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.

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.].

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.

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.

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.

Predictive Assessment of Quantitative Ultra-Widefield Angiographic Features for Future Need for Anti-VEGF Therapy in Diabetic Eye Disease.

The objective of this study was to identify biomarkers that predict a future need for anti-VEGF therapy in diabetic retinopathy (DR). Eyes with DR that underwent ultra-widefield angiography (UWFA) and had at least a 1 year follow-up were grouped based on future anti-VEGF treatment requirements: (1) not requiring treatment, (2) immediate treatment (within 3 months of UWFA), and (3) delayed treatment (after 3 months of UWFA). Quantitative UWFA features and clinical factors were evaluated. Random forest models were built to differentiate eyes requiring immediate and delayed treatment from the eyes not requiring treatment. A total of 173 eyes were included. The mean follow-up was 22 (range: 11-43) months. The macular leakage index, panretinal leakage index, presence of DME, and visual acuity were significantly different in eyes requiring immediate (n = 38) and delayed (n = 34) treatment compared to eyes not requiring treatment (n = 101). Random forest model differentiating eyes requiring immediate treatment from eyes not requiring treatment demonstrated an AUC of 0.91 ± 0.07. Quantitative angiographic features have potential as important predictive biomarkers of a future need for anti-VEGF therapy in DR and may serve to guide the frequency of a follow-up.

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.].

Deep learning-enabled ultra-widefield retinal vessel segmentation with an automated quality-optimized angiographic phase selection tool.

OBJECTIVES: To demonstrate the feasibility of a deep learning-based vascular segmentation tool for UWFA and evaluate its ability to automatically identify quality-optimized phase-specific images. METHODS: Cumulative retinal vessel areas (RVA) were extracted from all available UWFA frames. Cubic splines were fitted for serial vascular assessment throughout the angiographic phases of eyes with diabetic retinopathy (DR), sickle cell retinopathy (SCR), or normal retinal vasculature. The image with maximum RVA was selected as the optimum early phase. A late phase frame was selected at a minimum of 4 min that most closely mirrored the RVA from the selected early image. Trained image analysts evaluated the selected pairs. RESULTS: A total of 13,980 UWFA sequences from 462 sessions were used to evaluate the performance and 1578 UWFA sequences from 66 sessions were used to create cubic splines. Maximum RVA was detected at a mean of 41 ± 15, 47 ± 27, 38 ± 8 s for DR, SCR, and normals respectively. In 85.2% of the sessions, appropriate images for both phases were successfully identified. The individual success rate was 90.7% for early and 94.6% for late frames. CONCLUSIONS: Retinal vascular characteristics are highly phased and field-of-view sensitive. Vascular parameters extracted by deep learning algorithms can be used for quality assessment of angiographic images and quality optimized phase selection. Clinical applications of a deep learning-based vascular segmentation and phase selection system might significantly improve the speed, consistency, and objectivity of UWFA evaluation.

Real-Time Diabetic Retinopathy Severity Score Level versus Ultra-Widefield Leakage Index-Guided Management of Diabetic Retinopathy: Two-Year Outcomes from the Randomized PRIME Trial.

The prospective PRIME trial applied real-time, objective imaging biomarkers to determine individualized retreatment needs with intravitreal aflibercept injections (IAI) among eyes with diabetic retinopathy (DR). 40 eyes with nonproliferative or proliferative DR without diabetic macular edema received monthly IAI until a DR severity scale (DRSS) level improvement of ≥2 steps was achieved. Eyes were randomized 1:1 to DRSS- or PLI- guided management. At the final 2-year visit, DRSS level was stable or improved compared to baseline in all eyes, and mean PLI decreased by 11% (p = 0.73) and 23.6% (p = 0.25) in the DRSS- and PLI-guided arms. In both arms, the percent of pro re nata (PRN) visits requiring IAI was significantly higher in year 2 versus 1 (p < 0.0001). The percent of PRN visits receiving IAI during year 1 was significantly correlated with the percent of PRN visits with IAI during year 2 (p < 0.0001). Through week 104, 77.4% of instances of DRSS level worsening in the DRSS-guided arm were preceded by or occurred alongside an increase of PLI. Overall, consistent IAI re-treatment interval requirements were observed longitudinally among individual patients. Additionally, PLI increases appeared to precede DRSS level worsening, highlighting PLI as a valuable biomarker in the management of DR.

Real-Time Photographic- and Fluorescein Angiographic-Guided Management of Diabetic Retinopathy: Randomized PRIME Trial Outcomes.

