Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial.

BACKGROUND: Intravitreal aflibercept 8 mg could improve treatment outcomes and provide sustained disease control in patients with neovascular age-related macular degeneration (nAMD), with extended dosing compared with aflibercept 2 mg. METHODS: PULSAR is a phase 3, randomised, three-group, double-masked, non-inferiority, 96-week trial conducted across 223 sites worldwide. Adults with nAMD were randomised 1:1:1 to aflibercept 8 mg every 12 weeks (8q12), aflibercept 8 mg every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups. From week 16, patients in the aflibercept 8 mg groups had their dosing interval shortened if pre-specified dose regimen modification criteria denoting disease activity were met. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48. All patients with at least one dose of study treatment were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04423718) and is ongoing. FINDINGS: Of 1011 patients randomised to aflibercept 8q12 (n=336), 8q16 (n=338), or 2q8 (n=337) between Aug 11, 2020, and July 30, 2021, 1009 patients received study treatment (aflibercept 8q12 n=335; aflibercept 8q16 n=338; and aflibercept 2q8 n=336). Aflibercept 8q12 and 8q16 showed non-inferior BCVA gains versus aflibercept 2q8 (mean BCVA change from baseline +6·7 [SD 12·6] and +6·2 [11·7] vs +7·6 [12·2] letters). The least squares mean differences between aflibercept 8q12 versus 2q8 and 8q16 versus 2q8, respectively, were -0·97 (95% CI -2·87 to 0·92) and -1·14 (-2·97 to 0·69) letters (non-inferiority margin at 4 letters). The incidence of ocular adverse events in the study eye was similar across groups (aflibercept 8q12 n=129 [39%]; aflibercept 8q16 n=127 [38%]; and aflibercept 2q8 n=130 [39%]). INTERPRETATION: Aflibercept 8 mg showed efficacy and safety with extended dosing intervals, which has the potential to improve the management of patients with nAMD. FUNDING: Bayer AG and Regeneron Pharmaceuticals.

Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials.

BACKGROUND: Geographic atrophy is a leading cause of progressive, irreversible vision loss. The objectives of OAKS and DERBY were to assess the efficacy and safety of pegcetacoplan compared with sham treatment in patients with geographic atrophy. METHODS: OAKS and DERBY were two 24-month, multicentre, randomised, double-masked, sham-controlled, phase 3 studies, in which patients aged 60 years and older with geographic atrophy secondary to age-related macular degeneration were enrolled at 110 clinical sites and 122 clinical sites worldwide, respectively. Patients were randomly assigned (2:2:1:1) by central web-based randomisation system to intravitreal 15 mg per 0·1 mL pegcetacoplan monthly or every other month, or sham monthly or every other month using stratified permuted block randomisation (stratified by geographic atrophy lesion area at screening, history or presence of active choroidal neovascularisation in the eye not under assessment, and block size of six). Study site staff, patients, reading centre personnel, evaluating physicians, and the funder were masked to group assignment. Sham groups were pooled for the analyses. The primary endpoint was the change from baseline to month 12 in the total area of geographic atrophy lesions in the study eye based on fundus autofluorescence imaging, in the modified intention-to-treat population (ie, all patients who received one or more injections of pegcetacoplan or sham and had a baseline and at least one post-baseline value of lesion area). Key secondary endpoints (measured at 24 months) were change in monocular maximum reading speed of the study eye, change from baseline in mean functional reading independence index score, change from baseline in normal luminance best-corrected visual acuity score, and change from baseline in the mean threshold sensitivity of all points in the study eye by mesopic microperimetry (OAKS only). Safety analyses included patients who were randomly assigned and received at least one injection of pegcetacoplan or sham. The now completed studies are registered with ClinicalTrials.gov, NCT03525613 (OAKS) and NCT03525600 (DERBY). FINDINGS: Between Aug 30, 2018, and July 3, 2020, 1258 patients were enrolled in OAKS and DERBY. The modified intention-to-treat populations comprised 614 (96%) of 637 patients in OAKS (202 receiving pegcetacoplan monthly, 205 pegcetacoplan every other month, and 207 sham) and 597 (96%) of 621 patients in DERBY (201 receiving pegcetacoplan monthly, 201 pegcetacoplan every other month, and 195 sham). In OAKS, pegcetacoplan monthly and pegcetacoplan every other month significantly slowed geographic atrophy lesion growth by 21% (absolute difference in least-squares mean -0·41 mm2, 95% CI -0·64 to -0·18; p=0·0004) and 16% (-0·32 mm2, -0·54 to -0·09; p=0·0055), respectively, compared with sham at 12 months. In DERBY, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth, although it did not reach significance, by 12% (-0·23 mm2, -0·47 to 0·01; p=0·062) and 11% (-0·21 mm2, -0·44 to 0·03; p=0·085), respectively, compared with sham at 12 months. At 24 months, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth by 22% (-0·90 mm2, -1·30 to -0·50; p<0·0001) and 18% (-0·74 mm2, -1·13 to -0·36; p=0·0002) in OAKS, and by 19% (-0·75 mm2, -1·15 to -0·34; p=0·0004) and 16% (-0·63 mm2, -1·05 to -0·22; p=0·0030) in DERBY, respectively, compared with sham. There were no differences in key secondary visual function endpoints at 24 months. Serious ocular treatment-emergent adverse events were reported in five (2%) of 213, four (2%) of 212, and one (<1%) of 211 patients in OAKS, and in four (2%) of 206, two (1%) of 208, and two (1%) of 206 patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. New-onset exudative age-related macular degeneration was reported in 24 (11%), 16 (8%), and four (2%) patients in OAKS, and in 27 (13%), 12 (6%), and nine (4%) patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. INTERPRETATION: Pegcetacoplan, the first treatment approved by the US Food and Drug Administration for geographic atrophy, slowed geographic atrophy lesion growth with an acceptable safety profile. FUNDING: Apellis Pharmaceuticals.

