Vision loss reduction with avacincaptad pegol for geographic atrophy: a 12-month post hoc analysis of the GATHER1 and GATHER2 trials.

PURPOSE: To evaluate the impact of reduction in geographic atrophy (GA) lesion growth on visual acuity in the GATHER trials using categorical outcome measures. DESIGN: Randomized, double-masked, sham-controlled phase 3 trials. PARTICIPANTS: Aged ≥50 years with non-center point involving GA and best corrected visual acuity (BCVA) of 25-80 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye. METHODS: GATHER1 consisted of 2 parts. In Part 1, 77 patients were randomized 1:1:1 to avacincaptad pegol (ACP) 1 mg, ACP 2 mg, and sham. In Part 2, 209 patients were randomized 1:2:2 to ACP 2 mg, ACP 4 mg, and sham. In GATHER2, patients were randomized 1:1 to ACP 2 mg (n=225) and sham (n=223). A post hoc analysis of 12-month data for pooled ACP 2 mg and sham groups is reported. MAIN OUTCOME MEASURES: Proportion of study eyes that experienced ≥10-, ≥15-, or ≥20-BCVA ETDRS letter loss from baseline to month 12; time-to-event analysis of persistent vision loss of ≥10-, ≥15-, or ≥20-BCVA letters from baseline at ≥2 consecutive visits over 12 months; proportion of study eyes with BCVA loss to a level below driving eligibility threshold at month 12 among those eligible to drive at baseline. RESULTS: Lower proportions of study eyes experienced ≥10-, ≥15-, or ≥20-BCVA letter loss from baseline over 12 months with ACP 2 mg (11.6%, 4.0%, and 1.6%, respectively) vs sham (14.1%, 7.6%, and 4.5%, respectively). There was a reduction in the risk of persistent loss of ≥15-BCVA ETDRS letters with ACP 2 mg (3.4%) vs sham (7.8%) through 12 months. A lower proportion of study eyes treated with ACP 2 mg reached the threshold for driving ineligibility vs sham by 12 months. CONCLUSIONS: Treatment with ACP 2 mg delayed the risk of progression to persistent vision loss (ie, ≥10-, ≥15-, and ≥20-BCVA letter loss or BCVA loss to a level below driving eligibility threshold) vs sham over 12 months.

Macular Holes in Tractional Retinal Detachments Secondary to Diabetic Retinopathy.

Purpose: To characterize the visual outcomes and rate of macular hole (MH) closure with tractional retinal detachment (TRD) and proliferative diabetic retinopathy (PDR). Methods: Visit data of patients who had pars plana vitrectomy were retrospectively reviewed; patient demographics, other procedure(s), the MH closure rate, and visual outcomes were also collected. Paired t, Fisher exact, and Mann-Whitney U tests were performed. Results: Ten patients (10 eyes) developed a TRD MH; 3 distinct MH presentations were identified. At the 3-month follow-up, 90% of MHs remained closed without the need for further reoperation (n = 6, type 1 closure; n = 3, type 2 closure). All MHs were closed 12 months after the initial surgery, with 1 eye requiring a single reoperation. The mean visual acuity (VA) at baseline and at 12 months was 20/235 and 20/138, respectively. Conclusions: MHs in the setting of fibrovascular proliferation resulting from PDR present with varied morphology. There is a high rate of MH closure and a trend toward improved VA.

Comparing Three-Dimensional Digitally Enabled Intraoperative OCT With Conventional Microscope-Integrated OCT in Vitreoretinal Surgery: A Post Hoc Analysis of the DISCOVER Study.

