Uveitis in Behcet Disease inYears: The KKESH Uveit

J. FERNANDO AREVALO, ANDRES F. LASANASSER ABDULMOHSEN AL SABAANI, AMMAR

HASSAN A. AL DHIBI, AND THE KKESH

177184. 2015 by Elsevier Inc. All rights reserved.)King Khaled Eye Specialist Hospital, Al-Oruba Street, PO Box 7191,sions, typical skin lesions, or positive pathergy test. Intraoc-ular inflammation may involve the anterior or posteriorsegment or, more commonly, both segments. Intraocularinflammation clinically presents as episodic and recurrentiridocyclitis along with vitritis, retinitis, occlusive vascu-litis, and cystoid macular edema, alternating with periodsof inactive phases.1 Immunosuppresive therapy is the main-stay of treatment in these patients.12 Complications such asband keratopathy, glaucoma, vitreoretinal hemorrhage,retinal detachment, macular degeneration, epiretinal

Accepted for publication Oct 10, 2014.From the Retina Division, Wilmer Eye Institute, Johns Hopkins

University School of Medicine, Baltimore, Maryland (J.F.A.);Vitreoretinal and Uveitis Division, King Khaled Eye Specialist Hospital,Riyadh, Saudi Arabia (J.F.A., M.Y.A.J., N.A.A.S., A.M.A.-M.,Y.A.A.-Z., H.A.A.D.); Retina and Vitreous Service Clnica Privada deOjos, Mar del Plata, Argentina (A.F.L.); and College of Medicine, KingKhalid University, Abha, Saudi Arabia (N.A.A.S.).Inquiries to J. Fernando Arevalo, Chief of Vitreoretinal Division, The

Riyadh 11462, Kingdom of Saudi Arabia; e-mail: arevalojf@jhmi.edu PURPOSE: To describe the features ofBehcet-associateduveitis over a 25-year period. DESIGN: Retrospective observational case series. METHODS: A chart review of patients with Behcet-associated uveitis who were evaluated from January1986 to December 2011 at King Khaled Eye SpecialistHospital, Saudi Arabia. Demographic data, symptoms,type of uveitis, treatment, and complications were evalu-ated. The main outcome measures were presenting symp-toms, types of uveitis, treatment, and complications. RESULTS: There were 132 patients (232 eyes; 102male [77.3%]) evaluated with age of onset of 36.9 11.4 years. Panuveitis was the most common presenta-tion, affecting 118 patients (89.4%). Episodes were bilat-eral in 100 patients (75.8%). Baseline best-correctedvisual acuity (BCVA) was 20/125 in both eyes. Retinalvasculitis at presentation occurred in 61 eyes (26.3%),occlusive vasculitis in 59 eyes (25.4%), and macularedema in 42 eyes (18.1%). Common therapeutic manage-ment included oral corticosteroids in 123 patients(93.2%), intravenous steroid therapy in 35 patients(26.5%), cyclosporine in 98 patients (74.2%), andazathioprine in 65 patients (49.2%). Common anteriorsegment complications included glaucoma (44 eyes,19%) and cataracts (34 eyes, 14.7%). The most commonposterior segment complication was optic nerve atrophy.Cataract surgery was the most common surgery. At lastvisit, BCVA was better than 20/50 in 131 eyes (56.5%). CONCLUSIONS: Behcet-associated uveitis predominantlyaffects young men in Saudi Arabia. Bilateral panuveitisassociated with retinal vasculitis was the most commonmanifestation. More than 50% of patients maintained20/50 or better BCVA at final follow-up and were pri-marily managed with oral corticosteroids and other immu-nosuppressive agents. (Am J Ophthalmol 2015;159:0002-9394/$36.00http://dx.doi.org/10.1016/j.ajo.2014.10.013

2015 BY ELSEVIER INC.a Tertiary Center Over 25is Survey Study Group

VE, MOHANNA YOUSEF AL JINDAN,M. AL-MAHMOOD, YAHYA A. AL-ZAHRANI,UVEITIS SURVEY STUDY GROUP

BEHCET DISEASE IS A MULTISYSTEM INFLAMMATORY

disease of unknown etiology, characterized byrecurrent episodes of retinal vasculitis, uveitis, gen-

ital ulcers, oral ulcerations, and skin lesions.1,2 The diseaseis named for Hulusi Behcet, a Turkish dermatologist, whoin 1936 described the symptomatic triad of uveitis withrecurrent oral and genital ulcers.3 It should be noted thatin the 20th century at least 2 other clinicians reported caseswith similar findings: Shigeta4 from Japan in 1924 andAdamantiadis5 in 1931. Therefore, this disorder also isknown as Adamantiadis-Behcet syndrome. However, thedisease was known in ancient times, and Hippocrates waslikely the first to describe an association between ocularinflammation and oral and genital lesions.6