PURPOSE: To assess the safety and efficacy of as-needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by the real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes without diabetic macular edema (DME). DESIGN: Prospective, randomized phase 2 trial (PRIME). METHODS: A total of 40 eyes with nonproliferative (NPDR) or proliferative DR (PDR) received monthly IAIs until a DRSS improvement of ≥2 steps was achieved and eyes were randomized (1:1) to DRSS-guided or PLI-guided management strategies graded by a central reading center. Main outcome measurements included safety and changes in DRSS and PLI. RESULTS: Through week 52, 95% of eyes achieved a DRSS improvement of ≥2 steps. Following DRSS improvement, 97% of eyes required at least 1 PRN IAI. In eyes requiring PRN IAI and completing week 52, 100% and 59% experienced DRSS worsening (P = .01) in the DRSS- and PLI-guided arms, respectively. Through week 52, mean PLI decreased 18.2% (P = .49) and 54.6% (P <.0001), respectively, in the DRSS- and PLI-guided arms. NPDR versus PDR eyes at baseline achieved a DRSS improvement of ≥2 steps after a mean 4.9 and 3.6 IAIs (P = .03). Two eyes developed a PDR event at week 52 following 5 months of quiescence. CONCLUSIONS: The randomized PRIME study analyzed 2 imaging-based biomarkers to guide PRN management with IAI of DR without DME: DRSS level and PLI. Within the context of this study with limitations, most patients required IAI re-treatment every 3-4 months, and deterioration of PLI appeared to precede DRSS level worsening. Finally, these findings reaffirm the fact that close clinical follow-up is important even among eyes that achieve substantial DRSS improvements with apparently quiescent disease.

Automated Quality Assessment and Image Selection of Ultra-Widefield Fluorescein Angiography Images through Deep Learning.

Purpose: Numerous angiographic images with high variability in quality are obtained during each ultra-widefield fluorescein angiography (UWFA) acquisition session. This study evaluated the feasibility of an automated system for image quality classification and selection using deep learning. Methods: The training set was comprised of 3543 UWFA images. Ground-truth image quality was assessed by expert image review and classified into one of four categories (ungradable, poor, good, or best) based on contrast, field of view, media opacity, and obscuration from external features. Two test sets, including randomly selected 392 images separated from the training set and an independent balanced image set composed of 50 ungradable/poor and 50 good/best images, assessed the model performance and bias. Results: In the randomly selected and balanced test sets, the automated quality assessment system showed overall accuracy of 89.0% and 94.0% for distinguishing between gradable and ungradable images, with sensitivity of 90.5% and 98.6% and specificity of 87.0% and 81.5%, respectively. The receiver operating characteristic curve measuring performance of two-class classification (ungradable and gradable) had an area under the curve of 0.920 in the randomly selected set and 0.980 in the balanced set. Conclusions: A deep learning classification model demonstrates the feasibility of automatic classification of UWFA image quality. Clinical application of this system might greatly reduce manual image grading workload, allow quality-based image presentation to clinicians, and provide near-instantaneous feedback on image quality during image acquisition for photographers. Translational Relevance: The UWFA image quality classification tool may significantly reduce manual grading for clinical- and research-related work, providing instantaneous and reliable feedback on image quality.

Use of OCTA Capillary Perfusion Density Measurements to Detect and Grade Macular Ischemia.

BACKGROUND AND OBJECTIVE: To compare optical coherence tomography angiography (OCTA) capillary perfusion density (CPD) measurements of normal eyes and eyes with macular ischemia (MI). PATIENTS AND METHODS: AVATAR is an institutional review board-approved, prospective, observational imaging study using the Avanti RTVue XR HD. OCTA reports were reviewed for the presence of MI. Qualitative MI grading was performed, and CPD metrics in the superficial and deep fovea and parafovea were analyzed. A normal eye cohort was identified for comparative assessment. RESULTS: The MI and normal cohorts included 55 and 58 eyes, respectively. Compared to normal eyes, eyes with MI had significantly lower CPD values in all regions. There was a statistically significant correlation between qualitative MI grade and VA in the superficial (P = .003) and deep plexuses (P = .029). Only deep parafoveal CPD values demonstrated correlation with VA (P = .043). CONCLUSIONS: Eyes with MI determined by masked qualitative OCTA grading demonstrated significantly reduced CPD values compared to normal eyes. Categorical assessment of MI severity correlated with VA. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S30-S36.].

Conventional Microscope-Integrated Intraoperative OCT Versus Digitally Enabled Intraoperative OCT in Vitreoretinal Surgery in the DISCOVER Study.

