Mean Central Subfield Thickness Research Articles

Treatment Outcomes of Intravitreal Aflibercept for Uveitic Macular Edema.

To evaluate the efficacy of intravitreal aflibercept for UME (uveitic macular). A retrospective review of records of patients that received aflibercept for UME from January 2017 to August 2022 was conducted. The primary outcomes were mean change in visual acuity (VA) and central subfield thickness (CST) 6 and 12 months from the start of aflibercept treatment. A total of 16 eyes of 12 patients were included. Indications for treatment included eyes that had previously demonstrated a history of elevated intraocular pressure secondary to a steroid response (n = 10) or a history of non-response or partial response to local corticosteroids (n = 6). Fifteen eyes (94%) demonstrated a reduction in CST after their initial injection. At 6-months, mean VA gain was 2.6 ± 7.7 letters (p = 0.24) from a mean VA of 67.8 ± 10.7 letters at baseline and mean CST improved by 97.6 ± 113.5 μm (p = 0.004) from 458.6 ± 123.1 μm at baseline. Fourteen eyes had 12-months of follow up and received a median of 4 injections over 12 visits. The mean VA at 12-months remained stable compared to baseline (mean change of -1.4 ± 12.5 letters (p = 0.87)) while the CST improved by a mean of 90.9 ± 114.6 μm (p = 0.053) compared to baseline. Intravitreal aflibercept injections resulted in reduced central subfield thickness at all time-points. It appears to be an effective treatment alternative for UME, particularly for patients who are not responsive to local corticosteroids or who have contraindications to corticosteroid treatment.

Phase 1 Study of Tivozanib Eye Drops in Healthy Volunteers and Patients with Neovascular Age-related Macular Degeneration

PurposeTo evaluate the safety, pharmacokinetics, and exploratory efficacy of tivozanib eye drops in healthy volunteers and patients with neovascular age-related macular degeneration (nAMD). DesignThis multicenter, group-sequential dose escalation phase 1 study consisted of a placebo-controlled, double-masked study of healthy volunteers (Cohorts 1 and 2) and an open-label study of nAMD patients (Cohort 3). ParticipantsHealthy volunteers: Japanese or White men aged 20 to <50 years. Patients with nAMD with central subfield thickness ≥300 μm and best-corrected visual acuity score ≥23 letters in the study eye. MethodsIn the single-dose cohort of healthy men (Cohort 1: Steps 1–5), 1 or 2 tivozanib eye drops (30 μL/drop, 5-minute interval; 0.5, 1.0, and 2.0 w/v%) or placebo were administered in 1 eye once. In the multiple-dose cohort of healthy men (Cohort 2: Steps 1–6), 1 or 2 tivozanib eye drops (0.5, 1.0, and 2.0 w/v%) or placebo were administered 3 times daily (TID) in 1 eye for 21 days. In the multiple-dose cohort of nAMD patients (Cohort 3, Steps 1–3), 1 or 2 tivozanib eye drops (0.5 and 1.0 w/v%) were administered TID in 1 affected eye for 21 days. Main Outcome MeasuresThe safety outcome measures included adverse events (AEs). The pharmacokinetic outcome was serum tivozanib concentration. Among the exploratory efficacy outcomes, central subfield thickness (CST) was evaluated. ResultsIn total, 40, 48, and 28 participants were enrolled in Cohorts 1, 2, and 3, respectively. Serious AEs did not occur in Cohorts 1–3. The most frequent AE in multiple-dose cohorts was reversible punctate keratitis: placebo arm, 8.3% (healthy men, 1/12); tivozanib arm, 47.2% (healthy men, 17/36) and 14.3% (nAMD, 4/28). Serum tivozanib exposure increased dose-dependently and was similar in healthy men and patients with nAMD. In patients with nAMD, mean CST changes from baseline to Day 22 were −27.6 ± 54.88 (0.5 w/v%; 1 drop, TID), −35.6 ± 49.64 (1.0 w/v%; 1 drop, TID), and −43.7 ± 55.19 μm (1.0 w/v%; 2 drops, TID). ConclusionsTivozanib eye drops showed a favorable safety profile in healthy Japanese and White men and Japanese patients with nAMD.