Transorbital Ultrasound in the Diagnosis of Giant Cell Arteritis.

OBJECTIVES: The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. METHODS: Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. RESULTS: We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: ß=-1.91; p=0.029; EDV: ß=-0.57; p=0.032) and significantly elevated OND (ß = 0.79; p=0.003) compared with controls. RI did not significantly differ from controls (ß=-0.06, p=0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (p=0.048) and EDV (p=0.040). No association was found with RI (p=0.249), while a positive significant association was noted with OND (p<0.001). CONCLUSIONS: This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.

Single Center Experience with Voretigene Neparvovec Gene Augmentation Therapy in RPE65 Mutation-Associated Inherited Retinal Degeneration in a Clinical Setting.

PURPOSE: To assess the impact of baseline data on psychophysical and morphological outcomes of subretinal voretigene neparvovec (VN) (Luxturna, Spark Therapeutics, Inc.) treatment. DESIGN: Single-center, retrospective, longitudinal, consecutive case series. PARTICIPANTS: Patients with RPE65-biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) treated between February 2020 and March 2022 with VN and oral immunosuppression according to the manufacturer's recommendation by one surgeon (F.G.H.). METHODS: Retrospective analysis of surgical and clinical records, ancillary testing, and retinal imaging after VN therapy for RPE65-IRD. Descriptive statistics compared data at baseline up to 32 months post-treatment. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), low-luminance VA (LLVA), Goldmann visual fields (GVFs), chromatic full-field stimulus threshold (FST) testing (FST), scotopic and photopic 2-color threshold perimetry (2CTP), and multimodal retinal imaging. RESULTS: Thirty eyes of 19 patients were analyzed (10 pediatric patients < 20 years; 20 adult patients > 20 years of age; overall range: 8-40 years) with a median follow-up of 15 months (range, 1-32). The fovea was completely or partially detached in 16 eyes, attached in 12 eyes, and not assessable in 2 eyes on intraoperative imaging. Median BCVA at baseline was better in the pediatric group (P < 0.05) and did not change significantly independent of age. Meaningful loss of BCVA (≥ 0.3 logarithm of the minimal angle of resolution [logMAR]) occurred in 5 of 18 adult eyes, and a meaningful gain (≥-0.3 logMAR) occurred in 2 of 18 adult and 2 of 8 pediatric eyes. The LLVA and scotopic 2CTP improved considerably in pediatric patients. Scotopic blue FST improved at all ages but more in pediatric patients (8/8 eyes gained ≥ 10 decibels [dB]; P < 0.05). In pediatric patients, median GVF improved by 20% for target V4e and by 50% for target III4e (target I4e not detected). Novel atrophy developed in 13 of 26 eyes at the site of the bleb or peripheral of vascular arcades. Improvements in FST did not correlate with development of chorioretinal atrophy at 12 months. Mean central retinal thickness was 165.87 µm (± 26.26) at baseline (30 eyes) and 157.69 µm (± 30.3) at 12 months (26 eyes). Eight adult patients were treated unilaterally. The untreated eyes did not show meaningful changes during follow-up. CONCLUSIONS: These data in a clinical setting show the effectiveness of VN therapy with stable median BCVA and mean retinal thickness and improvements of LLVA, FST, and 2CTP up to 32 months. Treatment effects were superior in the pediatric group. We observed new chorioretinal atrophy in 50% of the treated eyes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A. DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials. PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older. METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen. MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112. RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112. CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

