Intravitreal Fasudil Monotherapy for Treatment of Refractory Diabetic Macular Edema: a Prospective, Interventional Case-series

Purpose: To evaluate the effect of three monthly intravitreal injections of a Rho-associated protein kinase (ROCK) inhibitor (Fasudil, Asahi Kasei Pharma Corporation, Tokyo, Japan) on refractory diabetic macular edema (DME).Study design: Prospective – clinical Methods: This interventional case series included 10 eyes of 10 patients with DME unresponsive to at least six previous intravitreal bevacizumab (IVB) injections. Eligible eyes underwent intravitreal injection of 0.025 mg/0.05 ml Fasudil. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated as functional and anatomical response indicators, respectively. Results: Mean age was 60.1±5.1 (range, 53-68) years. Five cases responded to treatment; two with both anatomical and functional response (reduction of CMT from 521 to 395 and from 390 to 301microns and improvement of BCVA from 0.3 to 0.1 LogMAR and 0.6 to 0.4 LogMAR, respectively) and three with only functional improvement (0.7 to 0.4; 0.7 to 0.4; and 0.3 to 0.1 LogMAR). Of note, cases with no significant CMT change had morphologic improvement of retinal microstructure to some extent. No adverse event was observed during the study period.Conclusion: Monotherapy with intravitreal injection of ROCK inhibitors seems to have moderate visual benefits in eyes with DME refractory to IVB. Such effects may be functionally significant without obvious anatomical improvement.

Evaluation of the Effect of Suprachoroidal Triamcinolone Injection on Refractory Diabetic Macular Edema

Purpose: To assess the safety and efficacy of supra choroidal triamcinolone injection (SCT) in cases of refractory diabetic macular oedema. Study Design: Interventional case series. Place and Duration of Study: Lahore General Hospital, Lahore, from July to December 2019. Methods: A total of 22 eyes of patients above 18 years of age, with either Type-1 or Type-2 diabetes mellitus and treatment resistant central Diabetic Macular Edema (DME) of 320 um or more (measured on Zeiss Cirrus HD-OCT) and Best Corrected Visual Acuity (BCVA) of less than or equal to 20/40 were included in the study. BCVA, Intra Ocular Pressure (IOP) and Central Subfield Thickness (CST) was recorded. After Supra-Choroidal triamcinolone (SCTA), patients were followed up at one and three months and same clinical parameters were recorded and the results were analysed. Results: out of 22 patients, 10 (45.45%) were males and 12 (54.54%) were females. Mean pre injection CST was 615.5 ± 200.28 um and Log MAR BCVA was 0.9 ± 0.20. Mean post injection CST at one and three months was 302.45 ± 52.45 and 301.66 ± 55.82 um. Mean post injection Log MAR BCVA at one and three months was 0.52 ± 0.3 and 0.40 ± 0.22. The results were statistically significant for pre and post injection CST at both one and three months (p-value < 0.00001). Pre and post injection BCVA was also statistically significant (p-value < 0.05). Conclusion: CST is a safe and effective means to reduce refractory diabetic macular edema and improve OCT macular thickness. Key Words: Diabetic macular edema, Suprachoroidal Triamcinolone, Central sub-field thickness.

Short-Term Outcomes of Refractory Diabetic Macular Edema Switch From Ranibizumab to Dexamethasone Implant and the Influential Factors: A Retrospective Real World Experience

Introduction: To evaluate the effectiveness and safety of intravitreal dexamethasone (DEX) implants in refractory diabetic macular edema (DME) treated by intravitreal ranibizumab.Materials and Methods: We retrospectively analyzed DME patients who received DEX implant treatment after being refractory to at least 3 monthly intravitreal ranibizumab injections. The main outcomes were best-corrected visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP).Results: Twenty-nine eyes of 26 patients who had previously received an average of 8.1 ± 4.4 ranibizumab injections were included. Patients received between one and three DEX implants during 12.4 ± 7.4 months of follow-up. The mean final CRT significantly decreased from 384.4 ± 114.4 μm at baseline to 323.9 ± 77.7 μm (p = 0.0249). The mean final BCVA was 51.4 ± 21.3 letters, which was not significant compared to baseline (44.9 ± 30.2 letters, p = 0.1149). Mean IOP did not increase significantly. All patients tolerated the treatment well without serious adverse events. Higher baseline CRT and worse BCVA correlated with better therapeutic responses.Conclusion: Switching to DEX implant is feasible and safe for treating patients of DME refractory to intravitreal ranibizumab in real world. Further larger-scale or multicenter studies would be conducted to explore different DEX treatment strategies for DME, such as first-line or early switch therapy, for better BCVA improvement.

Optical Coherence Tomography Biomarkers - Vitreous Status Influence in Outcomes for Diabetic Macular Edema Therapy with 0.19 mg Fluocinolone Acetonide Implant

Background: The 0.19 mg fluocinolone acetonide (FAc) implant (ILUVIEN®; Alimera Sciences Ltd, Hampshire, UK) was approved for the treatment of vision impairment associated with chronic and refractory diabetic macular edema (DME). Objectives: To quantitatively assess functional and structural features in non-vitrectomized and vitrectomized DME patients after being treated with a FAc implant Methods: Retrospective review of patients with DME receiving single intravitreal injection of the FAc implant. The study was designed to analyze the presence of quantitative structural OCT biomarkers at baseline and 12 months after FAc therapy according to vitreous status. Results: A total of 41 eyes from 30 patients were included in this study. At 12 months post-injection, vitrectomized patients had a lower central foveal thickness (CFT, p=0.017) and fewer hyperreflective dots (HRD, p=0.028) compared with non-vitrectomized. Thirty (73%) patients presented a significant functional improvement with 17 (42%) increasing at least 15 ETDRS letters. Overall, 22 (54%) eyes had a complete resolution of DME at 12 months visit. Patients who needed additional therapy had a higher prevalence of subretinal fluid (SRF, 42% vs 3% p=0.005) at baseline. Conclusions: This study supports the effectiveness of the FAc implant and reports significant changes at 12 months post-FAc injection.

