Baseline Best-corrected Visual Acuity Research Articles

Autologous internal limiting membrane transplantation achieves anatomic closure and functional improvement in the treatment of large, persistent macular holes

PurposeTo evaluate the clinical outcome of subretinal autologous internal limiting membrane (ILM) transplantation during pars-plana vitrectomy for persistent full-thickness macular hole (FTMH) repair.MethodsRetrospective, consecutive case series of 13 eyes (13 patients) undergoing small-incision vitrectomy with ILM transplantation and air tamponade for large persistent FTMH after prior unsuccessful vitrectomy with posterior hyaloid detachment and ILM peeling.Main outcome measurementsFor all eyes, high-definition spectral domain optical coherence tomography scans (SD-OCT Spectralis, Heidelberg Engineering GmbH, Germany) of the macula were routinely performed before surgery, 1 and 4 weeks after surgery, and at the final follow-up visit. Additionally, age, gender, axial length, macular hole diameter, biomicroscopic fundus evaluation and best‐corrected visual acuity (BCVA) at baseline, 1 and 4 weeks after surgery, and at the final follow-up visit were analyzed.ResultsAnatomic closure was achieved in all 13 cases (100% success rate). Closure pattern was classified in accordance with to Rossi et al. (Graefe’s Arch Clin Exp Ophthalmol 258(12):2629–2638, 2020). Mean baseline BCVA logMAR was 0.93, mean postoperative BCVA logMAR was 0.66 with a mean postoperative follow-up period of 11.4 months. No re-opening occurred during the observation period.ConclusionsPlacing an autologous ILM-transplant in the subretinal space beneath the margin of the FTMH can support anatomic restauration and functional improvement in large, persistent FTMHs.

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).

Optical coherence tomography characteristics and factors affecting visual acuity in diabetic papillopathy.

To analyse baseline imaging characteristics and factors affecting poor visual acuity in diabetic papillopathy. This was a retrospective, observational study conducted at a tertiary eye care centre in eyes with a diagnosis of diabetic papillopathy. Demographic data including age, gender, duration of diabetes, type of diabetes, HbA1c values and other systemic co-morbidities were recorded. Baseline best corrected visual acuity (BCVA), and various imaging characteristics were noted. 37 eyes of 22 patients with diagnosis of diabetic papillopathy were included [mean age of 46.6 ± 13.5 years, five (22.7%) females and 17 (77.3%) males]. Bilateral involvement was seen in 15 (68.2%) patients. The mean baseline BCVA was 0.51 ± 0.49 logMAR (Snellen equivalent 20/60). Two eyes (5.4%) had features of concurrent mild NPDR, 9 eyes (24.3%) had moderate NPDR, 10 eyes (27.03%) had severe NPDR while 16 (43.2%) other had PDR. All eyes had optic disc edema while 4 had disc pallor at presentation. Telangiectatic vessels/ neovascularisation of disc was present in 17 eyes (45.9%) detected either clinically or on optical coherence tomography (OCT) angiography. 11 (29.7%) eyes had a peripapillary cuff of subretinal fluid accompanying the disc edema. Sixteen eyes (43.2%) had centre involving macular edema seen on OCT. In eyes with a macular edema, the mean central macular thickness was 407.4 ± 71.42 microns at baseline. On assessing the baseline factors that contribute to the final visual acuity, presenting visual acuity was the only variable found to be statistically significant. Although described to have good visual outcome, eyes presenting with poor visual acuity tend to have worse vision on follow up. This may aid in prognosticating and guiding management plan.

Phacoemulsification in patients with diabetic macular edema - A real-world data of 75 eyes.

