Sodium-glucose cotransporter 2 inhibitor therapy reduces the administration frequency of steroid injection in patients with diabetic macular edema: A cohort study using the Japanese health insurance claims database.

AIMS/INTRODUCTION: Severe diabetic macular edema (DME) is often resistant to anti-vascular endothelial growth factor therapy. Steroids are particularly effective at reducing edema by suppressing inflammation; they are also used as an alternative to expensive anti-vascular endothelial growth factor therapy in some patients. Therefore, the use of steroids in DME reflects an unmet need for anti-vascular endothelial growth factor therapy. Notably, triamcinolone acetonide (TA) injections are widely used in Japan. Here, we evaluated the frequency of TA as an indicator of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in DME treatment using a health insurance claims database. MATERIALS AND METHODS: In this cohort study, we retrospectively analyzed the health insurance claims data of 11 million Japanese individuals from 2005 to 2019. The frequency and duration of TA injection after the initiation of SGLT2is or other antidiabetic drugs were analyzed. RESULTS: Among the 2,412 matched patients with DME, the incidence rate of TA injection was 63.8 times per 1,000 person-years in SGLT2i users and 94.9 times per 1,000 person-years in non-users. SGLT2is reduced the risk for the first (P = 0.0024, hazard ratio 0.66, 95% confidence interval 0.50-0.87), second (P = 0.0019, hazard ratio 0.53, 95% confidence interval 0.35-0.80) and third TA (P = 0.0053, hazard ratio 0.44, 95% confidence interval 0.25-0.80) injections. A subanalysis of each baseline characteristic of the patients showed that SGLT2is were effective regardless of the background factors. CONCLUSIONS: The use of SGLT2is reduced the frequency of TA injection in patients with DME. Therefore, SGLT2i therapy might be a novel, noninvasive and low-cost adjunctive therapy for DME.

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.

Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

AIM: We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. MATERIALS AND METHODS: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. RESULTS: Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. CONCLUSIONS: There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.

Efficacy and safety of transdermal electrical stimulation in patients with nonarteritic anterior ischemic optic neuropathy.

BACKGROUND: No effective treatment for NAION with strong evidence has been established till date. The aim of this investigator-led, prospective, non-randomized, open-label, uncontrolled multi-center exploratory clinical trial is to evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with NAION. METHODS: Five patients with monocular NAION underwent TdES (10-ms biphasic pulses, 1.0 mA, 20 Hz, 30 min) of the affected eye six times at 2-week intervals. The primary endpoint was the logarithm of the mini-mum angle of resolution (logMAR) visual acuity at 12 weeks compared with 0 weeks. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, and mean deviation (MD) of the Humphrey field analyzer (HFA) 10-2 and HFA Esterman test scores. Additionally, the safety of TdES was evaluated. RESULTS: LogMAR visual acuity improved by ≥ 0.1 in two eyes, and ETDRS visual acu-ity improved by ≥ 5 characters in one eye. The mean change in logMAR visual acuity from week 0 showed an increasing trend. The mean MD of HFA 10-2 showed no obvious change, while HFA Esterman score improved in four eyes. All patients completed the study according to the protocol, and no treatment-related adverse events were observed. CONCLUSIONS: TdES treatment may have improved visual acuity and visual field in some patients. Further sham-controlled study in larger cohort is needed on its effectiveness. TRIAL REGISTRATION: UMIN, UMIN000036220. Registered 15 March, 2019, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041261 .

Current Treatments for Diabetic Macular Edema.

