Deep learning-based algorithm for the detection of idiopathic full thickness macular holes in spectral domain optical coherence tomography.

BACKGROUND: Automated identification of spectral domain optical coherence tomography (SD-OCT) features can improve retina clinic workflow efficiency as they are able to detect pathologic findings. The purpose of this study was to test a deep learning (DL)-based algorithm for the identification of Idiopathic Full Thickness Macular Hole (IFTMH) features and stages of severity in SD-OCT B-scans. METHODS: In this cross-sectional study, subjects solely diagnosed with either IFTMH or Posterior Vitreous Detachment (PVD) were identified excluding secondary causes of macular holes, any concurrent maculopathies, or incomplete records. SD-OCT scans (512 × 128) from all subjects were acquired with CIRRUS™ HD-OCT (ZEISS, Dublin, CA) and reviewed for quality. In order to establish a ground truth classification, each SD-OCT B-scan was labeled by two trained graders and adjudicated by a retina specialist when applicable. Two test sets were built based on different gold-standard classification methods. The sensitivity, specificity and accuracy of the algorithm to identify IFTMH features in SD-OCT B-scans were determined. Spearman's correlation was run to examine if the algorithm's probability score was associated with the severity stages of IFTMH. RESULTS: Six hundred and one SD-OCT cube scans from 601 subjects (299 with IFTMH and 302 with PVD) were used. A total of 76,928 individual SD-OCT B-scans were labeled gradable by the algorithm and yielded an accuracy of 88.5% (test set 1, 33,024 B-scans) and 91.4% (test set 2, 43,904 B-scans) in identifying SD-OCT features of IFTMHs. A Spearman's correlation coefficient of 0.15 was achieved between the algorithm's probability score and the stages of the 299 (47 [15.7%] stage 2, 56 [18.7%] stage 3 and 196 [65.6%] stage 4) IFTMHs cubes studied. CONCLUSIONS: The DL-based algorithm was able to accurately detect IFTMHs features on individual SD-OCT B-scans in both test sets. However, there was a low correlation between the algorithm's probability score and IFTMH severity stages. The algorithm may serve as a clinical decision support tool that assists with the identification of IFTMHs. Further training is necessary for the algorithm to identify stages of IFTMHs.

Characterization of pentosan polysulfate patients for development of an alert and screening system for ophthalmic monitoring.

OBJECTIVE: Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis. Numerous reports have been published detailing retinal toxicity with the use of PPS. Studies characterizing this condition are primarily retrospective, and consequently, alert and screening systems need to be developed to actively screen for this disease. The goal of this study was to characterize ophthalmic monitoring trends of a PPS-using patient sample to construct an alert and screening system for monitoring this condition. METHODS: A single-institution retrospective chart review was conducted between January 2005 and November 2020 to characterize PPS use. An electronic medical record (EMR) alert was constructed to trigger based on new PPS prescriptions and renewals offering ophthalmology referral. RESULTS: A total of 1407 PPS users over 15 years was available for characterization, with 1220 (86.7%) being female, the average duration of exposure being 71.2 ± 62.6 months, and the average medication cumulative exposure being 669.7 ± 569.2 g. A total of 151 patients (10.7%) had a recorded visit with an ophthalmologist, with 71 patients (5.0%) having optical coherence tomography imaging. The EMR alert fired for 88 patients over 1 year, with 34 patients (38.6%) either already being screened by an ophthalmologist or having been referred for screening. CONCLUSIONS: An EMR support tool can improve referral rates of PPS maculopathy screening with an ophthalmologist and may serve as an efficient method for longitudinal screening of this condition with the added benefit of informing pentosan polysulfate prescribers about this condition. Effective screening and detection may help determine which patients are at high risk for this condition.

Functional Imaging of Mitochondria in Age-Related Macular Degeneration Using Flavoprotein Fluorescence.

