bucharest, Romania Mihaela Coroi M.D., Ph.D. Oradea, Romania Valeria Coviltir M.D., Ph.D. Bucharest, Romania Valeriu Cusnir M.D., Ph.D. Chisinau, Republic of Moldova Danut Costin M.D., Ph.D. Iasi, Romania Monica Gavris M.D., Ph.D. Cluj Napoca, Romania Karin Horvath M.D., Ph.D. Tg. Mures, Romania Sanda Jurja M.D., Ph.D. Constanta, Romania

Carmen Mocanu M.D., Ph.D. Craiova, Romania Cristina Nicula M.D., Ph.D. Cluj Napoca, Romania Monica Pop M.D., Ph.D. Bucharest, Romania Mihai Pop M.D., Ph.D. Bucharest, Romania Alina Popa-Cherecheanu M.D., Ph.D. Bucharest, Romania Vasile Potop M.D., Ph.D. Bucharest, Romania Speranta Schmitzer M.D., Ph.D. Bucharest, Romania Horia Stanca M.D., Ph.D. Bucharest, Romania Ioan Stefaniu M.D., Ph.D. Bucharest, Romania Simona Talu M.D., Ph.D. Cluj Napoca, Romania Liliana Voinea M.D., Ph.D. Bucharest, Romania Mihail Zemba, M.D., Ph.D. Bucharest, Romania

PUBLISHING EDITORS Consuela Madalina Gheorghe, Bucharest, Romania Dodu Petrescu, Bucharest, Romania Petrut Radu, Bucharest, Romania

EDITORIAL OFFICE "Dr. Carol Davila"Central Military University Emergency Hospital 134 Calea Plevnei Street, District 1, Bucharest, Romania Phone number/Fax: +40.21.3137189 E-mail:[email protected], Typesetting and cover graphic: P. Radu

Volume 61, Issue 2 April-June 2017

© All the rights on the journal belong to the Romanian Society of Ophthalmology. The partial reproduction of the articles or of the figures is possible only with the written consent of the Romanian Society of Ophthalmology. The responsibility of the articles’ originality belongs entirely to the authors.

Print ISSN 2457 – 4325 ISSN-L 2457 - 4325

Online ISSN 2501-2533 ISSN–L 2457-4325

Printed at ''Carol Davila'' University Press, 8 Eroilor Sanitari Blvd., 050474 Bucharest, Romania

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Romanian Journal of Ophthalmology Volume 61, Issue 2, April-June 2017

Contents

Editorial

Opinions regarding refractive surgery today in Romania Mircea Filip

81

Reviews Ocular posterior pole pathological modifications related to complicated pregnancy. A review Păun Vanessa Andrada, Ionescu Zamfir-Radu, Voinea Liliana, Cîrstoiu Monica, Baroș Alexandru, Pricopie Ștefan, Ciuluvică Radu

83

Pseudophakic bullous keratopathy Pricopie Stefan, Istrate Sanziana, Voinea Liliana, Leasu Costin, Paun Vanessa, Radu Ciuluvica

90

CAN Optical Coherence Tomography redefine amblyopia? Avram Elena

95

Insights in the treatment of congenital nasolacrimal duct obstruction Avram Elena

101

General articles

IRIDEX MicroPulse P3: innovative cyclophotocoagulation Gavris M. Monica, Olteanu Ioana, Kantor Erzsebet, Mateescu Radu, Belicioiu Roxana

107

Eyesight quality and Computer Vision Syndrome Bogdănici Camelia Margareta, Săndulache Diana Elena, Nechita Corina Andreea

112

Plateau Iris – Therapeutic options and functional results after treatment Feraru Crenguța, Bâlha Andrei, Aursulesei Victor, Filip Andrei, Pantalon Anca

117

Case reports

The effect of intravitreal bevacizumab in a rare case of retinal dystrophy with secondary cystoid macular edema Macovei Mioara-Laura, Nica Maria-Alexandra

123

Penetrating keratoplasty: from aid dependence to independence Macovei Mioara-Laura, Nica Maria-Alexandra

128

Orbital cellulitis and brain abscess – rare complications of maxillo-spheno-ethmoidal rhinosinusitis Constantin Farah, Niculescu Patricia-Alexandra, Petre Oana, Balasa Daniel, Tunas Alexandru, Rusu Ioana, Lupascu Mihai, Orodel Cristiana

133

Rare case of ocular tuberculosis in a diabetic patient: diagnostic and therapeutic dilemmas Pantalon Anca, Găman Emanuela, Crețu-Silivestru Iustina-Silvia, Danielescu Ciprian

137

Unilateral Eales’ disease a case report Nicolcescu Andreea, Mocanu Carmen, Dinu Loredana, Olaru Andrei, Ionete Mara, Stefanescu Dima Alin

144

Romanian Journal of Ophthalmology, Volume 61, Issue 2, April-June 2017. pp:81-82

EDITORIAL

81 Romanian Society of Ophthalmology

© 2017 doi:10.22336/rjo.2017.15

Opinions regarding refractive surgery today in Romania

Eyeglasses are medical devices whose purpose is to improve the sight deficiency of the eyes with

diopters. The reaction of the patients who find out that they have this need, at their first medical consultation, can be different: some of them accept it straightforward, some are more or less upset, and others cannot conceive this option. The patients from the last category look for a way to get out of this so-called “nightmare” because, for most of them, life without glasses is a strong desire.

The options are different, starting with not wearing glasses, the result being an unsatisfying compromise, which can have long-term consequences, starting from amblyopia to the impossibility/ difficulty of performing a specified task/ job (e.g. driving). Other options are contact lenses and refractive surgery by laser or other techniques.

Refractive surgery implies specific conditions that need to be evaluated by the doctor. Myopia (most frequently), hyperopia, and astigmatism can be treated through this type of surgery.

Generally, the current laser techniques used are PRK, Lasek, Lasik, SMILE. The most frequently used technique worldwide is Lasik, and, in Romania, both Lasik and PRK. ICL (lens implant in front of the crystalline lens) can be used in patients with high myopia or

hyperopia. Patients who require refractive surgery most often have myopia. Regarding the conditions they

have to accomplish, the diopters must be stable for at least one year before surgery and the patients must be at least 21 years old at the time of the surgery. As far as the age at the time of the surgery is concerned, people want to be perfect between the ages of 20 and 40 and, of course, this is the age group with the highest addressability.

Considering the indications, myopia up to 6 diopters, astigmatism up to 3 diopters and hyperopia up to 1.5 diopters can be corrected with PRK technique.

The interval can be extended up to 8 diopters for myopia, to 4.5 diopters for hyperopia and to 4 diopters for astigmatism with Lasik.

SMILE addresses only myopia, with or without astigmatism, and this technique extends the interval up to 10 diopters and even 15 diopters if astigmatism is added. The maximum age recommended for this procedure is 40-45 years.

Regardless the technique used for myopia correction, the patient must be advised about the problems he will encounter at the age of presbyopia.

Another goal that ophthalmologists are aiming is that of not wearing glasses either in presbyopia, meaning after the age of 40, nor in high hyperopia, in the onset of accommodative asthenopia. In this case, multifocal IOL implants are the most frequently used solution. The main question that arises is regarding the age. In a study that used well-known Romanian and foreign surgeons, the recommended age for this type of surgery was between 35 and 60 years. Personally, I choose the lower limit of this interval. What can we offer to a young patient aged 27 or 30, with a myopia or hyperopia impossible to treat with laser surgery, who desperately wants not to wear glasses? I believe that these patients can get surgery, too, after a thorough examination and information.

Multifocal IOL implants are used by surgeons in Romania, as well as in other countries, but, in general, in a small percentage of cases.

The results of this procedure are mainly very good. It takes a careful preoperative examination, as well as a discussion with the patient to

understand his needs, but also to disqualify from surgery those patients with unrealistic expectations

Romanian Journal of Ophthalmology 2017; 61(2): 81-82


© 2017

or jobs not suitable for this technique (e.g. nighttime drivers). Usually, a discussion about implanting multifocal IOLs is started after a normal aspect of the

macula is seen on tomography. The surgical technique has to be very good. What should be mentioned is that the surgeon who

uses this type of implants must have access to excimer laser, possibly femtosecond laser to correct a postoperative refractive error, a correction that is usually recommended 6 months after the surgery. What should also be mentioned is that Nd:YAG laser can be used even at 1 month after the surgery.

These procedures are expensive and generally not supported by the insurance companies anywhere in the world.

In my opinion, these multifocal IOLs offer very good results, but they can always be improved and all the producers constantly try to improve the quality of t

Mircea FILIP Amaoptimex, Bucharest


REVIEW

83

Romanian Society of Ophthalmology © 2017

doi:10.22336/rjo.2017.16

Ocular posterior pole pathological modifications related to complicated pregnancy. A review

Păun Vanessa Andrada*, Ionescu Zamfir-Radu**, Voinea Liliana* ***, Cîrstoiu Monica****, Baroș Alexandru*****, Pricopie Ștefan******, Ciuluvică Radu*******

*Ophthalmology Clinic, University Emergency Hospital, Bucharest, Romania **Department of Pathology, Pediatric Hospital, Pitești, Romania; Genetics Department, Faculty of Sciences, State University Pitești, Romania ***Ophthalmology Department, “Carol Davila” University of Medicine and Pharmacy; University Emergency Hospital, Bucharest, Romania ****Clinic of Obstetrics and Gynecology, University Emergency Hospital, Bucharest; “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania *****Ist Clinic of General Surgery, University Emergency Hospital, Bucharest; “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania ******Ophthalmology Clinic, University Emergency Hospital, Bucharest, Romania *******“Carol Davila” Dental Medicine University, Bucharest, Romania Correspondence to: Păun Vanessa Andrada, MD, Ophthalmology Clinic, University Emergency Hospital, Bucharest, 169 Splaiul Independenței Street, Code 050098, District 5, Bucharest, România, Phone: +4021 318 0522, E-mail: [email protected] Accepted: May 29th, 2017

Abstract Ocular posterior pole modification are a pathological manifestation in complicated pregnancies, especially when pregnancy induced hypertension is present (PIH), as well as in preeclampsia (PE) or eclampsia. Nonetheless, as the pregnancy evolves, the possibility for an aggravated evolution with HELLP syndrome, disseminated intravascular coagulation, and idiopathic thrombocytopenic purpura may have an ocular manifestation that, mainly, implies a loss of visual field or acuity, that, left unattended, may constitute a permanent impairment. Pregestational conditions like pituitary adenoma or genetic pedigree for complement factor H gene (1q31.1) single nucleotide mutations could lead to central serous chorioretinopathy or retinal detachment with severe, ischemic, central cilioretinal artery or vein occlusion and optic nerve atrophy. Furthermore, although subtle in many cases, any new visual symptoms during pregnancy should constitute an alarming factor for obstetrical reevaluation and ophthalmological approach in order to preserve the mother’s quality of life. Keywords: retina, pregnancy, preeclampsia, eclampsia, hypertension, anti-phospholipid syndrome, central serous chorioretinopathy, Sheehan’s syndrome

Introduction

Pregnancy is known to cause physiological changes in the parturient. These physiological changes may affect different organs and systems,

including the eyes and visual perception. As it is known in modern literature, these changes include physiologic and pathologic modifications, the latter being already significantly influenced by any preexisting condition that may remain undiagnosed prior to



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the ophthalmological consultation. Thus, regarding the above affirmations, we may subdivide the pathological changes into three categories, related to the time of onset: first time ocular pathology during pregnancy, modification of preexisting known or diagnosed ocular pathology and ocular complications of systemic diseases [1]. Certain diseases like Sheenan syndrome, eclampsia and preeclampsia are specific to pregnancy while other diseases like Graves disease, disseminated intravascular coagulation and intracranial hypertension are more likely to have an increased incidence or risk for complications during pregnancy. Furthermore, these diseases require pregestational silent morphological anomalies that undergo significant changes during pregnancy or labor, and may have a significant clinical presentation [2,3].

Preeclampsia

As it is already accepted, preeclampsia (PE) is defined as the presence of a systolic blood pressure, greater than 140 mmHg (SBP ≥ 140 mmHg) or a diastolic blood pressure greater than or equal to 90 mmHg (DBP ≥ 90 mmHg), values measured, in a previous normotensive female patient, on two different consultations that have to be at least 4 hours apart one from the other. In the case of an emergency diagnosis requirement, the SBP must be higher than 160 mmHg (SBP ≥ 160 mmHg) and a diastolic pressure as high as 110 mmHg (DBP ≥ 110 mmHg), occasion that allows immediate antihypertensive therapy [4]. Furthermore, impaired hepatic function, noticeable due to elevated liver enzymes concentrations and severe, pharmacologically nonresponsive, epigastric or upper abdominal pain, may become an immediate diagnostic clue. Progressive renal insufficiency, with initial proteinuria greater than 0.3 grams in a 24-hours duration urine specimen, new onset of any neurological disturbances, pulmonary oedema, and thrombocytopenia may help distinguish a general, systemic, multiple organic impairment [5].

Retinal dysfunction in preeclampsia female patients seems to be the most serious ocular complication, thus, implying fundoscopic examination, because retinal vascular changes are the immediate result of hypertension status, being, also, a mirror for any vascular changes. Therefore, the ophthalmoscopic examination for ocular fundus may become an important

screening consultation for different placental anomalies. The most common abnormality identified in the retina of PE patients is represented by arterioles narrowing, that may have visual symptoms when the spasm involved become focal or generalized, accompanied by exudates, hemorrhages, peripapillary or focal retinal edema, serous retinal detachment or, even acute ischemic optic neuropathy with transient visual blindness. Sometimes, complications may evaluate even further to retinal pigment epithelial lesions, severe macula edema with retinal detachment – this step being an emergency as it emerges to permanent blindness, central to retinal artery occlusion and rapid optic atrophy [6]. These pathological eventualities may express in 25% of the PE patients and 50% of the eclampsia patients with blurred vision, photopsia, scotomas, diplopia, amaurosis, and dyschromatopsia [7]. Cortical blindness associated with PE and pregnancy induced hypertension (PIH) is a documented entity, frequently encountered in a severely decreased visual acuity patient with normal pupillary light response, thus, consisting a differential diagnosis against cortical blindness or a functional symptom. In such situations, brain MRI examination with occipital lobe attenuation becomes confirmatory for the diagnosis. The required treatment implies fast blood pressure control, being the most successful pharmacological factor, as heparin and corticosteroids seem not to be significantly favorable [8]. The exudative retinal detachments are rarely seen in PIH or PE patients. The retinal pigmentary epithelium lesions, or Elscching spots, may sometimes be seen in a PE patient with prior choroidal infarcts and visual impairing. Macular edema or papilledema with retinal detachment requires pregnancy termination in order to save the mother’s vision: in this medical issue, ophthalmological surgery being futile [9]. Serous retinal detachments are encountered in severe cases of PE, being unconditionally related to a higher degree of choroidal perfusion impairment resulting in a subretinal leakage, sometimes, constituting in serous exudative retinal detachments visible as bullous, bilateral in the mandatory context of a PIH [6,10]. Although there are no explicit guidelines for the surgical procedures, fundus grade II and III changes (Table 1), i.e. hemorrhages and exudates, should be carefully assessed in order to terminate pregnancy trough cesarean section, with a maximum delay of 3 to 4


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weeks in favor of fetus maturity. Furthermore, retinal hemorrhage, transudate, papilledema in the context of PIH, retinal detachment should be a sufficient indication for the immediate gestation termination regardless of any delay possibility or fetal age [10]. Severe retinopathy changes are correlated with a compromised maternal-fetal circulation. It seems that the

progression of retinal vascular changes becomes a sign of increasing severity of PIH, thus, implying a higher mortality rate. Some studies suggested that PIH and fundus changes, in particular, are associated with low birth weight (p < 0.05), a lower 1 min Apgar score (less than 5 points) and in extreme situations, with stillbirth [11].

Table 1. Keith-Wanger-Barker (1939) Classification of hypertensive retinopathy [27].

Grade Classification;

Grade I Generalized retinal arteriolar narrowing or sclerosis;

Grade II Focal arterial narrowing; arteriovenous crossings; Moderate – Severe arterial sclerosis; Arterial light reflex – exaggerated;

Grade III Abnormalities seen in grades I and II; Retinal hemorrhages; Representative exudation; Cotton-wool spots.

Grade IV Abnormalities seen in grades I-II-III; Optic nerve and macular star swelling

Central serous chorioretinopathy

Central serous chorioretinopathy (CSR) can occur during the first and third trimester. The symptomatology consists in metamorphopsia, visual loss, scotomas, and light sensitivity. The CSR disease is represented by the serous detachment of the neurosensory retina, due to the choriocapillaris leakage at the retinal pigment epithelium occasioned by choroidal neovascularization. Although many mechanisms have been proposed for the CSR etiology, it seems that inflammation is not a key factor, since glucocorticoids rather aggravate than improve CSR. Strong evidence for a genetic contribution to the CSR pathogenesis has been documented in families of CSR patients, although no specific genotype or hereditary pattern has ever been associated with CSR. Genetic studies on single nucleotide mutations have been performed on different cohorts suffering from CSR. It seems that the complement factor H gene, located on the long arm of the first autosomal chromosome (1q31.3 – OMIM *134370, Fig. 1,2), involved in the macular age related degeneration (OMIM #610698) and in the complement factor H deficiency (OMIM #609814), is the most appropriate candidate for genetic inheritance as the encoded protein, i.e.

regulatory protein for complement activation of C3 fraction of complement, binds to adrenomedullin, a peptide that belongs to the calcitonin family, eliciting vasodilator effects on the choroid [12,13]. During pregnancy, CSR patients are more likely to have explicit hereditary history for this disease, either gestational related or spontaneous and is easily detected due to optical coherence tomography (OCT) as an elective diagnostic measure. Most of the examiners would identify a subretinal fluid with yellowish to white fibrinoid exudates in the macular area that might extend to papillomacular areas. In most cases, CSR is reversible in the postpartum period, in weeks to months duration [12]. The other proposed mechanisms for CSR association with gestation, include hemodynamic and hormonal alterations, changes in osmotic pressure with a decreased colloid counterpart and hypercoagulability. It is well known that plasma cortisol concentrations are elevated during pregnancy, having their highest levels during the third trimester, when CSR is most likely to occur. The differential diagnosis should include non-arteritic anterior ischemic optic neuropathy, posterior scleritis, and acute retinal necrosis due to the reactivation of



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Herpes simplex virus and herpes zoster that has been reported during pregnancy [14].

Fig. 1 Gene locus of complement H factor 1 on autosomal 1st chromosome (modified chart, from EMBL-EBI e! Chromosome)

Fig. 2 Genomic details of complement H factor gene (1q31.1) associated with familial autosomal dominant and recessive CSR (modified, from EMBL-EBI e! Chromosome).


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Vein and Artery Occlusion in the Retina of Pregnant females

Pregnancy is a circumstantial factor for the existence of hypercoagulability with visible modifications of platelets, clotting factors along with blood flow hemodynamics. The occlusion of the cilioretinal artery (CRA) is a possible condition encountered in females during gestation, with documented hypercoagulability. The incidence of arterial occlusion first depends on anatomical variations, most of the abnormal arteries arising from the temporal margin of the optic disc, while some of these anomalies may have a nasal aspect origin. Furthermore, the CRA occlusion depends on different quantifiable factors like: coagulation, biochemistry, sedimentation rate, C reactive protein, angiotensin converting enzyme, arterial pressure, homocysteine levels, rheumatoid factor, antinuclear, anticardiolipin, anti-neutrophil cytoplasmic antibodies, together with a positive serology for Rickettsia typhi, Epstein-Barr, varicella virus and cytomegalovirus. The real incidence of CRA obstruction is unknown, probably due to incidence frequency, being most likely during antiphospholipid syndrome when it occurs bilaterally [15]. The central retinal vein occlusion (CRV) is less common than CRA occlusion, the condition being mostly associated with PIH, preexisting arteriosclerosis and diabetes. A percent of 51% CRV obstruction female patients were smokers, compared to 40% of those who were diagnosed with CRA occlusion. Furthermore, there is an increase in the cerebrovascular disease and stroke risk, along with a myocardial infarction incidence. It seems that regular exercise and, paradoxically, alcohol intake are a protective factor against CRV occlusion [16].

The clinical symptomatology of CRA occlusion may present as a central, homogenous, visual loss that sometimes may occur in the peripheral field, thus, remaining unnoticed, while CRV occlusion may present as a painless monocular vision loss, with a severe prognosis, worse than CRA involvement. Angiography and OCT are essential tools used for the diagnosis in case of retinal vascular obstruction, thus, providing useful data based on measurements of retinal circulation. Indocyanine green angiography is elective in assessing choroidal hemodynamics abnormalities together with

hyperviscosity, with a subtle detection of neovascularization that could lead to leakage. The quality of OCT has been improved significantly in the last decade, providing larger resolutions that assure the detection of subretinal fluid as a complication of CRA obstruction. Nevertheless, in the case of a retinal atrophy, OCT helps identify subtle morphological variation in photoreceptors, as a predictive criterion for irreversible visual loss [17]. HELLP syndrome

The HELLP syndrome occurs in 0.1-0.8% of all pregnancies in female patients who suffered from no prior hypertension or proteinuria. The majority of gestations diagnosed with HELLP syndrome developed ascites after cesarean sections with a sudden decrease for platelets count. Furthermore, during post-partum immediate period, preexistent congestive heart failure might aggravate with a six-fold increase for adult respiratory distress syndrome [18]. In this context, retinal detachment is an unusual, but detectable phenomenon that occurs in 0.9% of the PIH patients complicated with the HELLP syndrome, being more common in these pathological situations than in preeclampsia and eclampsia alone. Retinal detachment is most likely to be observed during the last trimester of pregnancy, with unilateral serous subretinal fluid accumulation as a consequence of choroidal vascular damage, due to arteriolar vasospasm that would affect the retinal pigment epithelium and subsequent blood retinal barrier impairment, that would latter absorb during the first weeks in the post-partum period. As these situations are considered emergencies, a firm decision of cesarean section with delivery along with a timely ophthalmologic approach would provide the optimal prognosis for any possible visual sequelae [19].

Amniotic fluid embolism

Although rare, it might become a serious condition with fatal complications during gestation, with a high mortality above 80% accompanied by a noisy clinical tableau that includes shock and convulsions. In this situation, the occipital cortex, visual pathways and optic nerve may become involved with CRA obstruction [20].



