Short-term outcomes of intravitreal dexamethasone in relation to biomarkers in diabetic macular edema

Abstract

Purpose: The purpose of this study was to determine the effects of dexamethasone implant (0.7 mg) on biomarkers such as hyper-reflective dots, external limiting membrane integrity and disorganization of retinal inner layers in treatment-naïve patients, patients who received less than three anti-vascular endothelial growth factor injections and non-responder cases with diabetic macular edema and its effects on edema and visual acuity. Methods: This is a prospective study of treatment-naïve patients, patients who received less than three anti-vascular endothelial growth factor injections and non-responder patients with diabetic macular edema, treated with single dexamethasone implant. Pre- and post-injection-based best-corrected visual acuity, central macular thickness, hyper-reflective dots, external limiting membrane integrity and disorganization of retinal inner layers were assessed. Results: A total of 27 diabetic macular edema eyes, including 9 non-responder eyes, 9 eyes which received less than three anti-vascular endothelial growth factor injections and 9 treatment-naïve eyes, were included in this study. Baseline hyper-reflective dots were 22.22 ± 11.76, 30 ± 7.91 and 19.44 ± 8.82 which reduced to 3.33 ± 1.32, 9 ± 8.35 and 8.78 ± 2.53 four months after implant in treatment-naïve patients, patients who received less than three anti-vascular endothelial growth factor injections and non-responder cases, respectively. Baseline central macular thickness was 589.44 ± 175.37, 537 ± 181.81 and 673.11 ± 138.24 and the central macular thickness after dexamethasone implant was 272.11 ± 39.00, 336.44 ± 132.88 and 524.00 ± 200.39 in treatment-naïve patients, patients who received less than three anti-vascular endothelial growth factor injections and non-responder cases, respectively. External limiting membrane integrity was restored in two patients in each group, whereas two patients with disorganization of retinal inner layers in treatment-naïve group showed reorganization of retinal structures after treatment with dexamethasone implant. Conclusion: Better response to dexamethasone implant in cases with more hyper-reflective dots shows that these hyper-reflective dots can be used as a predictive biomarker. Dexamethasone implant might help in restoring external limiting membrane integrity and resolution of disorganization of retinal inner layers.

Role of hyper-reflective spots in predicting outcomes of intravitreal therapy in diabetic macular edema: A systematic review and meta-analysis

“…The results of the meta-analysis did not show a significant effect of baseline HRS on the change in visual acuity. However, eyes with treatment naive DME 15,16,[30][31][32]35,37,40 as against those with refractory DME 14,38,39 showed a positive correlation between HRS with VA gain (5/8 studies versus 0/3 studies) and CMT reduction (7/8 studies versus 1/3 studies). Also, eyes where HRS was associated with NSD at baseline responded better and showed a positive correlation between HRS and VA improvement and CMT reduction with in first 2-3 months.…”

“…Nineteen studies were identified (thirteen were retrospective cohort studies, 12,[15][16][17]24,26,[30][31][32][33][34][35][36] three were prospective cohort studies, 37,38,41 two were case series 14,39 and one was a case-control study 40 ). The quality score of the studies is shown in Table 1.…”

“…and Conbercept], 16,24,[30][31][32]35,36,40 11 studies to dexamethasone implant 12,14,26,[32][33][34][36][37][38][39]41 and 2 studies to the sequential use of anti-VEGF and dexamethasone. 15,17 The model of spectral domain OCT used, varied among the studies: 14 used SpectralisOCT™ (Heidelberg Engineering, Heidelberg, Germany), 12,[14][15][16][17]24,26,[30][31][32]34,35,38,39 3 used Cirrus HD-OCT™ (Carl Zeiss Meditec, Dublin, CA, USA), 33,37,41 1 each Retina scan™ (RS-3000 advance; Nidek) 40 and DRI-SSOCT Triton plus™ (Topcon Medical Systems Europe, Milano, Italy). 36 The measurement of HRS was done over different area sizes in the macula (12 studies used 3000µm area, 12,[14][15][16][17]26,…”

“…All 7 studies where intravitreal anti-VEGF injections were used 16,17,[30][31][32]35,40 and 6 out of the 7 studies where dexamethasone was used 17,26,32,34,37,39 reported a decrease in quantitative HRS. In the subgroup of patients whose macular edema did not respond to dexamethasone or IVB, there was no significant HRS reduction.…”

“…15,33,39 In the rest 6 studies, baseline HRS counts were correlated with final VA using regression/correlation statistics. 16,30,31,35,37,40 Three studies showed that higher HRS counts at baseline were associated with worse final VA. 31,35,38 Five studies showed no correlation between baseline HRS counts and final VA. 15,16,33,39,40 In a study by Cavalleri et al, 15 dexamethasone therapy resulted in a greater gain in VA in eyes with high baseline HRS counts compared to IVB.…”