Ординатура / Офтальмология / Английские материалы / Ocular Pathology_6th edition_Yanoff, Sassani_2009

A.Mutation of the RS1 gene appears to give rise to a dysfunctional adhesive protein, resulting in defective cellular adhesion that eventually leads to schisis formation.

B.The area of neural retinal involvement is similar to that found in reticular peripheral cystoid degeneration and retinoschisis, but di erent from the middle-layer neural retinal involvement of typical microcystoid peripheral neural retinal degeneration and retinoschisis.

C.In juvenile retinoschisis, the neural retinal spaces appear empty and do not stain for acid mucopolysaccharides.

V.Goldmann–Favre vitreoretinal dystrophy consists of juvenile retinoschisis and the following:

A.Vitreous degeneration and liquefaction and the formation of preretinal strands and cords

B.Secondary pigmentary and degenerative changes of the retina resembling RP

C.Leakage of fluorescein from retinal vessels

D.Hemeralopia with abolition of the ERG response and a progressive decrease in vision function

E.Cataracta complicata lens opacities

F.An autosomal-recessive heredity

VI. Wagner’s vitreoretinal dystrophy (Table 11.2) consists of:

A.Juvenile retinoschisis plus marked vitreous syneresis

B.No posterior pole involvement

C.Normal dark adaptation but a subnormal ERG

D.Cataracta complicata lens opacities

The polymorphous ocular signs of this disease may also include myopia, retinal pigmentation, neural retinal breaks, patchy areas of thinned RPE, chorioretinal atrophy, narrowing and sheathing of retinal vessels, extensive neural retinal areas of white with pressure, lattice degeneration of the neural retina, marked neural retinal meridional folds, and optic atrophy. The condition should be differentiated from snowflake vitreoretinal degeneration (SVD), a hereditary vitreoretinal degeneration characterized by multiple, minute, whitish-yellow dots in the peripheral neural retina. The genetic locus for SVD is in a region of chromosome 2q36, flanked by D28S2158 and D2S2202.

E.An autosomal-dominant heredity—mutations that cause Wagner’s disease (and also erosive vitreoretinopa-

thy) type I are linked to markers on the long arm of chromosome 5 (5q13–14) and type II the COL2A1 gene on locus 12q13–14.

Many cases previously reported as Wagner’s syndrome (and also Pierre Robin syndrome) probably represent Stickler’s syn-

drome (hereditary progressive arthro-ophthalmopathy). Stickler’ssyndrome (see Table 11.2), which has an autosomal-dominant inheritance pattern and shows ocular, orofacial, and skeletal abnormalities, can be divided into thre types: type I is caused by mutations in the COL2A1 gene on chromosome 12q13–14 in the nonhelical 3’ end of the type II procollagen gene; type II COL11A1 gene on locus 1p21; and type III COL11A2 gene on 6p22–23.

Choroidal Dystrophies

See pp. 346 in Chapter 9.

Stargardt’s Disease (Fundus Flavimaculatus)

I.Stargardt’s disease (Fig. 11.34) is inherited as an autoso- mal-recessive trait [the photoreceptor gene, ABCR or ABCA4 (also known as STGD1) on chromosome 1p21 is mutated in Stargardt’s disease].

The mechanism involved in the loss of vision is not known, although all-trans-retinol dehydrogenase, a photoreceptor outersegment enzyme, may be defective in Stargardt’s disease. Rarely, Stargardt’s disease is inherited as an autosomal-dominant trait. Linkage analysis of families with autosomal-dominant Stargardtlike macular dystrophy has shown the disease gene in one family on 13q34 and on 6q14 in other families. The gene responsible for dominant Stargardt macular dystrophy is a retinal photoreceptorspecific gene, ELOVL4.

II.Stargardt’s disease consists of two parts that may occur

simultaneously or independently: a macular dystrophy and a flecked neural retina (fundus flavimaculatus).

A. The macular dystrophy component

1.Initially, it is confined to the posterior pole, eventually leading to loss of central vision.

2.Reduced visual acuity is the initial symptom, and is usually first noted between the ages of 8 and 15 years.

3.In the early stages of reduced visual acuity, the macula may appear normal. Later, a horizontally oval area of atrophy and pigment dispersal develops in the fovea.

