retinal degeneration

Evidence for retinal disease can be seen within 3 years of age.  Three of 5 patients had no detectable responses on the ERG when tested at birth.  A 34-year-old female was noted to have advanced retinitis pigmentosa with attenuation of retinal vessels, choroidal atrophy, peripheral pigmentary deposits, and macular anomalies.  The posterior fundus may have a salt-and-pepper pigmentation.  Hypermetropia was present in all 5 patients.

Visual acuity varies widely and may be normal even among older patients.

Patients often complain of night vision problems before the age of 5 years.  Fundus changes of optic nerve pallor, retinal vessel attenuation, and bone spicule pigmentary clumping in the midperiphery are evident by the third decade of life.  Progressive RPE and choroidal atrophy in the macula have been described and may be progressive.  ERG responses are absent from at least 28 years of age.

Gaze evoked nystagmus and pigmentation in the macula are components of this syndrome and adults have some degree of retinal degeneration with poor vision eventually.  Optic atrophy and ptosis have been reported but rarely.   

In an 18 month infant, ectopia lentis, cataract, and myopia with poor vision were noted.  This individual subsequently developed retinal degeneration and a serous retinal detachment.

Many (probably most) patients have lens opacities and some have corneal opacities as well.  Nystagmus and strabismus have been described.  Pigmentary changes of a mottled nature can be present in the posterior pole and may be associated with retinal vessel attenuation and diminished ERG responses.  Retinal thinning can be demonstrated.  A mixture of hypo- and hyperautofluorescence is often visible.  Mild optic atrophy has been seen.  There is evidence for progressive visual loss, even late in life.  Eyebrows appear thick.    

The retina and vitreous are primarily affected in this disorder.  The age of onset is unknown but characteristic signs can be seen early in the second decade of life.   Early changes include thickening of the cortical vitreous and white dots in the superficial layers of the retina.  The latter are minute yellow-white crystalline deposits more common in the peripheral retina.  Many (83%) patients have early onset cataracts.  Corneal guttae are common (80% of patients).  The vitreous undergoes fibrillar degeneration with liquefaction and eventually appears optically empty.  Many patients experience symptoms of floaters.  The vitreous changes most closely resemble that seen in Wagner syndrome (143200) but with important differences.  In the latter disorder the vitreous changes are membranous, the retinal changes are deeper in location, RPE changes are evident, the choroid and RPE are involved, and the risk of retinal detachment is much higher.  Only 21% of patients with snowflake vitreoretinal degeneration have retinal detachments compared with about 50% in Wagner syndrome.  Retinal vasculature change such as perivascular sheathing and attenuation of arterioles may be seen in both disorders but occur far less commonly in snowflake degeneration.

Based on lack of visual symptoms, the photoreceptors are minimally involved.  Electrophysiologic studies reveal an elevated dark adaptation and reduced scotopic B waves.  Most patients retain excellent vision.  However, the optic nerve may have a waxy pallor and frequently appears flat and lacks a visible cup. 

Microphthalmia with microcornea, lens opacities, small and unresponsive pupils, and optic atrophy are the outstanding ocular features of this syndrome.  The eyes appear deeply set.  Some but not all have ERG evidence of rod and cone dysfunction.  The VEP is usually abnormal.  Short palpebral fissures have been described. 

The retina contains refractile glistening intraretinal crystals at all levels and choroidal vessels are said to be sclerosed.  The RPE atrophies and often forms pigment clumps.  The yellow-white crystals may be seen in the peripheral cornea and in the limbus.  Symptoms of night blindness and early vision loss begin about the third decade.  Night blindness is progressive as is the narrowing of the visual fields but this is highly variable between patients.  The visual field may show paracentral scotomas at some stage.  Central acuity can be normal until late in the disease when it becomes markedly impaired. Legal blindness can occur by the 5^th decade of life. 

The ERG may show lack of rod and cone responses late in the disease and color vision may be lost.  However, the ffERG and mfERGs show decreases in amplitude of scotopic and photopic responses in all patients, even younger ones.  The EOG becomes abnormal in late stages.  The degree of involvement may be asymmetrical.  Complex lipid inclusions can be seen histologically in choroidal, conjunctival and skin fibroblasts, as well as in keratocytes and lymphocytes.

Crystalline deposits have been detected mostly in the proximal portions of RPE cells adjacent to degenerated retinal  areas.  Most common are circular hyperrefractive structures in the outer nuclear layer adjacent to areas of degeneration.  Some patients have cystoid macular edema. Others in late stages have fundus changes that resemble choroideremia.

Enhanced S-cone syndrome, sometimes called Goldman-Favre syndrome, is a retinal disorder characterized by increased sensitivity to blue light, night blindness from an early age, and decreased vision.  Additional features include an optically empty liquefied vitreous, progressive foveal or peripheral retinoschisis, macular cysts, chorioretinal atrophy and pigmentary retinopathy as well as posterior subcapsular cataract formation.  Hyperopia is a feature, at least in childhood.   Enhanced S-cone syndrome is the only retinal disorder that has a gain of a subtype of photoreceptors, in this case the S-cones (short wave length) that detect blue light. Rod photoreceptors and red and green cone receptors are degenerated to a variable degree. Electroretinography shows an extinct rod photoreceptor response and hypersensitivity to shorter wavelengths.

There is considerable variation in the clinical features of NR2E3 mutations which has led to some confusion in the nosology.  Some cases are called juvenile retinoschisis, others are called retinitis pigmentosa, or clumped pigment retinopathy.  Central acuity ranges from near normal (20/40) in young people to 20/200 or worse especially in older adults.  Visual field constriction likewise varies from patient to patient.  Retinal pigmentary changes and the amount of cystic changes in the macula are somewhat age dependent.