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.

Proteomic investigations of human HERC2 mutants: Insights into the pathobiology of a neurodevelopmental disorder.

HERC2 is a giant protein with E3 ubiquitin ligase activity and other known and suspected functions. Mutations of HERC2 are implicated in the pathogenesis of various cancers and result in severe neurological conditions in Herc2-mutant mice. Recently, a pleotropic autosomal recessive HERC2-associated syndrome of intellectual disability, autism and variable neurological deficits was described; its pathogenetic basis is largely unknown. Using peripheral blood-derived lymphoblasts from 3 persons with homozygous HERC2 variants and 14 age- and gender-matched controls, we performed label-free unbiased HPLC-tandem mass spectrometry-based proteomic analyses to provide insights into HERC2-mediated pathobiology. We found that out of 3427 detected proteins, there were 812 differentially expressed proteins between HERC2-cases vs. controls. 184 canonical pathways were enriched after FDR adjustment, including mitochondrial function, energy metabolism, EIF2 signaling, immune functions, ubiquitination and DNA repair. Ingenuity Pathway Analysis® identified 209 upstream regulators that could drive the differential expression, prominent amongst which were neurodegeneration-associated proteins. Differentially expressed protein interaction networks highlighted themes of immune function/dysfunction, regulation of cell cycle/cell death, and energy metabolism. Overall, the analysis of the HERC2-associated proteome revealed striking differential protein expression between cases and controls. The large number of differentially expressed proteins likely reflects HERC2's multiple domains and numerous interacting proteins. Our canonical pathway and protein interaction network findings suggest derangements of multiple pathways in HERC2-associated disease.

Echocardiography and cardiac magnetic resonance-based feature tracking in the assessment of myocardial mechanics in tetralogy of Fallot: an intermodality comparison.

We investigated intermodality agreements of strains from two-dimensional echocardiography (2DE) and cardiac magnetic resonance (CMR) feature tracking (FT) in the assessment of right (RV) and left ventricular (LV) mechanics in tetralogy of Fallot (TOF). Patients were prospectively studied with 2DE and CMR performed contiguously. LV and RV strains were computed separately using 2DE and CMR-FT. Segmental and global longitudinal strains (GLS) for the LV and RV were measured from four-chamber views; LV radial (global radial strain [GRS]) and circumferential strains (GCS) measured from short-axis views. Intermodality and interobserver agreements were examined. In 40 patients (20 TOF, mean age 23 years and 20 adult controls), LV, GCS showed narrowest intermodality limits of agreement (mean percentage error 9.5%), followed by GLS (16.4%). RV GLS had mean intermodality difference of 25.7%. GLS and GCS had acceptable interobserver agreement for the LV and RV with both 2DE and CMR-FT, whereas GRS had high interobserver and intermodality variability. In conclusion, myocardial strains for the RV and LV derived using currently available 2DE and CMR-FT software are subject to considerable intermodality variability. For both modalities, LV GCS, LV GLS, and RV GLS are reproducible enough to warrant further investigation of incremental clinical merit.

Proteomic investigations of adult polyglucosan body disease: insights into the pathobiology of a neurodegenerative disorder.

Inadequate glycogen branching enzyme 1 (GBE1) activity results in different forms of glycogen storage disease type IV, including adult polyglucosan body disorder (APBD). APBD is clinically characterized by adult-onset development of progressive spasticity, neuropathy, and neurogenic bladder and is histologically characterized by the accumulation of structurally abnormal glycogen (polyglucosan bodies) in multiple cell types. How insufficient GBE1 activity causes the disease phenotype of APBD is poorly understood. We hypothesized that proteomic analysis of tissue from GBE1-deficient individuals would provide insights into GBE1-mediated pathobiology. In this discovery study, we utilized label-free LC-MS/MS to quantify the proteomes of lymphoblasts from 3 persons with APBD and 15 age- and gender-matched controls, with validation of the findings by targeted MS. There were 531 differentially expressed proteins out of 3,427 detected between APBD subjects vs. controls, including pronounced deficiency of GBE1. Bioinformatic analyses indicated multiple canonical pathways and protein-protein interaction networks to be statistically markedly enriched in APBD subjects, including: RNA processing/transport/translation, cell cycle control/replication, mTOR signaling, protein ubiquitination, unfolded protein and endoplasmic reticulum stress responses, glycolysis and cell death/apoptosis. Dysregulation of these processes, therefore, are primary or secondary factors in APBD pathobiology in this model system. Our findings further suggest that proteomic analysis of GBE1 mutant lymphoblasts can be leveraged as part of the screening for pharmaceutical agents for the treatment of APBD.