4.Ophthalmoscopically, the macula takes on a

“beaten-bronze atrophy”caused by a sharply defined

RPE atrophy.

a.The macula also shows a bull’s-eye configuration

(see p. 434 in this chapter for di erential diagnosis of bull’s-eye macula).

b.The peripheral neural retina may show areas that resemble RP.

Stargardt’s original report described numerous shark- fin-shaped spots around the papillofoveal area characteristic of fundus flavimaculatus (see later). Fundus flavimaculatus and Stargardt’s disease represent different ends of a spectrum of the same disease, the former in its pure form consisting of a pericentral tapetoretinal dystrophy and the latter in its pure form consisting of a central tapetoretinal dystrophy, but usually showing considerable overlap.

5.Dark adaptation and ERG are normal or only mildly abnormal in the purely central type, but are subnormal in the perifoveal and peripheral neural retinal type.

6.Fluorescein angiography shows fluorescence of the central fovea without leakage, often in a bull’s-eye configuration, suggesting defects in the RPE but an intact Bruch’s membrane.

a.In addition, in approximately 86% of cases, fluorescein angiography shows a dark fundus picture with a generalized diminution of background fluorescence.

b.An increased amount of lipofuscin-like material in the RPE causes the decreased fluorescence.

7.Histologically, there is a complete disappearance of the RPE and of the visual elements in the macular area.

The inner layers of the neural retina may show cystoid degeneration and calcium deposition.

B.The flecked neural retina (fundus flavimaculatus) component

The differential diagnosis of flecked neural retina includes ARMD, autosomal-dominant central pigmentary sheen dystrophy, crystalline dystrophy, benign familial fleck neural retina, Bietti’s crystalline dystrophy, canthaxanthine (skin-tanning agent), central and peripheral drusen retinopathy, cystinosis, dominant drusen of Bruch’s membrane (Doyne’s honeycomb dystrophy), familial flecked retina with night blindness, flecked retina of Kandori, fundus flavimaculatus, glycogen storage disease (GSD), gyrate atrophy, Hollenhorst plaques, Kjellin’s syndrome, juxtafoveal telangiectasis, oxylosis (primary, or secondary to long-standing neural retinal detachment, methoxyflurane general anesthesia, or ingestion of an oxalate precursor such as ethylene glycol, i.e., antifreeze), retinitis punctata albescens, ring 17 chromosome, Sjögren–Larsson syndrome, Sorsby’s pseudoinflammatory macular dystrophy, talc retinopathy (intravenous drug abusers), tamoxifen (antiestrogen medication), and nitrofurantoin medications.

1.Fundus flavimaculatus shows ill-defined, yellowish spots shaped like crescents, shark fins, fishtails, fish, or dots located at the level of the RPE.

2.Approximately 50% of eyes show a Stargardt-type macular dystrophy with a decrease in visual acuity.

3.The peripheral neural retina may show areas that resemble RP.

4.Dark adaptation and ERG are usually normal but may be subnormal.

5.Fluorescein angiography does not cause fluorescence of the spots in early lesions, and not all the spots fluoresce in late lesions.

a.The fluorescein shapes are irregular, soft, and fuzzy and show a marked tendency for confluence.

b.The fluorescein pattern clearly di erentiates the spots from drusen.

c.Fluorescein angiography shows a dark fundus

(see earlier).

6.Histologically, the RPE is solely involved—hence the abnormal electro-oculogram (EOG)—and shows:

a.PAS positivity and increased autofluorescence

b.Displacement of the nucleus from near the base of the cell to the center or apical surface

c.An increased amount of pigment granules, most of which are lipofuscin-like, in the center or near the apical surface of the cell, often at the level of the displaced nucleus

d.Great variation in RPE cell size, from much larger than normal to normal

Dominant Drusen of Bruch’s Membrane

Doyne’s Honeycomb Dystrophy; Malattia

Lèventinese; Hutchinson–Tay Choroiditis; Guttate

Choroiditis; Holthouse–Batten Superficial

Choroiditis; Family Choroiditis; Crystalline

Retinal Degeneration; Iridescent Crystals of the

Macula; Hyaline Dystrophies

I.Dominant drusen of Bruch’s membrane is a bilateral, symmetric, progressive disease whose onset is usually between 20 and 30 years of age.

A.It involves the posterior pole predominantly and results in loss of vision.

1.The posterior polar lesion consists of moderateto large-sized drusen, resembling soft drusen.

