Risk Factors for Worsening Morphology and Visual Acuity in Eyes with Adult-Onset Foveomacular Vitelliform Dystrophy.

PURPOSE: To explore clinical risk factors and OCT features associated with worse visual acuity (VA), progression of disease, choroidal neovascularization (CNV), and atrophy in eyes with adult-onset foveomacular vitelliform dystrophy (AOFVD). DESIGN: Single-center, retrospective, observational cohort study. PARTICIPANTS: Patients seen at Duke Eye Center between January 2012 and May 2023 with a diagnosis of AOFVD confirmed via OCT and fundus autofluorescence. METHODS: Baseline and final-visit images from eyes with AOFVD were examined. Disease stage was assigned, and presence of atrophy or CNV was determined. Clinical and OCT features associated with progression to atrophy and CNV were determined using t tests and chi-square analysis. Correlation with lower VA was determined using linear regression. MAIN OUTCOME MEASURES: Association of clinical characteristics and OCT features with worse VA, progression of disease, CNV, and atrophy as determined by independent t tests, chi-square analysis, and linear regression (P < 0.05). RESULTS: One hundred one eyes (63 patients) met inclusion criteria for this study, with mean follow-up duration of 48 months (standard deviation, 31 months). Fifty-one percent of eyes progressed beyond baseline staging during follow-up; among baseline stage 1 eyes, incidence of atrophy was 0.068/person-year; incidence of CNV was 0.022/person-year. Risk factors for worse final VA were baseline presence of vitreomacular traction ([VMT], P = 0.006), ellipsoid zone attenuation (P = 0.02), and increased lesion height and width (P < 0.001). Predictors of progression include diabetes mellitus (P = 0.01), statin use (P = 0.03), presence of hyperreflective foci (P = 0.01), and increased lesion width and volume (P = 0.03 and P = 0.04, respectively). Predictors of atrophy include the baseline presence of VMT (P = 0.02), decreased choroidal thickness (P = 0.03), and greater maximal height, width, and volume of the lesion (P = 0.03, P = 0.02, and P = 0.009, respectively). Lower baseline VA (P = 0.03) and increased lesion volume (P = 0.04) were associated with CNV. CONCLUSIONS: Clinical and OCT imaging features at baseline may prove useful in stratifying patient risk for progression, atrophy, CNV, and worse VA. Features such as statin use, diabetes, baseline VA, and laterality should be accounted for. OCT features, such as lesion size, VMT, ellipsoid zone attenuation, choroidal thickness, and hyperreflective foci, may impart greater risk of poor outcomes. Future prospective analysis accounting for the time to development of atrophy and CNV is needed. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Compartmental Exudative Dynamics in Neovascular Age-Related Macular Degeneration: Volumetric Outcomes and Impact of Volatility in a Phase III Clinical Trial.

PURPOSE: To examine retinal feature dynamics in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF therapy and the relationship of these features with visual acuity. DESIGN: Post hoc analysis of the phase III, randomized, HAWK nAMD clinical trial. PARTICIPANTS: Participants randomized to the brolucizumab 6 mg or aflibercept 2 mg arms of the trial. METHODS: Spectral-domain OCT scans collected at 4-week intervals were analyzed using an automated machine learning-enhanced segmentation and feature-extraction platform with manual verification. Quantitative volumetric measures of retinal and exudative features were exported at multiple timepoints over 48 weeks. Volatility of exudative features was calculated as the standard deviation of each feature value during the maintenance phase (week 12-48) of treatment. These features were examined for their associations with anatomic and functional outcomes. MAIN OUTCOME MEASURES: Longitudinal intraretinal fluid (IRF) and subretinal fluid (SRF) volume, subretinal hyperreflective material (SHRM) volume, ellipsoid zone (EZ) integrity (EZ-retinal pigment epithelium [RPE] volume/thickness), and correlation with best-corrected visual acuity (BCVA). RESULTS: Intraretinal fluid, SRF, and SHRM demonstrated significant volumetric reduction from baseline with anti-VEGF therapy (P < 0.001 at each timepoint). Ellipsoid zone integrity measures demonstrated significant improvement from baseline (P < 0.001 at each timepoint). Both EZ integrity and SHRM measures correlated significantly with BCVA at all timepoints (EZ-RPE volume: 0.38 ≤ r ≤ 0.47; EZ-RPE central subfield thickness: 0.22 ≤ r ≤ 0.41; SHRM volume: -0.33 ≤ r ≤ -0.44). After treatment initiation, correlations of IRF and SRF volume with BCVA were weak or nonsignificant. Eyes with lower volatility of IRF, SRF, and SHRM volumes during the maintenance phase showed greater improvements in EZ integrity (all P < 0.01) and greater gains in BCVA (all P < 0.01) at week 48 compared with eyes with higher volatility in those exudative parameters. CONCLUSIONS: Quantitative measures of SHRM volume and EZ integrity correlated more strongly with BCVA than retinal fluid volumes during treatment. High volatility of exudative parameters, including SRF, during the maintenance phase of treatment was associated with loss of EZ integrity and BCVA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Autoimmune-Related Retinopathy Presenting As Plaquenil Toxicity in Patients With Systemic Lupus Erythematosus.