Retinal and choroidal efficacy of switching treatment to faricimab in recalcitrant neovascular age related macular degeneration

Aim of this study was to evaluate the efficacy of switching treatment to faricimab in neovascular age-related macular degeneration (nAMD) from other anti-VEGF agents. Fifty-eight eyes of fifty-one patients with nAMD and a full upload series of four faricimab injections were included. Demographic data, multimodal imaging and treatment parameters were recorded. The primary outcome measures were changes in central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). A subgroup analysis was performed for eyes with prior ranibizumab (R) or aflibercept (A) treatment. Mean injection intervals before and after switching were comparable (33.8 ± 11.2 vs. 29.3 ± 2.6 days; p = 0.08). Mean CST of 361.4 ± 108.1 µm prior to switching decreased significantly to 318.3 ± 97.7 µm (p < 0.01) after the third faricimab injection, regardless of prior anti-VEGF treatment (p < 0.01). Although SFCT slightly improved for the whole cohort from 165.8 ± 76.8 µm to 161.0 ± 82,8 µm (p = 0.029), subgroup analysis did not confirm this positive effect (subgroup R: p = 0.604; subgroup A: p = 0.306). In patients with a suboptimal response to aflibercept or ranibizumab in nAMD, farcimab can improve CST and slightly improve or maintain SFCT. Further prospective randomized trials are warranted.

One-Year Anti-VEGF Therapy Outcomes in Diabetic Macular Edema Based on Treatment Intensity: Data from the Fight Retinal Blindness! Registry

PurposeTo compare one-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal vascular endothelial growth factor (VEGF) inhibitor injections were delivered. DesignCohort study ParticipantsThere were 2288 treatment-naïve eyes with DME starting intravitreal VEGF inhibitor therapy from 31 October 2015 to 31 October 2021 from the Fight Retinal Blindness! international outcomes registry. MethodsEyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n=1172) versus Group B with greater than the median (n=1116). Main Outcome MeasureMean visual acuity (VA) change after 12 months of treatment. ResultsThe mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8, 4.4) letters for eyes in Group A versus 5.2 (4.4, 5.9) letters for eyes in Group B (p=0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76, -61) μm and -85 (-92, -78) μm for eyes in Group A versus Group B, respectively (p=0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (p<0.001). Additionally, eyes that received more injections had a moderately greater CST reduction. ConclusionsThis registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy.

Initial response and 12-month outcomes after commencing dexamethasone or vascular endothelial growth factor inhibitors for retinal vein occlusion in the FRB registry

To compare baseline characteristics, initial response and 12-month efficacy and safety outcomes in eyes with branch and central retinal vein occlusion (BRVO and CRVO) treated with dexamethasone implants (DEX) or anti-vascular endothelial growth factor (anti-VEGF) we performed a multi-centre, retrospective and observational study using Fight Retinal Blindness! Registry. Of 725 eligible eyes, 10% received DEX initially with very frequent adjunctive anti-VEGF (BRVO-DEX 49%, CRVO-DEX 60%). The primary outcome of mean adjusted change in VA at 12 months with DEX and anti-VEGF initiated groups were not statistically significantly different (BRVO: DEX + 6.7, anti-VEGF + 10.6 letters; CRVO: DEX + 2.8, anti-VEGF + 6.8 letters). DEX initiated eyes had fewer injections and visits than anti-VEGF initiated eyes. The BRVO-DEX eyes had greater initial mean changes in VA and central subfield thickness (CST) and achieved inactivity sooner than BRVO-anti-VEGF eyes. The mean CST after the first three months was above 350 μm in all but the BRVO-anti-VEGF group, suggesting undertreatment. In routine care DEX is uncommonly used when available as initial treatment of BRVO and CRVO requiring supplemental anti-VEGF within the first year. The 12-month outcomes were similar, but DEX initiated eyes had fewer injections and visits but more episodes of raised IOP Vs those starting anti-VEGF.