Although there may be subtle differences, dominant drusen can be considered to be synonymous with Doyne’s honeycomb dystrophy and malattia lèventinese.

B.It is inherited as an autosomal-dominant trait.

The gene responsible has been mapped to the short arm of chromosome 2 (2p16–21) in both dominant drusen and malattia lèventinese. Other families map to 1q25–q31 and 6q14.

II. Dark adaptation and ERG are normal.

III.Fluorescein angiography shows multiple, sharply defined

fluorescent spots or flecks (see p. 441 in this chapter for di erential diagnosis of fleck retina) corresponding to the clinically seen lesions; some confluence of fluorescent areas

occurs, but there is no leakage of dye.

IV. Histologically, the lesions appear as large, soft drusen between the RPE and Bruch’s membrane.

The predominant ultrastructural features include deposition of a material composed of tubelike structures, vesicles, and membranous material between the basement membrane of the RPE and the inner collagenous layer of Bruch’s membrane.

expression. The Best’s disease gene lies on the long arm of chromosome 11 (11q13), the VMD2 gene.

C.Only approximately 1% of all cases of macular degeneration are attributable to Best’s disease.

II.Ophthalmoscopically, the central macula takes on an early egg-yolk appearance (the color is probably caused by lipofuscin pigment) that later becomes “scrambled” and pigmented.

The egg-yolk appearance of the macula is not always present and sometimes may never occur. The fundus may show only very slight changes or resemble the terminal stage of extensive central inflammatory chorioretinitis, or any stage in between.

III. Dark adaptation and ERG are usually normal.

A.EOG shows an abnormal light-peak/dark-trough ratio in a ected patients as well as in carriers.

B.Fluorescein angiography shows no leakage into the yellow deposits, but rather a transmission (window) defect in the area.

Multiple vitelliform cysts, macular and extramacular, may develop in patients who have Best’s disease. The cysts typically obstruct choroidal fluorescence and do not stain during the early phases, thus differentiating them from idiopathic serous detachment of the RPE.

IV. Histologically, RPE cells show a generalized enlargement,

flattening, and engorgement by abnormal lipofuscin and pleomorphic melanolipofuscin granules, most pronounced in the fovea. The outer nuclear layer attenuation is prominent.

V.Lesions similar to those seen in Best’s disease may occur

in patients without Best’s disease as part of ARMD, a condition called pseudovitelliform or adult vitelliform macular degeneration.

A.Pseudovitelliform macular degeneration can occur with nonspecific RPE changes, cuticular or basal laminar drusen, detachment of the RPE, and perifoveal retinal capillary leakage.

B.The visual acuity is decreased but usually stabilizes.

C.Dry ARMD may develop in some cases and, rarely, some of these pseudovitelliform lesions develop fullthickness holes.

Best’s Disease

Vitelliform Foveal Dystrophy; Vitelliform Macular

Degeneration; Vitelliruptive Macular

Degeneration; Exudative Central Detachment of

the Retina—Macular Pseudocysts; Cystic Macular

Degeneration; Exudative Foveal Dystrophy

I.Best’s disease (Fig. 11.35) is a bilateral, symmetric, progressive disease involving the RPE of the macular area with resultant loss of vision.

A.Its onset is usually before 15 years of age.

B.It has an autosomal-dominant mode of transmission with diminished penetrance and a highly variable

Dominant Progressive Foveal Dystrophy

I.The clinical picture of dominant progressive foveal dystrophy is quite similar to Stargardt’s disease (which has a recessive inheritance) except that it tends less toward involvement of the peripheral neural retina, occurs at a later age, and usually takes a less progressive course. It is inherited as an autosomal-dominant trait.

II.The one histologic study in a 78-year-old woman showed disappearance of the outer nuclear layer and receptors and pronounced changes in the RPE.

A similar entity, dominant slowly progressive macular dystrophy, differs only slightly from dominant progressive foveal dystrophy.

B

Dominant Cystoid Macular Dystrophy

I.Dominant cystoid macular dystrophy consists of macular cystoid edema with central bull’s-eye (see p. 434 in this chapter for di erential diagnosis of bull’s-eye macula) and peripheral neural retinal pigmentary disturbance, cells in the vitreous body, wrinkling of the internal limiting membrane, and axial hypermetropia.

A.It is inherited as an autosomal-dominant trait.

