CENTRAL SEROUSRETINOPATHY

By Dr. ANKUSH DEEPAK WEGINWAR

INTRODUCTION

Central serous chorioretinopathy (CSC /CSCR) most popularly known as “CSR (Central Serous Retinopathy)” is a sporadic disease of unknown etiology

Characterized by blister like serous detachment of neurosensory retina and retinal pigment epithelium (RPE) in the posterior pole of the eye.

The term “central” refers to the form of the disease causing visual symptoms due to the presence of serous detachments in the macular area

• Usually unilateral• May be associated with pigment epithelial detachment (PED)• Relative preservation of visual function despite prolonged separation of neural retina

from the retinal pigment epithelium

This condition was first described by

Von Graefe in 1866 as “Relapsing Central Luetic Retinitis”

1955 – Bennett – “Central Serous Retinopathy”

Synonyms:Central Serous RetinopathyCentral Serous Pigment EpitheliopathyCentral Serous Retinitis

EpidemiologyIncidence 1 in 22,000

o Accounts for about 5% of the cases attending the retina specialisto It is now considered to be one of the ten most common diseases of the posterior

segment of the eye

Age: 20 – 50 years

o Patients diagnosed at 50 years or older are found to have bilateral disease, demonstrate a decreased male predominance (2.6:1), and show more diffuse RPE changes

Gender: Male > female 6:1

Race: Whites and Asians>blacks

Causative Factors

Emotional stressType A personalityPhysical StrainsPregnancyPeople engaged in visually demanding workHelicobacter pylori infection has been reported to be associated with CSCSmoking,Alcohol consumption and allergic respiratory diseasesObstructive sleep apneaHyperopic eyeVasoconstrictive agents, endogenous hypercortisolism, Systemic corticosteroids, SLE,

Hypertension

RPE damaged via immunologic infectious

circulatory and neuronal mechanism

RPE secretsions in chorio retinal direction

towards retina

Choroidal fluid gets attracted into this area

Strong flow disrupts the diffusion barrier in this

area

PATHOPHYSIOLOGY

Psychogenic,Pregnancy,Type A personality,rais

ed cortisols

Adrenergic reaction causes damage to the choricapillaries

Hyperpermeability of

choriocapillaries

RPE cell degeneration

Secondary changes in RPE

causes leaks

Serous retinal detachment

Mechanism

o The presence of fibrin in the detached space itself indicates that there is sufficient alteration in the permeability of the choriocapillaries and the RPE

o As the choriocapillaris are fenestrated, the interstitial fluid within the choroid can be expected to have a large range of molecules

o Normally resorption of fluid and protein molecules within the choroid primarily occurs by free exchange through these fenestrated vessels and some excess amount is also drained through the sclera

o In acute CSC, the amount of fluid and solutes are definitely more than what the RPE

cells normally can cope with.

o The increase in interstitial hydrostatic pressure in the choroid drives the fluid towards the retina and leads to the development of PED

o Microrips at the junction of attached and detached RPE or along the decompensated RPE cells that cause fluid leak into the subretinal space. The micro rents usually occur in the parafoveal region

o Once the detachment occurs, it would continue to enlarge until sufficient normal RPE is exposed to the exuded fluid which would drain it out at a rate equal to the inflow rate through the leak

o Thus, the detached space in CSC has a dynamic environment into which, and from which, there is a continuous flux of water, ions, and protein

Role of Corticosteroids and the Catecholamines

It produce CSC by following mechanisms:

o Corticosteroids may cause increased capillary fragility and hyperpermeability

o Affect the production of nitric oxide, prostaglandins, and free radicals, which may affect the regulation of blood flow in the choroids

o Inhibit formation of collagen, which is the main component of Bruch’s membrane

o Alter ion water transport of epithelia

o May directly damage the RPE cells or their tight junctions;

o May delay any reparative process in damaged RPE cells , by suppressing the synthesis of extracellular matrix components and inhibiting fibroblastic activity

o Can influence the transcription and expression of adrenergic receptor genes and regulate adrenergic receptors

o Stimulation of adrenergic receptors within the choroidal circulation results in release of secondary messengers (e.g. cAMP ) and this may produce the vascular or RPE changes that result in CSC

o Increase catecholamine mediated vasoconstriction

Role of VEGF

o Vascular endothelial growth factor (VEGF) is produced by damaged retinal and choroidal cells when abnormal perfusion causes ischemia.

o By uncoupling endothelial cell-to cell junctions, VEGF causes vascular permeability and edema

o The affected RPE cells start leaking fluid that would move towards the retina as there is less resistance in this direction

Acute CSCR: self-resolving SRD (sub retinal detachment) within 4 months from the onset of symptoms

Non-resolving CSCR (or “persistent” CSCR): acute CSCR with duration of SRD longer than 4 months after onset of symptoms, often associated with elongated photoreceptor outer segments on SD-OCT.

