Original article
16 and 24 Gy Low-voltage X-ray Irradiation With Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration: 12-Month Outcomes

https://doi.org/10.1016/j.ajo.2013.01.015Get rights and content

Purpose

To describe the 12-month safety and efficacy outcomes of 16 or 24 Gy radiation using low-voltage x-ray irradiation in conjunction with intravitreal ranibizumab for neovascular age-related macular degeneration (AMD).

Design

Prospective, phase I, open-label, nonrandomized uncontrolled safety study.

Methods

setting: Institutional. study population: Neovascular AMD patients. intervention: One x-ray irradiation treatment at 16 or 24 Gy was administered externally through 3 locations in the inferior pars plana. After 2 initial monthly loading doses of ranibizumab, subsequent ranibizumab was administered according to predetermined criteria. main outcome measures: Visual acuity, number of ranibizumab injections, safety and efficacy metrics at 12 months.

Results

Forty-seven eyes of 47 patients were enrolled and completed 12 months of follow-up: 16 Gy (n = 28) and 24 Gy (n = 19). There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean visual acuity improved in both groups: +8.4 ± 11.9 letters and +7.8 ± 12 letters for 16 and 24 Gy, respectively. In both groups, 100% of subjects lost <15 letters, with 76% and 79% gaining ≥0 letters in the 16 Gy and 24 Gy groups, respectively. Patients received a mean of 1.0 additional injection over 12 months. The mean change in optical coherence tomography central subfield thickness from baseline to month 12 was −107 and −87 μm for the 16 Gy and 24 Gy groups, respectively.

Conclusion

One treatment of 16 or 24 Gy low-voltage x-ray therapy with as-needed ranibizumab appears safe in subjects with neovascular AMD at 12 months. An overall improvement in visual acuity was observed. No radiation-related adverse effects were reported.

Section snippets

Methods

This was a prospective, nonrandomized, open-label safety study of low-voltage radiation therapy and ranibizumab in subjects with neovascular AMD. Approval from the Institutional Review Board of Associacion Para Evitar La Ceguera En Mexico, I.A.P. (Mexico City, Mexico) and the government of Mexico for the use of the low-voltage stereotactic x-ray irradiation system for this trial of subjects with neovascular AMD was obtained prior to the start of the study. After proper informed consent was

16 Gy

Twenty-eight subjects were enrolled and treated, but 1 was subsequently excluded from the efficacy analysis as he was discovered to have had central retinal vein occlusion rather than CNV attributable to AMD. One subject died between the month 10 and month 11 follow-up visits, and another subject missed the month 12 visit; they are consequently not included in the aggregate 12-month visual acuity data presented in this paper. (These subjects' injection history is included, however.) Twenty-five

Discussion

In this phase I, open-label, single-center clinical trial, externally applied 16 or 24 Gy low-voltage x-ray irradiation with 2 loading doses of ranibizumab followed by adjunctive, as-needed ranibizumab injections demonstrated good safety and a visual acuity improvement in both treatment-naïve and previously treated subjects with neovascular AMD at 12-month follow-up.

There were no arterial thromboembolic events, endophthalmitis, or radiation-related complications including radiation retinopathy,

Virgilio Morales-Canton trained in ophthalmology and vitreoretinal surgery at the Asociacion para Evitar la Ceguera en Mexico, Mexico City, Mexico, followed by one year at the Eye Research Institute and Retina Associates at Harvard University. He has published dozens of papers, book chapters, and authored a book on diabetic retinopathy, in addition to presenting over 300 times at international meetings. In his current capacity as Chief of the Retina Department at Asociacion para Evitar la

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    Virgilio Morales-Canton trained in ophthalmology and vitreoretinal surgery at the Asociacion para Evitar la Ceguera en Mexico, Mexico City, Mexico, followed by one year at the Eye Research Institute and Retina Associates at Harvard University. He has published dozens of papers, book chapters, and authored a book on diabetic retinopathy, in addition to presenting over 300 times at international meetings. In his current capacity as Chief of the Retina Department at Asociacion para Evitar la Ceguera, he oversaw the Phase I clinical trial for radiation therapy of age-related macular degeneration, as well as numerous other clinical trials in retina. He has received numerous awards for his surgical videos.

    Darius M. Moshfeghi, MD, is an Associate Professor of Ophthalmology at Stanford University School of Medicine in Stanford, California. He serves as the Director of the Vitreoretinal Fellowship Program, Director of Pediatric Retinal Disease & Surgery, and the Director of Telemedicine in the Department of Ophthalmology. Additionally, he is the Founder and Director of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP). He continues to be actively involved in entrepeneurship and technology development.

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