Behcet disease occurs worldwide. However, its preva-lence varies considerably based on geographic locationand race. Prevalence rates vary from 1 per 10 000 inhabi-tants to 42 per 10 000 inhabitants from Japan and Turkey,respectively.7,8 In Saudi Arabia, Behcet disease is one ofthe most common causes of uveitis.9 In our most recent sur-vey it is second only to Vogt-Koyanagi-Harada syndrome(Arevalo et al. American Academy of OphthalmologyAnnual Meeting, Chicago, IL, 2012, unpublished data) asa cause of panuveitis (26% of patients). Although Behcetcan occur at any age, the usual age of onset is 2030 years.Ocular involvement has been reported in up to 70% of pa-tients with Behcet.10

Behcet is diagnosed based on specific clinical symptomsand signs, as there is no specific laboratory test. The BehcetDisease Research Committee of Japan devised a set ofcriteria for the diagnosis of Behcet disease in 1974,11 andthe International Study Group (ISG) for Behcet diseasepublished diagnostic criteria in 1990.1 According to ISGcriteria, the diagnosis of Behcet disease requires the pres-ence of recurrent oral ulceration in addition to at least 2other features: recurrent genital ulceration, typical eye le-177ALL RIGHTS RESERVED.

membrane, vein occlusion, and finally phthisis bulbi maybe encountered.In the current study, we retrospectively analyzed the de-

mographic and clinical features, ocular manifestations,complications, visual outcomes, and management of uve-itis in a large population of patients with Behcet diseasethat were seen over the last 25 years in a single tertiary cen-ter in Saudi Arabia.

PATIENTS AND METHODS

THIS WAS AN OBSERVATIONAL CASE SERIES. DATA WERE

collected by retrospective chart review. All patients diag-nosed with ocular Behcet disease from January 1986 toDecember 2011 at the King Khaled Eye Specialist Hospital(KKESH), Saudi Arabia, were recruited for a uveitis surveyaccording to a predetermined protocol. Out of 888 consec-utive uveitis patients (1455 eyes), 132 patients (14.9%)(232 eyes) with Behcet disease were evaluated. Patientswere referred to our institution from other centers withinSaudi Arabia and other countries from the Arabian Gulf,and some patients were self-referred. All patients withocular Behcet disease at initial diagnosis and treated at

FIGURE 1. Patient with Behcet disease. A 37-year-old man presentof recurrent oral aphthous ulcers. Clinical diagnosis of Behcet diseasvitreous haze 3D in the affected eye. (Top right) Left eye is unremarare observed in the right eye.

178 AMERICAN JOURNAL OFKKESH were included in this study. The clinical recordswere reviewed of 132 patients (232 eyes) diagnosed withocular Behcet. Only patients who met the 1990 ISG classi-fication criteria were included in this study.1 This studyfollowed the tenets of the 1964 Declaration of Helsinkiand was approved as a retrospective study by the KKESHHuman Ethics Committee/Institutional Review Board.Demographic information was collected based on self-reported data obtained at the initial visit via a uveitis ques-tionnaire, verbal history, and physical examination. Datawere collected on race, ethnicity, and country of origin.Best-corrected visual acuity (BCVA) was measured with

Snellen charts and the values were converted to logarithmof minimal angle of resolution equivalent units (logMAR)for statistical calculations. Ophthalmic examination wasperformed including slit-lamp biomicroscopy, dilatedfundus examination, and ancillary methods as required.Classification of uveitis, as well as grading of anterior and

posterior segment inflammation, was determined using theStandardization of Uveitis Nomenclature (SUN)criteria.13 The intraocular inflammation was consideredinactive or controlled if the inflammatory activity wasgraded

y sDisease duration was defined as the time interval be-tween the onset of ocular symptoms and diagnosis of uveitis