The purpose of this study was to evaluate the outcomes of phacoemulsification with intravitreal triamcinolone acetonide (IVTA) injection in patients with cataract and diabetic macular edema (DME) across the grades of diabetic retinopathy (DR). It was a retrospective observational study. The study included 70 patients (75 eyes) with cataract and clinically significant macular edema in diabetics with nonproliferative (61 eyes) or proliferative (14 eyes) DR who underwent phacoemulsification with IVTA. Visual outcome and progression of DME over 3 months were studied in terms of the best-corrected visual acuity (BCVA) and central macular thickness (CMT), respectively. The case records of 70 patients (75 eyes) were studied. The mean baseline BCVA (n = 75) in the logMAR scale ± SD was 0.92 ± 0.53. 3 weeks after the surgery, the mean BCVA improved to 0.39 ± 0.26 and the mean CMT (n = 40) was 382.57 ± 192.30 compared with the mean preoperative CMT of 480.57 ± 163.25 in the same set (P = 0.01). The mean CMT decreased at 3 weeks in 22 (55% of the eyes). An improvement of ≥2 lines was seen at 3 weeks in 52 (69.33%) eyes and in 49 (65.33%) eyes at 3 months. The mean CMT at 3 months was 445.51 ± 222.99 (n = 70) compared to the preoperative mean CMT of 470.72 ± 176.15 in the same set (P = 0.29). The mean CMT decreased at 3 months in 34 (48.5%) eyes. Phacoemulsification with IVTA injection improved the mean visual acuity at 3 weeks and 3 months in two-thirds of cases and decreased the mean CMT at 3 weeks in nearly half the numbers.

Frequency and visual outcomes of herpes simplex keratitis in a Kuwaiti tertiary referral center.

Herpes simplex virus (HSV), a cause of many ocular pathologies, may affect the corneal epithelium, stroma, or endothelium, with the epithelium as the most frequently affected location. We aimed to determine the frequency and visual outcomes of HSV keratitis over a 1-year period at Farwaniya Hospital, Kuwait. This prospective observational case series included patients diagnosed with HSV keratitis who presented to the outpatient or eye casualty department between September 2022 and September 2023. Full history, demographic profile, detailed ocular and slit-lamp examinations, and visual acuity assessments were recorded prior to and after treatment. Baseline corneal sensation was assessed in the four corneal quadrants using the cotton wisp test. Of the 227 patients who presented with infectious keratitis, 72 (31.7%) were diagnosed with HSV keratitis. The mean (SD) age was 45.86 (16.06) years, and 48 (66.7%) patients were male. The subtypes of HSV keratitis were endotheliitis in 27 (37.5%) patients, dendritic ulcer in 22 (30.6%), stromal keratitis with ulceration in 9 (12.5%) and without ulceration in 8 (11.1%), and geographic ulcer in 6 (8.3%). The mean baseline best-corrected distance visual acuity (BCDVA) differed significantly between the HSV keratitis subtypes (P < 0.001). Most patients (n = 70, 97.2%) had unilateral eye involvement, were treated within 1 - 2 weeks, and demonstrated improved BCDVA. Despite the improvement in BCDVA in all HSV keratitis subtypes, a significant difference in the median BCDVA remained after treatment (P < 0.001). Pairwise comparisons revealed a significantly better BCDVA after treatment in eyes with dendritic epithelial ulcers than in eyes with HSV stromal keratitis with ulceration (P = 0.003) or geographic epithelial ulcers (P = 0.005). After treatment, corneal haze and neovascularization were detected in 54 (75.0%) and 24 (33.3%) patients, respectively. We detected a substantial frequency of HSV keratitis in one of the governorates of Kuwait, with endotheliitis as the most common manifestation. Timely standard treatment interventions based on valid guidelines resulted in BCDVA improvement in all subtypes of HSV keratitis in our series, indicating the importance of early treatment. However, the BCDVA in eyes with dendritic epithelial ulcers remained substantially better than that in eyes with geographic epithelial ulcers or HSV stromal keratitis with ulceration, signifying the effect of the initial HSV keratitis subtype on visual outcomes. To our knowledge, this is the first study to highlight the frequency of HSV keratitis in a Kuwaiti hospital, and larger-scale research in this region is needed to further understand and manage the condition.

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.

Evaluation of the First-Dose Anti-VEGF Anatomical Response in Polypoidal Choroidal Vasculopathy Patients: Correlation with the Third-Dose Response and Risk Factor Analysis

Introduction: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. Methods: We retrospectively reviewed patients’ medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. Results: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. Conclusion: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV.

Optical coherence tomography angiography for macular microvessels in ischemic branch retinal vein occlusion treated with conbercept: predictive factors for the prognosis.

