Hereditary retinal dystrophies

Progressive cone dystrophy

This is a heterogeneous group of rare diseases. In patients with pure cone dystrophy, only the function of the cone system is affected. In cone-rod dystrophy, the function of the rod system is also affected, but to a lesser extent. In many patients with cone dysfunction, rod system disorders are added at the onset of the disease, so the term "cone-rod dystrophy" is more correct.

The type of inheritance is sporadic in most cases; of the remaining ones, autosomal dominant is more common, and less common is autosomal recessive, linked to the X chromosome.

It manifests itself in the 1st to 3rd decades of life as a gradual bilateral decrease in central and color vision, and may be accompanied by photophobia and mild pendulum-like nystagmus.

Symptoms (in order of appearance)

• In the fovea - no changes or non-specific changes in the form of pigment granules.
• Bull's-eye maculopathy is a classic but not constant symptom.
• Pigmentation in the form of "bone bodies" in the midperiphery, narrowing of the arterioles and temporal discoloration of the optic disc may appear.
• Progressive atrophy of the RPE in the macular region with "geographic" atrophy.
• Electroretinogram. Photopic - subnormal or unrecordable, KFFM is reduced, rod response is preserved for a long time.
• Electrooculogram is normal or subnormal.
• Dark adaptation. The cone "knee" is changed, later changes in the rod "knee" may join.
• Color vision: severe impairment of green and blue color perception without correlation with visual acuity.
• FAG in the bull's eye pattern reveals a rounded hypofluorescent "fenestrated" defect with a hypofluorescent center.

The prognosis depends on the degree of damage to the rod system: the greater the preservation, the more favorable the prognosis (at least in the medium term).

Differential diagnosis of bull's-eye maculopathy: chloroquine maculopathy, advanced Stargardt's dystrophy, fenestrated brilliant dystrophy, benign concentric annular macular dystrophy, and Batten disease.

Stargardt's dystrophy

Stargardt dystrophy (juvenile macular dystrophy) and yellow-spotted fundus are considered clinical variants of the same disease, differing in age of onset and prognosis.

The inheritance type is autosomal recessive, gene ABC4Rna 1p21-22. It manifests itself in the 1-2 decades of life as a bilateral gradual decrease in central vision, which may not correspond to changes in the fundus, and the child may be suspected of simulation.

Symptoms (in order of appearance)

• In the fovea - no changes or redistribution of pigment.
• Oval lesions with a snail track or bronze reflex that may be surrounded by white-yellow spots.
• Geographic atrophy may have a bull's eye appearance.
• Electroretinogram. Photopic - normal or subnormal. Scotopic electroretinogram is normal.
• Electrooculogram is subnormal in the advanced stage.
• Color vision: impaired perception of green and blue colors.
• FAG often reveals the phenomenon of "dark choroid" as a consequence of lipofuscin deposits in the RPE. The absence of normal fluorescence enhances the contours of the retinal vessels. "Geographic" atrophy manifests itself as a "finite" defect in the macula.
• The prognosis is unfavorable: after visual acuity decreases below 6/12, there is a rapid decrease in visual acuity to 6/60.

Yellow spotted fundus

The inheritance type is autosomal recessive. It manifests itself in adults, in the absence of changes in the macular area, it can be asymptomatic and be an accidental finding.

Symptoms (in order of appearance)

• Bilateral white-yellow spots with unclear borders at the level of RPE at the posterior pole and midperiphery. The spots are round, oval, linear, translucent or pisciform (shaped like a "fish tail").
• The fundus is bright red in 50% of cases.
• New spots appear, and old ones become blurrier and softer.
• In some cases, "geographic" atrophy develops.
• Electroretinogram. Photopic - normal or subnormal, scotopic - normal.
• The electrooculogram is subnormal.
• Color vision is not affected.
• FAG reveals a picture of a "silent" choroid. Fresh spots are manifested by an early block and late fluorescence, old ones - by "final" RPE defects.
• The prognosis is relatively good. Symptoms may not appear for many years unless the spot appears in the foveola or "geographic" atrophy develops.
• Differential diagnosis: dominant drusen, "white-dotted" fundus, early North Carolina dystrophy and benign "spotted" retina syndrome.