The effect of glycosylated hemoglobin levels on the response to intravitreal dexamethasone implant for treating diabetic macular edema

This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was − 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment.

Two-Year Follow-Up Study of Patients with Neovascular Age-Related Macular Degeneration Undergoing Anti-VEGF Treatment during the COVID-19 Pandemic

Background: regular intravitreal anti-vascular endothelial growth factor (VEGF) treatment is crucial for patients with neovascular age-related macular degeneration (nAMD), and delayed treatment can exacerbate disease progression. Methods: we compared the outcomes of on-time versus delayed intravitreal anti-VEGF treatment for patients with nAMD. This study was conducted during the coronavirus disease 2019 (COVID-19) pandemic with a 2-year follow-up period. The best-corrected visual acuity (BCVA) and anatomical findings were evaluated before the pandemic, during the pandemic, and at 6-, 12-, 18-, and 24-months post-pandemic. Results: The delayed and on-time groups comprised 54 and 72 patients, respectively. After the pandemic, the injection interval increased by 0.65 ± 1.51 months (p = 0.003), with 22.2% of the patients in the delayed group switching to the treat-and-extended regimen (p &lt; 0.001). The delayed group showed greater mean BCVA deterioration (p = 0.027) and central subfield thickness (p = 0.037) at 6 months and worse maximum subretinal fluid height (p = 0.022) at 18 months than the on-time group. No difference was observed between the groups in the second year. Conclusion: the negative effects of delaying anti-VEGF treatment because of the COVID-19 pandemic can be ameliorated by changing the treatment regimen and shortening treatment intervals.

Safety and Efficacy of CLS-TA by Anatomic Location of Inflammation: Results from the Phase 3 PEACHTREE Clinical Trial

ABSTRACT Purpose To explore the efficacy of CLS-TA, a proprietary suprachoroidal injectable suspension of triamcinolone acetonide, in noninfectious uveitis (NIU) with macular edema (ME), categorized by anatomic subtype. Methods Patients diagnosed with ME associated with NIU of any etiology and anatomic subtype were eligible for the phase 3 PEACHTREE trial of CLS-TA. Post-hoc analyses were performed, stratified by discrete anatomic subtype of uveitis (anterior, intermediate, posterior, and panuveitis.) Results Across all anatomic subtypes at 24 weeks, patients receiving CLS-TA at baseline and week 12 demonstrated mean increases in BCVA ranging from +12.1 to +15.9 letters, mean central subfield thickness (CST) improvement ranging from −120.1 µm to −189.0 µm, and IOP changes ranging from +0.5 to +3.1 mmHg. Overall, reports of adverse events were similar among subtypes. Conclusions Irrespective of the uveitic anatomic subtype among patients treated for ME associated with NIU, a clinical benefit in participants treated with CLS-TA was demonstrated, with a comparable safety profile.

XTEND: Two-Year Results from a Global Observational Study Investigating Proactive Dosing of Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration.

XTEND (NCT03939767) is a multicenter, observational, prospective study of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in routine clinical practice. The study aims to examine treatment outcomes of proactive intravitreal aflibercept (IVT-AFL) treatment regimens (fixed dosing or treat-and-extend) according to local marketing labels. Study eyes received IVT-AFL injections as per the local label. The mean changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month (M) 12 and M24 were measured and stratified by baseline factors. Treatment exposure and safety data were evaluated. Statistical analysis was descriptive. Overall, 1466 patients from 17 countries were treated. For the overall population, the mean ± standard deviation (SD) age was 78.7 ± 8.5 (range 50-100)years, and 891 patients (60.8%) were female. The mean ± SD baseline BCVA was 54.3 ± 20.3 letters and CST was 374 ± 126µm. At M12 and M24, mean (95% confidence interval [CI]) BCVA change was + 4.3 (3.4, 5.3) and + 2.3 (1.3, 3.3) letters, respectively. Mean (95% CI) CST was - 106 (- 114, - 99) μm and - 109 (- 117, - 102) μm at M12 and M24, respectively. At M24, 41.5% of patients had a BCVA ≥ 70 letters. Patients received a mean ± SD of 7.7 ± 2.7 injections by M12 and 10.8 ± 5.0 injections by M24 (3.1 injections between M12 and M24). Adverse events were consistent with the known safety profile of IVT-AFL. The 24-month results indicate that, in routine clinical practice, a proactive IVT-AFL regimen achieves functional improvements in patients with treatment-naïve nAMD. The proportion of patients achieving ≥ 70 letters at M24 increased, and patients with baseline BCVA ≥ 70 letters maintained vision regardless of the followed IVT-AFL label. ClinicalTrials.gov identifier: NCT03939767. A video abstract is available for this article. Supplementary file2 (MP4 364624 KB).

