Perifoveal Chorioretinal Atrophy after Subretinal Voretigene Neparvovec-rzyl for RPE65-Mediated Leber Congenital Amaurosis

William S. Gange, Robert A. Sisk, Cagri G. Besirli, Thomas C. Lee, Margaret Havunjian, Hillary Schwartz, Mark Borchert, Jesse D. Sengillo, Carlos Mendoza, Audina M. Berrocal, Aaron Nagiel

Research output: Contribution to journalArticlepeer-review


Purpose: To report an anatomic change following subretinal injection of voretigene neparvovec-rzyl (VN) for RPE65-mediated Leber congenital amaurosis. Design: Multicenter, retrospective chart review. Participants: Patients who underwent subretinal VN injection at each of 4 participating institutions. Methods: Patients were identified as having perifoveal chorioretinal atrophy if (1) the areas of atrophy were not directly related to the touch-down site of the subretinal cannula; and (2) the area of atrophy progressively enlarged over time. Demographic data, visual acuity, refractive error, fundus photographs, OCT, visual fields, and full-field stimulus threshold (FST) were analyzed. Main Outcome Measures: Outcome measures included change in visual acuity, FST, visual fields, and location of atrophy relative to subretinal bleb position. Results: A total of 18 eyes of 10 patients who underwent subretinal injection of VN were identified as having developed perifoveal chorioretinal atrophy. Eight of 10 patients (80%) developed bilateral atrophy. The mean age was 11.6 years (range, 5–20 years), and 6 patients (60%) were male. Baseline mean logarithm of the minimum angle of resolution visual acuity and FST were 0.82 (standard deviation [SD], 0.51) and −1.3 log cd.s/m2 (SD, 0.44), respectively. The mean spherical equivalent was −5.7 diopters (D) (range, −11.50 to +1.75 D). Atrophy was identifiable at an average of 4.7 months (SD, 4.3) after surgery and progressively enlarged in all cases up to a mean follow-up period of 11.3 months (range, 4–18 months). Atrophy developed within and outside the area of the subretinal bleb in 10 eyes (55.5%), exclusively within the area of the bleb in 7 eyes (38.9%), and exclusively outside the bleb in 1 eye (5.5%). There was no significant change in visual acuity (P = 0.45). There was a consistent improvement in FST with a mean improvement of −3.21 log cd.s/m2 (P < 0.0001). Additionally, all 13 eyes with reliable Goldmann visual fields demonstrated improvement, but 3 eyes (23.1%) demonstrated paracentral scotomas related to the atrophy. Conclusions: A subset of patients undergoing subretinal VN injection developed progressive perifoveal chorioretinal atrophy after surgery. Further study is necessary to determine what ocular, surgical delivery, and vector-related factors predispose to this complication.

Original languageEnglish (US)
JournalOphthalmology Retina
StateAccepted/In press - 2021
Externally publishedYes


  • Chorioretinal atrophy
  • Complications
  • Gene therapy
  • Leber congenital amaurosis
  • Luxturna
  • Outcomes Research
  • Subretinal injection
  • Voretigene neparvovec-rzyl

ASJC Scopus subject areas

  • Ophthalmology


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