Diabetic retinopathy is a major retinal disorder and a leading cause of blindness. Diabetic macular edema (DME) is an ocular complication in patients with diabetes, and it can impair vision significantly. DME is a disorder of the neurovascular system, and it causes obstructions of the retinal capillaries, damage of the blood vessels, and hyperpermeability due to the expression and action of vascular endothelial growth factor (VEGF). These changes result in hemorrhages and leakages of the serous components of blood that result in failures of the neurovascular units (NVUs). Persistent edema of the retina around the macula causes damage to the neural cells that constitute the NVUs resulting in diabetic neuropathy of the retina and a reduction in vision quality. The macular edema and NVU disorders can be monitored by optical coherence tomography (OCT). Neuronal cell death and axonal degeneration are irreversible, and their development can result in permanent visual loss. Treating the edema before these changes are detected in the OCT images is necessary for neuroprotection and maintenance of good vision. This review describes the effective treatments for the macular edema that are therefore neuroprotective.

Exploratory clinical trial to evaluate the efficacy and safety of transdermal electrical stimulation in patients with central retinal artery occlusion.

PURPOSE: To evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with central retinal artery occlusion (CRAO). METHODS: Five eyes of five patients with CRAO underwent TdES (10-ms biphasic pulses, 20 Hz, 30 min) six times at 2-week intervals. Only the affected eye was stimulated with 1.0-mA pulses in all patients. The primary endpoint was the best-corrected logMAR visual acuity. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, mean deviation of the Humphrey field analyzer (HFA) 10-2, and HFA Esterman test score. We also evaluated its safety. RESULTS: The logMAR visual acuity at 12 weeks was improved by 0.1 or more in two patients and was maintained in two patients compared to the baseline. No obvious changes in the mean logMAR visual acuity, ETDRS visual acuity, mean deviation, and HFA Esterman score were observed at 12 weeks compared to the baseline. All five enrolled patients completed the study according to the protocol. No treatment-related adverse events were observed during this study. CONCLUSION: In this study, logMAR visual acuity was slightly improved in two patients, confirming the safety of TdES. Since CRAO has no established treatment method, further research into the effects of TdES treatment in CRAO patients may be beneficial.

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.

Sodium-Glucose Co-Transporter 2 Inhibitors Reduce Macular Edema in Patients with Diabetes mellitus.

PURPOSE: To determine the efficacy of systemic sodium-glucose co-transporter 2 inhibitors (SGLT2i) on diabetic macular edema (DME). METHODS: The medical records of patients with DME with a central retinal thickness (CRT) ≥320 µm in men and 305 µm in women, more than 6 months after the initiation of diabetes mellitus treatment, were reviewed. The CRT and best-corrected visual acuity (BCVA) were evaluated before and after the initiation of systemic SGLT2i and non-SGLT2i treatments. RESULTS: There were 24 eyes of 19 patients with DME that were treatment naïve or had not received treatments for the DME within four months before the initiation of SGLT2i. In these patients, the BCVA had a 0.31 ± 0.39 logarithm of the minimum angle of resolution (logMAR) units at the baseline, and it did not improve significantly at 0.26 ± 0.29 logMAR units after the initiation of SGLT2i (p = 0.56). However, the SGLT2i treatment significantly reduced the CRT from 423.3 ± 79.8 µm to 379.6 ± 69.5 µm (p = 0.0001). In the same evaluation of 19 eyes of 14 patients with DME that were initiated with non-SGLT2i agents, there was no significant difference between the baseline BCVA and the BCVA after the initiation of non-SGLT2i (p = 0.47). The CRT increased significantly after the initiation of non-SGLT2i (p = 0.0011). In three eyes in which the SGLT2i treatments were administered at the time of anti-vascular endothelial growth factor (VEGF) treatments, the anti-VEGF treatment alone had only a limited effect on the DME, but the reduction in the DME was enhanced after the addition of SGLT2i. CONCLUSIONS: These findings indicate that systemic SGLT2i can reduce DMEs, and they suggest that SGLT2i may be an additional treatment option to anti-VEGF treatments for eyes with DMEs.

The Impact of Cataract Surgery on Contrast Visual Acuity and Retinal Sensitivity in Patients with Retinitis Pigmentosa.