Efficacy and Safety of Faricimab for Macular Edema due to Retinal Vein Occlusion: 24-Week Results from the BALATON and COMINO Trials

To evaluate the 24-week efficacy and safety of the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A inhibitor faricimab versus aflibercept in patients with vein occlusion. Phase 3, global, randomized, double-masked, active comparator-controlled trials: BALATON/COMINO (ClincalTrials.gov identifiers: NCT04740905/NCT04740931; sites: 149/192). Patients with treatment-naïve foveal center-involved macular edema resulting from branch (BALATON) or central or hemiretinal (COMINO) RVO. Patients were randomized 1:1 to faricimab 6.0 mg or aflibercept 2.0 mg every 4 weeks for 24weeks. Primary end point: change in best-corrected visual acuity (BCVA) from baseline to week 24. Efficacy analyses included patients in the intention-to-treat population. Safety analyses included patients who received ≥ 1 doses of study drug. Enrollment: BALATON, n = 553; COMINO, n = 729. The BCVA gains from the baseline to week 24 with faricimab were noninferior versus aflibercept in BALATON (adjusted mean change,+16.9 letters [95.03% confidence interval (CI), 15.7-18.1 letters] vs.+17.5 letters [95.03% CI, 16.3-18.6 letters]) and COMINO (+16.9 letters [95.03% CI, 15.4-18.3 letters] vs.+17.3 letters [95.03% CI, 15.9-18.8 letters]). Adjusted mean central subfield thickness reductions from the baseline were comparable for faricimab and aflibercept at week 24 in BALATON (-311.4 μm [95.03% CI,-316.4 to-306.4 μm] and-304.4 μm [95.03% CI,-309.3 to-299.4 μm]) and COMINO (-461.6 μm [95.03% CI,-471.4 to-451.9 μm] and-448.8 μm [95.03% CI,-458.6 to-439.0 μm]). A greater proportion of patients in the faricimab versus aflibercept arm achieved absence of fluorescein angiography-based macular leakage at week 24 in BALATON (33.6% vs. 21.0%; nominal P= 0.0023) and COMINO (44.4% vs. 30.0%; nominal P= 0.0002). Faricimab was well tolerated, with an acceptable safety profile comparable with aflibercept. The incidence of ocular adverse events was similar between patients receiving faricimab (16.3% [n= 45] and 23.0% [n= 84] in BALATON and COMINO, respectively) and aflibercept (20.4% [n= 56] and 27.7% [n= 100], respectively). These findings demonstrate the efficacy and safety of faricimab, a dual Ang-2/VEGF-A inhibitor, in patients with macular edema secondary to retinal vein occlusion. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2years: the REBA extension study.

To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting. Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24months of follow-up. Both treatment-naïve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications. The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-naïve group and switch therapy group, respectively. BCVA gain was + 9.2 (3.7) letters (p = 0.01) and + 7.7 (3.4) letters (p = 0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-naïve group (from 432.5 (68.4) to 283.0 (51.3) µm; p = 0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) µm; p = 0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24. Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted.

