Polypoidal Choroidal Vasculopathy

Figure 11-34 Polypoidal choroidal vasculopathy (PCV). A, Elevated, red-orange nodular and tubular lesions in the peripapillary and macular regions. B, Late fluorescein angiogram (860 seconds) shows hyperfluorescent polypoidal lesions (arrows) without apparent leakage. C, Dense subretinal hemorrhage in same patient as in A and B. Note the persistent redorange lesions nasal and superior to the optic disc. (Courtesy of Robert H. Rosa, Jr, MD.)

Rosa RH Jr, Davis JL, Eifrig CW. Clinicopathologic reports, case reports, and small case series: clinicopathologic correlation of idiopathic polypoidal choroidal vasculopathy. Arch Ophthalmol. 2002;120(4):502–508.

Macular Dystrophies

See BCSC Section 12, Retina and Vitreous, for additional discussion of the following topics.

Fundus flavimaculatus and Stargardt disease

Fundus flavimaculatus and Stargardt disease are thought to represent 2 ends of the spectrum of a disease process characterized by yellowish flecks at the level of the RPE, a generalized vermilion (reddish) color to the fundus on clinical examination, a dark choroid on fluorescein angiography (Fig 11-35A, B; see also Figs 12-7 and 12-8 in BCSC Section 12, Retina and Vitreous), and gradually decreasing visual acuity. The inheritance pattern is generally autosomal recessive, but autosomal dominant forms have been reported as well. Several genetic mutations have been observed in patients with a Stargardt-like phenotype, including the ABCA4, STGD4, ELOV4, and RDS/peripherin genes. Mutations in ABCA4 are responsible for most cases of Stargardt disease. The ABCA4 gene encodes a protein called RIM protein, which is a member of the adenosine triphosphate (ATP)-binding cassette transporter family. It is expressed in the rims of rod and cone photoreceptor disc membranes and is involved in the transport of vitamin A derivatives to the RPE. The most striking feature of Stargardt disease on light and electron microscopy is the marked engorgement of RPE cells (Fig 11-35C, D; see also Fig 12-9 in BCSC Section 12, Retina and Vitreous) with lipofuscin-like, PAS-positive material, with apical displacement of the normal RPE melanin granules.

Figure 11-35 Stargardt disease. A, Fundus photograph shows characteristic retinal flecks and pigment mottling in the macular region. B, Fluorescein angiogram (midphase) shows late hyperfluorescence in a “bull’s-eye” pattern in the central macula. Note the dark choroid (eg, absence of normal background choroidal blush), which is characteristic of Stargardt disease. C, Histology with periodic acid–Schiff (PAS) stain discloses hypertrophic RPE cells with numerous PAS-positive cytoplasmic granules containing lipofuscin. This histopathologic finding corresponds to the retinal flecks seen clinically. D, In advanced stages of Stargardt disease, geographic RPE atrophy with loss of the photoreceptor cell layer (asterisks) may be

observed. (Courtesy of Sander Dubovy, MD.)

Best disease

Best disease, or Best vitelliform macular dystrophy, is a dominantly inherited, early-onset macular degenerative disease that exhibits some histopathologic similarities to AMD. The diagnosis of Best disease is based on the presence of a vitelliform (resembling the yolk of an egg) lesion (see Fig 1210 in BCSC Section 12, Retina and Vitreous) or pigmentary changes in the central macula and a

reduced ratio of the light peak to dark trough in the electro-oculogram. Mutations in the VMD2 gene on chromosome 11 (11q13) encoding the bestrophin protein have been identified in Best disease. The gene product, bestrophin, localizes to the basolateral plasma membrane of the RPE and represents a family of chloride ion channels. Investigators have reported that bestrophins are volume-sensitive and may play a role in cell volume regulation in the RPE cells.

Fischmeister R, Hartzell HC. Volume sensitivity of the bestrophin family of chloride channels. J Physiol. 2005;562(Pt 2):477–491. Marmorstein AD, Marmorstein LY, Rayborn M, Wang X, Hollyfield JG, Petrukhin K. Bestrophin, the product of the Best vitelliform

macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium. Proc Natl Acad Sci USA. 2000;97(23):12758–12763.

Pattern dystrophies

The term pattern dystrophies refers to a heterogeneous group of inherited macular disorders characterized by varying patterns of pigment deposition in the macula at the level of the RPE. Recognized pattern dystrophies include butterfly-shaped pattern dystrophy (BPD), adult-onset foveomacular vitelliform dystrophy (AFMVD), reticular dystrophy, and fundus pulverulentus. BPD is characterized by a butterfly-shaped, irregular, depigmented lesion at the level of the RPE. AFMVD is characterized by the presence of slightly elevated, symmetric, round to oval, yellow lesions at the level of the RPE, which are typically smaller than the vitelliform lesion characteristic of Best disease (Fig 11-36). Optical coherence tomography (OCT) has demonstrated elevation of the photoreceptor layer, with localization of the dystrophic material between the photoreceptors and RPE. The most common genetic mutation associated with the pattern dystrophies is in the RDS/peripherin gene. Histologic studies reveal central loss of the RPE and photoreceptor cell layer, with a moderate number of pigment-containing macrophages in the subretinal space and outer neurosensory retina (see Fig 11-36). To either side, the RPE is distended with lipofuscin. Basal laminar and linear deposits are present throughout the macular region. The pathologic finding of pigment-containing cells with lipofuscin in the subretinal space correlates clinically with the vitelliform appearance. See BCSC Section 12, Retina and Vitreous, for further discussion.