PURPOSE: Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of age-related macular degeneration (AMD). Oxidized mitochondrial flavoprotein fluorescence (FPF) may serve as a quantifiable biomarker of oxidative stress, reported as either mean score for the entire image (intensity) or variability (heterogeneity). This study examines FPF intensity and heterogeneity across a large patient cohort of various Beckman stages of AMD. METHODS: This study enrolled patients with isolated AMD and healthy control patients with no retinopathy between 2018 and 2021. Multivariate logistic regression analysis included stage of AMD, age, gender, ethnicity, and smoking status. Analysis of Variance test compared mean FPF intensity and heterogeneity between disease states. RESULTS: Four hundred fifty-six eyes (228 AMD eyes, 228 age-matched control eyes) were included in the final multivariate analysis. Intermediate, geographic atrophy (GA), and neovascular AMD correlated with significantly increased FPF intensity (P < 0.001, respectively), while all AMD stages correlated with increased FPF heterogeneity (P < 0.001, respectively). FPF intensity and heterogeneity were significant negative predictors of visual acuity (P = 0.018 and 0.024, respectively). CONCLUSIONS: This prospective observational study further implicates mitochondrial damage in AMD pathophysiology. Long-term clinical trials will be needed to examine the predictive role of FPF imaging in patients over time. [Ophthalmic Surg Lasers Imaging Retina 2023;54:24-31.].

Association of Socioeconomic Health Care Disparities With Use of Anti-Vascular Endothelial Growth Factor and Visual Acuity Outcomes in Patients With Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: This study characterizes the impact of race, ethnicity, insurance status, and geographic location on anti-vascular endothelial growth factor (VEGF) use for the treatment of diabetic macular edema (DME). PATIENTS AND METHODS: This study is a retrospective cohort study. The American Academy of Ophthalmology Intelligent Research in Sight Registry was queried for patients diagnosed with DME who received at least one anti-VEGF injection between 2012 and 2020 (n = 203,707). Multivariate regression analyses investigated associations between race, ethnicity, insurance status, and geographic location and anti-VEGF use and visual outcomes. RESULTS: White race, non-Hispanic/Latino ethnicity, and private insurance were associated with higher use of anti-VEGF injections during a 60-month period (incidence rate ratio, 1.2, 1.25, and 1.17, respectively; P < .01). Furthermore, being of non-Hispanic/Latino ethnicity and having private health insurance were associated with higher longitudinal visual acuity (odds ratio, 1.44 [P = .02] and odds ratio, 1.43 [P < .01], respectively). CONCLUSION: Ethnicity and insurance status are associated with anti-VEGF use and visual acuity outcomes in DME. [Ophthalmic Surg Lasers Imaging Retina 2022; 53:380-391.].

Macular thickness fluctuation in neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor.

OBJECTIVE: To establish whether increased variability in macular thickness in neovascular age-related macular degeneration (nAMD) patients affects visual outcomes in clinical practice DESIGN: Retrospective cohort study PARTICIPANTS: Treatment-naive nAMD patients studied over 24 months METHODS: Central subfield thickness (CST) values from optical coherence tomography were collected quarterly from baseline to 24 months, and standard deviations (SDs) were calculated. The relationship was modeled with mixed-effects regression between CST SD and 24-month change in visual acuity (VA). Linear regression modeling determined predictors of CST SD. RESULTS: A total of 422 eyes with nAMD were studied. Baseline and 24-month CST values (mean ± SD) were 331.2 ± 97.6 and 253.4 ± 53.6 µm (Δ = -77.8 ± 104.7 µm, p < 0.001), with CST SD across 24 months of 42.0 ± 32.8 µm. Baseline and 24-month VA were 58.8 ± 19.2 and 62.4 ± 20.6 Early Treatment of Diabetic Retinopathy Study letters (Δ = +3.7 ± 20.8 letters, p = 0.008). CST SD over 24 months was a statistically significant negative predictor of 24-month change in VA (-15.41 [-20.98, -9.83] letters per 100 µm, p < 0.001). Quartile analysis of 24-month VA by CST SD showed a +11.2-letter difference between the first and last quartiles (p < 0.001). Baseline CST was a predictor of 24-month CST SD (24.88 [22.69, 27.06] µm per 100 µm, p < 0.001). CONCLUSIONS: Higher macular thickness fluctuations are related to poorer visual outcomes at 24 months in patients with nAMD treated with anti-vascular endothelial growth factor injections. Macular thickness variability may be an important prognostic factor of visual outcomes in nAMD eyes.