Faricimab Treat-and-Extend for Diabetic Macular Edema: Two-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials

PurposeTo evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend–based regimen (T&E) with up to every-16-week (Q16W) dosing in the YOSEMITE/RHINE (NCT03622580/NCT03622593) phase 3 trials of diabetic macular edema (DME). DesignRandomized, double-masked, noninferiority phase 3 trials. ParticipantsAdults with visual acuity loss due to center-involving DME. MethodsPatients were randomized 1:1:1 to faricimab 6.0 mg Q8W, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg Q8W. The T&E up to Q16W dosing regimen was based on central subfield thickness (CST) and best-corrected visual acuity (BCVA) change. Main Outcome MeasuresIncluded changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. ResultsIn YOSEMITE/RHINE (N=940/951), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92/96/100 average) with faricimab Q8W (YOSEMITE/RHINE, +10.7/+10.9 letters) or T&E (+10.7/+10.1 letters) were comparable with aflibercept Q8W (+11.4/+9.4 letters). The median number of study drug injections was lower with faricimab T&E (YOSEMITE/RHINE, 10/11 injections) versus faricimab Q8W (15 injections) and aflibercept Q8W (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was further improved during year 2, with >60% of patients on Q16W dosing and ∼80% on ≥Q12W dosing at week 96. Almost 80% of patients who achieved Q16W dosing at week 52 maintained Q16W dosing without an interval reduction through week 96. Mean CST reductions were greater, and more patients achieved absence of DME (CST <325μm) and absence of intraretinal fluid with faricimab Q8W or T&E versus aflibercept Q8W through year 2. Overall, faricimab was well tolerated, with a safety profile comparable to aflibercept. ConclusionsClinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to Q16W were maintained through year 2. Faricimab given as a personalized T&E–based dosing regimen supports the role of dual angiopoietin-2/VEGF-A inhibition to promote vascular stability and provide durable efficacy for patients with DME.

Normative optical coherence tomography reference ranges of the optic nerve head, nerve fiber layer, and macula in healthy Saudi children.

To use the Cirrus high-definition (HD)-OCT to establish normative data for the macula and optic disc in healthy Saudi children and to examine the effect of age and gender on these parameters. This retrospective study was carried out at King Abdulaziz University Hospital (KAUH), Saudi Arabia from November 2022 to April 2023. The study involved 135 full-term and healthy Saudi children aged 4-18 years who were evaluated at the KAUH ophthalmology clinic. Detailed demographic and ocular disease history data were obtained from the patients' medical records. The main outcome measures of the study included measurements of retinal nerve fiber layer (RNFL) thickness, macular thickness, and optic nerve head (ONH). The mean macular volume was 9.9mm3, the mean macular thickness was 275.9 μm, and the mean central subfield thickness was 240.6 μm. There was no significant association between age and the macular values, except for the superior inner macula. Boys had significantly thicker central macula than girls, while the RNFL quadrants were not different between age groups and genders. The mean values for RNFL thickness, disc area, rim area, and cup volume were 93.9 μm, 2mm2, 1.6mm2, and 0.3mm3, respectively. The vertical ratio of cup to disc was 0.4. Normative values for macular and optic nerve measures among Saudi children were established using the Cirrus HD-OCT device to serve as a reference.

