Phase I/II randomized study of proton beam with anti-VEGF for exudative age-related macular degeneration: long-term results - PubMed (original) (raw)

Clinical Trial

Lekha K Mukkamala et al. Eye (Lond). 2020 Dec.

Abstract

Background/objective: To determine if treatment of exudative age-related macular degeneration (eAMD) using proton beam therapy (PBT) combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is safe and effective long term.

Subject/methods: Thirty eyes with newly diagnosed eAMD were enrolled in a phase I/II prospective, sham-controlled double-masked university study. Eyes were randomized 1:1:1-24 GyE, 16 GyE or sham radiation, and treated with three initial monthly intravitreal ranibizumab or bevacizumab. Subsequent anti-VEGF reinjection was based on monthly optical coherence tomography and examination for 2 years and standard of care thereafter.

Results: A total of 23 eyes completed 2-year study follow-up, of which 16 maintained monthly follow-up. Mean best-correct visual acuity (BCVA) at 2 years was similar among treatment groups (p > 0.05). The 24 GyE group required fewer anti-VEGF injections when compared with the sham group at 2 years (4.67 ± 1.9 vs 9.67 ± 3.5; p = 0.017). Extended follow-up (mean 4 years) available in 22 eyes showed persistent reduced need for anti-VEGF therapy among eyes treated with 24 GyE compared with sham radiation (2.0 ± 1.6 vs 4.84 ± 2.4 per year, p = 0.008). New and increasing geographic atrophy (GA), noted in some eyes in all treatment groups, resulted in decreased mean BCVA from baseline for the 24 GyE group on extended follow-up (p = 0.009). Possible mild radiation retinopathy noted in 15% of eyes was not visually significant.

Conclusions: Initial treatment combining PBT (24 GyE) with intravitreal anti-VEGF therapy appears to decrease the need for anti-VEGF reinjection in eyes with newly diagnosed eAMD. Radiation retinopathy risk was low and does not appear visually significant. Long-term vision was limited by GA development especially in the 24 GyE group.

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Conflict of interest statement

SSP has received research support via employer from Allergan and Roche/Novartis for contracted clinical research exploring anti-VEGF drugs for treatment of retinal disorders including exudative AMD. None of the other authors have any conflict of interest to disclose.

Figures

Fig. 1

Fig. 1. Mean best-corrected visual acuity of study groups at baseline and follow-up.

Mean best-corrected visual acuity of study groups at baseline, 1 year, 2 years and last follow-up for participants who maintained 2-year study follow-up (n = 23; a) and whose who maintained monthly study follow-up for 2 years (n = 16; b). P values shown are compared with baseline (BL) using a two-tailed Student t test unless otherwise specified. P < 0.05 is statistically significant difference from baseline.

Fig. 2

Fig. 2. Mean number of anti-VEGF injections in study eye during follow-up.

Mean number of intravitreal anti-VEGF injections administered at year 1 and 2 for the cohort maintaining 2-year study follow-up (a; n = 23) and subgroup with that maintained monthly study follow-up for 2 years (b; n = 16). Mean number of intravitreal anti-VEGF injections per year based on treatment group during post-study period (striped) and total follow-up period (solid) for the total cohort seen at study center after study exit (c; n = 22). P values shown are compared with the sham radiation group using a two-tailed Student t test. An asterisk denotes statistical significance (P < 0.05).

Fig. 3

Fig. 3. Change in choroidal neovascular membrane size and leakage on fluorescein angiography at baseline and at 2 years follow-up among study groups.

a Mean size of choroidal neovascular membrane in disc areas at baseline and follow-up among eyes that had fluorescein angiography (FA) at 2 years for each study group. P value represents difference between groups; b Graph shows distribution of eyes in each study group with varying severity of leakage at baseline (left) and at 2 years follow-up (right). Leakage severity was graded as severe (3), moderate (2), mild (1), or none (0). P value represents difference between groups using ANOVA.

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