BACKGROUND AND OBJECTIVE: This study compared the surgeon experience between conventional microscope-integrated intraoperative optical coherence tomography (iOCT) and digitally enabled microscope-integrated iOCT in vitreoretinal surgery. PATIENTS AND METHODS: This is a post hoc case-control analysis of the DISCOVER study. Conventional microscope-integrated iOCT (Rescan 700, Zeiss) was compared with digitally enabled iOCT (Artevo 800, Zeiss). Compared variables included surgical field-based visualization (ie, ocular heads-up display in the conventional group; three-dimensional screen-based visualization in the digital iOCT group) and non-surgical field-based visualization (ie, review on the external two-dimensional monitor). RESULTS: A total of 200 patients were included. Surgical field-based visualization of iOCT was significantly higher in the digitally enabled group (P < 0.0001). Required endoillumination level was significantly lower in the digital iOCT group (P < 0.0001). Surgeons reported "significant" back discomfort and headache more frequently when using conventional iOCT (P = 0.003 and P = 0.001, respectively). CONCLUSIONS: Digitally enabled iOCT resulted in greater surgical visualization efficiency, appeared to require a lower illumination level, and may provide advantages for ergonomic-related discomfort. [Ophthalmic Surg Lasers Imaging Retina 2024;55:270-277.].

Ophthalmic sequelae of prematurity in late childhood and adulthood: A review.

Advances in the care of premature infants have resulted in unprecedented rates of survival of these infants into adulthood, including those born at very low gestational ages. Ophthalmologists have historically followed premature infants to assess for the presence of and potential need for treatment of retinopathy of prematurity. However, a growing body of literature suggests that the ophthalmic consequences of prematurity extended beyond retinopathy of prematurity and that ophthalmic sequelae of prematurity can endure through adulthood even among formerly preterm adults who were never diagnosed with retinopathy of prematurity. These abnormalities can include a range of both anterior segment and posterior segment sequelae, including higher rates of corneal aberrations, ocular hypertension, strabismus, foveal anomalies, and retinal tears and detachments. This review aims to summarise this literature, underscoring the importance of lifelong examinations and regular monitoring for these complications among adults who were born prematurely.

Characterizing the Journey of Geographic Atrophy Patients in Routine Ophthalmic Practice.

BACKGROUND AND OBJECTIVE: Geographic atrophy (GA) is a form of late-stage age-related macular degeneration (AMD). This study aims to characterize the journey of patients with GA in real-world ophthalmology practice. PATIENTS AND METHODS: This is a retrospective cohort study of 100 patients with GA and 100 with intermediate AMD (iAMD). RESULTS: Approximately one-third of GA patients' eyes had GA at the time of their initial AMD diagnosis, and nearly half of the iAMD patients' eyes had iAMD at that time. When holding confounders constant, GA patients experienced significantly worse visual acuity outcomes, and a significantly higher proportion required referrals for low vision evaluation, needed assistance for activities of daily living, failed to meet driving standards, and met criteria for legal blindness when compared to iAMD controls. CONCLUSIONS: Many patients have already progressed to GA by the time they receive an AMD diagnosis, emphasizing the importance of providing early detection and intervention, especially considering novel treatment options. [Ophthalmic Surg Lasers Imaging Retina 2024;55:204-210.].

