Multimodal widefield imaging for postoperative monitoring in patients treated with voretigene neparvovec

Abstract

Purpose : Gene augmentation therapy with voretigene neparvovec (VN) has recently been made available for the treatment of patients with RPE65 mutation associated inherited retinal degeneration (RPE65-IRD). In a subset of patients treated with VN, development of atrophy has been previously reported. Here, we identify safety endpoints and imaging modalities that allow assessment of atrophy development following therapy with VN.

Methods : Single center longitudinal analysis of different imaging modalities prior and post treatment with VN in patients treated with VN for RPE65-IRD. Qualitatively analysed imaging modalities included colour fundus photography (CFP, Clarus 700, Zeiss) and confocal scanning laser ophthalmoscopy (Spectralis OCT, Heidelberg Engineering) with 30° and 55° blue light fundus autofluorescence (BAF), 30° and 55° near infrared imaging (IR) as well as spectral-domain optical coherence tomography (SD-OCT) of the macula.

Results : We analysed 18 patients treated with VN (27 eyes treated, 9 fellow eyes untreated). Median age at time of treatment was 28 years (range 7 – 39) and median follow up period was 6 months (range 1-21). Widefield, 55° IR images were available in all patients in good quality and allowed detection of postoperative atrophy development in 7 eyes of 5 patients (26 % of all treated eyes). Acquisition of BAF images was only possible in 3 patients and failed in 15 patients due to low levels of BAF signals. Macular OCT was available in all patients but failed to detect atrophy development sufficiently. Widefield CFP was available and detected atrophy in all patients. However, atrophy development was less obvious in CFP compared with 55° IR and mean time to detect atrophy development with CFP was 4 months (range 1-8) compared to 3.3 months (range 1-8) using 55° IR imaging.

Conclusions : Early detection of atrophy development and progression following VN treatment might be easily missed due to disease specific abnormalities (nystagmus, absent or low levels of BAF, altered retina). Widefield near infrared images appear superior for identification compared with other imaging modalities. Automated detection and quantification of lesion growth based on serial IR images over time is currently explored in order to allow for accurate quantitative analyses.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.