Microvascular abnormalities and long-term efficacy after stereotactic radiotherapy under continued intravitreal anti-VEGF treatment for neovascular AMD

Abstract

BackgroundFor treatment of neovascular age-related macular degeneration (nAMD), multiple intravitreal injections of drugs targeting vascular endothelial growth factors (VEGF) result in a high burden for patients and healthcare systems. Low-energy stereotactic radiotherapy (SRT) might reduce the anti-VEGF need. This study evaluated the long-term efficacy and safety of adjunct SRT to anti-VEGF injections in a treat-and-extend regimen in nAMD.Methods50 consecutive patients were followed 3 years after single-session SRT, a safety analysis including standardised study imaging, and a reading centre based image analysis was performed after 2 years.ResultsAfter increase from baseline (4.24±0.66 weeks) to 12 months (7.52±3.05 weeks, p<0.001), mean recurrence-free anti-VEGF treatment interval remained stable at 24 (7.40±3.17, p=0.746) and 36 months (6.89±3.00, p=0.175). Mean visual acuity change was −5.8±15.9 and −11.0±20.1 letters at 24 and 36 months, respectively. 36% of eyes showed microvascular abnormalities (MVAs) on colour fundus photography and/or fluoresceine angiography most frequently located in parafoveal inferior and nasal regions.ConclusionIn real life, low-energy SRT was associated with a reduced anti-VEGF injection frequency through year 3. However, due to an observed visual acuity reduction and remarkable number of MVAs, a close follow-up of these patients is recommended. The real-life use, optimal treatment schedule and dose should be rediscussed critically.

Polypoidal Choroidal Vasculopathy after Stereotactic Radiotherapy for Neovascular Age-Related Macular Degeneration: A Case Report with Long-Term Follow-Up

“…This corresponds to the findings of the INTREPID trial as well as a few real-life analyses [5,6,[10][11][12]. However, like several patients in a real-life case series [8], our patient experienced the necessity of shortening of anti-VEGF treatment intervals in the third year after SRT. In both the INTREPID trial and the previous mentioned real-life analysis, SRT was associated with development of MVA occurring in the second and third year after SRT and being located most frequently in the parafoveal inferior and nasal region [7,8].…”

“…However, like several patients in a real-life case series [8], our patient experienced the necessity of shortening of anti-VEGF treatment intervals in the third year after SRT. In both the INTREPID trial and the previous mentioned real-life analysis, SRT was associated with development of MVA occurring in the second and third year after SRT and being located most frequently in the parafoveal inferior and nasal region [7,8]. While the parafoveal nasal appearance of more MVAs (mostly cotton wool spots) might be caused by the thicker retinal nerve fiber layer and its susceptibility to develop cotton wool spots the preference of the parafoveal inferior location remains unclear but was tried to be explained by the inferior part of the retina possibly being exposed to higher doses compared to the upper part due to the entrance of all 3 beams from the inferior sclera [8].…”

“…Retinal MVA found in color fundus photography and/or fluorescein angiography included nerve fiber infarcts, retinal hemorrhages, microaneurysms, luminal irregularities, focal areas of capillary closure, distended (bullous) arteriolar and venular tips, telangiectatic segments, and late staining of the vessel walls [7]. A reading center-based evaluation of real-life data confirmed these findings for clinical routine, too [8]. Yet, to the best of our knowledge, there are no reports on choroidal changes after adjunct SRT in nAMD so far.…”

“…In both the INTREPID trial and the previous mentioned real-life analysis, SRT was associated with development of MVA occurring in the second and third year after SRT and being located most frequently in the parafoveal inferior and nasal region [7,8]. While the parafoveal nasal appearance of more MVAs (mostly cotton wool spots) might be caused by the thicker retinal nerve fiber layer and its susceptibility to develop cotton wool spots the preference of the parafoveal inferior location remains unclear but was tried to be explained by the inferior part of the retina possibly being exposed to higher doses compared to the upper part due to the entrance of all 3 beams from the inferior sclera [8]. Our patient did not develop any of these retinal MVAs but choroidal changes such as multiple PCV lesions, most frequently located in the parafoveal inferior region, too.…”

Persistent and Poor-Responsive Cystoid Macular Edema after Stereotactic Radiotherapy in Neovascular Age-Related Macular Degeneration: A Case Report of Three Patients

“…SRT treatment, although still an experimental treatment, is known to be a safe and efficient procedure, but some long-term side effects are known. Radiation retinopathy (RR) is the most dreaded long-term complication of radiotherapy to the eye but because the SRT device delivers precisely targeted radiotherapy, and as the area of retinal exposure is extremely small a larger area of RR is not expected to develop 4 , 5 , 6 .…”