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Thrombotic thrombocytopenic purpura (Moschowitz’s disease or TTP)

Ocular changes are observed in 10% of the rare female patients with TTP, including fundus alterations that include retinal artery narrowing, hemorrhage, serous retinal detachment, and exudates. The most often met visual complaint includes scintillating scotomas, extraocular muscle paresis, and homonymous hemianopia. The ophthalmologist or gynecologist may observe anisocoria and subconjunctival hemorrhage [21]. Pituitary apoplexy (Sheehan syndrome)

Pituitary apoplexy is a pituitary gland enlargement due to the infarction and hemorrhage that occurred in local adenomas that become increasingly frequent in pregnancies, especially as a result of an uncontrolled postpartum hemorrhage. Symptomatology includes sudden headache, complete or as a bitemporal superior quadrant partial vision loss with accompanying ophthalmoplegia, due to cavernous sinus compression and subsequent involvement of the third, fourth and, rarely, the sixth cranial nerves. Therefore, the clinical presentation may evolve to mydriasis anisocoria and diplopia, sometimes, with a full Horner syndrome as a result of sympathetic fibers damage [22]. Disseminated intravascular coagulation

A frequently observed pathology in a wide range of obstetric complications during pregnancy, occasioned especially by pregnancy toxemia, illegal abortions, or placenta abruption is disseminated intravascular coagulation (DIC). The complication develops as a result of another aggravated, generalized, condition such as sepsis, hemolytic disorder, arterial abnormalities with coaguli formation – hemangioma, prosthetic grafts, autoimmunity – neoplasms, massive trauma. DIC occurs most likely, during gestation, in the context of intrauterine fetal demise, incomplete or septic abortions, PIH or eclampsia [23,24]. The pathogenesis of DIC relays on tissue factor-mediated initiation of coagulation activation insufficiently balanced by intrinsic physiologic anticoagulant pathways by impaired endogenous fibrinolysis. Furthermore, it seems that microangiopathic hemolytic anemia and vascular endothelial damage via platelet

adhesion and activation would facilitate diffuse, generalized, fibrin formation that could facilitate the onset of HELLP syndrome [25]. The choroid would be the mostly affected ocular structure in such a situation, increased coagula formation due to continuous platelet consumption and various coagulation factors activation with subsequent fibrinolysis would result in a deranged hemostasis followed by bleeding and widespread ischemia in all organs, thus, resulting in the thrombotic occlusion of CRA and posterior ciliary arteries. Ocular findings would show both eyes with external normal appearance, with delayed filling of the posterior choroid in fluorescein angiography [26].

Conclusions

Posterior pole modifications and retinal pathologies that arise during a complicated gestation may pose a serious threat to the mother’s visual acuity along with an impaired quality of life. Furthermore, a vascular caliber reduction in hypertensive disorders, either preexistent or de novo may become a sufficient evidence for maternal-fetal distressed circulation. Ocular symptomatology during pregnancy should not be disconsidered by medical professionals, thus, becoming a clue for an alarming situation that implies both the ophthalmologists and the gynecologists. Acknowledgements

The authors would like to thank the Ophthalmology Department and the Obstetrics and Gynecology Department and their wonderful medical staff both from “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania and from the University Emergency Hospital, Bucharest, Romania. Conflict of interests

The authors declare no conflict of interest.

References 1. Pilas-Pomykalska M, Czajkowskii J, Oszukowski P.

Ocular changes during pregnancy. Ginekol Pol. 2005 Aug; 76(8):655–60.

2. Abu Samra K. The eye and visual system in the preeclampsia/ eclampsia syndrome: What to expect?.


89


Saudi J Ophthalmol. 2013; 27(1):51–3. 3. Abbouda A, Trimboli P, Bruscolini A. A mild Grave’s

ophthalmopathy during pregnancy. Semin Ophthalmol. 2014 Jan; 29(1):8–10.

4. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet. Gynecol. 2013 Nov; 122(5):1122–31.

5. Namavar Jahromi B, Rafiee S. Coagulation Factors in Severe Preeclampsia. Iran Red Crescent Med J. 2009; 11(3 SP 321-324).

6. Reddy SC, Nalliah S, George SR, Kovil AP, Who TS. Fundus changes in pregnancy induced hypertension. Int J Ophthalmol. 2012 Dec 18; 5(6):694–7.

7. Park AJ, Haque T, Danesh-Meyer HV. Visual loss in pregnancy. Surv Ophthalmol. 2000; 45(3):223–30.

8. Trommer BL, Homer D, Mikhael MA. Cerebral vasospasm and eclampsia. Stroke. 1988 Mar; 19(3):326–9.

9. Saito Y, Tano Y. Retinal pigment epithelial lesions associated with choroidal ischemia in preeclampsia. Retina. 1998; 18(2):103–8.

10. Bakhda RN. Clinical study of fundus findings in pregnancy induced hypertension. J Fam Med Prim Care. 2016; 5(2):424–9.

11. Ravi R, Sinha S, Shikha S. Fundus Changes and Fetal Outcomes in Pregnancy Induced Hypertension: An Observational Study. Int J Sci fi c Study. 2014; 2(7):6–9.

12. Sunness JS, Haller JA, Fine SL. Central serous chorioretinopathy and pregnancy. Arch Ophthalmol (Chicago, III 1960). 1993 Mar; 111(3):360–4.

13. Daruich A, Matet A, Dirani A, Bousquet E, Zhao M, Farman N et al. Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis. Prog Retin Eye Res. 2015 Sep; 48:82–118.

14. Choudhary T, Chawla S, Ray R, Pereira S. Hypercortisolism induced atypical central serous chorioretinopathy in pregnancy. Med J Armed Forces India. 2015 Jul; 71, Supple:S55–9.

15. Vila-Arteaga J, Suriano MM, Martínez-Lajara A. Obstrucción de la arteria ciliorretiniana durante el embarazo. Arch Soc Esp Oftalmol.

16. Williamson T. Central retinal vein occlusion. Br J Ophthalmol. 1997; 81(8):698–704.

17. Rajagopal R, Apte RS. Seeing through thick and through thin: Retinal manifestations of thrombophilic and hyperviscosity syndromes. Surv Ophthalmol. 2016 Mar; 61(2):236–47.

18. El-Agwany AS, Abdelsadek AA. A rare case of normotensive {HELLP} syndrome complicated with massive ascites: Spontaneous resolution. Egypt J Anaesth. 2016; 32(1):155–8.

19. Pradeep AV, Rao S, Ramesh Kumar R. Partial HELLP syndrome with unilateral exudative retinal detachment treated conservatively. Saudi J Ophthalmol. 2014 Oct; 28(4):329–31.

20. Chang M, Herbert WN. Retinal arteriolar occlusions following amniotic fluid embolism. Ophthalmology. 1984 Dec; 91(12):1634–7.

21. Percival SP. Ocular findings in thrombotic thrombocytopenic purpura (Moschcowitz’s disease). Br J Ophthalmol. 1970 Feb; 54(2):73–8.

22. Muthukumar N, Rossette D, Soundaram M, Senthilbabu

S, Badrinarayanan T. Blindness following pituitary apoplexy: timing of surgery and neuro-ophthalmic outcome. J Clin Neurosci Off J Neurosurg Soc Australas. 2008 Aug; 15(8):873–9.

23. Gotovac M, Kastelan S, Lukenda A. Eye and pregnancy. Coll Antropol. 2013 Apr; 37 Suppl 1:189–93.

24. Samra KA. The eye and visual system in pregnancy, what to expect?. An in-depth review. Oman J Ophthalmol. 2013; 6(2):87–91.

25. Marti-Carvajal AJ, Comunian-Carrasco G, Pena-Marti GE. Hematological interventions for treating disseminated intravascular coagulation during pregnancy and postpartum. Cochrane database Syst Rev. 2011 Mar; (3):CD008577.

26. Hoines J, Buettner H. Ocular complications of disseminated intravascular coagulation (DIC) in abruptio placentae. Retina. 1989; 9(2):105–9.

27. Walsh JB. Hypertensive Retinopathy. Ophthalmology. 1982; 89(10):1127–31.


REVIEW

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doi:10.22336/rjo.2017.17

Pseudophakic bullous keratopathy

Pricopie Stefan*, Istrate Sanziana*, Voinea Liliana*, Leasu Costin*, Paun Vanessa*, Radu Ciuluvica**

*Ophthalmology Department, Bucharest Emergency University Hospital, Bucharest, Romania **Anatomy Department, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Correspondece to: Istrate Sanziana, MD, PhD, Ophthalmology Department, Bucharest Emergency University Hospital, Bucharest, 169 Splaiul Independentei Street, District 5, Bucharest, Romania, Mobile phone: +40726 535 515, E-mail: [email protected] Accepted: May 1st, 2017

Abstract Pseudophakic bullous keratopathy is characterized by corneal stromal edema with epithelial and subepithelial bullae due to cell loss and endothelial decompensation through trauma during cataract surgery. Patients present decreased vision, tearing, and pain caused by ruptured epithelial bullae. Cataract affects approximately 20 million people worldwide, and this complication can occur in 1 to 2% of the cataract surgeries. This study reviewed the bullous keratopathy etiopathogenesis and the clinical and surgical treatment available for this corneal disease. Keywords: corneal disease treatment, corneal surgery, bullous keratopathy, cataract extraction

Introduction

The cornea is a complex structure that is responsible for most of the refraction of the eye and, because of its highly exposed position, has a protective role, acting as a physical barrier to trauma and infection [1,2]. One of the most important property of the cornea is its transparency, which is a result of a number of factors: the absence of blood vessels, the regularity and smoothness of the covering epithelium, the regular arrangement of the extracellular and cellular components in the stroma, which is dependent on the state of hydration and metabolism of the stromal elements [2].

The cornea has one of the body’s highest density of nerve endings, with a subepithelial and a deeper stromal plexus, both supplied by the 1st division of the trigeminal nerve. This is the reason why disease processes like bullous

keratopathy are associated with pain, photophobia, and reflex lacrimation [1]. Corneal Pathophysiology

The average central thickness of the normal adult human cornea is approximately 550µm for Caucasians and it remains constant between the second and sixth decades, but varies with the time of day and race [3].

The cornea consists of five layers from anterior to posterior: epithelium, Bowman’s layer, stroma, Descemet’s membrane, and endothelium. The composition of the stroma is not uniform; the anterior stroma contains a higher ratio of dermatan sulfate to keratan sulfate, making the posterior stroma more likely to swell with excess water in states of endothelial dysfunction [4].

Immunohistochemical studies showed deposits of a specific extracellular matrix component, such as fibrilin-1 which belongs to


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the family of extracellular matrix proteins associated with elastic microfibrils and tenascin-C, which is a glycoprotein that has great importance in healing and is found in the posterior collagen layer or in the subepithelial fibrotic areas of corneas with bullous keratopathy [6].

Growth factors and cytokines influence cell proliferation, inflammation, scarring, and fibrosis. Elevated levels of interleukin-2 (IL-2), interleukin-8 (IL-8), growth factor insulin (IGF-1), transforming growth factor (TGF- β) and bone marrow factor - 4 (BMP-4) were found in corneas with bullous keratopathy. The interactions between growth factors and extracellular matrix degrading matrix metalloproteins are important and can be a mechanism for the loss of corneal transparency [6].

Corneal deturgescence is maintained by endothelial cell sodium/ potassium-activated adenosine triphosphatase) and by tight junctions between the endothelial cells that limit the ingress of fluid. By removing fluid from the stroma and limiting its entry, endothelial cells maintain the ordered arrangement of collagen and preserve the cornea’s transparency. In states of deficient endothelial cell density, a lack of tight junctions between the endothelial cells allows the increased entry of fluid into the stroma. The endothelial cells that remain may have a higher concentration of Na+, K+-ATPase as a compensatory mechanism to increase fluid removal [4].

The normal endothelial cell density is greater than 3500 cells/ 𝑚𝑚𝑚𝑚2 in children and gradually declines with age to approximately 2000 cells/ 𝑚𝑚𝑚𝑚2 in older people, with an average of 2400 cells/ 𝑚𝑚𝑚𝑚2 for adults [5]. After this, the average cell loss is about 0.6 percent per year with the development of edema when the cell density drops below 700 cells/ 𝑚𝑚𝑚𝑚2.

Etiopathogenesis

The main cause of bullous keratopathy is the loss of endothelial cells due to surgical trauma, especially in cataract surgery at sixth decade patients, with or without lens implantation [6,7].

The localized increase of temperature associated with the phacoemulsification probe

can lead to thermal damage to adjacent corneal tissue. Damage to the endothelium can be caused by high irrigation or aspiration rates that can result in turbulent flow with lens particles connected with it [10].

Also, the duration of phacoemulsification used during the surgery is very important because the ultrasound energy is associated with the production of free radicals, which are reactive species with one or more unpaired electrons in their outer orbits and can damage the corneal endothelium by oxidative stress [10].

Other etiologies include endothelial dystrophies such as Fuchs dystrophy, tumors of the anterior chamber such as myxoma, congenital abnormalities, like microcornea, acute and neovascular glaucoma, herpetic endotheliitis or surgeries that can lead to endothelial cell loss like trabeculectomy, intraocular lens scleral fixation, anterior chamber lens implants for aphakic correction and high ametropia, after argon laser, radial keratotomy [6].

Bullous keratopathy may occur in around 1 to 2% of the patients undergoing cataract surgery, which is about two to four million patients worldwide [6].

Treatment options

The clinical treatment for corneal edema should be based on topical hypertonic agents such as sodium chloride (5%), anti-inflammatory drugs, topical and/ or systemic antiglaucoma medications, because increased IOP can compromise endothelial cell function, corticosteroids, lubricants and sometimes, due to the pain experienced by the patients, therapeutic contact lenses to improve symptoms [10].

According to a study conducted in 2015, systemic L-cysteine facilitated corneal edema remission when administered in the postoperative period in patients after cataract surgery, thus advocating its concurrent use in patients developing bullous keratopathy.

An increased expression of several proinflammatory mediators at the protein level in the corneal epithelium was demonstrated in patients with pseudophakic corneal edema. These cytokines and MMP, which are a family of extracellular proteinases that degrade the extracellular matrix proteins, participate in the pathologic processes in the pseudophakic corneal edema and specifically contribute to the



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continuous degradation of Bowman’s layer and recurrent erosions of the corneal epithelium.

The MMPs have a pivotal role in a number of pathologic processes, including angiogenesis and wound healing, where matrix degradation takes place. MMP are activated by the “cysteine switch”. All modes of activation lead to a dissociation of Cys73 from the zinc atom with concomitant exposure of the active site.

Based on the presumption that high L-cysteine levels may act as regulatory substrate for MMPs, more studies should be conducted in order to establish the adjuvant role of systemic L-cysteine in pseudophakic bullous keratopathies [7].

The use of conjunctival flaps is effective but has been limited by its unacceptable cosmetic outcome [6].

Corneal transplantation is still the gold-

standard treatment for bullous keratopathy patients, as it provides symptomatic relief and visual rehabilitation [8]. Some limitations such as visual acuity recovery occur because of the high astigmatism and, although the cornea is the most commonly transplanted tissue in the body and corneal grafts high success rate, there is also the risk of rejection [6,9].

Penetrating keratoplasty refers to a full

thickness corneal transplant. In conventional posterior lamellar keratoplasty (LK) and the newer endothelial keratoplasty (EK) procedures, only the inner layers of the cornea are transplanted and there are multiple variants of this procedures that include deep lamellar EK, Descemet’s stripping (automated) EK (DSEK or DSAEK), Descemet’s membrane EK, and Descemet’s membrane automated EK [11].

The posterior lamellar keratoplasty technique requires surgical skill and hinders any necessary action in the anterior chamber, but it has the advantage of a lower risk of rejection and preservation of the receptor surface. It is a promising technique, but the endothelial cell loss is bigger than in penetrating keratoplasty [6].

In developing countries with a shortage of donor corneas and long waiting lists of patients awaiting corneal transplantation, patients need to be provided with relief of symptoms and, if possible, temporary improvement in vision [12].

Corneal collagen cross linking (CXL) with Riboflavin and ultraviolet A (UVA) radiations is a photochemical process that was introduced by Seiler and Spoerl at the University of Dresden for the treatment of corneal ectatic disorders such as keratoconus and post LASIK ectasias [13].

Corneal CXL is considered a new tool in the struggle for the temporary reduction in corneal edema in patients with bullous keratopathy. It has been found to improve corneal transparency, corneal thickness, and ocular pain after surgery [12].

The proposed mechanism of action is that riboflavin absorbs UVA light, which results in the production of free oxygen radicals. These highly reactive oxygen radicals then induce the cross-linking of corneal stromal collagen and strengthen the cornea [13].

Different studies showed that corneal CXL significantly improves corneal transparency, corneal thickness, and ocular pain one month postoperatively. This symptomatic relief probably resulted from CXL-induced stromal compaction and reduced bullae formation. However, it did not seem to have a long-lasting effect in decreasing pain and maintaining corneal transparency [12,14].

In 1999, Pires et al. successfully used amniotic membrane (AM) to control pain in patients with BK. They attributed their results to various protease inhibitors located in the stromal matrix of the AM, which are important for promoting epithelial healing and reducing stromal ulceration and inflammation [16].

AM facilitates re-epithelialization by providing a suitable substrate and a normal basement membrane, by promoting epithelial cell migration and adhesion. AM is also believed to produce several growth factors that support epithelial cells. When the amniotic membrane is applied to the cornea, keratocyte derived fibroblasts and myofibroblasts are known to migrate from the corneal stroma into the amniotic stroma. This contributes to the subepithelial fibrosis and also anchors the amnion epithelial sheet to the corneal surface [15].

Amniotic membrane transplant is effective in controlling pain in patients with pseudophakic bullous keratopathy and does not induce neovascularization, but is not the first treatment


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option because of the cost and needed time [6,15].

Anterior stromal puncture (ASP) is a

simple and popular interventional option in the management of pseudophakic bullous keratopathy with low cost and rare complications [6,15,17].

Immunohistochemical studies have demonstrated an increased expression of extracellular matrix proteins important for the adhesion of basal epithelial cells such as fibronectin, laminin, and type IV collagen at stromal puncture sites. The secretion of these basement membrane components would increase the epithelial adhesion in the underlying stroma, which is associated with subepithelial fibrosis, thus creating a barrier to liquid penetration into the subepithelial space and decreased subepithelial bubble formation [6,15].

Hsu et al. were able to clinically correlate an improvement in pain symptoms with varying degrees of subepithelial fibrosis and epithelial attachment [18].

Phototherapeutic keratectomy (PTK)

can improve pain by reducing corneal thickness and this would help the remaining endothelial cells maintain corneal hydration [6].

Several studies reported PTK to be elective in the management of patients with bullous keratopathy from a variety of etiologies; they reported that the bullae resolve and pain is abolished in a large proportion of patients treated with a superficial ablation [19,20].

The main sensory nerve plexus in the cornea, which is derived from the nasociliary branch of the ophthalmic division of the trigeminal nerve, is located in the stroma, in the immediately subepithelial region, with a lower density plexus deeper in the stroma [19]. The rationale for this treatment is the ablation of these nerve plexuses thereby reducing corneal sensation and, in addition, corneal scarring induces an increase of extracellular proteins such as laminin, fibronectin, type IV collagen and hemidesmosomes which promote a greater adhesion between the epithelium and stroma [6,19].

Deep PTK appears to be more successful in comparison with superficial PTK because of the

increased scarring associated may also result in an increased stability of the epithelium and a deep ablation has a superior effect on decreasing pain by the ablation of the neural plexus in the cornea [19].

The same reasoning as in PTK is used also for automated lamellar keratectomy but, in this case, a traditional microkeratome is used for the removal of the corneal tissue. It is a fast procedure, which can be an important factor for some elderly patients who present difficulties in undergoing longer surgeries while remaining in dorsal decubitus [6].

Conclusions

Although corneal transplantation is the treatment with the best results in improving pain and visual acuity, what has to be kept in mind is the research for alternative treatments for the patients with no visual potential or those who are waiting for an available cornea. For this group of patients, clinical therapy, use of therapeutic contact lens, systemic L-cysteine, anterior stromal puncture, conjunctival flaps, amniotic membrane transplantation, phototherapeutic keratectomy, and automated lamellar keratectomy can significantly improve the quality of life.

References

1. Kansky JJ, Bowling B. Clinical Ophthalmology - A systemic approach, Seventh edition, 2011, Elsevier Saunders, 168-172.

2. Forrester JV, Dick AD, McMenamin PG, Roberts F, Pearlman E. The Eye - Basic science in practice, Fourth edition, 2016, Elsevier, 15-22.

3. Jackson TL. Moorfields Manual of Ophthalmology, Second edition, 2014, JP Medical Publishers, 157-159.

4. Fernandez MM, Afshari NA. Endothelial Keratoplasty: From DLEK to DMEK. Middle East African Journal of Ophthalmology. 2010 Jan-Mar; 17(1):5–8. doi: 10.4103/0974-9233.61210.

5. American Academy of Ophthalmology. External disease and cornea. 2014-2015; 34.

6. Gonçalves Domingues E, Fields F, Paris F, Pereira Gomes JA, Costa de Farias C. Bullous keratopathy: etiopathogenesis and treatment. Arq. Bras. Oftalmol. Nov./Dec. 2008; 71(6) supl.0.

7. Iancu R, Voinea L, Ciuluvica R, Golu A, Dinu I, Leasu C, Pricopie S, Gradinaru S. The effect of systemic L-cysteine in myopic patients with corneal edema after cataract surgery. 2015.

https://dx.doi.org/10.4103%2F0974-9233.61210



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8. Siu GD, Young AL, Jhanji V. Alternatives to corneal transplantation for the management of bullous keratopathy. Current opinion in ophthalmology. Jul. 2014; 25(4):347-52.

9. Abud TB, Di Zazzo, Kheirkhah A, Dana R. Systemic Immunomodulatory Strategies in High-risk Corneal Transplantation. Journal of Ophthalmic & Visual Research. 2017 Jan-Mar; 12(1):81-92.

10. Feinbaum C. A new treatment modality with the Hyper CL soft contact lens. Ophthalmology Times Europe. May 2015.

11. Reinhart JW, Musch DC, Jacobs SD, Lee WB, Kaufman SC, Shtein RM. Deep Anterior Lamellar Keratoplasty as an Alternative to Penetrating Keratoplasty. American Academy of Ophthalmology. Jan. 2001; 118(1):209–218.

12. Ritu A, Manudhane A, Saran R, Goyal J, Gupta D. Role of Corneal Collagen Cross-Linking in Pseudophakic Bullous Keratopathy. American Academy of Ophthalmology Annual Meeting. November 2012, Chicago, Illinois.

13. Khan MS, Basit I, Ishaq M, Shakoor T, Yakub A, Intisar R. Corneal Collagen Cross Linking (CXL) in treatment of Pseudophakic Bullous Keratopathy. Pakistan Journal of Medical Sciences. 2016 Jul-Aug; 32(4):965–968.

14. Santhiago MR, Berti TB, Thomaz S, Netto MV. Collagen crosslinking with riboflavin and ultraviolet-A in eyes with pseudophakic bullous keratopathy. Journal of Cataract and Refractive Surgery. February 2010; 36(2):273-276.

15. dos Santos Paris F, Domingues Gonçalves E, Silveira de Queiroz Campos M, Hideo Sato E, Dua HS, Pereira Gomes JA. Amniotic membrane transplantation versus anterior stromal puncture in bullous keratopathy: a comparative study. Brazilian Journal of Ophthalmology. May 2010.

16. Pires RT, Tseng SC, Prabhasawat P et al. Amniotic membrane transplantation for symptomatic bullous keratopathy. Arch Ophthalmol. 1999; 117:1291–7.

17. Gomes JA, Haraguchi DK, Zambrano DU, Izquierdo Júnior L, Cunha MC, de Freitas D. Anterior stromal puncture in the treatment of bullous keratopathy: six-month follow-up. Cornea. 2001 Aug; 20(6):570-2.

18. Hsu JK, Rubinfeld RS, Barry P, Jester JV. Anterior stromal puncture. Immunohistochemical studies in human corneas. Archives of Ophthalmology. Aug. 1993; 111:1057–63.

19. Maini R, Sullivan L, Snibson GR, Taylor HR, Loughnan MS. A comparison of different depth ablations in the treatment of painful bullous keratopathy with phototherapeutic keratectomy. The British Journal of Ophthalmology. Aug. 2001; 85:912–915.