FIGURE 2. Patient with Behcet disease. Fluorescein angiographthe right eye. Same patient as in Figure 1.and time of presentation. For the purposes of this study,eyes that experienced only iridocyclitis were classified asanterior uveitis; posterior uveitis was defined as eyes thatexperienced retinitis, retinal vasculitis, diffuse vitritis,and/or papillitis; and panuveitis was classified as eyes thatexperienced retinitis, retinal vasculitis, diffuse vitritis,and/or papillitis in addition to iridocyclitis. The type andduration of therapy used for controlling the intraocularinflammation and the visual outcome were recorded. Com-plications, such as cataracts, glaucoma, and choroidalneovascularization, were noted.All data were collected in a Microsoft Office Excel 2007

spreadsheet (Microsoft Corp, Redmond, Washington,USA) and statistically analyzed by MedCalc Software forWindows 8.2.0.3 (MedCalc, Mariakerke, Belgium).

RESULTS

PANUVEITIS WAS THE MOST COMMON FORM OF OCULAR

presentation, affecting 118 of 132 patients (89.4%), followedby anterior uveitis in 10 patients (7.6%) and intermediateuveitis in 4 patients (3%). The mean follow-up was 97.5 680.9 months (range: 4298 months). One hundred and twopatients (77.3%) were male. Mean age at onset of diseasewas 36.96 11.4 years. Episodes were bilateral in 100 patients

VOL. 159, NO. 1 SURVEY OF UVEITIS IN BEHCET(75.8%). BaselineBCVAwas 20/125 (logMAR 0.86 0.8)in both eyes. Presenting visual acuity was equal to or better

hows peripheral vascular staining and cystoid macular edema inthan 20/50 (logMAR 0.4) in 87 eyes (37.5%) and 20/200 (logMAR 1) or worse in 89 affected eyes (38.4%).Mean intraocular pressure (IOP) was normal in all eyes.Retinal vasculitis at first presentation was found in 120 eyesand of those, about half (59/120, 49.1%)were occlusive cases(Figures 13). The most common location of retinalocclusive vasculitis was peripheral that was present in 37 of59 eyes (62.7%) with Behcet uveitis. These cases weretreated and controlled with immunosuppressive therapy.All the causes and modalities of treatment for occlusivevasculitis are presented in Table 1. Laser photocoagulation(either focal retinal photocoagulation or panretinal/scatterphotocoagulation) was performed for treatment of occlusivevasculitis based on etiology.Retinal detachment (RD) was present in 22 of 232 eyes

(9.4%); of those, an exudative retinal detachment (ERD)was diagnosed in 11 of 22 eyes (50%), tractional retinaldetachment (TRD) in 9 of 22 eyes (40.9%) (Figure 4),and a rhegmatogenous retinal detachment (RRD) in 2 of22 eyes (9.1%).Therapeutic management included oral systemic cortico-

steroids in 123patients (93.2%), intravenous steroid therapyin 35 patients (26.5%), immunosuppressive agents such ascyclosporine in 98 patients (74.2%), azathioprine in 65patients (49.2%), infliximab in 12 patients (9.1%), andmethotrexate in 6 patients (4.5%). Local steroid therapy(sub-Tenon triamcinolone) and intravitreal triamcinolone

179DISEASE OVER 25 YEARS

were administered in 14 (10.6%) and 5 patients (3.8%),respectively.We observed that the combination of drugs used for

the treatment of Behcet disease varied considerably overthe years. Therefore, we decided to divide our patientsinto different treatment groups according to the therapy

FIGURE 3. Patient with Behcet disease. After 2 months of systemisporine 150 mg, and colchicine 0.5 mg, postinflammatory vitreous care observed. Treatment included intravitreal triamcinolone 2 mg anand 2.

TABLE 1. Causes and Treatment of 59 Eyes With OcclusiveVasculitis Associated With Behcet Disease Over 25 Years

Diagnosis N (%) LP PRP IMT Observation

BRVO 12 (20.3%) 4 8

CRVO 2 (3.4%) 2

NVE 4 (6.8%) 4

NVD 4 (6.8%) 4

PV 37 (62.7%) 37

Total 59 (100%) 4 10 37 8

N number of eyes.BRVO branch retinal vein occlusion; CRVO central retinal

vein occlusion; IMT immunomodulatory therapy; LP retinallaser photocoagulation; NVD neovascularization of the disc;NVE neovascularization elsewhere; PRP panretinal photo-coagulation; PV peripheral vasculitis.

