LONGITUDINAL ELLIPSOID ZONE AND OUTER RETINAL INTEGRITY DYNAMICS AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To quantify ellipsoid zone (EZ) changes in integrity after epiretinal membrane (ERM) surgery, correlate findings to visual acuity, and determine predictors for prognosis. METHODS: A post hoc analysis of eyes undergoing ERM surgery pooled from the prospective DISCOVER intraoperative optical coherence tomography study and eyes undergoing conventional ERM surgery without intraoperative optical coherence tomography. Quantitative EZ features were extracted using a multilayer machine learning enabled automated segmentation platform after image analyst review/correction for segmentation accuracy. Visual acuity and EZ integrity were quantitatively assessed and correlated before and after ERM surgery. Multiple linear regression was performed to assess preoperative visual acuity and EZ features as predictors for improvement in visual acuity or EZ integrity. RESULTS: There were 177 eyes from 177 subjects that underwent ERM surgery from the DISCOVER and conventional arms. Improvement in visual acuity and multiple EZ integrity features was noted after ERM surgery, including EZ partial attenuation and EZ-retinal pigment epithelium (RPE) volume (P < 0.05). A reduction in EZ partial attenuation and increase in EZ-RPE central subfield thickness (EZ-RPE CST) was significantly correlated with improved visual acuity after ERM surgery (P < 0.05). More robust EZ-RPE CST at baseline predicted visual acuity improvement after ERM peel in regression modeling (ß = 0.005, P < 0.05). CONCLUSIONS: Longitudinal assessment of EZ features demonstrates significant postoperative improvement in multiple EZ integrity metrics after ERM surgery. Improving EZ integrity was correlated to improving the visual acuity. Ellipsoid zone integrity and visual acuity were significant predictors in regression modeling and may have value in clinical prognostication.

LONGITUDINAL ELLIPSOID ZONE DYNAMICS AFTER MACULAR HOLE REPAIR IN THE DISCOVER STUDY: Structure-Function Assessment.

PURPOSE: To evaluate association of the baseline macular hole (MH) geometric features and longitudinal ellipsoid zone integrity with the visual acuity outcome after surgical repair. METHODS: This was a post-hoc analysis of eyes in the DISCOVER study undergoing vitrectomy repair for MH. Anatomical and functional data were collected through one year postoperatively. An automated retinal layer segmentation platform was used for the assessment of outer retinal metrics and volumetric reconstruction of MH. Association of longitudinal ellipsoid zone features and baseline MH height, width, and volume with VA outcomes were investigated. RESULTS: Eighty-four eyes with MH were included. The mean baseline VA was 20 of 114 and increased to 20 of 45 (P < 0.001) at postoperative Month 12 (N = 45). Successful MH closure was achieved in 98.8% of cases. Ellipsoid zone integrity metrics significantly improved from baseline (P = 0.002) and postoperative Month 1 (P < 0.001) to post-operative Month 12. Ellipsoid zone metrics independently correlated with VA at all follow-up visits (P < 0.05). Increased baseline MH width and volume negatively correlated with the VA at postoperative Month 12 (P < 0.001). Preoperative VA and EZ integrity on optical coherence tomography were predictors for postoperative VA. CONCLUSION: Baseline MH volumetric parameters and EZ parameters were associated with VA outcomes after repair.

Implementation of the Addendum Guidelines for Peanut Allergy Prevention by US allergists, a survey conducted by the NIAID, in collaboration with the AAAAI.

BACKGROUND: In 2017, the Addendum Guidelines for the Prevention of Peanut Allergy were published with recommendations on early introduction of peanut-containing foods based on infants' clinical history. OBJECTIVE: We sought to conduct a nationwide US survey to assess Guidelines implementation among allergists and immunologists who manage infants for food allergy. METHODS: Survey invitations were delivered to 3281 nonretired, US members of the American Academy of Asthma, Allergy & Immunology, board certified in allergy and immunology. The survey assessed awareness and implementation of the Guidelines and barriers to implementation. Descriptive statistics were generated. RESULTS: Twenty-nine percent (946 of 3281) of surveyed allergists/immunologists responded, and 87.1% (825 of 946) of responders met eligibility criteria. Among eligible responders, 97.1% were aware of the Guidelines. Of these, 64.5% reported full implementation of the Guidelines as published, 34.4% reported partial implementation, and 1.1% reported using none of the Guidelines. Barriers to Guidelines use included parental (47.6%) and self (21.8%) concerns about allergic reactions, lack of referrals (33.6%), parents uninterested in early feeding (28.2%), and lack of clinic time (20.9%). The 2 most common deviations from the Guidelines were considering additional factors not specified in the Guidelines such as family history (50.2%) and conducting skin prick testing in non-high-risk children (43.9%). Of respondents using the Guidelines, 45.7% indicated they needed more education or training. CONCLUSIONS: Essentially all allergists/immunologists who responded to the survey reported full or partial Guidelines implementation. Parental concerns and lack of referrals are major identifiable barriers. Improved Guidelines messaging to parents and referring physicians is warranted.

