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PurposeTo assess associations between visual acuity (VA) and the status of the photoreceptor inner segment-outer segment (IS-OS) junction in a subset of patients in the Standard Care vs COrticosteroid for REtinal Vein Occlusion (SCORE) Study.MethodologyHigh-resolution time domain optical coherence tomography (OCT) scans of study eyes from a single site participating in the SCORE Study were evaluated. Integrity of the IS-OS junction in the central subfield was evaluated using a three-step scale: absent, abnormal or normal. Associations of the IS-OS status with ETDRS VA letter score and center point thickness (CPT) were investigated.ResultsBaseline OCTs of 42 eyes were evaluated. The IS-OS junction was absent in 30 (71%) and abnormal in 12 (29%). At month 12, the IS-OS junction was absent in 18 (43%), abnormal in 12 (28%), and normal in 12 (28%) eyes. At baseline, IS-OS status was significantly associated with CPT, but not with VA. At month 12, IS-OS status was significantly associated with CPT and VA, that is, absent or abnormal IS-OS was associated with increased CPT and worse VA. Change in IS-OS status was not associated with change in CPT (P=0.8). Worsening of IS-OS status was associated with loss of VA and improvement in IS-OS status to normal was associated with gain in VA (P=0.03).ConclusionIn this data set with long-term follow-up of OCTs as part of the SCORE Study, there is a correlation between change in IS-OS status and VA. This supports further evaluation of outer retinal morphology in larger data sets. [ABSTRACT FROM AUTHOR]

Objective: To investigate quantitative and qualitative changes in retinal structure using optical coherence tomography (OCT) and their associations with systemic or other risk factors in individuals with type 1 diabetes (T1D)., Research Design and Methods: In the Epidemiology of Diabetes Interventions and Complications (EDIC) study, OCT images were obtained during study years 25-28 (2019-2022) in 937 participants; 54% and 46% were from the original intensive (INT) and conventional (CONV) glycemic management treatment groups, respectively., Results: Average age for participants was 61 years old, diabetes duration 39 years, and HbA1c 7.6%. Participants originally in the CONV group were more likely to have disorganization of retinal inner layers (DRIL) (CONV 27.3% vs. INT 18.7%; P = 0.0003), intraretinal fluid (CONV 24.4% vs. INT 19.2%; P = 0.0222), and intraretinal cysts (CONV 20.8% vs. INT 16.6%; P = 0.0471). In multivariable models, sex, age, smoking, mean updated systolic blood pressure, and history of "clinically significant" macular edema (CSME) and of anti-VEGF treatment were independently associated with changes in central subfield thickness, while HbA1c, BMI, and history of CSME and of ocular surgery were associated with DRIL. Visual acuity (VA) decline was associated with significant thinning of all retinal subfields except for the central and inner nasal subfields., Conclusions: Early intensive glycemic management in T1D is associated with a decreased risk of DRIL. This important morphological abnormality was associated with a history of macular edema, a history of ocular surgery, and worse VA. This study reveals benefits of intensive glycemic management on the retina beyond features detected by fundus photographs and ophthalmoscopy., (© 2024 by the American Diabetes Association.)

Importance: High concordance in diabetic retinopathy (DR) outcomes between 7-field (7F) and ultra-widefield (UWF) images would allow for combining longitudinal assessments based on the 2 modalities both in clinical studies and clinical care., Objective: To compare 7F and UWF imaging with regard to DR severity and the associations of DR severity with risk factors, such as hemoglobin A1c, age, diabetes duration, and sex., Design, Setting, and Participants: This cross-sectional study describes the outcomes of the randomized clinical Diabetes Control and Complications Trial (DCCT) and its subsequent observational study, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Of the 1441 participants with type 1 diabetes in the DCCT, 1375 were enrolled in the EDIC study. Of the 1171 participants who were active between March 2019 and December 2021, 200° UWF color imaging and 7F fundus photographs were obtained for 785 participants once at the same visit. Central graders assessed 7F-UWF with a 7F template masking the retinal periphery and the full UWF image (UWF-global). Data were analyzed from January 2022 to March 2023., Exposures: Hemoglobin A1c was assessed quarterly during the DCCT and annually during the EDIC study using high-performance liquid chromatography., Main Outcomes and Measures: Retinopathy was determined independently for all imaging as mild, moderate, or severe nonproliferative DR (SNPDR) using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale for the 7F images and the global ETDRS grading scale for the UWF images. Panretinal and focal photocoagulation were self-reported or based on scarring location and pattern observed during grading. Proliferative DR (PDR) was defined by observed neovascularization or evidence of panretinal photocoagulation., Results: Among the 785 participants included in this study, 420 (53%) were male and 365 (47%) were female. The mean (SD) age was 61 (7) years. DR grading between UWF-7F and 7F imaging was correlated for all outcomes, including for severe outcomes, such as SNPDR (κ, 0.73; concordance, 96%), PDR (κ, 0.74; concordance, 97%), scatter photocoagulation (κ, 0.97; concordance, 99%), and focal photocoagulation (κ, 0.71; concordance, 98%). Most DR severity scores were within 1 step (1410 of 1529 [92%]), and 3% (51 of 1529) were more than 2 steps apart (κ, 0.45; 95% CI, 0.42-0.49; weighted κ, 0.63; 95% CI, 0.60-0.67) on the ETDRS severity scale. DR severity assessed within the UWF-global area was higher compared to 7F (median [IQR] UWF-global score, 3 [2-3] vs median 7F level score, 2.0 [1-3]; P < .001), although the 2 modalities were correlated (1225 of 1508 [81%] 1-step agreement; weighted κ, 0.41)., Conclusions and Relevance: Standard ETDRS 7F and UWF evaluations of DR were comparable for ETDRS severity levels as previously reported by Diabetic Retinopathy Clinical Research Retina Network reports. In addition, these evaluations of DR were comparable for DCCT/EDIT study outcomes and major study conclusions, suggesting that use of UWF imaging is not likely to introduce relevant measurement biases in future longitudinal studies., Trial Registration: ClinicalTrials.gov Identifiers: NCT00360815.

