The diagnostic usefulness of electroretinography (ERG) measurements in congenital PAX6-aniridia

Abstract

Purpose : Congenital PAX6-aniridia is associated with developmental ocular abnormalities making it a complex syndromic disorder rather than an isolated disease of the iris. The PAX6 gene plays a crucial role in normal fetal development of the eye and is a part of a transcriptional network that regulates photoreceptor specification. Here we focused on the characterization of retinal function by electroretinography (ERG) measurements and study the validity and usefulness of a hand-held electrophysiologic tool.

Methods : Genetically confirmed congenital aniridia patients underwent detailed ophthalmological examination including best -corrected visual acuity (BCVA) and fullfield ERG measurements using the RETeval system (LKC Technologies Inc., Gaithersburg, MD, USA) with sensor strip skin electrodes. Besides the ISCEV standards, we additionally recorded photopic negative responses (PhNR).

Results : Fifteen patients (8 female, 7 male, age 24.8±15 years, range 9 to 57 years) from eleven families with genetically confirmed mutations in the PAX6 gene were included. All patients had nystagmus, their BCVA varied between light perception and 0.3 logMAR (mean: 1.02±0.54) and showed a worsening with age (r_S=0.51). There was no significant difference in scotopic response ERG amplitudes between patients and controls (n=18), however, implicit times were significantly delayed (p <0.001). Photopic a- and b-wave implicit times were delayed (p<0.01 and p <0.001, respectively) and amplitudes were reduced (p <0.04), 30 Hz flicker latency was markedly prolonged (p <0.001), while response amplitudes did not differ significantly (p= 0.17). Although PhNR amplitudes and implicit times did not differ significantly from controls, W-ratio was considerably lower in patients (W= 0.89±0.1) than in controls (W= 1.09±0.05), indicating reduced signal transmitting through the layers of the retina. Dark and light adapted responses showed a tendency of worsening with age. ERG recordings were well-tolerated by patients.

Conclusions : To date, this is the largest ERG study in congenital aniridia. The results show that both photoreceptor-related functions and postreceptoral signal transmitting are affected in PAX6-related aniridia and suggest that retinal changes extend beyond the central macula. RETeval can be a useful screening device to obtain retinal function and disease progression in aniridia, with regard to an increased risk for glaucoma.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.