Diabetic macular edema and proliferative diabetic retinopathy treated with anti-vascular endothelial growth factor under the reimbursement policy in Taiwan

The purpose of this retrospective interventional case series is to compare the functional and anatomical outcomes in eyes with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) treated intravitreally with aflibercept or ranibizumab under the Taiwan National Insurance Bureau reimbursement policy. 84 eyes were collected and all eyes were imaged with spectral-domain optical coherence tomography (SD-OCT), color fundus photographs (CFPs), and fluorescein angiography (FA). At 24 months after therapy initiation, the logMAR BCVA improved from 0.58 ± 0.33 to 0.47 ± 0.38 (p < 0.01), the CRT decreased from 423.92 ± 135.84 to 316.36 ± 90.02 (p < 0.01), and the number of microaneurysms decreased from 142.14 ± 57.23 to 75.32 ± 43.86 (p < 0.01). The mean injection count was 11.74 ± 5.44. There was no intergroup difference in logMAR BCVA (p = 0.96), CRT (p = 0.69), or injection count (p = 0.81). However, the mean number of microaneurysms was marginally reduced (p = 0.06) in eyes treated with aflibercept at the end of the follow-up, and the incidence rates of supplementary panretinal photocoagulation (PRP) (p = 0.04) and subthreshold micropulse laser (SMPL) therapy sessions (p = 0.01) were also reduced. Multivariate analysis revealed that only initial logMAR BCVA influenced the final VA improvements (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.21 ~ 0.93, p < 0.01); in contrast, age (OR − 0.38, 95% CI − 6.97 ~ − 1.85, p < 0.01) and initial CRT (OR 0.56, 95% CI 0.34 ~ 0.84, p < 0.01) both influenced the final CRT reduction at 24 months. To sum up, both aflibercept and ranibizumab are effective in managing DME with PDR in terms of VA, CRT and MA count. Eyes receiving aflibercept required less supplementary PRP and SMPL treatment than those receiving ranibizumab. The initial VA influenced the final VA improvements at 24 months, while age and initial CRT were prognostic predictors of 24-month CRT reduction.

Factors Associated With the Presence of Foveal Bulge in Eyes With Resolved Diabetic Macular Edema

Purpose: To evaluate factors associated with the presence of foveal bulge (FB) in resolved diabetic macular edema (DME) eyes.Methods: A total of 165 eyes with complete integrity of ellipsoid zone (EZ) at the fovea and resolved DME were divided into two groups according to the presence of FB at 6 months after intravitreal injection of ranibizumab treatment. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), outer nuclear layer (ONL) thickness, height of serous retinal detachment (SRD) and non-SRD, and inner segment (IS) and outer segment (OS) lengths of the two groups were measured and compared at baseline and each follow-up. The correlations between the presence of FB and pre- and post-treatment factors were determined by logistic regression analysis.Results: At baseline, BCVA was significantly better, and CFT and incidence and height of SRD were significantly lower in the FB (+) group (all P &lt; 0.05). At 6 months, FB was present in 65 (39.39%) eyes. Post-treatment BCVA was significantly better and OS length was significantly longer in the FB (+) group at 6 months (all P &lt; 0.05). Multivariate analysis identified younger age, better BCVA, and lower CFT before treatment as significant predictors of the existence of FB at 6 months (all P &lt; 0.05). At 6 months, better BCVA and longer OS length were significantly correlated with the existence of FB (all P &lt; 0.05).Conclusions: Factors associated with the presence of FB after the resolution of DME include younger age, better baseline BCVA and lower baseline CFT, and better post-treatment BCVA and longer post-treatment OS length.

Current Management of Diabetic Macular Edema

Diabetic macular edema is a complication of diabetes mellitus (DM) which contributes significantly to the burden of visual impairment amongst persons living with diabetes. Chronic hyperglycemia triggers a cascade of pathologic changes resulting in breakdown of the retinal blood barrier. Understanding the pathophysiological and biochemical changes occurring in diabetes has led to developing novel therapeutics and effective management strategies for treating DME. The clinical utility of optical coherence tomography (OCT) imaging of the retina provides a detailed assessment of the retina microstructure, valid for individualization of patient treatment and monitoring response to treatment. Similarly, OCT angiography (dye-less angiography), another innovation in imaging of DME, provides an understanding of retinal vasculature in DME. From the earlier years of using retinal laser photocoagulation as the gold standard for treating DME, to the current use of intravitreal injection of drugs, several clinical trials provided evidence on safety and efficacy for the shift to intravitreal steroids and anti-vascular endothelial growth factor use. The short durability of available drugs leading to frequent intravitreal injections and frequent clinic visits for monitoring constitute an enormous burden. Therefore, extended durability drugs are being designed, and remote monitoring of DME may be a solution to the current challenges.

