Ординатура / Офтальмология / Английские материалы / Retinal and Vitreoretinal Diseases and Surgery_Boyd, Cortez, Sabates_2010

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71.Schaal S, Kaplan HJ, Tezel TH.Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor pharmacotherapy in age-related macular degeneration? Ophthalmology. 2008; 115:2199-205.

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Photodynamic therapy with intravitreal application of triamcinolone acetonide in age-related macular degeneration: functional results in 54 patients. Acta Ophthalmol. 2009;87:183-7.

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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, usually involving the macula with angiographically demonstrable choroidal hyperpermeability and RPE leakage. This condition was first described by von Graefe1 in 1866 as “Relapsing Central Luetic Retinitis”.

Demography

between 20 to 50 years of age. One recent study revealed mean annual age-adjusted incidences per 1,000,000 were 9.9 per men and 1.7 per women5. 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. Furthermore, these patients are more likely to have systemic hypertension or a history of corticosteroid use6. It is usually a self-limited disease, as the sensory detachment resolves spontaneously with fairly good recovery of vision, but in patients with recurrent episodes and chronic clinical course, significant visual loss can occur along with widespread RPE damage and retinal dysfunction.

Predisposing Conditions

The reported incidence of this disease in general population is one case a year in every 22,000 inhabitants2 and it accounts for about 5% of the cases attending the retina specialist3. It is now considered to be one of the ten most common diseases of the posterior segment of the eye4. It typically affects males

Psychological stress associated with sympathetic arousal has long been considered to be an important risk factor for development of CSC. As stress theory empathizes, negative stress (or distress) derives from a negative relationship between environment

(e.g. critical life events) and personality. A recent study7 observed personality based difficulties in emotional regulation associated with hostility in CSC cases. Association of type A personality with this ailment is now well established8. These types of people are also prone to hypertension and coronary heart disease.

CSC appears to be more common among Caucasians, Hispanics and Orientals9, but it is thought to be uncommon among African Americans10. A variant of CSC which is characterized by bullous exudative detachment is mostly seen in Asian countries, particularly in north-eastern part of it. CSC develops mostly in hyperopic eyes.

Cigarette smoking, uncontrolled systemic hypertension, pregnancy, allergic respiratory disease,11 use of Sildenafil citrate,12 systemic corticosteroid therapy,13 endogenous mineralo corticosteroid dysfunction,14 psoriasis,15 systemic lupus erythematosus,16 obstructive sleep apnea syndrome (OSAS)17 – appear to be probable risk factors.

A recent report18 from Europe suggests that Helicobacter Pylori mediated immune mechanism might be encountered in the pathophysiology of CSC.

Pathophysiology of CSC

The basic pathology of CSC is now considered to be an idiopathic choroidal vascular hyperpermeability19 and this excess permeability appears to be due to adrenergic alteration of the macular retina8. The RPE barrier damage is basically secondary to excessive work load of the ionic pumps, but could

also be primary as there are experimental evidences20, 21 of presence of adrenergic receptors in RPE. Several Indocyanine Green Angiography (ICGA) studies22-26 have shown presence of multiple hyperpermeable areas in the choroid, which were often bilateral though one eye was symptomatic. Several studies24,26 observed delayed filling of segments of choriocapillaries prior to the development of hyper-permeability. Kitaya et al24 were of the opinion that small, localized ischemic regions caused by non-perfusion or vasoconstriction of the choriocapillaries may induce collateral choriocapillary congestion around this region. However; a decrease in venous outflow of these areas may also have the effect of delaying the observed dye filling. The presence of fibrin in the detached space itself indicates that there is sufficient alteration in the permeability of the choriocapillaries and the RPE19. As the choriocapillaris are fenestrated, the interstitial fluid within the choroid can be expected to have a large range of molecules. 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 sclera19. In acute CSC, the amount of fluid and solutes are definitely more than what the RPE cells normally can cope with. Vascular endothelial growth factor (VEGF) is produced by damaged retinal and choroidal cells when abnormal perfusion causes ischemia. By uncoupling endothelial cell-to cell junctions, VEGF causes vascular permeability and edema27. The affected RPE cells start leaking fluid that would move towards the retina as there is less resistance in this direction. Several investigators22, 28-33 observed that the increase in interstitial hydrostatic pressure in the choroid drives the fluid towards the retina and leads to the development of PED