180 AMERICAN JOURNAL OFadministered. Visual outcomes and the treatment strategiesare summarized in Table 2. Only the combination of pred-nisone, cyclosporine, and infliximab demonstrated a signif-icant improvement in BCVA (P .032).The most common complications in the anterior segment

included glaucoma in 44 of 232 eyes (19%), followed by cat-aracts in 34 eyes (14.7%) and posterior synechiae in 14 eyes(6%). The most common posterior segment complicationsincluded optic nerve atrophy in 19 eyes (8.2%). Duringthe course of the disease, 60 eyes (25.9%) required surgery,of which 43 eyes (71.7%) underwent cataract surgery(Table 3), 7 eyes (11.7%) glaucoma surgery, 8 eyes(13.3%) posterior vitrectomy, and 2 eyes (3.3%) superficiallamellar keratectomy with ethylenediaminetetraacetic acidchelation. At last visit 20/50 (logMAR 0.4) or betterBCVA was achieved in 131 affected eyes (56.5%) and 20/200 (logMAR 1) or worse in 51 affected eyes (22%).

DISCUSSION

BEHCET DISEASE IS A MULTISYSTEM INFLAMMATORY

disease of unknown etiology, characterized by recurrent at-tacks of acute severe inflammation involving retinal

c therapy with oral administration of azathioprine 75 mg, cyclo-ondensations and complete resolution of cystoid macular edemad intravitreal bevacizumab 1.25 mg. Same patient as in Figures 1

JANUARY 2015OPHTHALMOLOGY

h a history of decreased visual acuity of his left eye. (Left) Dilatedat generates a tractional retinal detachment in the posterior pole.administered before vitrectomy. Note the vascular regression butsit after pars plana vitrectomy plus peeling and intraocular silicone

Prognosis for Behcet Disease Over 25 Years

Basal BCVA Final BCVA

P ValueRS logMAR ETDRS logMAR

150 0.9 6 0.6 20/80 0.6 6 0.8 .074

150 0.9 6 0.6 20/125 0.8 6 1.1 .436FIGURE 4. Patient with Behcet disease: a 29-year-old man witfundus examination shows a large fibrovascular proliferation th(Middle) Antiangiogenic therapy (1.25 mg of bevacizumab) wasalso increased fibrous contraction. (Right) First postoperative vioil. Retina is attached.

TABLE 2. Treatment Strategies and Visual

Patients, n (%) Eyes, n (%) ETD

PDAZACSP 44 (33.3%) 72 (31.1%) 20/PDCSP 35 (34.1%) 64 (27.6%) 20/arteries and veins.1,2 Ocular involvement occurs inapproximately 70% of patients and is associated with ahigh risk of blindness.15 We found that the mean age atonset of uveitis was 36.9 6 11.4 years, which is consistentwith other studies that have reported a range of onset be-tween 28.5 and 35 years.1618

Behcet disease is more prevalent along the ancient SilkRoad that extends from the eastern Mediterranean toJapan. Men are affected more than women, with a 10:1 ra-tio in these countries.19 The male predominance in ourstudy is very high (77.3%). There are no differences in ac-cess to health care based on sex in Saudi Arabia. Therefore,there is no bias in the estimation of male predominance inour study. The strongmale preponderance in our study con-curs with previous reports from countries along the ancientSilk Road.17,18,20 Male subjects comprised 63% of allpatients in Japan16 and 68% of all patients in Turkey.18

However, 1 report from Israel reported a lower male pre-ponderance at 53% of all patients.21 A report from Italyhad a population with an even distribution (50%) insex.22 A study from the United States reported a slightlygreater preponderance in female subjects (52.8%) in casesof Behcet disease that involved the posterior segment.23

Prednisone 16 (12.1%) 30 (12.9%) 20/125

PDAZA 16 (12.1%) 28 (12.1%) 20/80PDCSPIFX 10 (7.5%) 16 (6.9%) 20/200CSPAZA 5 (3.8%) 10 (4.3%) 20/40MTXCSP 4 (3.0%) 8 (3.4%) 20/100PDMTXIFX 2 (1.5%) 4 (1.7%) 20/50

AZA azathioprine; BCVA best-corrected visual acuity; CSP cyIFX infliximab; logMAR logarithm of the minimal angle of resolution;