PURPOSE: To determine the effects of cataract surgery on contrast visual acuity and retinal sensitivity in patients with retinitis pigmentosa. METHODS: Retinal sensitivity and contrast visual acuity were determined by microperimetry (MAIA) and contrast sensitivity acuity tester (CAT-CP), respectively, before and after cataract surgery. The significance of the correlations between visual acuity, retinal sensitivity, contrast visual acuity, improvements after surgery, and macular structure before and after cataract surgery was determined. RESULTS: Retinal sensitivity and contrast visual acuity were significantly improved after cataract surgery. The correlations among postoperative visual acuity, postoperative retinal sensitivities, and preoperative ellipsoid zone length were significant. The postoperative retinal sensitivity of the central 10° and the ellipsoid zone length was particularly significantly correlated. Preoperative contrast visual acuity and the amount of improvement and preoperative retinal sensitivity and the amount of improvement were significantly negatively correlated. The contrast visual acuity under both the 100% and 10% photopic and mesopic conditions improved significantly after cataract surgery. CONCLUSIONS: Cataract surgery in retinitis pigmentosa patients with preserved ellipsoid zones significantly improved retinal sensitivity and contrast visual acuity. Cataract surgery can be expected to improve retinal sensitivity and contrast visual acuity under various conditions, even if preoperative visual parameters are low, as long as the ellipsoid zone is preserved.

Effects of Cataract Surgery on Vision-Related Quality of Life in Patients with Retinitis Pigmentosa and the Predictive Factors of Quality of Life Improvement.

PURPOSE: To determine the effects of cataract surgery and preoperative factors on the vision-related quality of life (QOL) in patients with retinitis pigmentosa (RP). MATERIALS AND METHODS: This was a prospective, interventional study of 54 patients diagnosed with RP. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to determine the QOL before and after the cataract surgery. The correlations between the scores of the questionnaire and the best-corrected visual acuity (BCVA), macular structure, and degree of improvement of the NEI VFQ-25 scores were also determined. RESULTS: Statistically significant improvements were observed in the BCVA and all of the NEI VFQ-25 subscale scores except for color vision. The improvement of general vision was the largest. The postoperative BCVA of the better-seeing eye was more strongly and significantly correlated with the postoperative NEI VFQ-25 scores than that of the worse-seeing eye. All of the postoperative NEI VFQ-25 scores were significantly correlated with the length of the ellipsoid zone (EZ) of the photoreceptors. No significant correlation was found between the preoperative general vision, near vision, mental health scores, and EZ length. All of the preoperative NEI VFQ-25 scores except the social function and mental health scores were negatively and significantly correlated with the degree of improvement of the NEI VFQ-25 score. The EZ length was significantly correlated with the degree of improvement of the NEI VFQ-25 scores of the general vision, distance vision, mental health, dependency, and composite 9 scores. CONCLUSIONS: Cataract surgery can significantly improve the NEI VFQ-25 scores in RP patients. The EZ length can be used to predict the postoperative VFQ scores. We conclude that the NEI VFQ-25 is a useful method to evaluate the impact of cataract surgery on the BCVA in patients with RP.

Refractive errors after sutureless intrascleral fixation of intraocular lens.

PURPOSE: To determine the difference between the attempted and the achieved postoperative refractive error after sutureless intrascleral fixation of the haptics of an implanted intraocular lens (IOL). PATIENTS AND METHODS: This was a retrospective study of the medical charts of patients who had undergone sutureless intrascleral fixation of an IOL. The IOLs were fixed by inserting the haptics into scleral tunnels with or without flanges. The differences between the attempted and achieved postoperative refractive error (spherical equivalent) were determined. The relationships between the surgical options and the differences of the refractive error and degree of astigmatism were also determined. RESULTS: Two hundred and twenty-three eyes were studied. There was a myopic shift of - 0.38 ± 1.13 diopters (D). The mean of the differences between the achieved postoperative and the attempted refractive error was 0.89 ± 0.79 D. The achieved refractive error was significantly correlated with the attempted refractive error (P < 0.001, R2 = 0.631). The surgical procedures selected were not significantly associated with the differences between the attempted and achieved refractive error. The size of sclerocorneal incision and presence of sutures were significantly associated with the final degree of astigmatism (P = 0.006 and 0.008, respectively). CONCLUSIONS: The postoperative refractive error was significantly correlated with the attempted refractive error after intrascleral fixation of an IOL. The wound construction was associated with the postoperative degree of astigmatism.