To evaluate the predicative factors of visual prognosis using optical coherence tomography angiography (OCTA) in ischemic branch retinal vein occlusion (BRVO) patients with macular edema (ME) after anti-vascular endothelial growth factor (VEGF) treatment. In this retrospective analysis, data from 60 patients (60 eyes) with a definite diagnosis of ischemic BRVO with ME by fundus fluorescein angiography (FFA) were studied. The eyes with ME according to spectral domain optical coherence tomography (SD-OCT) underwent intravitreal conbercept (IVC) and 3+pro re nata (PRN) regimen. The injection times were recorded. Two weeks after injection, fundus laser photocoagulation was performed in the non-perfusion area of the retina. The patients were followed up once a month for 6mo. The best-corrected visual acuity (BCVA), foveal avascular zone (FAZ), and A-circularity index (AI), at 6mo and the baseline were compared. All patients showed significant improvement in BCVA from 0.82±0.32 to 0.39±0.11 logMAR (P<0.001). The mean central macular thickness (CMT) significantly decreased from 476.22±163.54 to 298.66±109.23 µm. Both the FAZ area and AI at 6mo were significantly higher than those at the baseline: the FAZ area increased (0.38±0.02 vs 0.39±0.02 mm2, P<0.05); the AI increased (1.27±0.02 vs 1.31±0.01, P=0.000). The baseline BCVA showed a significantly positive correlation with the baseline FAZ area, FAZ perimeter (PERIM) and AI, final visual gain (FVG) and injection times, respectively (P<0.001). FVG showed a significantly negative correlation with the FAZ area, PERIM, AI and injection times, but a significantly positive correlation with vessel densities (VDs) 300 µm area around FAZ (FD-300; P<0.001). Injection times was positively correlated with the baseline FAZ area, and AI, but inversely correlated with the baseline FD-300 (P<0.001). However macular ischemia was noted in 5 cases during follow-up. Using OCTA to observe macular ischemia and quantify parameters can better predict the final visual prognosis of patients before treatment. The changes in FAZ parameters may influence the visual prognosis and injection times.

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.

A Pilot Study: Assessment of Therapeutic Effects 670 nm Photobiomodulation on Amblyopia

Purpose: To evaluate positive effects of photobiomodulation in amblyopia treatment in patients with 8-13 year of age. Study Design: interventional case series. Place and Duration of Study: Shahid Beheshti University of Medical Sciences, Iran. Methods: This study was conducted on 16 subjects with strabismic amblyopia. Subjects were assigned to two groups: Photobiomodulation (PBM) and control group. In the PBM group, patients used a portable device (Warp 10, Quantum device) in home 3 times a week. The amblyopic eye were irradiated by a device which emitted670 nm red light with 25 Joules/cm2 energy for 4 minutes. After irradiation, patients performed near work for 10 minutes. In the control group, patients were treated by using part time occlusion of non-amblyopic eye and near work for 3 months. Ophthalmic assessments including best corrected visual acuity (BCVA), refractive evaluation, slit lamp biomicroscopy, and funduscopy were performed before and four weeks, and three months after treatment. Results: In the PBM group, the mean baseline BCVA was 0.24 ± 0.15 that improved to 0.49 ±0.24 in the third month after treatment. In the control group, the mean initial BCVA was 0.30 ± 0.20 that increased to 0.44 ± 0.23 after three months. Our results showed improvement of 2.50 ± 1.16 lines in the PBM group (P&lt;.001) and 1.38 ± 0.72 lines in the control group (P=0.040). Our assessments showed no adverse related to the PBM in patients. Conclusion: PBM facilitates and accelerates the occlusion therapy in amblyopia and it can be considered a treatment option for amblyopia.

Prevention of Ocular Toxicity Using Protective Contact Lenses in Multiple Myeloma Patients Receiving Belantamab Mafodotin, Pomalidomide and Dexamethasone: A Sub-Study of the Cmrg-007 Trial