Purpose: To report 3 cases of autoimmune retinopathy (AIR) in patients with systemic lupus erythematosus (SLE) to explore the association between these conditions and highlight additional clinical consideration of AIR in patients presenting with atypical retinopathy in the context of hydroxychloroquine use. Methods: The medical and clinical follow-up records of 3 clinical cases were reviewed. The eligibility criteria were the absence of other retinopathy or systemic autoimmune diseases. Results: All patients had a long-standing diagnosis of SLE and had been taking hydroxychloroquine at a dose exceeding the American Academy of Ophthalmology recommendations. All 3 patients had extensive retinal degeneration atypical in appearance for drug toxicity alone. Examination, imaging, electroretinograms, and autoantibody assays eventually led to the diagnosis of AIR. Conclusions: Further study of the AIR and SLE may reveal an association between these conditions. In patients with SLE presenting with retinal degeneration, AIR may be underdiagnosed.

Based on the Real-Life Data of Türkiye; Comparison of Anatomical and Functional Outcomes of Phakic and Pseudophakic Patients in Wet Type Age-Related Macular Degeneration.

Objectives: The aim of the study was comparison of wet-type age-related macular degeneration in phakic and pseudophakic patients in terms of anatomical and functional success based on the real-life data of Türkiye. Methods: The multicenter retrospective real-life study data of the. retinal study group were used in this study. Among 867 eyes of 867 patients were included in the study. Patients were divided into two groups according to the status of the lens; phakic group and pseudophakic group. The follow-up period of the two groups, the number of injections at the 1st, 2nd, and 3rd years, and changes in the central macular thickness (CMT, µ) and visual acuity (VA, logMAR) of the patients at the beginning, 6th, 12th, 24th, and 36th months were examined. Results: In our study, the number of injections in the 1st, 2nd, and 3rd years, respectively, was 4.2±2.0, 1.8±1.9, and 1.0±1.7 in the phakic group, and 3.9±2.0, 1.7±1.9, and 0.8±1.4 in the pseudophakic group. When the two groups were compared in terms of the number of injections, there was a statistically significant difference in the 1st year, but there was no significant difference in the 2nd and 3rd years (p=0.001, p=0.350, and p=0.288, respectively). There was no statistically significant difference between the groups in terms of CMT in the baseline, 6th, 12th, 24th, and 36th months (p=0.991, p=0.327, p=0.652, p=0.599, and p=0.873, respectively). Although there was no difference in VA between groups at the beginning (p=0.052), the phakic group showed statistically better VA in controls at 3rd, 6th, 12th, 24th, and 36th months (p=0.001, p=0.001, p=0.000, p=0.000, and p=0.003, respectively). Conclusion: Differences in the number of injections and visual results between phakic and pseudophakic patients in wet type AMD may necessitate the creation of different treatment and follow-up protocols.

Results of anti-VEGF treatment for neovascular AMD in eyes with different baseline visual acuity in Turkish population-based on real life data-Bosphorus retina study group.

BACKGROUND: To investigate the anatomical and visual outcomes of the patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (anti-VEGF), according to the baseline best-corrected visual acuity (BCVA) based on the multicenter real-life data. METHODS: Five-hundred-ninety patients who had taken the Pro Re Nata (PRN) treatment regimen with three loading doses and at least one year of follow-up were included. The patients were divided into three groups according to the baseline BCVA: Group 1 (BCVA ≥ 1.3 Logmar), Group 2 (1.3 Logmar > BCVA ≥ 0.3 Logmar), and Group 3 (BCVA ≤ 0.2 Logmar). BCVA, central macular thickness (CMT), and the number of injections and visits were evaluated. RESULTS: There were 175, 322, and 93 patients in Group 1, Group 2, and Group 3, respectively. The number of visits and injections in the 1st year was not different between the groups (p = 0.58 and p = 0.08) and was 7.09 and 4.41 (Group 1), 6.59 and 5.58 (Group 2), 6.77 and 4.08 (Group 3). There was a significant difference in CMT between the baseline and 12th month in Group 1 and Group 2 (p < 0.001, p < 0.001, respectively) but not in Group 3 (p = 0.84). BCVA was significantly better in the 12th month in Group 1 (p < 0.001), slightly worse in Group 2 (p = 0.79), and significantly worse in Group 3 (p < 0.001). CONCLUSION: This study provides evidence that an inadequate number of injections cannot protect vision. Moreover, it can cause vision loss, especially in the eyes with good vision.