Recurrent CSCR: episode of acute CSCR following a previous episode with complete SRD resolution

Chronic CSCR (formerly “diffuse retinal epitheliopathy”): chronic chorioretinopathy with widespread RPE decompensation with or without SRD, associated or not with active leakage sites

Inactive CSCR: patients with history of acute CSCR but without SRD at the time of evaluation

Blurred vision

Positive Scotoma

Micropsia

Metamorphsia

Imapired Colour vision

Impared Night vision

Entoptics

Light flashes

Photophobia

Impaired depth perception

Headache

Chromatopsia

Cyanopsia

SYMPTOMS

Presentation:

Unilateral blurred vision with a relative scotoma in the central visual field Unilateral metamorphopsia and/or micropsia Patients with extrafoveal involvement may be asymptomatic

Visual acuity:

VA ranges from 6/5 to 6/60, usually 6/9 – 6/12 Acquired hyperopia

SIGNS Relative hyperopia Positive photostress test Fundus

o A round to oval sensory retinal detachment is present at the posterior poleo In some small PED within the serous detachment may be evidento Absent foveal reflexo Small dot like deposits in the posterior of retina which is believed to be the

precipitates of plasma proteins including fibrin

Fundus photograph of CSC with fibrin deposit

Fundus photograph of CSC with subretinal precipitates

CSC in Women

o There is a significant difference in the male to female ratio in CSC cases.

o Cortisol responses to psychologic stress was found to be more in male than in female

o CSC in otherwise healthy women tends to occur at an older age than men.

o Conditions commonlyc associated with CSC in women are

Pregnancy Systemic lupus erythematosus.

o Elevation of catecholamine, corticosteroids, estrogen and other hormone levels during pregnancy may be responsible for it

o Increased levels of prostacyclin during the second and third trimester may be another important factor.

Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation

Atypical Presentation of CSC

Bullous or Severe variant of CSC Cystoid macular edema Ring retinal pigment epithelial window defect Leopard spot pattern Secondary choroidal vascularization Retinal telangiectasia with lipid deposition CSC simulating pattern dystrophy CSC with retinitis pigmentosa Choroidal folds without any evidence of underlying scleritis and with episcleritis

Natural History

CSC is a self-limited disease, but runs a very unpredictable course.

However, the natural course of the disease seems to have 4 distinct patterns

(1) CSC with a single resolving episode(2) Recurrent resolving CSC –recovery is complete before the recurrence(3) Recurrent chronic CSC –recurrence before full recovery (4) Chronic CSC - following a single episode without any appreciable recovery

o The symptoms / sensory retinal detachment (SRD) persist beyond the usual period of recovery, that is, 6 months.

o In majority (80 to 90%) spontaneous resolution occurs within 1 to 6 months and in 20% it lingers for more than this period 6-12 months

o But even after recovery, the quality of vision is not the same as before in all the cases.

o The improvement of vision may continue for more than 1 year following resolution.

Poor visual outcome may also be due to development of cystic degeneration of the macula or cystoid macular edema or due to development of a macular choroidal neovascular membrane

Bilaterality of CSC

o CSC was once considered as a unilateral disease, but now the literature documents 5-35% incidence of bilateral CSC.

o This tendency increases with age.

According to Gass , approximately 10 to 25% develop symptomatic detachment in the opposite eye. Bujarborua et al found the overall prevalence of bilateral pathology of CSC to be 44.54%

at the initial visit using FA as the only investigative procedure.

Yannuzzi et al (1979) reported that 10% of the patients of their series had a concomitant acute SRD in the fellow eye and additional 12% developed the same during the followup period ranging from 2 to 8 years.

They also observed RPE atrophy and pigmentary changes in about 80% of the fellow eyes by the end of their period of observation.