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

PURPOSE: A subset of patients with neovascular age-related macular degeneration (nAMD) experience treatment burden and suboptimal response with anti-VEGF therapy. The aim of this study was to investigate the effect of switching to a novel, bispecific agent, faricimab, in patients with nAMD currently treated with anti-VEGF. DESIGN: Retrospective, noncomparative cohort study. SUBJECTS: Patients with nAMD previously treated with anti-VEGF and switched to intravitreal faricimab injection (IFI) at the Cleveland Clinic's Cole Eye Institute. METHODS: Switching and administration schedule of IFI was at the discretion of the clinician. Visual acuity (VA) and macular OCT parameters, including central subfield thickness (CST), maximum pigment epithelial detachment (PED) height, and presence of subretinal (SRF) or intraretinal fluid (IRF), were assessed at baseline (day of first IFI) and after each IFI. MAIN OUTCOME MEASURES: Central subfield thickness and presence of IRF or SRF after ≥ 3 IFIs. RESULTS: One hundred twenty-six eyes of 106 patients were included in the analysis with a mean follow-up time of 24.3 ± 5.2 weeks. Before switching to IFI, patients received a mean of either aflibercept (20.0 ± 8.4, mean ± standard deviation), bevacizumab (7 ± 8.9), ranibizumab (1.9 ± 8.5), or brolucizumab (0.3 ± 1.6) injections. The most common agent used before switching to IFI was aflibercept (n = 110, 87%), and the mean treatment interval with any anti-VEGF was 5.6 ± 1.6 weeks before switching. Central subfield thickness was reduced from baseline after the first IFI (266.8 ± 64.7 vs. 249.8 ± 58.6 µm, P = 0.02) and persisted over the 3 IFIs (P = 0.01). Pigment epithelial detachment height was reduced after the third IFI (249.6 ± 179.0 vs. 206.9 ± 130.0 µm, P = 0.01). The mean VA (62.9 vs. 62.7 approximate ETDRS letters, P = 0.42) and interval between injections (6.3 vs. 5.7 weeks, P = 0.16) was similar after the third IFI compared with baseline. Eleven (8.7%) eyes were switched back to their previous anti-VEGF, including 2 (1.6%) eyes from 1 patient with intraocular inflammation requiring cessation of IFI. There were no other adverse events from switching. CONCLUSIONS: Switching to faricimab resulted in a reduction in mean CST (-11.6 µm, P = 0.01) and PED height (-44.2 µm, P = 0.01) after 3 injections, with stable VA and at a similar treatment interval to prior anti-VEGF therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effect of Prefilled vs Vial-Drawn Syringes on Sustained Increases in Intraocular Pressure in Patients Treated With Aflibercept.

Purpose: To evaluate the effect of syringe type on developing sustained intraocular pressure (IOP) increases. Methods: This retrospective cohort study included patients in a single academic center receiving antivascular endothelial growth factor (anti-VEGF) injections from 2012 to 2022 for various indications. Patients were grouped by anti-VEGF treatment of either vial-drawn or prefilled syringe delivery. Trends in IOP were recorded for 1 year after treatment began. Development of sustained IOP increase, ocular hypertension, and glaucoma was recorded. Sustained IOP increase was defined as ≥5 mm Hg above baseline for at least 4 weeks. Results: Of 257 total patients, 6 (2.3%) developed sustained IOP increases throughout the study's duration. No significant differences were noted with respect to prefilled versus vial-drawn syringe status on the development of sustained IOP increases or incident glaucoma (IOP: 1.8% vs 2.7%, respectively, P = .65; glaucoma: 0.0% vs 2.0%, respectively, P = .14). Patients treated with prefilled syringes were significantly less likely to develop ocular hypertension (2.8% vs 8.8%, P < .05). Conclusions: This study found that aflibercept intravitreal injection with prefilled syringes was not associated with a significant increase in IOP-related adverse effects when compared with those treated with vial-drawn syringes.

Evaluation and Comparison of Ophthalmic Scientific Abstracts and References by Current Artificial Intelligence Chatbots.

Importance: Language-learning model-based artificial intelligence (AI) chatbots are growing in popularity and have significant implications for both patient education and academia. Drawbacks of using AI chatbots in generating scientific abstracts and reference lists, including inaccurate content coming from hallucinations (ie, AI-generated output that deviates from its training data), have not been fully explored. Objective: To evaluate and compare the quality of ophthalmic scientific abstracts and references generated by earlier and updated versions of a popular AI chatbot. Design, Setting, and Participants: This cross-sectional comparative study used 2 versions of an AI chatbot to generate scientific abstracts and 10 references for clinical research questions across 7 ophthalmology subspecialties. The abstracts were graded by 2 authors using modified DISCERN criteria and performance evaluation scores. Main Outcome and Measures: Scores for the chatbot-generated abstracts were compared using the t test. Abstracts were also evaluated by 2 AI output detectors. A hallucination rate for unverifiable references generated by the earlier and updated versions of the chatbot was calculated and compared. Results: The mean modified AI-DISCERN scores for the chatbot-generated abstracts were 35.9 and 38.1 (maximum of 50) for the earlier and updated versions, respectively (P = .30). Using the 2 AI output detectors, the mean fake scores (with a score of 100% meaning generated by AI) for the earlier and updated chatbot-generated abstracts were 65.4% and 10.8%, respectively (P = .01), for one detector and were 69.5% and 42.7% (P = .17) for the second detector. The mean hallucination rates for nonverifiable references generated by the earlier and updated versions were 33% and 29% (P = .74). Conclusions and Relevance: Both versions of the chatbot generated average-quality abstracts. There was a high hallucination rate of generating fake references, and caution should be used when using these AI resources for health education or academic purposes.