B.Fluorescein angiography shows the changes typical of cystoid macular edema in some, but not all, cases.

C.Sometimes a lamellar macular hole may develop.

II. The histology is unknown.

Fenestrated Sheen Macular Dystrophy

I.This autosomal-dominant condition starts in childhood as a yellowish, refractile sheen that contains red fenestrations in the macular neural retina.

A.In the early stage small, red, demarcated lesions deep

in the nonthickened neural retina have been called fenestrations.

B.By the third decade, an annular zone of hypopigmentation of the RPE appears and then progressively enlarges around the area of the sheen.

C.The hypopigmented area is surrounded by an area of hyperpigmentation (bull’s-eye appearance—see p. 434 in this chapter for di erential diagnosis of bull’s-eye macula).

II.Fluorescein angiography shows no abnormalities in the neural retina and an intact choriocapillaris perfusion.

III. The histology is unknown.

North Carolina Macular Dystrophy

I. North Carolina macular dystrophy is an autosomal-domi- nant, slowly progressive macular dystrophy, fully penetrant, with highly variable expressivity.

The chromosomal locus for this retinal macular dystrophy gene (MCDR1) is found on the long arm of chro-

mosome 6 (6q14–q16.2)

II.In younger people, the characteristic fundus abnormalities consist of numerous drusen-like deposits mainly in the macula, and in older people, geographic atrophy in the macula.

III. A ected individuals show a light iris and choroid, prolonged dark adaptation, and increased light sensitivity.

IV. Histopathology

A.Discrete macular lesion characterized by focal absence of photoreceptor cells and RPE

B.Bruch’s membrane is attenuated and the choriocapillaris is focally atrophic.

Familial Internal Limiting Membrane Dystrophy

I.Familial internal limiting membrane dystrophy, a type of sheen retinal dystrophy, is probably inherited as an auto- somal-dominant trait.

A.The characteristic fundus finding is a glistening inner retinal surface throughout the posterior pole.

B.ERG demonstrates a selective diminution of the b wave.

II.Histologically, the internal limiting membrane of the neural retina shows areas of di use, irregular thickening and undulation.

A.Inner schisis cavities and cystoid spaces in the inner nuclear layer are also seen.

B.Electron microscopy of the retinal capillaries shows endothelial cell swelling, pericyte degeneration, and basement membrane thickening.

Central Pigmentary Sheen Dystrophy

I.Central pigmentary sheen dystrophy is a familial (probably autosomal-dominant), bilateral, symmetric, mild pigmentary maculopathy involving the posterior pole that has a variable e ect on visual acuity.

A.The posterior pole shows a di use yellowish sheen associated with yellow dots or flecks (see p. 441 in this chapter for di erential diagnosis of fleck neural retina).

B.The peripheral fundus is normal.

II.Fluorescein angiography shows a transmitted hyperfluorescence without leakage.

C.Ophthalmoscopically, the fundus may be normal, show nonspecific foveal RPE changes (hypopigmentation, mottling, atrophic appearing), a bull’s-eye macula (see p. 434 in this chapter for di erential diagnosis of bull’s- eye macula), or peripheral hypopigmentation and hyperpigmentation.

Alström’s syndrome, an autosomal-recessive, congenital, progressive cone–rod retinal degeneration associated with infan- tile-onset obesity, can be confused with cone–rod dystrophy.

II.Histologically, a loss of photoreceptors occurs mainly in the central macula, along with attenuation of the RPE.

A.Reduced numbers of cones occur to a lesser extent around the macula and in the periphery of the neural retina.

B.Electron microscopy shows an accumulation of abnormal lipofuscin granules in the RPE and marked enlargement and distortion of the cone photoreceptor pedicles.

Annular Macular Dystrophy (Benign Concentric

Annular Macular Dystrophy)

I.Annular macular dystrophy is characterized by a depigmented ring around an intact central macular area.

With time, the dystrophy, which is inherited as an auto-

somal-dominant trait, takes on the functional characteristics of a cone–rod dystrophy.

II.The dystrophy locus maps to the BCAMID defect with chromosome 6, region p12.3-q16. A leu579Pro mutation

in the IMPGI gene may play a causal role. III. The histology is unknown.

Cone–Rod Dystrophy

I.Cone–rod dystrophy (also called cone dystrophy) represents a clinically heterogeneous group of disorders, characterized by a decrease in previously normal vision usually in the first two decades of life, with normal or only minimally abnormal fundi.