Four Cases of Rhegmatogenous Retinal Detachment That Recurred More than 10 Years after Initial Reattachment by Pars Plana Vitrectomy.

PURPOSE: The purpose of this report was to present our findings in 4 cases of rhegmatogenous retinal detachment (RRD) that recurred 10, 11, 12, and 17 years after a reattachment surgery by pars plana vitrectomy (PPV). METHODS: Four cases of a recurrent RRD had undergone scleral buckling surgery and vitrectomy. PATIENTS: The recurrence of the RRD was observed 10-17 years after the successful attachment by PPV. The macula was detached in all cases, and none of the eyes had severe proliferative vitreoretinopathy. The cause of the recurrence was a new retinal break in 3 eyes and a reopening of an old retinal break in the other eye. The new breaks had a punched-out shape and had neither a horseshoe tear nor an atrophic hole associated with lattice degeneration. PPV combined with scleral buckling was performed, and a reattachment was achieved in all cases. The best-corrected visual acuity (BCVA) at the last visit ranged from 20/30 to 20/25, but the BCVA in 1 eye was 20/200 because of amblyopia. CONCLUSIONS: We experienced 4 rare cases of a recurrent retinal detachment 10-17 years after the primary RRD. PPV and scleral buckling were effective and the anatomical and the functional outcomes were good.

Characteristics and surgical outcomes of rhegmatogenous retinal detachments that develop after intravitreal injections.

PURPOSE: To determine the frequency and characteristics of rhegmatogenous retinal detachments (RRDs) that develop after an intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent. STUDY DESIGN: A retrospective review of the medical charts. METHODS: The charts of patients who received intravitreal injections for age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO), or myopic choroidal neovascularization (mCNV) between 2013 and 2020 were reviewed. We included the RRD cases that developed within 90 days of the most recent intravitreal injection. The baseline characteristics and surgical outcomes were analyzed. RESULTS: A total of 3040 patients received 28,190 intravitreal injections. Seven eyes of 7 cases developed a RRD. There were 6 cases of AMD and one of DME, with an incidence of one in 4027 injections (0.025%). The retinal break was in the superior quadrants in 5 eyes (71%), and in the inferior quadrants in 2 eyes. All eyes had a posterior vitreous detachment. The average number of injections before the development of RRD was 14.1 (range: 2-39). Four eyes were treated by vitrectomy, and 3 by scleral buckling. The primary success rate was 86%, and the final reattachment rate was 100%. The best-corrected visual acuity was 0.41 ± 0.26 logarithm of minimal angle of resolution (logMAR) units before developing the RRD, 0.78 ± 0.78 logMAR units before the surgery for RRD, and 0.45 ± 0.47 logMAR units at the final visit. CONCLUSIONS: The incidence of RRD after an intravitreal injection is very low (0.025%), and it can be reattached with recovery of the visual acuity.

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).

Comparisons of surgical outcomes after epiretinal membrane peeling in the myopic eyes with long to that with normal axial length.