Effectiveness of a Hydrophilic Curcumin-Based Formulation in Coadjuvating the Therapeutic Effect of Intravitreal Dexamethasone in Subjects With Diabetic Macular Edema

Purpose: This study evaluates if the addition of a curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC; Diabec®, Alfa Intes, Italy) to intravitreal injections of dexamethasone (DEX-IVT) can affect the morphological retinal characteristics, extending the steroid re-treatment period in patients with diabetic macular edema (DME).Methods: A randomized controlled clinical trial was carried out in DME patients, randomly assigned to receive DEX-IVT or DEX-IVT and a CHC. The evaluation of the mean difference of central retinal thickness (CRT) was the primary aim. Secondary aims were the evaluations of best-corrected visual acuity, differences in the predetermined retinal layer thickness, the number/time of re-treatment, and the assessment of safety.Results: A total of 73 DME patients were included (35 in the control group and 38 in the combined therapy group). In both the control and combined therapy groups, the mean CRT change from T0 to the 6 months’ evaluation was significant (p = 0.00). The mean CRT result was significantly different at month 4 (p = 0.01) between the control and combined therapy groups, with a greater reduction in the combined therapy group, in particular, in patients with ≤10 years of diabetes. A trend of CRT reduction in the combined therapy group has been observed also considering patients with subfoveal neuroretinal detachment. In addition, we observed that the reduction of inner retinal layer thickness was greater in the combination group, in comparison with controls.Conclusion: The combination of a CHC to DEX-IVT is a promising therapeutic option in case of DME, in particular, for patients with early-stage diabetes and with an inflammatory phenotype. Further studies will be necessary to confirm these findings.

The role of optical coherence tomography angiography biomarkers in assessing the outcome of long-term anti-VEGF therapy of diabetic macular edema

The purpose of the study was to assess the changes of biomarkers of diabetic macular edema activity by optical coherence tomography angiography (OCTA) data and the relationship of these biomarkers with the response to anti-VEGF therapy during a two-year follow-up. Material and methods. The study included 59 patients (101) eyes, averagely aged 60.27 ± 9.50 years. The average number of intravitreal injections of aflibercept over the treatment period was 12.87 ± 3.50. The initial size of the foveolar avascular zone (FAZ) area — 0.37 ± 0.22 mm2 , and the acircularity index — 0.56 ± 0.14 remained unchanged after 5 months: 0.36 ± 0.24 mm2 and 0.56 ± 0.12, respectively, and being practically in the same level in 12 and 24 months. The large FAZ area, noted in the group where disorganization of retinal inner layers (DRIL) was observed (0.39 ± 0.21 mm2 ), correlated with a lower visual acuity (r = 0.67, p = 0.003). The acircularity index remained unchanged; no significant differences were found in the DRIL patient groups. After 5 loading injections, the average initial density of vessels in the macular region increased from 12.33 ± 3.86 mm to 12.75 ± 1.14 mm, after 1 year it was 13.48 ± 1.15 mm, after 2 years — 13.25 ± 3.39 mm. The average density of retinal perfusion increased at the 5th month from 29.81 ± 10.85 % to 31.55 ± 2.34 %, after 12 months to 32.91 ± 3.45, and by the end of the observation period to 31.41 ± 9.79 %. In the DRIL group, the baseline vascular density and mean perfusion volume were significantly lower: 11.17 ± 2.09 mm vs. 13.49 ± 1.14 mm and 28.40 ± 4.53 % vs. 31.20 ± 2.44 %). Conclusion. DRIL, a biomarker reflecting impaired capillary blood flow in the superficial capillary plexus and correlating with functional results, can be used as a predictor of antiangiogenic therapy effectiveness. After antiangiogenic therapy with DMO, the microcirculation indices (FAZ and acircularity) remained stable, and the vascular density and perfusion volume tended to increase, which testifies to the absence of ischemic damage.