Early Treatment Diabetic Retinopathy Study Letters Research Articles

6/0 prolene double-flanged IOL sutureless scleral fixation with a 27-gauge needle for intraocular lens surgery.

To report our initial experience of a modified intraocular lens (IOL) scleral fixation technique using 6/0 prolene in a double-flanged sutureless technique with a 27-gauge needle. 29 consecutive patients with IOL surgery were retrospectively reviewed between December 2021 and October 2023. Early Treatment Diabetic Retinopathy Study (ETDRS) letters, spherical equivalent (SE), astigmatism axial degree and intraocular pressure (IOP) were evaluated at baseline, and 1, 2, 3, and 6 months postoperatively. Surgery-related complications were evaluated during follow-up. ETDRS letters or SE at 1, 2, 3, and 6 months postoperation was significantly improved compared to baseline levels. Patients with younger (estimate [SE] = 8.011 [2.485], p = 0.006), preoperative lens drop (estimate [SE] = 8.621 [2.906], p = 0.009), idiopathic cataract (estimate [SE] = 6.021 [2.099], p = 0.048), high baseline ETDRS letters (estimate [SE] = 15.449 [2.352], p < 0.001), or low baseline SE (estimate [SE] = 6.357 [2.406], p = 0.018) had the greatest improvement in ETDRS letters during follow-up. Patients with preoperative lens or IOL dislocation had a greater postoperative SE improvement than those with preoperative lens or IOL subluxation (dislocation vs. subluxation: estimate [SE] = -189.235 [70.692], p = 0.016). There were no cases of vitreous hemorrhage, cystoid macular edema, endophthalmitis, subluxation or dislocation were observed during the 6-month follow-up. Our modified IOL scleral fixation technique is a simple, safe, efficient method that avoids haptic manipulation and slippage, reduces postoperative complications, achieves completely sutureless surgery, and results in an achievement of surgical refractive goals.

Efficacy and Safety of Ranibizumab Biosimilar QL1205 in Neovascular Age-Related Macular Degeneration: A Phase III Randomized Trial

This study aimed to demonstrate the clinical equivalence of biosimilar QL1205 and reference ranibizumab, Lucentis®, in patients with neovascular age-related macular degeneration (nAMD). This was a multi-center, double-blinded, randomized controlled phase 3 trial. Treatment-naïve patients with active nAMD were randomly assigned to receive QL1205 or reference ranibizumab. Patients received intravitreal injection of QL1205 or reference ranibizumab at a dose of 0.5 mg in the study eye once every four weeks for 48 weeks. The primary endpoint was change in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8 compared to baseline level. Biosimilarity of QL1205 to reference ranibizumab was assessed with an equivalence range for the difference in BCVA letters between -3.49 and +3.49. Between June 27, 2019 and June 8, 2021, 616 patients were randomized to the QL1205 group (n=308) and the reference ranibizumab group (n=308). The mean improvement of BCVA was +6.3±9.13 ETDRS letters in the QL1205 group and +7.3±8.82 ETDRS letters in the reference ranibizumab group at week 8. Both the 90% confidence interval (CI) [-2.23, 0.13] and 95% CI [-2.46, 0.36] of the difference between the two treatment groups (P=0.1434) were within the predefined equivalence range. Safety profiles were manageable in both groups. QL1205 was biosimilar to reference ranibizumab regarding clinical efficacy, ocular and systemic safety, as well as immunogenicity and pharmacokinetics profiles in the treatment of patients with nAMD.

XOLARIS: A 24-Month, Prospective, Natural History Study of 201 Participants with Retinitis Pigmentosa GTPase Regulator-Associated X-Linked Retinitis Pigmentosa