Purpose: We quantify the association between visit adherence and visual acuity (VA) in retinal vein occlusions (CRVO)., Methods: The SCORE2 protocol included a visit every 4 weeks (every 28-35 days) during the first year. Visit adherence was measured as follows: number of missed visits, average and longest (avg and max days) visit interval, and average and longest (avg and max missed days) and unintended visit interval. Avg and max missed days were categorized as on time (0 days), late (>0-60 days), and very late (>60 days). The primary outcome was a change in the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity letter score (VALS) between baseline study visit and last attended visit during Year 1, using multivariate linear regression models controlling for numerous demographic and clinical factors., Results: After adjustment, for each visit missed, patients lost 3.0 letters (95% CI: -6.2, 0.2) of vision ( p  = .07). On average, the 48 patients who missed at least 1 visit lost 9.4 letters (95% CI: -14.4, -4.3, p  < .001) of vision after adjustment. Average days and maximal intervals between visits were not associated with changes in VALS ( p  > .22) for both comparisons. However, when a visit was missed, the average missed days between missed visits and the max missed interval were both associated with loss of VALS (both variables: 0 days missed as reference, late [1-60 days] -10.8 letters [95% CI: -16.9, -4.7], very late [>60 days] -7.3 letters [95% CI: -14.5, -0.2]; p  = .003 for both)., Conclusions: Visit adherence is associated with VALS outcomes in CRVO patients.

Purpose: The purpose of this study was to compare diabetic retinopathy (DR) severity levels assessed from 7 standard-field stereoscopic color photographs on a 35° fundus camera to both Clarus and Optos ultrawidefield color images., Design: Cross-sectional, comparative imaging study., Participants: Participants with DR imaged at a single-center retina practice., Methods: Participants were imaged on 3 cameras at a single visit with the Topcon 35° fundus camera, Clarus, and Optos. The DR Severity Scale (DRSS) level was determined within the 7-field (7F) area of each image set using the ETDRS scale. An additional global DRSS was assigned for both Clarus and Optos images using the entire visible retina. Weighted kappa (wκ) measured the agreement between cameras., Main Outcome Measures: The primary outcome was a 3-way comparison of DRSS level within the 7F area imaged on the 3 cameras. Secondary outcomes included a comparison of the DRSS obtained with standard 7F imaging to the global DRSS of Clarus and Optos and a comparison of the global DRSS between Clarus and Optos only., Results: Ninety-seven eyes (50 participants) were evaluated. Agreement within 1-step of ETDRS levels between standard 7F imaging and Clarus 7F was 90.1% (wκ = 0.65), and with Optos 7F in 85.9%, (wκ = 0.58). Agreement within 1-step between standard 7F imaging and Clarus global was 88.9% of eyes (wκ = 0.63), and Optos global was 85.7%, (wκ = 0.54). Agreement between Clarus and Optos global DR level within 1-step was 89.1% (wκ = 0.68). Intergrader agreement for the 7F ETDRS level was 96% for standard 7F imaging, 98% for Clarus, and 95.5% for Optos., Conclusions: These findings suggest that when evaluating the 7F area on Clarus and Optos, DR severity grades are comparable to standard 7F imaging. However, it is important to understand the unique attributes and differences of each fundus camera when changing the type of system used in a clinical setting due to upgrading equipment. Additionally, if the facility has access to > 1 device, there should not be an exchange between cameras for the same patient., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)