Juvenile disease Best

Juvenile Best disease (vitelliform dystrophy) is a rare condition that develops in 5 stages. The inheritance pattern is autosomal dominant.

• Stage 0 (previtelliform) is characterized by a subnormal electrooculogram in the absence of complaints and a normal fundus.
• Stage 1 is characterized by a redistribution of pigment in the macular area.
• Stage 2 (vitelliform) develops in the 1st-2nd decades of life and is characterized by changes in the macular region that resemble an egg yolk cyst: subretinal deposition of lipofuscin. Visual acuity is normal or slightly reduced.
• Stage 3 (pseudohypopyon) occurs when lipofuscin is partially absorbed. Over time, the entire contents of the cyst are absorbed without affecting visual acuity.
• Stage 4 (cyst rupture): When a cyst ruptures, a "scrambled egg" appearance occurs and visual acuity is reduced.

Electroretinogram is normal. Electrooculogram is sharply reduced at all stages and in carriers with normal fundus. Color vision is impaired according to the decrease in visual acuity. FAG reveals a block of choroidal fluorescence in the vitelliform stage.

The prognosis is relatively favorable until the 5th decade of life, when visual acuity decreases. Legal blindness in some patients is caused by scarring of the macular region, SNM, "geographical" atrophy, formation of central ruptures, which can cause detachment.

Adult vitelliform foveomacular dystrophy

The disease is classified as a "pattern dystrophy". But compared to the changes in Best's disease, the foveolar lesions are smaller, appear later and do not evolve.

The type of inheritance is possibly autosomal dominant, gene at locus 6p21-22.

It manifests itself in the 4th-6th decades of life in the form of a slight metamorphopsia, often discovered by chance.

Symptoms: bilateral, symmetrical, round, slightly protruding yellow subretinal lesions measuring approximately 1/3 of the disc diameter.

• Electroretinogram is normal.
• Electrooculogram is normal or slightly subnormal.
• Color vision: mild disturbances along the tritan axis.
• FAG reveals central hypofluorescence surrounded by a ring of hyperfluorescence.

The prognosis is favorable in most cases.

Multifocal disease Best

Multifocal Best disease is extremely uncommon and can occur in the absence of a family history. In adulthood, the disease can present acutely and be difficult to diagnose.

Family Friends

Familial drusen (Doyne's honeycomb choroiditis, malattla levantinese) are considered an early manifestation of age-related macular degeneration.

The inheritance pattern is autosomal dominant with full penetrance and variable expressivity. Gene EFEMP1 on 2p16.

Symptoms

• mild degree is characterized by a few small hard drusen, limited to the macular zone. Changes usually appear in the 3rd decade of life, the course is favorable;
• the average degree is characterized by large soft drusen at the posterior pole and in the parapapillary zone. Changes occur in the
  3rd decade of life and can sometimes be accompanied by a slight decrease in visual acuity;
• the advanced stage is rare and occurs after the 5th decade of life, and is sometimes complicated by SIM or “geographical” atrophy;
• malattia levantinese resembles familial drusen: small, numerous, basal laminar drusen, spoke-like or radially oriented, centered in the fovea and parapapillary zone. Most patients do not complain until the 4th or 5th decade of life, when SIM or "geographical" atrophy occurs.

Electroretinogram is normal. Electrooculogram is subnormal in the developed stage. FAG reveals hyperfluorescent spots with clear borders, similar to "finite" defects. They appear more clearly than during clinical examination.

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Pseudoinflammatory macular dystrophy Sorsby

Sorsby pseudoinflammatory macular dystrophy (hereditary hemorrhagic dystrophy) is a rare and severe disease. The inheritance type is autosomal dominant, with full penetrance, the TIMP3 gene is on 22ql2.1-1.3.2. It manifests itself in the 5th decade of life as bilateral exudative maculopathy.

Symptoms (in order of appearance)

• "white-yellow" confluent, drusen-like deposits along the vascular arcades, nasal to the disc on the mid-periphery.
• SIM and exudative maculopathy.
• Subretinal scar.

Electroretinogram is initially normal but may decrease as the disease progresses. Electrooculogram is normal.

The prognosis is unfavorable due to maculopathy. In some patients, progression of peripheral chorioretinal atrophy leads to deterioration of vision in the 7th decade of life.