20. Thomann U, Meier-Gibbons F, Schipper I. Phototherapeutic keratectomy for bullous keratopathy. The British Journal of Ophthalmology. 1995; 79:335–8.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Haraguchi%20DK%5BAuthor%5D&cauthor=true&cauthor_uid=11473154

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zambrano%20DU%5BAuthor%5D&cauthor=true&cauthor_uid=11473154

https://www.ncbi.nlm.nih.gov/pubmed/?term=Izquierdo%20J%C3%BAnior%20L%5BAuthor%5D&cauthor=true&cauthor_uid=11473154

https://www.ncbi.nlm.nih.gov/pubmed/?term=Izquierdo%20J%C3%BAnior%20L%5BAuthor%5D&cauthor=true&cauthor_uid=11473154

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cunha%20MC%5BAuthor%5D&cauthor=true&cauthor_uid=11473154

https://www.ncbi.nlm.nih.gov/pubmed/?term=de%20Freitas%20D%5BAuthor%5D&cauthor=true&cauthor_uid=11473154


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Romanian Society of Ophthalmology © 2017 doi:10.22336/rjo.2017.18

CAN Optical Coherence Tomography redefine amblyopia?

Avram Elena Ophthalmology Department, Medlife Băneasa Hyperclinic, Bucharest, Romania Correspondence to: Elena Avram, MD, Ophthalmology Department, Medlife Băneasa Hyperclinic, Bucharest, 10 București-Ploiești Highway, Code 013693, Bucharest, Romania, Mobile phone: +40741 608 980, E-mail: [email protected] Accepted: May 29th, 2017

Abstract Introduction: For many years, amblyopia was regarded as a disorder of the visual system in which an organic cause could not be identified. Optical Coherence Tomography opens new horizons in understanding the etiopathology of amblyopia and seems to highlight morphologic anomalies in the retina of the amblyopic eye. Purpose: The objective of this paper is to analyze the macular thickness, optic nerve changes, and choroidal thickness found in patients diagnosed with amblyopia based on trials reported in the literature. Material and methods: This study analyzes 30 clinical trials regarding amblyopia evaluation with Optical Coherence Tomography. The research articles analyzed were published between 2006 - 2016 and were identified on PubMed database. Results: 19 research studies focused on macular and nerve optic changes, 7 on choroidal changes and 6 on retinal changes after occlusion. The results were discussed according to the type of amblyopia, alteration of macular thickness, optic nerve changes, ganglion cell layer changes, and alteration of choroidal thickness. Conclusions: The results are of great variability, and it seems that macula and choroid involvement is more frequently suggested compared with optic nerve involvement. Keywords: amblyopia, Optical Coherence Tomography, macular thickness, choroid thickness Abbreviations: OCT = Optical Coherence Tomography, RNFL = Retinal Nerve Fiber Layer, GCC = Ganglion Cell Complex, ACD = Anterior Chamber Depth, BCVA = Best Corrected Visual Acuity

Introduction

For many years, amblyopia has been considered a disorder of the visual system that represents unilateral or bilateral reduction of visual acuity in which an organic cause could not be detected [1].

New horizons in understanding the etiopathology of amblyopia are offered by Optical Coherence Tomography (OCT) which

seems to highlight morphologic anomalies in the retina of the amblyopic eye.

A series of studies that aimed to analyze macular thickness, optic nerve morphology and also choroidal thickness in the amblyopic eye have been published in the last years. The results are often contradictory because, as Kim says, when conducting an OCT in patients with anisometropia it is important to correct the magnification of the device according to



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refraction and axial length of the eye. Also, results differ depending on the device used [2].

Another limitation regarding correct interpretation of OCT in children emerges from the inexistence of international established normative values of macular and retinal nerve fiber layer (RNFL) parameters in children [3].

Objective

The purpose of this paper is to analyze the macular thickness, optic nerve changes, ganglion cell layer changes and the choroidal thickness found in adults and children diagnosed with amblyopia based on trials reported in the literature.

Material and methods

30 clinical trials published between 2006 and 2016 regarding OCT evaluation in amblyopia were identified on PubMed database and results were discussed according to:

Type of amblyopia; Alteration of macular thickness; Optic nerve and ganglion cell layer

changes; Alteration of choroidal thickness; Retinal morphologic changes after

occlusion.

Results

• Macular thickness (volume) Using OCT equipment, several researchers

analyzed in their studies morphologic changes in the macula thickness of amblyopic patients and the results are of great variability (Table 1).

Table 1. Macular thickness in amblyopic eye [2,4-7,10,12,17-19,32]

Patient age Type of amblyopia

Mean central macular thickness (µm)

Amblyopic eye

Contralateral eye

Normal subject

eye P

Alotaibi (2011) 5 – 12 years Anisometropia,

Strabismus 259.3

± 16.67 255.6

± 21.34 – 0.195

Al-Haddad (2011) 20 ± 12 years Anisometropia,

Strabismus 273.8 – 257.9 0.001

Wang (2012) 7 – 11 years (8.82 ± 1.47) Anisometropia 157.96

± 15.82 151.72 ± 13.95 – 0.045

Firat (2013) 5 – 23 years (12.6 ± 5.4)

Anisometropia, Strabismus

258.25 ± 18.31

258.75 ± 19.54

248.62 ± 10.57 0.06

Wu (2013)

5 – 16 years (9.7 ± 1.9) Anisometropia 257.1

± 15.8 258.6 ± 13.9 – 0.80

Kim (2013) 7.45 ± 2.57 years Congenital cataract 237.05

± 37.74 226.67 ± 34.71

233.74 ± 27.11

0.137 0.792

Araki (2014)


± 18.11 231.67 ± 15.17 – 0.099

Yalcin (2014)

8 – 14 years (10.5) Anisometropia 220

± 38.25 202.87 ± 31.01

198.91 ± 22.50 0.025

Yakar (2015)


± 23.22 263.90 ± 22.84 – 0.342

Demircan (2015)

5 – 12 years Anisometropia

260.71 ± 14.48

254.29 ± 14.79

– 0.001

13 – 42 years 265.61 ± 22.42

267.11 ± 24.52 0.483

Regarding anisometropic amblyopia:

Park found in the group of patients he studied in 2011 that the ganglion cell layer

thickness and internal plexiform layer were thinner than in the control group. He also noticed that other retinal layers (nerve fibre


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layer, inner nuclear layer, outer plexiform layer, outer nuclear layer) presented significant differences in thickness at several macular locations [8];

Wang (2012) stated that the average thickness of the foveola is thicker than in normal eyes, but other regions have no significant difference [4];

Wu (2013) showed in his study that hyperopic anisometropic amblyopic eyes have a thicker foveola than the contralateral eyes [5];

Araki (2014) concluded that there are significant differences between amblyopic and fellow eyes that are independent of abnormalities in the visual cortex. He showed that the macular outer retinal thickness (1 and 3 mm regions) is significantly thicker in „lazy eyes” [6];

Demircan (2015) discovered that in patients age 5-42 years the mean central macular thickness in the amblyopic eyes was thicker patients under 12 years [7].

After studying anisometropic and strabic ambliopic patients:

The Sydney Childhood Eye Study (2009) affirmed that in children aged 6 to 12 years, central macular thickness may be increased in „lazy eyes”, although it is uncertain if this precedes or follows the development of amblyopia [9];

Al-Haddad (2011) showed in his study that the mean macular thickness was significantly increased in amblyopic eyes compared with fellow eyes. This difference remained significant in the anisometropic group but not in the strabic group. The mean RNFL thickness was similar in amblyopic and fellow eyes [10];

In 2013 Tugcu claimed that in patients with combined (anisometropic and strabismic) amblyopia and in patients with anisometropic amblyopia the thickness of ganglion cell complex (GCC) was significantly increased in both amblyopic and nonamblyopic eyes compared to healthy patients. The strabismic amblyopia group presented with significant reduction in GCC thickness and increased foveal thickness compared to nonamblyopic eyes. He did not found significant differences in morphological and functional measures among amblyopic groups but he detected significant differences in the retinal morphology of both amblyopic and

nonamblyopic eyes compared with healthy control subjects [11];

Rajavi (2014) showed that the average foveal thickness of children with moderate and severe amblyopia was 10 microns thicker compared with the congener eye or the control group. Also, male patients had a mean macular thickness thicker than female patients and there was no correlation between the types of amblyopia and macular morphology changes [12];

Szigeti (2014) revealed that there are subtle changes that affect the outer nuclear layer of the fovea suggesting the possible involvement of the photoreceptors [13].

Concerning deprivational amblyopia: Kim (2013) investigated OCT changes in

deprivational amblyopia due to congenital cataract and concluded that the mean macular thickness in amblyopic eyes was not different from the contralateral eye or control group, but noticed a thickening of the nasal RNFL compared with the fellow eye or control group [2];

Long (2016) stated that 3 months after surgery, unilateral pediatric cataract patients show no significant interocular anatomical parameters differences except for anterior chamber depht (ACD) and that the parameters evaluated by OCT were not significantly correlated with the final BCVA [14].

Also, there are scientists like Kee (2006) Repka (2009), Firat (2013) and Yakar (2015) who claim the inexistence of differences between amblyopic patients and the control group in their studies regarding macula morphology [15-18].

• RNFL and Optic nerve changes Studies regarding morphologic changes of

the RNFL and optic nerve disc in amblyopic patients highlighted with the help of OCT show inconstancy in finding a pattern (Table 2).

Wu (2013) affirmed in his study that hyperopic anisometropic amblyopic eyes have thicker peripapillary RNFL than the contralateral eyes [5]. Also, after analyzing patients with anisometropic amblyopia Araki (2014) concluded that there are significant differences between amblyopic and fellow eyes: mean RNFL thickness significantly thicker, rim area significantly larger and smaller C/D ratio, in the amblyopic eyes [6].



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Some scientist such as Kee (2006), Repka (2009), Huynh (2009), Firat (2013), Yalcin (2014), Demircan (2015) and Yakar (2015) claimed that there are no differences in RNFL

and optic nerve disc morphology between amblyopic patients and control groups [7,9,15-19].

Table 2. RNFL Thickness in amblyopic eye [2,5-7,12,15-19,32]

Patient age Type of amblyopia

RNFL Thickness (µm)

Amblyopic eye Contralateral eye

Normal subject eye P

Kee (2006)

4 – 17 years (8.5)


107.2 ± 16.2

106.7 ± 16.5

108.8 ± 11.3

0.810 0.615

Repka (2009) 9.2 ± 1.5 years Anisometropia,

Strabismus 111.4 (10.4) 109.6 (11.4) – 0.13

Alotaibi (2011) 5 – 12 years Anisometropia,

Strabismus 112.16 ± 12.67

106 ± 8.91 – <0.0001

Wu (2013)

5 – 16 years (9.7 ±1.9) Anisometropia 113.9

± 7.2 109.2 ± 6.9 – 0.02

Firat (2013)

5 – 23 years (12.6 ± 5.4)


113.22 ± 21.47

111.57 ± 18.25

109.96 ± 11.31 0.13

Kim (2013) 7.45 ± 2.57 years Congenital cataract 99.64

± 10.11 97.28

± 12.34 95.38 ± 9.74

0.429 0.286

Araki (2014)


± 9.21 107.03 ± 8.74 – 0.004

Yalcin (2014)

8 – 14 years (10.5) Anisometropia 101

± 10.77 104.4

± 10.95 105.08 ± 10.10 0.285

Yakar (2015)


± 12.94 109.70 ± 9.42 – 0.621

Demircan (2015)

5 – 12 years Anisometropia

111 ± 19.23

105.67 ± 14.77 –

0.848

13 – 42 years 103.69 ± 8.3

100.92 ± 7.61 0.363

• Choroidal thickness

Morphological changes of the choroid evidenced with the help of OCT were studied by some researchers who certified that in amblyopic patients the subfoveolar area is significantly higher than in the congener eye or control group [20-25]. However, Celik (2016) stated that, in young Turkish adults with hyperopic anisometropic amblyopia, the subfoveal choroidal, ganglion cell complex, macular and RNFL thickness measurements were not statistically significant between hyperopic anisometropic amblyopic eyes and normal fellow eyes [25].

• Are there morphologic changes after occlusion?

6 studies were identified regarding the effect of optical correction and occlusion on the retina, optic nerve and choroid morphology.

Oner (2016) analyzed central choroidal thickness before and after 6 months of occlusive treatment and reported no thickness reduction of the central choroid after amblyopia treatment. While Miki (2010), Tugcu (2013), and Yassin (2015) did not found differences between macular thickness and RNFL thickness before and after occlusion therapy, Pang (2011) stated that the central macular thickness was reduced after treatment compared with peripheric macular thickness in which changes were not noticed [26-30].

Also, Liu (2010) stated that some children with various types of amblyopia who failed to achieve normal visual acuity after treatment show macular abnormality on OCT examination [31].


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Conclusions

Today, with the help of OCT, a new controversy regarding the presence of morphologic retinal changes in patients diagnosed with amblyopia arises. This opens new horizons in better defining amblyopia and can confirm if ocular structure are affected or not. In the last years, scientists have been trying to determine if morphologic changes in the macula, optic nerve, or choroid of amblyopic patients exist. The results are of great variability and, it seems that macula and choroid involvement is more frequently suggested compared with optic nerve involvement.

Disclosure

None.

References 1. Avram E, Stănilă A. Functional amblyopia. Oftalmologia.

2013; 57(4):3-8. 2. Kim YW, Kim SJ, Yu YS. Spectral-domain optical

coherence tomography analysis in deprivational amblyopia: a pilot study with unilateral pediatric cataract patients. Graefes Arch Clin Exp Ophthalmol. 2013; 251(12):2811–2819.

3. Molnar A, Holmström G, Larsson E. Macular thickness assessed with spectral domain OCT in a population-based study of children: normative data, repeatability and reproducibility and comparison with time domain OCT. Acta Ophthalmol. 2015; 93(5):470-5. doi: 10.1111/aos 12695.

4. Wang XM, Cui DM, Zhen L, Yang X, Huo LJ, Liu X, Zeng JW. Characteristics of the macula in amblyopic eyes by optical coherence tomography. International Journal of Ophthalmology. 2012; 5(2):172-176. doi:10.3980/j.issn.2222-3959.2012.02.11.

5. Wu SQ, Zhu LW, Xu QB, Xu JL, Zhang Y. Macular and peripapillary retinal nerve fiber layer thickness in children with hyperopic anisometropic amblyopia. Int J Ophthalmol. 2013; 6(1):85–89.

6. Araki S, Miki A, Yamashita T, Goto K, Haruishi K, Ieki Y, Kiryu J. A comparison between amblyopic and fellow eyes in unilateral amblyopia using spectral-domain optical coherence tomography. Clinical Ophthalmology. 7;8:2199-207. doi: 10.2147/OPTH.S69501.

7. Demircan S, Gokce G, Yuvaci I, Ataş M, Başkan B, Zararsiz G. The Assessment of Anterior and Posterior Ocular Structures in Hyperopic Anisometropic Amblyopia. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 2015; 21:1181-1188. doi:10.12659/MSM.893979.

8. Park KA, Park DY, Oh SY. Analysis of spectral-domain optical coherence tomography measurements in amblyopia: a pilot study. Br J Ophthalmol. 2011; 95(12):1700–1706.

9. Huynh SC, Samarawickrama C, Wang XY, Rochtchina E, Wong TY, Gole GA, Rose KA, Mitchell P. Macular and nerve fiber layer thickness in amblyopia: the Sydney Childhood Eye Study. Ophthalmology. 2009; 116(9):1604-9. doi: 10.1016/j.ophtha.2009.03.013.

10. Al-Haddad CE, Mollayess GM, Cherfan CG, Jaafar DF, Bashshur ZF. Retinal nerve fibre layer and macular thickness in amblyopia as measured by spectral-domain optical coherence tomography. Br J Ophthalmol. 2011; 95(12):1696-9. doi: 10.1136/bjo.2010.195081.

11. Tugcu B, Araz-Ersan B, Kilic M, Erdogan ET, Yigit U, Karamursel S. The morpho-functional evaluation of retina in amblyopia. Curr Eye Res. 2013; 38(7):802–809.

12. Rajavi Z, Moghadasifar H, Feizi M, Haftabadi N, Hadavand R, Yaseri M, Sheibani K, Norouzi G. Macular Thickness and Amblyopia. Journal of Ophthalmic & Vision Research. 2014; 9(4):478-483. doi:10.4103/2008-322X.150827.

13. Szigeti A, Tátrai E, Szamosi A, Vargha P, Nagy ZZ, Németh J, Cabrera DeBuc D, Somfai GM. A Morphological Study of Retinal Changes in Unilateral Amblyopia Using Optical Coherence Tomography Image Segmentation. Ablonczy Z. ed. PLoS ONE. 2014; 9(2):e88363. doi:10.1371/journal.pone.0088363.

14. Long E, Chen J, Liu Z, Lin Z, Cao Q, Zhang X, Li X, Luo L, Lin H, Chen W, Liu Y. Interocular anatomical and visual functional differences in pediatric patients with unilateral cataracts. BMC Ophthalmol. 2016; 3;16(1):192. doi: 10.1186/s12886-016-0371-5.

15. Kee SY, Lee SY, Lee YC. Thicknesses of the Fovea and Retinal Nerve Fiber Layer in Amblyopic and Normal Eyes in Children. Korean Journal of Ophthalmology. KJO. 2006; 20(3):177-181. doi:10.3341/kjo.2006.20.3.177.

16. Repka MX, Kraker RT, Tamkins SM, Suh DW, Sala NA, Beck RW. Retinal Nerve Fiber Layer Thickness in Amblyopic Eyes. American Journal of Ophthalmology. 2009; 148(1):143-147. doi:10.1016/j.ajo.2009.01.015.

17. Firat PG, Ozsoy E, Demirel S, Cumurcu T, Gunduz A. Evaluation of peripapillary retinal nerve fiber layer, macula and ganglion cell thickness in amblyopia using spectral optical coherence tomography. Int J Ophthalmol. 2013; 6(1):90–94.

18. Yakar YK, Kan E, Alan A, Alp MH, Ceylan T. Retinal Nerve Fibre Layer and Macular Thicknesses in Adults with Hyperopic Anisometropic Amblyopia. J Ophthalmol. 2015; 2015: 946467. doi:10.1155/2015/946467.

19. Yalcin E, Balci O. Peripapillary retinal nerve fiber layer and foveal thickness in hypermetropic anisometropic amblyopia. Clinical Ophthalmology. 2014; 8:749-753. doi:10.2147/OPTH.S58541.

20. Aygit ED, Yilmaz I, Ozkaya A, Alkin Z, Gokyigit B, Yazici AT, Demirok A. Choroidal thickness of children’s eyes with anisometropic and strabismic amblyopia. J AAPOS. 2015 Jun; 19(3):237-41. doi: 10.1016/j.jaapos.2015.03.013.

21. Kantarci FA, Tatar MG, Uslu H, Colak HN, Yildirim A, Goker H et al. Choroidal and peripapillary retinal nerve fiber layer thickness in adults with anisometropic



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amblyopia. Eur J Ophthalmol. 2015; 25:437±442. doi: 10.5301/ejo.5000594.

22. Nishi T, Ueda T, Hasegawa T, Miyata K, Ogata N. Choroidal thickness in children with hyperopic anisometropic amblyopia. Br J Ophthalmol. 2014; 98: 228±232. doi: 10.1136/bjophthalmol-2013-303938.

23. Xu J, Zheng J, Yu S, Sun Z, Zheng W, Qu P, Chen Y, Chen W, Yu X. Macular choroidal thickness in unilateral amblyopic children. Invest Ophthalmol Vis Sci. 2014; 55:7361–7368. doi:10.1167/iovs.14-14439.

24. Nishi T, Ueda T, Mizusawa Y, Shinomiya K, Semba K, Mitamura Y, Sonoda S, Uchino E, Sakamoto T, Ogata N. Choroidal Structure in Children with Anisohypermetropic Amblyopia Determined by Binarization of Optical Coherence Tomographic Images. PLoS One. 2016 Oct 13; 11(10):e0164672. doi: 10.1371/journal.pone.0164672.

25. Celik E, Çakır B, Turkoglu EB, Doğan E, Alagoz G. Evaluation of the retinal ganglion cell and choroidal thickness in young Turkish adults with hyperopic anisometropic amblyopia. Int Ophthalmol. Int Ophthalmol. 2016; 36(4):515-20. doi: 10.1007/s10792-015-0157-4.

26. Öner V, Bulut A. Does the treatment of amblyopia normalise subfoveal choroidal thickness in amblyopic children?. Clin Exp Optom. 2016; 18. doi: 10.1111/cxo.12483.

27. Miki A, Shirakashi M, Yaoeda K, Kabasawa Y, Ueki S, Takagi M, Abe H. Retinal nerve fiber layer thickness in recovered and persistent amblyopia. Clin Ophthalmol. 2010; 20(4):1061–1064.

28. Tugcu B, Araz-Ersan B, Kilic M, Erdogan ET, Yigit U, Karamursel S. The morpho-functional evaluation of retina in amblyopia. Curr Eye Res. 2013 Jul; 38(7):802-9. doi: 10.3109/02713683.2013.779721.

29. Yassin SA, Al-Tamimi ER, Al-Hassan S. Macular and retinal nerve fiber thickness in recovered and persistent amblyopia. Int Ophthalmol. 2015 Dec; 35(6):833-42. doi: 10.1007/s10792-015-0055-9.

30. Pang Y, Goodfellow GW, Allison C, Block S, Frantz KA. A prospective study of macular thickness in amblyopic children with unilateral high myopia. Invest Ophthalmol Vis Sci. 2011; 14;52(5):2444-9. doi: 10.1167/iovs.10-5550.

31. Liu H, Zhong L, Zhou X, Jin Q. Macular Abnormality Observed by Optical Coherence Tomography in Children With Amblyopia Failing to Achieve Normal Visual Acuity After Long-Term Treatment. J Pediatr Ophthalmol Strabismus. 2010; 47:17-23. doi: 10.3928/01913913-20091019-06.

32. Alotaibi AG, Al Enazi B. Unilateral amblyopia: Optical coherence tomography findings. Saudi Journal of Ophthalmology. 2011; 25(4):405-409. doi:10.1016/j.sjopt.2011.06.001.


REVIEW

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Insights in the treatment of congenital nasolacrimal duct obstruction

Avram Elena Ophthalmology Department, Medlife Băneasa Hyperclinic, Bucharest, Romania Correspondence to: Elena Avram, MD, Ophthalmology Department, Medlife Băneasa Hyperclinic, Bucharest, 10 București-Ploiești Highway, Code 013693, Bucharest, Romania, Mobile phone: +40741 608 980, E-mail: [email protected]

Accepted: May 27th, 2017

Abstract Introduction: Congenital nasolacrimal duct obstruction is one of the most common causes of epiphora in newborns and the main cause of this condition is the persistence of Hasner membrane. Several treatment options are available, like conservative treatment, probing, irrigation, or more complex techniques. Objective: The objective of this paper is to discuss the efficiency of different treatment options addressing congenital nasolacrimal duct obstruction based on trials reported in literature. Methods: Clinical trials were identified on PubMed. The results were discussed regarding patient age, type of treatment and efficiency of the treatment. Results: 41 trials were reviewed. The rate of resolution according to different treatment options was the following: conservative treatment 14.2-96%, probing 78-100%, irrigation 33-100%, silicon tube intubation 62-100%, inferior turbinate fracture 54.7-97%, balloon dacryocystoplasty 77%, endoscopic intranasal surgery 92.72%, and dacryocystorhinostomy 88.2-93.33%. Conclusions: The first choice in uncomplicated cases should be a conservative treatment, which can be followed until the age of 1 year, while in complicated cases other solutions should be considered. Keywords: congenital nasolacrimal duct obstruction, probing, dacryocystorhinostomy Abbreviations: CNDO = Congenital nasolacrimal duct obstruction, DCR = Dacryocystorhinostomy, MCI = Monocanalicular intubation, BCI = Bicanalicular intubation

Introduction

In the management of congenital nasolacrimal duct obstruction (CNDO), very complex and noninvasive treatment options can be used: conservative treatment, probing, irrigation, silicon tube intubation, inferior turbinate fracture, balloon dacryocystoplasty, endoscopic intranasal surgery, or dacryocystorhinostomy. It is important that the

technique we choose to be in correlation with the etiology of the disease and the complexity of the case.