Fluctuations in macular thickness in patients with diabetic macular oedema treated with anti-vascular endothelial growth factor agents.

PURPOSE: To evaluate retinal thickness fluctuations in patients with diabetic macular oedema (DMO) treated with anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: Visual acuity (VA) and central subfield thickness (CST) were collected at baseline, 3, 6, 9 and 12 months. Retinal thickness fluctuation was quantified by standard deviation (SD) of CST across 12 months. A mixed effects regression model evaluated the relationship between CST SD and VA at 12 months. Multiple linear regression analysis was performed to investigate predictors of CST SD. RESULTS: Mean baseline and 12-month VAs were 63.5 ± 15.7 and 69.0 ± 13.8 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (change = +5.1 ± 16.1 letters, p < 0.001). Mean baseline and 12-month CSTs were 396.9 ± 109.7 and 337.7 ± 100.7 µm (change = -59.2 ± 114.8 µm, p < 0.001). Retinal thickness variability across the first 12 months was 59.4 ± 43.6 µm. Stratification of patient eyes by CST SD demonstrated 9.7 letters difference in 12-month VA between first and fourth quartiles. Significant predictors of CST SD include baseline CST, injection type, laser treatment, and DR stage. CONCLUSIONS: Larger retinal thickness fluctuations are associated with poorer visual outcomes in eyes with DMO treated with anti-VEGF injections. Retinal thickness variability may be an important prognostic biomarker for DMO patients.

Race and Socioeconomic Status in Anti-VEGF Treatment of Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: Although people of low socioeconomic status (SES) and certain racial groups are at greater risk of developing diabetic macular edema (DME), the extent these high-risk groups experience treatment differences is unknown. This study characterizes anti-vascular endothelial growth factor (anti-VEGF) injection use for DME. PATIENTS AND METHODS: Data were collected from an electronic health record at the Cole Eye Institute, Cleveland Clinic Foundation for patients who received anti-VEGF treatment for DME between 2012 and 2019 (N = 500). RESULTS: White patients on average received more injections over a 1-year period than Black patients (4.93 ± 3.14 vs 3.20 ± 2.43; P < .0001) and had fewer no-show appointments (1.39 ± 2.08 vs 3.23 ± 3.39; P < .0001). There is an association between living in communities with lower average incomes and receiving fewer anti-VEGF injections (3.06 ± 2.70 vs 4.88 ± 3.19; P = .005). CONCLUSIONS: DME treatment differs based on race and SES. Racial and SES associations with anti-VEGF injections present potential obstacles for delivering optimal ophthalmic care. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:578-585.].

Student becomes teacher: training faster deep learning lightweight networks for automated identification of optical coherence tomography B-scans of interest using a student-teacher framework.

This work explores a student-teacher framework that leverages unlabeled images to train lightweight deep learning models with fewer parameters to perform fast automated detection of optical coherence tomography B-scans of interest. Twenty-seven lightweight models (LWMs) from four families of models were trained on expert-labeled B-scans (∼70 K) as either "abnormal" or "normal", which established a baseline performance for the models. Then the LWMs were trained from random initialization using a student-teacher framework to incorporate a large number of unlabeled B-scans (∼500 K). A pre-trained ResNet50 model served as the teacher network. The ResNet50 teacher model achieved 96.0% validation accuracy and the validation accuracy achieved by the LWMs ranged from 89.6% to 95.1%. The best performing LWMs were 2.53 to 4.13 times faster than ResNet50 (0.109s to 0.178s vs. 0.452s). All LWMs benefitted from increasing the training set by including unlabeled B-scans in the student-teacher framework, with several models achieving validation accuracy of 96.0% or higher. The three best-performing models achieved comparable sensitivity and specificity in two hold-out test sets to the teacher network. We demonstrated the effectiveness of a student-teacher framework for training fast LWMs for automated B-scan of interest detection leveraging unlabeled, routinely-available data.

Ophthalmology Provider Ratings and Patient, Disease, and Appointment Factors.

