Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept.

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Randomized clinical trial comparing intravitreal aflibercept combined with subthreshold laser to intravitreal aflibercept monotherapy for diabetic macular edema.

To compare the efficacy and safety of intravitreal aflibercept with three loading doses + pro re nata regimen combined with subthreshold laser application to that of IVA monotherapy on eyes with diabetic macular edema. This was a phase 4 clinical trial with a prospective, randomized, and parallel investigator-driven protocol. Patients with DME were randomly assigned to the IVA monotherapy group (n = 25) or the IVA + SL combination therapy group (n = 26). The main outcome measures were the number of IVA injections and the changes in the best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) at the final evaluation at 96 weeks. The mean number of IVA injections in the monotherapy group was 5.86 ± 2.43 and it was 6.05 ± 2.73 in the IVA + SL group at 96 weeks, and this difference was not significant (P = 0.83). The differences in the mean changes of the CRT (P = 0.17) and the BCVA (P = 0.31) were also not significant between the two groups throughout the follow-up period. We conclude that adjunct of SL to anti-VEGF therapy does not reduce the number of necessary intravitreal injections.

Comparisons of One to Three Monthly Injections of Aflibercept for Diabetic Macular Edema by Practical Protocol.

The purpose of this study was to compare the efficacies of one initial intravitreal injection of aflibercept followed by a pro re nata (PRN; 1+PRN) regimen to those of three consecutive monthly injections followed by the PRN (3+PRN) regimen for diabetic macular edema (DME) with practical protocols. The medical records of 95 eyes of 71 cases that were diagnosed with DME and had received intravitreal aflibercept (IVA) injections were reviewed. Fifty-seven eyes had received IVA with the 1+PRN regimen, and 38 eyes had received IVA with the 3+PRN regimen. The best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean number of injections of the 1+PRN group was 2.9 ± 1.7, which was significantly fewer than that of the 3+PRN group at 4.6 ± 1.4 (P < 0.001). The change of the mean BCVA before and after the IVA at 12 months of the 3+PRN group was -0.14 ± 0.17 logMAR units which was significantly better than that of the 1+PRN group of -0.045 ± 0.25 logMAR units (P = 0.02). The change of the CMT before and after the IVA at 6 months of the 3+PRN group was -141.3 ± 152.4 µm which was significantly more than that of the 1+PRN group at -86.1 ± 117.8 µm (P = 0.013). Although the mean number of injections was more than that in the 1+PRN regimen, the 3+PRN regimen had better visual outcomes at 12 months. In a practical protocol, we recommend the 3+PRN regimen for patients with DME (IRB#3541).

The Use of Inner Retinectomy to Relieve Inner Retinal Foreshortening Causing Retinal Detachment in the Setting of Branch Retinal Vein Occlusion.

A 61-year-old Japanese woman presented with impairment of her left vision due to macular schisis secondary to branch retinal vein occlusion. Her left vision was 20/50, and schisis was observed inferotemporally. She underwent phacoemulsification and aspiration, implantation of the intraocular lens, and removal of the epiretinal membrane and internal limiting membrane. Her visual acuity stabilized ~20/50 for two and a half years after the initial surgery. However, she developed macula-involving retinal detachment, and her visual acuity declined to counting fingers. She underwent pars plana vitrectomy and removal of the residual vitreous cortex together with the inner retina within the area of vein occlusion. After the removal of silicone oil and the addition of an encircling buckle, the retina remained attached and visual acuity improved to 20/60 at one year after the final surgery. The combination of rhegmatogenous and tractional detachment in the area of schisis was suspected, and vitrectomy with inner retinectomy was effective.

Efficacy of One-Year Treatment with Aflibercept for Diabetic Macular Edema with Practical Protocol.

The purpose of this study was to determine the efficacy of one-year treatment of diabetic macular edema (DME) with intravitreal aflibercept (IVA) injections on a practical protocol. The medical records of 51 eyes of 43 patients who were diagnosed with DME and had received IVA treatments were reviewed. The best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean number of IVA injections was 3.8 ± 2.4. The mean BCVA was significantly better and the CMT was thinner after the IVA at all follow-up times (P < 0.05). The BCVA was better in eyes with a serous retinal detachment (SRD) than without a SRD (P < 0.01). There was a significant correlation between the photoreceptor outer segment (PROS) length and BCVA at the baseline and at 12 months after the IVA (P < 0.05). A fewer number of IVA injections significantly improved the BCVA and the CMT in eyes with DME after one-year treatment. IVA was more effective in the SRD+ group than in the SRD- group. The PROS length may be a predictive marker for visual outcomes after one-year treatment with IVA for DME (IRB#2272).