night blindness

Retinitis pigmentosa is clinically similar to that of nonsyndromal RP and produces symptoms of nightblindness by adolescence.  The ERG is severely reduced and visual fields are constricted.  Rods seem to be more severely affected than cones.  A loss of thickness in the outer nuclear layer in USH2C and USH2A types has been described.  The fundus often contains patches of hyperfluorescence which become larger and often coalesce in older patients.  The retinal disease is progressive but more slowly than in type I.  Eventually by the 4^th to 5^th decades the visual field is constricted to 5-10 degrees.  It can result in blindness.  Cataracts are common and some patients have cystic changes in the macula.

The fundus dystrophy of retinitis pigmentosa in Usher syndrome is indistinguishable from isolated retinitis pigmentosa.   Night blindness begins by about 10 years of age and the ERG by that time is often markedly diminished or absent.  Patches of hyperfluorescence are seen in younger individuals and these enlarge and coalesce with age.  Tunnel vision occurs early as the peripheral visual field is constricted to 5-10 degrees by midlife.  The retinal disease is progressive and blindness may be the final result.

A retinitis pigmentosa-like retinopathy is the major ocular manifestation of this disease.  There is typical night blindness and visual field constriction.   Rod ERG responses are usually subnormal.  However, central acuity is also reduced due to a degenerative maculopathy.   Cataracts and optic atrophy are common.  The macula may undergo progressive degeneration and optic atrophy is not uncommon.  Some patients have defective pupillary responses.

There exist a considerable number of disorders often classified under the heading of 'flecked retina' syndrome.  Prior to the modern genomic period, distinctions among them were based on the clinical picture, functional abnormalities, and electrophysiological studies.  The nosology is becoming clearer as more individuals are genotyped and we can expect further discrimination of these disorders in the near future.

White or yellow discrete dots are found throughout the fundus.  These are most dense in the midperiphery RPE and the macula is generally not involved.  This is most common in patients with fundus albipunctatus who have a nonprogressive disease.  Stationary night blindness is the predominant symptom.  However, patients with mutations in RDH5 may have more serious cone involvement and progressive macular disease.  Visual acuity varies from near normal to severe loss.  Photopic ERGs may be normal but only low scotopic responses can be recorded in such patients.  Cone dysfunction is more severe in older patients.

The distinctive feature of Oguchi disease is the peculiar and distinctive discoloration of the fundus under various light conditions, known as the Mizuo phenomenon.  Typically, the fundus assumes a golden or gray-white coloration under light adapted conditions but this disappears during acute dark adaptation and only reappears after prolonged time spent in darkness.  Rod dark adaptation is markedly delayed while that of cones is normal.  Single flash cone and 30Hz flicker responses are markedly reduced.  Visual acuity, visual fields and color vision are all normal.   A- and b-waves on single flash ERG are decreased or absent under lighted conditions but increase after prolonged dark adaptation.  Night blindness is present from birth without progression.

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.

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defects in visual signal transduction within rod photoreceptors or in defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  However, the photopic ERG can be abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

Congenital stationary night blindness disorders are primarily rod dystrophies presenting early with symptoms of nightblindness and relative sparing of central vision.  Nystagmus and photophobia are usually not features.  Dyschromatopsia and loss of central acuity can develop later as the cones eventually become dysfunctional as well but these symptoms are much less severe than those seen in cone-rod dystrophies.  The amount of pigmentary retinopathy is highly variable.

This disorder (CSNBAD3), one of three autosomal dominant CSNB conditions, is known primarily from  a single large family in Southern France.  All affected individuals descended from Jean Nougaret from which the eponym is derived.  The published pedigree by F. Cunier in 1838 is probably the first illustrating autosomal dominant inheritance of a human disease.  Rod a-waves are completely absent suggesting complete lack of rod function.  Night vision in dim conditions was reduced but not with bright backgrounds.  Daytime vision is normal as is color vision.  Rare patients have peripheral pigmentary changes with visual field restriction.