The purpose of the current study is to examine how nonmodifiable sociodemographic, disease, appointment, management, and survey factors correlate with provider rating. This was a retrospective cross-sectional study conducted on 29 857 patient Clinician and Group Consumer Assessment of Healthcare Providers and Systems surveys collected from January 2017 to January 2019 at a tertiary eye center. We included surveys of patients aged 18 years or older, who answered at least 4 of 6 subfield questions, and completed the survey within 90 days of the appointment. The main outcome was the odds of receiving top box score (TBS) of 10/10 on the survey question regarding overall provider rating. The results showed that the variables with higher odds of TBS included higher overall appointment attendance (odds ratio [OR]: 2.66 [95% CI: 1.23-5.75], P = .013); older patient age (OR 2.44 [95% CI: 2.08-2.87], P < .001]; higher percentage of survey questions completed (OR: 2.02 [95% CI: 1.79-2.27], P < .001); better best corrected visual acuity (OR: 1.85 [95% CI: 1.3-2.64], P = .001); optometry clinic visit (OR: 1.25 [95% CI: 1.15-1.36], P < .001); having procedures (OR: 1.19 [95% CI: 1.04-1.36], P = .013), surgery scheduled (OR: 1.18 [95% CI: 1.03-1.36], P = .020], or refraction done (OR: 1.16 [95% CI: 1.08-1.25], P < .001); being seen by male providers (OR: 1.11 [95% CI: 1.04-1.17], P = .001); and having additional eye testing performed (OR: 1.06 [95% CI: 1.00-1.13], P = .048). Variables associated with lower odds of TBS included longer time to complete survey (OR: 0.42 [95% CI: 0.3-0.58], P = .001); new patient encounter (OR: 0.62 [95% CI: 0.58-0.65], P < .001); and glaucoma (OR: 0.66 [95% CI: 0.59-0.75], P < .001), cornea (OR: 0.79 [95% CI: 0.71-0.87], P < .001), or comprehensive clinic visits (OR: 0.86 [95% CI: 0.79-0.94], P < .001). Thus, nonmodifiable factors may affect the provider rating, and these factors should be studied further and accounted for when interpreting the results of patient experience surveys.

Real-World Treatment Patterns in a Population With Neovascular AMD Treated With Anti-VEGF Agents.

BACKGROUND AND OBJECTIVES: To characterize mean number of injections, injection type, and injection frequency during the first year of treatment; assess factors significantly related to injection interval; and identify predictive factors related to patient outcomes. PATIENTS AND METHODS: A retrospective, noncomparative, nonrandomized cohort study of ocular treatment with intravitreal injections of bevacizumab, ranibizumab, and aflibercept in eyes with neovascular age-related macular degeneration (nAMD). Data from January 1, 2012, through March 31, 2018, were systematically extracted from the electronic medical record system at Cole Eye Institute. Eligible patients had three or more injections within the first 12 months of treatment and received no prior injections. RESULTS: Patients received an average 8.12 ± 2.45 injections, and 45% of patients received injections at an interval of 8 weeks or less (≤q8 weeks), 33% received injections at 8 to 12 weeks (q8-12 weeks), and 22% received injections at greater than 12 weeks (>q12 weeks). Age (P = .007) and initial central subfield thickness (CST) (P = .043) had statistically significant trend relationships (P = .007) with injection interval, whereas younger patients and patients with higher CST measurements tended to have shorter injection intervals. Injection interval was a significant predictor of visual acuity (VA) and CST. Patients receiving injections at q8-12 weeks were more likely to have better VA outcomes than patients with injection intervals at ≤q8 weeks (odds ratio [OR] = 1.66 [1.16, 2.37]; P = .005). Patients receiving injections at >q12 weeks did not show a significant improvement in VA (P = .06) and were more likely to have worse CST outcomes than patients receiving injections at ≤q8 weeks (OR = 1.95 [1.17, 3.26]; P = .011). CONCLUSION: A significant portion of patients receive injections at an interval longer than every 8 weeks. Age and baseline CST had a significant relationship with injection interval. Injection interval was a significant predictor of VA and CST at 1 year. Patients with an injection interval of >q12 weeks tended to have less VA improvement and CST reduction compared to the ≤q8 weeks and q8-12 weeks groups. These findings suggest an extended injection interval >q12 weeks may be at the expense of potential VA improvement. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:190-198.].

