Faculty Collaboration Database

In Vivo Assessment of Retinal Phenotypes in Axenfeld-Rieger Syndrome. Invest Ophthalmol Vis Sci 2024 Apr 01;65(4):20

Date

04/08/2024

Pubmed ID

38587439

Pubmed Central ID

PMC11005067

DOI

10.1167/iovs.65.4.20

Scopus ID

2-s2.0-85190399640 (requires institutional sign-in at Scopus site)

Abstract

PURPOSE: Axenfeld-Rieger syndrome (ARS) is characterized by ocular anomalies including posterior embryotoxon, iridocorneal adhesions, corectopia/iris hypoplasia, and developmental glaucoma. Although anterior segment defects and glaucoma contribute to decreased visual acuity, the role of potential posterior segment abnormalities has not been explored. We used high-resolution retinal imaging to test the hypothesis that individuals with ARS have posterior segment pathology.

METHODS: Three individuals with FOXC1-ARS and 10 with PITX2-ARS completed slit-lamp and fundus photography, optical coherence tomography (OCT), OCT angiography, and adaptive optics scanning light ophthalmoscopy (AOSLO). Quantitative metrics were compared to previously published values for individuals with normal vision.

RESULTS: All individuals demonstrated typical anterior segment phenotypes. Average ganglion cell and inner plexiform layer thickness was lower in PITX2-ARS, consistent with the glaucoma history in this group. A novel phenotype of foveal hypoplasia was noted in 40% of individuals with PITX2-ARS (but none with FOXC1-ARS). Moreover, the depth and volume of the foveal pit were significantly lower in PITX2-ARS compared to normal controls, even excluding individuals with foveal hypoplasia. Analysis of known foveal hypoplasia genes failed to identify an alternative explanation. Foveal cone density was decreased in one individual with foveal hypoplasia and normal in six without foveal hypoplasia. Two individuals (one from each group) demonstrated non-foveal retinal irregularities with regions of photoreceptor anomalies on OCT and AOSLO.

CONCLUSIONS: These findings implicate PITX2 in the development of the posterior segment, particularly the fovea, in humans. The identified posterior segment phenotypes may contribute to visual acuity deficits in individuals with PITX2-ARS.

Author List

Untaroiu A, Reis LM, Higgins BP, Walesa A, Zacharias S, Nikezic D, Costakos DM, Carroll J, Semina EV

Authors

Joseph J. Carroll PhD Director, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
Deborah M. Costakos MD Chair, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anterior Eye Segment
Corneal Diseases
Eye Abnormalities
Eye Diseases, Hereditary
Glaucoma
Humans
Retina