RETINAL LEAKAGE INDEX DYNAMICS ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN EYES TREATED WITH INTRAVITREAL AFLIBERCEPT FOR PROLIFERATIVE DIABETIC RETINOPATHY IN THE RECOVERY STUDY.

PURPOSE: Characterization of leakage indices on ultra-widefield fluorescein angiography in proliferative diabetic retinopathy treated with intravitreal aflibercept. METHODS: Prospective study enrolling subjects for treatment of proliferative diabetic retinopathy randomized 1:1 to receive 2-mg intravitreal aflibercept every 4 weeks (2q4) or every 12 weeks (2q12). Ultra-widefield fluorescein angiography images obtained at baseline, 24, and 48 weeks were analyzed using a semiautomated leakage segmentation platform. Panretinal and zonal leakage indices were calculated. RESULTS: Forty eyes of 40 subjects were included, and mean age was 48 ± 12.1 years. Mean number of injections was 11 ± 1.7 in the 2q4 arm and 4 ± 0.4 in the 2q12 arm. Median baseline leakage index in the 2q4 and 2q12 groups was 5.1% and 4.3%, respectively (P = 0.28). At 24 and 48 weeks, the 2q4 group significantly improved to 1.1% (-79%, P < 0.0001). At Week 24, the 2q12 group demonstrated nonsignificant improvement (3.4%; -21%, P = 0.47); by Week 48, improvement was significant (1.4%; -68%, P = 0.02). The 2q4 group resulted in lower leakage index compared with the 2q12 group at 24 weeks (1.1% vs. 3.4%, respectively; P = 0.008), but by 48 weeks, leakage index was similar between both groups (1.1% vs. 1.4%, respectively; P = 0.34). CONCLUSION: Proliferative diabetic retinopathy treated with intravitreal aflibercept demonstrated significant leakage index reductions at 1 year. Monthly dosing provided more rapid reduction in leakage index compared with quarterly dosing. TRIAL REGISTRATION: RECOVERY study (NCT02863354); https://clinicaltrials.gov/ct2/show/NCT02863354.

Quantitative Ultra-Widefield Angiography and Diabetic Retinopathy Severity: An Assessment of Panretinal Leakage Index, Ischemic Index and Microaneurysm Count.

PURPOSE: To investigate the relationship between the diabetic retinopathy (DR) severity and quantitative ultra-widefield angiographic metrics, including leakage index, ischemic index, and microaneurysm count. DESIGN: Retrospective image analysis study. METHODS: Eyes with DR that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color photography were identified. All eyes were laser-naive and had not received any intravitreal pharmacotherapy within 6 months of UWFA. Each eye was graded for DR severity. Quantitative angiographic parameters were evaluated with a semiautomated analysis platform with expert reader correction, as needed. Angiographic parameters included panretinal leakage index, ischemic index, and microaneurysm count. Clinical characteristics analyzed included age, gender, race, hemoglobin A1C level, hypertension, systolic blood pressure, diastolic blood pressure, and smoking history. MAIN OUTCOME MEASURES: Association of DR severity with panretinal leakage index, ischemic index, and microaneurysm count. RESULTS: Three hundred thirty-nine eyes were included with mean age of 62±13 years. Forty-two percent of eyes were from women and 57.5% were from men. Distribution of DR severity was as follows: mild NPDR in 11.2%, moderate NPDR in 23.9%, severe NPDR in 40.1%, and PDR with 24.8%. Panretinal leakage index [mild NPDR (mean = 0.51%), moderate NPDR mean = 1.20%, severe NPDR (mean = 2.75%), and PDR (mean = 5.84%); P<2×10-16], panretinal ischemic index [mild NPDR (mean = 0.95%, moderate NPDR (mean = 1.37%), severe NPDR (mean = 2.80%), and PDR (mean = 9.53%); P<2×10-16], and panretinal microaneurysm count [mild NPDR (mean = 36), moderate NPDR (mean = 129), severe NPDR (mean = 203), and PDR (mean = 254); P<5×10-7] were strongly associated with DR severity. Multivariate analysis demonstrated that ischemic index and leakage index were the parameters associated most strongly with level of DR severity. CONCLUSIONS: Panretinal leakage index, panretinal ischemic index, and panretinal microaneurysm count are associated with DR severity. Additional research is needed to understand the clinical implications of these parameters related to progression risk, prognosis, and implications for therapeutic response.