Efficacy and Safety of Brolucizumab for Diabetic Macular Edema

Despite the effectiveness of existing anti-vascular endothelial growth factor (VEGF) therapies, a need remains for further treatment options to improve response rates and/or reduce injection or monitoring frequency in patients with diabetic macular edema (DME). To evaluate the efficacy and safety of brolucizumab vs aflibercept dosed every 4 weeks in participants with DME. This 52-week, double-masked, phase 3 randomized clinical trial included treatment-naive adults and adults who had previously received anti-VEGF therapy. Data were collected from September 2019 to March 2020, and data were analyzed from April 2020 to February 2021. Brolucizumab, 6 mg, intravitreal injection every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks. Participants were randomized 2:1 to brolucizumab, 6 mg, or aflibercept, 2 mg. The primary end point was change from baseline in best-corrected visual acuity at week 52. Secondary end points were the proportion of participants with a 2-step improvement or greater from baseline in Diabetic Retinopathy Severity Scale score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, change from baseline in central subfield thickness, and safety at week 52. A total of 517 participants were randomized to brolucizumab (n = 346) or aflibercept (n = 171); 299 (57.8%) were male, and the mean (SD) age was 60.7 (10.2) years. Brolucizumab was noninferior to aflibercept in best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score) change from baseline at week 52 (brolucizumab, 12.2-letter improvement; aflibercept, 11.0-letter improvement; difference, 1.1; 95% CI, -0.6 to 2.9; noninferiority margin, 4; P < .001). Brolucizumab was superior to aflibercept for the proportion of eyes without subretinal and intraretinal fluid (brolucizumab, 144 of 346 [41.6%]; aflibercept, 38 of 171 [22.2%]; difference, 20.0%; 95% CI, 12.5to 28.6; P < .001) and mean central subfield thickness change from baseline at week 52 (brolucizumab, -237.8 μm; aflibercept, -196.5 μm; difference, -41.4; 95% CI, -58.9 to -23.8; P < .001). Incidence of intraocular inflammation was 4.0% (14 of 346) in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, incidence of retinal vasculitis was 0.9% (3 of 346) and 0.6% (1 of 171), respectively, and incidence of retinal vascular occlusion was 0.3% (1 of 346) and 0.6% (1 of 171). One participant in the brolucizumab arm had retinal artery occlusion. In these study participants with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms; some superior anatomic improvements were noted in the brolucizumab arm. No new safety concerns were identified. ClinicalTrials.gov Identifier: NCT03917472.

Multimodal Structural and Functional Characterization of Retinal Vasculopathy with Cerebral Leukoencephalopathy

ObjectiveTo describe and quantify the structural and functional consequences of retinal vasculopathy and cerebral leukoencephalopathy (RVCL) on the neurosensory retina. DesignCross-sectional descriptive study from December 2021 to December 2022 ParticipantsRVCL patients (n=9, 18 eyes) recruited from the RVCL Research Center at Washington University in St. Louis MethodsRVCL patients underwent comprehensive ophthalmological evaluation including Optical Coherence Tomography (OCT), Optical Coherence Tomography Angiography (OCT-A), ultra-wide-field (UWF) fundus imaging, retinal autofluorescence, dark adaptation, electroretinography (ERG), Goldmann kinetic perimetry, and fluorescein angiography (FA). Main Outcomes MeasuresComprehensive characterization from various modalities including: best corrected visual acuity, central subfield thickness (μm) from OCT, foveal avascular zone (mm2) from OCT-A, dark adaptation rod intercept (sec), cone response in ERG, and presence or absence of vascular abnormalities, leakage, neovascularization, and nonperfusion on FA. ResultsA total of 18 eyes from 9 individuals were included in this study. The best-corrected visual acuity ranged from 20/15 to 20/70. The mean central subfield thickness from OCT was 275.8 μm (range 217-488 μm). The mean foveal avascular zone (FAZ) from OCT-A was 0.65 mm2 (range 0.18-1.76 mm2). On dark adaptometry, the mean time was 5.02 minutes (range 2.9 - 6.5 min) with 1 individual with impaired dark adaptation. ERG demonstrated mild cone response impairment in 4 eyes. On FA, there was evidence of macular and peripheral capillary non-perfusion in 16 of 18 eyes and notable areas of vascular leakage and retinal edema in 5 of the 18 eyes. ConclusionsThis study illustrates the phenotypic spectrum of disease and may be clinically valuable for aiding diagnosis, monitoring disease progression, and further elucidating the pathophysiology of RVCL to aid in the development of therapies.

Neovascular Age-Related Macular Degeneration in a Predominantly Black Population.

We intend to study the characteristics and outcomes of an understudied patient population with neovascular age-related macular degeneration (nAMD). This retrospective study evaluated presenting features and outcomes in a predominantly Black patient population with nAMD. A multivariate regression explored baseline characteristics predictive of 1-year vision. Sixty-three eyes were included. The median (interquartile range) baseline vision was 20/300 (20/80 to counting fingers). Patients' baseline optical coherence tomography findings showed a mean central subfield thickness of 336 µm; 80% (n = 35) and 41% (n = 18) had fluid and central scarring, respectively. The primary predictor for vision at year-one was baseline vision (P = 0.03, 95% CI: 0.04 to 0.91). All of those who gained ≥ 3 lines of vision lacked central scarring at baseline. Further studies are needed to investigate how to improve earlier detection and treatment of nAMD in this patient population. [Ophthalmic Surg Lasers Imaging Retina 2023;54:580-584.].