Management of Patients With DME With Good Visual Acuity in Routine Clinical Practice.

BACKGROUND AND OBJECTIVE: To determine outcomes of eyes with diabetic macular edema (DME) and best visual acuity (BVA) of 20/25 or better in routine clinical practice. PATIENTS AND METHODS: Retrospective study of 72 patients with DME and BVA of 20/25 or better. Patients were divided by anti-vascular endothelial growth factor (VEGF) treatment regimen: early (Group A), delayed (Group B), and none (Group C). RESULTS: Group A had higher baseline central subfield thickness (CST) (325 ± 62 µm) compared to Groups B (292 ± 24 µm) and C (296 ± 35 µm) (P = .033). All groups had similar 24-month CST (299 ± 62 µm, 280 ± 64 µm, 296 ± 65 µm; P = .61). There was no difference in baseline BVA among groups (81.9 ± 2.4, 83.2 ± 2.4, 82.4 ± 2.5 Early Treatment Diabetic Retinopathy Study [ETDRS] letters, respectively; P = .290), but at 6 months, Group A had lower BVA (76.6 ± 9.6 ETDRS letters) than groups B (81.9 ±3.3 ETDRS letters) and C (82.4 ± 5.0 ETDRS letters) (P = .008). There was no difference among groups in 24-month BVA (78.9 ± 6.6, 78.4 ± 12.3, and 80.6 ± 6.9 ETDRS letters, respectively; P = .448). CONCLUSION: Although observation may be indicated in eyes with stable BVA and CST less than 300 µm, anti-VEGF stabilizes BVA in eyes with CST greater than 300 µm and eyes with declining BVA. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:247-256.].

Determining the Location of the Fovea Centralis Via En-Face SLO and Cross-Sectional OCT Imaging in Patients Without Retinal Pathology.

Purpose: The purpose was to establish the position of the fovea centralis to the optic nerve via en-face, near-infrared spectral domain optical coherence tomography (NIR-OCT) in healthy patients. This may shed light on physiological variability and be used for studying subtle cases of foveal ectopia in macular pathology and after retinal detachment. Methods: SD-OCT data of 890 healthy eyes were retrospectively analyzed. Exclusion criteria included axial myopia causing tilting of the optic disc, peripapillary atrophy >1/3 the width of the disc, macular images excluding greater than half of the optic disc, and patients unable to maintain vertical head positioning. Two independent reviewers measured the horizontal and vertical distance from the fovea to the optic disc center and optic disc diameter via cross-sectional and en-face scanning laser ophthalmoloscopy OCT imaging. Results: 890 eyes were included in the study. The right and left eyes differed in the horizontal distance from the fovea to the disc center (4359 vs. 4248 µm, P < 0.001) and vertical distance from the fovea to the disc center (464 µm vs. 647, P < 0.001). This corresponded to a smaller angle between the right and left eyes (6.07° vs. 8.67°, P < 0.001). Older age was associated with a larger horizontal (P = 0.008) and vertical distance (0.025). These differences persisted after correcting for axial length in the 487 patients with axial-length data. Conclusions: This study compares the position of the fovea centralis among individuals without macular pathology on a micron level basis. The significant variability between right and left eyes indicates that contralateral eye evaluation cannot be reliably used. Rather, true foveal ectopia requires assessments of preoperative and postoperative NIR-OCT scans. This finding is relevant to retinal detachment cases and evaluation of subtle foveal ectopia. Translational Relevance: This finding is relevant to retinal detachment cases and evaluation of subtle foveal ectopia.

Racial, Ethnic, and Insurance-Based Disparities Upon Initiation of Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema in the US.