The DISCOVER Study 3-Year Results: Feasibility and Usefulness of Microscope-Integrated Intraoperative OCT during Ophthalmic Surgery.

PURPOSE: To report the 3-year assessment of feasibility and usefulness of microscope-integrated intraoperative OCT (iOCT) during ophthalmic surgery. DESIGN: Prospective, consecutive case series. PARTICIPANTS: Adult participants undergoing incisional ophthalmic surgery with iOCT imaging who consented to be enrolled in the Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) study. METHODS: The DISCOVER study is a single-site, multisurgeon, institutional review board-approved investigational device prospective study. Participants included patients undergoing anterior or posterior segment surgery who underwent iOCT imaging with 1 of 3 prototype microscope-integrated iOCT systems (i.e., Zeiss Rescan 700, Leica EnFocus, or Cole Eye iOCT systems). Clinical characteristics were documented, iOCT was directed by the operating surgeon at predetermined surgical time points, and each surgeon completed a questionnaire after surgery to evaluate the usefulness of iOCT during surgery. MAIN OUTCOME MEASURES: Feasibility of iOCT based ability to obtain an OCT image during surgery and usefulness of iOCT based on surgeon reporting during surgery. RESULTS: Eight hundred thirty-seven eyes (244 anterior segment cases and 593 posterior segment cases) were enrolled in the DISCOVER study. Intraoperative OCT demonstrated feasibility with successful image acquisition in 820 eyes (98.0%; 95% confidence interval [CI], 96.8%-98.8%). In 106 anterior segment cases (43.4%; 95% CI, 37.1%-49.9%), the surgeons indicated that the iOCT information impacted their surgical decision making and altered the procedure. In posterior segment procedures, surgeons reported that iOCT enabled altered surgical decision making during the procedure in 173 cases (29.2%; 95% CI, 25.5%-33.0%). CONCLUSIONS: The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.

FACTORS ASSOCIATED WITH DEVELOPMENT OF DISSOCIATED OPTIC NERVE FIBER LAYER APPEARANCE IN THE PIONEER INTRAOPERATIVE OPTICAL COHERENCE TOMOGRAPHY STUDY.

PURPOSE: To assess the relationship of dissociated optic nerve fiber layer (DONFL) and intraoperative membrane-peeling dynamics as visualized using intraoperative optical coherence tomography (OCT), and to evaluate the functional implications of DONFL. METHODS: This was a post hoc analysis of eyes undergoing membrane peeling for vitreomacular interface disorders in the prospective PIONEER intraoperative OCT study. Retinal layer measurements in preincision and postpeel intraoperative OCT images were obtained. The primary outcome was development of DONFL appearance on spectral domain OCT at 6-month follow-up. Secondary outcomes included correlation of DONFL with surgical technique, surgical indication, intraoperative OCT findings, and retinal sensitivity. RESULTS: Ninety-five eyes were included. The prevalence of DONFL at 6 months was 36%. Increased inner retinal layer thickness on intraoperative OCT immediately after membrane peeling was associated with development of DONFL (P < 0.01). Macular hole repair was significantly associated with DONFL appearance. Peel technique (forceps vs. diamond-dusted membrane scraper) was not associated with DONFL. There was no difference in retinal sensitivity or visual acuity between eyes with or without DONFL. CONCLUSION: Acute postpeel increase in inner retinal thickness and macular hole repair were associated with development of DONFL appearance. However, it is unclear whether the surgical indication (e.g., macular hole) or the surgical manipulations performed (e.g., internal limiting membrane peeling) is the major factor that has an impact on DONFL appearance. Overall, these findings suggest that one mechanism in the development of DONFL appearance may be intraoperative trauma to the inner retina, potentially during internal limiting membrane peeling (e.g., macular hole repair).