ObjectiveTo improve the understanding of the natural disease progression of retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP). DesignA multicenter, prospective, observational natural history study over 24 months. ParticipantsMale participants aged ≥7 years with a pathogenic variant in the RPGR gene, a best-corrected visual acuity (BCVA) score of ≥34 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and a mean 68-loci retinal sensitivity (assessed by microperimetry) of 0.1–20 decibels (dB). MethodsParticipants were divided into subgroups based on their BCVA score at baseline: 34–73 (lower BCVA) or ≥74 (higher BCVA) ETDRS letters. There were 7 visits over 24 months. Main Outcome MeasuresChange from baseline in BCVA, retinal sensitivity, low luminance visual acuity (LLVA), fixation stability, contrast sensitivity, visual field, anatomical measures, 25-item Visual Function Questionnaire (VFQ-25), intraocular pressure, and adverse events (AEs). ResultsOverall, 201 participants were included. The mean (standard deviation [SD]) age was 30.3 (11.9) years in the lower BCVA subgroup (n=170) and 27.7 (10.1) years in the higher BCVA subgroup (n=31). The study eye baseline mean (SD) BCVA scores were 59.4 (10.30) and 77.3 (3.95) in the lower and higher BCVA subgroups, respectively; the lower BCVA subgroup had lower retinal sensitivity in the study eye at baseline than the higher BCVA subgroup. Over 24 months, there were small observed changes in BCVA, retinal sensitivity, LLVA, fixation, contrast sensitivity, and fundus photography findings. There were observed mean (SD) changes at 24 months in the lower and higher BCVA subgroups of −1.01 (4.67) and 0.03 (5.83) dB-steradians in the volume of full-field hill of vision, −330.6 (869.51) and −122.7 (22.01) μm in distance from foveal center to the nearest border of preserved fundus autofluorescence, −104.3 (277.80) and −207.1 (171.01) μm in central ellipsoid width, and −2.8 (9.7) and −0.6 (7.6) in VFQ-25 composite score, respectively. There was 1 death from completed suicide. There were no ocular serious AEs, and most AEs were mild/moderate. ConclusionsThis study provides evidence of the slow natural progression of XLRP over 24 months in both subgroups and provides important functional, anatomical, and safety data.

Natural History of Visual Acuity and Microperimetry-Based Functional Outcome Measures of the Macula in Patients with Geographic Atrophy: A Retrospective Chart Review Study in Germany.

Background/Objectives: Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) leading to the progressive and irreversible loss of visual function. Characteristics of GA include atrophic lesions resulting from the loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. During GA progression, atrophic lesions typically advance from the macular periphery to the center, affecting foveal light sensitivity and visual acuity. This study analyzed changes in light sensitivity and visual acuity during the natural course of GA progression using the topographic analysis of structural and functional changes based on Early Treatment Diabetic Retinopathy Study (ETDRS) charts, multimodal imaging, and microperimetry assessment. Methods: Medical chart data of GA patients between 2014 and 2022 from the Internationale Innovative Ophthalmochirurgie GbR (I.I.O.) research center (Düsseldorf, Germany) were retrospectively analyzed. All patient eyes fulfilling the phase 3 OAKS study inclusion criteria were included and followed up for 60 months. The imputation of missing measurements and dropouts was performed by linear mixed models. Results: A total of 20 GA eyes from 13 GA patients were included in the study. At the index, 53.8% of patients had bilateral GA, with 70.0% of the eyes showing multifocal GA and 30.0% subfoveal encroachment (SFE). A total of 35.0% of the eyes had 2-5, and 15.0% over 20, areas of atrophy. Over time, the GA lesion size increased from 6.4 mm2 to 11.8 mm2 (1.08 mm2/year). After an average observation time of 2.9 years, 78.6% of the initially unaffected study eyes developed SFE. The percentage of study eyes without visual impairment decreased from 55.0% to 30.0%, with mean normal-luminance best-corrected visual acuity (NL-BCVA) reducing from 63.7 to 55.7 ETDRS letters. The share of absolute scotoma points in microperimetry assessment increased from 15.7% to 43.5% while overall average macular sensitivity declined from 15.7 dB to 7.4 dB. Conclusions: The substantial deterioration of macular outcomes and visual function was comprehensively detected. The results were a documentation of structural and functional aspects of the natural progression of GA for a 60-month follow-up, providing a typical outline for AMD patients with GA.

Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials

PurposeDRCR.net Protocol T data suggest the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME enrolled in faricimab phase 3 trials with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA ≤20/50. DesignYOSEMITE/RHINE were identically designed, multicenter, randomized, double-masked, active comparator–controlled, noninferiority trials. ParticipantsAdults aged ≥18 years with center-involving macular edema secondary to type 1 or 2 diabetes. MethodsPatients were randomized to faricimab every 8 weeks (Q8W), faricimab per a personalized treat-and-extend–based regimen (T&E), or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intent-to-treat population with baseline BCVA ≤20/50 (ETDRS letters <69). Main Outcome MeasuresChanges in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. ResultsIn YOSEMITE/RHINE, 220/217 patients in the faricimab Q8W; 220/219, faricimab T&E; and 219/214, aflibercept Q8W arms had baseline BCVA ≤20/50. In both trials, mean change in ETDRS BCVA was comparable between treatments at years 1 and 2. In YOSEMITE, adjusted mean (95% CI) change from baseline in CST (μm) at year 1 was greater with faricimab Q8W (–232.8 [–243.5, –222.1]) and faricimab T&E (–217.4 [–227.9, –206.9]) versus aflibercept Q8W (–190.4 [–200.9, –179.8]; P<0.0001 and P=0.0004, respectively). The pattern was similar in RHINE: faricimab Q8W, –214.2 (–225.3, –203.1); faricimab T&E, –206.6 (–217.4, –195.7); aflibercept Q8W, –186.6 (–197.7, –175.5); P=0.0006 and P=0.0116 for faricimab arms versus aflibercept, respectively. In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. Median time to first CST <325 μm and first absence of intraretinal fluid was shorter in the faricimab arms versus aflibercept, with fewer injections on average. ConclusionsIn patients with DME and baseline ETDRS BCVA ≤20/50, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept over 2 years of treatment.

