High-resolution imaging analysis of foveal hypoplasia with a novel PAX6 mutation

Abstract

Purpose : The PAX6 mutation cause a variety of ocular malformations, such as aniridia and foveal hypoplasia (FVH). The lack of foveal avascular zone (FAZ) in FVH was previously reported using optical coherence tomography angiography (OCTA). Also cone photoreceptor dimension by adaptive optics (AO) imaging in FVH caused by albinism was previously reported (McAllister &Carroll, 2011). However, structural feature using AO in FVH with PAX6 mutation remains unclear. This study tested the hypothesis that the cone density in FVH with a novel PAX6 mutation decrease as previously reported FVH with albinism in vivo.

Methods : Four eyes from two cases, 6 y.o. boy(case1) and his mother 40 y.o.(case2) who had FVH in both eyes underwent genetic analysis and ophthalmological examinations including SD-OCT, OCTA（Cirrus 5000^TM, Zeiss）and AO fundus camera (rtx1^TM, Imagine eyes). Cone density was measured at 1deg to 4deg in horizontal in case1, 1deg to 8deg horizontal in case2, using 80x80 pixels square images obtained by AO. The results were compared with previously published histological normative data (Curcio et al, 1990) and our normal control data.

Results : Genetic analysis revealed a novel mutation in PAX6(c.275T, p.V92A) in two cases with FVH.
Decimal BCVA of case1 was 1.0(20/20) in both eyes, case2 were 1.0(20/20) in the right eye, 0.9(20/23) in the left eye. Case 1 showed almost normal iris, Case2 showed full iris with slightly abnormal architecture in both eyes. All eyes showed lack of foveal reflex in fundus examination. Grade3 FVH was defined by absence of foveal pit, photoreceptor outer segment lengthening and extrusion of plexiform layers, and presence of outer nuclear layer widening in SD-OCT. All eyes had lack of FAZ in the capillary plexus in superficial layer by OCTA. Cone density were 3.5-3.6 x10⁴(cone/mm²) at 1 deg, 2.0-2.4x10⁴ (cone/mm²) at 2 deg, 1.1-1.6x10⁴ (cone/mm²) at 4deg temporal. Decreased cone packing and slightly reduced cone density in all eccentricities were found.

Conclusions : Grade 3 FVH with a novel mutation in PAX6(c.275T, p.V92A) showed lack of FVA in superficial layer as previously reported. AO analysis revealed that cone density of FVH with PAX6 was decreased similar to that of FVH with albinism. The cone density at 1 deg was close to histological 2 deg in normal data.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.