Longitudinal Quantitative Ultrawidefield Angiographic Features in Diabetic Retinopathy Treated with Aflibercept from the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement Trial.

OBJECTIVE: To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement (PRIME) diabetic retinopathy (DR) clinical trial. DESIGN: Post hoc analysis of the PRIME prospective randomized DR clinical trial comparing intravitreal aflibercept treatment based on the DR severity score (DRSS) or quantitative leakage index for DR improvement (ClinicalTrials.gov identifier: NCT03531294). PARTICIPANTS: Patients were enrolled with a DRSS level of 47A to 71A and best-corrected visual acuity of 20/800 or better. Key exclusion criteria were previous intravitreal injection, panretinal photocoagulation, vitrectomy, central-involving macular edema, or vitreous hemorrhage. METHODS: A previously validated, machine learning-based qUWFA analysis platform was used for panretinal leakage index assessment and differentiation of generalized and perivascular leakage phenotypes. Additionally, microaneurysm count and ischemic index were quantified in panretinal and macular regions. The trends in these biomarkers and therapeutic response were studied over 1 year. MAIN OUTCOME MEASURES: Longitudinal trends of qUWFA biomarkers. The impact of these qUWFA metrics on treatment response was assessed by studying their associations with time to 2-step DRSS improvement and number of treatment-free days. RESULTS: Forty eyes from 40 subjects with DR were enrolled. Lower baseline generalized leakage was noted in eyes that attained the 2-step DRSS improvement in < 16 weeks (1.9% vs. 2.8%; P = 0.026). Baseline macular perivascular-generalized leakage ratio had a significant correlation with the number of treatment-free days (r = 0.4; P = 0.012). At the end of 1 year, therapy significantly reduced the mean panretinal (3.9% vs. 5.8%; P = 0.002) and macular (6.2% vs. 12.2%; P = 0.008) generalized leakage indices compared with baseline, as well as the mean panretinal perivascular leakage index (1.5% vs. 2.3%; P = 0.002). The mean panretinal ischemic index demonstrated a small but likely clinically insignificant decrease from 12.5% at baseline to 11.6% at year 1 (P = 0.016). CONCLUSIONS: Down-trending leakage indices and microaneurysm counts were demonstrated over 1 year of anti-VEGF therapy. At baseline, DR eyes with lower generalized leakage responded to therapy more rapidly. Eyes with greater perivascular leakage relative to generalized leakage showed a longer-lasting anti-VEGF treatment response. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Analysis of retinal alterations utilizing intraoperative OCT following surgical interventions with novel ILM forceps in the DISCOVER study.

This study aimed to assess retinal alterations following membrane peeling procedures using novel ILM Forceps with laser ablated surface with the help of intraoperative optical coherence tomography (iOCT). A post-hoc analysis was performed to evaluate iOCT findings in eyes that underwent membrane peeling procedures with the novel ILM Forceps. Pre-peel and post-peel iOCT videos and images were evaluated for each eye to assess for post-peel anatomic alterations. Surgical video/iOCT scan correlation was conducted to evaluate the etiology of anatomic alterations. Thirty-two eyes were included in the analysis. Three eyes (9%) had focal full thickness retinal elevations identified on iOCT following tissue-instrument interaction with the ILM Forceps. Two eyes (6%) had focal inner retinal elevations and one eye (3%) had a full-thickness retinal elevation that were not related to direct tissue-instrument interaction but rather indirect peeling forces. iOCT-identified architectural alterations related to direct-tissue instrument interaction were relatively infrequent (< 10%) with similar frequency to previously reported alterations with other surgical instruments.

Automated Evaluation of Ellipsoid Zone At-Risk Burden for Detection of Hydroxychloroquine Retinopathy.