Reducing Treatment Burden for Age-Related Macular Degeneration Patients: A Systematic Review of Ranibizumab Port Delivery System

Introduction &amp; ObjectivesRanibizumab port delivery system (PDS) is a newly developed method that provides a continuous,long-term supply of ranibizumab into the vitreous, reducing the burden of monthly intravitrealinjection visits for neovascular age-related macular degeneration (nAMD) patients. This review aimsto evaluate the efficacy and safety of ranibizumab PDS in nAMD.&#x0D; MethodsAn extensive literature search was performed on 4 online databases: PubMed, Cochrane, ProQuest,and ScienceDirect. The inclusion criteria are human studies comparing ranibizumab port deliverysystem and intravitreal ranibizumab, English language, with full-text journal available. The mainoutcome measurements are best-corrected visual acuity (BCVA) in Early Treatment DiabeticRetinopathy Study (ETDRS) letters, central foveal thickness (CFT), and adverse events.&#x0D; ResultsTwo randomized controlled trials (RCTs) with a total of 638 adults were evaluated. At week 96,ranibizumab PDS reported observed mean BCVA changes from baseline (-1.0; +4.2; ETDRS letters)compared to monthly intravitreal ranibizumab (-1.1; +6.1; ETDRS letters). However, there was anincrease in mean CFT changes from baseline (+9.9; +22.3 vs ?1.3; ?35.8, ?m) and severe adverseevents frequency (22; 4 vs 4; 0) with ranibizumab PDS versus monthly intravitreal ranibizumab,respectively.&#x0D; ConclusionRanibizumab PDS showed comparable visual outcomes to intravitreal ranibizumab whiledemonstrating inferior anatomical outcomes and higher incidence of severe adverse effects. Despitethis, with fewer treatment visits required for up to 24 weeks, ranibizumab PDS can potentiallyreduce the treatment burden in nAMD patients with poor compliance. Further studies are needed toprovide better patient eligibility guidelines and recommendations for adverse event management ofranibizumab PDS.

Reducing Treatment Burden for Age-Related Macular Degeneration Patients: A Systematic Review of Ranibizumab Port Delivery System

Introduction &amp; ObjectivesRanibizumab port delivery system (PDS) is a newly developed method that provides a continuous,long-term supply of ranibizumab into the vitreous, reducing the burden of monthly intravitrealinjection visits for neovascular age-related macular degeneration (nAMD) patients. This review aimsto evaluate the efficacy and safety of ranibizumab PDS in nAMD.&#x0D; MethodsAn extensive literature search was performed on 4 online databases: PubMed, Cochrane, ProQuest,and ScienceDirect. The inclusion criteria are human studies comparing ranibizumab port deliverysystem and intravitreal ranibizumab, English language, with full-text journal available. The mainoutcome measurements are best-corrected visual acuity (BCVA) in Early Treatment DiabeticRetinopathy Study (ETDRS) letters, central foveal thickness (CFT), and adverse events.&#x0D; ResultsTwo randomized controlled trials (RCTs) with a total of 638 adults were evaluated. At week 96,ranibizumab PDS reported observed mean BCVA changes from baseline (-1.0; +4.2; ETDRS letters)compared to monthly intravitreal ranibizumab (-1.1; +6.1; ETDRS letters). However, there was anincrease in mean CFT changes from baseline (+9.9; +22.3 vs ?1.3; ?35.8, ?m) and severe adverseevents frequency (22; 4 vs 4; 0) with ranibizumab PDS versus monthly intravitreal ranibizumab,respectively.&#x0D; ConclusionRanibizumab PDS showed comparable visual outcomes to intravitreal ranibizumab whiledemonstrating inferior anatomical outcomes and higher incidence of severe adverse effects. Despitethis, with fewer treatment visits required for up to 24 weeks, ranibizumab PDS can potentiallyreduce the treatment burden in nAMD patients with poor compliance. Further studies are needed toprovide better patient eligibility guidelines and recommendations for adverse event management ofranibizumab PDS.