Background: Belantamab mafodotin (belamaf) is a monomethyl auristatin-F containing antibody drug conjugate that targets BMCA on myeloma cells. Single agent belamaf has shown clinical meaningful activity in relapsed/refractory multiple myeloma (RRMM) but ocular adverse events (AEs) affect 53-72% of trials'participants. In DREAMM-2, prophylactic corticosteroid eye drops did not effectively reduce the risk of keratopathy. It is therefore imperative that strategies to mitigate corneal AEs be explored. This 2-part study is designed to evaluate belamaf and pomalidomide/dexamethasone (Pd) in RRMM. Here we report the efficacy and ocular AEs of patients (pts) receiving 2.5 mg/kg (maximum tolerated dose) or 1.92 mg/kg IV belamaf and administrated on various schedules aimed to define the optimal balance of efficacy and tolerability. We also present results of an ocular sub-study exploring the use of bandage contact lens (BCLs) to reduce the risk and severity of belamaf-associated ocular AEs. Methods: Eligibility: &amp;gt; 1 prior lines of therapy (LoT), lenalidomide, proteasome inhibitors exposed, and refractory to the last LoT. Pd was administered per standard of care and belamaf (1.92 or 2.5 mg/kg) Q4W or 2.5 mg/kg Q8W, Q12W or SPLIT equally on days 1 and 8, Q4W. Pts enrolled on the ocular sub-study received the recommended part two dose (RP2D): 2.5 mg /kg Q8W. A BCL (Bausch and Lomb Pure Vision) was placed in the right (R) eye for the 1st 2 doses of belamaf with the left (L) eye serving as control. Subsequently, BCLs were placed in both eyes. Pts wore BCLs for up to 28 days after each belamaf dose. Evaluation by an eyecare specialist for a comprehensive eye exam and BCL placement occurred every 15-28 days during BCLs use and prior to each belamaf dose. Corneal findings were graded (Gr) by the keratopathy and visual acuity (KVA) scale and findings of local infection were reported. Keratitis prophylaxis during BCLs use included gatifloxacin 0.3% or tobramycin 1.3% eye drops. Results: This analysis comprises 92 pts including 14 on the ocular sub-study. Baseline best corrected visual acuity (BCVA) and ocular comorbidities were similar across all cohorts: with median 20/20 BCVA 46.7% R and 50% L eye. Abnormal fundoscopy was 21.7% in R and 16.3% in L eye. There was a trend to lower incidence and less severity of ocular AEs for the 1.92 mg/kg dose (Table 1). Gr 3-4 keratopathy, decrease in BCVA and subjective Gr &amp;gt;2 blurred vision by CTCAE were 33.3% (4/12), 41.7% (5/12) and 25% (3/12) for the 1.92 mg/kg and 75% (9/12), 75% (9/12) and 33.3% (4/12) for 2.5 mg/kg Q4W cohorts. Preliminary data indicated superior clinical efficacy (ORR, &amp;gt;VGPR rate and mPFS) for the 2.5 mg/kg dose, 100% (12/12), 91.7% (11/12) and 25.1 months (11.8-NYR) versus 66.7% (8/12), 63.6% (7/12) and 16.9 months (5.3-19.7) for the 1.92 mg/kg dose (Table 2). To preserve efficacy but reduce ocular AEs additional cohorts exploring 2.5 mg/kg dosed every 8 and 12 weeks were included. Extended dosing schedules showed lower rates of Gr 3-4 keratopathy, decrease in BCVA, and Gr ≥2 blurred vision: 58.3% (7/12), 91.7% (11/12) and 16.7% (2/12) of pts treated Q8W; and 58.3%, 58.3% and 16.7% (2/12) of pts treated Q12W versus the Q4W schedule. Importantly, the efficacy was preserved with ORRs of 91.7% (11/12) and 100% (11/11), &amp;gt;VGPR rates of 83.3% (10/12) and 63.6% (7/11) and mPFS of 18.3 months (95% CI: 10.1-NYR) and 22.5 (95% CI: 8.9-NYR) for Q8W and Q12W groups, respectively. In the ocular sub-study, assessment of R and L eye during the first 2 belamaf doses showed a significant delay in onset of BCVA decrease in the R eye (p&amp;lt;0.0001) compared to the L. Comparing pts treated at the RP2D, moderate to severe (Gr ≥2) keratopathy and decrease BCVA were significantly lower (p=0.0004 and 0.010), in the BCL cohort versus no-BCL group. Further there was a trend towards less symptomatic blurred vision (p=0.256). BCL pts were able to complete 90% of the pre-planned belamaf cycles compared to 70% in the RP2D no-BCL group (p=0.029). No cases of infectious keratitis were reported in the BCL cohort. Conclusions: Our data suggest that extended dosing intervals may be a significant step forward in mitigating corneal AEs of belamaf. This preliminary report on the efficacy of BCLs in 14 pts demonstrates a decrease in moderate to severe corneal AEs and reduction in dose holds for corneal AEs, noting however a short follow up at this time. The data support the further evaluation of BCLs in preventing belamaf associated ocular toxicities.