International Classification System for Ocular Complications of Anti-Vascular Endothelial Growth Factor Agents in Clinical Trials.

OBJECTIVE: Complications associated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies are inconsistently reported in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process. DESIGN: Systematic review and Delphi consensus process. PARTICIPANTS: 25 international retinal specialists participated in the Delphi consensus survey. METHODS: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists that voted on inclusion, exclusion, rephrasing, and addition of complications. As well, surveys determined specifiers for the selected complications. This iterative process helped refine the final classification system. MAIN OUTCOME MEASURES: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration. RESULTS: After screening 18,229 articles, 130 complications were initially categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 (70%) complications after three rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 (52%) complications in the final list. A total of 14 (11%) complications met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds were also excluded from the final classification system after the Delphi process terminated. In addition, 47 out of 75 (63%) proposed complication specifiers were included based on participant agreement. CONCLUSION: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses.

Ocular drug delivery systems: glaucoma patient perceptions from a German university hospital eye clinic.

PURPOSE: This study aimed to report on glaucoma patients' beliefs and illness perceptions and to investigate their opinion on ocular drug delivery devices (ODD). METHODS: We performed a cross-sectional study in a large tertiary-referral outpatient glaucoma clinic, with 102 patients. Validated anonymized questionnaires were used. We investigated the awareness and acceptance regarding ODD (contact lenses (CLs), punctal plugs (PPs), subconjunctival implants, anterior chamber (AC) injections, and drug-emitting stents) and looked at factors that could influence a patient's decision for having an ODD. RESULTS: Sixty-three patients (61.8%) confirmed they would rather have ODD than keep their eye-drops (38.2%). The most important factors influencing their decision were effectiveness and long-lasting effect. A large proportion of patients reported a preference for CLs (48.0%), PPs (52.9%), or drug-emitting stents (44.1%). When comparing patients who preferred ODD (group-1) versus eye-drops (group-2), significantly more patients in group-1 were worried (p < 0.001) or felt disrupted (p < 0.001) by their use of eye-drops. A significantly greater share of patients in group-1 showed acceptance towards CLs (60.3% vs. 38.5%; p = 0.032), AC injections (38.1% vs. 12.8%, p = 0.006), or drug-emitting stents (54% vs. 28.2%, p = 0.023), whilst there were no significant differences regarding the acceptance of PPs (p = 0.363) or subconjunctival implants (p = 0.058). CONCLUSION: ODD for the treatment of glaucoma were broadly deemed acceptable by patients in this study. Effectiveness and long-lasting effect were the most important factors for a decision towards having an ODD. The majority of patients who preferred an ODD felt severely affected by their disease and were negatively influenced by their glaucoma medication intake.

Evaluation of the test-retest and inter-mode comparability of the Impact of Vision Impairment questionnaire in people with chronic eye diseases.