BACKGROUND: Screening for hydroxychloroquine (HCQ) retinopathy is crucial to detecting early disease. A novel machine-learning-based optical coherence tomography (OCT) biomarker, Ellipsoid Zone (EZ) At-Risk, can quantitatively measure EZ alterations and at-risk areas for progressive EZ loss in a fully automated fashion. The purpose of this analysis was to compare the EZ At-Risk burden in eyes with HCQ toxicity to eyes without toxicity. METHODS: IRB-approved image analysis study of 83 subjects on HCQ and 44 age-matched normal subjects. SD-OCT images were reviewed for evidence of HCQ retinopathy. A ML-based, fully automatic measurement of the percentage of the macular area with EZ At-Risk was performed. RESULTS: The mean age for HCQ subjects was 67.1 ± 13.2 years and 64.2 ± 14.3 years for normal subjects. The mean EZ At-Risk macular burden in the "toxic" group (n = 38) was significantly higher (10.7%) compared to the "non-toxic" group (n = 45; 2.2%; p = 0.023) and the "normal" group (1.4%; p = 0.012). Additionally, the amount of EZ At-Risk burden was significantly correlated with the HCQ dose based on the actual (p = 0.016) and ideal body weight (p = 0.033). CONCLUSIONS: The novel biomarker EZ-At Risk was significantly higher in subjects with evidence of HCQ retinopathy as well as significantly associated with HCQ dose. This novel biomarker should be further evaluated as a potential screening tool for subjects on HCQ.

Ellipsoid Zone Integrity and Visual Function in Dry Age-Related Macular Degeneration.

In this longitudinal retrospective image analysis, conducted on patients diagnosed with dry age-related macular degeneration (AMD) and 5 years of follow-up imaging data, the study aimed to investigate the relationship between ellipsoid zone (EZ) integrity on spectral domain optical coherence tomography (SD-OCT) and visual acuity (VA). Using a machine learning-enabled feature extraction tool, quantitative EZ parameters were derived from SD-OCT images. The analysis revealed significant correlations between EZ integrity metrics and VA. Eyes with excellent VA (≥20/25 Snellen) exhibited higher EZ integrity, including less EZ attenuation, thicker ellipsoid zone-retinal pigment epithelium (EZ-RPE) thickness, and higher EZ intensity, in contrast to eyes with worse VA (≤20/40 Snellen). Additionally, eyes with geographic atrophy (GA) in the foveal region displayed compromised EZ integrity compared to those without GA. Notably, baseline EZ integrity metrics were predictive of future VA loss. These findings suggest that quantitative SD-OCT measurements of EZ integrity could potentially detect early changes in dry AMD and serve as valuable indicators for predicting future functional outcomes. Furthermore, these measurements hold promise for use in clinical trial screenings, offering insights into the progression of the disease and its impact on visual acuity. This study underscores the importance of EZ integrity assessment in understanding and managing dry AMD.

Correlation Between Blue Fundus Autofluorescence and SD-OCT Measurements of Geographic Atrophy in Dry Age-Related Macular Degeneration.

PURPOSE: To compare fundus autofluorescence (FAF) and spectral domain optical coherence tomography (OCT) measurements of geographic atrophy (GA) area and to analyze lesion area changes measured by spectral domain OCT in GATHER1. DESIGN: An assessment reliability analysis using prospective, randomized, double-masked phase 2/3 clinical trial data. METHODS: GATHER1 examined the efficacy and safety of avacincaptad pegol (ACP) for GA treatment. A post hoc analysis was performed to identify correlations between FAF- and OCT-based measurements of GA. GA area was measured on blue-light FAF images using semiautomatic segmentation software with support from OCT and near-infrared imaging. Machine-learning enhanced, multilayer segmentation of OCT scans were reviewed by human readers, and segmentation errors were corrected as needed. GA area was defined as total RPE loss on cross-sectional B scans. Time points included Months 0, 6, 12, and 18. Additionally, OCT-based GA-area changes between ACP and sham were analyzed. RESULTS: There was a strong correlation (r = 0.93) between FAF and OCT GA area measurements that persisted through 18 months. Mean (SD) differences between OCT and FAF GA measurements were negligible: 0.11 mm2 (1.42) at Month 0, 0.03 mm2 (1.62) at Month 6, -0.17 mm2 (1.81) at Month 12, and -0.07 mm2 (1.78) at Month 18. OCT assessments of GA growth revealed a 30% and 27% reduction at Months 12 and 18, respectively, between ACP and sham, replicating FAF measurements from GATHER1. CONCLUSIONS: The strong correlation between blue FAF and OCT measurements of GA area supports OCT as a reliable method to measure GA lesion area in clinical trials.

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.].

Longitudinal analysis of aqueous humour cytokine expression and OCT-based imaging biomarkers in retinal vein occlusions treated with anti-vascular endothelial growth factor therapy in the IMAGINE study.

