Same-Day Bilateral Intravitreal Dexamethasone Implants for the Treatment of Diabetic Macular Edema.

INTRODUCTION: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations. RESULTS: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule. CONCLUSIONS: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME.

Early Screening for Diabetic Retinopathy in Newly Diagnosed Type 2 Diabetes and Its Effectiveness in Terms of Morbidity and Clinical Treatment: A Nationwide Population-Based Cohort.

Purpose: To characterize the association between the frequency of screening for diabetic retinopathy (DR) and the detection of DR in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods: This nationwide population-based cohort study used data from the National Health Insurance Research Database to identify adult patients who were newly diagnosed with T2DM between 2000 and 2004. Data from their follow-up Diabetic retinopathy (DR) treatments over the next 10 years following diagnosis were also analyzed. Results: The 41,522 subjects were respectively assigned to a periodic screening group (n = 3850) and nonperiodic screening group (n = 37,672). Significant differences were observed between the two groups in terms of age, Charlson Comorbidity Index (CCI), sex, DR treatment, and the prevalence of DR. The association between periodic screening and DR treatment, only the elderly, female, and patient with severe CCI status showed the significance in the further stratified analysis. Conclusion: Periodic screening (annual or biannual screening in the first 5 years) was more effective than nonperiodic screening in detecting instances of DR in the middle-to-advanced aged group but not among younger patients. Screening pattern did not have a significant effect on the likelihood of DR-related treatment during the 5-year follow-up. It appears that a tight screening schedule for the first 5 years after diagnosis with diabetes is not necessary.

Therapeutic effect of simultaneous intravitreal dexamethasone and aflibercept on diabetic macular edema.

AIMS: To report the effect of simultaneous intravitreal dexamethasone (DEX) and aflibercept for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 102 eyes of 81 patients with DME. Patients were selected into two groups. The control group consisted of 50 eyes treated with aflibercept alone, and the combination group consisted of 52 eyes treated with simultaneous DEX implant and aflibercept injection. The primary endpoints were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 6. The secondary endpoint was the interval of retreatment. RESULTS: Baseline BCVA increased and CRT decreased at 6 months in both groups. Pseudophakic eyes in the combination group exhibited significantly greater BCVA improvement compared with phakic eyes (p = 0.031). Fewer intravitreal treatments were required for eyes treated with combination therapy than for those treated with aflibercept alone (1.56 ± 0.54 vs. 4.04 ± 1.26, p < .0001), with a mean retreatment interval of 3.66 ± 0.69 months. CONCLUSIONS: Simultaneous intravitreal DEX and aflibercept achieved non-inferior improvement of visual and anatomic outcomes compared with aflibercept alone for DME, but exhibited a significantly longer treatment interval and superior visual outcome in pseudophakic eyes. This therapeutic approach is considered a valid strategy for treating DME in the era of COVID-19.

Bilateral cytomegalovirus retinitis comorbid with diabetic macular edema.

Cytomegalovirus (CMV) retinitis comorbid with diabetic retinopathy is uncommon. We report a case of bilateral CMV retinitis and diabetic retinopathy in a patient who underwent pancreas transplantation and share the experience of the treatment outcome. An 18-year-old male diagnosed with type-1 diabetes mellitus received pancreas transplantation and immunosuppressive therapy suffered from progressively blurred vision in both eyes for several days. His visual acuity was 20/100 in the right eye and 20/50 in the left eye. Ophthalmic examination revealed bilateral diabetic macular edema (DME) without intraocular inflammatory signs in either eye. The DME subsided after 2 monthly intravitreal injections of aflibercept. However, bilateral panuveitis with CMV retinitis was observed after antivascular endothelial growth factor therapy. The retinitis subsided gradually but completely after systemic and intravitreal antiviral therapy. However, bilateral DME recurred and persisted despite repeated injections of aflibercept during the resting follow-up period. Our case suggests that CMV retinitis can coexist with other retinal diseases, including diabetic retinopathy. Treatment is difficult in such cases.