Visual Acuity in Patients Requiring Intravitreal Injections: Short-Term and Long-Term Effects of Delay in Care.

Purpose: To assess the short-term and long-term effects of a delay in care on visual acuity (VA) in patients requiring intravitreal injections. Methods: This retrospective cohort study comprised patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) receiving intravitreal injections. The visual and anatomic outcomes at the next completed visit and at the 1-year follow-up were studied. Results: Of 1172 patients, 38% had a delay in care (mean 5.7 weeks). Compared with baseline, these patients lost VA (Early Treatment Diabetic Retinopathy Study letters) (mean -2.13 ± 0.49 SE) in the short-term (P = .0003) and had a thicker central subfield. Patients with no delay in care had a net VA gain (0.97 ± 0.39) (P = .0067). There was no difference in VA between 1 year and the baseline in either group. Long term, patients with nAMD in both groups had VA loss (no delay in care: -1.76 ± 0.60; delayed care: -2.44 ± 0.78) (P = .0005 and P = .0114, respectively). Patients with DME and no delay in care maintained gains in vision (4.68 ± 1.86) but those with delayed care did not (1.72 ± 2.24) (P = .0202 and P = .3756, respectively). In both groups, patients with RVO had no significant difference in vision from baseline. Conclusions: In patients requiring intravitreal injections, a delay in care of 5.7 weeks affected vision outcomes in the short term but not the long term.

Identifying geographic atrophy.

PURPOSE OF REVIEW: Age-related macular degeneration (AMD) is one of the leading causes of blindness and can progress to geographic atrophy (GA) in late stages of disease. This review article highlights recent literature which assists in the accurate and timely identification of GA, and monitoring of GA progression. RECENT FINDINGS: Technology for diagnosing and monitoring GA has made significant advances in recent years, particularly regarding the use of optical coherence tomography (OCT). Identification of imaging features which may herald the development of GA or its progression is critical. Deep learning applications for OCT in AMD have shown promising growth over the past several years, but more prospective studies are needed to demonstrate generalizability and clinical utility. SUMMARY: Identification of GA and of risk factors for GA development or progression is essential when counseling AMD patients and discussing prognosis. With new therapies on the horizon for the treatment of GA, identification of risk factors for the development and progression of GA will become critical in determining the patients who would be appropriate candidates for new targeted therapies.

Outcomes in patients with retinal vein occlusion with good baseline visual acuity.

BACKGROUND: Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) are first-line therapy for macular oedema in retinal vein occlusion (RVO). Appropriate management for RVO with good visual acuity at diagnosis has not been evaluated. The purpose of this study is to analyse the visual and anatomic outcomes from anti-VEGF treatment among RVO patients with good vision at baseline. METHODS: This retrospective cohort study evaluated patients diagnosed with macular oedema secondary to RVO from January 2012 to February 2021 at a tertiary ophthalmic centre. Patients had a Snellen acuity of 20/32 or better at diagnosis. Three cohorts were compared: patients with no anti-VEGF treatment, delayed anti-VEGF treatment (initial injection >30 days post-diagnosis) and immediate anti-VEGF treatment (initial injection ≤30 days post-diagnosis). Central subfield thickness (CST) and best visual acuity (BVA) were collected at diagnosis and 6-, 12- and 24-month follow-up appointments. RESULTS: Among 131 eyes, mean BVA values among treatment groups did not differ at 6-, 12- or 24-month follow up visits (P = 0.521, 0.426, 0.356, respectively). The percentage of eyes with at least a 5-letter BVA decrease at 24 months was 24.1%, 65.0% and 30.8% in the no treatment, delayed and immediate treatment groups respectively (P = 0.010). There was no significant difference in the percentage of eyes with at least a 10% decrease in CST at 24 months among groups (P = 0.095). CONCLUSIONS: Close observation with initiation of treatment in patients with good visual acuity with macular oedema secondary to RVO as indicated has similar outcomes in the setting of routine clinical practice.