A.It is most often inherited as an autosomal-dominant trait, although autosomal-recessive and X-linked inheritance patterns have been reported.

Autosomal-dominant cone–rod dystrophy has been localized to chromosomes 1q12–q24, 6p21.1, 19q13.3, and 17p12–. At least nine genes have been identified: CRX, GUCY2D, AIPL1, GUCA1A, GCAP1, RIMS1, and UNC119. The autosomal-recessive cone–rod dystrophy locus is 1p21–p13; ABCA4 and RDH5 are causative genes. RPGR is the causative gene for the X-linked recessive form.

B.At least four functionally distinct subtypes of cone–rod dystrophy exist.

Retinitis Punctata Albescens (Albipunctate

Dystrophy; Fundus Albipunctatus;

Panretinal Degeneration)

I.Retinitis punctata albescens is a bilateral,symmetric disease that may extend to the peripheral neural retina, characterized by flecks (flecked neural retina) and white-dot or punctate lesions with maximum density in the equatorial region; see p. 441 in this chapter for di erential diagnosis of fleck neural retina.

The hereditary pattern is not clear; both dominant and recessive forms may exist.

Mutations of the 11-cis retinal dehydrogenase (RDH5) gene cause retinitis punctata albescens, and probably also cause a progressive cone dystrophy.

II.Two types have been described.

A.Stationary retinitis punctata albescens (fundus albipunctatus) shows little or no constriction of visual

fields, normal or mildly subnormal ERG, good central

vision, white dots in the fundus, and no pigmentary changes.

1.Although the physiologic (functional) defects appear to be stable, the fundus lesions can evolve from flecks in childhood to relatively permanent punctate dots that increase in number over the years.

2.Fundus albipunctatus is a form of congenital station-

ary night blindness.

Congenital stationary night blindness is most often caused by a primary defect of the rod system. Autosomal-dominant and recessive (RDH5; 12q13q14) and X-linked inheritance patterns of the disease have been described. Most cases of congenital stationary night blindness have normal fundi; two with abnormal fundi are fundus albipunctatus and Oguchi’s disease.

B.Progressive retinitis punctata albescens (also called retinitis punctata albescens) shows increasing constriction of visual fields, deterioration of central vision, anomalies of color vision, night blindness, extinguished ERG, mild to moderate optic atrophy, and occasionally some retinal pigmentary changes and is a variant of RP.

III.Fluorescein shows multiple areas of fluorescent staining without leakage, corresponding to the dot lesions.

IV. No pathologic specimens have been studied histologically, but the defect is suspected of being at the level of the RPE, probably similar to drusen.

Central Retinitis Pigmentosa (Central

Retinopathia Pigmentosa; Retinopathia

Pigmentosa Inversa; Retinitis Pigmentosa Inversa;

Pericentral Pigmentary Retinopathy)

I.Central RP shows the changes of classic RP but is confined to the posterior pole.

A.It is presumably inherited as an autosomal-recessive trait.

B.It may have a pericentral location.

II.Dark adaptation and ERG are normal or only minimally subnormal.

III.Histologically, the changes are the same as those of classic RP.

Pigmentary macular changes may also be seen in ARMD, and inherited diseases such as Bardet–Biedl syndrome, Bassen–Kornzweig syndrome, Batten–Mayou disease, Cockayne’s syndrome, familial hypobetalipoproteinemia, Hallervorden–Spatz syndrome, Hallgren’s syndrome, Hooft’s syndrome, patterned dystrophy of the RPE, Pelizaeus–Merzbacher disease, Refsum’s disease, Stargardt’s disease, and others.

Retinitis Pigmentosa (Retinopathia Pigmentosa;

Pigmentary Degeneration of the Retina)

I.RP (Fig. 11.36) is a bilateral, symmetric, progressive disease whose onset is in early adult life.

A.It starts in the equatorial area of the retina and spreads centrally and peripherally, but more rapidly in the latter direction.

B.The inheritance pattern may be autosomal-dominant or recessive (about 40% of patients), X-linked, digenic, mitochondrial, or sporadic.