BACKGROUND AND OBJECTIVE: To compare conventional microscope-integrated intraoperative optical coherence tomography (iOCT) and digitally enabled microscope-integrated iOCT in vitreoretinal surgery. PATIENTS AND METHODS: In this post-hoc analysis of the DISCOVER prospective iOCT study, two surgical groups were compared: (1) conventional iOCT and (2) digitally enabled iOCT. Surgeon questionnaires were collected immediately following surgery. RESULTS: A total of 187 subjects were included in the study: 91 in the conventional iOCT group and 96 in the digitally enabled iOCT group. There were no differences in surgeon-perceived iOCT utility between the two groups. There was significantly higher surgical field-based visualization of the iOCT datastream in the digitally enabled iOCT group (67.7% vs. 3.3%; P < .0001). Reported significant back discomfort (1.0% vs. 18.7%; P < .0001) and headaches (5.2% vs. 20.9%; P < .002) were lower in the digitally enabled iOCT group. CONCLUSIONS: Feasibility and utility of iOCT were similar in both groups. Digitally enabled iOCT datastream enabled increased attention on the surgical field during OCT review. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S37-S43.].

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.

Intraoperative OCT-Assisted Retinal Detachment Repair in the DISCOVER Study: Impact and Outcomes.

PURPOSE: The purpose of this study is to evaluate intraoperative OCT (iOCT) utility and outcomes during retinal detachment (RD) repair. DESIGN: The Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) intraoperative OCT study is a prospective Institutional Review Board-approved study. PARTICIPANTS: Participants in the DISCOVER study undergoing surgical repair for RD. METHODS: This was a post hoc analysis of eyes in the DISCOVER study undergoing surgical repair for RDs. Inclusion criteria included iOCT after perfluorocarbon liquid placement and at least 6 months follow-up. Exclusion criteria included severe retinal pathology unrelated to RD. Surgeons completed standardized questionnaires after each case evaluating the iOCT instrument's utility. Functional and surgical outcome data were collected at the latest available time point between 6 and 12 months. Outcomes were evaluated in 2 groups: uncomplicated primary and complex cases. MAIN OUTCOME MEASURES: Intraoperative OCT utility, single-surgery success, and visual acuity outcomes. RESULTS: A total of 103 eyes were included in this study: 51 uncomplicated primary and 52 complex cases. Intraoperative OCT provided valuable information in 36% of cases. In 12% of cases, iOCT data directly altered surgical decision making. There was a significantly higher rate of valuable iOCT feedback in complex cases compared with primary cases (50% vs. 22%, P < 0.01). Among primary cases, 48 (94%) had successful single surgery repair with a mean postoperative visual acuity of 20/47 compared with the complex group's 75% single surgery success (n=39) and mean postoperative visual acuity of 20/92. CONCLUSIONS: This study affirms the potential impact of iOCT in assisting select cases of RD repair, particularly with complex pathology. The single surgery success rate was good with more than 80% of cases successfully repaired with 1 surgery.

Longitudinal ellipsoid zone and subretinal fluid mapping following ocriplasmin injection in the prospective observational ORBIT trial.

BACKGROUND: Ocriplasmin is approved for the treatment of symptomatic vitreomacular traction (VMT). However, several retrospective reports have identified ellipsoid zone (EZ) alterations on spectral domain optical coherence tomography (SDOCT) after ocriplasmin injection. This report quantitatively analysed outer retinal changes after intravitreal ocriplasmin. METHODS: Ocriplasmin Research to Better Inform Treatment is a prospective, observational phase IV clinical study where subjects received a single intravitreal injection of ocriplasmin for symptomatic VMT. Macular cube scans were imported into a semiautomated EZ mapping and fluid feature extraction software for SDOCT analysis. Change in visual acuity, VMT release, macular hole (MH) closure, EZ integrity/volume and subretinal fluid (SRF) volume on SDOCT macular cube scans were recorded and analysed. RESULTS: This analysis included 55 participants with 6 months of follow-up. Intravitreal ocriplasmin injection caused VMT release in 67% and MH closure in 82% of participants. Visual acuity improved by 4.5 letters (p<0.05) in the whole cohort and by 6.0 letters (p<0.05) in participants with VMT release. EZ volume was reduced by 23.4% at week 1 (p<0.001) and recovered to baseline by between months 3 and 6. EZ volume loss at week 1 did not correlate with ETDRS acuity at final visit. CONCLUSION: Ocriplasmin treatment resulted in VMT release, MH closure and visual acuity gains in a significant portion of eyes. EZ volume was significantly reduced at week 1, but recovered to baseline levels by final follow-up and was not associated with final visual acuity.