REDUCING TREATMENT BURDEN FOR AGE-RELATED MACULAR DEGENERATION PATIENTS: A SYSTEMATIC REVIEW OF RANIBIZUMAB PORT DELIVERY SYSTEM

Introduction and Objective: Ranibizumab port delivery system (PDS) is a newly developed method that provides a continuous, long-term supply of ranibizumab into the vitreous, reducing the burden of monthly intravitreal injection visits for neovascular age-related macular degeneration (nAMD) patients. This review aims to evaluate the efficacy and safety of ranibizumab PDS in nAMD. Methods: An extensive literature search was performed on 4 online databases: PubMed, Cochrane, ProQuest, and ScienceDirect. The inclusion criteria are human studies comparing ranibizumab port delivery system and intravitreal ranibizumab, English language, with full-text journal available. The main outcome measurements are best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters, central foveal thickness (CFT), and adverse events. Result: Two randomized controlled trials (RCTs) with a total of 635 adults were evaluated. At week 96, ranibizumab PDS reported observed mean BCVA changes from baseline (-1.0; +4.2; ETDRS letters) compared to monthly intravitreal ranibizumab (-1.1; +6.1; ETDRS letters). However, there was an increase in mean CFT changes from baseline (+9.9; -15.3 vs ?1.3; -21.3, µm) and more severe adverse events frequency (22; 4 vs 4; 0) with ranibizumab PDS versus monthly intravitreal ranibizumab, respectively. Conclusion: Ranibizumab PDS showed comparable visual outcomes to intravitreal ranibizumab while demonstrating marginally inferior anatomical outcomes and higher incidence of severe adverse effects. Despite this, with fewer treatment visits required for up to 24 weeks, ranibizumab PDS can potentially reduce the treatment burden in nAMD patients with poor compliance. Further studies are needed to provide better patient eligibility guidelines and recommendations for adverse event management of ranibizumab PDS.

A Prospective, Observational, Non-interventional Clinical Study of Participants With Choroideremia: The NIGHT Study

The NIGHT study aimed to assess the natural history of choroideremia (CHM), an X-linked inherited chorioretinal degenerative disease leading to blindness, and determine which outcomes would be the most sensitive for monitoring disease progression. A prospective, observational, multicenter cohort study. Males aged ≥18 years with genetically confirmed CHM, visible active disease within the macular region, and best-corrected visual acuity (BCVA) ≥34 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline were assessed for 20 months. The primary outcome was the change in BCVA over time at Months 4, 8, 12, 16, and 20. A range of functional and anatomical secondary outcome measures were assessed up to Month 12, including retinal sensitivity, central ellipsoid zone (EZ) area, and total area of fundus autofluorescence (FAF). Additional ocular assessments for safety were performed. A total of 220 participants completed the study. The mean BCVA was stable over 20 months. Most participants (81.4% in the worse eye and 77.8% in the better eye) had change from baseline > -5 ETDRS letters at Month 20. Interocular symmetry was low overall. Reductions from baseline to Month 12 were observed (worse eye, better eye) for retinal sensitivity (functional outcome; -0.68 dB, -0.48 dB), central EZ area (anatomical outcome; -0.276 mm2, -0.290 mm2), and total area of FAF (anatomical outcome; -0.605 mm2, -0.533 mm2). No assessment-related serious adverse events occurred. Retinal sensitivity, central EZ area, and total area of FAF are more sensitive than BCVA in measuring the natural progression of CHM.

Safety Results for Geographic Atrophy Associated with Age-Related Macular Degeneration Using Subretinal Cord Blood Platelet-Rich Plasma