Short-Term Outcomes of Faricimab in Patients with Neovascular Age-Related Macular Degeneration on Prior Anti-VEGF Therapy

A subset of patients with neovascular age related macular degeneration (nAMD) experience treatment burden and suboptimal response with anti-vascular endothelial growth factor (anti-VEGF) therapy. The aim of this study was to investigate the effect of switching to a novel bi-specific agent, faricimab, in patients with nAMD currently treated with anti-VEGF. Retrospective, non-comparative cohort study. Patients with nAMD previously treated with anti-VEGF and switched to intravitreal faricimab injection (IFI) at the Cleveland Clinic's Cole Eye Institute. Switching and administration schedule of IFI was at the discretion of the clinician. Visual acuity (VA) and macular optical coherence tomography (OCT) parameters, including central subfield thickness (CST), maximum pigment epithelial detachment (PED) height and presence of subretinal (SRF) or intraretinal fluid (IRF), were assessed at baseline (day of first IFI) and after each IFI. CST and presence of IRF or SRF after at least 3 IFI. 126 eyes of 106 patients were included in the analysis with a mean follow-up time of 24.3±5.2 weeks. Prior to switching to IFI, patients received a mean of either aflibercept (20.0±18.4, mean±SD), bevacizumab (7±8.9), ranibizumab (1.9±8.5), or brolucizumab (0.3±1.6) injections. The most common agent used prior to switching to IFI was aflibercept (n=110, 87%), and the mean treatment interval with any anti-VEGF of 5.6±1.6 weeks prior to switching. CST was reduced from baseline after the first IFI (266.8±64.7 vs 249.8±58.6um, p=0.02) and persisted over the 3 IFIs (p=0.01). PED height was reduced after the 3rd IFI (249.6±179.0 vs 206.9±130.0um, p=0.01). Mean VA (62.9 vs 62.7 approximate EDTRS letters, p=0.42) and interval between injections was similar after the 3rd IFI compared to baseline (6.3 vs 5.7 weeks, p=0.16). Eleven (8.7%) eyes were switched back to their previous anti-VEGF, including 2 (1.6%) eyes from 1 patient with intraocular inflammation requiring cessation of IFI. There were no other adverse events from switching. Switching to faricimab resulted in a reduction in mean CST (-11.6um, p=0.01) and PED height (-44.2um, p=0.01) after 3 injections with stable VA and at a similar treatment interval to prior anti-VEGF therapy.

Short-pulse laser plus subthreshold diffuse laser for serous retinal detachment in dome-shaped macula

BackgroundFirst described by Gaucher and associates in 2008, dome-shaped macula (DSM) is an anterior convex protrusion of the macula visible on OCT (optical coherence tomography). Visual impairment in DSM results mainly from sub-foveal serous retinal detachment (SRD). Herein, this original study from retrospective data analysis evaluate the anatomical and functional effects of Pascal® short-pulse (SP) laser plus endpoint management (EpM) subthreshold diffuse laser (SDL) in patients with SRD due to DSM.MethodsThis retrospective study included seven consecutive patients (eight eyes) with SRD secondary to dome-shaped macula who underwent a comprehensive ophthalmological evaluation including logMAR BCVA, slit-lamp biomicroscopy, indirect ophthalmoscopy, and spectral-domain optical coherence tomography (SD-OCT) (Spectralis; Heidelberg Engineering, Germany) before combined Pascal® SP laser plus EpM-SDL with 1 to 6 month intervals, postoperatively, with a mean ± standard error (SE) follow-up time of 12.92 ± 1.34 months.ResultsEight eyes from seven patients were analyzed in this study. At baseline, mean BCVA (LogMAR) ± standard error (SE) and mean CST (central subfield thickness)(µm) ± SE were 0.6125 ± 0.14 and 412.50 ± 24.65, respectively. After a mean follow-up time of 12.92 ± 1.34 months, mean CST (µm) ± SE and BCVA (LogMAR) ± SE were 294.75 ± 19.68 (p = 0.0078) and 0.4537 ± 0.12 (p = 0.0313), respectively. A statistically significant reduction in mean CST and an improvement in mean BCVA were noted after SRD resolution with laser therapy application. The mean serous retinal detachment resolution time (months) ± SE was 3.75 ± 1.08. No adverse events were registered, including enlargement of atrophic alterations and choroidal neovascularization.ConclusionsThe novel combined laser modality with Pascal® SP laser plus EpM-SDL treatment may induce subretinal fluid regression and BCVA improvement 1 year after treatment in DSM patients with SRD.