North Carolina Macular Dystrophy

North Carolina macular dystrophy is a rare, severe disorder. The inheritance pattern is autosomal dominant with complete penetrance and highly variable expressivity, the MCDRI gene is on 6q.

Symptoms and prognosis

• stage I: white-yellow, drusen-like inclusions in the periphery and in the macular region develop in the first decade of life and may be asymptomatic throughout life;
• Stage 2: Deep, confluent inclusions in the macular area. The long-term prognosis is less favorable, as exudative maculopathy may develop;
• Stage 3: bilateral coloboma-like atrophic changes in the macular region with varying degrees of visual acuity reduction.

Electroretinogram is normal. Electrooculogram is normal. FAG in stages 1 and 2 reveals transmission defects and late staining.

Butterfly macular degeneration

Butterfly macular dystrophy is a rare disease with a relatively favorable course. The type of inheritance is presumably autosomal dominant. It manifests itself in the 2nd-5th decades of life, usually discovered by chance. A slight decrease in central vision is possible.

Symptoms

The yellow pigment in the fovea is triradiate. Fine dispersed dyspigmentation may be found at the periphery.

Electroretinogram is normal. Electrooculogram is pathological. FAG reveals corresponding hypofluorescence zones.

The prognosis is favorable.

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Dominant cystoid macular edema

Dominant cystoid macular edema is a rare and severe disease. The inheritance type is autosomal dominant, the gene is localized on 7q. It manifests itself in the 1-2 decades of life by a gradual decrease in central vision.

Symptoms.

Bilateral CME is not controlled by systemic acetazolamide. Electroretinogram is normal. Electrooculogram is normal or subnormal. FAG reveals a "flower petal" pattern of foveal sweating.

The prognosis is unfavorable due to the subsequent development of "geographic" atrophy.

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Crystalline dystrophy

This disease is characterized by the deposition of crystals in the retina and on the periphery of the cornea. The type of inheritance is linked to the X chromosome or autosomal recessive. It manifests itself in the 3rd decade of life by progressive loss of vision.

Symptoms (in order of appearance)

White-yellow crystals are disseminated throughout the fundus. Local atrophy of the RPE and choriocapillaris in the macula. Diffuse atrophy of the choriocapillaris. Gradual fusion and expansion of atrophic zones to the periphery of the retina.

Electroretinogram is subnormal. Electrooculogram is subnormal.

The prognosis is uncertain, the rate of progression is individual.

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Alport syndrome

Alporl syndrome is a rare anomaly of the glomerular basement membrane caused by mutations in several different genes, each of which codes for the synthesis of different forms of type IV collagen, the main component of the basement membrane. It is characterized by chronic renal failure, often associated with sensorineural hearing loss.

The inheritance type is dominant, linked to the X chromosome.

Symptoms

Disseminated, pale, yellow spots in the perimacular area with an intact fovea and normal visual acuity. Larger spots at the periphery, some merging with each other.

• Electroretinogram is normal.
• Other ophthalmological manifestations: anterior lenticonus, sometimes posterior polymorphic corneal dystrophy.

The prognosis is favorable.

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Benign familial mottled retina

Benign familial "spotted" retina is a very rare disease, asymptomatic, discovered by chance. The type of inheritance is autosomal recessive.

Symptoms

• Widespread white-yellow spots at the level of RPE with an intact macula. Foci of various shapes extend to the far periphery.
• Electroretinogram is normal.

The prognosis is favorable.

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Congenital rod monochromacy

The inheritance type is autosomal recessive.

Symptoms

• Visual acuity 6/60.
• The macula appears normal, hypoplasia is possible.
• Congenital nystagmus and photophobia.

Electroretinogram. Photopic is pathological, scotopic may be subnormal, CFFF < 30 Hz. Color vision is completely absent; all colors appear as shades of gray.

Incomplete rod monochromacy

The inheritance pattern is autosomal recessive or X-linked.

Symptoms

• Visual acuity 6/12-6/24.
• The macula appears normal.
• There may be nystagmus and photophobia.

Electroretinogram photopic - pathological, scotopic - normal. Color vision residual.

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Cone monochromacy

The type of inheritance is unknown.

Symptoms

• Visual acuity 6/6-6/9.
• Normal macula.
• Nystagmus and photophobia are absent.

Electroretinogram is normal. Color vision is completely absent.