Purpose The purpose of this study is to examine the impact of the timing of the steroid switch on both visual and anatomical outcomes in diabetic macular edema (DME) eyes that have shown an inadequate response to multiple intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. In the treatment of DME, anti-VEGF injections are typically the initial course of action. However, in cases where DME persists despite anti-VEGF treatment, intravitreal dexamethasone implants (Ozurdex®, Allergan Inc., Irvine, CA) are often utilized. Despite this, there remains a lack of consensus regarding the optimal timing for transitioning to steroid treatment. This study aims to shed light on the potential benefits of adjusting the timing of the steroid switch in cases of recalcitrant DME.  Methods The eyes (n = 105) of 77 patients with recalcitrant DME were included in this retrospective, interventional, comparative study comprising three groups: participants switched to steroid implants after three anti-VEGF injections (Group I), four to six anti-VEGF injections (Group II), and more than six anti-VEGF injections (Group III). Anti-VEGF treatment failure was defined as a central retinal thickness (CRT) of ≥300 microns and/or a lack of visual improvement (≤1 line of visual gain according to Snellen acuity). The last follow-up took place after 10-12 weeks of Ozurdex® injections. Results Improvement was observed in 19 eyes (46%), 17 eyes (50%), and 10 eyes (33%) in Groups I, II, and III, respectively, after switching to dexamethasone implants. The best overall results (an improvement in vision and stabilization) were seen in Group II (32 eyes, 94%). The decrease in CRT was statistically significant in all three groups.  Conclusion Intravitreal dexamethasone implants improved functional and morphological outcomes in anti-VEGF-resistant DME eyes. After four to six anti-VEGF injections, switching to a steroid implant resulted in the best functional results.

BACKGROUND: The aim of this study was to assess the efficacy and safety of fluocinolone acetonide implant (FAci) injected 1 month after the last dexamethasone intravitreal implant (DEXi) in chronic diabetic macular oedema (DME) patients.
METHODS: Retrospective multicentric study conducted in pseudophakic patients with chronic DME frequently treated with dexamethasone intravitreal implant (DEXi; time to DME recurrence ≤ 6 months), receiving FAci 1 month after the last DEXi, with at least a 6-month follow-up. Best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography, intraocular pressure (IOP) and additional treatments were assessed on the day of FAci injection (M0), 1 (M1) and 3 months (M3) later and then every 3 months.
RESULTS: A total of 41 eyes from 34 patients were included. At M0, patients\' mean age was 68.7 ± 9.8 years, the mean DME duration was 63.9 ± 22.9 months, the mean interval between two DEXi was 14.2 ± 3.3 weeks. M12 data were available for 71% of patients. At baseline, the mean BCVA, CMT and IOP were 63.2 ± 16.6 letters, 299.4 ± 103.3 µm, and 16.2 ± 4.5 mmHg, respectively, and remained stable during the follow-up. At M12, 14% of patients required additional intravitreal treatments.
CONCLUSIONS: In pseudophakic patients with chronic DME showing good response to DEXi but requiring repeated injections every < 6 months, switching to FAci 1 month after the last DEXi was effective and safe. Further prospective randomized controlled studies are needed to confirm these findings, and to determine the best interval between the last DEXi and the first FAci.

OBJECTIVE: Diabetes requires ongoing monitoring and care to prevent long-term adverse health outcomes. In Canada, quarantine restrictions were put into place to address the coronavirus-2019 (COVID-19) pandemic in March 2020. Primary care diabetes clinics limited their in-person services and were advised to manage type 2 diabetes (T2D) through virtual visits and reduce the frequency of routine diabetes-related lab tests and screening.
METHODS: This retrospective cross-sectional study used de-identified patient records from a primary care electronic medical records database in Ontario, Canada, to identify people with T2D who had at least 1 health-care touchpoint between March 1, 2018, and February 28, 2021. Outcomes were described on a monthly or yearly basis: 1) number of people with primary care visits (in-person vs virtual); 2) number of people with referrals; 3) number of people with each of the vital/lab measures; and 4) results of the vital/lab measures.
RESULTS: A total of 16,845 individuals with T2D were included. Compared with the pre-pandemic period, the COVID-19 period had a 16.8% reduction in the T2D population utilizing any primary care and an increase of 330.4% in the number of people with at least 1 virtual visit. Compared with the pre-pandemic period, fewer people had vital/lab measures in the pandemic period. However, among the people with the test results available, the average values for all tests were similar in the pre- and pandemic periods.
CONCLUSIONS: Further research is needed to understand the impact of the reduction of in-person clinical care on the entire population with T2D.