Purpose: To assess the relationship between best-corrected visual acuity (BCVA) and anatomic features in patients with macular edema (ME) related to retinal vein occlusion (RVO)., Design: Post hoc analysis of 3 clinical trials, which included verified diagnoses, protocol refractions, and the assessment of OCT and fluorescein angiography (FA) images at a masked reading center., Participants: Patients diagnosed with RVO-ME., Methods: Correlation analyses were performed to determine the correlation between BCVA and macular anatomy at baseline and at 12 and 24 weeks and between changes from baseline to 12 and 24 weeks., Main Outcome Measures: The correlations between BCVA and central subfield thickness (CST), ellipsoid zone (EZ) integrity, intraretinal fluid (IRF), subretinal fluid, central leakage, and ischemia were assessed., Results: In a total of 828 eyes with RVO-ME, the mean age, BCVA, and CST at baseline was 64.7 years, 51.1 letters, and 656.9 μm, respectively. At baseline, a moderate negative correlation was observed between BCVA and CST (r = - 0.56, P < 0.001). At weeks 12 and 24, the mean BCVA of eyes with definitely abnormal (absent) EZ was statistically significantly worse than that of eyes with normal EZ. At week 12, a moderate negative correlation was observed between changes in BCVA and changes in CST (r = - 0.35, P < 0.001), with a similar degree of association noted at week 24 (r = - 0.35, P < 0.001). At weeks 12 and 24, eyes that showed any improvement in central IRF showed a greater improvement in BCVA than eyes that showed no improvement worsening (week 12: 463 eyes, 18.3 letters vs. 177 eyes, 13.0 letters, respectively, P < 0.001) and (week 24: 332 eyes, 20.2 letters vs. 131 eyes, 13.3 letters, respectively, P < 0.001). With respect to the correlation between baseline BCVA and fluorescein leakage or capillary nonperfusion, the Pearson correlation coefficients were - 0.41 (P < 0.001) and - 0.16 (P = 0.060), respectively., Conclusions: In addition to CST, there are important clinically relevant relationships between BCVA and both OCT and FA anatomic features in patients with RVO-ME., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine glycemic and nonglycemic risk factors that contribute to the presence of diabetic retinopathy (DR) before and after the onset of type 2 diabetes (T2D)., Research Design and Methods: During the Diabetes Prevention Program (DPP) and DPP Outcome Study (DPPOS), we performed fundus photography over time in adults at high risk for developing T2D, including after they developed diabetes. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system, with DR defined as typical lesions of DR (microaneurysms, exudates, hemorrhage, or worse) in either eye., Results: By DPPOS year 16 (∼20 years after random assignment into DPP), 24% of 1,614 participants who had developed T2D and 14% of 885 who remained without diabetes had DR. In univariate analyses, using results from across the entire duration of follow-up, American Indian race was associated with less frequent DR compared with non-Hispanic White (NHW) race, and higher HbA1c, fasting and 2-h plasma glucose levels during an oral glucose tolerance test, weight, and history of hypertension, dyslipidemia, and smoking, but not treatment group assignment, were associated with more frequent DR. On multivariate analysis, American Indian race was associated with less DR compared with NHW (odds ratio [OR] 0.36, 95% CI 0.20-0.66), and average HbA1c was associated with more DR (OR 1.92, 95% CI 1.46-1.74 per SD [0.7%] increase in HbA1c)., Conclusions: DR may occur in adults with prediabetes and early in the course of T2D. HbA1c was an important risk factor for the development of DR across the entire glycemic range from prediabetes to T2D., (© 2022 by the American Diabetes Association.)

Purpose: The curation of images using human resources is time intensive but an essential step for developing artificial intelligence (AI) algorithms. Our goal was to develop and implement an AI algorithm for image curation in a high-volume setting. We also explored AI tools that will assist in deploying a tiered approach, in which the AI model labels images and flags potential mislabels for human review., Design: Implementation of an AI algorithm., Participants: Seven-field stereoscopic images from multiple clinical trials., Methods: The 7-field stereoscopic image protocol includes 7 pairs of images from various parts of the central retina along with images of the anterior part of the eye. All images were labeled for field number by reading center graders. The model output included classification of the retinal images into 8 field numbers. Probability scores (0-1) were generated to identify misclassified images, with 1 indicating a high probability of a correct label., Main Outcome Measures: Agreement of AI prediction with grader classification of field number and the use of probability scores to identify mislabeled images., Results: The AI model was trained and validated on 17 529 images and tested on 3004 images. The pooled agreement of field numbers between grader classification and the AI model was 88.3% (kappa, 0.87). The pooled mean probability score was 0.97 (standard deviation [SD], 0.08) for images for which the graders agreed with the AI-generated labels and 0.77 (SD, 0.19) for images for which the graders disagreed with the AI-generated labels ( P  < 0.0001). Using receiver operating characteristic curves, a probability score of 0.99 was identified as a cutoff for distinguishing mislabeled images. A tiered workflow using a probability score of < 0.99 as a cutoff would include 27.6% of the 3004 images for human review and reduce the error rate from 11.7% to 1.5%., Conclusions: The implementation of AI algorithms requires measures in addition to model validation. Tools to flag potential errors in the labels generated by AI models will reduce inaccuracies, increase trust in the system, and provide data for continuous model development., (© 2022 by the American Academy of Ophthalmology.)

Importance: The development of artificial intelligence (AI) and other machine diagnostic systems, also known as software as a medical device, and its recent introduction into clinical practice requires a deeply rooted foundation in bioethics for consideration by regulatory agencies and other stakeholders around the globe., Objectives: To initiate a dialogue on the issues to consider when developing a bioethically sound foundation for AI in medicine, based on images of eye structures, for discussion with all stakeholders., Evidence Review: The scope of the issues and summaries of the discussions under consideration by the Foundational Principles of Ophthalmic Imaging and Algorithmic Interpretation Working Group, as first presented during the Collaborative Community on Ophthalmic Imaging inaugural meeting on September 7, 2020, and afterward in the working group., Findings: Artificial intelligence has the potential to improve health care access and patient outcome fundamentally while decreasing disparities, lowering cost, and enhancing the care team. Nevertheless, substantial concerns exist. Bioethicists, AI algorithm experts, as well as the Food and Drug Administration and other regulatory agencies, industry, patient advocacy groups, clinicians and their professional societies, other provider groups, and payors (i.e., stakeholders) working together in collaborative communities to resolve the fundamental ethical issues of nonmaleficence, autonomy, and equity are essential to attain this potential. Resolution impacts all levels of the design, validation, and implementation of AI in medicine. Design, validation, and implementation of AI warrant meticulous attention., Conclusions and Relevance: The development of a bioethically sound foundation may be possible if it is based in the fundamental ethical principles of nonmaleficence, autonomy, and equity for considerations for the design, validation, and implementation for AI systems. Achieving such a foundation will be helpful for continuing successful introduction into medicine before consideration by regulatory agencies. Important improvements in accessibility and quality of health care, decrease in health disparities, and lower cost thereby can be achieved. These considerations should be discussed with all stakeholders and expanded on as a useful initiation of this dialogue., (Published by Elsevier Inc.)