Objective

The objective of this paper was to analyze the efficiency of different treatment options



© 2017

addressing CNDO, based on trials reported in literature.

Methods

Clinical trials were identified on PubMed. The results were discussed regarding patient age, type of treatment and efficiency of treatment.

Results

• Conservative treatment At present, the current trend is to indicate a

conservative treatment and expect spontaneous remission of CNDO. Conservative treatment

entails: lacrimal sac compression and massage, rigorous hygiene of the eyelids and, if there is any purulent discharge, antibiotic eye drops (netilmicin). It is generally recommended up to the age of 12 months and then, depending on the severity of the symptoms, other therapeutic options can be discussed. The success rate is between 14.2% and 96% depending on the patients’ age (Table 1). It seems that compliance to treatment is a key factor. Karti compared two groups, one in which parents regularly applied lacrimal sac massage with a remission of 92.2% and another group with parents who did not regularly apply lacrimal sac massage, with a success rate of 77.7% of the cases [3].

Table 1. Success rate of conservative treatment during the first 12 months of life [1,2]

Patient age Kakizaki H (2008)

PEDIG (2012)

1 month 82.9% - 2 months 82.4% - 3 months 80% - 4 months 79.3% - 5 months 76% - 6 months 68.4% - 7 months 66.7% 69% 8 months 64.7% 68% 9 months 57.1% 55%

10 months 33.3% 67% 11 months 14.2% -

• Probing This method has long been considered the

first choice treatment in CNDO and it can be performed under local anesthesia before the age of 4-6 months or under general anesthesia [4,5].

The right moment of probing remains controversial, the main problem being the possibility of spontaneous resolution during the first 12 months of life. However, it is advisable to be performed before the age of 12 months if complications appear.

Some physicians prefer to approach the nasolacrimal duct from the upper punctum while others from the lower punctum or from both sides. The punctum is dilated. The probe is introduced vertically. The lid is pulled laterally and the probe is advanced horizontally until it reaches the nasal wall of the lacrimal sac. The lateral traction is released and the probe is

turned 90 degrees and directed downward, posteriorly and laterally.

There are several probing techniques: – Probing guided with soft cannula which

implies that a plastic intravenous catheter sheath is supported intraluminal with a guiding metal probe and has a success rate of 89.8% [6];

– Probing with manually bent Bowman probes that mimic the natural curve of the nasolacrimal duct have a success rate of 91.4%, while straight Bowman probes have a success rate of 76.2% [7];

– Endoscopic assisted probing allows a direct visualization of the nasolacrimal duct and avoids the formation of false routes, its efficiency varying between 92.3% and 100% [8-10].

Success rate of probing varies between 78 and 100% (Table 2) and decreases with the age of the patient. Takahashi showed that the


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success rate in the second probing is lower than in the first [14].

Main side effects of this therapeutic approach are creating false routes and

epithelium damage due to scarring strictures tear.

Table 2. Success rate after probing [4,5,11-13]

Patients’ age Success rate Type of anesthesia

Abrishami M (2009)

15 – 24 months 76%

general 25 – 36 months 67.7% 37 – 48 months 90% 49 – 60 months 60% > 60 months 75%

Arora S (2012)

< 36 months 78% general > 36 months 50%

Rajabi MT (2014)

24 – 36 months 85% general 37 – 48 months 63%

49 – 60 months 50%

Hung CH (2015)

< 6months 90.1%

topical

6 – 11 months 79.6% 12 – 17 months 76.8% 18 – 23 months 73.5% 24 – 35 months 75% 36 – 60 months 33%

Le Garrec J (2016) < 12 months 76.7% topical

• Irrigation This technique, with an efficiency of 33 -

100% according to various authors, involves injecting saline solution with or without antibiotic in the lacrimal pathways and is considered less invasive than probing. It can affect the tear ducts epithelium and can lead to the pulmonary aspiration of the fluids used [15,16].

• Silicon tube intubation Lacrimal pathways prosthesis with silicone

tubes is indicated in ineffective conservative treatment, failed probing, or presence of strictures.

There are two main types of silicone tubes used: monocanalicular (Mono Crawford, Monoka, Masterka) and bicanalicular (Crawford, Bika, Infant - Bika, Goldberg, Ritleng) and it is recommended that this invasive maneuver is performed under endoscopic control.

According to various authors, the success rate is between 62% and 100% [17-26]. Also Kassif showed that the rate of spontaneous resolution after unsuccessful intubation with silicone tube is 80% [26].

Several studies in which monocanalicular intubation (MCI) with bicanalicular intubation (BCI) results were compared were published. Some scientists like Rajabi showed that BCI is more effective while others, like Lee or Komínek, did not find a significant difference between the two groups [19,23,24]. Also regarding MCI, Andalib and Rajabi reported better results with Monoka stent than with Masterka stent [24,25].

Complications encountered are: symptoms relapse due to premature removal, atony of lacrimal punctum, corneal erosions, displacement, injury to the nasal mucosa and lower cone during the recovery procedure of the dislodged silicone tube [17-26].

• Inferior turbinate fracture The use of inferior turbinate fracture

usually associated with probing is recommended when there is a narrow space around the nasolacrimal duct ostium.

This technique has a controversial efficiency. Ab. Attarzadeh and Katowitz did not found a high rate of success while Havins reported no failure when applying inferior nasal conchae fracture [27-29].



© 2017

• Balloon dacryocystoplasty Dilatation with balloon catheter or balloon

dacryocystoplasty is performed by inserting a guide wire with a deflated balloon attached through the punctum in the nasolacrimal duct. The balloon is gently inflated with liquid and the pressure created opens up and expands the blocked duct. The balloon is deflated and removed. The success rate is 77% [30].

Hu compared balloon catheter dilatation with silicon intubation after a failed probing and obtained a 64.7% remission rate in the first group and an 86.1% remission rate in the second group [31]. This method is beginning to be proposed as an alternative to silicone tube intubation, having a lower rate of complications like epistaxis and lacrimal duct laceration [32].

• Endoscopic intranasal surgery Proposed by Korkmaz, this new technique

consists in an endoscope-guided inspection of the Hasner valve area, irrigation, incision of the imperforate Hasner membrane valve and again irrigation. The success rate is 92.72% [33].

• Dacryocystorhinostomy Dacryocystorhinostomy (DCR) involves

creating an anastomosis between the lacrimal sac and the nasal mucosa by means of a localized bone resection of the nose wing. It represents the last resort when other therapeutic methods have failed.

There are two types of DCR, external and internal (endonasal/ endoscopic). The success rate of the two surgical approaches in children is relatively the same (Table 3). Choung indicated that combining DCR with silicone tube intubation prevents failure, while Pakdel showed that this technique is not superior [38,39].

Kamal published a study in which he applied circumostial Mitomicin C during external and endoscopic DCR with an anatomical success rate of 97.3% and a functional success rate of 96.4% [40].

Table 3. Success rate of internal and external DCR [34-37]

Success rate External DCR Internal DCR

Hartikainen J (1998) 89.1% 90.2%

Cokkeser Y 88.2% 89.2%

(2000) Vivek KP (2013) 90% 86.67% Dey AK (2014) 93.33% 90%

Conclusions

During the last years, many trials regarding congenital nasolacrimal duct obstruction have been published, making it possible to conclude that the first treatment choice in uncomplicated cases should be a conservative treatment which can be applied until the age of 1 year. In complicated cases, a complex management should be taken into consideration.

In the last years, new techniques have been developed and classic techniques have been improved, which enhances the outcome of CNDO.

Disclosure

None.

References

1. Kakizaki H, Takahashi Y, Kinoshita S, Shiraki K, Iwaki M. The rate of symptomatic improvement of congenital nasolacrimal duct obstruction in Japanese infants treated with conservative management during the 1st year of age. Clinical Ophthalmology. 2008; 2(2):291-294.

2. Pediatric Eye Disease Investigator Group. Resolution of Congenital Nasolacrimal Duct Obstruction with Nonsurgical Management. Archives of Ophthalmology. 2012; 130(6):730-734. doi:10.1001/archophthalmol.2012.454.

3. Karti O, Karahan E, Acan D, Kusbeci T. The natural process of congenital nasolacrimal duct obstruction and effect of lacrimal sac massage. Int Ophthalmol. 2016; 36(6):845-849. doi: 10.1007/s10792-016-0208-5.

4. Le Garrec J, Abadie-Koebele C, Parienti JJ, Molgat Y, Degoumois A, Mouriaux F. Nasolacrimal duct office probing in children under the age of 12 months: Cure rate and cost evaluation. J Fr Ophtalmol. 2016; 39(2):171-7. doi: 10.1016/j.jfo.2015.06.009.

5. Hung CH, Chen YC, Lin SL, Chen WL. Nasolacrimal Duct Probing under Topical Anesthesia for Congenital Nasolacrimal Duct Obstruction in Taiwan. Pediatr Neonatol. 2015; 56(6):402-7. doi: 10.1016/j.pedneo.2015.04.001.

6. Yuksel D, Ozer PA. Long-term results of probing guided with soft cannula in children with congenital nasolacrimal ductobstruction. Jpn J Ophthalmol. 2014; 58(1):94-9. doi: 10.1007/s10384-013-0289-x.

7. Serin D, Buttanri IB, Sevim MS, Buttanri B. Primary probing for congenital nasolacrimal duct obstruction with manually curved Bowman probes. Clinical


105


Ophthalmology (Auckland, NZ). 2013; 7:109-112. doi:10.2147/OPTH.S39926.

8. Theodoropoulou S, Sutherland MS, Haddow K, Blaikie A. Success rates of endoscopic-assisted probing for congenital nasolacrimal duct obstruction in children. J Laryngol Otol. 2013; 127(8):794-8. doi: 10.1017/S0022215113001370.

9. Sasaki H, Takano T, Murakami A. Direct endoscopic probing for congenital lacrimal duct obstruction. Clin Exp Ophthalmol. 2013; 41(8):729-34. doi: 10.1111/ceo.12108.

10. Fujimoto M, Ogino K, Matsuyama H, Miyazaki C. Success rates of dacryoendoscopy-guided probing for recalcitrant congenital nasolacrimal ductobstruction. Jpn J Ophthalmol. 2016; 60(4):274-9. doi: 10.1007/s10384-016-0445-1.

11. Abrishami M, Bagheri A, Salour S-H, Mirdehghan SA. Late Probing for Congenital Nasolacrimal Duct Obstruction. Journal of Ophthalmic & Vision Research. 2009; 4(2):102-104.

12. Arora S, Koushan K, Harvey JT. Success rates of primary probing for congenital nasolacrimal obstruction in children. J AAPOS. 2012; 16(2):173-6. doi: 10.1016/j.jaapos.2011.12.151.

13. Rajabi MT, Abrishami Y, Hosseini SS, Tabatabaee SZ, Rajabi MB, Hurwitz JJ. Success rate of late primary probing in congenital nasolacrimal duct obstruction. J Pediatr Ophthalmol Strabismus. 2014 Nov-Dec; 51(6):360-2. doi: 10.3928/01913913-20140909-02.

14. Takahashi Y, Kakizaki H, Chan WO, Selva D. Management of congenital nasolacrimal duct obstruction. Acta Ophthalmol. 2010 Aug; 88(5):506-13. doi: 10.1111/j.1755-3768.2009.01592.x.

15. Marr JE, Drake-Lee A, Willshaw HE. Management of childhood epiphora. Br J Ophthalmol. 2005; 89:1123-1126. doi:10.1136/bjo.2005.069286.

16. Casady DR, Douglas RMD, Meyer Dale RMD, Simon John WMD, Stasior George OMD, Zobal-Ratner Jitka LMD. Stepwise treatment paradigm for congenital nasolacrimal duct obstruction. Ophthal. Plas. Reconstr. Surg. 2006; 22:243–7. doi: 10.1097/01.iop.0000225750.25592.7f.

17. Lim CS, Martin F, Beckenham T, Cumming RG. Nasolacrimal duct obstruction in children: outcome of intubation. J. AAPOS. 2004; 8:466–472.

18. Peterson NJ, Weaver RG, Yeatts RP. Effect of short-duration silicone intubation in congenital nasolacrimal duct obstruction. Ophthal. Plast. Reconstr. Surg. 2008; 24:167–171.

19. Komínek P, Cervenka S, Matousek P. Does the length of intubation affect the success of treatment for congenital nasolacrimal duct obstruction?. Ophthal. Plast. Reconstr. Surg. 2010; 26(2):103-5. doi: 10.1097/IOP.0b013e3181b8e0aa.

20. Memon MN, Siddiqui SN, Arshad M, Altaf S. Nasolacrimal duct obstruction in children: outcome of primary intubation. J. Pak. Med. Assoc. 2012; 62(12):1329-32.

21. Fayet B, Katowitz WR, Racy E, Ruban JM, Katowitz JA. Pushed monocanalicular intubation: an alternative stenting system for the management of congenital nasolacrimal duct obstructions. J. AAPOS. 2012; 16(5):468-72. doi: 10.1016/j.jaapos.2012.07.003.

22. Yu G, Hu M, Wu Q, Cao WH, Fan YW, Lin Q, Liu W. Factors affected therapeutic results in treatment of children congenital nasolacrimal duct obstruction by Ritleng lacrimal intubation. Zhonghua Yan Ke Za Zhi. 2012; 48(5):423-7.

23. Lee H, Ahn J, Lee JM, Park M, Baek S. Clinical effectiveness of monocanalicular and bicanalicular silicone intubation for congenital nasolacrimal duct obstruction. J. Craniofac. Surg. 2012; 23(4):1010-4. doi: 10.1097/SCS.0b013e31824dfc8a.

24. Rajabi MT, Zavarzadeh N, Mahmoudi A et al. Bicanalicular versus monocanalicular intubation after failed probing in congenital nasolacrimal duct obstruction. International Journal of Ophthalmology. 2016; 9(10):1466-1470. doi:10.18240/ijo.2016.10.16.

25. Andalib D, Mansoori H. A comparison between monocanalicular and pushed monocanalicular silicone intubation in the treatment of congenital nasolacrimal duct obstruction. International Journal of Ophthalmology. 2014; 7(6):1039-1042. doi:10.3980/j.issn.2222-3959.2014.06.24.

26. Kassif Y, Rehany U, David M, Popko A, Rumelt S. The course of epiphora after failure of silicone intubation for congenital nasolacrimal duct obstruction. Graefe’s Arch Clin Exp Ophthalmol. 2005; 243:758. doi:10.1007/s00417-004-1115-4.

27. At Tarzadeh Ab, Sajjadi M, Owji N, Reza Talebnejad M, Fa Rvardin M. Inferior turbinate fracture and congenital nasolacrimal duct obstruction. European Journal of Ophthalmology. 2006; 4:520-524.

28. Katowitz JA, Welsh MG. Timing of initial probing and irrigation in congenital nasolacrimal duct obstruction. Ophthalmology. 1987; 94:698-705.

29. Havins WE, Wilkins RB. A useful alternative to silicone intubation in congenital nasolacrimal duct obstructions. Ophthalmic Surg. 1983; 14:666-70.

30. Pediatric Eye Disease Investigator Group. Balloon Catheter Dilation and Nasolacrimal Intubation for Treatment of Nasolacrimal Duct Obstruction Following a Failed Probing. Archives of Ophthalmology. 2009; 127(5):633-639. doi:10.1001/archophthalmol.2009.66.

31. Hu M, Wu Q, Fan YW, Cao WW, Lin Q, Yu G. Comparison of balloon catheter dilatation and silicon intubation as the secondary treatment for congenital nasolacrimal duct obstruction after failed primary probing. Zhonghua Yan Ke Za Zhi. 2016; 52(2):123-8. doi: 10.3760/cma.j.issn.0412-4081.2016.02.009.

32. Yu G, Hu M, Wu Q, Cao WH, Fan YW, Lin Q, Liu W. Balloon dacryocystoplasty in the treatment of congenital nasolacrimal duct obstruction after previous unsuccessful surgery. Zhonghua Yan Ke Za Zhi. 2011; 47(8):698-702.

33. Korkmaz H, Korkmaz M, Karakahya RH, Serhatlı M. Endoscopic intranasal surgery for congenital nasolacrimal duct obstruction-a new approach. Int. J. Pediatr. Otorhinolaryngol. 2013; 77(6):918-21. doi: 10.1016/j.ijporl.2013.03.005.

34. Hartikainen J, Grenman R, Puukka P, Seppa H. Prospective randomized comparison of external dacryocystorhinostomy and endonasal laser dacryocystorhinostomy. Ophthalmology. 1998; 105:1106–1113.



© 2017

35. Cokkeser Y, Evereklioglu C, Er H. Comparative external versus endoscopic dacryocystorhinostorny: results in 115 patients (130 eyes). Otolaryngology Head and Neck Surgery. 2000; 123(4):488-491.

36. Vivek KP, Debajit D, Uttal TB, Pinpo T. A Comparative Study between Conventional and Endoscopic Dacryocystorhinostomy. IOSR-JDMS. 2013; 6(2):38-40.

37. Dey AK, Gayen GC, Jana S, Ghorai S, Sarkar A, Ganguly P. External and Endoscopic Dacryocystorhinostomy in Nasolacrimal Duct Obstruction: A Comparative Study. IJHSR. 2014; 4(12):115-120.

38. Choung HK, Khwarg SI. Selective non-intubation of a silicone tube in external dacryocystorhinostomy. Acta Ophthalmologica Scandinavica. 2007; 85:329–332. doi:10.1111/j.1600-0420.2006.00827.x.

39. Pakdel F. Silicone Intubation Does not Improve the Success of Dacryocystorhinostomy in Primary Acquired Nasolacrimal Duct Obstruction. Journal of Ophthalmic & Vision Research. 2012; 7(3):271-272.

40. Kamal S, Ali MJ, Naik MN. Circumostial injection of mitomycin C (COS-MMC) in external and endoscopic dacryocystorhinostomy: efficacy, safety profile, and outcomes. Ophthal. Plast. Reconstr. Surg. 2014; 30(2):187-90. doi: 10.1097/IOP.0000000000000102.


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IRIDEX MicroPulse P3: innovative cyclophotocoagulation Gavris M. Monica*, Olteanu Ioana*, Kantor Erzsebet*, Mateescu Radu*, Belicioiu Roxana* *Laser Optisan Clinic, Cluj-Napoca, Romania Correspondence to: Gavris Maria Monica, MD, Ophthalmologist, Associated member of Laser Optisan Clinic, Laser Optisan Clinic, Cluj-Napoca, 55 General Traian Mosoiu Street, Code 400132, Cluj-Napoca, Romania, Mobile phone: +40745 654 595, +40745 239 595, E-mail: [email protected] Accepted: January 15th, 2017

Abstract Purpose: To present the new IRIDEX MicroPulse P3 (MP3) technology in patients with refractory glaucoma and our preliminary results at 1 week and 1 month postoperatively. Methods: IRIDEX MP3 laser cyclophotocoagulation was performed in 7 eyes of 7 patients under retrobulbar anaesthesia with lidocaine 2% in the operating room. Each eye received two treatments of 80-90s over the superior and inferior hemisphere, avoiding the temporal- and nasal-most clock hours. 810nm IRIDEX MP3 was set to 31,3% duty cycle (0,5ms treatment pulse followed by 1,1 ms of rest). Postoperative topical steroids were prescribed for 1 week. Results: Mean IOP decrease at 1 week was 60,3% and 33,4% at 1 month, with a mean topical hypotensive treatment reduction of 0,71 therapeutic agents. The procedure was safe in all cases and effective in 71% of the patients. Neovascular glaucoma patients registered high IOP levels 1 month postoperatively in spite of medical and MP3 laser treatment. BCVA remained unchanged after undertaking the laser procedure. No significant inflammation, discomfort, or pain was reported. There were no complications such as hypotony, phthisis bulbi, and macular edema. Conclusions: IRIDEX MP3 represents an innovation in cyclophotocoagulation. It is non-destructive, repeatable, non-invasive, with a high safety profile. A mean IOP decrease of 33,4% was registered at 1 month. Patient comfort and recovery are favorable. Long-term results will prove its efficacy in the future. Keywords: IRIDEX, MicroPulse P3, IOP, glaucoma, cyclophotocoagulation, laser

Introduction

Traditional cyclophotocoagulation was introduced as a treatment method to reduce IOP by decreasing the production of aqueous humour via the destruction of the ciliary epithelium.

The method was initially applied to patients with recalcitrant glaucoma and few treatment options, but gained popularity in recent years and was found more effective than

the medical therapy of lowering the IOP, but determined a series of complications: hypotony (up to 10% of the cases), phthisis bulbi, and macular oedema [1]. Therefore, the development of a new IOP lowering device with a greater safety profile was necessary.

The Micropulse P3 glaucoma device powered by Cyclo G6 Glaucoma Laser System revolutionized cyclophotocoagulation. The new technology takes a continuous wave of laser and



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breaks it into a series of repetitive pulses separated by pauses that prevent thermal build-up in the tissue [2]. This is the first non-incisional, non-invasive laser for the treatment of glaucoma that has a favorable profile and a series of unique features. The procedure can be repeated as much as needed to treat the patient regardless of the previous glaucoma therapy. Particularly good candidates for this therapy method are patients who live alone, for whom surgery would be difficult and inconvenient and patients with compliance difficulties, unable to follow a long-term treatment scheme [3] (Fig. 1).

Purpose The aim of our study was to present the

new IRIDEX MicroPulse P3 (MP3) technology in patients with refractory glaucoma and our preliminary results at 1 week and 1 month postoperatively.

Patients and Methods

Patients A prospective case series included 7 eyes of

7 patients with narrow-angle glaucoma [2], open-angle glaucoma [2], inflammatory glaucoma [1] and neovascular glaucoma [2], all female patients aged between 21 and 73 years, with a mean age of 60,85 years, treated in November 2016, at Laser Optisan Clinic, Cluj-Napoca.

The following baseline data were collected prior to the treatment: age, sex, ocular history, glaucoma diagnosis-nonresponsive to maximal

medical therapy with or without previous surgical intervention, best-corrected Snellen visual acuity (BCVA), glaucoma medications, slit-lamp examination findings of the anterior and posterior pole. All patients signed an informed consent. IRIDEX MP3 laser cyclophotocoagulation was performed in all cases without complications during or after the procedure.

Method

The procedure was performed in the operating room, following retrobulbar anaesthesia with lidocaine 2%, each eye received two treatments of 80-90s over the superior and inferior hemisphere avoiding the temporal- and nasal-most clock hours, by moving the probe over 6 clock hours at every 10 seconds, perpendicular and posterior to the limbus [2] (Fig. 2).

The treatment was carried out with the

810nm IRIDEX MP3 laser set to a 31,3% duty cycle (0,5ms treatment pulse followed by 1,1ms of rest) (Fig. 3).

Fig. 1 IRIDEX MicroPulse P3 treatment probe

Fig. 2 IRIDEX MicroPulse P3 treatment method

Fig. 3 MicroPulse P3 device


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Glaucoma treatment was not discontinued and the patients were examined 1 week and 1 month postoperatively. The surgeon was able to start reduce the hypotensive medication depending on how quickly the pressure fell to the value of 10mmHg or below.