Biosimilars for retinal diseases: United States-Europe awareness survey (Bio-USER - survey).

PURPOSE: To assess the awareness of biosimilar intravitreal anti-VEGF agents among retina specialists practicing in the United States (US) and Europe. METHODS: A 16-question online survey was created in English and distributed between Dec 01, 2021 and Jan 31, 2022. A total of 112 respondents (retinal physicians) from the US and Europe participated. RESULTS: The majority of the physicians (56.3%) were familiar with anti-VEGF biosimilars. A significant number of physicians needed more information (18.75%) and real world data (25%) before switching to a biosimilar. About one half of the physicians were concerned about biosimilar safety (50%), efficacy (58.9 %), immunogenicity (50%), and their efficacy with extrapolated indications (67.8 %). Retinal physicians from the US were less inclined to shift from off-label bevacizumab to biosimilar ranibizumab or on-label bevacizumab (if approved) compared to physicians from Europe (p=0.0001). Furthermore, physicians from the US were more concerned about biosimilar safety (p=0.0371) and efficacy compared to Europe (p= 0.0078). CONCLUSIONS: The Bio-USER survey revealed that while the majority of retinal physicians need additional information regarding the safety, efficacy and immunogenicity when making clinical decisions regarding their use. Retinal physicians from US are more comfortable in continuing to use off-label bevacizumab compared to physicians from Europe.

Characterization of ophthalmology virtual visits during the COVID-19 pandemic.

OBJECTIVES: To characterize the use of virtual visits, as well as compare the characteristics to in-person visits during the pandemic period. METHODS: This retrospective study included patients who had virtual and in-person ophthalmology visits from March 19, 2020, to July 31, 2020, in a large multispecialty ophthalmic center. Exclusion criteria included patients aged less than 18 years old; canceled, incomplete, mislabelled, and duplicated visits. 2943 virtual and 56,174 in-person visits were identified. A random sample of 3000 in-person visits was created. Each visit was analyzed as an individual data point. RESULTS: 2,266 virtual visits (2,049 patients, 64.3% female, mean [SD] age 64.3 [16.6] years old) and 2590 in-person visits (2509 patients, 59.5% female, 65.9 [15.8] years old) were included. Most virtual visits were classified as comprehensive ophthalmology (34.6%), optometry-related (19.5%), and oculoplastics (13.0%). For in-person visits, the most common specialties were optometry (29.8%), comprehensive ophthalmology (23.9%), and retina and uveitis (17.3%). The most common diagnoses in the virtual group were from the eyelids, lacrimal system, and orbits group (26.9%), while in the in-person groups were choroid and retina conditions (19.3%). CONCLUSIONS: Numerous ocular conditions were evaluated and managed through virtual visits, and external complaints and oculoplastic consults appear to be well-suited to the virtual format. Further studies focusing on visual outcomes and patient experience will be beneficial.

Visual, Anatomic Outcomes, and Natural History of Retinal Nerve Fiber Layer Schisis in Patients Undergoing Epiretinal Membrane Surgery.