PURPOSE: To compare the outcomes of vitrectomy with removal of an idiopathic epiretinal membrane (ERM) in the myopic eyes with long axial length (AL) to that in the eyes with normal AL. METHODS: This was a retrospective, observational, case-control study. Fifty-six eyes of 56 patients with an idiopathic ERM were studied. Twenty-eight of these eyes had an axial length longer than 26.0 mm (Group A), and the other 28 eyes had axial lengths < 26.0 mm (Group B). The age and visual acuity of the two groups were not significantly different. All subjects were treated by vitrectomy and peeling of the ERM with a 25- or 27-gauge system. The postoperative best-corrected visual acuity (BCVA) and optical coherence tomographic findings were determined at 3 and 6 months postoperatively. RESULTS: The mean BCVA improved from 0.35 ± 0.25 to 0.15 ± 0.25 logMAR units in the eyes with the long AL and from 0.35 ± 0.25 to 0.10 ± 0.21 logMAR units in the eyes with normal AL at 6 months postoperatively (both P < 0.001). The postoperative BCVA was not significantly different between the two groups at 6 months (P = 0.221). The central macula was thinner in the eyes of Group A than Group B (P < 0.001). The restorations of the ellipsoid zone and the external limiting membrane were observed in both groups, but the interdigitation zone was less frequently restored in Group A (P < 0.001). CONCLUSIONS: Vitrectomy with the removal of the epiretinal membrane is effective in attaining a good BCVA even in the myopic eyes with long AL.

Sodium-Glucose Cotransporter 2 Inhibitors Improve Chronic Diabetic Macular Edema.

PURPOSE: Diabetic macular edema (DME) is a vision-threatening condition that develops in diabetic patients. The first-line therapy for DME is intravitreal injections of antivascular endothelial growth factor (anti-VEGF) agents; however, the high frequency of repeat injections, invasiveness of the procedure, and high cost are drawbacks for this treatment. The purpose of this report is to present our findings in 3 patients with chronic DME whose edema was resolved soon after oral doses of sodium-glucose cotransporter-2 (SGLT2) inhibitors were used. Case Presentation. Case 1 was a 66-year-old woman diagnosed with moderate nonproliferative diabetic retinopathy (DR) with DME that had developed a decade earlier. The DME persisted for 4 years in the left eye. The addition of oral empagliflozin, a SGLT2 inhibitor, led to a marked improvement of the DME after one month, and this improvement continued over two years. Case 2 was a 68-year-old woman who was diagnosed with preproliferative DR with bilateral DME. The addition of oral dapagliflozin led to the improvement of the DME after two months, and this improvement continued over one year. Case 3 was a 61-year-old woman who was diagnosed with moderate nonproliferative DR with DME. Oral luseogliflozin was given which led to better glycemic control, and her left central retinal thickness (CRT) was markedly reduced after only two weeks. This reduction was maintained in her left eye for six months without any additional ophthalmic procedures. CONCLUSIONS: Although this study involved only three cases, our findings indicate that SGLT2 inhibitors might have possible efficacy for chronic DME.

Effects of Switching from Anti-VEGF Treatment to Triamcinolone Acetonide in Eyes with Refractory Macular Edema Associated with Diabetic Retinopathy or Retinal Vein Occlusion.

PURPOSE: To evaluate the efficacy of switching from intravitreal antivascular endothelial growth factor (VEGF) agents to triamcinolone acetonide (TA) in eyes with diabetic macular edema (DME) or with retinal vein occlusion-associated macular edema (RVO-ME) on the resolution of the macular edema (ME). METHODS: The medical records of 11 eyes of 11 patients with DME and 9 eyes of 9 patients with RVO-ME whose MEs were refractory to anti-VEGF treatment were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and the mean interval of the recurrences were measured during the anti-VEGF treatment and after switching to the TA injections. RESULTS: Switching to TA injections significantly increased the mean interval for recurrences from 9.2 ± 2.7 weeks to 22.3 ± 12.9 weeks in eyes with DME (P = 0.006). In eyes with RVO-ME, the mean period of recurrence was 12.3 ± 5.6 weeks before and 11.6 ± 4.4 weeks after the switch (P = 0.44). The mean interval for recurrence was extended to more than 8 weeks in 7 of 11 eyes with DME, but none of the eyes with RVO-ME had a prolongation of more than 4 weeks. An elevation of the IOP was observed in 3 of the 20 eyes after the TA injection. CONCLUSIONS: These findings indicate that switching to TA injections can be a good option for DME eyes refractory to anti-VEGF injections but not for the RVO-ME eyes.