Quantitative Ultra-Widefield Angiographic Features and Associations with Diabetic Macular Edema.

PURPOSE: To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and microaneurysms. DESIGN: Retrospective image analysis study. PARTICIPANTS: Eyes with diabetic retinopathy that had undergone spectral-domain OCT, UWFA, and ultra-widefield fundus photography. METHODS: OCT images were analyzed to determine the presence or absence of DME, central subfield thickness (CST), and subretinal fluid. Using a semiautomated analysis platform, UWFA images were segmented for ischemia, leakage, and microaneurysms with manual correction as needed. Clinical variables, including age, gender, race, hemoglobin A1C levels, blood pressure, cholesterol levels, use of blood thinners, smoking status, and lens status also were evaluated. MAIN OUTCOME MEASURES: Factors associated with the presence and severity of DME. RESULTS: A total of 304 eyes (156 right eyes, 148 left eyes) from 178 diabetic patients were analyzed in the study. Panretinal leakage index, microaneurysm count, and ischemic index were not significantly different between eyes with and without DME in univariate assessment. Zonal assessments of macular microaneurysms and macular leakage index values revealed that eyes with DME showed a significantly higher microaneurysm count (P = 0.001) and leakage index (P < 0.0001) in the posterior pole compared with eyes without DME. Severity of macular thickening (i.e., CST) was associated significantly with macular leakage index and posterior pole microaneurysm count (P = 0.0002 and P = 0.03, respectively). In addition to posterior pole leakage index and microaneurysm count, DME was associated with older age (P < 0.01), higher systolic blood pressure (P < 0.001), and white race (P = 0.03). Multivariate assessment confirmed the independent association of presence of DME with macular leakage index and macular microaneurysm count (P < 0.01). CONCLUSIONS: Quantitative measures of leakage index and microaneurysm count in the posterior pole on UWFA images were associated with the presence and severity of DME. Panretinal analyses were not linked to DME as strongly. Additional research is needed to determine the role of quantitative UWFA in predicting DME development and characterizing patient prognosis.

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.

Intraoperative OCT Features and Postoperative Ellipsoid Mapping in Primary Macula-Involving Retinal Detachments from the PIONEER Study.

PURPOSE: Intraoperative OCT (iOCT) has enabled visualization of subtle structural details during surgical interventions, including retinal detachment repair. The purpose of this study was to evaluate iOCT findings during retinal detachment repair and to assess their impact on anatomic and functional outcomes, including outer retinal integrity. DESIGN: The PIONEER Intraoperative and Perioperative OCT Study is a prospective cohort, institutional review board-approved study. PARTICIPANTS: Participants in the PIONEER undergoing surgical repair for primary macula-involving retinal detachment. METHODS: This was a post hoc analysis of all eyes in the PIONEER undergoing surgical repair with primary macula-involving retinal detachments. Inclusion criteria included iOCT after perfluorocarbon liquid (PFO) placement, visualization of the foveal center on iOCT, and images of sufficient quality for quantitative assessment of submacular fluid volume. Exclusion criteria included recurrent retinal detachment, proliferative vitreoretinopathy, and a lack of postoperative OCT data after gas bubble resolution. Subretinal fluid volume on iOCT imaging was quantified. Qualitative review of iOCT images was performed for visualization of outer retinal bands, fluid, and retinal corrugations. Postoperative OCT images were analyzed using an ellipsoid zone (EZ) mapping platform to evaluate and quantify outer retinal metrics. Postoperative OCT images also were reviewed qualitatively for persistent subretinal fluid. Associations between various anatomic and functional outcomes were assessed. MAIN OUTCOME MEASURES: Presence of intraoperative subretinal fluid under PFO tamponade, postoperative persistent subretinal fluid, postoperative visual acuity at 1 year, and EZ integrity at 1 year. RESULTS: Fifteen eyes of 15 patients were analyzed. All 15 eyes (100%) showed subretinal fluid on iOCT. All eyes demonstrated spontaneous fluid resolution on follow-up OCT imaging. Increased intraoperative subretinal fluid volume under PFO tamponade trended toward significantly worse visual acuity outcome (P = 0.07). Postoperative quantitative EZ integrity at 12 months directly correlated with visual outcome (P = 0.01). CONCLUSIONS: Intraoperative subretinal fluid persists under PFO tamponade with high frequency in eyes undergoing retinal detachment repair, but this fluid does not seem to be associated with persistent postoperative subretinal fluid. Postoperative EZ integrity is associated with visual acuity outcome, and intraoperative subretinal fluid volume under PFO tamponade also may be linked to visual outcomes.