UNASSIGNED: The foveal avascular zone (FAZ) has been reported to decrease after anti-VEGF injections in diabetic macular edema (DME) in the long term. This study aimed to present the changes in swept-source OCT angiography after vitrectomy in patients with DME.
UNASSIGNED: Retrospective interventional study.
UNASSIGNED: Thirty-five eyes were included (mean age: 62 years).
UNASSIGNED: Patients were followed for 12 months after vitrectomy with internal limiting membrane peeling for DME.
UNASSIGNED: The following parameters were measured: central retinal thickness (CRT), central choroidal thickness, superficial FAZ, deep FAZ (dFAZ), and vessel density in the superficial and deep retinal layers (dVD).
UNASSIGNED: The CRT and superficial FAZ significantly decreased after surgery (401 μm-338 μm; P < 0.00, 401 μm-293 μm; P < 0.001, respectively). Initial visual acuity (VA) improved from 20/160 (0.97 logarithm of the minimum angle of resolution [LogMAR]) to 20/80 (0.62 LogMAR) (P < 0.001). The vessel density in the superficial retinal layers rate was 42.3% and decreased after surgery, reaching 41.6% at the end of the follow-up. The dVD rate 1 week after surgery was 28.9% and remained stable throughout the observation period. The most important prognostic factors for the final VA were preoperative VA and preoperative CRT, while the dFAZ and dVD at the time of edema resolution also correlated with the final VA.
UNASSIGNED: The superficial FAZ decreases after vitrectomy, which might indicate that vitrectomy has a protective effect on DME, similar to anti-VEGF injections. Prognostic factors for better final functional results are better initial VA and lower CRT before vitrectomy, in addition to a lower dFAZ diameter and a higher dVD at the moment of edema resolution.
UNASSIGNED: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

UNASSIGNED: To evaluate the safety and preliminary efficacy of THR-687 in patients with center-involved diabetic macular edema (DME).
UNASSIGNED: Phase 1, open-label, multicenter, 3 + 3 dose-escalation study with 3-month follow-up.
UNASSIGNED: Patients 18 years of age or older with visual impairment resulting from DME.
UNASSIGNED: Single intravitreal injection of THR-687 (0.4 mg, 1.0 mg, or 2.5 mg).
UNASSIGNED: The primary outcome measure was the incidence of dose-limiting toxicities (DLTs). The secondary outcome measure was the incidence of adverse events (AEs), including the occurrence of laboratory abnormalities. Exploratory outcome measures included changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST), assessments of ischemia and leakage on fluorescein angiography, and THR-687 levels in plasma.
UNASSIGNED: Twelve patients were treated: 3 patients received 0.4 mg of THR-687, 3 patients received 1.0 mg of THR-687, and 6 patients received 2.5 mg of THR-687. Most patients were men (9/12 patients). Their mean age was 57.8 years. No DLTs or serious AEs were reported at any of the dose levels tested. Overall, 9 AEs in the study eye were reported for 5 of 12 patients. Of those, 4 AEs in 3 of 12 patients were deemed treatment related by the investigator, all of which were mild, started on the day of the injection, and had resolved within 28 days without treatment. Overall, mean gains from baseline in BCVA were observed at all study visits with a rapid onset (7.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters at day 7) and a durability up to the end of the study (8.3 ETDRS letters at month 3). A mean decrease in CST was observed up to month 1. Overall, the mean BCVA gains and CST decreases were highest at the highest THR-687 dose level tested. THR-687 was undetectable in plasma at 7 days after the injection.
UNASSIGNED: At all dose levels tested, a single intravitreal injection of THR-687 was safe and well tolerated. Preliminary efficacy was observed by a rapid gain in BCVA with 3 months\' durability and a decrease in CST up to 1 month after the injection.