Ocular syphilis with optic disc neovascularization treated with bevacizumab evaluated by OCT angiography and electroretinography.

We present our findings in an atypical case of ocular syphilis with optic disc neovascularization that was treated with intravitreal bevacizumab and followed by multimodal imaging and electroretinography. A 29-year-old man presented with a chief complaint of night blindness of one-year duration. Our initial examination showed that an optic disc neovascularization was present, and the optical coherence tomographic (OCT) images showed a reduction in the length of the ellipsoid zone of both eyes. Fluorescein angiography showed leakage from the optic disc neovascular tissue, and the presence of nonperfused areas in the peripheral retina. Blood test was strongly positive for syphilis. He was administered oral amoxicillin and prednisolone. He was also treated with an intravitreal injection of bevacizumab which led to a rapid suppression of the neovascularization. However, panretinal photocoagulation had to be performed because OCT angiography and fluorescein angiography detected residual neovascularization. Although these treatments suppressed the activity of the ocular syphilis, electrophysiological improvements were not seen even 1 year after the initial treatment. OCT angiography and electroretinogram are useful techniques for monitoring the effectiveness of the treatments.

Nonperfused Peripheral Retinal Area in Eyes with Chronic Rhegmatogenous Retinal Detachment.

We report two cases of chronic rhegmatogenous retinal detachment with a nonperfused peripheral retinal area. Case 1 was an 84-year-old woman who presented with a bullous retinal detachment of the inferior retina and a best-corrected visual acuity of 20/500. A small horseshoe tear was detected in the peripheral superior retina. Fluorescein angiography showed a wide area of nonperfused retina in the inferior retina. The retina was successfully reattached by scleral buckling surgery. Case 2 was a 40-year-old woman who presented with a shallow retinal detachment involving the macula. There were multiple retinal breaks at the pars plana that were secondary to blunt trauma. Fluorescein angiography revealed a wide area of nonperfused retina in the inferior peripheral retina. She underwent scleral buckling surgery, and the retina was successfully reattached. Our findings indicate that clinicians should examine the peripheral retina carefully especially with fluorescein angiography to search for nonperfused areas in eyes with chronic rhegmatogenous retinal detachment.

Safety and Efficacy of Ranibizumab and Luseogliflozin Combination Therapy in Patients with Diabetic Macular Edema: Protocol for a Multicenter, Open-Label Randomized Controlled Trial.

INTRODUCTION: Diabetic macular edema (DME) threatens daily life activities such as reading and driving and reduces the patients' quality-of-life. Recently, anti-vascular endothelial growth factor (VEGF) agents have become a first-line therapy in DME. However, therapy with anti-VEGF agents has several problems: repeated invasive injections are required; medical costs are high; and a certain proportion of patients with DME are resistant to treatment with anti-VEGF agents. While sodium-glucose co-transporter 2 (SGLT2) inhibitors have been widely used for the treatment of type 2 diabetes mellitus (T2DM), the effects of a combination therapy with anti-VEGF agent and SGLT2 inhibitor on DME are not yet known. METHODS: This study enrolls subjects with T2DM and DME, randomizes them into either a study agent treatment group (treated with ranibizumab as anti-VEGF agent and luseogliflozin as SGLT2 inhibitor) or a control group (treated with ranibizumab and glimepiride), and observes the subjects for 52 weeks after initiation of treatment. Planned outcomes: The primary endpoint is intergroup difference in the number of intravitreal anti-VEGF injections to the study eye from baseline to week 48. Secondary and exploratory endpoints include safety and ophthalmologic and internal medical clinical parameters. REGISTRATION: This study is registered at the University Hospital Medical Information Network Clinical Trial Registry (UMIN000033961) and Japan Registry of Clinical Trials (jRCTs031180210).