BACKGROUND/OBJECTIVES: Retinal vein occlusion (RVO) is the second most common retinal vascular disorder. Despite promising advances with anti-VEGF therapy, select patients are unresponsive to therapy. A precision medicine-based approach for therapeutic decision-making based on underlying biomarkers may facilitate treatment based on the underlying pathway. This study aims to identify the baseline and longitudinal cytokine profiles of RVO-related macular oedema and correlating these expression profiles with higher order OCT features using a novel retinal segmentation and feature extraction platform. SUBJECTS/METHODS: The IMAGINE study is a post-hoc assessment of aqueous humour cytokines with correlation to higher level analysis of imaging studies. OCT scans underwent machine learning enhanced segmentation of the internal limiting membrane (ILM), ellipsoid zone (EZ) and retinal pigment epithelium (RPE), as well as evaluating volumetric fluid metrics. Samples of aqueous humour were obtained at baseline, as well as months 4 and 9 prior to treatment. These samples were analysed for the expression of multiple cytokines. Patients were divided into Responders and Non-Responders based on OCT profiles. Additionally, patients were categorised as a Rebounder if their CST increased by 50% after initial improvement. RESULTS: Twenty-six eyes were included. The OCT-based response schema identified 21 Responders (81%) and 5 Non-Responders (19%). VEGF levels directly correlated with intraretinal fluid volume and angiogenin was inversely correlated with fluid indices. Multiple cytokines, including ANGPTL4, were directly correlated with ellipsoid zone disruption. The baseline VEGF levels were significantly higher in all responders compared to Non-Responders (p = 0.02). Rebounders tended to have significantly decreased levels of angiogenin and TIMP-1 (p = 0.019, p = 0.015). CONCLUSIONS: Cytokine expression was linked to specific OCT features and treatment response in RVO. Identification of an imaging phenotype that could serve as a surrogate for underlying active disease pathways could enhance treatment decision-making and precision medicine.

Automated Identification and Segmentation of Ellipsoid Zone At-Risk Using Deep Learning on SD-OCT for Predicting Progression in Dry AMD.

BACKGROUND: The development and testing of a deep learning (DL)-based approach for detection and measurement of regions of Ellipsoid Zone (EZ) At-Risk to study progression in nonexudative age-related macular degeneration (AMD). METHODS: Used in DL model training and testing were 341 subjects with nonexudative AMD with or without geographic atrophy (GA). An independent dataset of 120 subjects were used for testing model performance for prediction of GA progression. Accuracy, specificity, sensitivity, and intraclass correlation coefficient (ICC) for DL-based EZ At-Risk percentage area measurement was calculated. Random forest-based feature ranking of EZ At-Risk was compared to previously validated quantitative OCT-based biomarkers. RESULTS: The model achieved a detection accuracy of 99% (sensitivity = 99%; specificity = 100%) for EZ At-Risk. Automatic EZ At-Risk measurement achieved an accuracy of 90% (sensitivity = 90%; specificity = 84%) and the ICC compared to ground truth was high (0.83). In the independent dataset, higher baseline mean EZ At-Risk correlated with higher progression to GA at year 5 (p < 0.001). EZ At-Risk was a top ranked feature in the random forest assessment for GA prediction. CONCLUSIONS: This report describes a novel high performance DL-based model for the detection and measurement of EZ At-Risk. This biomarker showed promising results in predicting progression in nonexudative AMD patients.

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%.

Longitudinal assessment of quantitative ultra-widefield ischaemic and vascular parameters in sickle cell retinopathy.

PURPOSE: To evaluate longitudinal quantitative ischaemic and vasculature parameters, including ischaemic index, vessel area, length and geodesic distance in sickle cell retinopathy (SCR) on ultra-widefield fluorescein angiography (UWFA). METHODS: Optimal UWFA images from two longitudinal timepoints of 74 eyes from 45 patients with SCR were aligned and a common region of interest was determined. A deep-learning augmented ischaemia and vascular segmentation platform was used for feature extraction. Geodesic distance maps demonstrating the shortest distance within the vascular masks from the centre of the optic disc were created. Ischaemic index, vessel area, vessel length and geodesic distance were measured. Paired t-test and linear mixed effect model analysis were performed. RESULTS: Overall, 25 (44 eyes) patients with HbSS, 14 (19 eyes) with HbSC, 6 (11 eyes) with HbSthal and other genotypes were included. Mean age was 40.1±11.0 years. Mean time interval between two UWFA studies was 23.0±15.1 months (range: 3-71.3). Mean panretinal ischaemic index increased from 10.0±7.2% to 10.9±7.3% (p<0.005). Mean rate of change in ischaemic index was 0.5±0.7% per year. Mean vessel area (p=0.020) and geodesic distance (p=0.048) decreased significantly. Multivariate analysis demonstrated baseline ischaemic index and Goldberg stage are correlated with progression. CONCLUSION: Longitudinal ischaemic index and retinal vascular parameter measurements demonstrate statistically significant progression in SCR. The clinical significance of these relatively small magnitude changes remains unclear but may provide insights into the progression of retinal ischaemia in SCR.