PurposeTo evaluate the safety of subretinal injection of cord blood platelet-rich plasma (CB-PRP) and its possible effect in eyes affected by geographic atrophy (GA) associated with dry age-related macular degeneration (d-AMD). DesignInterventional, open-label study started in January 2021 with at 12 months of follow-up (the Si.Cord Study). This study was a single-center, nonrandomized, sequential-assigned clinical trial conducted in Rome, Italy, at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (ClinicalTrials.gov_NCT04636853). Subjects, Participants, and ControlsThirteen patients (26 eyes) with bilateral d-AMD-related GA were enrolled. One eye from each patient (with more advanced GA) underwent CB-PRP treatment, and the fellow eye was considered the control. All patients participated in follow-up at 12 months. InterventionAll 13 eyes received 23-gauge (G) vitrectomy and subretinal injection of CB-PRP using a 41-G needle. Main Outcomes and MeasuresBest corrected visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study (ETDRS) letters, central macular thickness using optical coherence tomography (OCT) and atrophic area measured on en-face OCT images were assessed at baseline, 1, 3, 6 and 12 months. ResultsThe BCVA in the treated group was 34.46 ± 20.8 ETDRS at baseline; 40.84 ± 20.52 at 1 month; 40.07 ± 20.34 at 3 months; 39.38 ± 19.84 at 6 months and 35.84 ± 18.38 at 12 months. In the untreated group, the BCVA was 53 ± 21.1 ETDRS letters at baseline; 51.54 ± 20.99 at 1 month; 46.62 ± 19.47 at 3 months; 46.85 ± 18.58 at 6 months and 43.92 ± 17.97 at 12 months (two-way ANOVA: interaction of treatment by eye or time, p= -0.084). Central macular thickness (CMT) did not show a significant inter-eye difference at 12 months (p=0.97). The atrophic geographic areas tended to increase in both treated and fellow eyes at 12 months (p<0.0001). No inflammatory reaction, endophthalmitis, retinal detachment, uveitis, or other complications due to the subretinal injection of CB-PRP were observed during the follow-up. ConclusionsSubretinal injection of CB-PRP could be safely used for d-AMD in its GA form. Despite its safety, a larger cohort of patients, and probably a new way of administration, will be needed in order to understand whether the CB-PRP could have a role in the GA treatment.

Maintenance of Vision Needed to Drive after Intravitreal Anti-VEGF Therapy in Patients with Neovascular Age-related Macular Degeneration and Diabetic Macular Edema

To evaluate the association between intravitreal anti-VEGF therapy and visual acuity (VA)/driving vision maintenance over 4 years in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME). Retrospective, observational, clinical practice cohort study using data from the Vestrum Health database. Initial diagnosis (January 1, 2014 to June 30, 2019) of nAMD or DME and ≥ 1 year of treatment/follow-up history. The VA analysis required 4 years of treatment/follow-up history. For the driving vision maintenance analysis, patients required Snellen VA of 20/40 or better at baseline and for ≥ 6 months during year 1 after index intravitreal anti-VEGF treatment in the better-seeing eye. A loss-of-driving event was the first clinic visit with VA worse than 20/40 sustained for ≥ 6 consecutive months. Kaplan-Meier analyses estimated the probability of maintaining driving vision over 4 years stratified by year-1 injection number. Cox proportional hazard models examined associations between baseline clinical characteristics and year-1 injection frequency and the risk of losing driving vision. Mean change in VA over time and by baseline VA, driving vision maintenance probability over time and stratified by anti-VEGF injection frequency, and baseline factors predictive of driving vision maintenance. In year 1, the nAMD and DME cohorts gained 8.5 and 9.5 ETDRS letters, respectively. Between years 1 and 4, patients with nAMD and DME lost 6.6 and 2.7 ETDRS letters, respectively. The probability of maintaining driving vision over 4 years was 56% (nAMD) and 72% (DME); among patients who received 1 to 5, 6 to 7, and ≥ 8 anti-VEGF injections in year 1, corresponding probabilities were 50%, 56%, and 65% (nAMD; P < 0.001) and 63%, 72%, and 77% (DME; P < 0.001). Baseline factors associated with driving vision loss included older age, worse index VA, geographic atrophy (nAMD), and worsening baseline diabetic retinopathy (DME). Older age and worse index VA were risk factors for driving vision loss, whereas a greater year-1 injection number was associated with driving vision maintenance through year 4, supporting early initiation and frequent anti-VEGF injections for maintaining driving vision in nAMD or DME. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ten-year real-world outcomes of antivascular endothelial growth factor therapy in neovascular age-related macular degeneration using pro re nata regimen

Background/aimsTo analyse long-term outcomes of antivascular endothelial growth factor (anti-VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD) using pro re nata (PRN) regimen in a single-centre clinical...

Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results

To report 2-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD). Phase 3, randomized, multicenter, open-label, active-comparator trial. Patients with previously treated nAMD diagnosed within 9 months of screening and responsive to anti-vascular endothelial growth factor therapy. Patients were randomized 3:2 to PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab). Patients were followed through 4 complete refill-exchange intervals (∼2 years). Change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline averaged over weeks 60 and 64, and weeks 88 and 92 (noninferiority margin, -3.9 ETDRS letters). PDS Q24W was noninferior to monthly ranibizumab, with differences in adjusted mean change in BCVA score from baseline averaged over weeks 60/64 and 88/92 of +0.4 (95% confidence interval [CI], -1.4 to +2.1) and -0.6 ETDRS letters (95% CI, -2.5 to +1.3). Anatomic outcomes were generally comparable between arms through week 96. Through each of 4 PDS refill-exchange intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS Q24W patients assessed did not receive supplemental ranibizumab treatment. PDS ocular safety profile was generally unchanged from primary analysis. Prespecified ocular adverse events (AEs) of special interest were reported in 59 (23.8%) PDS and 17 (10.2%) monthly ranibizumab patients. Most common AE of special interest reported in both arms was cataract (PDS Q24W, 22 [8.9%]; monthly ranibizumab, 10 [6.0%]). Events in the PDS Q24W arm included (patient incidence) 10 (4.0%) conjunctival erosions, 6 (2.4%) conjunctival retractions, 4 (1.6%) endophthalmitis cases, and 4 (1.6%) implant dislocations. Serum ranibizumab sampling showed that the PDS continuously released ranibizumab over the 24-week refill-exchange interval and ranibizumab serum concentrations were within the range experienced with monthly ranibizumab. PDS Q24W showed noninferior efficacy to monthly ranibizumab through approximately 2 years, with approximately 95% of PDS Q24W patients not receiving supplemental ranibizumab treatment in each refill-exchange interval. AEs were generally manageable, with learnings continually implemented to minimize PDS-related AEs.

Prediction of visual function from automatically quantified optical coherence tomography biomarkers in patients with geographic atrophy using machine learning

Geographic atrophy (GA) is a vision-threatening manifestation of age-related macular degeneration (AMD), one of the leading causes of blindness globally. Objective, rapid, reliable, and scalable quantification of GA from optical coherence tomography (OCT) retinal scans is necessary for disease monitoring, prognostic research, and clinical endpoints for therapy development. Such automatically quantified biomarkers on OCT are likely to further elucidate structure–function correlation in GA and thus the pathophysiological mechanisms of disease development and progression. In this work, we aimed to predict visual function with machine-learning applied to automatically acquired quantitative imaging biomarkers in GA. A post-hoc analysis of data from a clinical trial and routine clinical care was conducted. A deep-learning automated segmentation model was applied on OCT scans from 476 eyes (325 patients) with GA. A separate machine learning prediction model (Random Forest) used the resultant quantitative OCT (qOCT) biomarkers to predict cross-sectional visual acuity under standard (VA) and low luminance (LLVA). The primary outcome was regression coefficient (r2) and mean absolute error (MAE) for cross-sectional VA and LLVA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. OCT parameters were predictive of VA (r2 0.40 MAE 11.7 ETDRS letters) and LLVA (r2 0.25 MAE 12.1). Normalised random forest feature importance, as a measure of the predictive value of the three constituent features of GA; retinal pigment epithelium (RPE)-loss, photoreceptor degeneration (PDR), hypertransmission and their locations, was reported both on voxel-level heatmaps and ETDRS-grid subfields. The foveal region (46.5%) and RPE-loss (31.1%) had greatest predictive importance for VA. For LLVA, however, non-foveal regions (74.5%) and PDR (38.9%) were most important. In conclusion, automated qOCT biomarkers demonstrate predictive significance for VA and LLVA in GA. LLVA is itself predictive of GA progression, implying that the predictive qOCT biomarkers provided by our model are also prognostic.

Diabetic Macular Edema and Diode Subthreshold Micropulse Laser: A Randomized Double-Masked Noninferiority Clinical Trial

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.

Impact of Persistent Retinal Fluid in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice.

To determine whether quantification of intraretinal fluid (IRF) and subretinal fluid (SRF) can be used as a biomarker for predicting visual prognosis in routine clinical practice. Retrospective, nonrandomized cohort study review of patients with neovascular age-related macular degeneration from January 1, 2012, to March 1, 2018. In the 286-patient cohort, the mean baseline, 6-month, and 12-month best-corrected visual acuity (BCVA) was 60.24 ± 18.63, 65.57 ± 16.56, and 65.61 ± 17.37 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively (P < .001). The regression coefficient in the linear mixed effects regression model quantifying the association between eyes in the fourth and first quartile of IRF and 12-month BCVA was -4.14 (95% CI, -6.65 to -1.63) (P = .001) ETDRS letters. The regression coefficient quantifying the association between eyes in the fourth and first quartile of SRF and 12-month BCVA was -0.7 (95% CI, -3.07 to 1.27) (P = .56) ETDRS letters. IRF and SRF are valuable biomarkers for BCVA outcomes in treatment-naïve neovascular age-related macular degeneration in routine clinical practice. [Ophthalmic Surg Lasers Imaging 2022;53:317-324.].