Autosomal-dominant RP loci have been mapped on chromosomes 3q (rhodopsin), 6p (peripherin/RDS), 7p, 7q, 8cen, 17p, 17q, and 19q. Evidence suggests that at least 11 diffferent genes can cause dominant RP but only four have been identified: rhodopsin (RHO), retinal degeneration slow (RDS), neural retinal leucine zipper (NRL), and RP1. Autosomal-recessive RP loci have been mapped on chromosomes 1q, 3q, 4p, 4cen, 5q, 6p, 11p, 11q, 14q, 15q, and 16q. Digenic RP loci have been mapped on chromosomes 6p and 11q. The rhodopsin and the peripherin/RDS genes account for perhaps 25% of all cases of autosomal-dominant RP. In fact, over 70 different mutations in the rhodopsin gene have been shown to cause RP. The gene for X-linked RP, the most severe form of the disease, has been localized within a 1/cM region at Xp21. At least two loci exist on the X chromosome: RP2 at the proximal (Xp11) region of the short arm; and RP3 distal to RP2. The degree of central vision loss is mildest in cases of autosomal-dominant inheritance and most severe in X-linked recessive inheritance. Most, if not all, adult heterozygous (X-linked type) women have detectable degenerative changes in the fundus, mainly peripheral atrophy of the RPE.

C.The primary defect (a form of apoptosis) appears to be in the receptors and is gene-determined (see p. 23 in

Chapter 1).

II.Night blindness is an early symptom and marked vision impairment a late symptom.

A.The tetrad of bone–corpuscular neural retinal pigmentation; pale, waxy optic disc; attenuation of retinal blood vessels; and posterior subcapsular cataract (see Fig.

10.16C) is characteristic.

B.Some degree of vitreous degeneration is found in almost all patients.

C.Three types of central macular lesion may be seen:

1.Atrophy with RPE thinning (hypopigmentation) and mottled transmission on fluorescein angiography (most common, approximately 58%)

Blacks who have RP are approximately twice as likely as whites to have an atrophic-appearing macular lesion.

2.Cystoid macular edema and leakage of fluorescein from foveal retinal capillaries (approximately 23%)

3.Cystic macular lesions with radial, inner neural retinal traction lines, often associated with epiretinal membranes which cause a surface wrinkling (approximately 19%)

D.RP may be associated with an exudative vasculopathy that may be derived from abnormal retinal blood vessels (resembling Coats’ disease) or from abnormal choroidal blood vessels.

E.Mulberry drusen of the optic nerve or peripapillary neural retina may be seen in approximately 20% of cases, regardless of genetic subtype.

III.Dark adaptation is markedly abnormal, as is the ERG, which is usually extinguished.

Fluorescein study shows a mottled hyperfluorescence involving the posterior and pre-equatorial eyegrounds, even when minimal ophthalmoscopic changes are present.

In most cases of secondary RP, fluorescein shows a mottled hyperfluorescence only in areas of abnormal pigmentation, thereby differing from primary RP.

IV. Histologically, the earliest changes are in the RPE and rods and cones, mainly in the equatorial region.

A.With progression, all rods and cones disappear except for rods in the far periphery and cones in the fovea.

B.The RPE undergoes both degeneration and proliferation, most marked from the equator posteriorly almost to the posterior pole.

1.Intrasensory neural retinal migration of pigment-

filled macrophages and of RPE occurs.

2.The pigment tends to collect and remain around blood vessels, which accounts for the clinical bone– corpuscular appearance.

C.Bruch’s membrane remains intact, even in the latest stages of the disease.

D.An epiretinal glial membrane may be present on the peripapillary neural retina and also over the optic disc.

Traumatic chorioretinopathy, which can resemble primary RP to a marked degree both clinically and histologically, is usually accompanied by interruptions of Bruch’s membrane and true chorioretinal scars. If no chorioretinal scars are present histologically, the diagnosis of primary RP may be made. If chorioretinal scars are present histologically, however, the diagnosis remains uncertain because eyes blind from primary RP are often also traumatized and, therefore, have secondary chorioretinal scars.

V.Secondary RP (Table 11.3).

Clumped Pigmentary Retinal Dystrophy

(Clumped Pigmentary Retinal Degeneration)

I.Clumped pigmentary retinal dystrophy is characterized by numerous clumped pigment deposits throughout the mid peripheral fundus.

A.The onset of night blindness varies from the first to the sixth decade of life.

B.The ERG amplitude is reduced.

C.Peripheral visual field loss is present.