DIAGNOSIS

Distance & Near Visual Acuity testing Retinoscopy Amsler Grid Photostress test/Dazzling time/Re adaptation time Ophthalmoscopy

Special investigations

FFA ICG OCT

FFA critical to detect the extent of the retinal abnormalities and to exclude the presence of other ocular pathology

INVE

STIG

ATIO

NS

FFA

ICG

OCT

FFA

Fluorescein angiography in CSC reveals various types of leaks at the level of RPE depending on the stage of the disease. These leaks are seen in about 95% of all cases of all types of CSC

Smoke-stack appearance:• Small hyperfluorescent spot in the early phase due to leakage of dye through the RPE• Fluorescein passes into the subretinal space and ascends vertically until the upper border, like a

smoke-stack, in the late venous phase• The dye then spreads laterally, taking on a “mushroom” or “umbrella” configuration until entire

area of detachment is filled

Ink-blot appearance:

• Seen in 93% cases• Leakage point/s with uniform dye filling is appreciated• Most common location – upper nasal quadrant• Least common location – lower temporal quadrant

In majority of cases (60%), the point leak that appear in the initial phase of the angiography slowly and symmetrically spread in all sides to about l/4th DD (inkblot type)

This type of leak probably suggests late phase of the active disease process and the active stage itself may be of variable duration

Point Leaks:

o Some leaks do not expand much. These are the so called minimally expanding point leak, whose expansion is always less than l/5th disc diameter in size.

o These types of leaks are usually found in subtle serous detachment of the retina.

o Besides these - diffuse leak, decompensatory leak, window defects of various sizes and PEDs are visible on FA.

ICG

o ICGA is one of the most important investigations in CSC because it demonstrates the choroidal vascular abnormalities and can act as a guide to treatments such as photodynamic therapy.

o Common findings in patients with CSC are multi focal areas of hyper fluorescence in the early and mid phases of the study, which then fade in the late phase of the study

a) Depicting FA findings and b) Depicting the ICGA findings of the same fundus showing multiple hyperpermeable areas

OCTo OCT can detect detachments that remained undetected in FA.o It can also detect subretinal deposits like fibrin and subretinal precipitates

a) Sub sensory fluid accumulation in CSC b) Detected shallow SRD along with PED

Fundus picture and OCT image showing subretinal fibrin deposit

Recently introduced Ultra-high resolution OCT provides an axial resolution of approximately 3 μm that allows improved visualization of the external limiting membrane (ELM), photoreceptor inner and outer segment junctions (IS / OS) and identification of pathologic changes in the microstructure of the photoreceptor layer.

Fourier-domain OCT (FD-OCT) provides a three dimensional view of these structures

Fundus Autofluorescence (FAF) in CSCo This technique is designed to document the presence of lipofuscin in the RPE

o Lipofuscin is a mixture of proteins, lipids, and small chromatophores generated as by-products of the retinoid cycle.

o The accumulation of lipofuscin in the RPE is due to impaired or overwhelmed lysosomal activity, leading to incompletely

digested cellular debris

o The presence of FAF is thought to correspond to the accumulation or dispersion of lipofuscin in the subretinal space or RPE

FAF typically shows hypofluorescence at the leakage point and over the area of neurosensory detachment due to blockage by subretinal fluid

The subretinal yellow dots observed clinically might demonstrate hyperfluorescence

In chronic-recurrent CSC, hyperfluorescence is common in areas of residual neurosensory detachment.

Other tests

Multifocal ERG has been used to identify focal regions of decreased retinal function, even in asymptomatic or clinically inactive eyes.

Microperimetry has also shown that, despite clinical resolution of CSR, there is lower retinal sensitivity in the macula even once visual acuity returned to 20/20

Macular hole

Optic pit

Malignant Hypertension

AMD

Idiopathic uveal effusion syndrome

Ocular histoplasmosis syndrome

Vogt-Koyanagi-Harada’s disease

Pathological myopia

Choroidal tumors

Differential Diagnosis

Treatment

Observation

Medical

Surgical

Management

Non-Drug Treatment

Reduce stress levels: Biofeedback, meditation, taking a philosophical approach to adversityYoga Avoid caffeine containing drinks ( caffeine stimulatesnthe pituitary gland and increases the

cortisol level )Avoid excess alcohol consumption. Try to avoid “ cortisone treatments ” as far as possible (Monitor cortisol level if possible) Avoid unnecessary stress like disease (any form of infection increases cortisol levels),

excessive exercise, crash diets, jet lag, pain, lack of sleep etc

It has been recommended that if symptoms persist for more than 3 months, further active treatments should be considered

Medical Treatment

Ketoconazole: Anti-fungal drug of Imidazole group Adrenocorticoid antagonist Lowers the endogenous cortisol level in CSC cases after 4 weeks treatment with 600 mg

per day dose of the drug The median visual acuity, lesionnheight and the greatest linear dimension remained

unchanged during the month of treatment. It seems therapeutic effect would require longer time.