Normative Data for Macular Thickness and Volume for Optical Coherence Tomography in a Diabetic Population without Maculopathies.

The purpose was to establish normative data for the macular thicknesses and volume using spectral-domain optical coherence tomography (SD-OCT) in a diabetic population without maculopathies for use as a reference in diabetic retinopathy (DR) and diabetic macular edema screening programs. This was an observational study nested in a cohort of diabetics from a telemedicine DR screening program. Each patient underwent SD-OCT centered on the fovea. Macular thickness and volume were described and compared using the built-in normative database of the device. Quantile regression models for the 97.5% percentile were fitted to evaluate the predictors of macular thickness and volume. A total of 3410 eyes (mean age, 62.25 (SD, 0.22) years) were included. Mean (SD) central subfield thickness (CST) was 238.2 (23.7) µm, while center thickness (CT), average thickness (AT), and macular volume (MV) were 205.4 (31.6) µm, 263.9 (14.3) µm, and 7.46 (0.40) mm3, respectively. Para- and perifoveal thicknesses were clinically and statistically significantly thinner in our population than in the normative reference database. The 97.5% percentile of the thickness of all sectors was increased in males and in the para- and perifovea among those with DR. All ETDRS sectors were thinner in patients with diabetes than in the reference population, except for the CST, which was the most stable parameter that only changed with sex. The upper cutoff limit to detect diabetic macular edema (DME) was different from that of the reference population and was influenced by conditions related to diabetes, such as DR. Therefore, specific normative data for diabetic patients should be used for the screening and diagnosis of DME using SD-OCT.

Aflibercept for Diabetic Macular Edema in Real-Life Practice in GREece: Three-Year Outcomes of the ADMIRE Study

ABSTRACT Purpose To evaluate the efficacy and safety of intravitreal aflibercept injections for diabetic macular edema (DME) treatment in a tertiary referral center in Greece. Methods ADMIRE was a prospective, observational cohort study of patients with DME. Efficacy was assessed by change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month 36 after treatment with intravitreal aflibercept in treatment-naive patients and previously treated patients. Safety was evaluated by recording any patients-reported events. Results Participants in the study were 94 patients with DME, 70 treatment naive and 24 previously treated with ranibizumab. At month 36 of the follow-up period, the mean change in BCVA was +7.4 letters compared to baseline (p < .001). The mean change in BCVA in treatment-naive patients was +8.9 letters and differed significantly compared to previously treated patients (+5.9 letters, p = .041). In addition, patients who received a loading dose of 5 monthly injections at the initiation of treatment provided better VA outcomes (+11.4 vs. +6.1 letters, p < .001). Accordingly, the mean CST at month 36 (369.6 ± 72.8 μm) was significantly decreased compared to baseline (479.2 ± 68.3 μm, p < .001). Overall, the mean number of injections at month 36 was 13.4. Safety analysis showed that the reported ocular adverse events during the 36-month study period were mild and not sight-threatening. Conclusion Intravitreal aflibercept was found to be safe and effective for the treatment of DME in real-life in a Greek population. Treatment-naive patients and those who received a loading dose of five consecutive monthly injections at initiation of treatment exhibited better outcomes, suggesting that early and effective treatment may prevent vision loss.