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.

Gluten-free diet does not appear to induce endoscopic remission of eosinophilic esophagitis in children with coexistent celiac disease.

BACKGROUND: Celiac disease and eosinophilic esophagitis are usually considered to be separate gastrointestinal diseases; however, it appears that they may coexist more often than would be expected. It is unknown whether eosinophilic esophagitis in patients with celiac disease responds to a gluten-free diet. OBJECTIVES: To examine the clinical, endoscopic and histological features of children with both conditions to evaluate whether eosinophilic esophagitis responds to a gluten-free diet. METHODS: From January 1, 2009, to June 30, 2011, the medical records of children <18 years of age diagnosed with eosinophilic esophagitis and/or celiac disease were reviewed. Patients with clinical, endoscopic and histological diagnoses of both diseases were identified and included. These findings were analyzed, as were laboratory results, treatment and follow-up. RESULTS: During the study period, there were 206 celiac disease patients, 86 eosinophilic esophagitis patients and nine (4.4% of total celiac) patients with both diagnoses. Gluten-free diet was the primary treatment for both conditions in seven of nine (78%) cases. In six of these seven (86%) patients, no endoscopic or histological improvement of eosinophilic esophagitis was observed, while in one patient, histological remission of esophageal eosinophilia occurred while on a gluten-free diet. CONCLUSION: The prevalence of eosinophilic esophagitis in patients with celiac disease was 4.4%, confirming a higher than expected prevalence of eosinophilic esophagitis compared with the general population. In patients with celiac disease, a gluten-free diet did not appear to induce remission of coexistent endoscopic and histological features of eosinophilic esophagitis.

Five-Year Visual Acuity Outcomes of Fovea-Involving Rhegmatogenous Retinal Detachments Following Pars Plana Vitrectomy (PPV) or Combined PPV/Scleral Buckle.

BACKGROUND AND OBJECTIVE: Macular involvement is considered a poor prognostic factor for visual recovery after rhegmatogenous retinal detachment (RRD) repair. Few prior studies report outcomes longer than 2 years after repair with pars plana vitrectomy (PPV) or combined PPV/scleral buckle (SB). The purpose of this study is to evaluate long-term (at least 5 years) visual outcomes following fovea-involving RRD repair with PPV or PPV/SB. PATIENTS AND METHODS: This retrospective case series evaluated eyes that underwent fovea-involving RRD repair with PPV or PPV/SB. Eyes with single surgery anatomic success and 5 years or more of follow-up were included. Eyes with other ophthalmic pathology affecting central vision were excluded. Paired analysis compared changes in best visual acuity (BVA) between two timepoints. RESULTS: Fifty-one eyes were included. Median (interquartile range, IQR) time to final follow-up was 7 (IQR: 3) years. Median pre-operatively BVA was 19.95 (IQR: 41.25) letters and improved to 80.15 (IQR:15.05) letters and 80.16 (IQR: 8.80) letters at the 1-year and final follow-up, respectively (P < 0.001). Thirteen of 45 eyes (28.89%) had an improvement in BVA of at least 10 letters from the 1-year to the final follow-up. Average BVA was 20/40 or better in 35/45 eyes (75.56%) at 1-year and 45/51 eyes (88.24%) at final follow-up. No eye had an average BVA of 20/200 or worse at final follow-up. CONCLUSIONS: Patients with fovea-involving RRD successfully repaired with PPV or PPV/SB have favorable long-term visual acuity outcomes. BVA may continue to significantly improve even beyond 1 year after surgery. The majority of patients have a BVA of 20/40 or better 5 years after surgery. [Ophthalmic Surg Lasers Imaging Retina 2022;53:674-680.].

Hair Transplantation Complicated by Methicillin-resistant Staphylococcus Aureus Sepsis and Endogenous Endophthalmitis.