VOL. 159, NO. 1 SURVEY OF UVEITIS IN BEHCETWe found that the most common forms of ocular presen-tationwere panuveitis, followed by anterior uveitis, affecting118 patients (89.4%) and 10 patients (7.6%), respectively.Intermediate uveitis was observed in 4 patients (3%).Studies from other countries have also reported that panu-veitis was the most frequent ocular manifestation in patientswith Behcet-associated uveitis.2427

The frequency of bilateral involvement ranges between78% and 95% in many studies.8,18,2830 Similarly, we

0.8 6 0.9 20/100 0.7 6 1.2 .551

0.6 6 0.5 20/100 0.7 6 1 .726

1 6 0.3 20/50 0.6 6 0.4 .032

0.3 6 0.3 20/25 0.1 6 0.1 .433

0.7 6 0.8 20/30 0.2 6 0.7 .091

0.4 6 0.3 20/50 0.4 6 0.5 .677

closporine; ETDRS Early Treatment Diabetic Retinopathy Study;MTX methotrexate; PD prednisone.

TABLE 3. Eyes With Behcet Disease That UnderwentSurgical Procedures Owing to Cataracts

Procedure Eyes (n) Percentage

PHACO IOL 21 48.8%PHACO alone 15 34.9%

LA IOL 6 14.0%EECC IOL 1 2.3%Total 43 100%

EECC extracapsular surgery; IOL intraocular lens;LA lens aspiration; PHACO phacoemulsification.

181DISEASE OVER 25 YEARS

8,18,32,33

FO; NoultaH.Tugal-Tutkun and associates18 evaluated 880 patientswith Behcet disease and found that vitritis and retinalvasculitis were the most common findings of uveitis andwere eventually observed in every patient with panuveitis(89%). The second most common ocular finding of uveitiswas retinitis (51.6%).18 Similarly, our patients with panu-veitis (n 118) had retinal vasculitis in 51.7% of cases(n 61) and occlusive vasculitis in 50.0% of affectedeyes (n 59).Visual prognosis in Behcet disease prior to the 1980s was

poor. Turkey and Japan have a high incidence of Behcetdisease.7,8 Studies from these countries indicated the riskof blindness was high.8,31,32 For example, patients becameblind over an average of 3 years after the onset of ocularsymptoms31 and achieved BCVA of 20/200 or worse within4 years in 50%90% of cases.32 However, the prevalence oflegal blindness was reported to be 25% inNorthAmerica.33

Mishima and associates8 and Mamo and associates32 foundthat more than 50% of the Japanese Behcet patients had avisual acuity of 20/200 or less in 5 years of follow-up. How-ever, the 1992 statistics from Japan showed a markedimprovement in visual prognosis, with only 20% of the pa-tients with a final visual acuity of

intcriptudorer An (VaniEidUve13. Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization ofUveitis Nomenclature (SUN) Working Group. Standardiza-tion of uveitis nomenclature for reporting clinical data. Re-sults of the First International Workshop. Am J Ophthalmol2005;140(3):509516.

14. Nussenblatt RB, Palestine AG, Chan CC, Roberge F.Standardization of vitreal inflammatory activity in inter-mediate and posterior uveitis. Ophthalmology 1985;92(4):467471.

15. Verity DH,Wallace GR, Vaughan RW, StanfordMR. Behcetdisease: from Hippocrates to the third millennium. Br JOphthalmol 2003;87(9):11751183.

ish patients with Behcet disease and ocular inflammation. EurJ Ophthalmol 2008;18(4):563566.

28. Atmaca LS. Fundus changes associated with Behcet disease.Graefes Arch Clin Exp Ophthalmol 1989;227(4):340344.

29. Barra C, Belfort R Jr, Abreu MT, et al. Behcets disease inBrazil - a review of 49 cases with emphasis on ophthalmicmanifestations. Jpn J Ophthalmol 1991;35(3):339346.

30. Ambresin A, Tao Tran V, Spertini F, Herbort CP. Behcet dis-ease in western Switzerland: epidemiology and analysis ofocular involvement. Ocul Immunol Inflamm 2002;10(1):5363.M.Y.A.J., N.A.A.S., A.M.A.-M, Y.A.A.-Z.), management, analysis, andA.M.A.-M, Y.A.A.-Z.); and preparation, review, or approval of the manus

The King Khaled Eye Specialist Hospital (KKESH) Uveitis Survey SHassan A. Al-Dhibi (Principal Investigator), J. Fernando Arevalo (Vitre

itis), Mohanna Yousef Al Jindan (Anterior Segment and Uveitis), Nasse(Pediatrics, Vitreoretinal and Uveitis), Sulaiman Mohammad Al SulimaUveitis), Abdulaziz Adel Al Rushood (Vitreoretinal), Yahya A. Al-Zahrand Uveitis), Hassan Mohamad Al Taweel (Pediatrics and Uveitis), Sultan(Anterior Segment and Uveitis), Dhafer Saad Al Qahtani (Glaucoma andand Uveitis).