and 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. Kitaya et al24 observed foveal choroidal blood flow in eyes with CSC to be 45% less than the fellow normal eyes. Several Optical Coherence Tomography (OCT) studies34-36 noticed thickening of retinal layers in acute CSC. This finding indicates that enough of serous fluid enters the retinal stroma in the acute phase of the disease and retinal separation usually occurs in the posterior pole where the leaks develop. 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.28 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.37

Central Serous Chorioretinopathy

311

production of nitric oxide, prostaglandins, and free radicals, which may affect the regulation of blood flow in the choroids; Inhibit formation of collagen, which is the main component of Bruch’s membrane; Alter ion water transport of epithelia; May directly damage the RPE cells or their tight junctions; May delay any reparative process in damaged RPE cells, by suppressing the synthesis of extracellular matrix components and inhibiting fibroblastic activity; Can influence the transcription and expression of adrenergic receptor genes and regulate adrenergic receptors. 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; Increase catecholamine mediated vasoconstriction; Epinephrine could induce apoptosis in a doseand time-dependent manner in animal RPE cells. Such studies in human RPE cells are still lacking.42

Corticosteroids were once used for the treatment of CSC, but now it has turned out to be a precipitating factor for the development of CSC.8,38-40 In the published reports, almost all the routes of administration of corticosteroid have been implicated for the development or exacerbation of this disease. Garg et al41 found statistically significant higher incidence of endogenous cortisol level in urine and plasma of patients suffering from CSC.

Corticosteroids and the catecholamines can produce CSC by following mechanisms: Corticosteroids may cause increased capillary fragility and hyperpermeability; Affect the

Symptoms

The most frequent complaints are: blurred vision, positive scotoma, micropsia and metamorphopsia. The fall of vision is usually mild, but may be alarming. There may be mild aching pain in the eye, impaired colour vision; blurred near vision; impaired night vision; spontaneous entoptics; light flashes; photophobia and impaired depth perception. Sometimes migraine-like headache may precede or accompany the onset. Sometimes patient develops chromatopsia and in such a situation patient feels that they are seeing

the objects through yellow or brown glass. Rarely patients also complain of cyanopsia.

Signs

CSC usually develops in the posterior pole of the eye as round or ovoid blisterlike sensory retinal detachment of various sizes. The subretinal serous fluid is usually clear, but patchy turbidity may be seen due to presence of fibrin (Figure 1a). After few weeks of onset of the disease, tiny irregular white or yellow flecks become deposited on the posterior surface of the retina (Figure 1b). A recent OCT study43 suggests that early granular deposits may be composed of fragments of photoreceptor outer segments that accumulate when the phagocytosis photoreceptor outer segment material is disrupted by the serous detachment of the retina.

Retinal Pigment Epithelial

Detachment (PED)

Isolated PEDs may be seen in addition to sensory retinal detachment. PEDs may vary in size, but they are usually less than 0.25 disc diameter. At times PED lying under CSC is difficult to appreciate and it needs fluorescein angiography or OCT for detection. Giovannini et al44 observed choroidal hyperpermeability in 83.3% and irregular choroidal venous dilation in 33.3% of cases at the site or within an area of one disc diameter size from the PED. The Idiopathic PEDs are a variant of CSC. Spitznas45 categorized these as Type II CSC.

Subretinal Fibrin Deposit in CSC

In the initial phase, the subretinal fibrin produces a pale hazy appearance of the