PURPOSE: The main objective of this study is to assess the test-retest and inter-administration mode reliability of the Impact of Vision Impairment profile (IVI), a common patient-reported outcome measure (PROM) for people with chronic eye diseases. METHODS: The IVI was administered to adult patients with stable, chronic eye diseases two to four times per participant (average intervals between administrations 12 to 20 days; maximum two phone interviews, paper administration, electronic administration) by two trained interviewers. Rasch models were fit to the data. Intra-class correlation coefficients (ICCs), mean differences and Cronbach's alpha between test-retest administrations (two phone interviews) and inter-mode comparisons were calculated. RESULTS: Two hundred-sixteen patients (mean age 67 ± 12 years, 40% male) were included in the study. The IVI met all psychometric requirements of the Rasch model, and the division into the domains of functional items (IVI_F) and emotional items (IVI_E) corresponded to the German validation study. ICCs (all for IVI_F and IVI_E, respectively) for the retest administrations were 0.938 and 0.912, and 0.853 and 0.893 for inter-mode comparisons phone/paper, 0.939 and 0.930 for phone/electronic, and 0.937 and 0.920 for paper/electronic (all p < 0.01). Mean differences (all for IVI_F and IVI_E, respectively) for the retest administrations were 2.8% and 0.7% and ranged from 2.0% to 6.2% and from 0.4 % to 4.9% between administration modes. Cronbach's alpha ranged from 0.886 to 0.944 for retest and inter-mode comparisons. CONCLUSION: Due to the high test-retest reliability and the almost equally high comparability of different modes of administration of the IVI, the study endorses its use as a robust PROM to capture vision-related quality of life. Our results further support the use of the IVI as an endpoint in clinical trials and may simplify implementing it in both clinical trials or real-world evidence generation by offering multiple administration modes with high reliability.

Ellipsoid Zone recovery in Macular Telangiectasia Type 2 (MacTel).

PURPOSE: To describe imaging features of Macular Telangiectasia Type 2 (MacTel) eyes experiencing ellipsoid zone (EZ) recovery. METHODS: MacTel patients with EZ-recovery were identified from the Natural History and Observational Registry Study and underwent retinal imaging including optical coherence tomography (OCT) and fundus photography. Eyes were graded according to the classification system by Gass and Blodi, the EZ-loss area was measured and OCT parameters were assessed by two independent readers. Parameters were analysed for their presence prior to EZ-recovery. RESULTS: Twenty-four eyes of 21 patients (12 female, 57.12%; mean age 68 ± 8.54 years) were included in this study and followed for 21.25 ± 12.79 months. At baseline, mean EZ-loss area was 0.036 ± 0.028 mm2 and 0.01 ± 0.013 mm2 at follow-up (p<0.001). A persisting external limiting membrane overlaying the EZ-loss was detected in 16 cases (66%) and hyperreflective changes in the outer retina were present in 18 cases (75%). Best corrected visual acuity was 0.23 (20/32) ± 0.33 logMar at baseline and 0.34 (20/40) ± 0.34 logMar at follow up (p=0.3). CONCLUSION: Distinct OCT features precede ellipsoid zone recovery in MacTel and warrant further studies investigating implications for patient care and clinical trial interpretation.

QUANTITATIVE AUTOFLUORESCENCE IN CENTRAL SEROUS CHORIORETINOPATHY.