Vitreomacular traction in diabetic retinopathy.

Vitreomacular traction (VMT) has unique presentations in eyes with diabetic retinopathy (DR). This study aimed to investigate the characteristics and clinical course of VMT in DR. A retrospective case series. Thirty eyes from 30 patients with DR and concurrent VMT were retrospectively enrolled. Baseline and final best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) characteristics were reported. Linear regression models were used to analyze the correlating factors for visual outcome. Of the 30 eyes, a thickened posterior hyaloid membrane was noted in all cases and multi-layered traction from different directions in 14 eyes (46.7%). Twenty-one eyes (70%) had tractional macular retinoschisis, seven (23.3%) had foveal detachment, five (16.7%) had a lamellar macular hole, and three (10%) had a full-thickness macular hole, including two with macular hole retinal detachment. Three eyes had spontaneous release of the VMT within 3 months of observation. For the remaining 27 eyes receiving operations, the VMT, full-thickness macular hole, and serous foveal detachment all resolved postoperatively with residual macular schisis in 6 eyes (22.2%) only. None of the baseline OCT characteristics were associated with postoperative BCVA (P > .05). VMT in DR had a thickened posterior hyaloid, and many of them had multi-layered traction and/or concurrent macular retinoschisis. Lamellar macular hole, full-thickness macular hole, or concurrent retinal detachment may also occur. Spontaneous resolution of VMT rarely occurred, and those who underwent operation for VMT had improved vision and macular structures with resolution of the macular hole and retinal detachment.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2mg (0.05ml) in the study eye every 4weeks for the first 3months, followed by 2mg every 8weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changeswas - 1.1 letters(95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

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.

Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial

PurposeThe purpose of this study was to assess the safety, tolerability, and potential efficacy of topical elamipretide in patients affected with Leber’s Hereditary Optic Neuropathy (LHON). DesignThis Phase 2, prospective, randomized, vehicle controlled, single-center clinical trial involved administration of elamipretide (MTP-131) topical ophthalmic solution to LHON patients over a 52-week double-masked treatment period (DMTP), followed by an open extension label (OLE) for up to 108 additional weeks of treatment. SubjectsTwelve patients affected with LHON were included in this study. Patients between ages 18 and 50 with decreased vision, for at least one year and no more than ten years, and a genetically confirmed diagnosis of m.11778G>A LHON were eligible for this trial. MethodsFor the first 52 weeks of the study, patients were randomized to one of two arms, elamipretide in both eyes or elamipretide in one eye and vehicle in the other eye, followed by an OLE where both eyes were treated with elamipretide. Main outcome measuresThe primary outcome measure was the assessment of adverse events from the administration of topical elamipretide 1% and the primary efficacy endpoint was change in best corrected visual acuity (BCVA). Secondary outcome measures included changes in color vision, visual field mean deviation, and electrophysiological outcomes. ResultsElamipretide was well tolerated with the majority of treatment-emergent adverse events (TEAEs) being mild to moderate and resolving spontaneously. The change from baseline in BCVA in elamipretide-treated eyes was not significantly different from the vehicle eyes at any time point. Six of 12 subjects met the criteria for clinically relevant benefit (CRB). In the post-hoc analysis, change from baseline in mean deviation in the central visual field was significantly greater in elamipretide treated eyes versus the vehicle eyes. Compared to baseline, both treatment groups showed improvement in color discrimination and contrast sensitivity in the OLE. ConclusionsElamipretide treatment was generally well tolerated with no serious adverse events reported. Although this study did not meet its primary BCVA efficacy endpoint, improvements across assessments on visual function during the OLE, and the post-hoc findings of the HVF central region, were encouraging and require further exploration.

Real-world outcomes of intravitreal bevacizumab treat-and-extend for cystoid macular oedema secondary to central retinal vein occlusion.