Machine Learning-Based Automated Detection and Quantification of Geographic Atrophy and Hypertransmission Defects Using Spectral Domain Optical Coherence Tomography.

The current study describes the development and assessment of innovative, machine learning (ML)-based approaches for automated detection and pixel-accurate measurements of regions with geographic atrophy (GA) in late-stage age-related macular degeneration (AMD) using optical coherence tomography systems. 900 OCT volumes, 100266 B-scans, and en face OCT images from 341 non-exudative AMD patients with or without GA were included in this study from both Cirrus (Zeiss) and Spectralis (Heidelberg) OCT systems. B-scan and en face level ground truth GA masks were created on OCT B-scan where the segmented ellipsoid zone (EZ) line, retinal pigment epithelium (RPE) line, and bruchs membrane (BM) line overlapped. Two deep learning-based approaches, B-scan level and en face level, were trained. The OCT B-scan model had detection accuracy of 91% and GA area measurement accuracy of 94%. The en face OCT model had detection accuracy of 82% and GA area measurement accuracy of 96% with primary target of hypertransmission on en face OCT. Accuracy was good for both devices tested (92-97%). Automated lesion size stratification for CAM cRORA definition of 250um minimum lesion size was feasible. High-performance models for automatic detection and segmentation of GA area were achieved using OCT systems and deep learning. The automatic measurements showed high correlation with the ground truth. The en face model excelled at identification of hypertransmission defects. The models performance generalized well across device types tested. Future development will include integration of both models to enhance feature detection across GA lesions as well as isolating hypertransmission defects without GA for pre-GA biomarker extraction.

Exploring the angiographic-biologic phenotype in the IMAGINE study: quantitative UWFA and cytokine expression.

BACKGROUND: This study investigates the association of intraocular cytokine expression and ultrawide-field fluorescein angiography (UWFA) quantitative imaging biomarkers and their association with angiographical feature response after antivascular endothelial growth factor (VEGF) therapy in diabetic macular oedema (DME). METHODS: The IMAGINE DME study is a post hoc imaging biomarker and intraocular cytokine assessment from the DAVE study, a prospective DME clinical trial that included aqueous humour sampling and UWFA imaging. Fifty-four cytokines associated with inflammation and angiogenesis were evaluated through multiplex arrays. UWFA parameters were assessed using an automated feature analysis platform to determine ischaemic and leakage indices and microaneurysm (MA) count. Eyes were classified into UWFA responder or non-responder groups based on longitudinal quantitative UWFA parameter improvement. Cytokine expression was correlated with UWFA metrics and evaluated in the context of therapeutic response. RESULTS: Twenty-one eyes were included with a mean age of 55±10 years. Increased panretinal leakage index correlated with VEGF (r=0.70, p=0.0005), angiopoietin-like 4 (r=0.77, p=4.6E-5) and interleukin (IL)-6 (r=0.64, p=0.002). Panretinal ischaemic index was associated with tissue inhibitor of metalloproteinases 1 (TIMP-1, r=0.49, p=0.03) and peripheral ischaemia correlated with VEGF (r=0.45, p=0.05). MA count correlated with increased monocyte chemotactic protein-4 (MCP-4, r=0.60, p=0.004) and platelet and endothelial cell adhesion molecule 1 (PECAM-1, r=0.58, p=0.005). Longitudinal MA reduction was associated with decreased baseline VEGF and urokinase receptor (uPAR) (p<0.05). High baseline VEGF and IL-6 were associated with dramatic reduction in macular leakage (p<0.05). CONCLUSIONS: Baseline and longitudinal quantitative UWFA imaging parameters correlated with multiple aqueous humour cytokine concentrations, including VEGF and IL-6. Further research is needed to assess the possible implications of using these findings for evaluating treatment response.

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.].