BACKGROUND/PURPOSE: Central serous chorioretinopathy (CSC) is associated with pachychoroid and dysfunctional retinal pigment epithelium. Autofluorescence (AF) is typically altered. The authors performed this study to quantify these alterations using quantitative AF (qAF) in patients with CSC and in their fellow eye in comparison with a healthy control group. METHODS: Patients with CSC and healthy controls were recruited prospectively. All patients received a full clinical examination including best-corrected visual acuity, enhanced depth imaging-optical coherence tomography, and qAF. Quantitative autofluorescence images were taken with a confocal scanning laser ophthalmoscope (Heidelberg Engineering). Quantitative autofluorescence values were assessed in specified regions of the inner eight and the middle ring of the Delori grid. RESULTS: In total, 141 eyes of 77 patients with CSC were included. Ninety eyes had a manifest CSC (group 1) while 51 fellow eyes (group 2) did not show signs of CSC. There were no significant differences of qAF values between these two groups: mean qAF values were 241.3 (inner eight) and 212.8 (middle ring) in group 1 and 235.9 (inner eight) and 210.0 (middle ring) in group 2 ( P = 1.0 and 1.0). We compared these eyes with healthy controls comprising 39 eyes. Quantitative autofluorescence signals (inner eight: 164.7; middle ring: 148.9) differed significantly compared with both CSC manifest ( P < 0.001) and fellow eyes ( P < 0.001). CONCLUSION: Our results show that patients with CSC have increased qAF values in both eyes with manifest CSC and asymptomatic, clinically unremarkable fellow eyes in comparison with healthy controls. This finding suggests that qAF alterations are present even before clinical signs can be observed.

LASER FLARE PHOTOMETRY IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: An Evaluation of 2,487 Cases.

PURPOSE: Exploratory analysis associated with the prospective, multicenter, randomized PRIVENT trial. To characterize the associations between laser flare photometry and anatomical and epidemiological features of rhegmatogenous retinal detachment (RRD). METHODS: The authors measured laser flare values of all 3,048 prescreened patients excluding those with comorbidities. A mixed regression analysis evaluated the strength of the influencing factors like age, sex, lens status, and presence and extent of RRD on laser flare. RESULTS: Rhegmatogenous retinal detachment was more frequent in men (65.8%) than in women (34.2%, P < 0.001) and in right (52%) than in left eyes (48%, P = 0.045). Phakic RRD affected less quadrants and was less likely to be associated with macula-off status than pseudophakic RRD (48.4% vs. 58.0% macula off, 23% vs. 31% ≥3 quadrants, P < 0.001). Laser flare of affected eyes was significantly higher compared with fellow eyes (12.6 ± 15.2 vs. 8.3 ± 7.4 pc/ms, P < 0.001). The factors age, sex, lens status, presence of RRD, and the number of quadrants affected were independent influencing factors on laser flare. R 2 was 0.145 for phakic and 0.094 for pseudophakic eyes. CONCLUSION: The results indicate that there may be more factors affecting laser flare than previously assumed. This might limit flare as predictive value for PVR and retinal redetachment.

Knowledge about age-related eye diseases in the general population in Germany.

BACKGROUND: With a rising prevalence of age-related eye diseases, prevention and early diagnosis of these conditions are key goals of public eye health. Disease-related knowledge in the general public supports these goals but there is little data available. Thus, we have assessed knowledge of cataract, glaucoma, age-related macular degeneration (AMD) and diabetic eye disease in the German adult general population in a cross-sectional study and identified target groups for health education interventions. METHODS: Knowledge assessment content was identified based on a literature review, expert input, and a list of items was generated after a qualitative selection process. The resulting 16-item instrument (4 items per condition) was administered to 1,008 participants from a survey panel, demographically representative of the adult German population. Test properties were evaluated based on a Rasch model and multiple correspondence analysis (MCA). Binary-logistic regression analysis was performed to investigate associations with age, sex, education level, employment status, marital status, income, reported health status, visual difficulties, and recent general practitioner (GP) and ophthalmologist consultations. RESULTS: Replies were correct for a median of 9 out of 16 (range 2 - 16) items, which differed between conditions (p < 0.0001). Most responses were correct for cataract items (median: 3 / 4) and least were correct for AMD items (median: 2 / 4). 27%, 9%, 1% and 19% of respondents replied correctly to all cataract, glaucoma, AMD and diabetic eye disease-related items, respectively. Rasch analysis suggested an adequate targeting of items and in MCA, no evidence of multidimensionality was present. Older age, being retired, decreased general health and recent GP or ophthalmology consultations were significantly associated with more knowledge about common eye conditions (p ≤ 0.005). GP or ophthalmology consultations remained significant in a multivariable model (p ≤ 0.011). CONCLUSIONS: Knowledge gaps regarding eye health are considerable in the German general population and should therefore be addressed in educational interventions targeting the public. Special attention when designing such campaigns needs to be paid to infrequent users of the healthcare system. Knowledge of AMD seems to be poorer compared to other eye conditions.

Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials.

BACKGROUND: Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD). METHODS: TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300). FINDINGS: Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]). INTERPRETATION: Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD. FUNDING: F Hoffmann-La Roche.

Antiplatelet and anticoagulant therapy in patients with submacular hemorrhage caused by neovascular age-related macular degeneration.

PURPOSE: Patients with extensive submacular hemorrhage (SMH) caused by age-related macular degeneration (AMD) have a poor visual prognosis despite surgical intervention. Systemic blood-thinning drugs, which are commonly prescribed in the same age group, are known to increase the risk of severe hemorrhage in many parts of the body. This study aimed to investigate whether systemic blood-thinning drugs have an impact on the severity of SMH and if there are differences between the different types of blood-thinning medication. METHODS: We reviewed the medical records of patients who suffered from surgically treated SMH between 2020 and 2022. All patients received a full ophthalmologic examination upon presentation including best-corrected visual acuity (BCVA) and optical coherence tomography. Other characteristics that were recorded included size of hemorrhage, blood-thinning therapy, and reason for intake. RESULTS: A total of 115 patients with a mean age of 82 years were included in this retrospective analysis. Eighty-three patients (72.2%) were on blood-thinning therapy. The mean size of SMH was 32.01 mm2. Mean BCVA at initial presentation was 1.63 logMAR and 1.59 logMAR 1 year after surgery. The size of SMH was significantly larger in patients on blood-thinning medication (35.92 mm2 vs. 21.91 mm2) (p = 0.001) and their BCVA postoperatively was worse with 1.68 logMAR compared to 1.30 logMAR after 1 year (p = 0.503). Patients with vitamin K antagonists had larger SMH size and worse outcomes regarding BCVA compared to direct oral anticoagulants. CONCLUSION: Blood thinners in patients with AMD affect the severity of SMH. Consequently, the indication for their intake should be critically evaluated.

Patient-reported vision impairment in low luminance predicts multiple falls.

BACKGROUND: Visual impairment is an independent risk factor for falling. Whether this extends to patient-reported visual difficulties has not been assessed to date. We have evaluated whether patient-reported visual difficulties in low-contrast and low luminance situations are a risk factor for falls and concerns about falling. METHODS: Baseline assessments in outpatients with varying degrees of visual impairment aged ≥ 60 years included the Vision Impairment in Low Luminance (VILL) questionnaire and socio-demographic data; prospective follow-up assessments included falls over 12 months, the Falls Efficacy Scale (FES-I) and the VILL. The VILL was scored using Rasch models, and the FES-I was categorized following published guidelines. Associations were investigated using logistic regression analysis, controlling for age, visual acuity and known risk factors of falling. RESULTS: We included 112 participants (74 women, mean age 70 ± 7 years). Twenty-seven participants recalled any falls and eleven recalled multiple falls at follow-up. Higher VILL reading subscale and mobility subscale scores at baseline were significantly associated with reporting less multiple falls at follow-up (OR 0.559 [0.333-0.936], p = 0.027 and OR 0.595 [0.377-0.940], p = 0.026). VILL scores were significantly associated with concerns about falling (high versus low: p ≤ 0.004, reading, mobility and emotional subscales; high versus moderate: p = 0.004, emotional subscale). CONCLUSIONS: Patient-reported visual difficulties under low illumination and in low-contrast conditions are predictive of multiple falls in the future, have an additional predictive value over established risk scores, and are associated with concerns to fall. Current fall risk assessments may benefit from the inclusion of such assessments, e.g. the VILL questionnaire.

High-Impact Actions to Reduce the Carbon Dioxide Footprint in an Ophthalmic Operation Room: A Narrative Review.