The purpose of this study was to report the real-world treatment outcomes using a treat-and-extend intravitreal bevacizumab protocol in cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO). We conducted a retrospective case series of consecutive adult patients with CMO secondary to CRVO who presented between 1st January 2019 and 31st December 2021. All included patients were treated with bevacizumab using a treat-and-extend protocol, were followed up for a minimum of 6months and had a clinical examination including best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) at every visit. The primary outcome measure was mean change in BCVA. Thirty-three eyes of 33 patients were included in the study. The mean change in BCVA from baseline was + 24.5 (Median 18, SD 21.5) letters, with a mean follow-up duration of 18.5 (SD 8.9) months. The mean number of injections was 9.5 (SD 1.9) in year 1 and 7.8 (SD 2.8) in year 2. 87.9% of patients were still requiring active treatment, with a maximum interval achieved of 4-weekly in 18.2%, 6-weekly in 42.4%, 8-weekly in 6.1%, 10-weekly in 15.2%, and 12-weekly in 6.1%. The mean maximum interval achieved of those requiring ongoing treatment was 6.8 (SD 2.4) weeks. Multiple regression analyses showed that a higher baseline BCVA was negatively associated with mean visual acuity gain (P < 0.001) and positively associated with final BCVA (P < 0.001). The use of intravitreal bevacizumab in a treat-and-extend regimen is effective in treating CMO secondary to CRVO, in a real-world setting.

Non-Invasive Treatment of Early Diabetic Macular Edema by Multiwavelength Photobiomodulation with the Valeda Light Delivery System.

Diabetes is associated with ocular complications including diabetic macular edema (DME). Current therapies are invasive and include repeated intravitreal injections and laser therapy. Photobiomodulation (PBM) is a treatment (Tx) that utilizes selected wavelengths of light to induce cellular benefits including reduction of inflammation and edema. This single-center, open-label, post-hoc analysis explored the utility of multiwavelength PBM in subjects with DME. Analysis included review of data from patients undergoing standard clinical care with an approved and marketed PBM medical device, the Valeda® Light Delivery System. Subjects with early-stage DME with good vision (Best-corrected visual acuity (BCVA) > 20/25, logMAR > 0.1) were evaluated in clinic and treated with one series of multiwavelength PBM (Tx delivered 3x/week over 3-4 weeks; total of 9 Tx sessions). Clinical, anatomical, and safety parameters were assessed in addition to subjective quality of life. A total of 30 eyes (19 subjects) were analyzed. Subjects were predominately male (68.4%) with a mean age of 56 ± 14 years. Reductions in central retinal thickness (CRT), resolution of intraretinal fluid (IRF) and improvement in diabetic retinopathy severity scale scores were observed following PBM treatment in select patients. Baseline BCVA remained stable over the follow-up observation period of 3 months post-PBM. Approximately 64% of patients reported subjective improvements in their ocular condition and decreased influence in everyday life. Detailed OCT evaluations confirmed no safety issues related to phototoxicity up to 16 months. Early-stage DME subjects treated with Valeda multiwavelength PBM showed improvements in clinical and anatomical parameters. The Valeda multiwavelength PBM approach demonstrates a favorable safety profile with no signs of phototoxicity following an independent OCT review. PBM therapy may offer an alternative, non-invasive treatment strategy with a unique mechanism and modality for patients with early-stage DME.

Machine Learning Models for Predicting Long-Term Visual Acuity in Highly Myopic Eyes

High myopia is a global concern due to its escalating prevalence and the potential risk of severe visual impairment caused by pathologic myopia. Using artificial intelligence to estimate future visual acuity (VA) could help clinicians to identify and monitor patients with a high risk of vision reduction in advance. To develop machine learning models to predict VA at 3 and 5 years in patients with high myopia. This retrospective, single-center, cohort study was performed on patients whose best-corrected VA (BCVA) at 3 and 5 years was known. The ophthalmic examinations of these patients were performed between October 2011 and May 2021. Thirty-four variables, including general information, basic ophthalmic information, and categories of myopic maculopathy based on fundus and optical coherence tomography images, were collected from the medical records for analysis. Regression models were developed to predict BCVA at 3 and 5 years, and a binary classification model was developed to predict the risk of developing visual impairment at 5 years. The performance of models was evaluated by discrimination metrics, calibration belts, and decision curve analysis. The importance of relative variables was assessed by explainable artificial intelligence techniques. A total of 1616 eyes from 967 patients (mean [SD] age, 58.5 [14.0] years; 678 female [70.1%]) were included in this analysis. Findings showed that support vector machines presented the best prediction of BCVA at 3 years (R2 = 0.682; 95% CI, 0.625-0.733) and random forest at 5 years (R2 = 0.660; 95% CI, 0.604-0.710). To predict the risk of visual impairment at 5 years, logistic regression presented the best performance (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.816-0.912). The baseline BCVA (logMAR odds ratio [OR], 0.298; 95% CI, 0.235-0.378; P < .001), prior myopic macular neovascularization (OR, 3.290; 95% CI, 2.209-4.899; P < .001), age (OR, 1.578; 95% CI, 1.227-2.028; P < .001), and category 4 myopic maculopathy (OR, 4.899; 95% CI, 1.431-16.769; P = .01) were the 4 most important predicting variables and associated with increased risk of visual impairment at 5 years. Study results suggest that developing models for accurate prediction of the long-term VA for highly myopic eyes based on clinical and imaging information is feasible. Such models could be used for the clinical assessments of future visual acuity.