PURPOSE: To describe a case of endogenous endophthalmitis as a complication from hair transplantation. METHODS: Case report of a 53-year-old male with history of recent hair transplantation. RESULTS: The patient presented with a febrile illness and blurry vision one week after hair transplantation. Infectious workup included blood cultures positive for Methicillin-resistant Staphylococcus aureus and he was treated with intravenous antibiotics. Initial ocular exam demonstrated 20/30 and hand motions in the right and left eyes, respectively, with significant vitritis. He underwent vitreous tap and injections of vancomycin and dexamethasone in both eyes and removal of purulent staple from site of recently transplanted hair. His ocular and systemic symptoms improved. Approximately 3 months after initial clearing of the initial infection he had recurrence of bacteremia that prompted repeat intravitreal and systemic antibiotics. His vision returned to baseline with mild residual optic nerve pallor and atrophic retinal changes in the left eye. CONCLUSION: Hair transplantation is associated with minimal systemic complications, but in rare cases, sepsis is possible and can result in intraocular seeding causing endophthalmitis. MRSA endogenous endophthalmitis frequently results in negative vitreous taps and treatment outcomes in the literature have been shown to vary widely including a return to baseline vision as in the described case.

A CASE REPORT OF CHRONIC ENDOPHTHALMITIS SECONDARY TO AQUAMICROBIUMterrae.

PURPOSE: Chronic postoperative endophthalmitis is a known complication of cataract surgery. Here, we report a case of chronic endophthalmitis following uncomplicated cataract surgery secondary to the atypical bacterium Aquamicrobium terrae . METHODS: Retrospective case report of a single patient with endophthalmitis secondary to A. terrae. RESULTS: A 61-year-old healthy patient presented with recurrent iridocyclitis following uncomplicated cataract surgery. Repeated attempts to taper off topical steroid eyedrops were unsuccessful. Anterior chamber paracentesis cultures and vitrectomy cultures grew the same gram-negative bacillus, A. terrae , on six different occasions. The patient was treated initially with a series of intravitreal ceftazidime injections and adjuvant oral minocycline with recurrence of inflammation necessitating pars plana vitrectomy with intraocular lens removal and total capsulectomy. Inflammatory episodes recurred until residual capsule fragments were ablated using endoscopic vitrectomy. Since ablation over 18 months ago, no further recurrences have occurred and the patient has excellent visual outcome. CONCLUSION: A. terrae is a gram-negative bacillus recovered from polluted soil. This is the first case of postoperative endophthalmitis secondary to A. terrae and the first description of human infection caused by this newly identified microbe.

Impact of Baseline Quantitative OCT Features on Response to Risuteganib for the Treatment of Dry Age-Related Macular Degeneration: The Importance of Outer Retinal Integrity.

OBJECTIVE: The purpose of the study was to perform a post hoc analysis to explore the effect of baseline anatomic characteristics identified on OCT on best-corrected visual acuity (BCVA) responses to risuteganib from the completed phase II study in subjects with dry age-related macular degeneration (AMD). DESIGN: Post hoc analysis of a randomized, double-masked, placebo-controlled, phase II study. SUBJECTS: Eyes with intermediate dry AMD with BCVA between 20/40 and 20/200. Patients with concurrent vision-influencing or macula-obscuring ocular pathologies were excluded. METHODS: Patients were randomized to receive a 1-mg intravitreal risuteganib injection or a sham injection at baseline. A second 1-mg intravitreal injection of risuteganib was given at week 16 to those in the treatment arm. Two independent, masked reading centers evaluated the baseline anatomic characteristics on OCT to explore features associated with positive responses to risuteganib. MAIN OUTCOME MEASURES: Treatment response was defined as a gain of ≥ 8 letters in BCVA from baseline to week 28 in the treatment arm, compared with baseline to week 12 in the sham group. Anatomic parameters, measured by retinal segmentation platforms, including measures of retinal thickness were compared between the responders and nonresponders to risuteganib. RESULTS: Thirty-nine patients completed the study and underwent analysis. In the treatment arm, 48% of eyes demonstrated treatment responses, compared with 7% in the sham group. In the quantitative anatomic assessment, enhanced ellipsoid integrity, greater outer retinal thickness, and decreased geographic atrophy were associated with increased BCVA gains to risuteganib. CONCLUSIONS: This post hoc analysis demonstrated that baseline OCT features may help determine the likelihood of a functional response to risuteganib. The characterization of higher-order OCT features may provide important information regarding biomarkers for treatment response and could facilitate optimized clinical trial enrollment and enrichment.

