Phenotypic Spectrum of the Foveal Configuration and Foveal Avascular Zone in Patients With Alport Syndrome

Abstract

spectrum of the foveal configuration and foveal avascular zone in patients with Alport syndrome. Invest Ophthalmol Vis Sci. 2020;61(2):5. https://doi.org/10.1167/iovs.61.2.5 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 mm 2 vs. 0.21 ± 0.09 mm 2 ; 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 mm 2 vs. 0.21 ± 0.09 mm 2 ; 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.

Structural, Microvascular, and Functional Findings Associated with Fovea Plana

“…Hypopigmented fundus, in association with nystagmus and decreased macular thickness, was found in both of our cases of ocular albinism 4 . Irregularity in central macular thickness and a temporal thinning of the macular neuroretina was confirmed in our patient with Alport syndrome 5 .…”

“…Fovea plana is already described in cases of oculocutaneous albinism and PAX6-associated aniridia 2 , 4 . It is also observed in hyperopia 3 , as well as in inherited diseases such as achromatopsia 4 , incontinentia pigmenti 18 , Alport syndrome 5 , posterior microphthalmos 3 , Goldmann-Favre syndrome 19 , Prader-Willi syndrome 20 , septo-optic dysplasia 21 , situs inversus of the optic disc 22 , and glucose-6-phosphate dehydrogenase deficiency 23 . An absence of a foveal pit as an isolated finding is less common and is usually accompanied by nystagmus 24 .…”

“…Developmental arrest of the fovea pit is proposed to lead to varying degrees of foveal hypoplasia, though representing different stages of this morphological abnormality 1 . In conjunction with the underlying pathology, the fovea pit could be present in a heterogenic way, ranging from isolated fovea plana, foveal dysgenesis, or foveal aplasia and could be associated with conditions such as albinism, prematurity, hyperopia, and hereditary diseases 2 , 3 , 4 , 5 , 6 , 7 , 8 . In all these conditions, an irregular persistence of the inner retinal layers, including the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer, has been observed at the fovea 9 , 10 , 11 .…”

“…Via OCT imaging, some structural patterns could be identified as hallmarks of the disease. For instance, an elevated papillomacular fold is a characteristic feature for posterior microphthalmos [3], decreased foveal thickness for albinism or achromotopsia [4], and irregular "staircase foveopathy" for Alport syndrome [5].…”

Quantitative Optical Coherence Tomography Angiography Biomarkers for Alport Syndrome

“…VD and FAZ measurement are the most commonly used metrics. Hess et al [22] state that the FAZ value of AS patients ranged from enlarged, in the staircase foveopathy, to its absence, in the foveal hypoplasia cases. We report a FAZ and VD values of the SCP lower in patients with AS than healthy subjects, but this difference is not statistically significant.…”