Association of Changes in Macular Perfusion With Ranibizumab Treatment for Diabetic Macular Edema

Abstract

IMPORTANCE Anti-vascular endothelial growth factor treatment is the first-line therapy in the treatment of center-involving diabetic macular edema. Data on capillary perfusion changes under repeated treatment in a possibly compromised vascular network are limited.OBJECTIVE To evaluate the association of repeated ranibizumab injections on macular perfusion in patients with diabetic macular edema. DESIGN, SETTING, AND PARTICIPANTSThis study analyzed prospectively collected data from the 12-month RESTORE core study and the 24-month open label RESTORE extension study, which assessed the efficacy and safety of ranibizumab in patients with visual impairment due to diabetic macular edema. Of 345 patients with center-involving diabetic macular edema who had enrolled in the 12-month RESTORE core study, 240 entered the 24-month RESTORE extension study. Of these, 83 (34.6%) received ranibizumab, 83 (34.6%) received ranibizumab and laser combination therapy, and 74 (30.8%) received laser monotherapy in the first year of the study; 208 completed the 24-month extension study. Fluorescence angiography images were taken from each participant twice each year graded by Vienna Reading Center on severity of capillary loss in the parafoveal area, regularity of the foveal avascular zone outline, and measurement of the size of the foveal avascular zone, following a standardized protocol. Data analysis took place from July 2014 through December 2017.MAIN OUTCOMES AND MEASURES Change in 3 fluorescence angiography perfusion parameters over the course of treatment.RESULTS Mean (SD) patient age was 62.6 (8.8) years; 124 of 208 (59.2%) were male and 197 of 208 (94.6%) were white. The number of patients with definite altered foveal avascular zone regularity at baseline was 103 of 240 patients (42.9%); another 118 patients (49.2%) had questionably altered regularity at baseline. Definitive capillary loss was found in 65 of 240 patients (27.1%) at baseline. Mean (SD) foveal avascular zone size at baseline was 0.261 (0.232) mm 2 in ranibizumab monotherapy, 0.231 (0.219) mm 2 in ranibizumab and macular laser combination therapy, and 0.201 (0.13) mm 2 in laser monotherapy. No treatment arm experienced significant increase in foveal avascular zone size at any time in the study period. At month 36, ranibizumab monotherapy resulted in a mean increase of 0.073 mm 2 (95% CI, 0.005-0.142 mm 2 ) and combination therapy resulted in a mean increase of 0.117 mm 2 (95% CI, 0.045-0.188 mm2), but no changes were statistically significant. No changes occurred in foveal avascular zone regularity in any treatment group, and no differences were found in capillary loss around the fovea in the 3 treatment groups; neither element could be correlated with visual acuity or central retinal thickness.CONCLUSIONS AND RELEVANCE Repeated ranibizumab treatment was not associated with impaired macular perfusion in our study cohort. Because our data do not suggest a harmful effect of anti-vascular endothelial growth factor therapy on capillary integrity, patients with severe m...

Clinical effect of conbercept on improving diabetic macular ischemia by OCT angiography

“…In addition, repeated anti-VEGF therapy on macular perfusion in patients with DME did not cause treatment-related significant changes in FAZ sizes and capillary loss around the fovea. Patients with DME who had severe ischemia still achieved favorable changes in BCVA and central macular thickness after long-term anti-VEGF therapy [ 6 , 7 ]; thus, anti-VEGF therapy may be an alternative for such patients. Therefore, patients with severe macular ischemia receiving anti-VEFG therapy should be individualized, and they need a comprehensive assessment of possible risks and closer follow-up to prevent the worsening of ischemia.…”

“…In the past decade, some clinical studies suggested that blocking VEGF might be harmful to retinal vascular integrity, especially in patients with preexisting retinal ischemia; in these patients, anti-VEGF therapy aggravated retinal ischemia because retinal nonperfusion (RNP) areas enlarged after anti-VEGF therapy [5,6]. However, increasing studies have shown that retinal ischemia does not worsen after anti-VEFG therapy but has no retinal reperfusion in the preexisted RNP areas [7][8][9]. After anti-VEGF treatment, the proportion of patients with ≥2-step DR severity score improvement is greater in patients with MNP at baseline [10].…”

Association of macular perfusion status with microvascular parameters up to the far periphery in diabetic retinopathy using multimodal imaging

“…The extent of retinal nonperfusion assessed by fluorescein angiography was found to be decreased 1 month after treatment [ 35 ] and reported unchanged in other studies after 6–12 month [ 33 , 35 ]. No significant differences were reported in parafoveal vascular densities, FAZ, vascular caliber changes or reperfusion before and up to 12 month after anti-VEGF therapy [ 28 – 32 ]. However, other authors demonstrated transient changes in vascular parameters, namely FAZ enlargement and retinal arteriolar vasoconstriction 4–6 weeks after anti-VEGF injections [ 36 , 37 ].…”

Clinical effect of conbercept on improving diabetic macular ischemia by OCT angiography

“…In addition, repeated anti-VEGF therapy on macular perfusion in patients with DME did not cause treatment-related significant changes in FAZ sizes and capillary loss around the fovea. Patients with DME who had severe ischemia still achieved favorable changes in BCVA and central macular thickness after long-term anti-VEGF therapy [7,17]; thus, anti-VEGF therapy may be an alternative for such patients. Therefore, patients with severe macular ischemia receiving anti-VEFG therapy should be individualized, and they need a comprehensive assessment of possible risks and closer follow-up to prevent the worsening of ischemia.…”

“…In the past decade, some clinical studies suggested that blocking VEGF might be harmful to retinal vascular integrity, especially in patients with preexisting retinal ischemia; in these patients, anti-VEGF therapy aggravated retinal ischemia because retinal nonperfusion (RNP) areas enlarged after anti-VEGF therapy [5,6]. However, increasing studies have shown that retinal ischemia does not worsen after anti-VEFG therapy but has no retinal reperfusion in the preexisted RNP areas [7][8][9]. Meanwhile, few studies indicated that anti-VEGF therapy could reduce RNP progression.…”