IDIOPATHIC CNV

Patients presenting with idiopathic CNV usually have unilateral CNV and have a low risk of developing CNV in the fellow eye. There are no known ocular or systemic associations with idiopathic CNV.2

ETIOLOGY AND PATHOGENESIS

The mechanisms involved in the pathogenesis of CNV are not fully understood. Aging and genetically determined changes in the RPE– Bruch’s membrane–choriocapillaris complex are important in inducing CNV, and wound-healing responses are instrumental for their progression and resolution.1 Studies of eyes with CNV obtained surgically or postmortem have led to the concept that the development of CNV represents a wound repair response to a specific stimulus provided by the underlying disease. There are three basic CNV growth patterns: (1) subRPE, between the RPE and Bruch’s membrane (type 1); (2) subretinal, between the retina and RPE (type 2); and (3) both subRPE and subretinal (combined). The type 1 pattern of CNV is the most typical pattern seen in AMD and starts with multiple ingrowth sites. The type 2 growth pattern likely occurs with single or few ingrowth sites and may occur in focal disease processes, such as POHS.18

Angiogenesis plays a causal role in the development of CNV in AMD. Vascular endothelial growth factor (VEGF) has been implicated as a major angiogenic stimulus responsible for neovascularization in AMD. VEGF stimulates angiogenesis through the promotion of endothelial cell proliferation and survival, vascular permeability, and recruitment of leukocytes.19 Although the pathogenesis of CNV formation in other diseases may be different from that in AMD, preliminary evidence showing improvements in response to antiangiogenic therapy suggests that VEGF is also important in CNV attributable to causes other than AMD.

The pathogenesis of CNV due to non-AMD causes is often related to inflammation in close proximity to Bruch’s membrane or breaks in Bruch’s membrane, as in angioid streaks or lacquer cracks in myopia.2 The pathogenesis of CNV in POHS is not clearly defined, but is believed to be related to focal infection or inflammation of the choroid at the time of systemic infection or autoimmune trigger. Choroidal scars represent a focal disruption of Bruch’s membrane which leads to the formation of CNV. The stimulus that promotes the progression of some atrophic scars to neovascularization, while others remain quiescent, remains unknown.9,12 The growth of new vessels in cases of inflammation suggests that inflammation, or injury resulting from inflammation, may be a driving stimulus for neovascularization.2

DIAGNOSIS AND ANCILLARY TESTING

MYOPIA

Myopic CNV is typically seen on biomicroscopy as a small, flat, grayish, subretinal membrane with hyperpigmented borders. The membranes are usually less than 1 disc diameter in size and are located in the subretinal space (type 2). Most myopic CNV is subfoveal or juxtafoveal with minimal subretinal fluid, hemorrhage, or exudate.

Fluorescein angiography (FA) is used to confirm the diagnosis of CNV. Myopic CNV tends to have a classic pattern of leakage on FA, with transit-phase hyperfluorescence followed by minor leakage in late phases (Figure 23.1). Indocyanine green (ICG), which is minimally absorbed by the RPE and blood, may allow better differentiation of CNV when subretinal hemorrhage or surrounding atrophy is present. FA and ICG angiography also help to detect subtle lacquer cracks.3,20

Optical coherence tomography (OCT) produces high resolution cross-sectional images of the retina and is useful in evaluating CNV and other macular pathologies. OCT can aid in treatment decisions by localizing CNV and detecting the presence of associated retinal thickening

or subretinal fluid. Fluid accumulation within the neurosensory retina is usually moderate with myopic CNV (Figure 23.1).3,20

PRESUMED OCULAR HISTOPLASMOSIS SYNDROME

Presumed ocular histoplasmosis is a clinical diagnosis and relies on observation of characteristic fundus lesions in one or both eyes. The diagnosis of POHS is typically based on the presence of: (1) multiple discrete, atrophic choroidal scars in the macula or periphery that appear “punched out” of the inner layers of the choroid (histo spots); (2) peripapillary atrophy; and (3) CNV, or a fibrovascular disciform macular scar from resolution of CNV (Figure 23.2). In POHS, there is an absence of anterior chamber or vitreous inflammation. On fundus examination, the CNV appears as a yellow-green subretinal discoloration, sometimes surrounded by a pigment ring. In advanced cases, a central disciform scar from subretinal fibrosis is seen, and active CNV can be observed at the peripheral edge of the scar.8,9,12 Patients with POHS generally have type 2 (subretinal) CNV.

Fluorescein angiography is performed to evaluate for CNV in patients with symptomatic visual loss or any signs of exudation. Areas of RPE atrophy, as with histo spots, will stain on FA. POHS commonly exhibits a classic CNV pattern, with early hyperfluorescence and late leakage (Figure 23.2).21 OCT is performed to evaluate for intraretinal or subretinal fluid.

ANGIOID STREAKS

Angioid streaks are seen on ophthalmoscopy as irregular dark red to brown bands located deep to the retina and radiating from the optic disc. Fluorescein angiography can help to delineate the presence of angioid streaks when the ophthalmoscopic appearance is subtle. On FA, angioid streaks are variably hyperfluorescent depending on the condition of the overlying RPE (Figure 23.3). Transmission defects are seen in areas of thin RPE overlying an intact choriocapillaris. When present, CNV shows the classic increase in size and intensity of fluorescence as the angiogram progresses. Angioid streaks appear more prominent on ICG than on FA and fundus photography.15,16

INFLAMMATORY CAUSES

MCP is characterized by fundus lesions similar to those seen in POHS, including chorioretinal atrophic spots, peripapillary scarring, CNV, and linear streaks in the periphery. However, unlike POHS, patients with MCP have recurrent bouts of intraocular inflammation and are more likely to develop new chorioretinal atrophic lesions. MCP commonly presents with anterior and posterior chamber inflammation, and optic disc swelling may be seen.2,13

FA findings for MCP vary with the amount of intraocular inflammation. During quiescent periods, patients show scattered transmission defects in areas of chorioretinal atrophy. During active inflammation, retinal vascular leakage and late staining of the optic nerve may be seen. ICG angiography of active MCP shows numerous hypofluorescent spots and broad areas of hypofluorescence, corresponding to blind spots on visual field testing.2

There are two distinct subtypes or closely aligned disorders of MCP: punctate inner choroidopathy, characterized by smaller and more numerous lesions, and diffuse subretinal fibrosis, characterized by a prominent deposition of fibrosis associated with a multifocal choroiditis.2

DIFFERENTIAL DIAGNOSIS

AMD is the leading cause of CNV and should be considered in the differential diagnosis in virtually all cases. AMD is usually seen in patients older than 50 years of age. It is typically a bilateral process with associated clinical features of drusen, RPE atrophy, and focal pigmentary changes. Neovascular AMD is characterized by intraretinal or

Pharmacotherapy to Amenable Diseases Retinal • 3 section