Germany's health care footprint accounts for 5.2% of the national emissions footprint which results in 0.71 tons of CO2 emission per capita. Thus, the health sector has a responsibility to take climate action. Surgery is a resource-intensive health care activity, requiring expensive equipment, sterilization procedures, advanced operative technologies, and obligatory life support systems. We spotlight the situation in a department of ophthalmology with frequent anesthesia services and highly standardized procedures. This narrative review discusses high-impact actions which result in a major reduction of the CO2 footprint according to the global road map for health care decarbonization, considering both the ophthalmic and anesthesiologic point of view.

Clinical outcomes of the PAUL® glaucoma implant: One-year results.

BACKGROUND: To report one-year outcomes from a single-centre cohort undergoing PAUL® Glaucoma Implant (PGI) surgery. METHODS: Retrospective review of patients undergoing PGI surgery at the University Eye Hospital Bonn, Germany, from April 2021 to September 2021. RESULTS: Forty-five eyes of 41 patients were included. Qualified and complete success rates (95% CI) were 95.6% (88.9%-100%) and 73.3% (60%-86.7%) for Criterion A (IOP ≤ 21 mmHg), 84.4% (73.3%-93.3%) and 74.4% (51.1%-80.0%) for Criterion B (IOP ≤ 18 mmHg), 62.2% (48.9%-75.6%) and 46.7% (31.2%-62.2%) for Criterion C (IOP ≤ 15 mmHg) and 26.7% (13.3%-40.0%) and 22.2% (11.1%-33.3%) for Criterion D (IOP ≤ 12 mmHg), respectively. Mean IOP decreased from 26.1 mmHg (7-48 mmHg) to 12.0 mmHg (3-24 mmHg) (reduction of 48.83%) after 12 months with a reduction of IOP-lowering agents from 0.5 (0-3). One eye (2.2%) needed an injection of viscoelastic due to significant hypotony with AC shallowing, and four eyes (8.9%) developed choroidal detachments due to hypotony which resolved without further interventions after 6 weeks. Three patients (6.7%) developed tube exposure which required conjunctival revision with an additional pericardial patch graft. An intraluminal prolene stent was removed in 19 eyes (42.2%) after a mean time period of 8.4 months (2-12 m). Mean IOP before the removal was 21.9 mmHg (12-38 mmHg) and decreased to 11.3 mmHg (6-16 mmHg). CONCLUSIONS: PGI surgery is an effective procedure for reducing IOP and pressure-lowering therapy. An intraluminal prolene stent impedes hypotony in the early postoperative phase and enables further IOP lowering without additional interventions during the postoperative course.

Histopathological Changes in Corneal Ectasia. / Histopathologische Veränderungen bei kornealen Ektasien.

Corneal ectasia comprises keratoconus, keratoglobus, pellucid marginal degeneration, and iatrogenic keratectasia. In all forms of corneal ectasia, there is a thinning of the cornea, usually accompanied by steepening of the cornea, leading to irregular astigmatism. Here, we provide an overview of histopathologic alterations of the various corneal ectasias. Furthermore, histologic changes after surgical procedures that are performed in severe cases of corneal ectasia, such as corneal cross-linking and penetrating keratoplasty (pKPL), as well as refractive surgical procedures that may lead to postsurgical ectasia are presented. In addition to a literature review, histopathologic archival material was reviewed and examined to illustrate the specific histologic changes.

Efficacy and Safety of Biosimilar FYB201 Compared with Ranibizumab in Neovascular Age-Related Macular Degeneration.

PURPOSE: This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD). DESIGN: This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study. PARTICIPANTS: A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239). METHODS: Patients received FYB201 or reference ranibizumab 0.5 mg by intravitreal (IVT) injection in the study eye every 4 weeks. MAIN OUTCOME MEASURES: The primary end point was change from baseline in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks before the third monthly IVT injection. Biosimilarity of FYB201 to its originator was assessed via a 2-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters. RESULTS: The BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was -0.4 ETDRS letters with a 90% confidence interval (CI) of -1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups. CONCLUSIONS: FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD.

Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial.

PURPOSE: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD. DESIGN: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis. PARTICIPANTS: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry. METHODS: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy. MAIN OUTCOME MEASURES: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon. RESULTS: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified. CONCLUSIONS: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.