Purpose: To evaluate the association between baseline demographic and spectral domain OCT (SD-OCT) features with visual acuity (VA) in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2) over 2 years., Design: Post hoc analysis of prospective clinical trial data., Participants: A total of 362 SCORE2 participants with macular edema secondary to central retinal (CRVO) or hemiretinal vein occlusion (HRVO)., Methods: Spectral domain OCT volume scans were assessed at the SCORE2 reading center at baseline, month 01 (M01), month 06 (M06), month 12 (M12), and month 24 (M24) for central subfield thickness (CST), subretinal fluid, intraretinal fluid, vitreoretinal interface abnormalities, disorganization of retinal inner layers (DRIL), and ellipsoid zone (EZ) within the central subfield (CSF)., Main Outcome Measures: Visual acuity at M06, M12, and M24., Results: Mean baseline age was 68.9 years. Mean VA at M01 was 63.2 letters, and CST was 299.7 μm. At M01, subretinal fluid was seen in 28.5% intraretinal fluid in 67.2%, DRIL was seen in 73.8%, mostly within the CSF, and the EZ was absent in 9.8 and patchy in 31.7%. In multivariate analysis including all M01 demographics and SD-OCT parameters and their association with VA at M06, M12, and M24, VA at M01 remained significant across all time points up to M24 (P < 0.001)., Conclusions: In this 2-year follow-up of eyes that were treated with both per protocol and off protocol for RVO, VA at M01 was an important predictor of long-term vision and change in vision. Establishing predictors of visual recovery helps identify causes for poor responders to treatment in patients with RVO., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated whether dietary carotenoids lutein and zeaxanthin (L/Z) in the serum and macula were associated with central retinal arteriole and venule calibers in a follow-up ancillary study among older women in the Women's Health Initiative., Methods: Among 390 women who participated in Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) (2016-2019), we investigated associations between serum L/Z at Women's Health Initiative baseline (1994-1998), and macular pigment optical density (MPOD) at CAREDS baseline (2001-2004), with central retinal vessel caliber in CAREDS2. MPOD was measured using heterochromatic flicker photometry (0.5° from the foveal center) in CAREDS baseline and CAREDS2. Vessel calibers were measured from fundus photographs (CAREDS2). We also explored associations in women with stable MPOD (±0.10 optical density units) over 15 years (n = 106), given the long-term increases in MPOD related to diet patterns and supplement use. Associations were investigated using linear modeling., Results: In the full sample (n = 390), higher serum L/Z (tertile 3 vs. 1) was positively associated with arteriole caliber (mean ± SE, 145.0 ± 1.4 µm vs. 140.8 ± 1.4 µm; P = 0.05) and venule caliber (214.6 ± 2.2 µm vs. 207.5 ± 2.2 µm; P = 0.03). MPOD was also associated with wider vessel calibers (tertile 3 vs. 1), but the trend was only statistically significant for venules (144.4 ± 1.4 µm vs. 141.1 ± 1.4 µm [P = 0.12] and 213.3 ± 2.1 µm vs. 206.0 ± 2.1 µm [P = 0.02], respectively.) Most associations were strengthened in women with stable MPOD over 15 years, including between MPOD and arteriole caliber (149.8 ± 2.6 µm vs.135.8 ± 3.0 µm; P = 0.001)., Conclusions: Higher L/Z status in serum and retina was associated with larger central retinal vessel calibers. Prospective studies and clinical trials are needed to elucidate whether L/Z supplementation prevents vision loss through increasing blood flow.

Purpose: To compare Early Treatment Diabetic Retinopathy Study (ETDRS) severity levels between standard 7-field imaging and ultra-widefield (UWF) imaging and to incorporate peripheral diabetic retinopathy (DR) lesions into the ETDRS grading system., Design: Cross-sectional Study., Participants: Paired images from 192 eyes (189 participants) with diabetic retinopathy were included., Methods: The ETDRS levels were determined by masked graders in 3 ways: standard 7-field imaging, UWF within the 7-field region (7-field UWF imaging), and the entire UWF image (global ETDRS imaging)., Main Outcome Measures: Percentage agreement between 7-field and UWF imaging for ETDRS levels., Results: Of the 166 paired images evaluated, exact agreement was found in 48.8% of eyes between standard 7-field and 7-field UWF ETDRS levels with a weighted κ value of 0.59 (95% confidence interval [CI], 0.5-0.68). Agreement rates varied with DR severity and were least in early DR (30.8%) and moderate nonproliferative DR (26.5%) groups. In 156 eyes with 7-field UWF ETDRS and global UWF ETDRS levels, exact agreement was found in 143 eyes (92%), with a weighted κ value of 0.9 (95% CI, 0.9-0.98). The peripheral lesions contributed to a higher DR severity in 8% and changed the eye to a proliferative DR level in 2%. Reproducibility of the 3 ETDRS evaluations was comparable with a weighted κ value of 0.57 with standard 7-field imaging, 0.65 with 7-field UWF imaging, and 0.60 with global ETDRS scale imaging., Conclusions: Moderate agreement was found in the ETDRS DR severity scale between standard 7-field and UWF imaging, indicating caution in interchanging data from the 2 methods. Both methods showed good reproducibility for clinical trial outcome of 2-step change. The global ETDRS scale provides a comprehensive score to incorporate peripheral changes into the ETDRS scale. The implications of the global scale on progression rate are yet to be determined., (© 2021 by the American Academy of Ophthalmology.)

