fleck retina

Stargardt disease or fundus flavimaculatus is a progressive form of juvenile macular degeneration with considerable clinical and genetic heterogeneity.  It may be considered a syndromal cone-rod dystrophy because of overlapping clinical features such as loss of color vision and photophobia in some patients.  Adding to the confusion is the fact that mutations in at least 4 genes are responsible for similar clinical characteristics.  Due to the lack of diagnostic distinctions and the wide range of nonspecific clinical manifestations, Stargardt disease and fundus flavimaculatus are discussed here as a single entity.

Onset of vision loss is often noted late in the first decade of life usually with rapid progression.  However, some patients are asymptomatic until much later, even into the fifth decade.  There is evidence that patients with an early onset have a worse prognosis compared to those with a later onset.  Nevertheless, large series of patients contain at least 23% with 20/40 or better acuity, about 20% with 20/50 -20/100, 55% have 20/200-20/400, and a small number have vision less than 20/400. 

Some color discrimination is lost and photophobia may be a complaint.  Dark adaptation is prolonged but nightblindness does not usually occur and peripheral visual fields are normal.  The posterior pole characteristically has yellowish pisciform, round, and linear subretinal lipofuscin deposits which often extend to the equator.  These may be present before clinical symptoms are present.  Histopathology reveals accumulations of this material in RPE cells.  Atrophy of the RPE in the same region is often visible as well but these changes may be subtle initially.  Some patients have peripheral pigment clumping which may resemble the bone spicule configuration seen in retinitis pigmentosa.  However, retinal vessel caliber is normal in Stargardt disease.  Extensive macular disease can be associated with temporal pallor of the optic nerve.  The ERG shows reduced photopic responses with normal or near normal scotopic tracings.  Fluorescein angiography often reveals more extensive disease than seen on fundoscopy.  Window defects are common in the macula where the RPE is atrophied.  The flecks may be hypo- or hyperfluorescent.  Over 50% of patients have patches of angiographically dark choroid in the posterior pole which is thought to be secondary to transmission blockage by lipofuscin accumulations in the RPE. 

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 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.

This disorder is usually included in listings of flecked retina syndrome but few reports exist.  Irregular flecks of variable size are distributed in the equator and posteriorly up to but excluding the macula.  Some disturbances of the RPE are seen and some degree of night blindness is usually present.  It seems to be a stable disorder.