Analysing early changes of photoreceptor layer thickness following surgery in eyes with epiretinal membranes.

To analyse short-term changes of mean photoreceptor thickness (PRT) on the ETDRS-grid after vitrectomy and membrane peeling in patients with epiretinal membrane (ERM). Forty-eight patients with idiopathic ERM were included in this prospective study. Study examinations comprised best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) before surgery, 1 week (W1), 1 month (M1) and 3 months (M3) after surgery. Mean PRT was assessed using an automated algorithm and correlated with BCVA and central retinal thickness (CRT). Regarding PRT changes of the study eye in comparison to baseline values, a significant decrease at W1 in the 1 mm, 3 mm and 6 mm area (all p-values < 0.001), at M1 (p = 0.009) and M3 (p = 0.019) in the central 1 mm area, a significant increase at M3 in the 6 mm area (p < 0.001), but no significant change at M1 in the 3 mm and 6 mm area and M3 in the 3 mm area (all p-values > 0.05) were observed. BCVA increased significantly from baseline to M3 (0.3LogMAR-0.15LogMAR, Snellen equivalent = 20/40-20/28 respectively; p < 0.001). There was no correlation between baseline PRT and BCVA at any visit after surgery, nor between PRT and BCVA at any visit (all p-values > 0.05). Decrease in PRT in the 1 mm (p < 0.001), 3 mm (p = 0.013) and 6 mm (p = 0.034) area after one week correlated with the increase in CRT (449.9 µm-462.2 µm). Although the photoreceptor layer is morphologically affected by ERMs and after their surgical removal, it is not correlated to BCVA. Thus, patients with photoreceptor layer alterations due to ERM may still benefit from surgery and achieve good functional rehabilitation thereafter.

Retinal vascular arcade angle as a biomarker for visual improvement after epiretinal membrane surgery.

To investigate the changes in the temporal vascular angles after epiretinal membrane (ERM) surgery and utilize the angles to predict visual outcomes. A total of 168 eyes from 84 patients with unilateral ERM who underwent vitrectomy were enrolled from a single institution. The angles of temporal venous (anglevein) and arterial arcades (angleartery) were measured on fundus photographs. The relationships between the angles and the best-corrected visual acuity (BCVA) were explored and multivariable logistic models and receiver operating characteristic (ROC) curves were analyzed to identify the factors that predicted visual outcomes. At baseline, both angleartery and anglevein were narrower in the eyes with ERM than the fellow eyes (p < 0.001 and 0.007) but had no correlation with the baseline BCVA (p = 0.754 and 0.804). Postoperatively, the angleartery and anglevein significantly widened (both p < 0.001) and a greater BCVA improvement was associated with a greater widening of the angleartery (p = 0.029) and anglevein (p = 0.050). Multivariable logistic analyses found a narrower baseline angleartery compared to the fellow eye had a higher chance for BCVA improvement ≧ 2 lines (Odds ratio = 0.97; 95% CI, 0.94-0.99; p = 0.016). ROC curve showed the baseline difference in the angleartery between bilateral eyes predicted BCVA improvement ≧ 2 lines (area under the curve = 0.74; p = 0.035), and a 0.73 sensitivity and 0.80 specificity with a cut-off value of -27.19 degrees. The retinal vascular angles widened after ERM surgery and the fundus photograph-derived angles may serve as a highly-accessible biomarker to predict postoperative visual outcomes.