REFERENCES

1. International Study Group for Behcet Disease. Criteria fordiagnosis of Behcet disease. Lancet 1990;335(8697):10781080.

2. Sakane T, Takeno M, Suzuki N, Inaba G. Behcet disease. NEngl J Med 1999;341(17):12841291.

3. Behcet H. Uber rezivierende, aphtose, durch ein Virus verur-sachte Geschwiire am Mund, am Auge und an den Genita-lien. Dermatol Wochenschr 1937;105:11521157.

4. Shigeta T. Recurrent iritis with hypopyon and its patholog-ical findings. Acta Soc Ophthalmol Jpn 1924;28:516521.

5. Adamantiadis B. Sur un cas diritis a hypopyon recidevante.Ann Ocul 1931;168:271274.

6. Feigenbaum A. Description of Behcet syndrome in the Hip-pocratic third book of endemic diseases. Br J Ophthalmol1956;40(6):355357.

7. Azizlerli G, Kose AA, Sarica R, et al. Prevalence of Behcetdisease in Instanbul, Turkey. Int J Dermatol 2003;42(10):803806.

8. Mishima S, Masuda K, Izawa Y, Mochizuki M, Namba K. Theeighth Frederick HVerhoeff Lecture. Behcet disease in Japan:ophthalmologic aspects. Trans Am Ophthalmol Soc 1979;77:225279.

9. Islam SM, Tabbara KF. Causes of uveitis at The Eye Center inSaudi Arabia: a retrospective review. Ophthalmic Epidemiol2002;9(4):239249.

10. Yazici H, Fresko I, Yurdakul S. Behcet syndrome: diseasemanifestations, management, and advances in treatment.Nat Clin Pract Rheumatol 2007;3(3):148155.

11. Behcet Disease Research Committee of Japan. Behcet dis-ease: guide to diagnosis of Behcet disease. Jpn J Ophthalmol1974;18:291294.

12. Jabs DA, Rosenbaum JT, Foster CS, et al. Guidelines for theuse of immunosuppressive drugs in patients with ocular in-flammatory disorders: recommendations of an expert panel.Am J Ophthalmol 2000;130(4):492513.VOL. 159, NO. 1 SURVEY OF UVEITIS IN BEHCETerpretation of the data (A.F.L., M.Y.A.J., H.A.A.D., J.F.A., N.A.A.S.,t (J.F.A., A.F.L., M.Y.A.J., N.A.A.S., A.M.A.-M, Y.A.A.-Z, H.A.A.D.).y Group.tinal and Uveitis), Ammar M. Al-Mahmood (Anterior Segment and Uve-bdulmohsen Al Sabaani (Anterior Segment), Hanan Nasser Al Shamsiitreoretinal and Uveitis), Mohammed Ali Al Shamrani (Pediatrics and(Vitreoretinal and Uveitis), Mosa Barakat Al Harbi (Anterior Segmentah Al Zaaidi (Anterior Segment and Uveitis), Turki Abdullah Al Ghamdiitis), Vishali Gupta (Vitreoretinal and Uveitis), Igor Kozak (Vitreoretinal

16. Kitaichi N, Miyazaki A, Iwata D, Ohno S, Stanford MR,Chams H. Ocular features of Behcet disease: an internationalcollaborative study. Br J Ophthalmol 2007;91(12):15791582.

17. Yoshida A, Kawashima H, Motoyama Y, et al. Comparison ofpatients with Behcet disease in the 1980s and 1990s.Ophthal-mology 2004;111(4):810815.

18. Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, HuseyinAltunbas H, Urgancioglu M. Uveitis in Behcet disease: ananalysis of 880 patients. Am J Ophthalmol 2004;138(3):373380.

19. Evereklioglu C. Current concepts in the etiology and treat-ment of Behcet disease. Surv Ophthalmol 2005;50(4):297350.