Treatment of chronic diabetic macular oedema with intravitreal fluocinolone acetonide implant; real-life analysis of outcomes during overall treatment period.

To assess the clinical efficacy of the fluocinolone acetonide (FA) intravitreal implant (Iluvien, Alimera Sciences) over a 12-month period in a population resistant to treatment with first-line anti-VEGF agents. This study is a retrospective cohort study assessing functional and anatomical outcomes in 13 eyes of 12 patients treated for diabetic macular oedema (DMO) with a single fluocinolone implant (FA) (Iluvien) under real-world conditions. The follow-up period includes the time of first intravitreal treatment (incl anti-VEGF or short-lasting steroids) given until 12 months post FA implant insertion. Primary outcomes were best corrected visual acuity (BCVA), measured using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale, and central foveal thickness (CFT), measured using Topcon 3DOCT-2000 (Topcon Inc) SD-OCT imaging. Mean BCVA and CFT were measured before anti-VEGF treatment, after anti-VEGF treatment, at the time of Iluvien implant insertion, and 6 and 12 months after Iluvien implant insertion. The t-paired sample test was used to ascertain statistical significance of changes in comparison of two samples while the ANOVA analysis was used in comparison of three or more samples. The baseline BCVA (SD) of the cohort prior to initiation of anti-VEGF treatment was 47.45 (12.27) ETDRS letters whilst the mean CFT (SD) was 579 (203) microns. Following completion of anti-VEGF therapy, the mean improvement in vision was 8.9 ETDRS letters (p = 0.1) whilst the mean reduction in CFT was 197 microns (p = 0.028). Mean BCVA (SD) at the time of insertion of the FA implant was 55.15 (11.16) ETDRS letters and mean (SD) CFT at time of insertion of the FA was 454.62 μm (109.51). Following the 12-month treatment period with the FA implant, BCVA (SD) was 62.15 (10.25) ETDRS letters (p = 0.0331) and the mean (SD) CFT was 404.36 μm (142.92), a change of -50.26 μm from baseline (p = 0.0369). This study has shown that statistically significant improvements in BCVA and CFT can be achieved over a 12-month period with the Iluvien implant. The implant has been shown to be a safe option in the treatment of DMO and may have a role to play in achieving good functional and anatomical outcomes in DMO while also reducing the frequency of follow-up appointments required to maintain stable vision in the working-age population.

To investigate treat and extend versus pro re nata regimen in neovascular age-related macular degeneration: results from the IDEM study

The purpose of this study is to report the 24-month outcomes of a pro re nata (PRN) compared with a treat and extend (T&E) regimen in patients previously treated for neovascular age-related macular degeneration (nAMD). This was a 2-year prospective, single-center study. Previously treated patients for nAMD were randomized into two regimen groups: T&E and PRN groups. Main outcome measured was change in best corrected visual acuity (BCVA) from baseline to month 24. Secondary outcomes encompassed anatomical features such as central retinal thickness (CRT), number of intravitreal injections (IVI), and visits required. A total of 124 eyes received the T&E (n = 61) or PRN (n = 63) regimen. At month 24, the mean BCVA change was -4.4 early treatment diabetic retinopathy study (ETDRS) letters (T&E) and -3.4 ETDRS letters (PRN), with a difference of +1.1 ETDRS letters (95% CI [-2.25]; p = 0.006). The mean change in CRT was -10.6 µm (T&E) and -7.9 µm (PRN), with a difference of +2.6 µm (95% CI [+19.2]; p = 0.004). The T&E group had received a mean of +4.6 more injections (95% CI [-7.06; -2.12]; p < 0.001) at month 24. There was statistically proven non-inferiority between the PRN and T&E regimens in terms of visual and anatomical outcomes at 24 months, with significantly more IVI administered in the T&E regimen.