Purpose: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data., Design: Consensus meeting., Participants: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists., Methods: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components., Main Outcome Measures: A consensus classification of neovascular AMD., Results: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated., Conclusions: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Artifacts can affect optical coherence tomographic angiography (OCTA) images and may be associated with misinterpretation of OCT scans in both clinical trials and clinical settings., Objectives: To identify the prevalence and type of artifacts in OCTA images associated with quantitative output and to analyze the role of proprietary quality indices in establishing image reliability., Design, Setting, and Participants: This cross-sectional study evaluated baseline OCTA images acquired in multicenter clinical trials and submitted to the Fundus Photograph Reading Center in Madison, Wisconsin, between January 1, 2016, and December 31, 2018. Images were captured using the 3 mm × 3 mm and/or 6 mm × 6 mm scan protocol with commercially available OCTA systems. Artifacts, including decentration, segmentation error, movement, blink, refraction shift, defocus, shadow, Z offset, tilt, and projection, were given a severity grade based on involvement of cross-sectional OCT and area of OCT grid affected., Main Outcomes and Measures: Prevalence and severity of OCTA artifacts and area under the receiver operating characteristic curve (AUC) of quality indices with image reliability., Results: A total of 406 OCTA images from 234 eyes were included in this study, of which 221 (54.4%) were 6 mm × 6 mm scans and 185 (45.6%) were 3 mm × 3 mm scans. At least 1 artifact was documented in 395 images (97.3%). Severe artifacts associated with the reliability of quantitative outputs were found in 217 images (53.5%). Shadow (26.9% [109 images]), defocus (20.9% [85 images]), and movement (16.0% [65 images]) were the 3 most prevalent artifacts. Prevalence of artifacts did not vary with the imaging system used or with the scan protocol; however, the type of artifacts varied. Commercially recommended quality index thresholds had an AUC of 0.80 to 0.83, sensitivity of 97% to 99%, and specificity of 37% to 41% for reliable images., Conclusions and Relevance: Findings from this study suggest that artifacts associated with quantitative outputs on commercially available OCTA devices are highly prevalent and that identifying common artifacts may require correlation with the angiogram and cross-sectional OCT scans. Knowledge of these artifacts and their implications for OCTA indices appears to be warranted for more accurate interpretation of OCTA images.

Purpose: To describe the sequence of events leading to development of geographic atrophy (GA) in age-related macular degeneration with fundus autofluorescence (FAF) imaging., Design: Post hoc analysis of FAF images from the Age-Related Eye Disease Study 2., Participants: Fundus autofluorescence images of 120 eyes (109 patients) with incident GA and at least 2 years of preceding FAF images., Methods: Images of incident GA were stacked and aligned over FAF images of preceding annual visits. The regions of retina where incident GA developed were assessed on prior years' FAF images. These regions, defined as precursor lesions, were classified into minimal change autofluorescence, predominant hypoautofluorescence (decreased autofluorescence), predominant hyperautofluorescence (increased autofluorescence), and mixed autofluorescence. The natural progression in precursor lesions leading to GA formation and their associations with incident GA size and GA enlargement rate were evaluated., Main Outcome Measures: Incident GA area and enlargement rate and precursor pattern frequency., Results: Incident GA had a mean area of 1.00 mm 2 (range, 0.15-8.22 mm 2 ) and an enlargement rate of 0.97 mm 2 /year (standard deviation, 1.66 mm 2 /year). Predominant hypoautofluorescence was the most common precursor lesion, increasing from 42% to 81% over 3 years before onset of GA. Almost 30% of eyes showed minimal change autofluorescence 3 years before GA. Among the other precursors, 70% progressed to predominant hypoautofluorescence before GA developed. The type of precursor lesions was not associated with incident GA area. Geographic atrophy evolving from minimal change autofluorescence precursor lesions was associated with faster GA enlargement rates compared with other precursor lesion classes., Conclusions: Using image registration, we identified changes in autofluorescence images before the onset of GA. Decreased autofluorescence was the most common change, although minimal changes also were seen in one third of the images. Incident GA that arises from predominantly normal autofluorescence is associated with faster enlargement rates compared with GA arising from abnormal autofluorescence. Faster GA enlargement rates also were associated with incident GA size, area of surround abnormal autofluorescence, and presence of reticular pseudodrusen., (Copyright © 2019 American Academy of Ophthalmology. All rights reserved.)