POSTOPERATIVE INNER NUCLEAR LAYER MICROCYSTS AFFECTING LONG-TERM VISUAL OUTCOMES AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To investigate the risk factors and long-term visual impact of microcysts in the inner nuclear layer developed after epiretinal membrane (ERM) surgery. METHODS: This study used a retrospective review of medical records, operative video and images of patients who had undergone idiopathic ERM surgery with more than 12 months of follow-up. RESULTS: This study enrolled 44 patients (44 eyes) with ERM and a mean follow-up period of 30.2 months. The visual acuity improved from a mean of 6/22.8 to 6/12 (P < 0.001). Results indicated that a final visual acuity greater than 0.5 was associated with younger age, better preoperative visual acuity, a complete postoperative inner segment and outer segment line, and absence of inner nuclear layer microcysts. The visual acuity difference between patients with and without inner nuclear layer microcysts emerged in the first month and continued throughout the entire study period. Shorter duration of visual symptoms, more severe grade of ERM with paravascular abnormalities, and retinal petechiae immediately after the peeling of the ERM are risk factors of microcysts. CONCLUSION: This study suggests that inner nuclear layer microcysts are induced shortly after surgery and have long-term visual effects. Factors associated with this side effect suggest that severity, acuteness, and adhesiveness of ERM may play a significant role in visual outcomes.

Laminin modification subretinal bio-scaffold remodels retinal pigment epithelium-driven microenvironment in vitro and in vivo.

Advanced age-related macular degeneration (AMD) may lead to geographic atrophy or fibrovascular scar at macular, dysfunctional retinal microenvironment, and cause profound visual loss. Recent clinical trials have implied the potential application of pluripotent cell-differentiated retinal pigment epithelial cells (dRPEs) and membranous scaffolds implantation in repairing the degenerated retina in AMD. However, the efficacy of implanted membrane in immobilization and supporting the viability and functions of dRPEs, as well as maintaining the retinal microenvironment is still unclear. Herein we generated a biomimetic scaffold mimicking subretinal Bruch's basement from plasma modified polydimethylsiloxane (PDMS) sheet with laminin coating (PDMS-PmL), and investigated its potential functions to provide a subretinal environment for dRPE-monolayer grown on it. Firstly, compared to non-modified PDMS, PDMS-PmL enhanced the attachment, proliferation, polarization, and maturation of dRPEs. Second, PDMS-PmL increased the polarized tight junction, PEDF secretion, melanosome pigment deposit, and phagocytotic-ability of dRPEs. Third, PDMS-PmL was able to carry a dRPEs/photoreceptor-precursors multilayer retina tissue. Finally, the in vivo subretinal implantation of PDMS-PmL in porcine eyes showed well-biocompatibility up to 2-year follow-up. Notably, multifocal ERGs at 2-year follow-up revealed well preservation of macular function in PDMS-PmL, but not PDMS, transplanted porcine eyes. Trophic PEDF secretion of macular retina in PDMS-PmL group was also maintained to preserve retinal microenvironment in PDMS-PmL eyes at 2 year. Taken together, these data indicated that PDMS-PmL is able to sustain the physiological morphology and functions of polarized RPE monolayer, suggesting its potential of rescuing macular degeneration in vivo.

Focal Nonperfusion of Deep Retinal Capillary Plexus in Eyes With Epiretinal Membranes Revealed by Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To evaluate the leakage pattern in eyes with idiopathic epiretinal membranes (ERM) using fluorescein angiography (FA) and the structure of the retinal capillary plexus with optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: The authors enrolled patients with idiopathic macular ERM in the consecutive case series study. All patients were evaluated using FA at the central macula area and OCTA at the central 3 mm × 3 mm. RESULTS: Six patients (seven eyes) with ERM completed this preliminary study. The authors examined five eyes that showed increased macular thickness without a lamellar hole and two eyes that showed combined ERM with a lamellar hole. In the five eyes with ERM alone, the irregular focal hypofluorescent areas in FA corresponded to the locations of absent or low flow signals within vasculatures in the deep retinal capillary plexus seen in OCTA, whereas most of the superficial retinal capillary plexus was not affected, except vascular tortuosity in OCTA. In the two eyes combined with lamellar hole, OCTA showed central cystic lesions without vasculatures, but no low flow signals within vasculatures in the deep retinal capillary plexus beyond the hole. These focal irregular, absent, or low flow signals within vasculatures in the deep retinal plexus improved 1 month after surgical removal of the ERM in one eye. CONCLUSION: Mechanical stress exerted from the ERM might affect deep retinal capillary flow more profoundly than the superficial capillary flow, which would account for the fluorescence changes seen in FA. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:404-409.].

Long-Term Topical Ganciclovir and Corticosteroids Preserve Corneal Endothelial Function in Cytomegalovirus Corneal Endotheliitis.