The double-edged sword of inflammation in inherited retinal degenerations: Clinical and preclinical evidence for mechanistically and prognostically impactful but treatable complications.

We present retrospective data from our clinical research efforts of the past several years alongside a review of past and current clinical and preclinical data independently by several investigators supporting our clinical evidence for the importance of inflammation in inherited retinal degenerations (IRDs). We show how inflammation is a complicating factor in IRDs but, if recognized and managed, also a great opportunity to mitigate disease severity immediately, improve patient prognosis and quality of life, extend the treatment windows for gene-specific and agnostic therapeutic approaches, mitigate the impact of inflammatory complications on the accurate estimate of vision changes in IRD natural history studies, improve the chances of safer outcomes following cataract surgery, and potentially reduce the likelihood of inflammatory adverse events and augment the efficacy of viral vector-based treatment approaches to IRDs. Manuscript contribution to the field. Inflammation has been suspected to be at play in IRDs since the beginning of the 1900s and became a research focus through the early 1990s but was then largely abandoned in favor of genetic-focused research. Thanks to regained cognizance, better research tools, and a more holistic approach to IRDs, the recent reappraisal of the role of inflammation in IRDs has brought back to the surface its importance. A potential confounder in natural history studies and a limiting factor in clinical trials if not accounted for, inflammation can be managed and often offers an opportunity for immediately improved prognosis and outcomes for IRD patients. We present our retrospective clinical evidence for connections with a measurable secondary autoimmune component that can develop in IRDs and contribute to vision loss but is at least in part treatable. We also present ample lines of evidence from the literature corroborating our clinical observations at the preclinical level.

Longitudinal Quantitative Ultrawide-field Fluorescein Angiography Dynamics in the RUBY Diabetic Macular Edema Study.

OBJECTIVE: The purpose of this study was to evaluate the longitudinal change in quantitative ultrawide-field angiographic (UWFA) parameters and correlate them with functional outcomes and spectral domain-OCT metrics. DESIGN: This study is a post hoc analysis of the phase II RUBY study: a prospective, randomized trial of patients with diabetic macular edema (DME) treated with either intravitreal aflibercept injection (IAI) or combined IAI/nesvacumab (antiangiopoietin 2 mAb). SUBJECTS: Subjects with DME that underwent UWFA across all treatment groups (n = 44). METHODS: A machine learning-enabled feature extraction system generated panretinal quantitative UWFA metrics, including leakage, ischemia, and microaneurysm (MA) burden. Zonal assessments were performed corresponding to the macula, midperiphery, and far periphery. MAIN OUTCOME MEASURES: Changes in ischemic area and index (proportion of nonperfusion in analyzable retina), leakage area and index (proportion of leakage in analyzable retina), and MA count at baseline, week 12, week 24, and week 36 were analyzed. Spectral-domain-OCT quantitative metrics, such as central subfield thickness, ellipsoid zone (EZ) integrity parameters, intraretinal fluid (IRF) volume, and subretinal fluid (SRF) volume were extracted via a machine learning-enhanced OCT feature extraction platform and analyzed. Additionally, the effect of these changes on best-corrected visual acuity (BCVA) was evaluated. RESULTS: Mean panretinal leakage index, zonal leakage area, and panretinal MA count improved significantly between baseline and week 36. Panretinal ischemic index decreased between baseline and week 36, with some aspects showing significant improvement. Mean BCVA significantly improved from baseline to week 36. There was a significant inverse correlation between change in BCVA and change in macular leakage area. A direct correlation was observed between both baseline macular leakage area and panretinal leakage index with IRF volume, SRF volume, and EZ disruption on OCT. CONCLUSIONS: Assessment of UWFA parameters demonstrates a significant improvement in panretinal leakage index, leakage area, and MA burden in eyes treated with IAI with or without nesvacumab. A numeric reduction in panretinal ischemic index and area was noted. The analysis also shows the critical association of leakage with visual and OCT features. This highlights the potential role of UWFA in disease burden assessment, with leakage parameters serving as a primary end point. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Bacillary Detachment in Neovascular Age-Related Macular Degeneration: Incidence, Clinical Features, and Response to Anti-VEGF Therapy.