Results

Patients were examined at 1 week and 1 month postoperatively. The recovery period was favorable and patients did not experience any significant discomfort or pain. MP3 does not destroy the eye’s ciliary body or cause inflammation. Because it is a non-incisional procedure, in which the system’s probe is placed directly on the sclera [4], the risk of bleeding and infection is eliminated (Fig. 4).

A mean IOP decrease of 60,3% was

observed at 1 week postoperatively (34,7% to 71,9% from baseline) and 33,4% 1 month after the procedure (0% to 60,8% from baseline). In 3 cases, medication was reduced by 1 therapeutic agent, in 1 case by 2 and in 3 cases medical treatment remained unchanged after 1 month, resulting in a mean reduction of topical hypotensive medication of 0,71 agents. Best corrected Snellen VA was stable before and after treatment, ranging from wlp to 0,8.

The MP3 laser treatment was considered successful in 71% of the cases. Unsatisfactory results were obtained in 2 cases of neovascular glaucoma, a secondary glaucoma generally associated with a poor prognosis. If clinical hypotensive treatment is not sufficient, a more complex approach is required: panretinal photocoagulation, intravitreal anti-VEGF therapies, and surgical procedures for intraocular pressure control [5].

All patients were re-examined at 3, 6, 12, and 18 months postoperatively and retreatment could be performed within the 18 months follow-up period (Table 1).

Table 1. 18 months follow-up period of the patients Preop

IOP Preop treatment

DT (S) 1 week postop PIO

1 week postop PIO change

Treatment after 1 month

1 month postop PIO

1 month postop PIO change

Case #1 PNAG 59 years old

26 5 80 12 53,8% 3 20 23%

Case #2 PNAG 71 years old

33 4 80 12 63,6% 3 20 39,3%

Case #3 POAG 73 years old

23 5 80 15 34,7% 4 14 39,1%

Case #4 POAG 61 years

40 5 90 14 65% 4 21 47,5%

Fig. 4 MP3 laser delivery



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old Case #5 SIG

46 3 90 13,7 70,2% 3 18 60,8%

Case #6 SNG

57 2 90 16 71,9% 2 43 24,5%

Case #7 SNG

27 2 90 10 62,9% 2 27 0%

• All patients received a retrobulbar injection of 2% lidocaine • All cases were treated with a range of 80-90 seconds per hemisphere and 2000 mW

Discussions

Cyclophotocoagulation with the IRIDEX MicroPulse P3 device represents a new tissue-sparing technology used in simple and complex glaucoma cases. While standard cyclophotocoagulation (CPC) involves ciliary body destruction by targeting the ciliary epithelium and stroma resulting in a reduction in aqueous secretion and IOP, MP3 administers a series of repetitive, short pulses of laser energy separated by rest periods, unlike conventional CPC, which delivers continuous, high intensity energy to the ciliary body [6].

The procedure is non-invasive, easily undertaken, and well tolerated, with transscleral application, eliminating bleeding and postoperative infection risks. Postoperative inflammation and pain are insignificant and hospital admission is not required (Fig. 5).

1 week postoperatively, a mean IOP

decrease of 60,3% was observed, under unchanged glaucoma medication. 1 month after the laser procedure, the average IOP decreased by 33,4% from baseline, combined with a mean reduction of 0,71 therapeutic agents in ocular hypotensive medications.

The treatment was delivered with an excellent safety profile. No cases of hypotony, phthisis bulbi, or macular edema were observed [7].

IRIDEX MP3 cyclophotocoagulation was successful in 71% of the cases. Unsatisfactory IOP values were observed at 1 month in neovascular glaucoma patients: the first case presented a mean IOP decrease of 24,5% but remained outside the normal range and the second case presented no IOP decrease from baseline at 1 month. These results showed the need of a more complex therapeutic approach in such cases, where the IOP lowering treatment was not enough.

Patients were re-examined at 3, 6, 12 and 18 months postoperatively. If IOP reached values of 10mmHg or below, glaucoma medication could be reduced. Retreatments could be performed at 6-8 weeks after the first treatment, within the 18 months follow-up period, if required.

Conclusions

1. IRIDEX MicroPulse P3 represents an innovation in cyclophotocoagulation. MP3 programming takes a continuous wave and breaks it into a series of short, repetitive pulses separated by pauses in order to prevent thermal build-up and damage.

2. MP3 therapy is a non-destructive, repeatable, non-invasive procedure, with a high safety profile.

3. A mean IOP decrease of 33,4% was registered 1 month postoperatively. Patient comfort and recovery were favorable. There was less inflammation, no bleeding and no infection risk associated with the procedure.

4. Further studies and results will prove its long-term efficacy in the future.

Fig. 5 IRIDEX MP3 procedure


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References 1. Radcliffe NM. Redefining cyclophotocoagulation with

modified LASER delivery. Ophthalmology Times Europe. 2016 Mar; 12(1):34-6.

2. Noecker RJ. Micropulse P3 Glaucoma Device Revolutionizes Cyclophotocoagulation. Insert to Glaucoma Today. 2015 Mar/ Apr; 13(2):1-2.

3. Radcliffe N. Revolutionize treatment to simple and complex glaucoma cases with the new Micropulse P3 Procedure. Insert to Glaucoma Today. 2015 Jul/ Aug; 13(4):1-2.

4. Pelc C. Control IOP without incisions. Ophthalmology Management. 2015 Apr; 19(4):76-82.

5. Rodrigues GB, Abe RY, Zongalli C, Sodre SL, Donini FA, Costa DC et al. Neovascular glaucoma: a review. Int J Retina Vitreous. 2016 Nov; 14;2:26.

6. Aquino MC, Bartan K, WT Tan AM, Song C, Li X, Loon SC et al. Micropulse versus continuous wave transscleral diode cyclophotocoagulation in refractory glaucoma: a randomized exploratory study. Clin Experiment Ophthalmol. 2015; 43(1):1-7.

7. Noecker RJ. TCP gaining traction for glaucoma cases with good vision potential. Special to Ophthalmology Times. 2015 Aug; 40:1-2.


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doi:10.22336/rjo.2017.21

Eyesight quality and Computer Vision Syndrome

Bogdănici Camelia Margareta, Săndulache Diana Elena, Nechita Corina Andreea Surgery II Department, Discipline of Ophthalmology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași, Romania; “Sf. Spiridon” Hospital, Iaşi, Romania Correspondence to: Bogdănici Camelia Margareta, MD, Surgery II Department, Discipline of Ophthalmology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași, 16 Independenţei Street, Code 700115, Iaşi, Romania, Phone: +0232 217 781, E-mail: [email protected] Accepted: February 4th, 2017

Abstract The aim of the study was to analyze the effects that gadgets have on eyesight quality. A prospective observational study was conducted from January to July 2016, on 60 people who were divided into two groups: Group 1 – 30 middle school pupils with a mean age of 11.9 ± 1.86 and Group 2 – 30 patients evaluated in the Ophthalmology Clinic, “Sf. Spiridon” Hospital, Iași, with a mean age of 21.36 ± 7.16 years. The clinical parameters observed were the following: visual acuity (VA), objective refraction, binocular vision (BV), fusional amplitude (FA), Schirmer’s test. A questionnaire was also distributed, which contained 8 questions that highlighted the gadget’s impact on the eyesight. The use of different gadgets, such as computer, laptops, mobile phones or other displays become part of our everyday life and people experience a variety of ocular symptoms or vision problems related to these. Computer Vision Syndrome (CVS) represents a group of visual and extraocular symptoms associated with sustained use of visual display terminals. Headache, blurred vision, and ocular congestion are the most frequent manifestations determined by the long time use of gadgets. Mobile phones and laptops are the most frequently used gadgets. People who use gadgets for a long time have a sustained effort for accommodation. A small amount of refractive errors (especially myopic shift) was objectively recorded by various studies on near work. Dry eye syndrome could also be identified, and an improvement of visual comfort could be observed after the instillation of artificial tears drops. Computer Vision Syndrome is still under-diagnosed, and people should be made aware of the bad effects the prolonged use of gadgets has on eyesight. Keywords: eyesight quality, refractive errors, ocular congestion, gadgets, Computer Vision Syndrome

Introduction

It is estimated that 60 million people were diagnosed with Computer Vision Syndrome (CVS) [1]. CVS represents a group of visual (Fig. 1) and extraocular symptoms associated with the sustained use of visual display terminals [2].

Fig. 1 Ocular symptoms


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These symptoms are [2]: visual symptoms, ocular symptoms, asthenopia, light sensitivity, musculoskeletal and general symptoms (Fig. 2). The visual symptoms are related to blurred vision: constant blurred vision, post work distance blur and intermittent blurred vision at near. Ocular surface related symptoms are itching eyes, burning eyes, foreign body sensation and sore eyes. Patients who work in front of a VDT for more than 4 hours per day can develop dry eye disease. Ocular complaints can also be related with the dysfunction of meibomian glands [3]. Some patients complain of excessive tears and excessive blinking [4].

The prevalence of asthenopia among the gadgets users is estimated between 55% and 81%. Prolonged use of gadgets can cause removal of the near point of convergence, deviation of phoria for near vision and inaccurate accommodative response [2]. These modifications are only temporary and do not have a permanent effect on accommodation [5]. Some of the musculoskeletal symptoms are represented by neck pain, back pain and shoulder pain, which are frequently related to the use of computers [2]. CVS can also generate general symptoms that are not directly linked with eyes and occur towards the end of the day like irritability, increased nervousness, general fatigue, drowsiness. CVS is temporary and it is heightened by inadequate lighting condition [4]. Children use computers more and more for both school and recreation purposes and start to develop early symptoms similar to adults. They also develop musculoskeletal symptoms because computer stations are mostly designed for adult use and may not be suitable for children [2]. Many of the symptoms in CVS can be prevented with proper eye care, patient education and by providing a proper working environment [6].

Material and methods

The study was a prospective observational one, conducted from January to July 2016, on 60

people, who were divided into two groups: Group 1 (screening), consisting of 30 middle school students from “Dimitrie A. Sturdza” School, Iași, and a second group (Group 2), of 30 patients from “Sf. Spiridon” Ophthalmology Clinic Hospital, Iași. Selected patients from Group 1 had a mean age of 11.9 ± 1.86 years (limits 8-15 years), and from Group 2, the mean age was 21.36 ± 7.16 years (limits 8-43 years). Students in Group 1 were all from urban areas and the majority of the patients in Group 2 (53%) were from rural areas. A questionnaire was used to collect data regarding the gadget’s impact on eyesight. We were particularly interested in the types of display used, the amount of time spent in front of the device per day and the symptoms felt by the patients. The following investigations were made in all the selected cases: visual acuity (VA) corresponding with Snellen test, objective refraction (OR), binocular vision (BV), fusional amplitude (FA) and Schirmer’s test. Refraction values were calculated by using spherical equivalent (SEq), which represented the sphere’s value plus half of the cylinder’s value. Data were statistically analyzed by using Student’s t-test (statistically significant at p ≤ 0.05).

Results

In Group 1, the mean visual acuity (VA) of the right eye (RE) without correction was 0.91 ± 0.42 (limits between 0.16 and 1.5). For the left eye (LE), the mean VA without correction was 0.89 ± 0.44 (limits between 0.16 and 1.5). The mean VA with correction for the RE was 1.08 ± 0.20 (limits between 0.8 and 1.5) and for the LE 1.08 ± 0.22 (limits between 0.6 and 1.5). In Group 2, the mean VA without correction for the RE was 0.93 ± 0.29 (limits between 0.1 and 1.6) and for the LE was 0.88 ± 0.31 (limits between 0.05 and 1.6). VA with correction for the RE was 1.01 ± 0.13 (limits between 0.7 and 1.2) and for the LE was 0.97 ± 0.3 (limits between 0.1 and 1.5). P values were not statistically significant (Table 1).

Fig. 2 CVS symptoms



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Table 1. Comparative values of visual acuity (without and with correction) Without correction With correction

Group 1 Group 2 Group 1 Group 2

Average VA - RE 0.91±0.42 0.93±0.29 1.08±0.20 1.01±0.13 P value Group 1 vs. Group 2 (RE)

0.813 0.380

Average VA - LE 0.89±0.44 0.88±0.31 1.08±0.22 0.97±0.3 P value Group 1 vs. Group 2 (LE)

0.935 0.337

By analyzing the VA, it was found that there

were more patients with amblyopia in Group 1 than in Group 2. The following classification was used for amblyopia: relative amblyopia – VA between 0.8 and 0.9, easy amblyopia – VA between 0.5 and 0.8, medium amblyopia – VA between 0.3 and 0.5, serious amblyopia – VA between 0.1 and 0.3 and severe amblyopia - VA less than 0.1.

In Group 1, 16.66% had relative amblyopia and 6.66% medium amblyopia in the RE, and 10% had relative amblyopia, 10% easy amblyopia and 3.33% medium amblyopia in the LE. In Group 2, 6.66% had relative amblyopia and 3.33% easy amblyopia in the RE, and 6.66% had relative amblyopia and 3.33% severe amblyopia in the LE. The present study was also used as screening for diagnosing amblyopia.

Regarding the optical correction, more than 60% in both groups had an optical correction (60% in Group 1 and 67% in Group 2). In Group 1, the refractive errors (in SEq) for the RE had a mean value of 0.675 ± 0.921 D and for the LE 0.837 ± 1.075 D. In Group 2, the mean value for the RE was 0.983 ± 1.245 D and for the LE was 1.131 ± 1.287 D (Fig. 3a,b).

In both groups, the main type of ametropia was astigmatism (66.6% in Group 1 and 68.3% in Group 2). In 26.7%, myopic astigmatism was found for the LE in Group 1, and in 33.3% in Group 2. Other types of ametropia found were myopia (5% in Group 1 and 11.6 % in Group 2), hyperopia (13.3% in both groups), and anisometropia (15% in Group 1 and 6.6% in Group 2). Anisometropia could be a cause for amblyopia, which could explain the higher number of patients with amblyopia in Group 1 compared to Group 2, as it was previously seen.

All the patients in both groups had binocular vision with all three stages except for one patient in Group 1, who only had first stage of binocular vision (Fig. 4). Fusional amplitude (FA) had values under 25º for all the patients in both groups. When the value of FA dropped under 30º, patients could complain of accommodative asthenopia symptoms such as eye pain, blurry vision, frontal headache (p = 0.216 was not statistically significant).

Fig. 3a Refractive errors - Group 1 (SEq)

Fig. 3b Refractive errors - Group 2 (SEq)


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Among subjective ocular signs, blurred

vision prevailed in both groups, with a statistically significant difference (p = 0.0039). Other subjective ocular signs present were burning sensation, diplopia, and foreign body sensation.

In Group 2, 63.33% of the patients had headache, while in Group 1, 30% (p = 0.007 - statistically significant). Ocular congestion was present in 26.66% of the patients in Group 1 and 20% in Group 2. Also, in 30% of the cases, both groups presented excessive blinking. Dry eye syndrome was identified in 10% of the subjects in Group 1 and in 16% of those in Group 2 (Fig. 5 a,b).

Mobile phones, TV, and laptops are the

most frequently used gadgets (Fig. 6). The average time spent in front of a device per day was 2.56 h in Group 1, and 3.3 h in Group 2. In Group 2, 50% of the patients affirmed that they spend more than 4 h per day in front of a device (p = 0.004 - statistically significant).

Discussions

Computers are part of modern life, but many people are experiencing a variety of ocular symptoms related to computer use, such as eyestrain, tired eyes, irritation, redness, blurred vision, and double vision [5]. More and more people are now using different types of gadgets, especially smart phones. With the unprecedented growth of users of handheld devices, it is estimated that almost 84% of the

Fig. 4 Distribution of cases according to FA

Fig. 5a Subjective ocular signs – Group 1

Fig. 5b Subjective ocular signs – Group 2

Fig. 6 Distribution of cases according to the type of gadgets used



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world’s population will use these by the end of 2018 [2]. In our study, mobile phones, TV, and laptops were the most frequently used gadgets by our patients. The average time spent in front of a device per day was between 2.6 and 4 h.

Using gadgets for a long time can produce ocular asthenopia. In fact, visual complaints were reported by 75% of the users who work 6–9 hours in front of a screen compared to 50% of the other workers. A small, transient myopic shift seems to occur after computer use, but its significance with respect to creating permanent myopic change is unknown [7]. In this study, among subjective ocular signs, blurred vision prevailed in both groups, with a statistically significant difference (p = 0.0039). Other subjective ocular signs present were burning sensation, diplopia, and foreign body sensation.

In our study, myopic astigmatism for LE was found in 26.7% of the cases in Group 1, and in 33.3% in Group 2. Other types of ametropia found were myopia (5% in Group 1 and 11.6 % in Group 2). It is reported that during a prolonged deskwork on a computer or other gadgets, sustained effort for accommodation is required. A small amount of myopic shift has been objectively recorded by various studies on near work induced transient myopia, which produces ocular fatigue [2,8].

In this techno-age, children as young as two years old are given touch screen devices like iPads to play with and learn [9]. The mean age in our selected group was 11.9 ± 1.86 years (limits 8-15 years). It is important to control the lacrimal film and how the patient blinks, because dry eye is intimately related to CVS as either cause or effect [10].

The major strength of this study was that it was the first prospective observational study performed in Romania that analyzed the effects that gadgets have on eyesight quality. This study was limited by the small sample size, and the fact that it did not include a follow up examination of the patients.

Conclusions

Myopic astigmatism and myopia were the main types of ametropia in both study groups. The fusional amplitude was one of the main indicators necessary for the study. Following the

use of gadgets, the subjective signs that stood out were blurred vision, headache, and ocular congestion. Mobile phones and laptops were the most frequently used gadgets with an average usage of 1 to 4 hours per day. Computer Vision Syndrome is still under-diagnosed, and people should be made aware of the bad effects the prolonged use of gadgets has on eyesight.

References

1. Ranasinghe P, Wathurapatha WS, Perera YS, Lamabadusuriya DA, Kulatunga S, Jayawardana N et al. Computer vision syndrome among computer office workers in a developing country: an evaluation of prevalence and risk factors. BMC Research Notes. 2016; 9:150.

2. Parihar JKS, Jain VK, Chaturvedi P, Kaushik J, Jain G, Parihar KS. Computer and visual display terminals (VDT) vision syndrome (CVDTS). Medical Journal Armed Forces India. 2016; 72(3):270–276.

3. Wu H, Wang Y, Dong N, Yang F, Lin Z, Shang X el al. Meibomian Gland Dysfunction Determines the Severity of the Dry Eye Conditions in Visual Display Terminal Workers. Plos One. 2014; 9(8):e105575.

4. Bhootra AK. Computer Vision Syndrome. In: Basics of Computer Vision Syndrome. 2014, New Delhi, Jaypee Brothers Medical Publishers, 11-18.

5. Blehm C, Vishnu S, Khattak A, Mitra S, Yee RW. Computer vision syndrome: review. Survey of Ophthalmology. 2005; 50(3):253–262.

6. Loh K, Reed S. Understanding and Preventing Computer Vision Syndrome. Malays Fam Physician. 2008; 3(3):128–130.

7. Mutti D, Zadnik K. Is computer use a risk factor for myopia?. J Am Optom Assoc. 1996; 67:521–530.

8. Vasudevan B, Ciuffreda KJ. Additivity of near work-induced transient myopia and its decay characteristics in different refractive groups. Invest Ophthalmol Vis Sci. 2008; 2:836–841.

9. Barthakur R. Internet Journal of Medical Update. 2013; 8(2):1-2.

10. Uchino M, Schaumberg DA, Dogru M et al. Prevalence of dry eye disease among Japanese visual display terminal users. Ophthalmology. 2008; 115(11):1982-1988.


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Plateau Iris – Therapeutic options and functional results after treatment

Feraru Crenguța* **, Bâlha Andrei**, Aursulesei Victor**, Filip Andrei**, Pantalon Anca*

*“Gr. T. Popa” University of Medicine and Pharmacy, Iași, Romania **Department of Ophthalmology, “Sf. Spiridon” University Hospital, Iași, Romania Correspondence to: Pantalon Anca, MD, PhD, Department of Ophthalmology, “Sf. Spiridon” University Hospital, Iaşi, 1 Independenței Square, Code 700115, Iaşi, Romania, Mobile phone: +40740 686 865, E-mail: [email protected] Accepted: May 25th, 2017

Abstract We present the therapeutic options and functional results in patients with plateau iris (syndrome or configuration) in consecutive case series. Material and method: Our study included newly diagnosed patients with acute angle closure by “plateau iris” (configuration or syndrome), between June 2016 and April 2017. Series of 8 consecutive patients met the inclusion criteria, all being females. All the patients underwent an individualized treatment according to the underlying mechanism and evolution. Functional results (visual acuity, IOP, topical medication) were reported in the current paper. Results: For 10 months, we diagnosed 14 eyes, from 9 patients with acute angle closure by Plateau Iris, distributed as it follows: 6 eyes with closed angle glaucoma (optic disk and visual field changes), 8 eyes with plateau iris syndrome and 2 eyes with plateau iris configuration. 7/ 8 patients were misdiagnosed with primary open angle glaucoma, whereas only one patient had the correct diagnosis of closed angle glaucoma and underwent peripheral laser iridotomy. As treatment options in our study, we recommended and performed argon laser peripheral iridoplasty + iridotomy in 10/ 14 eyes, cataract lens was extracted in 4 eyes and then replaced with PC-IOL, whereas 2 eyes required a filtering anti-glaucoma surgery (trabeculectomy + PI). 2 eyes from the same patient could not be treated as intended as the patient refused the treatment. In this unique case, Pilocarpine (4%) was temporarily indicated. Conclusion: Plateau iris represents a diagnostic trap, but based on a thorough gonioscopic examination and a good patient history, the right diagnosis can be made, all along with a correct therapeutic approach. Keywords: plateau iris, therapy options

Introduction

Plateau Iris syndrome is a relatively uncommon form of primary angle closure glaucoma that is seen more often than pupillary block angle in younger adults (3rd or 4th decade) [1]. Plateau Iris syndrome is defined as a

persistently narrow angle capable of closure in spite of a patent iridotomy. Plateau Iris is an ocular condition that requires appropriate diagnosis and treatment in order to prevent vision loss. The early recognition and intervention are key components to a good overall prognosis in this patient population [2].



© 2017

Patients may develop angle closure, either spontaneously or after pupillary dilation [3], but more commonly, patients are asymptomatic and the diagnosis is made on a thorough gonioscopic examination. Additionally, AS-OCT and UBM enhance the diagnosis in plateau iris syndrome/ configuration.

Depending of the status of the complications or at the moment of diagnosis, treatment in such patients might differ from case to case. As such, the options are summarized in Fig. 1.

The primary treatment modality for patients with Plateau Iris configuration is surgical [3]. However, many clinicians will first treat with miotic agents such as pilocarpine to prevent pupillary dilation from leading to surgery. A low dose or dilute pilocarpine can produce the thinning of the iris and facilitate the opening of the angle by pulling the iris away from the trabecular meshwork.

The surgical management is the primary treatment modality in patients with Plateau Iris configuration or syndrome. A patent iridotomy may be therapeutic in reducing risks of angle closure. However, in some patients, laser iridotomy may not significantly alter the anterior chamber depth or anatomy. Even after a successful iridotomy produces what appears to be a well-opened angle, periodic gonioscopy remains crucial because these patients may have incomplete Plateau iris syndrome or the angle may narrow further with age because of the enlargement of the lens.

Argon laser peripheral iridoplasty (ALPI) is the method of choice to effectively open an angle

that remains occluded after successful laser iridotomy. It is highly effective, and the effect is maintained for years [4]. Yet, even after a successful opening of the angle, regular gonioscopy is mandatory.