Switching to intravitreal fluocinolone acetonide implant for refractory diabetic macular edema: 12- and 24-month results

Purpose: To report visual and anatomical outcomes of chronic/refractory diabetic macular edema (DME) treated with intravitreal fluocinolone acetonide implant. Setting: Retrospective, one arm, multicentric study. Method: Between 2013 and 2018, 27 consecutive eyes of 25 patients with chronic/refractory DME were treated with a fluocinolone acetonide intravitreal implant. Best registered visual acuity (BRVA), central retinal thickness (CRT), and Goldmann tonometry intraocular pressure (IOP) were assessed at 12 and 24 months. The need for IOP lowering treatment as well as top-up therapy during the follow-up were also assessed. Results: The duration of DME prior to treatment in our study was 54 ± 24 months. The baseline mean BRVA of 0.7 ± 0.34 logMAR improved to 0.5 ± 0.3 ( p = 0.01) at 12 months and 0.46 ± 0.3 ( p = 0.04) at 24 months. At 12 months, BRVA improved in 14 eyes (52%), stabilized in 5 eyes (20%), and decreased in 3 eyes (11%). At 24 months, BRVA improved further in 6 eyes (24%), stabilized in 3 eyes (12%), and decreased in 6 eyes (24 %). Mean CRT decreased from 497 ± 176 to 349 ± 186 μm at 12 months ( p = 0.0005) and to 267 ± 104 μm at 24 months ( p = 0.001). Only five eyes required additional treatment for DME and only three eyes required treatment for raised IOP. Discussion: Our results show that the visual and the anatomical improvements achieved by a single injection of a fluocinolone acetonide implant were maintained up to 24 months with minimal additional therapy even in eyes with a long and heavy history; however, IOP monitoring remains essential.

Three-year outcomes of vitrectomy combined with intraoperative dexamethasone implantation for non-tractional refractory diabetic macular edema

This retrospective, consecutive interventional study investigated the long-term clinical outcomes of combined vitrectomy with intraoperative dexamethasone implants for non-tractional refractory diabetic macular edema (DME). The study included 43 eyes from 39 participants with DME that had continued for more than 6 months despite repeated non-surgical treatment. Postoperative changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated over 3 years. A Kaplan–Meier curve was obtained for any additional non-surgical treatment, and the average number of non-surgical treatments required for DME before and after surgery was compared. Other postsurgical complications were also investigated. The logMAR BCVA improved from 0.526 ± 0.417 (20/67) preoperatively to 0.294 ± 0.374 (20/39) 3 years postoperatively (p < 0.001, generalized estimating equation). The CMT improved from 478 ± 122 μm preoperatively to 314 ± 90 μm 3 years postoperatively (p < 0.001, generalized estimating equation). Additional non-surgical treatment was not required for 29 (67%) eyes. The average number of annual non-surgical treatments decreased from 5.04 times preoperatively to 0.34 times postoperatively. Seventeen (40%) eyes developed temporary ocular hypertension after surgery, which normalized after antihypertensive eye drop instillation. In conclusion, vitrectomy combined with intraoperative dexamethasone implantation provides satisfactory long-term clinical outcomes for non-tractional refractory DME while reducing the number of intraocular injections for DME.

Micropulse laser in patients with refractory and treatment-naïve center–involved diabetic macular edema: short terms visual and anatomic outcomes

Purpose: The purpose of the study is to describe visual and anatomic outcomes of 5774nm micropulse laser photocoagulation in eyes with either treatment-naïve or refractory diabetic macular edema (DME) at 3 months. Methods: This was a prospective case series that recruited 23 consecutive patients (33 eyes) with center-involved DME that was either treatment-naïve or had not responded to prior treatment. Micropulse therapy was performed with the Easy Ret 577 (Quantel Medical, Cournon d’Auvergne, France) diode laser in a high-density manner in eyes with treatment-naïve or refractory DME. The primary outcome was the change of best-corrected visual acuity (BCVA; logMAR) at 1 and 3 months. Secondary outcomes were changes in the central macular thickness (CMT), thickness area, macular volume, and macular capillary leakage at 1 and 3 months. Results: There were no significant changes in BCVA at 3 months, with mean ± standard deviation (SD) of −0.08 ± 0.01 ( p = 0.228) and + 0.01 ± 0.01 ( p = 0.969) for treatment-naïve and refractory groups, respectively. The change in CMT at 3 months was statistically but not clinically significant in the treatment-naïve group only (mean ± SD; –30 ± 130 µm; p = 0.011). The macular volume and area thickness change were not statistically significant ( p = 0.173 and p = 0.148 for macular volume and area thickness, respectively) in the treatment-naïve group. There was no difference concerning the leakage area in both groups. No adverse events were reported. Conclusion: We concluded that micropulse 577nm laser therapy maintained the visual acuity and macular thickness at 3 months in both treatment-naïve and refractory DME.