INTRODUCTION

Choroidal neovascularization (CNV) represents a pathologic growth of new blood vessels extending from the choroid into the subretinal or subretinal pigment epithelium (subRPE) space. A significant cause of vision loss, CNV results from a wide range of disorders that affect the RPE–Bruch’s membrane–choriocapillaris complex.1 CNV due to agerelated macular degeneration (AMD) is the leading cause of irreversible severe vision loss among the elderly in the developed world. In patients younger than 50 years of age, CNV may occur as a secondary manifestation of various inherited and acquired conditions, including angioid streaks, high myopia, trauma, and infectious and inflammatory diseases. Idiopathic CNV refers to neovascularization which develops from an unknown etiology.2

DISEASE PREVALENCE

The prevalence of myopia in developed countries is reported to be between 11% and 36%, with degenerative myopia affecting up to onethird of the myopic population. The prevalence of degenerative myopia varies significantly among races and ethnic groups, from 0.2% in Egypt to 18% in Japan.3 In the United States, myopia affects up to 25% of the population, with approximately 2% demonstrating high myopia.4 A higher prevalence of myopia has been associated with younger birth cohorts, females, a higher educational level, higher socioeconomic classes, and near working habits.3 CNV is the most common visionthreatening complication of high myopia, affecting 5–10% of eyes with high myopia.5,6 In one series, high myopia was the most common cause of CNV in young patients, accounting for 62% of CNV cases in patients younger than 50 years of age.7

Presumed ocular histoplasmosis syndrome (POHS) is an inflammatory syndrome associated with systemic infection by Histoplasma capsulatum, a dimorphic fungus endemic in the soil in the Ohio and Mississippi river valleys of the United States. Epidemiologic studies have found the prevalence of POHS to range from 1.6 to 5.3%.8 POHS occurs mostly in Caucasians in the second to fifth decade of life, with some studies reporting a higher prevalence in women.9 POHS is the second leading cause of CNV in young patients, accounting for 12% of CNV cases in this age group.7

CNV due to angioid streaks, or linear breaks in Bruch’s membrane, has been found to account for 5% of CNV cases in young patients. The remainder of CNV cases in young patients have been attributed to various hereditary, traumatic, or inflammatory disorders (4%) or considered idiopathic (17%) when no definitive etiology could be determined.7

RISK FACTORS

MYOPIA

Degenerative myopia, usually occurring in individuals with greater than 6 diopters of myopia or an axial length greater than 26 mm, is characterized by a progressive elongation of the globe associated

with typical chorioretinal degenerative changes in the posterior pole.3 Increasing axial length, posterior staphyloma, and lacquer cracks have been associated with a higher risk for myopic CNV.6,10,11 One study found patchy chorioretinal atrophy and lacquer cracks to be the most important lesions in high myopia predisposing to the development of CNV. This study also found a higher incidence of CNV development in the fellow eyes of patients with pre-existing CNV (34.8%) than in eyes of patients without pre-existing CNV (6.1%).6

PRESUMED OCULAR HISTOPLASMOSIS SYNDROME

POHS is most common in the Ohio and Mississippi river valleys, where 60–80% of the population have been exposed to H. capsulatum and react positively to the histoplasmin skin antigen. The association between POHS and H. capsulatum is based on epidemiologic studies demonstrating a positive histoplasmin skin test in most patients with POHS. However, studies have identified patients with typical POHS findings who have not been exposed to H. capsulatum, indicating that this organism may be only one of several possible pathogens. Human leukocyte antigen (HLA) subtypes DRw2 and B7 have been found to be associated with POHS, suggesting a possible genetic or autoimmune predisposition to the development of POHS following infection with H. capsulatum or other causative pathogens.8,9,12 Secondary CNV occurs in fewer than 5% of POHS patients with atrophic scars in the macular area. The chorioretinal scars may indicate focal infection or inflammation of the choroid, which leads to a disruption of Bruch’s membrane and a stimulus for the development of CNV.2,9,12

OTHER INFLAMMATORY CAUSES

Active inflammation may lead directly to CNV, such as in cases of posterior uveitis, serpiginous choroidopathy, sarcoidosis, or syphilis. The most common inflammatory cause of CNV, however, is multifocal choroiditis and panuveitis (MCP), a disease of unknown etiology characterized by fundus lesions similar to those seen in POHS. Patients with MCP may develop CNV during episodes of active inflammation or from macular scars in periods without inflammation.2 MCP occurs predominantly in myopic women between the second and sixth decades of life. The disease is bilateral in the majority of patients, although it frequently presents asymmetrically.2,13,14

ANGIOID STREAKS

Angioid streaks represent linear breaks in a thickened, calcified, and abnormally brittle Bruch’s membrane. Angioid streaks may occur in isolation or as an ocular manifestation of several systemic diseases, including pseudoxanthoma elasticum (PXE), Paget’s disease (osteitis deformans), sickle cell anemia, and Ehlers–Danlos syndrome. PXE, a primary disorder of elastic tissue, is the most common cause of angioid streaks. Greater than 50% of cases of angioid streaks have PXE, and 80–87% of patients with PXE show evidence of angioid streaks. Angioid streaks have been reported in 8–15% of patients with Paget’s disease and in 1–2% of patients with sickle hemoglobinopathy. Angioid streaks almost always occur bilaterally. In surveys of patients with angioid streaks, CNV has been reported to occur in 44–57% of patients.15–17