Aim of study

The therapeutic options and functional results in patients with “plateau iris” (syndrome or configuration) in consecutive case series.

Material and method

Our study included newly diagnosed patients with acute angle closure by “plateau iris” (configuration or syndrome), between June 2016 and April 2017. All the patients were females, with a mean age of 52.8 +/ - 2.91 years (range between 29–71 years old). The mean decimal visual acuity –BCVA - was 0.81 +/ - 0.19 (range = 0.03–1), 7 were diagnosed with hyperopia and 2 with emmetropia.

The previous diagnosis in 5 cases was open angle glaucoma/ juvenile glaucoma, 1 patient being misdiagnosed with recurrent uveitis. Documented closed angle glaucoma was met in one patient, whereas in another one symptoms of intermittent angle closure were noticed.

Baseline mean IOP was 23.8 +/ - 2.45 mmHg, range (12-40 mmHg). Related to topical medication, 39% (7 eyes) had 1 medication, 17% (3 eyes) had 2 topical substances, 11% (2 eyes) were under 3 IOP lowering medications. There was no need for the IOP to be controlled by any topical substance in 6 eyes (33%).

In 56% of the cases, the diagnosis was Plateau Iris syndrome, in 33% it was Plateau Iris configuration, and 11% were already in the closed angle glaucoma state based on an initial plateau iris configuration.

Papillo-perimetric changes were found in 6 eyes, whereas in 7 cases, disk and structural changes were detected. No changes were detected in 6 eyes. The distribution of cases was as it follows (Fig. 3). The final IOP was 15.1 mmHg; in 2 eyes from the same patient, the IOP was not sufficiently controlled and reached levels > 21 mmHg under Pilocarpine (4%), as the patient did not agree with the surgical intervention and preferred this more “non-invasive” type of treatment. After treatment (laser, surgical – trabeculectomy, cataract

Fig. 1 Therapeutic options in plateau iris


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extraction, miotics administration), the medication changed as shown in Fig. 2. The various options in therapy and their distribution in the study group are depicted in Fig. 3.

Clinical case

For an eloquent clinical example, this study presented the case of a 63-year-old female

patient (doctor), complaining about bilateral red, irritated eyes, foreign body sensation, and itching. She had been diagnosed with primary open angle glaucoma for 15 years and had undergone topical IOP lowering treatment with PGA (Travatan®) for a while. Since the inefficacy of this treatment was clear, the treatment regimen was changed to a fixed combination (beta-blocker and carbonic anhydrase inhibitor – Cosopt® in the OD and the same medication plus alpha agonist Brimonidine (Brimonal®) in the OS.

The atypical treatment regimen was emphasized in this patient, as a POAG rarely does not respond to a PGA, and the information regarding the family history was also recollected, as the father of this patient had also been diagnosed with glaucoma at a certain point in his life and followed the treatment. A more thorough anamnesis was restarted and it was found out that the patient had been suffering from Basedow ophthalmopathy and had underwent subtotal thyroidectomy at 30 years old. No exophthalmia was visible, but only an upper lid retraction syndrome. A mild binocular diplopia episode developed when the patient was 48 years old. The substitution hormonal therapy medication was ceased for 2 years. Indeed, the father of this patient had a closed angle glaucoma and he underwent laser treatment in one eye and peripheral iridotomy and trabeculectomy in the other. At the last presentation, the anterior segment showed a conjunctival congestion in both eyes, more visible in the RE, altogether with a marked follicular inflammatory reaction (Fig. 4-6).

Fig. 2 Medication changes after treatment in the current study

Fig. 3 Treatment options in the study group

Fig. 4 OD - Marked conjunctival congestion



© 2017

IOP in the OD was at that moment 26 mmHg (Cosopt® + Brimonal®) and 19 mmHg in the OS under Cosopt®. Fundus examination can be visualized in Fig. 7, 8.

The visual field examination (HFA II, c24-2, Sita Fast, Zeiss®) showed no functional defect (Fig. 9a,b) and the OCT (Triton 3000®, Nidek) exam in the OD pointed out the sector RNFL thinning in the superior disk quadrant (Fig. 10).

Fig. 5 OD - Congestion and inflammatory changes – follicles in the tarsal conjunctiva

Fig. 6 OD - Mild conjunctival congestion

Fig. 7 OD Fundus examination. C/ D ratio = 0.5. superior nothing visible

Fig. 8 OS Fundus examination. C/ D ratio = 0.4.

Fig. 9a Normal VF in the OD


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Gonioscopy revealed an iris with a steep insertion before flattening centrally (iris drapes over the ciliary body producing the double “hump” aspect on indentation) (Fig. 11).

In this context, the diagnosis of bilateral “plateau iris” was established and the patient was indicated laser treatment (peripheral argon laser iridoplasty and peripheral iridotomy). After laser treatment was applied, the postoperative evolution was favorable. In the next 7-10 days after Brimonal cessation in the RE, the follicular inflammatory reaction diminished completely. At 6 months, the IOP was 16 mmHg (under topical Cosopt®) and gonioscopy confirmed an open angle bilaterally. This patient was monitored at each 3 months for the IOP, and at each 6 months, she underwent a complete examination, including perimetry, OCT scan, and gonioscopy. As a general advice in her situation, the patient was advised to avoid dim light activities.

Discussions

Patients with plateau iris tend to be hyperopic, female, and younger than 50 years. In a US-based chart review of the patients under the age of 60, Stieger et al. found the prevalence of plateau iris with recurrent angle-closure symptoms to be 54%, despite the initial iridotomy or iridectomy [5]. In a study from Singapore, Kumar et al. [6] used ultrasound biomicroscopy (UBM) to show that

Fig. 9b Normal VF in the OS

Fig. 10 OCT examination

Fig. 11 Double hump aspect in indentation gonioscopy in the LE



© 2017

approximately one-third of the patients over the age of 50 with primary angle closure had a plateau iris after laser iridotomy. There is also evidence to suggest that this anatomical predisposition may be familial, with an autosomal dominant inheritance pattern [7].

If recognized, the prognosis for patients with plateau iris (syndrome/ configuration) is generally good, if the condition is treated before vision loss occurs. Regular follow up with serial gonioscopy ensures that the proper interventions and treatment modalities are initiated when necessary because angle-closure may develop years after successful iridotomy or iridoplasty. Routine screening for the development of glaucoma should also be performed.

To obtain this, we highly recommend a thorough history of the patient and a high degree of suspicion from the clinician, when conventional medications for glaucoma (PGA in our case) do not work as expected (“plateau iris” configuration/ syndrome vs. true POAG) or when a high discrepancy between structural/ functional damage and the IOP level is met in a glaucoma suspect. Gonioscopy should be mandatory in any glaucoma case we examine and a discrepancy of the AC depth central vs. periphery should alert the clinician regarding certain lines to follow in the diagnosis.

Commonly reported side effects of brimonidine ophthalmic include blurred vision, burning sensation of eyes, drowsiness, eye pruritus, follicular conjunctivitis, headache, local ocular hypersensitivity reaction, ocular hyperemia, stinging of eyes, foreign body sensation, and xerostomia [8]. Therefore, the clinician should be aware of them and act accordingly to the patients’ local tolerance and to the best IOP control.

In conclusion, plateau iris is under diagnosed and it is not that uncommon as previously thought. A careful anamnesis, clinical data and the correct interpretation, gonioscopy and adjunctive imaging technology should be taken into account for each patient with this underlying condition. Based on gonioscopic aspects (closed angle by apposition or by contact, iris insertion and aspect) and the degree of structural and functional deficit, therapeutic options must be individualized for each case.

References

1. Kiuchi Y, Kanamoto T, Nakamura T. Double hump sign in indentation gonioscopy is correlated with presence of Plateau Iris configuration regardless of patent iridotomy. J Glaucoma. 2009; 18(2):161-164.

2. Shukla S, Damji KF, Harasymowycz P, Chialant D, Kent JS, Chevrier R, Buhrmann R, Marshall D, Pan Y, Hodge W. Clinical features distinguishing angle closure from pseudoplateau versus Plateau Iris. Br J Ophthalmol. 2008; 92(3):340-344.

3. http://eyewiki.aao.org/Plateau_Iris. 4. Ritch R, Tham C, Lam D. Long-term success of argon

laser peripheral iridoplasty in the management of PIS. Ophthalmology. 2004; 111:104-8.

5. Stieger R, Kniestedt C, Sutter F et al. Prevalence of Plateau Iris syndrome in young patients with recurrent angle closure. Clin Experiment Ophthalmol. 2007; 35(5):409-413.

6. Kumar RS, Baskaran M, Chew PT et al. Prevalence of Plateau Iris in primary angle closure suspects an ultrasound biomicroscopy study. Ophthalmology. 2008; 115(3):430-434.

7. Etter JR, Affel EL, Rhee DJ. High prevalence of Plateau Iris configuration in family members of patients with Plateau Iris syndrome. J Glaucoma. 2006; 15(5):394-398.

8. https://www.drugs.com/sfx/brimonidine-ophthalmic-side-effects.html.

http://eyewiki.aao.org/Plateau_Iris


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The effect of intravitreal bevacizumab in a rare case of retinal dystrophy with secondary cystoid macular edema

Macovei Mioara-Laura, Nica Maria-Alexandra Ophthalmology Department, “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest, Romania Correspondence to: Nica Maria-Alexandra, MD, Ophthalmology Department, “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest, 134 Plevnei Street, District 1, Bucharest, Romania, Phone: +40745 384 229, E-mail: [email protected] Accepted: April 19th, 2017

Abstract The authors presented a clinical case of retinitis punctate albescens in a 26-year-old female patient, with a family history of typical retinitis pigmentosa (father) and bilateral cystoid macular edema treated with anti-VEGF (bevacizumab). Keywords: Retinitis punctata albescens, anti-VEGF, cystoid macular edema

Introduction

This disorder is often considered to belong to the category of retinal diseases known as flecked retina syndrome. Retinitis punctata albescens (RPA) is a rare form of non-syndromic, generally referred to as a subtype of autosomal recessive retinitis pigmentosa with specific characteristics.

RPA is an inherited retinal dystrophy characterized by progressive night blindness and presence of small white dots on the retina. Furthermore, the scotopic ERG waveforms usually do not regenerate. RPA prevalence is currently estimated at 1/800 000 people [1,3].

Material and methods – Case report

A 26-year-old female accidentally presented in our clinic, along with her father, previously known with typical retinitis pigmentosa, who was scheduled for cataract surgery. Having established the diagnosis, an ophthalmological exam was suggested for the daughter. The patient history revealed that she had been suffering from night blindness ever

since and decreased vision for a few months. However, she had never addressed an ophthalmologist.

At presentation, her best-corrected visual acuity was RE: 0.6 nc, LE: 0.4 nc. The IOP was normal in both eyes BE IOP: 13 mmHg on non-contact tonometry.

Slit-lamp examination of the anterior segment revealed no abnormal findings. In order to examine the posterior segment (Fig. 1,2), pharmaceutical mydriasis with 0.5% tropicamide and 1% cyclopentolate ophthalmic solutions was used.

Fig. 1 *Attenuation and narrowing of the retinal vessels,*retinal atrophy, *waxy pallor of the optic disc, *absence of foveal reflex with intraretinal cystic areas



© 2017

The OCT showed an increased retinal thickens with hyporeflective cysts, suggestive for CME. Fluorescein angiography was proposed, but refused by the patient (Fig. 3,4).

The visual fields revealed ring scotoma in both eyes, with a preserved central vision (mild tunnel vision) (Fig. 5,6).

Fig. 2 *Typical small white dot-like spots in the periphery

Fig. 3 *Macular OCT of the right eye

Fig. 4 *Macular OCT of the left eye

Fig. 5 *Visual field of the right eye


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The electroretinogram (ERG) presents dramatic diminution in a- and b- waves’ amplitudes (Fig. 7), first the scotopic system (rods) is affected and then the photopic system (cones). The multifocal electroretinogram (mfERG) (Fig. 8,9) showed significant reductions in response to the amplitudes in the macular areas and a higher but also inappropriately lower response amplitude at the fovea.

The diagnosis of Retinitis Punctate Albescens with Cystoid Macular Edema in both eyes was established based on the family history, clinical findings, and investigations.

Treatment with topical dorzolamide, BE, was started for three times per day, oral acetazolamide 500 mg daily, and aspacardin 100 mg daily. After 3 days, the patient presented with dizziness, paresthesia, and palpitations [2]. The oral treatment was stopped and other therapeutic options were discussed: intravitreal Triamcinolone acetonide, although studies revealed insignificant effects [4,6], and intravitreal anti-VEGF agents, with recent studies demonstrating an effect in lowering fluid accumulation [5].

Bevacizumab 1,25mg/ 0,05 ml was injected in both eyes, one week apart.

2 weeks later, at the first follow-up, the BCVA was RE: 1, LE: 0.8 nc. The OCT revealed a

Fig. 6 *Visual field of the left eye

Fig. 7 *Scotopic and photopic electroretinogram

Fig. 8 *Multifocal electroretinogram of the right eye

Fig. 9 *Multifocal electroretinogram of the left eye



© 2017

central retinal thickness of RE: 281 µm (Fig. 10), LE: 294 µm (Fig. 11), a significant decrease, from about 400 and 450 µm previously. She was followed-up monthly for the next 6 months, presenting a stable evolution. She is expected for further examinations at every 6 months or if a loss in visual acuity is experienced.

Discussion

• RPA is a rod-cone dystrophy, a subtype of RP; so far, there has been no available treatment; however, the correct diagnosis provides the basis for counseling school or career choices;

• Genetic testing provides important information for prognosis, as well as risk assessment to family members. The National Eye Institute (NEI) is currently creating the eyeGENE Network, which aids in the recruitment of patients interested in participating in future clinical trials related to genetic eye diseases.

• On long term, we expect the narrowing of visual fields, photophobia, decrease in central vision leading to irreversible blindness.

• The particularity of this case is that the patient presented accidentally in our clinic, without having had a previous ophthalmologic exam, although having had night blindness and a family history of typical RP; macular involvement is frequent, usually as progressive macular atrophy, rarely with CME;

• Usually, oral and topical carbonic anhydrase inhibitors deliver good results in RPA with secondary CME; however, due to unpleasant side effects, intravitreal Bevacizumab was administered, with favorable results on short and medium term.

Fig. 10 *Macular OCT of the right eye

Fig. 11 *Macular OCT of the left eye


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Financial Disclosures The authors have no financial interests to

disclose.

References

1. Dessalces E, Bocquet B, Bourien J, Zanlonghi X, Verdet R, Meunier I, Hamel CP. Early-Onset Foveal Involvement in Retinitis Punctata Albescens With Mutations in RLBP1. JAMA Ophthalmol. 2013; 131(10):1314-1323. doi:10.1001/jamaophthalmol.2013.4476.

2. Sandeep G et al. Topical Dorzolamide for the Treatment of Cystoid Macular Edema in Patients With Retinitis Pigmentosa. American Journal of Ophthalmology. 141(5), 850-858.

3. Katajakunnas M, Mäntyjärvi M. Retinitis punctata albescens. Acta Ophthalmologica. 1989; 67:703–709. doi:10.1111/j.1755-3768.1989.tb04405.x.

4. Scorolli LM, Meduri A, Morara M, Trombetta JC, Scalinci SZ, Ferreri G, Meduri RA. Treatment of Cystoid Macular Edema in Retinitis Pigmentosa With Intravitreal Triamcinolone Acetonide. Invest. Ophthalmol. Vis. Sci. 2005; 46(13):522.

5. Qazi HA. Protocol: Effect of intravitreal bevacizumab (avastin) in the treatment of macular edema: A systematic review of randomized controlled trials. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2012; 17(12):1180-1187.

6. Scorolli L, Morara M, Meduri A, Reggiani LB, Ferreri G, Scalinci SZ, Meduri RA. Treatment of Cystoid Macular Edema in Retinitis Pigmentosa With Intravitreal Triamcinolone. Arch Ophthalmol. 2007; 125(6):759-764. doi:10.1001/archopht.125.6.759.


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doi:10.22336/rjo.2017.24

Penetrating keratoplasty: from aid dependence to independence

Macovei Mioara-Laura, Nica Maria-Alexandra Ophthalmology Department, “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest, Romania Correspondence to: Nica Maria-Alexandra, MD, Ophthalmology Department, “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest, 134 Plevnei Street, District 1, Bucharest, Romania, Phone: +40745 384 229, E-mail: [email protected] Accepted: May 5th, 2017

Abstract The authors present five cases of bilateral corneal disorders, on which they performed penetrating keratoplasty. All five patients were clinically blind and after the surgery on one eye, they gained their visual independence. Visual acuity, intraocular pressure, fundus examination, and ultrasonography were used to evaluate the patients before and after the surgery. Keywords: penetrating keratoplasty, corneal dystrophy, bullous keratopathy

Introduction

The idea of restoring clarity to an opaque cornea has existed for far longer than the means to achieve it have been available. In 1905, Zirm performed the first successful human penetrating keratoplasty (PK) and thus the first successful human organ allograft [1].

Corneal blindness is the 4th cause of blindness globally [2]. Studies showed that visual loss is considered to have the strongest impact on the quality of life and it was included in the “worst thing that could happen” category [3]. Corneal transplantation has the best rate of survival and is the oldest and most frequent type of transplantation performed on humans [4]. Penetrating keratoplasty (PK) is a technique that allows the replacement of the central affected cornea with a healthy corneal graft from a donor. Nowadays, the advances in diagnosing certain disorders, the conservative surgical approach

and changes in surgical practice, have influenced the indication for PK, which have been in a continuous change since 1940.

Material and methods - Clinical cases

1. A 39-year-old patient diagnosed with BE: Pupillary pseudophakic - Fyodorov. Bullous keratopathy. Myopia. (Fig. 1,2). On clinical examination VA RE = HM (Fig. 1), VA LE = HM (Fig. 2), IOP BE - normal intraocular pressure (digital palpation) and A, B mode on ultrasonography: axial myopia, no other pathological changes. PK was performed on the RE, and, after 7 months, BCVA RE = 0,3 (Fig. 3).


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2. A 86-year-old patient diagnosed with BE: Corneal dystrophy. Senile cataract. On clinical examination VA RE = HM (Fig. 3), VA LE = HM (Fig. 4), IOP BE - normal intraocular pressure (digital palpation) and A, B mode on ultrasonography: no pathological changes. After PK on the LE, BCVA LE = 0,3 (Fig. 5). Four months later, after PK, she presented with band keratopathy on the LE (Fig. 6) and her visual acuity decreased again to hand movement. We performed an excision of the superficial deposits, superficial lamellar keratectomy and finally we applied a thin layer of amniotic membrane. She came for her monthly check-up and her uncorrected vision was restored to 0.25 (Fig. 7).

Fig. 1 RE Bullous keratopathy

Fig. 2 LE Bullous keratopathy preoperative

Fig. 3 RE 7 months after PK and RE Corneal dystrophy

Fig. 4 LE preoperative



© 2017

3. A 72-year-old patient RE: history of penetrating trauma (phthisis bulbi). Lipid keratopathy. LE: pseudophakic eye (scleral-sutured IOL). Bullous keratopathy. Paracentral leukoma. Secondary glaucoma. On clinical examination VA RE = NLP (Fig. 8), VA LE = HM (Fig. 9), IOP LE - normal intraocular pressure (digital palpation), IOP RE - hypotonic globe and A, B mode on ultrasonography LE: no pathological changes, RE - disorganized globe. Four months after PK, her BCVA LE = 0.4 (Fig. 10).

Fig. 5 LE after PK

Fig. 6 Band keratopathy 4 months after PK

Fig. 7 LE 5 months after PK

Fig. 8 RE Phthisis bulbi

Fig. 9 LE Bullous keratopathy


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4. Clinical case: A 37-year-old patient BE: Macular corneal dystrophy. On clinical examination VA LE = 0.1 (Fig. 11), VA RE = 0.08 (Fig. 12), IOP BE - normal intraocular pressure (digital palpation), A, B mode on ultrasonography: no pathological changes. Six months after PK, her BCVA RE - 0,4 (Fig. 13).

5. A 38-year-old patient BE: Macular corneal dystrophy. On clinical examination VA BE = 0.04 (Fig. 14), IOP BE - normal intraocular pressure (digital palpation), A, B mode on ultrasonography: no pathological changes. We performed PK on his left eye and five years after surgery his BCVA LE = 0.5 (Fig. 15).

Fig. 10 LE 4 months after PK

Fig. 11 LE Macular corneal dystrophy

Fig. 12 RE Macular corneal dystrophy

Fig. 13 RE, 6 months after PK

Fig. 14 RE Corneal

dystrophy



© 2017

Conclusions

The purpose of PK in advanced and bilateral corneal disorders is determinant; this technique offers patients the ability to become independent of the family and society and physical, emotional, social, and economic rehabilitation, thus improving the quality of life. In Romania and in some other countries the only limitation in performing PK is the lack of corneal donors.

Financial Disclosures

The authors have no financial interests to disclose.

References

1. Zuberbuhler B, Tuft S, Gartry D, Spokes D. Corneal surgery essentials techniques. 2013.

2. http://www.who.int/blindness/causes/priority/en/index8.html

3. http://www.arvo.org/AEVRsurvey 4. Hjortdal J. Corneal transplantation. 2016, Springer.

Fig. 15 LE 1 year after PK


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Orbital cellulitis and brain abscess – rare complications of maxillo-spheno-ethmoidal rhinosinusitis

Constantin Farah*, Niculescu Patricia-Alexandra*, Petre Oana*, Balasa Daniel**, Tunas Alexandru**, Rusu Ioana**, Lupascu Mihai***, Orodel Cristiana*** *Department of Ophthalmology, Clinical Emergency County Hospital, Constanta, Romania ** Department of Neurosurgery, Clinical Emergency County Hospital, Constanta, Romania ***ENT Department, Clinical Emergency County Hospital, Constanta, Romania Correspondence to: Constantin Farah, MD, PhD, Department of Ophthalmology, Clinical Emergency County Hospital, Constanta, 145 Tomis Boulevard, Code 900591, Constanta, Romania, Mobile phone: +40722 328 657, E-mail: [email protected] Accepted: May 8th, 2017

Abstract Sinus infections can be complicated by ocular infections and, in late phases, by brain parenchyma infection. The article debates the case of a 12-year-old patient suffering from paucisymptomatic maxillo-spheno-ethmoidal rhinosinusitis, which was later complicated by orbital cellulitis, ending with the development of a brain abscess. The treatment is complex, initially targeting the source of the infection through draining the collection by middle maxillary antrostomy and anterior posterior ethmoidectomy, then the ablation of the brain abscess and postoperatively with prolonged massive antibiotherapy. Keywords: orbital cellulitis, rhinosinusitis, brain abscess, E. Coli Abbreviation: URI = upper respiratory infection, CT = computer tomography, MRI = magnetic resonance imaging, BA = brain abscess, VAS = visual scale of pain, ENT = ear, nose, throat, RE VA = right eye visual acuity, RE = right eye, CSF = cerebrospinal fluid

Introduction

Rhinosinusitis is becoming an increasingly common diagnosis in children and can be a frustrating problem. More young children are attending day care centers, increasing the transmission of URIs. Environmental pollutants and allergens predispose children to rhinosinusitis [1].

Normal paranasal physiology requires patency of the ostia, normal mucociliary clearance, and normal secretions. When any one of these changes appears, ostial obstruction, retention of secretions and infection can occur [1].

Adenoid hyperplasia and infections may predispose a child to rhinosinusitis. Large or infected adenoids may produce nasal obstruction and symptoms of rhinosinusitis. The adenoids may serve as a reservoir for pathogenic bacteria [1].