PURPOSE: This study characterizes the association of risk factors including race, ethnicity, and insurance status with presenting visual acuity (VA) and diabetic retinopathy (DR) severity in patients initiating treatment with anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME). DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: The Academy Intelligent Research in Sight (IRIS) Registry database was queried for patients who initiated anti-VEGF injection treatment for DME between 2012 and 2020 (n = 203 707). METHODS: Multivariate regression analyses were conducted to understand how race, ethnicity, insurance status, and geographic location were associated with baseline features. MAIN OUTCOME MEASURES: Visual acuity and DR severity. RESULTS: Patients on Medicare and private insurance presented with higher baseline VA compared with patients on Medicaid (median of 2.31 and 4.17 greater Early Treatment Diabetic Retinopathy Scale [ETDRS] letters, respectively P < 0.01). White and non-Hispanic patients presented with better VA compared with their counterparts (median of 0.68 and 2.53 greater ETDRS letters, respectively; P < 0.01). Black and Hispanic patients presented with a worse baseline DR severity compared with White and non-Hispanic patients (odds ratio, 1.23 and 1.71, respectively; P < 0.01). CONCLUSIONS: There are ethnic and insurance-based disparities in VA and disease severity upon initiation of anti-VEGF therapy for DME treatment. Public health initiatives could improve timely initiation of treatment.

Visual outcomes following cataract surgery in age-related macular degeneration patients.

OBJECTIVE: To evaluate visual acuity (VA) outcomes, prognostic factors, and changes in disease severity in patients with age-related macular degeneration (AMD) undergoing cataract surgery. DESIGN: Retrospective cohort study PARTICIPANTS: Patients with AMD or healthy control patients who underwent cataract surgery between 2012 and 2017. METHODS: Eyes were categorized into 3 AMD groups-intermediate AMD (iAMD), fovea-involving geographic atrophy (GA), neovascular AMD (nAMD)-and 3 preoperative VA-matched control groups (iAMDc), fovea-involving geographic atrophy control (GAc), neovaascular AMD control (nAMDc). RESULTS: We compared 216 iAMD, 35 GA, and 184 nAMD eyes with 130, 31, and 129 controls. At postoperative month 12 (POM12), VA increased significantly in iAMD and nAMD (+10.1 ± 14.5 and +9.7 ± 18.9 letters, p < 0.001), but not in GA (p = 0.68). All control groups showed significant VA gains (iAMDc: +17.1 ± 9.7, GAc: +30 ± 12.9, and nAMDc: +26.4 ± 15.6 letters, p < 0.001). For AMD groups, POM12 VA and gain in VA were significantly lower than that of controls (p < 0.01), and better preoperative VA predicted smaller VA gains (p ≤ 0.007). Longer duration of AMD in iAMD, ellipsoid zone disruption in nAMD, and lower central subfield thickness in GA were associated with poorer VA outcomes (p < 0.05). Development of nAMD occurred in 8 iAMD eyes and was associated with longer duration of disease (p = 0.001). For nAMD eyes, injection frequency did not vary between the 12-month pre- and postoperative periods (p = 0.051). CONCLUSIONS: Cataract surgery improves VA for patients with iAMD and nAMD, albeit not to the level of those without retinal pathology. Preoperative VA, AMD duration, and optical coherence tomography parameters may be important prognostic factors for cataract surgery in patients with AMD.

CONSEQUENCES OF LAPSES IN TREATMENT WITH VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN ROUTINE CLINICAL PRACTICE.