Purpose: To compare the angle structures during surgery using anterior segment (AS) OCT in children with and without glaucoma., Design: Prospective comparative study, with single masked grader evaluating AS OCT images., Participants: This study included a total of 44 eyes of 8 children with glaucoma and 14 children without glaucoma undergoing ophthalmic surgery with general anesthesia. The median age for the glaucoma group was 6 months (range, 0.5-108 months), and that for the nonglaucoma group was 42 months (range, 14-95 months)., Methods: An Envisu C2300 handheld OCT with a high-resolution AS lens was used to capture videos of temporal and nasal quadrant anterior chamber angles from each eye. Still images of the temporal and nasal angles were selected and then graded by a masked ophthalmologist examiner to determine whether Schlemm's canal (SC) was visible, if abnormal tissue was present in the angle, and whether intrascleral lumens were present. Clinical correlation with severity of glaucoma was performed after AS OCT images were graded., Main Outcome Measures: Presence or absence of SC on AS OCT in glaucomatous and nonglaucomatous eyes., Results: Schlemm's canal was present in 7 of 13 glaucomatous eyes compared with 27 of 27 nonglaucomatous eyes. In patients with unilateral glaucoma, absence of SC was noted only in the affected eye. Eight eyes with glaucoma showed abnormal tissue over the angle and SC. Intrascleral lumen and collector channels were found in both groups. Two patients with severe stenosis of SC during glaucoma angle surgery showed absent SC on AS OCT., Conclusions: Intraoperative AS OCT identified differences in the presence and characteristics of SC and the anterior chamber angle in pediatric patients with and without glaucoma. Further studies are needed to determine clinical correlation., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy., Design: Randomized sham-controlled clinical trial., Participants: Ninety-nine study eyes of 67 eligible participants were enrolled., Methods: Single-masked randomized clinical trial of 24 months' duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a sham procedure., Main Outcome Measures: The primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups., Results: Among the 67 participants who were randomized (mean age, 62±8.9 years; 41 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes. The difference in mean area of photoreceptor loss was 0.05±0.03 mm 2 (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly with the changes in the area of photoreceptor loss (r = 0.86; P < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than that of the treated group (decrease, 15.81±8.93 dB; P = 0.07). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the sham group and 2 of 48 persons (4%) in the treated group., Conclusions: In participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify the development and progression of macular retinal pigment epithelial atrophy in eyes with neovascular (CNV) age-related macular degeneration (AMD) and to correlate with visual acuity (VA)., Design: Cohort study., Participants: Age-Related Eye Disease Study 2 (AREDS2) participants with intermediate AMD enrolled in a randomized controlled clinical trial of oral supplements. Analyses were conducted in the subset of AREDS2 participants who were also enrolled in the fundus autofluorescence ancillary (FAF) ancillary study., Methods: Color photographs and FAF images were evaluated in eyes that developed CNV. Presence of geographic atrophy (GA) prior to the incidence of CNV and the development of macular atrophy following incident CNV were assessed. Areas of hypoautofluorescence representing atrophy were measured for area and macular involvement. Enlargement rate of atrophy and change in visual acuity over time were analyzed., Main Outcome Measures: incidence and enlargement rate of atrophy and VA changes in eyes with incident CNV., Results: Incident CNV developed in 334 (9.2%) of eyes evaluated in the AREDS2 FAF substudy. Of these, 40% had macular atrophy at incidence of CNV with half of these attributable to pre-existing GA. Atrophy developed in 14.7 % of eyes over 4 years of follow-up. Mean area of atrophy was largest in eyes with pre-existing GA and CNV (5.17 mm 2 , p<0.001), and atrophy involved the center of the macula in > 65% of eyes. Mean VA letter score at the annual visit in which CNV was documented was similar in the three groups with atrophy; eyes with CNV and pre-existing GA, incident atrophy at the first visit with CNV, and atrophy during follow up (60 letters). Enlargement rate of atrophy was also similar in eyes in the three groups (1.23 - 1.86 mm 2 , p = 0.47). Eyes with macular atrophy lost more visual acuity compared to eyes without atrophy, particularly after 2 years of follow-up (-10.9 vs. - 3.6 letters, p = 0.07)., Conclusion: Atrophy is commonly seen in neovascular AMD and often can be attributed to pre-existing GA. Macular atrophy and GA appear to be a continuum of the same disease process and are both associated with poor vision.