Acetazolamide (Diamox) Also shown to be effective Given in a tapering dose for 6 weeks has been shown to reduce the time for subjective

and objective CSR resolution But it can not prevent recurrences and Final visual recovery did not differ much from the control group. Moreover, this drug is having considerable side affects like paresthesias, nervousness,

and gastric upset and allergies

Bevacizumab (Avastin):

Antibodyvto VEGF (0.05 ml/1.25 mg intravitreal) Reduces the choroidal hyperpermeability Reverse the changes. Originally it was tried in chronic CSC cases. Now it has been tried in acute cases with encouraging result.

Beta-blockers

Metoprolol, Nadolol, and Trimepranol have been used with controversial results.

One recent double blind randomized controlled clinical trial from Iran found that Propanolol (20mg twice daily) cuts short the period of recovery and thereby eliminates the need for laser therapy.

But it does not have any effect on visual recovery and its effect on recurrence rate could not be commented as it had a short term follow-up

Laser Photocoagulation in CSC

Light to moderate intensity applications of all modalities of laser like ruby, argon, krypton, diode and dye laser photocoagulation help in resolution of the detachment in CSC

Accelerates the resolution of the detachmentlowers the recurrence rate

MOA:

1. Beam destroys the cluster of diseased pigment epithelium cells, thus stopping the secretion of fluid beneath the neurosensory retina

2. Resulting scar helps to transport fluid back into the choriocapillaris

Indications:

Persistence of serous detachment beyond 3-4 months Recurrences in eyes with visual deficit from previous episodes Presence of permanent visual deficit from previous episodes in the fellow eye Development of chronic signs such as cystic changes in the neurosensory retina or

widespread RPE abnormalities Occupational or other patient needs that require prompt restoration of vision or

stereopsis

Technique 2 – 3 low to moderate intensity burns applied to the leakage site

spot size of 200µm, for 0.1 seconds

to produce mild graying of the RPE Decreases of duration of detachment.

Advantages

Decreased durationDecreased recurrence

Complications

Choroidal neovascularizationCentral scotoma

Should be avoided if the leak is within 500mm from the centre of the foveal avascular zone

Careful follow up required as 2 – 5% of eyes treated with photocoagulation develop CNV

Photodynamic Therapy (PDT) in CSC Use of verteporfin and PDT was first reported in 2003 in the setting of CSC. Yannuzziet al89 used ICG angiography to first identify areas of choroidal hyperpermeability, which

were subsequently treated by PDT.

Most papers describe resolution of subretinal fluid within 1 month of treatment.

Mechanism o Postulated to be caused by short-term choriocapillaris hypoperfusion and long-term choroidal

vascular Remodeling

The application of conventional PDT in CSC can result RPE atrophy Choroidal ischemia Secondary choroidal neovascularization

To enhance the efficacy of PDT in treating CSC while minimizingits side effects, the dose of verteporfin has been reduced and the time interval between infusion and laser application has also been

ICG mediated photothrombosis is a technique using a low-intensity laser combined with ICG dye infusion to treat focal areas of hyperpermeability in the choroid.

Submacular Surgery in CSCThe current treatment options for the treatment of subfoveal or juxtafoveal choroidal neovascularization in CSC do not preserve macular function.

Cooper et al did submacular surgery for removal of choroidal neovascularization in 10 cases.

It was observed that the eyes, in which the central retinal RPE was preserved had the best visual outcome and the best cases for surgery appeared to be the eyes in which the neovascularization lied anterior to the RPE.

Removal of such membranes could leave the underlying foveal pigment epithelium intact.

As the choroidal neovascular membrane develops in CSC from a focal rather than diffuse abnormality of RPE, it offers the potential for preservation of central retinal pigment epithelium

Course and Outcome of CSRSelf-limiting and 90% of the cases will show spontaneous recovery within a few months

CSC recurs in about 50% of the patients within the first year

A history of psychiatric illness is associated with a higher rate of recurrence

Small proportion of patients develop RPE atrophy, CNV development (in up to 6% of patients), and transformation into PCV (Polypoidal choroidal vasculopathy)

Patients whose VA recovered might be left with residual symptoms such as metamorphopsia, scotoma, and reduced contrast sensitivity.

REFERENCES

Stephen Ryan text book of RETINA 3rd edn Retinal and Vitreoretinal diseases and Surgery by

Samuel Boyd Kanski 8th edn Parsons Diseases of the Eye 22nd edn