First Author: J.K.Luttrull USA
Co Author(s): D.B. Chang D.K. Luttrull 0 0 0 0 0 0 0 0 0
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To evaluate the effect of subthreshold diode micropulse laser (SDM) in eyes tolerant to anti-VEGF drugs.
A private vitreoretinal subspecialty practice.
Acquired loss of drug effectiveness, or tolerance, is the most common reason for treatment failure in eyes with choroidal neovascularization (CNVM) in age-related macular degeneration (ARMD). High-density/low-intensity subthreshold diode micropulse laser (SDM) treatment has been found effective in the treatment of retinal vascular disease, central serous chorioretinopathy, and other disorders without adverse treatment effect. It has been proposed that SDM works by normalizing retinal pigment epithelium (RPE) function. We hypothesized that if correct, SDM might restore responsiveness to anti-vascular endothelial growth factor (VEGF) drugs in eyes tolerant and unresponsive to anti-VEGF medication. SDM was performed in consecutive eyes unresponsive to all anti-VEGF drugs. Loss of drug response, or tolerance, was defined as at least 4 consecutive monthly drug injections without improvement by OCT, including at least 2 consecutive final monthly injections of aflibercept. One month after the last ineffective aflibercept injection, SDM was performed. No drug was injected at the time of SDM treatment to so as not to interfere with the development of the laser effects on the RPE. One month later each eye was re-evaluated by OCT and monthly aflibercept therapy resumed.
10 consecutive eyes of 9 patients, aged 74-97 years, treated with SDM for anti-VEGF drug tolerance were identified. The number of pre – SDM drug injections, including bevacizumab, ranibizumab, and aflibercept, ranged 4 – 67 per eye (avg. 29). Nine eyes were tolerant to all drugs. One eye was not treated pre-SDM with ranibizumab, but was unresponsive to both bevacizumab and aflibercept. Between January 2013 and September 2014 a single SDM laser treatment was performed in each eye after confirmation of drug tolerance. One month later, 2 eyes were slightly improved and 4 significantly worsened by OCT. Aflibercept therapy was resumed one month post - SDM. Two months post - SDM and one month after re-challenge with aflibercept, 8 / 10 eyes were improved, with complete resolution of exudation in 2 eyes. By three months following SDM and a second post-SDM injection of aflibercept in 8/10 eyes, all eyes (10/10) were improved with complete resolution of exudation in 6/10 eyes, and Central Foveal Thickness and Maximum Macular Thickness both significantly improved (both p=0.0078, Wilcoxon signed rank tests). Overall visual acuity was unchanged. No eye showed evidence of adverse treatment effect or laser-induced retinal damage.
SDM has been found to be therapeutically effective in a number of unrelated retinal disorders without causing any known retinal damage or adverse treatment effect. These observations, together with the literature on near-infrared laser tissue effects, suggest that the effect of SDM is to normalize RPE function. As tolerance to retinal anti-VEGF drugs may reflect in part drug-induced alteration of RPE cytokine production (both up and down regulation) in response to high pharmacologic doses of drug, we hypothesized that if SDM was able to normalize (“reset to default”) the function of drug-tolerant RPE, SDM might return the RPE to its original, drug responsive state. Our findings, that SDM was indeed able to restore responsiveness to anti-VEGF drugs in drug-tolerant exudative AMD support this hypothesis, and suggest that SDM may have a role as an adjuvant to pharmacologic treatment of age-related CNVM by maintaining and maximizing drug sensitivity