To determine clinical effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT) < 400 μm.
Pragmatic, multicenter, allocation-concealed, double-masked, randomized, noninferiority trial.
Adults with center-involved DME < 400 μm and best-corrected visual acuity (BCVA) of > 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes.
Randomization 1:1 to 577 nm SML or SL treatment. Retreatments were allowed. Rescue with intravitreal anti-vascular endothelial growth factor therapies or steroids was permitted if 10 or more ETDRS letter loss occurred, CRT increased > 400 μm, or both.
Primary outcome was mean change in BCVA in the study eye at 24 months (noninferiority margin 5 ETDRS letters). Secondary outcomes were mean change from baseline to month 24 in binocular BCVA; CRT and mean deviation of Humphrey 10-2 visual field in the study eye; percentage meeting driving standards; EuroQoL EQ-5D-5L, 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), and Vision and Quality of Life Index (VisQoL) scores; cost per quality-adjusted life-years (QALYs) gained; adverse effects; and number of laser and rescue treatments.
The study recruited fully (n = 266); 87% of SML-treated and 86% of SL-treated patients had primary outcome data. Mean ± standard deviation BCVA change from baseline to month 24 was -2.43 ± 8.20 letters and -0.45 ± 6.72 letters in the SML and SL groups, respectively. Subthreshold micropulse laser therapy was deemed not only noninferior but also equivalent to SL therapy because the 95% confidence interval (CI; -3.9 to -0.04 letters) lay wholly within both upper and lower margins of the permitted maximum difference (5 ETDRS letters). No statistically significant difference was found in binocular BCVA (0.32 ETDRS letters; 95% CI, -0.99 to 1.64 ETDRS letters; P = 0.63); CRT (-0.64 μm; 95% CI, -14.25 to 12.98 μm; P = 0.93); mean deviation of the visual field (0.39 decibels (dB); 95% CI, -0.23 to 1.02 dB; P = 0.21); meeting driving standards (percentage point difference, 1.6%; 95% CI, -25.3% to 28.5%; P = 0.91); adverse effects (risk ratio, 0.28; 95% CI, 0.06-1.34; P = 0.11); rescue treatments (percentage point difference, -2.8%; 95% CI, -13.1% to 7.5%; P = 0.59); or EQ-5D, NEI-VFQ-25, or VisQoL scores. Number of laser treatments was higher in the SML group (0.48; 95% CI, 0.18-0.79; P = 0.002). Base-case analysis indicated no differences in costs or QALYs.
Subthreshold micropulse laser therapy was equivalent to SL therapy, requiring slightly higher laser treatments.

OBJECTIVE: The aim of this study was to compare the results of vitrectomy performed in patients\' worse eyes with diabetic macular edema to the results of continuous anti-VEGF treatment performed in patients\' fellow eyes.
METHODS: A retrospective interventional study of 14 patients with diabetic macular edema in both eyes. The better eye was always qualified for aflibercept injections (group 1), and the worse eye was scheduled for vitrectomy (group 2). The follow-up lasted 12 months. The following parameters were measured: visual acuity (V), central retinal thickness (CRT), maximum retinal thickness (MRT), central choroidal thickness (CCT), superficial fovea avascular zone (sFAZ) and deep fovea avascular zone (dFAZ), and vessel density at the level of superficial (sVD) and deep (dVD) retinal vessels.
RESULTS: None of the analyzed factors differed between groups with statistical significance at any timepoint. The time of recovery of vision was identical in both eyes (F = 0.91, p = 0.449). The final sFAZ was significantly smaller for group 2 (median 196 μm) than for group 1 (median 375 μm; U = 101.0; p = 0.022; r = 0.44).
CONCLUSIONS: Both techniques resulted in similar improvements in visual acuity and decreases in CRT after 1 year. sFAZ decreased in all eyes, with a higher extent after vitrectomy.