OBJECTIVE: To evaluate the incidence of bacillary layer detachment among patients with neovascular age-related macular degeneration (nAMD) and their response to anti-VEGF therapy. DESIGN: Post hoc analysis of the OSPREY clinical trial, a prospective, double-masked, phase II study comparing 6-mg brolucizumab with 2-mg aflibercept over 56 weeks. PARTICIPANTS: Participants with treatment-naive nAMD at the initiation of the trial were included in the analysis (n = 81). METHODS: Spectral-domain OCT (SD-OCT) scans were obtained at 4-week intervals throughout the OSPREY study and were segmented automatically using a proprietary, machine learning-enabled higher-order feature-extraction platform. MAIN OUTCOME MEASURES: The presence of bacillary detachment, and in these eyes the effect of anti-VEGF therapy on change from baseline in visual acuity (VA), central subfield thickness (CST), retinal fluid volumes, subretinal hyper-reflective material (SHRM) volume, subretinal pigment epithelium (sub-RPE) fluid volume, and ellipsoid zone (EZ) integrity at week 56. RESULTS: Bacillary detachment was identified in 7.4% (6 of 81) eyes, which had higher fluid volumes, increased CST, EZ attenuation, and increased sub-RPE volume at baseline compared with eyes without bacillary detachment. Anti-VEGF treatment resulted in the resolution of bacillary detachment in 100% of the eyes. In eyes with bacillary detachment at baseline, the anti-VEGF treatment decreased CST, fluid burden, and SHRM volumes throughout the treatment course; however, there was no significant change from baseline in VA, sub-RPE volume, or EZ integrity throughout the 56-week course of anti-VEGF treatment. CONCLUSIONS: Bacillary detachment is an OCT signature that is identifiable in a notable proportion of nAMD eyes. Anti-VEGF therapy resulted in 100% resolution of bacillary detachment and significant decreases in CST and SHRM volume; however, improvements in VA may have been limited by persistent EZ attenuation.

Corneal epithelial defects following vitreoretinal surgery: incidence and outcomes from the DISCOVER study.

AIM: To investigate the incidence, risk factors, clinical course, and outcomes of corneal epithelial defects (CED) following vitreoretinal surgery in a prospective study setting. METHODS: This was a post-hoc analysis of all participants in DISCOVER intraoperative optical coherence tomography study. Subjects with CED 1d after surgery without intraoperative corneal debridement was defined as the postoperative CED group. Subjects who underwent intraoperative debridement were defined as intraoperative debridement group. Eyes were matched 2:1 with controls (eyes without postoperative CED) for comparative assessment. The primary outcomes were the incidence of CED on postoperative day one and the incidence of required intraoperative debridement. Secondary outcomes included time to defect closure, delayed healing (>2wk), visual acuity (VA) and presence of scarring at one year and cornea consult. RESULTS: This study included 856 eyes that underwent vitreoretinal surgery. Intraoperative corneal debridement was performed to 61 (7.1%) subjects and postoperative CED developed spontaneously in 94 (11.0%) subjects. Significant factors associated with postoperative CED included prolonged surgical duration (P=0.003), diabetes mellitus (P=0.04), postoperative ocular hypotension (P<0.001). Prolonged surgical duration was associated with intraoperative debridement. Delayed defect closure time (>2wk) was associated with corneal scar formation at the end of the 1y in all epithelial defect subjects (P<0.001). The overall rate of corneal scarring for all eyes undergoing vitrectomy was 1.8%. CONCLUSION: Prolonged duration of surgery is the strongest factor associated with both intraoperative debridement and spontaneous postoperative CED. Delayed defect closure is associated with a greater risk of corneal scarring at one year. The overall rate of corneal scarring following vitrectomy is low at <2%.

Risk Classification for Progression to Subfoveal Geographic Atrophy in Dry Age-Related Macular Degeneration Using Machine Learning-Enabled Outer Retinal Feature Extraction.

BACKGROUND AND OBJECTIVE: To evaluate the utility of spectral-domain optical coherence tomography biomarkers to predict the development of subfoveal geographic atrophy (sfGA). PATIENTS AND METHODS: This was a retrospective cohort analysis including 137 individuals with dry age-related macular degeneration without sfGA with 5 years of follow-up. Multiple spectral-domain optical coherence tomography quantitative metrics were generated, including ellipsoid zone (EZ) integrity and subretinal pigment epithelium (sub-RPE) compartment features. RESULTS: Reduced mean EZ-RPE central subfield thickness and increased sub-RPE compartment thickness were significantly different between sfGA convertors and nonconvertors at baseline in both 2-year and 5-year sfGA risk assessment. Longitudinal change assessment showed a significantly higher degradation of EZ integrity in sfGA convertors. The predictive performance of a machine learning classification model based on 5-year and 2-year risk conversion to sfGA demonstrated an area under the receiver operating characteristic curve of 0.92 ± 0.06 and 0.96 ± 0.04, respectively. CONCLUSIONS: Quantitative outer retinal and sub-RPE feature assessment using a machine learning-enabled retinal segmentation platform provides multiple parameters that are associated with progression to sfGA. [Ophthalmic Surg Lasers Imaging. 2022;53:31-39.].