The incidence of complications from pediatric rhinosinusitis is greater than in adults [1].

According to Sarafoleanu Codrut, among the contiguity complications of sinusitis, the orbital cellulitis and the brain abscess can be frequently found located in the frontal lobe [2].

According to M. Yanoff & J. S. Duker, the orbit and the adnexa of the eye are important locations for primary and secondary pathologies



© 2017

because various types of tissue, such as vascular, bone, nervous, muscle and glandular are present at that level. The tumors and inflammations can secondarily invade the orbit from periorbital regions, such as the paranasal sinuses, the eyelids, and the intracranial compartments [3].

Orbital cellulitis is an acute serous and diffuse inflammation of the cellular-adipose tissue of the orbit. The cause can be exogenous (posttraumatic) or through propagation of a nearby inflammatory process [4].

Orbital complications are the most common problem associated with rhinosinusitis and have the highest incidence in children [1]. The source of infections of the orbit is usually the ethmoid sinuses, but may also be the frontal and maxillary sinuses. The routes of spread are direct, hematogenous, by arterial or venous thrombophlebitis, and lymphatic. The medial orbital wall is an ineffective barrier against the spread of infection because it has natural dehiscences, suture lines, and thin bone [1 ].

The most common bacteria are Staphylococcus and Streptococcus in adults, and in children, Haemophilus Influenzae. E. Coli and Pseudomonas are the rarest [3].

Brain abscess is defined as a focal intracranial infection that is initiated as an area of cerebritis and evolves into a collection of pus surrounded by a vascularized capsule. Given their location, the approach to brain abscesses often presents diagnostic and therapeutic challenges [5].

Brain abscess may arise from hematogenous spread, contiguous spread, or direct trauma [6].

The clinical manifestations of brain abscess may run the gamut from indolent to fulminant; most are related to the size and location of the space-occupying lesion within the brain and the virulence of the infecting organism [5].

The classic triad of fever, headache, and focal deficit is present in less than 50%. Headache, usually dull and poorly localized is present in more than 70% of the cases, and is so nonspecific as to be a potential cause of diagnostic delays [7].

Case report

A 12-year-old patient presented herself in the Department of Ophthalmology for a pronounced inflammatory eyelid edema on the right eye, frontal and occipital moderate headache, without exophthalmia, without fever.

Ophthalmological examination in internment: RE eyelid inflammatory marked edema with sudden onset, closed eyelid slot, local induration, local pain and calor, VAS 4/ 10, especially on palpation, RE VA = 1. The ENT examination at internment: normal. Neurological examination in internment: normal.

Imaging tests (brain CT and brain MRI) highlight right frontal lobe abscess (Fig. 2 – yellow arrow), medial orbital wall osteitis – right orbit (Fig. 1 – blue arrow, Fig. 2 – blue arrow), maxillary sinusitis, right ethmoidal and sphenoidal sinusitis (Fig. 1 – red arrow, Fig. 2 – red arrow).

Fig. 1 Preoperative Head CT-Scan (blue arrow – orbital cellulitis and osteitis, red arrow - sinusitis)

Fig. 2 Preoperative Head MRI (blue arrow - orbital cellulitis, red arrow - sinusitis, yellow arrow - brain abscess)


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The course of treatment was decided while following the results of the imaging tests. This first included the ENT surgical treatment, in order to progressively clear the infection sources, then, secondly, the neurosurgical treatment.

The resection of the inflamed masses at the middle meatus was performed after endoscopically draining the collection through middle maxillary antrostomy, anterior posterior ethmoidectomy. Adenoidectomy was performed on the cavum. Wanted result: dissection of the maxillary and ethmoidal sinuses.

After 24 hours, the neurosurgical intervention was performed: frontal basal craniotomy with the excision of a grey-yellow purulent-granulomatous collection. Bacteriological test: E. Coli.

The revaluation imaging tests (brain CT and brain MRI) highlighted the remission of the intracranial purulent collection (Fig. 3), remission of the inflammatory phenomenon on the right orbit, with the recreation of bone structure on the lateral wall of the right ethmoidal lateral mass and the superior wall of the right orbit (Fig. 4).

Postoperatively, under intensive antibiotic treatment (Vancomycin, Meropenem, Gentamicin, Ceftriaxone, Cortisone, vitamins), clinical evolution in favorable, the patient continued with antibiotherapy in an Infectious Diseases Department until healing, according to the international protocols.

N.B.: After surgery, the antibiotherapy lasted 8 weeks.

Discussion

The probability diagnostic pleaded for preseptal cellulitis, infirmed by the CT test, which highlighted orbit cellulitis in association with maxilla-spheno-ethmoidal rhinosinusitis and brain abscess.

Although symptoms in sinusitis are often associated with fever and purulent nasal discharge, in our case, the patient was paucisymptomatic.

A contiguity infection from the sinus to the intracranial cavity – CSF, has a higher contamination probability. The CSF composition (glucose, proteins, water) and a constant 37oC temperature is an excellent breeding ground for bacteria cultures: 1 ml of CSF contains maximum 5 white elements, compared to 1 ml of blood that has 5.000–10.000 white elements, which means

Fig. 3 Postoperative Head MRI (yellow arrow - BA remission)

Fig. 4 Postoperative Head CT-Scan (blue arrow - orbital cellulitis and osteitis remission; red arrow - sinusitis remission)



© 2017

that bacteria do not have to be extremely virulent to create meningocerebral infections, meaning that less virulent or saprophytes, can develop fast once they reach the levels of CSF. Also, in encapsulated infections, the bacteria resist even more because of the capsule, even when being incompletely formed, which massively decreases antibiotic penetration, which already penetrate the hematoencephalic barrier very slowly.

The enteric gram-negative bacilli (e.g. E. Coli) are isolated in 23-33% of the patients with brain abscess, through fronto-ethmoidal or sphenoidal sinusitis [8].

In a rat model of experimental brain abscess, E. Coli failed to cause infection in the skin, but abscess formation in brain tissue was induced [5].

The case particularity consists in the ophthalmologic debut of a very virulent pathology that had very few symptoms and clinical signs.

Without further investigation, the evolution of this case would have been unfavorable, even bad.

The attention given even to an inflammatory eyelid edema without exophthalmia can prevent the delay of providing an etiological diagnostic.

Conclusions

Surgical treatment (maxillary sinus and ethmoidal dissection and brain abscess excision) represents an important part of the therapeutical strategy of these lesions.

According to the abibiogram, prolonged (8 weeks in this case) antibiotic treatment has offered the possibility of a full healing of both the sinus and cerebral regions and of the orbital osteitis.

The antibiotics used had a maximum penetrability both for CSF and bone tissue levels.

References

1. Levine HL, Pais Clemente M. Sinus Surgery, Endoscopic and Microscopic Approaches. Pediatric Rhinosinusitis. 2005; 121-123,127,128

2. Sarafoleanu C. Rinologia. Urgente Rinosinuzale. 2003. 3. Yanoff M, Duker JS. Ophtalmology. 3rd Edition, 2009,

part 12: Orbit and Oculoplastics, Section 3: Orbit and

lacrimal gland, Orbital diseases (Jonathan J. Delta). 1450.

4. Cernea P. Tratat de oftalmologie. Orbita. Inflamatiile orbitei. 1997; 901-902.

5. Youmans. Neurological Surgery. 6th Ed., ch. 43: Brain Abscess, 2011, 588,592,590

6. Greenberg MS. Handbook of Neurosurgery. 7th Ed., 16.6. Cerebral Abscess, 2010, 350.

7. Shmidek & Sweet. Operative Neurological Techniques. 5th Ed., Vol. 2, Section XVII, Suppurative Intracranial Infections, 2006, 1593.

8. Youmans. Neurological Surgery. 6th Ed., ch. 43, Brain Abscess, table 43-1: Predisposing conditions and probable etiologic agents in Brain Abscess, 2011, 589.


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doi:10.22336/rjo.2017.26

Rare case of ocular tuberculosis in a diabetic patient: diagnostic and therapeutic dilemmas

Pantalon Anca*, Găman Emanuela*, Crețu-Silivestru Iustina-Silvia*, Danielescu Ciprian* ** *“Sf. Spiridon” University Hospital, Iași, Romania *“Gr. T. Popa” University of Medicine and Pharmacy Iași, Romania Correspondence to: Pantalon Anca, MD, PhD, Department of Ophthalmology, “Sf. Spiridon” University Hospital, Iaşi, 1 Independenței Square, Code: 700115, Iaşi, Romania, Phone: +40740 686 865, E-mail: [email protected] Accepted: May 29th, 2017

Abstract We present the case of a patient who was diagnosed by chance with macular hypopyon during a conventional interdisciplinary examination. The clinical context and the association of a systemic disease, such as uncontrolled type 1 diabetes, rendered further investigations in this patient. Due to his immunocompromised status, etiology such as ocular fungi, lymphomas, tuberculosis was taken into account. Thorough complex investigations oriented the diagnosis towards ocular tuberculosis involvement. Keywords: ocular tuberculosis, Quantiferon, diabetes

Introduction

Recent reports from the World Health Organization (WHO) mention that nearly two billion people, or one-third of the world’s population are infected by tuberculosis and that roughly 10% of the infected people are symptomatic [1]. Tuberculosis affects the lungs in 80% of the patients, while in the remaining 20% the disease may affect other organs, including the eye. Uveitis can be seen concurrently with tuberculosis, but a direct association is difficult to prove. Ocular tuberculosis is usually not associated with clinical evidence of pulmonary tuberculosis, as up to 60% of the extrapulmonary tuberculosis patients may not have pulmonary disease. The most frequently met ocular forms of TB are granulomatous chronic iridocyclitis, periphlebitis (Eales disease), choroiditis, or optic neuropathy associated with ethambutol.

The diagnosis of tuberculous uveitis is often problematic and in nearly all reported cases, the diagnosis was only presumptive. Tuberculous uveitis is a great mimicker of various uveitis entities and it can be considered in the differential diagnosis of any type of intraocular inflammation. It is still unknown if ocular manifestations result from a direct mycobacterium infection or hypersensitivity reaction and this is reflected in the management of tuberculous uveitis, which, if left untreated, inevitably leads to blindness [2]. The risk for tuberculosis in diabetic patients is greater than in the general population [3].

We present the clinical case of a 43-year-old male patient, who was referred to our clinic by the Diabetes and Metabolic Diseases Clinic for a routine fundus examination, without any subjective complaints (ocular or systemic).

As personal history, in 2015, the patient was diagnosed with non-proliferative diabetic



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retinopathy – moderate form developed on the background of an uncontrolled diabetes firstly diagnosed in 1990. Systemic complications attributed to DM in this case were also diabetic nephropathy (stage III) and peripheral neuropathy, altogether with secondary arterial hypertension and hypercholesterolemia. Pulmonary tuberculosis was established as a diagnosis in 2005, but the patient did not follow the full therapy regimen and skipped most follow up visits in the Pneumology Clinic.

The ophthalmological examination in January 2016 revealed a normal VA (1 nc, decimal scale) and good IOP in both eyes (13 mm Hg). The anterior segment examination can be followed in Fig. 1-2 and revealed only a mild form of episcleritis (positive 1% Phenylephrine test).

Fundus examination as revealed in Fig. 3-5 proved the presence of microaneurysms, rare hard exudates in the central macular area in the OD and an intraretinal inkblot hemorrhage adjacent to the supero-temporal venous branch (Fig. 3), IRMA in the superonasal quadrant. Superior to the central macular region, a hypopyon was clearly visible (Fig. 4). Exudates were visible near the optic disk (< 1PD) in the OS cotton wool, few hard exudates in the macular area and IRMA in the nasal quadrant.

Fig. 1 OD - Anterior segment examination: mild conjunctival congestion with episcleral vessels dilation

Fig. 2 OS - Anterior segment examination: normal

Fig. 3 OD - Fundus examination (moderate non-proliferative diabetic retinopathy)

Fig. 4 OD - Macular hypopyon


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In this context and taking into account his general status (uncontrolled diabetes) and personal history of tuberculosis, we recommended pneumology reevaluation, QuantiFERON® testing and follow up visit in ophthalmology after 4 weeks. No treatment was administered either systemically or topically.

At the later visit in February 2016, the aspect was stationary in both eyes, no sign of active intraocular inflammation was noticed, yet the positive Quantiferon® test (20 IU/ ml, normal range < 8 IU/ ml) alerted regarding a possible relapse of a TB infection with ocular involvement. Mantoux skin test was borderline positive (15mm/ 72h) at that time.

A thoracic X-ray and pneumology consult were part of the following assessment of this patient. Despite the stationary ocular lesions in the OD (Fig. 6), in July 2016, a full systemic exam revealed an impaired general state.

Thus, marked weight loss (BMI = IMC = 19 kg/ m2), dyspnea, coughing were identified. The general exam revealed that the blood pressure was 130/ 80 mmHg, heart rate = 120 bpm and respiratory rate = 24 bpm. Crackles were present in the lower third of the left hemithorax. Despite the negative repeated sputum exams for Mycobacterium tuberculosis, thoracic X-ray (Fig. 7) pointed out a possible pulmonary TB reactivation in this patient, therefore a fiberoptic bronchoscopy with bronchoalveolar lavage and trans-bronchial biopsies was performed on the lower left lobe.

Direct exams for regular bacteria, fungi in the bronchoalveolar lavage were negative; optic microscopy (acid-fast bacilli) was positive for Mycobacterium tuberculosis. Culture from the bronchoalveolar lavage also showed the presence of Mycobacterium tuberculosis.

The trans-bronchial biopsies showed non-specific inflammatory changes. In hematoxylin eosin coloring (Fig. 8), the lung tissue fragment contained multiple granulomatous lesions and caseous necrosis, epithelioid histiocytes and giant multinucleous cells, rare lymphocytes. The alveoli space was occupied by acidophilus material and activated macrophages. There was an intense staining of the material present within the pulmonary alveoli (PAS+) in PAS coloring (Fig. 9). Due to changes in histology, a supposition of alveolar proteinosis was raised in this case, in addition to the pulmonary tuberculosis.

Laboratory analysis showed anemia, normal renal function, poor glycemic control, inflammatory changes and anti-infectious leukocyte response, ventilatory dysfunction with altered oxygen saturation. No other parameters were modified, nor were other infectious causes found (including negative HIV serology).

Fig. 5 OS - Fundus examination (moderate non-proliferative diabetic retinopathy)

Fig. 6 Macular hypopyon – stationary aspect at 6 months after presentation (no treatment was followed)



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The patient’s parameters were WBC count = 12,200/ mm3; RBC count = 3.67 million/ mm3; ESR = 29.4%; Hemoglobin = 10g%; Platelets = 545,000/ mm3; Glucose = 223 mg/ dL, Urea = 22mg/ dL. Creatinine = 0.8mg/ dL, Na = 136mEq/ L; K = 4,7mEq/ L; Ca = 9.7mg/ dL, Mg = 1.6mg/ dL, AST: 44 UI/ L; ALT: 13 UI/ L, Total bilirubin: 0.4 mg/ dl (direct: 0.1 mg/ dl), Prothrombin time: 68% (13.3" INR: 1.24). APTT: 32", ABG's (FI02 = 0,21): pH: 7.4; PaO2:76.5mmHg; PaCO2: 40.4mmHg; HCO3 = 25.1mEq/ L; SatO2 = 95.3%.

According to WHO tuberculosis treatment guidelines [1], a standard anti-TB treatment (ATT) was planned. Thus, in the first 8 weeks, the patient was recommended Rifampin, Isoniazid, Ethambutol, and Pyrazinamide, then for the next 18 weeks a regimen with: Rifampin and Isoniazid should have been followed. Ambulatory follow up was recommended after the first 2 months. The last visit showed no change in the hypopyon appearance, a fact that pleaded more for a local delayed hypersensitivity reaction than for an acute intraocular infection, which should have responded to the antimicrobial treatment.

Discussions

The WHO reported an increasing number of TB infections in both the low/ middle-income and high-income countries due to multidrug-resistant TB, HIV and global migration [1]. This globalization and resurgence of TB means that ophthalmologists now see a spectrum of diseases: from eyes with obvious clinical OTB to mildly symptomatic patients with uveitis associated with an occult TB infection [4].

The term “ocular TB” describes an infection with the M. tuberculosis species that can affect any part of the eye (intraocular, superficial, or surrounding the eye), with or without systemic involvement. “Secondary ocular TB” is defined as an ocular involvement as a result of seeding by hematogenous spread from a distant site or direct invasion by contiguous spread from adjacent structures.

Fig. 7 Thoracic X-ray: areas of non-homogenous condensation in both lungs, more prominent on the left side; bilateral hilar lymphadenopathy

Fig. 8 Lung biopsy (HE coloring)

Fig. 9 Lung biopsy (PAS coloring)


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Intraocular tuberculosis (TB) is rare and represents a great mimicker of various clinical entities, therefore should be considered in the differential diagnosis of any ocular inflammatory condition. Primary ocular localization is rare (direct inoculation); therefore, cases that are more frequent occur via secondary hematogenous dissemination from remote sites (lungs, most frequently). Ocular involvement in tuberculosis signals an active infection; still, some cases represent only remote immune reactions (delayed hypersensitivization type IV). Ocular inflammation could be unilateral or bilateral; sometimes inflammation of one eye starts months or years before the other [4]. Forms of uveitis can reach the anterior segment, intermediate or posterior segment or all together (panuveitis).

Posterior uveitis is the most common presentation of intraocular TB, with lesions predominantly present in the choroid, such as focal, multifocal or serpiginous choroiditis, solitary or multiple choroidal nodules (tubercles), choroidal granuloma (tuberculoma), neuroretinitis, subretinal abscess, endophthalmitis, panophthalmitis, and retinal vasculitis, which is frequently ischemic in nature, and may lead to proliferative vascular retinopathy with recurrent vitreous hemorrhage, rubeosis iridis, and neovascular glaucoma [5]. The retina can indirectly be involved with ocular tuberculosis due to an associated choroiditis, but direct retinal involvement is rare [6]. In the event of primary retinal involvement, the presentation is either as a presumed tubercular retinal vasculitis or as Eales’ disease, an associated vasculitis thought to represent a hypersensitivity reaction to tuberculosis [7]. Vitritis, retinal hemorrhages, and neovascularization are also regularly associated [6]. Periphlebitis is often present in Eales’ disease as well, but there is no other evidence of intraocular inflammation [6].

Our patient manifested none of the above-mentioned clinical features. Moreover, he exhibited an excellent visual acuity that was maintained during the 12 months follow up interval, therefore, we considered it unnecessary to perform any supplementary investigations (OCT exam, fluorescein angiography, etc.) to document potential changes in the posterior segment. Anyhow, the clinical findings

mentioned above are suggestive, but nonspecific and it is still unknown if ocular manifestations result from a direct mycobacterial infection or a hypersensitivity response to mycobacteria [8]; this being reflected on the management of TB uveitis.

Moreover, due to the Jarisch-Herzheimer reaction, after the initiation of any antituberculostatic treatment, some patients manifest exacerbation of the intraocular inflammation, but in our case, the eye remained silent after 2 months of ATT. Yet this lack of response could be attributed to the general immune status of the patient. This also supports the hypothesis that the appearance of the macular hypopyon was based on a hypersensitivity reaction and not a real intraocular infection/ inflammation due to MBT localization.

In most studies, the diagnostic criteria for presumed ocular tuberculosis were: residence or migration from the areas endemic in TB, previous history of contact with TB-infected patients, presence of suggestive ocular findings, exclusion of other known causes of ocular inflammation, corroborative evidence such as a positive TST (tuberculin skin test), positive interferon-gamma release assays (QuantiFERON), and a positive response to conventional ATT without recurrence. An extraocular evidence of TB in a patient with ocular inflammation also aids in diagnosing intraocular TB [9].

Especially when poorly controlled, the functional damage to the polymorphonuclear neutrophils (adherence, chemotaxis and bactericidal activity), together with a dysfunction of the monocyte macrophage system and of cellular immunity, determine a greater risk of infections or impaired immune response in diabetic individuals [3]. In these individuals, the risk for tuberculosis is 2.0 to 3.6 times greater than in the general population [3].

Quantiferon tests (IGRA) are based on gamma interferon production by T cells sensitized to specific antigens, which are specific to MTB and therefore are not influenced by BCG and most nontuberculous bacteria. IGRAs are more specific and sensitive than PPD tests in detecting active pulmonary TB infections [10]. However, they are less sensitive in diagnosing latent TB infections. Also, Quantiferon is more



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specific in diagnosing TB-associated uveitis, and serves as a better diagnostic tool if used in conjunction with the TST [11]. The accuracy of diagnosing TB uveitis increases when both tests are used in combination with suggestive clinical signs [11].

Based on the entire assessment of this patient we chose not to treat OTB with any topical medication, since the general treatment follows the same guidelines as for active pulmonary and extrapulmonary and was recommended as it follows - first 8 weeks Rifampin, Isoniazid, Ethambutol and Pyrazinamide, then the next 18 weeks Rifampin and Isoniazid. An escalation of corticosteroids may have been helpful in case of increased ocular inflammation during treatment, but it was not the case of our patient. On the other hand, response to treatment in OTB is slow, therefore at 2 months follow up the stationary aspect of the “macular hypopyon”. We have used this term “macular hypopyon” to describe what appeared to be an accumulation of white material in front of the macula with a horizontal level (fluid-like). The term has been borrowed from the description of an endophtalmitis, where it describes an accumulation of pus on the macula due to the supine position [12] similar to what we found in our patient, but we could not identify exactly the composition in the pre-retinal deposit. Therefore a differential diagnosis should also take into account a preretinal hemorrhage where the blood has degraded and took this aspect.

A particularity of this case was the incidental manner of discovering a relapse of pulmonary TB via a routine ophthalmological fundus examination. A corroboration of personal history, clinical aspect, and systemic status oriented the diagnosis of ocular TB. Modern laboratory measurements (Quantiferon), combined with old standard tests (TST) aided a more accurate, yet still not certain OTB diagnosis. However, the detection of acid-fast bacilli (AFB) with Ziehl-Neelsen or auramine rhodamine stains has a low yield even from the aqueous or vitreous [6], cultures are time-consuming (6-8 weeks) and other techniques (e.g. PCR), which attempt to isolate MTB from the ocular samples, may be challenged by the low sample volume and the paucibacillary nature of the disease. Alternatively, the poor positive

outcome of these methods may be explained by the second hypothesis of OTB, being an immune-mediated mechanism of inflammation.

Therefore, obtaining histopathologic evidence is preferable, but difficult to obtain in adequate size to support the diagnosis of ocular tuberculosis. In this case, the typical histology aspect was obtained only from the pulmonary biopsy. Altogether, this exam also detected another incidental association in this patient (alveolar proteinosis) which could confound the thoracic X-ray interpretation in a tuberculosis case. The incidence of PAP in the general population is 1 in 2 million people [13], with a 3 to 1 male-to-female predominance. Almost 80% of the patients are between 20 and 50 years old, although it has also been described in newborns and school age children [14] and in the elderly [15]. The main symptom is exertion dyspnea. Many patients present with dry cough or with opalescent and viscous sputum. Asthenia and weight loss may be present and these could also be confounders for our patient. Fever is more common in the secondary form and was not the situation here. Chest pain and hemoptysis are not frequent in the primary form. The physical examination is nonspecific, with predomination of crackles in the affected areas [13]. The most common X-ray pattern is a symmetrical, bilateral, alveolar infiltrate, predominantly in the lower lobes, as it was the case in this patient.