Objective/purpose: To evaluate efficacy and safety of monthly intravitreal injections of sirolimus, an immunosuppressive drug, for the treatment of age-related macular degeneration associated geographic atrophy (GA)., Design: Randomized, controlled, single-masked multi-center phase 2 clinical trial of intravitreal sirolimus vs. sham therapy in AREDS2 clinical centers., Subjects: Participants with GA., Methods: Participants eligible in one eye were randomly assigned to a monthly intravitreal injection of sirolimus (20 µL [440 µg]) or sham treatment while participants with two study eyes were assigned to a monthly intravitreal injection in a randomly-selected eye. Best-corrected visual acuities (BVCA), spectral domain optical coherence tomography (OCT), fundus color photography and fundus autofluorescence (FAF) images were obtained at baseline and every 6 months until visit month 24., Main Outcome Measures: Rate of progression of GA (mm 2 /year) measured on color fundus photograph from baseline to 24 months. Secondary outcome measures include change in BVCA, worsening of vision by ≥3 lines, and changes in area of GA measured on FAF and OCT., Results: 52 participants (mean age 79 years) were enrolled with 27 study eyes assigned to sirolimus from May 2012 to March 2014. The baseline median area of GA was 4.73 DA (12.01 mm 2 ). The mean (standard deviation) growth rates of GA detected on color fundus photographs were 2.27 (2.17) mm 2 and 1.91 (2.27) mm 2 at month 12, and 4.94 (2.96) mm 2 and 5.72 (3.97) mm 2 at month 24, for the sirolimus and sham groups, respectively. There was no statistically significant difference in the GA growth rates between the two treatment groups (P=0.33). Median visual acuity changes and incidence of 15-letter loss from baseline were not different between the 2 treatment groups (p=0.19). The intervention was stopped early because of sterile endophthalmitis that occurred in 3 participants in the sirolimus group. Participants were followed for safety until the study was closed in May 2015 due to lack of efficacy., Conclusion: Sirolimus did not result in different rates of GA growth in this phase 2 study. Immunosuppression may be important for some stages of the AMD process but may not necessarily be the main pathway for the development of GA., Competing Interests: Conflict of interest: Gary Gensler: None Traci Clemons: None Amitha Domalpally: None Ronald P Danis: None Barbara Blodi: None Jack Wells Michael Rauser John Hoskins Baker Hubbard: None Michael Elman Gary Fish Alexander Brucker: none Alan Margherio: none Emily Y. Chew: none

Purpose: To compare measurements of area of geographic atrophy (GA) and change in GA area from color photographs and fundus autofluorescence (FAF) images., Design: The Age-Related Eye Disease Study 2 (AREDS2) was a prospective multicenter randomized clinical trial evaluating progression of dry age-related macular degeneration (AMD) using color photographs at annual visits over a 5-year study period. The FAF images were acquired in a subset of participants who joined the FAF ancillary study at any of the annual visits over the study period., Participants: The AREDS2 FAF ancillary study included 8070 corresponding color and FAF visits of 2202 participants with variable follow-up., Methods: Corresponding color and FAF images were independently evaluated at a central reading center for GA area measurement, lesion growth, and involvement of the macula center., Main Outcome Measures: Presence, area, growth rate of GA, and involvement of center of macula from color and FAF images., Results: Hypoautofluorescence was visible in 2048 visits (25.4%). Agreement for the presence of GA between the 2 modalities had a kappa of 0.79, with 23% of visits with hypoautofluorescence not presenting with GA on color photographs. Percentage agreement for GA presence ranged from 43% at baseline to 81% at year 5 with improving agreement over time. The mean difference in GA area between the 2 modalities was 0.5 mm 2 , with larger areas on FAF. Growth rate of GA was 1.45 mm 2 from color photographs and 1.43 mm 2 from FAF images. The center of the macula was involved in 51% of color photographs and 56% with FAF images., Conclusions: Geographic atrophy may be detected earlier by the use of FAF images, but over the course of the study, the 2 modalities become comparable. Progression of GA area is comparable between color photographs and FAF images, but evaluating involvement of the center of the macula may differ, probably because of macular pigmentation blocking autofluorescence., (Copyright © 2016 American Academy of Ophthalmology. All rights reserved.)

Purpose: We tested variants in genes related to lutein and zeaxanthin status for association with age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS)., Methods: Of 2005 CAREDS participants, 1663 were graded for AMD from fundus photography and genotyped for 424 single nucleotide polymorphisms (SNPs) from 24 candidate genes for carotenoid status. Of 337 AMD cases 91% had early or intermediate AMD. The SNPs were tested individually for association with AMD using logistic regression. A carotenoid-related genetic risk model was built using backward selection and compared to existing AMD risk factors using the area under the receiver operating characteristic curve (AUC)., Results: A total of 24 variants from five genes (BCMO1, BCO2, NPCL1L1, ABCG8, and FADS2) not previously related to AMD and four genes related to AMD in previous studies (SCARB1, ABCA1, APOE, and ALDH3A2) were associated independently with AMD, after adjusting for age and ancestry. Variants in all genes (not always the identical SNPs) were associated with lutein and zeaxanthin in serum and/or macula, in this or other samples, except for BCO2 and FADS2. A genetic risk score including nine variants significantly (P = 0.002) discriminated between AMD cases and controls beyond age, smoking, CFH Y402H, and ARMS2 A69S. The odds ratio (95% confidence interval) for AMD among women in the highest versus lowest quintile for the risk score was 3.1 (2.0-4.9)., Conclusions: Variants in genes related to lutein and zeaxanthin status were associated with AMD in CAREDS, adding to the body of evidence supporting a protective role of lutein and zeaxanthin in risk of AMD.