II. An autosomal-recessive mode of inheritance is suggested.

III.Histologically, the clinically observed clumped pigmentation is caused by the accumulation of melanin granules in RPE cells.

The photoreceptors in the areas of clumped pigmentation show considerable generation.

Hereditary Pigmented Paravenous

Chorioretinal Atrophy

I. Hereditary pigmented paravenous chorioretinal atrophy is characterized by bone spicule pigment accumulation in a paravenous distribution.

II.The abnormal ERG suggests a localized dystrophy and the abnormal EOG suggests a more widespread

phenomenon.

III.The condition can be inherited, but the inheritance pattern is uncertain.

Pigment Epithelial Dystrophy

I. The condition, which occurs at birth or shortly thereafter, consists of myopia, nystagmus, and an RPE dystrophy that appears to be stationary or slowly progressive.

It is inherited as an autosomal-dominant trait.

II. Ophthalmoscopically, the RPE shows changes from a mild peripapillary sheen often associated with an irregularity of foveal reflex, or a loss of it, to an advanced stage that shows a geographic loss of RPE, increased visibility of choroidal vasculature, and pigment clumping.

III.Tests of visual function (visual acuity, perimetric fields, ERG, and EOG) tend to be altered in proportion to the retinal dystrophy.

IV. The histologic lesion is unknown but presumed to be at the level of the RPE.

Central Areolar Pigment Epithelial Dystrophy

I.Central areolar pigment epithelial dystrophy is characterized by childhood onset, good visual acuity, and nonprogression.

It has an autosomal-dominant inheritance pattern with a late onset and variable expressivity.

II.Ophthalmoscopically, a central, areolar, depigmented, sharply demarcated area is noted that involves the RPE.

III.Retinal function studies are negative. Fluorescein angiography shows a transmission (window) defect.

IV. The histologic lesion is unknown, but it is presumed to be at the level of the RPE.

Patterned Dystrophies of the Retinal Pigment Epithelium (Reticular Dystrophy or Sjögren Dystrophia Reticularis Laminae Pigmentosae Retinae; Butterfly-Shaped Pigment Dystrophy of the Fovea; Macroreticular or Spider Dystrophy)

I.Patterned dystrophies of the RPE are bilateral and symmetric, characterized by foveal involvement with preservation of good vision, and have an autosomal-recessive inheritance pattern.

Mutations of the peripherin/RDS gene may be associated with patterned dystrophies of the RPE, autosomal-dominant RP, and fundus

flavimaculatus. Macroreticular (macular) pattern dystrophy may be associated with maternally inherited diabetes and deafness, associated with a mutation of mitochondrial DNA [the substitution of guanine for adenine (A–G) at position 3243 of leucine transfer RNA]. Different members of the same family may show the three varieties (i.e., reticular dystrophy, butterfly-shaped foveal pigment dystrophy, and macroreticular or spider dystrophy). Patients who have adult-onset foveomacular dystrophy (AOFMD) may show a frameshift null mutation in the RDS/peripherin gene on chromosome 6p21. A rare case of patterned dystrophy has been reported to be associated with McArdle’s disease, a type V GSD.

II.Ophthalmoscopic appearance

A.Reticular dystrophy—the macula shows a fishnet-like pattern with an accumulation of dark pigment, surrounded by a finely meshed network of polygonally arranged pigment with densification at the sites of the knots of the network.

B.Butterfly-shaped foveal pigment dystrophy—the fovea shows a small, delicate pigmentary pattern, resembling a butterfly, at the level of the RPE.

C.Macroreticular or spider dystrophy—the macula shows a branching pigmentary pattern, resembling a spider, at

the level of the RPE.

III.Retinal function test results are normal, except for a subnormal EOG in the butterfly-shaped pigment dystrophy

of the fovea.

IV. Fluorescein angiography is similar in all three varieties, showing nonfluorescent bands or segments surrounded by areas of nonleaking hyperfluorescence.

V.Histologic study shows focal, abrupt transition from intact retina to a small area of RPE hypertrophy to photoreceptor and RPE atrophy.

Bietti’s Crystalline Dystrophy (Bietti’s Tapetoretinal Degeneration with Marginal Corneal Dystrophy, Crystalline Retinopathy)

I.Bietti’s crystalline dystrophy (Fig. 11.37) consists of small, yellow-white, glistening intraretinal crystals in the poste-