OBJECTIVE: To evaluate retinal hard exudates (HEs) progression in patients with cystoid macular edema (CME) secondary to diabetic retinopathy (DR) or branch retinal vascular occlusion (BRVO) after intravitreal injections of ranibizumab (IVR) treatment and identify the risk factors for the deterioration of HEs.
METHODS: This retrospective study enrolled 288 eyes with center-involving CME secondary to DR or BRVO from 288 patients (one eye per patient). All patients were treated with three loading doses of ranibizumab intravitreally at a monthly interval. The morphologic features of HEs were observed, and the HEs areas were quantified using a semi-automatic method at baseline, 1 month after the first dose of IVR and 1 month after the third dose of IVR therapy. HEs progression was defined as having a > =2-grade increase in the HEs severity scale. The best-corrected vision acuity (BCVA) and alterations in HEs areas were compared between DR and BRVO groups. And logistic regression analyses were used to identify the risk factors for HEs exacerbation.
RESULTS: Morphological changes of retinal HEs occurred in all eyes after IVR therapy, although HEs area was not significantly changed in some eyes. DR group has a higher percentage of eyes with progressed HEs area than the BRVO groups (34.9% vs. 21.8%, P = 0.019) 1 month after the first dose of IVR. Both DR and BRVO groups had a decreased percentage of enlarged HEs 1 month after the third injection, but the DR group is still higher than the BRVO group (17.1% vs. 8.4%, P = 0.027). At baseline, there was no correlation between VA and HEs areas. After the first and third doses of IVR, there still was no consistent correlation between HEs severity and change in VA over time. Furthermore, CME with subretinal fluid (SRF) is associated with a higher risk of HEs progression (P = 0.001). Long CME duration and high serum low-density lipoprotein cholesterol (LDL-C) level were identified as risk factors for HEs progression following IVR treatment in both univariable and multivariable regression analyses (Odds ratio (OR) = 1.88, P = 0.012 and OR = 1.14, P = 0.021, respectively).
CONCLUSIONS: Alterations in the area of retinal HEs are widely observed after IVR treatment for CME. The eyes with CME secondary to DR have a higher percentage of progressed HEs than the BRVO eyes. DME with SRF, extended duration of CME, and high LDL-C level are potential risk factors of deteriorated HEs after IVR treatment.

OBJECTIVE: To identify baseline characteristics of subjects enrolled in the READ-3 study that would predict the response of macular edema to ranibizumab (RBZ) therapy at year 1.
METHODS: In this post hoc analysis of the READ-3 randomized, multicenter phase 2 clinical trial, subjects with diabetic macular edema (DME) were randomized to receive monthly intravitreal injections of RBZ (0.5 or 2.0 mg) for 6 consecutive injections followed by as-needed treatments based on pre-defined retreatment criteria. In this sub-study, subjects were divided into three groups (persistent, rebound, and resolved) based on edema status at month 12 (M12). Multi-logistic regression was utilized to assess the probability of edema outcomes M12, based on the baseline characteristics.
RESULTS: One hundred twenty-three out of 152 subjects were analyzed for this sub-study. A significant difference was observed in the baseline (BL) central subfield thickness (CST) among the study groups (p < 0.05). BL CST was a significant predictor for edema outcome at M12 with > 80% probability of the subject having persistent edema if BL CST was > 570 μm (p < 0.05). This association persisted when controlled for the dose of RBZ (relative risk (RR), 1.007; p < 0.05). BL CST was also a significant predictor for having persistent edema at M12 in subjects without vitreomacular adhesion (VMA) (> 80% probability of edema persistence at CST > 570 μm [RR, 1.006; p < 0.05]). However, in the presence of VMA, BL CST was no longer a significant predictor of having persistent edema at month 12 (RR, 1.005; p > 0.05).
CONCLUSIONS: Subjects with high CST (> 570 μm) at baseline may not benefit from repeated intravitreal injections of anti-VEGF for resolution of edema.

The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient\'s evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR.
Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom.
Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease.
A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists).
Primary outcome: sensitivity of the new pathway.
specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings.
The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%-99%) and specificity of 31% (95% CI, 23%-40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%-91%] and 48% [95% CI, 41%-56%], respectively) or UWF images (83% [95% CI, 75%-89%] and 54% [95% CI, 46%-61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%-93%] and 49% [95% CI, 42%-56%], respectively, for UWF versus 80% [95% CI, 69-88%] and 40% [95% CI, 34%-47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists\' assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits.
The new pathway has acceptable sensitivity and would release resources. Users\' suggestions should guide implementation.