Ординатура / Офтальмология / Английские материалы / Oxford American Handbook of Ophthalmology_Tsai, Denniston, Murray_2011

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RETINITIS PIGMENTOSA 457

Table 13.22 Associations of retinitis pigmentosa (selected)

Table 13.23 Genes involved in retinitis pigmentosa (selected)

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Adult vitelliform degeneration

Adult vitelliform degeneration (includes adult-onset foveomacular vitelliform dystrophy of Gass) describes a vitelliform appearance occurring in minimally symptomatic adults with a near-normal EOG. There is no clear inheritance pattern, although some cases with mutations of VMD2 and peripherin/RDS have been described.

Familial drusen

This is a rare autosomal dominant condition with variable expression. The different patterns seen have traditionally been described separately as Doynes honeycomb dystrophy and malattia leventinese. However, it is thought that these reflect the varied phenotype of the same condition, all arising from mutations in EFEMP1. It appears that these mutations result in abnormal basement membrane formation at the level of the RPE.

Clinical features

Usually only mild symptoms occur; yellow-white drusen are at the posterior pole, are often confluent, and may be small or large

Investigations

ERG: normal; EOG: mild abnormality.

Pattern dystrophy

This rare group of conditions shows abnormal pigment patterns at the level of the RPE. Different phenotypes may be seen in the same family, hence they are probably best grouped collectively rather than separately under the traditional descriptive names—butterfly dystrophy, etc.

Inheritance is usually autosomal (recessive > dominant) and is in some cases linked to mutations in the peripherin/RDS gene.

Clinical features

Usually only mild symptoms occur; abnormal pigment patterns are at the posterior pole.

Investigations

ERG is normal; EOG shows mild abnormality.

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MACULAR DYSTROPHIES (2) 461

Macular dystrophies (2)

Dominant CME

This very rare autosomal dominant disease (Ch7q) appears to selectively affect Muller’s cells, causing multilobulated cystoid spaces arising from the inner nuclear layer. Clinically and on FA the appearances are of typical CME.

Sorsby’s macular dystrophy

This very rare autosomal dominant disease arises from mutations in a regulator of extracellular matrix (TIMP3, Ch22). It usually causes significant dVA from age 40 years, when exudative maculopathy develops with subsequent scarring, atrophy, and even choroidal neovascularization.

North Carolina macular dystrophy

This rare autosomal dominant disease was initially described in North Carolina but has been identified in a number of families worldwide. It links to MCDR1, Ch6q. Onset is from birth. The phenotype varies from normal VA with a few drusen to hand movements (HM) acuity with a macular coloboma or subsequent CNV.

The macular lesions are present at birth and are stable in each individual but can be highly variable within family members.

Progressive bifocal chorioretinal atrophy

This rare autosomal dominant disease has only been described in the UK, and, like North Carolina macular dystrophy, links to Ch6q. This is a bizarre pattern of progressive chorioretinal atrophy that spreads from two foci located just temporal and just nasal to the disc.

Onset is from birth, and the visual loss is severe.

Cone degenerations

This group of disorders causes selective loss of cone photoreceptors with dVA, color vision abnormalities, and central scotomata. The macula may show only a mild granularity or marked central atrophy.

Central areolar choroidal dystrophy

This rare autosomal dominant disease links to Ch17p and usually presents in young adults. There is slowly progressive loss of central vision, with central geographic atrophy, including loss of the underlying choriocapillaris.

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Choroidal dystrophies

The choroidal dystrophies are inherited, potentially blinding conditions in which the primary clinical abnormality is atrophy of the RPE and choroid. The codependence of retina and choroid is well demonstrated by the discovery that in choroideremia the underlying defect is probably in the rod photoreceptors, where stop mutations in the CHM gene prevents its normal production of Rab escort protein (REP-1).

Choroideremia

This rare X-linked recessive condition causes significant disease from childhood in males, but usually only asymptomatic “moth-eaten” peripheral pigmentary disturbance in female carriers.

Clinical features

•Nyctalopia, visual field loss (e.g., ring scotoma), later dVA (usually in middle age).

•RPE/choroidal atrophy: initially mid-peripheral, patchy, and superficial (choriocapillaris); later central, diffuse, and deeper choroidal atrophy to expose the sclera; retinal vessels and optic disc are relatively preserved.

•Other: cataract (posterior subcapsular), early vitreous degeneration.

Investigations and treatment

There is reduction in ERG (rod responses affected before cone responses) with prolongation of b-wave implicit time.

Useful vision is retained until late in the disease course; supportive treatment and genetic counseling may be offered.

Gyrate atrophy

This rare autosomal recessive condition arises from mutations in the OAT gene. This encodes for ornithine aminotransferase, which, with cofactor B6, catalyses the conversion of ornithine to glutamic-G-semialdehyde and then to proline.

Two clinical subtypes are seen according to whether treatment with B6 lowers plasma ornithine levels. Responders appear to have a milder form of disease. Disease is usually symptomatic from late childhood.

Clinical features

•Nyctalopia, peripheral field loss, later dVA.

•RPE/choroidal atrophy: well-defined circular patches initially midperipheral and superficial (choriocapillaris); later confluent, diffuse fundus (relative sparing of macular, retinal vessels, and optic disc) and deeper choroidal atrophy; ERM, CME.

•Other: myopia, cataract (posterior subcapsular).

Investigations

•Early reduction in ERG (rod responses affected before cone responses); less marked changes in B6-responsive group.

•Plasma ornithine: 10–15xnormal level; also elevated in urine and CSF.

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Albinism

Abnormalities in the synthesis of melanin result in pigment deficiency of the eye alone (ocular albinism) or of the eye, skin, and hair (oculocutaneous albinism). Although there is wide phenotypic variation, the visual acuity is generally reduced because of macular hypoplasia. In most patients there also appears to be increased decussation of the temporal fibers at the chiasm.

Ocular albinism

Classic ocular albinism (Nettleship–Falls albinism) represents 10% of all albinism. It is X-linked, the OA1 gene being implicated in melanosomes function. Ocular features may be severe despite an otherwise normal appearance. Female carriers may show mild, patchy features of the disease, including a “mud-splattered” fundus.

Clinical features

•dVA, photophobia.

•Nystagmus, strabismus, ametropia, iris hypopigmentation/ transillumination, macular hypoplasia, fundus hypopigmentation.

Treatment

The main priority is to correct ametropia (± tinted lenses for photophobia) and prevent amblyopia. Consider surgery for strabismus and some cases of nystagmus.

Oculocutaneous albinism

Oculocutaneous disease is autosomal recessive and accounts for most albinism. It arises from abnormalities in several components of melanogenesis: type I = tyrosinase (Ch11q), type II = p product (Ch15q, probably a transporter), and type III = tyrosinase-related protein 1 (Ch9p) (Table 13.25).

Clinical features

•Ophthalmic: as for ocular albinism.

•Systemic: there is variable hypopigmentation of skin and hair (blond).

Treatment

• As for ocular albinism.