PURPOSE: To evaluate the anatomic and visual outcomes of patients with idiopathic epiretinal membranes (ERMs) complicated by schisis of the retinal nerve fiber layer (sRNFL) in routine clinical practice. DESIGN: Retrospective case-control study. PARTICIPANTS: Patients undergoing idiopathic ERM surgery at Cole Eye Institute from 2013 to 2021. METHODS: Patients were grouped by the presence or absence of sRNFL before surgery. Preoperative and postoperative data were collected regarding visual acuity (VA), changes in central subfield thickness (CST) over time, and presence of cystoid macular edema. MAIN OUTCOME MEASURES: Frequency of sRNFL in patients undergoing idiopathic ERM surgery. RESULTS: Overall, 48 (53.9%) of 89 patients presented with sRNFL. Schisis of the retinal nerve fiber layer patients presented with significantly decreased VA compared with those without (58.63 ± 12.48 vs. 67.68 ± 7.84 ETDRS letters, P < 0.001, respectively). At the final follow-up after ERM removal, there was no significant difference in final VA in patients with sRNFL compared with those without (71.16 ± 2.93 vs. 74.11 ± 2.76, P = 0.467). At presentation, patients with sRNFL had greater CST than those without (454 ± 10.01 vs. 436 ± 0.23, P = 0.23). This difference persisted at the 90-day follow-up after ERM removal (402 ± 8.08 vs. 375 ± 10.19 µm, P = 0.043). The resolution of sRNFL was reported at postoperative week 1 in 30 (96.7%) of 31 cases. CONCLUSIONS: Schisis of the retinal nerve fiber layer is a microstructural feature in > 50% of idiopathic ERMs in routine clinical practice and carries visual significance on presentation and anatomic significance postoperatively. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Representation of Race and Ethnicity in Randomized Clinical Trials of Diabetic Macular Edema and Retinal Vein Occlusion Compared to 2010 US Census Data.

Importance: Diverse enrollment and adequate representation of racial and ethnic minority groups in randomized clinical trials (RCTs) are valuable to ensure external validity and applicability of results. Objective: To compare the distribution of race and ethnicity in RCTs of diabetic macular edema (DME) and macular edema from retinal vein occlusion (RVO) to that of US Census data. Design, Setting, and Participants: This was a cross-sectional retrospective analysis comparing racial and ethnic demographic characteristics of US-based RCTs of DME and RVO between 2004 and 2020 with 2010 US Census data. PubMed and ClinicalTrials.gov were searched to screen for completed phase 3 RCTs with published results. Of 169 trials screened, 146 were excluded because they were incomplete, did not report race and ethnicity, or were not based in the US, and 23 trials were included (15 DME and 8 RVO). The number and percentage of American Indian or Alaska Native, Asian, Black, Hispanic, Native Hawaiian or Other Pacific Islander, and White participants was recorded in each RCT. The demographic distribution and proportion was compared to the reported distribution and proportion in the 2010 US Census using the χ2 test. Main Outcomes and Measures: Overrepresentation, underrepresentation, or representation commensurate with 2010 US Census data in the racial and ethnic populations of RCTs of retinal vascular disease. Results: In 23 included RCTs of DME and RVO, there were a total of 38 participants (0.4%) who identified as American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander (groups combined owing to small numbers), 415 Asian participants (4.4%), 904 Black participants (9.6%), 954 Hispanic participants (10.1%), and 7613 White participants (80.4%). By comparison, the 2010 US Census data indicated that 1.1% of the US population self-reported as American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander (groups combined for comparison in this study), 4.8% self-reported as Asian, 12.6% as Black or African American, 16.3% as Hispanic, and 63.7% as White. American Indian or Alaska Native and Hawaiian or Other Pacific Islander participants were underrepresented in 2 trials, neither overrepresented nor underrepresented in 20, and not overrepresented in any of the included trials. Asian participants were underrepresented in 10 trials, overrepresented in 4, and neither overrepresented nor underrepresented in 8. Black participants were underrepresented in 9 trials, overrepresented in 2, and neither overrepresented nor underrepresented in 11. Hispanic participants were underrepresented in 15 trials, overrepresented in 2, and neither overrepresented nor underrepresented in 5. White participants were underrepresented in 2 trials, overrepresented in 14, and neither overrepresented nor underrepresented in 7. The χ2 values comparing RCT demographic distribution to US 2010 Census data were significantly different in 22 of 23 included RCTs. Conclusions and Relevance: The findings in this study indicated a discrepancy between racial and ethnic demographic data in RCTs of DME and RVO and the US population according to the 2010 Census. White study participants were most frequently overrepresented, and Hispanic study participants were most frequently underrepresented. These findings support the need for more efforts to recruit underrepresented racial and ethnic minorities to improve external validity in trial findings.