Retinal Basement Membrane Abnormalities and the Retinopathy of Alport Syndrome

Abstract

The Alport dot-and-fleck retinopathy results primarily from abnormalities in the ILM/nerve fiber layer rather than in Bruch's membrane. Thinning of the ILM/nerve fiber layer contributes to the retinopathy, lozenge, and macular hole, possibly through interfering with nutrition of the overlying retina or clearance of metabolic by-products.

Unusual macular thickness in Alport syndrome: case report

“…The latter was first described by Usui et al (7) , and by other authors (Table 1). Recently, Savige et al, evaluated a case series of patients with AS and macular changes and found similar alterations to the described case (8) . The authors suggest that mutation of COLA4 gene causes a structural modification in the internal limiting mem brane, inner nuclear and nerve fiber layer due to owing to a molecular alteration of type IV collagen.…”

“…This change would cause a thinning and fragility of retinal layers resulting from the structural collagen changeover. The thinning was statistically significant at the foveal and temporal region of macula (8) . Colville et al, described the same macu lar alteration named as "lozenge" or "dull macular reflex" in a group of patients with AS, and highlighted the importance of acknowledging the findings with the aid of redfree image and its correlation with diagnosis and poor prognosis of the disease (10) .…”

Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes

“…Dots and flecks may be seen in the macula, with the flecks sometimes outlining a macular "lozenge". The macular flecks appear to be related to hyper-reflectivity of the ILM on OCT imaging, and the macular "lozenge" appears to be related to temporal macular thinning (Savige et al, 2010). Mid-peripheral retinal flecks are also commonly observed, and at least in some patients, these have the appearance of mid-peripheral drusen.…”

Retinal Abnormalities Characteristic of Inherited Renal Disease

“…45 The dots and flecks in Alport syndrome are not technically drusen because they affect the internal limiting membrane rather than the RPE. 46 They are smaller than the drusen in membranoproliferative glomerulonephritis type 2 and do not involve the macula. The drusen in dense deposit disease are large and soft and Alport syndrome affects 1 in 10,000 individuals 47 and accounts for 2% of adults with ESRD.…”

“…Sixty percent of patients have a mutation in the CHD7 gene 34 which codes for a DNAbinding protein involved in early embryonic development. Ninety percent of chil- 46 Membranoproliferative glomerulonephritis Nephronophthisis 141 Bardet-Biedl syndrome 142 Alagille syndrome 143,77 MELAS syndrome 80,81 Kearns-Sayre syndrome 82 LCAT deficiency 115 Cystinosis 129 Oxalosis 121 Fabry disease 144,145 39 Loss of these genes produces ocular and genitourinary anomalies, respectively. The iris is deficient, and the optic nerve and fovea are hypoplastic.…”