PURPOSE: Evaluating outcomes in patients receiving intravitreal antivascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration whom experience a lapse in treatment. METHODS: A retrospective chart review evaluating 3,304 patients ≥18 years who experienced treatment lapses ≥3 months compared with control counterparts. Demographic information, macular thickness as measured by central subfield thickness, and visual acuity were collected at baseline, the first postlapse appointment, and at 3, 6, and 12 months after the lapse for the study group. RESULTS: Lapse (n = 241) and control patients (n = 241) had similar baseline visual acuity and central subfield thickness (Early Treatment Diabetic Retinopathy Study: 58.9 ± 20.2 [20/63] vs. 59.2 ± 20.1 [20/63]; central subfield thickness: 252.4 ± 63.2 µm vs. 259.8 ± 66.2 µm, P = 0.21). Analysis revealed that lapse patients experienced a significant increase in central subfield thickness after lapse when compared with controls (279.4 ± 86.9 µm vs. 253.7 ± 65.9 µm, P < 0.01), which normalized on resumption of treatment (259.1 ± 79 µm vs. 246.8 ± 57.6 µm, P = 0.06). Study patients also experienced loss in the visual acuity after lapse when compared with controls (52.9 ± 23.6 Early Treatment Diabetic Retinopathy Study [20/100] vs. 59.9 ± 20.8 [20/63] Early Treatment Diabetic Retinopathy Study, P < 0.01) that did not recover through 12 months of follow-up. CONCLUSION: Patients with neovascular age-related macular degeneration who have lapses in care are at risk for poorer outcomes. Although macular thickness normalizes on resumption of treatment, their decline in the visual acuity does not recover.

Infectious and Sterile Endophthalmitis in Eyes with Glaucoma Drainage Device from Two Large Ophthalmic Institutions.

PURPOSE: To describe the predisposing factors, presentation, management, and outcome of glaucoma drainage implant (GDI)-associated endophthalmitis. DESIGN: Retrospective chart review. PARTICIPANTS: Eyes that developed GDI-associated endophthalmitis between December 1, 2011, and December 23, 2019, at the Duke Eye Center and Cole Eye Institute. METHODS: Patient data search was performed on the basis of diagnostic codes for GDI and endophthalmitis. Endophthalmitis was defined clinically according to each physician's discretion. Eyes with infection source other than GDI were excluded. Worse vision was defined as a decrease of more than 2 Snellen lines. Data were collected on baseline demographics, systemic and ocular comorbidities, ocular surgical history, best-corrected visual acuity (BCVA), intraocular pressure (IOP), clinical presentation, eye culture results, and treatments performed. Statistical analysis included the paired t test and odds radio calculations. MAIN OUTCOME MEASURES: Visual acuity and IOP at final follow-up. RESULTS: Thirty cases (0.7%) of GDI endophthalmitis were identified among 4073 GDIs performed at the 2 institutions with active follow-up. Device exposure was identified in 20 eyes (67%) on presentation. The average follow-up after presentation was 22.4 ± 25 months. The most frequently identified organism on culture was Streptococcus pneumoniae. Same-day injection of intravitreal antibiotics was the universal first-line therapy. From baseline to final follow-up, the mean BCVA decreased from -0.84 ± 0.77 to -1.30 ± 0.93 (logarithm of the minimum angle of resolution, P = 0.02). Mean IOP did not change from baseline to final visit in the overall cohort (16.2 ± 8.2 mmHg to 14.6 ± 9.4 mmHg, P = 0.30) and in the subgroup that underwent tube explant (15.9 ± 5.5 mmHg to 15.2 ± 10.4 mmHg, P = 0.97). Eighteen of 20 tube exposure cases (90%) underwent tube explant, 1 underwent tube revision, and 1 re-epithelialized. CONCLUSIONS: Glaucoma drainage implant-associated endophthalmitis was correlated with poor visual outcome. Immediate intravitreal antibiotic delivery was a universal first-line therapy. Tube exposure was a necessary risk factor for late-onset endophthalmitis and required surgical removal or repair.

Impact and Characterization of Delayed Pan-Retinal Photocoagulation in Proliferative Diabetic Retinopathy.

