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. 2023 Oct 5;13(10):1484.
doi: 10.3390/biom13101484.

Outcomes and Adverse Effects of Voretigene Neparvovec Treatment for Biallelic RPE65-Mediated Inherited Retinal Dystrophies in a Cohort of Patients from a Single Center

Peter Kiraly  1   2 , Charles L Cottriall  1   2 , Laura J Taylor  1   2 , Jasleen K Jolly  2   3 , Jasmina Cehajic-Kapetanovic  1   2 , Imran H Yusuf  1   2 , Cristina Martinez-Fernandez de la Camara  1   2 , Morag Shanks  4 , Susan M Downes  1   2 , Robert E MacLaren  1   2 , M Dominik Fischer  1   2   5
Affiliations

Outcomes and Adverse Effects of Voretigene Neparvovec Treatment for Biallelic RPE65-Mediated Inherited Retinal Dystrophies in a Cohort of Patients from a Single Center

Peter Kiraly et al. Biomolecules. .

Abstract

Our study evaluated the morphological and functional outcomes, and the side effects, of voretigene neparvovec (VN) gene therapy for RPE65-mediated inherited retinal dystrophies (IRDs) in 12 eyes (six patients) at the Oxford Eye Hospital with a mean follow-up duration of 8.2 (range 1-12) months. All patients reported a subjective vision improvement 1 month after gene therapy. Best-corrected visual acuity (BCVA) remained stable (baseline: 1.28 (±0.71) vs. last follow-up: 1.46 (±0.60); p = 0.25). Average white Full-Field Stimulus Testing (FST) showed a trend towards improvement (baseline: -4.41 (±10.62) dB vs. last follow-up: -11.98 (±13.83) dB; p = 0.18). No changes in central retinal thickness or macular volume were observed. The side effects included mild intraocular inflammation (two eyes) and cataracts (four eyes). Retinal atrophy occurred in 10 eyes (eight mild, two severe) but did not impact FST measurements during the follow-up period. Increased intraocular pressure (IOP) was noted in three patients (six eyes); four eyes (two patients) required glaucoma surgery. The overall safety and effectiveness of VN treatment in our cohort align with previous VN clinical trials, except for the higher occurrence of retinal atrophy and increased IOP in our cohort. This suggests that raised IOP and retinal atrophy may be more common than previously reported.

Keywords: IRD; RPE65-mediated inherited retinal dystrophies; adverse effects; functional outcomes; gene therapy; high IOP; retinal atrophy; voretigene neparvovec.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Mean best-corrected visual acuity (BCVA) (p = 0.25), (B) mean Full-Field Stimulus Testing (FST, more negative values represent a higher threshold) (p = 0.18), (C) central retinal thickness (CRT) (p = 0.34) changes from baseline to the last visit. Each datapoint represents an eye.
Figure 2
Figure 2
Development of retinal atrophy (Patient 3). Pseudo-color images showing the right eye (RE) (A) and the left eye (LE) (B) prior to gene therapy, at 6 months after the surgery ((RE) (C), (LE) (D)), and at 12 months after the surgery ((RE) (E), (LE) (F)).
Figure 3
Figure 3
Worsening of fovea-involving retinal atrophy (Patient 3). Optical coherence tomography images showing the fovea prior to gene therapy (A) and at the 12-month follow-up (B). Goldmann visual field in the same patient prior to gene therapy (C) and at the 12 months follow-up (D); best-corrected visual acuity (BCVA); Full-Field Stimulus Testing (FST).
Figure 4
Figure 4
Development of retinal atrophy 1 week after gene therapy (Patient 6). Pseudo-color images prior to gene therapy (A) and one week after (B). The green arrow indicates the touch-down site of the subretinal cannula, the red arrows represent the area of new retinal atrophy, and the blue circle indicates the area of the raised bleb.
See this image and copyright information in PMC

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