Visual Outcomes Associated With Patterns of Macular Edema Resolution in Central Retinal Vein Occlusion Treated With Anti–Vascular Endothelial Growth Factor Therapy

It is unclear how visual outcomes vary between patterns of macular edema (ME) resolution in eyes with central retinal vein occlusion (CRVO). To assess best-corrected visual acuity (BCVA) outcomes at 100 weeks based on macular fluid resolution patterns by 52 and 100 weeks among patients receiving anti-vascular endothelial growth factor therapy for CRVO-related ME. Post hoc analysis of the prospective, 3-arm, double-masked, randomized noninferiority trial Lucentis, Eylea, Avastin in Vein Occlusion (LEAVO), which evaluated intravitreal aflibercept (2.0 mg/0.05 mL), bevacizumab (1.25-mg/0.05 mL), or ranibizumab (0.5 mg/0.05 mL) over 100 weeks in adult patients (18 years and older) with CRVO-related ME with BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 19 to 78 in the study eye (approximate Snellen equivalent, 20/400 to 20/32, respectively) from December 2014 to December 2016 at 44 UK National Health Service ophthalmology departments. A total of 140 of 154 eyes were randomized to aflibercept, 144 of 154 randomized to bevacizumab, and 141 of 155 randomized to ranibizumab. Data were analyzed from January 2019 to March 2019. Persistent ME included eyes with central subfield thickness (CST) 320 μm or greater, and persistently dry macula (no ME) included eyes with CST less than 320 μm at 52 and 100 weeks. Recurrent ME included eyes that did not meet the criteria for persistently dry or wet. If CST was missing, the closest intervening visit was carried forward. Adjusted mean BCVA at 100 weeks. The mean (SD) age of the 425 included participants was 69.2 (12.7) years, and 243 participants (57.2%) were men. A total of 425 eyes from 425 participants were included. By 100 weeks, 117 eyes (28.5%) were persistently dry, 44 (10.7%) were persistently wet (with ME), and 250 (60.8%) had recurrent ME. Persistent ME at 100 weeks was associated with worse VA compared with dry macula (adjusted difference, -10.98 ETDRS letters; 95% CI, -16.19 to -5.76; P < .001) and recurrent ME (adjusted difference, -5.39 letters; 95% CI, -10.15 to -0.64; P = .03). By 52 weeks, individuals with persistent ME also had poorer 100-week BCVA compared with individuals with dry macula (adjusted difference, -7.39; 95% CI, -11.72 to -3.05; P < .001) and recurrent ME (adjusted difference, -3.92; 95% CI, -8.05 to 0.20; P = .06). By 100 weeks, more eyes treated with bevacizumab had persistently wet macula than those treated with aflibercept (26 of 140 [18.6%] vs 7 of 134 [5.2%]; difference, 13.3%; 95% CI, 5.9 to 20.8; P < .001) or ranibizumab (11 of 137 [8%]; difference, 10.5%; 95% CI, 2.7 to 18.4; P = .01). These findings suggest that attempts should be made to maintain persistently fluid-free macula for optimal visual acuity outcomes.

Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration

To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). Phase 3, open-label, randomized, visual acuity assessor-masked noninferiority and equivalence trial. Patients with nAMD diagnosed within 9 months of screening previously treated with and responsive to anti-vascular endothelial growth factor therapy. Patients were randomized 3:2 to treatment with the PDS with ranibizumab 100 mg/ml with fixed 24-week (Q24W) refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5-mg injections every 4 weeks (monthly ranibizumab). Primary end point was change in best-corrected visual acuity (BCVA) EarlyTreatment Diabetic Retinopathy Study letter (letters) score from baseline averaged over weeks 36 and 40 (noninferiority margin,-4.5 letters; equivalence margin, ±4.5 letters). Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with the PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab. Baseline BCVA was 74.4 letters (PDS Q24W arm) and 75.5 letters (monthly ranibizumab arm; Snellen equivalent, 20/32). Adjusted mean change in BCVA score from baseline averaged over weeks 36 and 40 was+0.2 letters (standard error [SE], 0.5letters) in the PDS Q24W arm and+0.5 letters (SE, 0.6 letters) in the monthly ranibizumab arm (difference, -0.3 letters; 95% confidence interval, -1.7 to 1.1 letters). PDS Q24W was both noninferior and equivalent to monthly ranibizumab. Of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4%) did not receive supplemental ranibizumab treatment before the first refill-exchange procedure, including 4 patients who discontinued treatment before the first refill-exchange procedure. Prespecified ocular adverse events of special interest were reported in 47 patients (19.0%) in the PDS Q24W arm and 10 patients (6.0%) in the monthly ranibizumab arm, which included, in the former arm, 4 (1.6%) endophthalmitis cases, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions. Most ocular adverse events in the PDS Q24W arm occurred within 1 month of implantation. Archway met its primary objective and PDS Q24W demonstrated noninferior and equivalent efficacy to monthly ranibizumab, with 98.4% of PDS-treated patients not receiving supplemental treatment in the first 24-week interval.