20. Keino H, Okada AA. Behcet disease: global epidemiology ofan Old Silk Road disease. Br J Ophthalmol 2007;91(12):15731574.

21. Krause I, Yankevich A, Fraser A, et al. Prevalence and clin-ical aspects of Behcet disease in theNorth of Israel.Clin Rheu-matol 2007;26(4):555560.

22. Salvarani C, Pipitone N, Catanoso MG, et al. Epidemiologyand clinical course of Behcet disease in the Reggio Emilia areaof Northern Italy: a seventeen-year population-based study.Arthritis Rheum 2007;57(1):171178.

23. Kacmaz RO, Kempen JH, Newcomb C, et al. Systemic Immu-nosuppressive Therapy for Eye Diseases Cohort Study Group.Ocular inflammation in Behcet disease: incidence of ocularcomplications and of loss of visual acuity. Am J Ophthalmol2008;146(6):828836.

24. Chung YM, Lin YC, Tsai CC, et al. Behcet disease with uve-itis in Taiwan. J Chin Med Assoc 2008;71(10):509516.

25. Khairallah M, Attia S, Yahia SB, et al. Pattern of uveitis inBehcet disease in a referral center in Tunisia, North Africa.Int Ophthalmol 2009;29(3):135141.

26. Yang P, Fang W, Meng Q, et al. Clinical features of Chinesepatients with Behcet disease. Ophthalmology 2008;115(2):312318.

27. Saenz-Frances F, Elas de Tejada M, Martnez de la Casa JM,et al. Ocular inflammatory signs observed in a cohort of Span-183DISEASE OVER 25 YEARS

31. Boyd SR, Young S, Lightman S. Immunopathology of thenoninfectious posterior and intermediate uveitides. SurvOphthalmol 2001;46(3):209233.

32. Mamo JG. The rate of visual loss in Behcet disease. ArchOphthalmol 1970;84(4):451452.

33. Michelson JB, Chisari FV. Behcet disease. Surv Ophthalmol1982;26(4):190203.

34. Mochizuki M. Up-to-date treatment for Behcet disease.AsianMed J 1998;41:320325.

35. TakeuchiM, Kezuka T, Sugita S, et al. Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis inBehcets disease: a multicenter study. Ophthalmology 2014;121(10):18771884.

36. Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A,VanGelder RN. Expert panel recommendations for the use ofanti-tumor necrosis factor biologic agents in patients withocular inflammatory disorders. Ophthalmology 2014;121(3):785796.

37. Deuter CM, Zierhut M, Mohle A, Vonthein R,Stobiger N, Kotter I. Long-term remission after cessationof interferon-a treatment in patients with severe uveitisdue to Behcets disease. Arthritis Rheum 2010;62(9):27962805.

38. Mesquida M, Molins B, Llorenc V, et al. Current and futuretreatments for Behcets uveitis: road to remission. Int Ophthal-mol 2014;34(2):365381.184 AMERICAN JOURNAL OF JANUARY 2015OPHTHALMOLOGY

Biosketch

Dr J. Fernando Arevalo is The Edmund F. and Virginia B. Ball Professor of Ophthalmology and Retina faculty at Johns

Hopkins University in Baltimore, USA, and Chief of the Retina Division of the King Khaled Eye Hospital in Riyadh,

Saudi Arabia. In addition, Dr Arevalo is the current Executive Vice President of the Pan-American Association of

Ophthalmology. Dr Arevalo has made significant contributions to the understanding and treatment of vitreoretinal

diseases, uveitis and intraocular inflammation, and ocular oncology.VOL. 159, NO. 1 184.e1SURVEY OF UVEITIS IN BEHCET DISEASE OVER 25 YEARS

Biosketch

Dr Hassan A. Al Dhibi is a Senior Academic Consultant at the King Khaled Eye Specialist Hospital (KKESH), chief of the

Uveitis Division, and a member of the Vitreoretinal Disease and Surgery Division. He is also a clinical assistant professor in

the College of Medicine, King Saud Unviersity (KSU). Dr Dhibis major interest is Clinical research in uveitis and diabetic

retinopathy. He was involved in several major research projects and has given over 70 presentations at various conferences.184.e2 JANUARY 2015AMERICAN JOURNAL OF OPHTHALMOLOGY

Uveitis in Behet Disease in a Tertiary Center Over 25 Years: The KKESH Uveitis Survey Study GroupPatients and MethodsResultsDiscussionReferences