Purpose: To investigate characteristics of the foveal pit and the foveal avascular zone (FAZ) in patients with Alport syndrome (AS), a rare monogenetic disease due to mutations in genes encoding for collagen type IV.
Methods: Twenty-eight eyes of nine patients with AS, and five autosomal-recessive carriers and 15 eyes from 15 age-similar healthy control subjects were examined using optical coherence tomography (OCT) and OCT-angiography (OCT-A). Foveal configuration and FAZ measures including the FAZ area, circularity, and vessel density in the central 1° and 3° were correlated.
Results: Foveal hypoplasia was found in 10 eyes from seven patients with either genotype. In contrast, a staircase foveopathy was found in seven eyes of four X-linked AS patients. The average FAZ area did not differ significantly between AS patients and control subjects (mean ± SD 0.24 ± 0.24 mm2 vs. 0.21 ± 0.09 mm2; P = 0.64). Five eyes showed absence or severe anomalies of the FAZ with crossing macular capillaries that was linked to the degree of foveal hypoplasia on OCT images leading to a significant inverse correlation of FAZ area and foveal thickness (r = -0.88; P < 0.001). In contrary, female patients with X-linked mutations exhibited a significantly greater FAZ area (0.48 ± 0.30 mm2 vs. 0.21 ± 0.09 mm2; P = 0.007), in line with OCT findings of a staircase foveopathy.
Conclusions: The foveal phenotypic spectrum in AS ranges from foveal hypoplasia and absence of a FAZ to staircase foveopathy with an enlarged FAZ. Because the development of the FAZ and foveal pit are closely related, these findings suggest an important role for collagen type IV in foveal development and maturation.