Further follow up is needed as relapses are silent and frequent in immunocompromised patients, therefore a multidisciplinary approach is required to further manage this case.

Conclusion

We presented a case of presumed ocular tuberculosis with a single non-specific lesion (macular hypopyon) and no active ocular inflammation associated with it, in a diabetic young patient. Recent advances in diagnostic tools for OTB immunological techniques (Quantiferon) have improved the specificity of making this diagnosis. However, the clinical diagnosis of OTB remains a complex issue, as these investigations are mainly adjunctive and complementary, while the clinical manifestations of OTB are highly variable.


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References

1. WHO Global tuberculosis control: key findings from the December 2009 WHO report. Wkly Epidemiol Rec. 2010; 85(9):69–80.

2. Shakarchi FI. Ocular tuberculosis: current perspectives. Clin Ophthalmol. 2015; 9:2223–2227.

3. Pereira-Silva JL, Marinho MMMA, Veloso TVB, Coelho Filho JC. Pulmonary Alveolar Proteinosis and tuberculosis in a diabetic patient: a rare or a seldom diagnosed association?. Braz J Infect Dis. Aug. 2002; 6(4).

4. Ang M, Chee SP. Controversies in ocular tuberculosis. Br J Ophthalmol. doi:10.1136/bjophthalmol-2016-309531.

5. Floros J, Lin HM, Garcia A et al. Surfactant protein genetic marker alleles identify a subgroup of tuberculosis in a mexican population. J Infect Dis. 2000; 182:1473-8.

6. Samson MC, Foster CS. Tuberculosis. In: Foster CS, Vitale AT, editors. Diagnosis and Treatment of Uveitis. 2002, Philadelphia, WB Saunders Company, 264–272.

7. Gupta A, Bansal R, Gupta V, Sharma A, Bambery P. Ocular signs predictive of tubercular uveitis. Am J Ophthalmol. 2010; 149(4):562–570.

8. Fergusson JS, Voelker DR, McCormack FX, Schlesinger LS. Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lecitin interations resulting in reduced phagocytosis of the bacteria by macrophages. J Immunol. 1999; 163:312-21.

9. Sidobre S, Nigou J, Puzo G, Riviere M. Lipoglycans are putative ligands for the human pulmonary surfactant protein A attachment to mycobacteria. Critical role of the lipids for lecitin-carbohydrate recognition. J Biol Chem. 2000; 275:2415-22.

10. Parchand S, Tandan M, Gupta V, Gupta A. Intermediate uveitis in Indian population. J Ophthalmic Inflamm Infect. 2011; 1(2):65–70.

11. Ang M, Wong W, Ngan CC, Chee SP. Interferon-gamma release assay as a diagnostic test for tuberculosis-associated uveitis. Eye. 2012; 26(5):658–665.

12. Kuhn F. Ocular Traumatology. 2008, Springer, 438. 13. Shah PL, Hansell D, Lawson PR et al. Pulmonary

alveolar proteinosis: clinical aspects and concepts on pathogenesis. Thorax. 2000; 55:67-77.

14. Mahut B, Delacourt C, Scheinmann P et al. Pulmonary alveolar proteinosis: experience with eight pediatric cases and a review. Pediatrics. 1996; 97:117-22.

15. Prakash UB, Barham SS, Carpenter HA et al. Pulmonary alveolar phospholipoproteinosis: experience with 34 cases and review. Mayo Clin Proc. 1987; 62:499-518.


GENERAL ARTICLE

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doi:10.22336/rjo.2017.27

Unilateral Eales’ disease a case report Nicolcescu Andreea*, Mocanu Carmen**, Dinu Loredana*, Olaru Andrei**, Ionete Mara*, Stefanescu Dima Alin** *Department of Ophthalmology, Clinical Emergency Hospital, Craiova, Romania **Department of Ophthalmology, University of Medicine and Pharmacy of Craiova, Craiova, Romania Correspondence to: Mocanu Carmen, MD, Department of Ophthalmology, University of Medicine and Pharmacy of Craiova, Craiova, 2 Petru Rares Street, Code 200349, Craiova, Romania, E-mail: [email protected] Accepted: May 20th, 2017

Abstract Introduction. Eales disease is an idiopathic peripheral vascular occlusive disease characterized by inflammation, ischemia, and retinal neovascularization and is hallmarked by recurrent vitreous hemorrhages and vision loss. Case report. We present a case of a 48-year-old female with recurrent floaters and decreased vision in her right eye. The onset of symptoms was in 2007 when a diagnose of retinal vasculitis was made. She had no accompanying systemic signs and symptoms and no history of ocular trauma or previous tuberculosis infection. The eye condition was managed only with intermittent focal laser treatment, because the general treatment with steroids was not efficient and poorly tolerated. After the laser treatment, the visual acuity completely recovered and there was no recurrence of vitreous hemorrhage. The case particularity was the unilaterality after 9 years from the onset. Keywords: Eales, recurrent floaters, focal laser

Introduction

Eales disease is an idiopathic peripheral retinal vasculopathy that affects the peripheral retinal vasculature, leading to retinal non-perfusion or ischemia, retinal neovascularization and vitreous hemorrhage. There may be perivasculitis, phlebitis, dilated aneurismal changes shunt vessels and even macular edema [1].

Case report

We present the case of a 48-year-old myopic female with recurrent floaters, and decreased vision in her right eye.

From the medical history, we found that the onset of the symptoms was in 2007, when a

diagnose of retinal vasculitis was made. She had no accompanying systemic sign and symptoms and no history of ocular trauma or previous tuberculosis infection. The eye condition was managed only with intermittent focal laser treatment because the general treatment with steroids was not efficient and poorly tolerated.

The symptoms reoccurred in November 2015 when she was admitted in the Eye Clinic with vitreous hemorrhage in her right eye.

At presentation, her best corrected visual acuity was 0,5 for the right eye and 0,9 for the left eye, with a spherical myopic correction (-3,75). By the applanation of tonometry, the intraocular pressure was 15 mmHg for both eyes. On the external examination and slit-lamp


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examination, the findings of the anterior pole were within normal limits. The fundus of each eye was examined after a pharmaceutical mydriasis with 1% tropicamide and 10% phenylephrine hydrochloride ophthalmic solution.

Fundus examination of the left eye was normal (Fig. 2).

After the vitreous hemorrhage was gone, at

the fundus examination of the right eye we noticed: retinal neovascularization, fibrovascular proliferation, peripheral non-perfusion, collaterals, vascular sheathing, and peripheral BRVO (Fig. 3).

Fig. 1 Right eye: Vitreous hemorrhage and the retina – blurry vision

Fig. 2 Fundus examination of left eye is normal



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Fluorescein angiography revealed peripheral non-perfusion and retinal neovascularization with leakage in the right eye (Fig. 4) and was normal for the left eye (Fig. 5).

Fig. 3 Right eye after the vitreous hemorrhage is gone: NVE, fibrovascular proliferation, peripheral non-perfusion, collaterals, vascular sheathing, peripheral BRVO

Fig. 5 FA on the left eye is normal

Fig. 4 FA on the right eye: peripheral non-perfusion; retinal neovascularization with leakage


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Other etiology was excluded, because of the possible causes of this condition. Hematologic diseases were ruled out as possible causes of the condition. Normal chest X-ray and negative tuberculin PPD test ruled out the tuberculosis infection. Systemic lupus erythematosus was ruled out (normal antinuclear antibody, rheumatoid factor or C-reactive protein, negative C3 C4).

The raised erythrocyte sedimentation rates (28/ 46 mm) and elevated cholesterol (331 mg/ dl) were not specific enough for a particular explanatory condition either.

Based on the medical history, the fundus aspect and paraclinical investigation, and the diagnosis of Eales disease was established in the right eye.

Focal laser treatment of the areas of new vessels was performed in the right eye, FA- guided. The evolution was favorable after the laser treatment, the new vessels regressed, the visual acuity completely recovered and there was no recurrence of vitreous hemorrhage (Fig. 5).

The patient had a follow up period; at every 3 months, the reoccurrence of new vessels in the right eye and eventually the involvement of the left eye being monitored.

Discussions

Eales Diseases have the name of Henry Eales, who, in 1880, described five young men with recurring vitreous and retinal hemorrhages associated with constipation and epistaxis [4].

The etiology is unknown, no definite cause has been found for Eales disease, being considered idiopathic. It tends to occur in males of Asian origin in their second decade of life (20-40 years old) [3]. Moreover, it has been related to tuberculosis exposure and hypersensitivity to tuberculoprotein and tubercle bacilli have been identified in pathology specimens [6]. Other immune-mediated mechanisms, such as predominant T-cell involvement, have also been demonstrated through experimental studies [5]. Associations have also been made with retinal S-antigen and HLA B5, DR1, DR4, and patients with autoimmune disease. Support has been found for oxidative stress, as increased accumulation of lipid peroxide, increased carboxy methyl lysine, decreased glutathione, and decreased vitamins C

Fig. 6 Right eye: aspect after laser treatment



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and E. Similarly, increased vascular endothelial growth factor (VEGF) results have been found in retinal neovascularization [2].

Peripheral retinal vessels first became inflammated, sheathed, and then occluded. The loss of perfusion leads to retinal neovascularization that causes recurrent vitreous hemorrhages. It is initially asymptomatic, but then progresses through general stages of the disease [2].

Early stage, inflammatory: various stages of periphlebitis may be found, venous dilatation and perivascular exudates can be found as well [2].

Middle stage, ischemic: characterized by capillary ischemia, demarcation between perfused and non-perfused zones is marked by veno-venous shunts, venous beadings, and microaneurysms [2].

Late stage, proliferative: neovascularization occurs at the junction between perfused and non-perfused retina that leads to recurrent vitreous hemorrhages with or without retinal detachment [2].

Eales disease tends to occur peripherally, but macular edema and disc neovascularization may also occur. Patients may present with decreased vision, photopsia and floaters unilaterally or bilaterally [2].

Fluorescein angiography shows leakage of the sheathed vessels, retinal vascular tortuosity and telangiectasias, shunt vessels, venous stasis, capillary non-perfusion, retinal neovascularization [2].

Eales disease is a clinical diagnosis of exclusion, chest X-ray; the Montoux tuberculin shin test might be helpful (because the Mycobacterium tuberculosis DNA has been found in the vitreous of patients with Eales disease). Hemoglobin electrophoresis can assess the sickle cell retinopathy. VDRL is useful for syphilis and anti-nuclear antibody (ANA); it can also indicate systemic lupus erythematosus. Serum angiotensin converting enzyme and a chest X-ray can point to sarcoidosis [2].

In the early or inflammatory stage, oral prednisone (1-1,5 mg/ kg tapered over 6-8 weeks) is recommended in patients with involvement of two quadrants, with maintenance dose (15-20 mg per day for up to 2 months) if needed [2].

However, in patients with macular edema or involvement of three quadrants, intravitreal triamcinolone acetonide has shown improvement in visual acuity [7].

Non-steroidal immunosuppressive agents are reserved for those in whom steroids are ineffective or contraindicated [2]. Intravitreal anti-VEGF therapy may be successful with vascular nonperfused and retinal neovascularization; however, its effects may cause vitreoretinal contraction [8].

In patients with exposure to tuberculosis, anti tubercular therapy can be administered for 9 months, but it is reserved for patients with massive infiltration, nodule formation, and venous obliteration [2].

For patients with a later stage disease retinal neovascularization, laser scatter photocoagulation (peripheral pan-retinal photocoagulation) in the areas of retinal non-perfusion induces regression of neovascularization. When optic disc neovascularization is present, panretinal photocoagulation laser is recommended. Pars plana vitrectomy is necessary for non-resolving vitreous hemorrhage and/ or retinal detachment (whether tractional, rhegmatogenous, or combined). Endolaser treatment may be applied at the time of surgery. Vitrectomy for non-resolving vitreous hemorrhage should be performed no later than 6 months following the onset of hemorrhage [2].

Eales disease is a diagnosis of exclusion. In the absence of other systemic conditions, peripheral retinal inflammation and recurrent vitreous hemorrhages are important defining features.

Laboratory tests are not sensitive or specific for Eales disease but may be helpful in detecting systemic causes of retinal vasculitis or peripheral retinal non-perfusion.

With the proper treatment, the prognosis of Eales disease is good. The major cause of visual loss is recurrent vitreous hemorrhages. Complications of neovascularization, such as retinal detachment and neovascular glaucoma, may contribute to significant vision loss, however, blindness is rare, and vision less than 20/ 200 occurs in less than 1% of the patients [2].


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Case particularity

Eales disease is considered a bilateral disease in up to 90% of the patients, although symptoms often present unilaterally [2]. The particularity of this case is the unilaterality after 9 years from the onset.

References

1. Yannuzzi LA. The Retinal Atlas. Retinal Vascular Diseases, Eales’ Disease. 2010, Elsevier, 433-38.

2. Mwndoza KA, Lauer A. Eales Disease. American Academy of Ophthalmology. 2015. http://eyewiki.org/Eales_Disease.

3. Kanski JJ, Bowling B. Clinical Ophthalmology a systematic approach. Eales Disease. Seventh edition, 2011, Elsevier, 583-86.

4. Nussenblatt RB, Whitcup SM. Uveitis: Fundamentals and Clinical Practice. Eales’ Disease, Fourth Edition, 2010, Elsevier, 356-359.

5. Garg SJ. Color Atlas & Synopsis of Clinical Ophthalmology Wills Eye Institute. Uveitis; Eales’ Disease. 2012; 101-103.

6. Terese KL, Deepa P, Terese J et al. Association of mycobacteria with Eales’ disease. Indian J. Med Res. 2007; 126(1):56-62.

7. Agrawal S, Agrawal J, Agrawal TK. Intravitreal triamcinolon acetonide in Eales disease. Retina. 2006; 26(2):227-229.

8. Gupta SR, Flaxel CJ. The use of a vascular endothelial growth factor inhibitor (ranibizumab) in macular edema due eales disease. Retin. Cases Brief Rep. 2012; 6(1):112-124.

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observations, emphasizing new information Abstract length is limited to 250 words. Abbreviations must be defined at first mention in the abstract, and again at first mention in the main manuscript text. Do not cite references in abstract, and limit use of acronyms and abbreviations. After the Abstract, insert three to five keywords for use as indexing terms, separated by semicolons. These words may later be copyedited to conform to journal style. Abbreviations Create a list of non-standard abbreviations and non-standard acronyms used in the manuscript text. The list should be included in the manuscript and placed after the abstract, before the Introduction. The list should be entitled “Abbreviations.” Its content will not count toward the word limit. All abbreviations and acronyms should be expanded upon first usage in the text, and thereafter the abbreviation/acronym should be used. Text Main headings include Introduction, Methods, Results, and Discussion (IMRAD form). • Manuscripts must be DOUBLE LINE SPACED, including

references and figure legends, using Arial, font size 11. • Leave 2 cm margins on all sides. • Number all pages--including Figures with legends and

Tables. Use SI units of measure in all manuscripts. For example, molar (M) should be changed to mol/L; mg/dL to mmol/L; and cm to mm. Units of measure previously reported as percentages (i.e. hematocrit) are expressed as a decimal fraction. Measurements currently not converted to SI units in biomedical applications are blood and oxygen pressures, enzyme activity, H+ concentration, temperature, and volume. The SI unit should be used in text, followed by the conventionally used measurement in parentheses.


http://www.icmje.org/

Methods The print version of the Methods should provide sufficient information for the reader to understand the basic methodology. There is no preset space allocation for the description of methods. Because of space restrictions, it is recommended that in the print version the Methods section be limited to essential new information. Methods that are essentially the same as those presented in previous publications should be cited or succinctly summarized rather than detailed in the print version. For animals used in experiments, state the species, strain, number used, and other pertinent descriptive characteristics. When describing surgical procedures on animals, identify the preanesthetic and anesthetic agents used and state the amount or concentration and the route and frequency of administration for each. The use of paralytic agents, such as curare or succinylcholine, is not an acceptable substitute for anesthetics. For other invasive procedures on animals, report the analgesic or tranquilizing drugs used. If none were used, provide justification for such exclusion. Generic names of drugs must be given. Manuscripts that describe studies on humans must indicate that the study was approved by an institutional review committee and that the subjects gave informed consent. Please provide sex-specific and/or racial/ethnic-specific data, when appropriate, in describing outcomes of epidemiologic analyses or clinical trials; or specifically state that no sex-based or racial/ethnic-based differences were present. Reports of studies on both animals and humans must indicate that the procedures followed were in accordance with institutional guidelines. One must prove that experiments on live vertebrates are ethically accepted and are following national and international rules for animal laboratories. Any information that may lead to the identification of a patient must be excluded from the content of the article. When photos of admitted patients are sent, they must have their consent and authors take full responsibility of the material. If materials contain medical research on human subjects, the author must enclose a declaration that confirms consent of all those subjects, in conformity with World’s Medical Association Declaration, issued in Helsinki. Acknowledgements The Acknowledgments section should include any personal thanks to individuals who assisted in the performance of the studies and/or in the preparation of the manuscript. Authors must provide written permission from all individuals who are listed in the Acknowledgments section of the manuscript, because readers may infer their endorsement of data and conclusions. The corresponding author must sign the Acknowledgment Section of the Copyright Transfer Agreement, certifying that (1) all persons who have made substantial contributions to the manuscript (i.e., data collection, analysis, or writing or editing assistance), but who do not fulfill authorship criteria, are named with their specific contributions in the Acknowledgments section of the manuscript; (2) all persons named in the Acknowledgments section have provided the corresponding author with written permission to be named in the manuscript; and (3) if an Acknowledgments section is not included, no other persons besides the authors have made substantial contributions to this manuscript.

Sources of Funding The Sources of Funding section should include all sources of research support, including public and private entities, commercial or institutional support, and any substantial contributions by individuals.

Disclosures In the Disclosures section, authors must disclose any and all relationships that could be perceived as real or apparent conflict(s) of interest. If authors have nothing to disclose, they must state "None." Conflicts of interest pertain to relationships with and/or ownership interests in pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject matter of the article. Relationships include, but are not limited to, employment by an industrial concern, ownership of stock, membership on a standing advisory council or committee, being on the board of directors, or being publicly associated with the company or its products. Ownership interest includes any stock, stock option, partnership, membership or other equity position in an entity regardless of the form of the entity, or any option or right to acquire such position, and any rights in any patent or other intellectual property. Other areas of real or perceived conflict of interest could include receiving honoraria or consulting fees or receiving grants or funds from such corporations or individuals representing such corporations. References References must conform to Pubmed requirements. Authors must ensure accuracy of reference data. Verify all entries against original sources. All authors must be listed in each reference. Do not use "et al". Cite references in numerical order according to first mention in the text. Personal communications, unpublished observations, and submitted manuscripts are not legitimate references and must be cited in the text only (not in the reference list) as "(author name, unpublished data, [year])." All submitted manuscripts that are pertinent to the manuscript under consideration must accompany the submission. Personal communications and unpublished observations must be accompanied by a letter from the source approving use of the information. All references will be written in the following order: name (of the author), initial letter of the surname (of the author), title of the article, source (name of the book, magazine, etc), year of publication, volume, issue (if applicable), first page, last page (of the source). Example: Langlois J, Rutland-Brown W, Wald M. The epidemiology and impact of traumatic brain injury: a brief overview.J Head Trauma Rehabil. 2006; 21: 375-378. The references will not contain internet sources. All references which are originally taken from an international database (i.e. Scopus, MedLife, etc.), should respect the same order of the elements mentioned above, but should necessarily contain a “doi” after the year of the publication, instead of the page numbers of the paper. Example: Langlois J, Rutland-Brown W, Wald M. The epidemiology and impact of traumatic brain injury: a

brief overview. 2006; doi:10.1111/j.1464-410X.2009.08495.x. All references which are originally taken from books, should contain the following details in this specific order: name(s) and surname(s) of the author(s), chapter of the book (if applicable), the title of the book, year of publication, the city of publication, the name of the publishing house, first page, last page (of the source). Example: Hojat M. Does empathy predict career choice and professional success? Empathy in Patient Care, 2006, New York, Springer Verlag, 205-209 We recommend you to use only peer-reviewed journals. Figures Acceptable electronic figure file formats for publication are: jpg and .tiff Color figures must be in CMYK mode, not RGB mode. Color figures and line drawings must be at least 600 dpi resolution. Grayscale and black/white figures must be at least 300 dpi resolution. Combination color, grayscale and line art must be 600 dpi or higher. The use of digital media for image acquisition and processing introduces the potential for inadvertent distortion of data. To prevent such distortion, data should neither be added to, nor removed from, an image by digital manipulation. Figures assembled from multiple images must indicate the separation of the parts by lines. Linear adjustment of contrast, brightness or color must be applied equally to all parts of an image. Authors must be prepared to submit the original, unaltered files from which the submitted figures were derived, if requested by the editorial office. Graphics downloaded from the Web are not acceptable for print. Web graphics, usually in GIF or JPEG format, have a resolution of only 72 dpi, which does not meet the standard for peer review nor publication. Figure parts should be clearly labeled. Letters and labels must be uniform in size and style within each figure and, when possible, between figures. The font size must be 10 point or higher. Symbols and abbreviations must be defined in the figure or its legend. Avoid headings on the figure. Heading information should appear in the figure legend. Provide a short title (in the legend, not on the figure itself) and an explanation in brief but sufficient detail to make the figure intelligible without reference to the text (unless a similar explanation has been given in another figure). Figure legends are included in the word limit.

Tables Include table(s) in the main manuscript document as text, not as an image. Table(s) are included in the word limit. Number tables using Arabic numerals, and supply a brief, informative title for each table. Table text must be consistent in size and style with main manuscript text. Supply brief column headings. Indicate footnotes in this order: *, †, ‡, §, ||, #, ** Use only horizontal borders above, and below the column headings and at the bottom of the table. Use extra space to delineate rows and columns. Abbreviations/symbols used in a table but not already defined in the main text must be defined in the table or table legend. Do not use colors for tables, use only default .1 black borders. Tables must be placed 1 per page at the end of the manuscript, after the references. Copyright information A letter signed by the main author of the article, which will be sent via mail together with the manuscript, will contain copyright transfer to Romanian Journal of Ophthalmology. The full responsibility for all written information in the article belongs to authors. Conflict of Interest Policy Authors are responsible for the published materials and other conflicts of interests regarding subjects included in their work. Authors must mention all the funding received for research and other financial or personal connections linked to the article, in their work. Order of publication The order in which the articles appear in the journal is determined by: • date of arrival • editorial priorities • compliance with the above mentioned

recommendations • peer-review recommendations

Priorities can be decided for some articles, requested either by the editors or by being of special interest. For urgent communications (phone, fax, e-mail), the following address may be used as well: " Dr. Carol Davila"Central Military University Emergency Hospital 134 Calea Plevnei Street, District 1, Bucharest, Romania Phone number/Fax: +40.21.3137189, E-mail: [email protected] Please also consider downloading the following documents: Authors' recommendations Authorship responsibility form Copyright transfer agreement

Sponsors of Romanian Journal of Ophthalmology

Alcon, Amaoptimex, Argusoptik, Biosooft, BK Medical, Essilor, HOYA, Kemblimed, KRKA, Laboratoire Thea, Nova Lenti, Novartis, Opticiris, RECKITT BENCKISER, Romger General, Santen, Sifi, Sover Optica, Spectra Vision, Sun Wave Pharma, Valeant Bausch Lomb

http://www.medandlife.ro/assets/files/authors'%20recommendations.pdf

http://www.medandlife.ro/assets/files/authorship%20responsibility%20form.pdf

http://www.medandlife.ro/assets/files/copyright%20transfer%20agreement.pdf

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