PURPOSE: The American Academy of Ophthalmology recommends that patients diagnosed with proliferative diabetic retinopathy (PDR) be considered for pan-retinal photocoagulation (PRP) treatment within 1 month of diagnosis. This study aimed to investigate the effect delayed treatment had on visual outcomes and to characterize the medical and socioeconomic factors that contributed to delayed treatment of PDR. DESIGN: Retrospective clinical study. METHODS: This study examined 259 patients diagnosed with PDR and treated with PRP from 2015 to the present. Visual acuity (VA) outcomes through 24 months were compared among patients treated the day of diagnosis, and at 1-14 days, 14-31 days, and >31 days post-treatment. The relationships between time to treatment (days between PDR diagnosis and PRP) and medical comorbidities (coronary artery disease and/or myocardial infarction, heart failure, chronic kidney disease, dialysis, stroke, inpatient admission), laboratory values (hemoglobin A1c, blood urea nitrogen, serum creatinine), and socioeconomic factors (health insurance, median household income of ZIP code, and distance from ZIP code to treatment site) were examined. RESULTS: Mean time to treatment for all patients was 27.8 ± 41.4 days. VA was significantly decreased in patients who received PRP after 31 days compared with those treated on the day of diagnosis at 12 (P < .001) and 24 (P = .03) months post-treatment. Inpatient admission between diagnosis and treatment was significantly associated with an increase in time to treatment (86.5 ± 50.2 days; P < .001). CONCLUSIONS: In patients with diagnosed PDR, a delay in PRP treatment beyond 31 days was associated with worse visual outcomes than those treated earlier. Hospital admissions significantly delayed PRP delivery.

Age-related differences in presentation and outcomes of anti-VEGF treatment of retinal vein occlusion.

OBJECTIVE: To assess age-related differences at baseline and treatment outcomes in patients with retinal vein occlusion (RVO) and macular edema treated with anti-vascular endothelial growth factor (VEGF) therapy DESIGN: Single-centre retrospective chart review. PARTICIPANTS: 295 treatment-naïve RVO patients. METHODS: 295 RVO patients included were separated into age quartiles: group A (22-61 years), group B (62-70 years), group C (71-79 years), and group D (80-95 years). Outcomes including central subfield thickness (CST), cubic volume, cubic average thickness, and visual acuity (VA) were collected at baseline and at 6 and 12 months after treatment. The primary outcome of the study was the CST at 12 months after anti-VEGF therapy. RESULTS: Mean baseline CST for groups A, B, C, and D was 406.3 ± 161.2 µm, 463.4 ± 165.5 µm, 470.6 ± 187 µm, and 427.3 ± 187.2 µm, respectively. No significant differences in CST were observed between groups at baseline, 6 months, or 12 months (p ≥ 0.08). Mean baseline VA for groups A, B, C, and D was 55.8 ± 19.5, 54.4 ± 19.8, 54.7 ± 19, and 51.4 ± 20.4 Early Treatment Diabetic Retinopathy letters, respectively. VA did not differ significantly between age groups at baseline, 6 months, or 12 months (p ≥ 0.06). CONCLUSIONS: The presentation of RVO and the visual outcomes of anti-VEGF therapy do not vary based on age.

Functional imaging of mitochondria in retinal diseases using flavoprotein fluorescence.

Mitochondria are critical for cellular energy production and homeostasis. Oxidative stress and associated mitochondrial dysfunction are integral components of the pathophysiology of retinal diseases, including diabetic retinopathy (DR), age-related macular degeneration, and glaucoma. Within mitochondria, flavoproteins are oxidized and reduced and emit a green autofluorescence when oxidized following blue light excitation. Recently, a noninvasive imaging device was developed to measure retinal flavoprotein fluorescence (FPF). Thus, oxidized FPF can act as a biomarker of mitochondrial dysfunction. This review article describes the literature surrounding mitochondrial FPF imaging in retinal disease. The authors describe the role of mitochondrial dysfunction in retinal diseases, experiments using FPF as a marker of mitochondrial dysfunction in vitro, the three generations of retinal FPF imaging devices, and the peer-reviewed publications that have examined FPF imaging in patients. Finally, the authors report their own study findings. Goals were to establish normative reference levels for FPF intensity and heterogeneity in healthy eyes, to compare between healthy eyes and eyes with diabetes and DR, and to compare across stages of DR. The authors present methods to calculate a patient's expected FPF values using baseline characteristics. FPF intensity and heterogeneity were elevated in diabetic eyes compared to age-matched control eyes, and in proliferative DR compared to diabetic eyes without retinopathy. In diabetic eyes, higher FPF heterogeneity was associated with poorer visual acuity. In conclusion, while current retinal imaging modalities frequently focus on structural features, functional mitochondrial imaging shows promise as a metabolically targeted tool to evaluate retinal disease.