PURPOSE: To report the long-term outcomes of topical ganciclovir (GCV) and corticosteroids as a maintenance therapy for cytomegalovirus (CMV) corneal endotheliitis. METHODS: This retrospective study included 10 eyes of 9 patients diagnosed with CMV corneal endotheliitis with a minimum 1-year follow-up at a tertiary referral hospital between 2008 and 2014. CMV corneal endotheliitis was defined by corneal edema associated with typical keratic precipitates (KPs) and a positive CMV polymerase chain reaction from aqueous humor taps. Patients receiving long-term topical 0.5% GCV and topical corticosteroids without discontinuation were included. The final corneal condition and endothelial cell density (ECD) were reported. RESULTS: The mean age was 45.6 ± 11.7 years. The mean follow-up duration was 48 ± 25 months. All patients exhibited typical coin-shaped and/or linear KPs. A significant resolution of corneal edema and decreased KPs were achieved within 1 month in all patients after initiating topical 0.5% GCV every 2 hours and topical corticosteroids twice a day. The dose frequency was gradually tapered to GCV 4 times and corticosteroids once or twice a day as a maintenance therapy. All 10 eyes had a clear graft or corneas at the end of this study. The mean ECD was 1630 ± 699 cells per millimeter square before treatment and 1776 ± 834 cells per millimeter square at the end of the study period. CONCLUSIONS: Topical 0.5% GCV and corticosteroids as a maintenance regimen without interruption effectively preserved long-term corneal endothelial function.

Haploinsufficiency of RCBTB1 is associated with Coats disease and familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) belongs to a group of genetically and clinically heterogeneous disorders in retinal vascular development. To date, in approximately 50% of patients with FEVR, pathogenic mutations have been detected in FZD4, LRP5, TSPAN12, NDP and ZNF408. In this study, we identified two heterozygous frameshift mutations in RCBTB1 from three Taiwanese cases through exome sequencing. In patient-derived lymphoblastoid cell lines (LCLs), the protein level of RCBTB1 is approximately half that of unaffected control LCLs, which is indicative of a haploinsufficiency mechanism. By employing transient transfection and reporter assays for the transcriptional activity of ß-catenin, we demonstrated that RCBTB1 participates in the Norrin/FZD4 signaling pathway and that knockdown of RCBTB1 by shRNA significantly reduced nuclear accumulation of ß-catenin under Norrin and Wnt3a treatments. Furthermore, transgenic fli1:EGFP zebrafish with rcbtb1 knockdown exhibited anomalies in intersegmental and intraocular vessels. These results strongly support that reduced RCBTB1 expression may lead to defects in angiogenesis through the Norrin-dependent Wnt pathway, and that RCBTB1 is a putative genetic cause of vitreoretinopathies.

Combination therapy with intravitreal bevacizumab and macular grid and scatter laser photocoagulation in patients with macular edema secondary to branch retinal vein occlusion.

PURPOSE: To assess the efficacy of combined intravitreal bevacizumab (IVB) and macular grid and scatter laser photocoagulation in the treatment of macular edema secondary to branch retinal vein occlusion (BRVO) over a 12-month period. METHODS: A prospective, interventional case series study was conducted in 20 patients. Patients were treated with 3 monthly IVB injections, followed by macular grid laser and scatter laser photocoagulation to nonperfused ischemic retina. Repeated IVB injections were performed on an as-needed basis when patients had recurrent macular edema. RESULTS: The best-corrected visual acuity of 20/40 or better was achieved in 17 eyes (85%) and a vision gain of 3 lines or more was noted in 12/20 eyes (60%). Mean visual acuity improved from 0.68 logMAR at baseline to 0.28 logMAR at 3 months, 0.26 logMAR at 6 months, and 0.26 logMAR at 12 months (P<0.01). The mean central macular thickness (CMT) was 442 µm at baseline and decreased to 266, 264, 300, and 294 µm at 1, 3, 6, and 12 months' follow-up, respectively (P<0.01). A mild rebound CMT increase was noted at 6 months, which was reduced after bevacizumab reinjection. Ten patients (50%) required repeated IVB injections. Fifteen eyes (75%) have complete edema resolution on optical coherence tomography scan at the 12-month return visit. Overall, patients received an average of 4 injections during the 12-month period. No adverse ocular or systemic events were observed following injections. CONCLUSIONS: Early IVB injections in combination with subsequent macular grid and scatter laser photocoagulation treatment significantly improved vision and reduced macular edema secondary to BRVO. Further studies are warranted to evaluate the long-term outcomes and safety.