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.].

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.

Longitudinal Assessment of Ellipsoid Zone Mapping Parameters in Retinal Venous Occlusive Disease With Associated Macular Edema.

Purpose: This work evaluated the longitudinal dynamics of ellipsoid zone (EZ) integrity in retinal vein occlusion (RVO) with macular edema and their relation to outcomes. Methods: Clinical characteristics and optical coherence tomography data of patients with RVO and associated macular edema were collected at baseline and at 3 and 12 months. Macular cube scans were exported into EZ and retinal-layer analysis software. Longitudinal EZ parameters and visual acuity (VA) outcomes were regressed and correlated. Results: The study included 108 eyes of 108 patients; all eyes were treated with antivascular endothelial growth factor therapy at the baseline visit. VA improved from 20/97 at baseline to 20/52 at 3 months and 12 months (P < .001), correlating with EZ integrity at each time point (P < .001). At 12 months following initiation of antivascular endothelial growth factor therapy, EZ partial attenuation and EZ total attenuation improved over 12 months from 16.4% to 8.5% (P < .001) and from 12.3% to 5.9% (P < .001), respectively. VA improvement from baseline to 12 months correlated with improvement of EZ partial and total attenuation (P < .001). Baseline EZ characteristics did not predict VA outcomes, but at 3 months, EZ parameters did predict improvement in visual outcomes by 12 months (P < .01). Conclusions: EZ and outer retinal integrity are correlated with functional outcomes in RVO. Following treatment, EZ integrity improves and is associated with functional improvement. In RVO baseline, EZ features were not associated with 1-year VA outcomes, but evaluation of EZ integrity at 3 months was linked to 1-year outcomes.

Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study.

PURPOSE: To identify biomarkers for predicting response to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype. DESIGN: The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial. METHODS: Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers. RESULTS: Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (-24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = -0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01). CONCLUSIONS: OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.

Epiretinal Membrane Surgery Using Intraoperative OCT-Guided Membrane Removal in the DISCOVER Study versus Conventional Membrane Removal.

PURPOSE: To provide a comparative assessment of clinical outcomes between patients undergoing intraoperative OCT (iOCT) and conventional surgery for pars plana vitrectomy (PPV) with epiretinal membrane (ERM) peel. DESIGN: Case-control retrospective, comparative assessment. PARTICIPANTS: Patients undergoing PPV with membrane peel for ERM with eyes pooled from the prospective Determination of Feasibility of Intraoperative Spectral Domain Microscope Combined/Integrated OCT Visualization During En Face Retinal and Ophthalmic Surgery (DISCOVER) iOCT study and eyes undergoing conventional ERM surgery without iOCT. METHODS: Visual acuity and OCT assessment before ERM surgery and at 1-, 3-, 6-, and 12-month follow-up after standard small-gauge PPV with iOCT feedback (iOCT DISCOVER group) or PPV with compulsory internal limiting membrane (ILM) peeling (conventional group). Visual acuity, central subfield thickness (CST), reoperation rate, and ERM recurrence were determined by record review and post hoc assessment of clinical OCTs after ERM peel. MAIN OUTCOME MEASURES: Visual acuity and ERM recurrence. RESULTS: A total of 262 eyes were included. Visual acuity (VA) improved 11.9 letters in the iOCT group (P < 0.0001) and 12.1 letters in the conventional group (P < 0.0001) at 12 months after ERM surgery. Visual acuity improvement did not differ between the iOCT and conventional groups at 1, 3, 6, or 12 months after surgery (P > 0.05 for each time point). Preoperative mean CST decreased in the iOCT group (P < 0.0001) and conventional group (P < 0.0001) with no difference between groups in CST reduction at 12 months (P = 0.36). No reoperations or visually significant recurrent ERMs occurred in either cohort. CONCLUSIONS: Intraoperative OCT-guided ERM removal without mandated ILM peeling provided similar VA and anatomic results to conventional ILM peeling for ERM. Future randomized prospective studies are needed to assess fully the possible role of iOCT in ERM surgery and to evaluate the potential impact of nonfoveal ERM persistence or recurrence in comparison with conventional surgery.

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.

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.

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.