Comparison of two different treatment regimens' efficacy in neovascular age-related macular degeneration in Turkish population-based on real life data-Bosphorus RWE Study Group.

AIM: To compare two different anti-vascular endothelial growth factor (anti-VEGF) treatment regimens'-a priori pro re nata (PRN) and PRN regimen following the loading phase-anatomical and functional results in neovascular age-related macular degeneration (nAMD) patients. METHODS: Totally 544 nAMD patients followed and treated with aflibercept (n=135) and ranibizumab (n=409) at 9 different centers between 2013 and 2015 were enrolled into this retrospective multicenter study. Patients with initial best corrected visual acuity (BCVA) interval of 1.3-0.3 (logMAR) and a minimum follow-up of 12mo were included. Patients under two different regimens-a priori pro re nata (1+PRN) or 3 consecutive intravitreal injections followed by a PRN regimen (3+PRN)-were compared in BCVA at 3th, 6th and 12th months, and in central macular thickness (CMT) at 6th and 12th months. The total study group, intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) groups were evaluated separately. RESULTS: The mean CMT decreased in the 1+PRN (n=101) regimen from 407 to 358 and 340 µm and in the 3+PRN (n=443) group from 398 to 318 and finally to 310 µm at months 6 and 12, respectively. Anatomically, the CMT reduction at 6th month (48.5 vs 76.4; P<0.05) was statistically significant in favor of 3+PRN group. BCVA changed in 1+PRN group from 0.77 to 0.78, 0.75 and 0.75; in 3+PRN group from 0.81 to 0.69, 0.72, and 0.76 at months 3, 6, and 12, respectively. Visual gain was statistically better in 3+PRN group at 3th month (-0.01 vs 0.12; P<0.001). In IVR group, CMT reduction was in greater in 3+PRN at 6th (44 vs 72) and 12th month (61 vs 84), but statistically insignificant. The 3+PRN group revealed statistically better visual results at 3th month (-0.02 vs 0.11, P<0.05). In IVA group, although statistically insignificant, CMT reduction (61 vs 89, 6th month; 85 vs 97, 12th month) and visual gain (0.02 vs 0.16; 0.02 vs 0.14; 0.05 vs 0.11) was found in favor of 3+PRN group at all visits. CONCLUSION: The loading dose of anti-VEGF treatments in nAMD leads to significantly better anatomical and functional results, regardless of the agent, specially in early follow-up interval.

Real-World Outcomes of Anti-VEGF Treatment for Neovascular Age-Related Macular Degeneration in Turkey: A Multicenter Retrospective Study, Bosphorus Retina Study Group Report No: 1.

OBJECTIVES: To evaluate the real-world outcomes of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in neovascular age-related macular degeneration (nAMD) patients. MATERIALS AND METHODS: Multicenter, retrospective, interventional, non-comparative study. The records of nAMD patients treated with an anti-VEGF agent on a pro re nata treatment regimen basis between January 2013 and December 2015 were reviewed. The patients who completed a follow-up period of 12 months were included. Primary outcome measures of this study were the visit and injection numbers during the first year. RESULTS: Eight hundred eighty eyes of 783 patients met the inclusion criteria for the study. Mean number of visits at month 12 was 6.9±2.5 (range: 1-15). Mean number of injections at month 12 was 4.1±1.9 (range: 1-11). Mean visual acuity at baseline and months 3, 6, and 12 was 0.90±0.63 LogMAR (range: 0.0-3.0), 0.79±0.57 LogMAR (range: 0.0-3.0), 0.76±0.57 LogMAR (range: 0.0-3.0), and 0.79±0.59 LogMAR (range: 0.0-3.0), respectively. Mean central retinal thickness at baseline and months 6 and 12 was 395±153 µm (range: 91-1582), 330±115 µm (range: 99-975), and 332±114 µm (range: 106-1191), respectively. CONCLUSION: The numbers of visits and injections were much lower than ideal and were insufficient with the pro re nata treatment regimen.