Purpose: To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT)., Design: Cohort within a randomized clinical trial., Participants: We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment., Methods: Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs)., Main Outcome Measures: Development of GA., Results: By 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43-4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16-2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40-3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34-3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29-0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95% CI, 0.35-0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95% CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31-0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17-2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3., Conclusions: Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objectives: To review the frequency and nature of idiopathic macular telangiectasia and to classify the disorders based on new clinical and imaging observations., Methods: A combined retrospective and prospective analysis of newly diagnosed patients seen over a period of 3 years. Patients were identified based on the Gass-Blodi classification and were studied with biomicroscopy, fluorescein angiography, and optical coherence tomography., Results: Ten patients associated with aneurysmal telangiectasia (Gass-Blodi group 1) and 26 patients with perifoveal telangiectasia (Gass-Blodi group 2) were recruited. None with occlusive telangiectasia (Gass-Blodi group 3) were identified. New observations based on clinical, fluorescein angiographic, and optical coherence tomographic findings were made., Conclusions: Our series was similar to that in the Gass-Blodi study in terms of frequency. New observations in groups 1 and 2 have expanded our knowledge of the clinical spectrum of these disorders. A simplified classification termed idiopathic macular telangiectasia with 2 distinct types (type I, or aneurysmal telangiectasia, and type II, or perifoveal telangiectasia) was proposed to produce a better understanding of the entities and to enhance teaching and research. The third type, occlusive telangiectasia, has been omitted from our classification based on its rarity and presence of capillary nonperfusion rather than macular telangiectasia as the primary abnormality.

Purpose: To investigate the cause of visual acuity (VA) loss in patients with neovascular age-related macular degeneration (AMD) receiving monthly ranibizumab injections in the pivotal ranibizumab phase III trials., Design: Retrospective analysis., Participants: The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the treatment of Neovascular AMD (MARINA) and Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trials., Methods: Demographics and lesion characteristics at baseline and month 24 were compared in patients with ≥15 letters VA loss and patients with ≥15 letters VA gain from baseline to month 24. Additional evaluations of fundus photographs from these patients were performed to assess features of non-exudative AMD, such as geographic atrophy (GA) and retinal pigment epithelium (RPE) abnormalities., Main Outcome Measures: Differences in lesion characteristics between patients who lost versus gained ≥15 letters of VA from baseline to month 24., Results: At month 24, 9% of ranibizumab-treated patients from MARINA and 10% of ranibizumab-treated patients from ANCHOR had lost ≥15 letters VA; 30% of ranibizumab-treated patients from MARINA and 38% of ranibizumab-treated patients from ANCHOR had gained ≥15 letters VA. Baseline characteristics associated with VA loss at month 24 included older age, better VA, and larger lesions. At month 24, an increased area of RPE abnormality was associated with VA loss in both the MARINA (P = 0.0008) and ANCHOR (P = 0.0046) trials. Increased total lesion area at month 24 was associated with VA loss in both trials. In MARINA, the increase in total lesion area was attributable to an increase in the angiographic designation of atrophic scar among VA losers (P = 0.0043), but in ANCHOR it was attributable to an increased area of choroidal neovascularization (CNV) (P = 0.039) but not an increased area of leakage (P = 0.17). Increased areas of GA, fibrosis, and hemorrhage were not associated with VA loss., Conclusions: Vision loss after 2 years of monthly ranibizumab therapy was associated with lesion characteristics commonly associated with suppressed CNV, such as pigmentary abnormalities, atrophic scar, and the absence of leakage. Future VA improvements in patients receiving ranibizumab therapy may require preservation of photoreceptor and RPE function rather than strategies that target CNV., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the association between healthy diet scores and prevalence of nuclear cataract in women., Methods: The association between healthy diet scores, which reflect adherence to the US dietary guidelines, and prevalence of nuclear cataract determined 4 to 7 years later was assessed in a sample of Women's Health Initiative Observational Study participants (aged 50-79 years) residing in Iowa, Wisconsin, and Oregon. Scores on the 1995 Healthy Eating Index, which reflect adherence to 1990 guidelines, were assigned from responses to food frequency questionnaires at the Women's Health Initiative baseline (1994-1998). Presence of nuclear cataract was determined from slitlamp photographs and self-reports of cataract extractions were assessed from May 1, 2001, to January 31, 2004, in 1808 women participating in the Carotenoids in Age-Related Eye Disease Study., Results: Having a high 1995 Healthy Eating Index score was the strongest modifiable predictor of low prevalence of nuclear cataract among numerous risk factors investigated in this sample. The multivariate-adjusted odds ratio for high vs low quintile for diet score was 0.63 (95% confidence interval, 0.43-0.91). Higher prevalence of nuclear cataract was also associated with other modifiable factors (smoking and marked obesity) and nonmodifiable factors (having brown eyes, myopia, and high pulse pressure). Vitamin supplement use was not related to cataract., Conclusion: These data add to the body of evidence suggesting that eating foods rich in a variety of vitamins and minerals may contribute to postponing the occurrence of the most common type of cataract in the United States.

Objective: To evaluate the relationship between dietary lutein plus zeaxanthin and intermediate age-related macular degeneration (AMD)., Design: Women aged 50 to 79 years in Iowa, Wisconsin, and Oregon with intake of lutein plus zeaxanthin above the 78th (high) and below the 28th (low) percentiles at baseline in the Women's Health Initiative Observational Study were recruited 4 to 7 years later into the Carotenoids in Age-Related Eye Disease Study (CAREDS), when the presence of AMD was determined by fundus photographs. Logistic regression analyses examined the prevalence of AMD in 1787 CAREDS participants, after accounting for potential covariates., Results: The prevalence of intermediate AMD was not statistically different between the high and low lutein plus zeaxanthin intake recruitment groups after adjusting for age (odds ratio, 0.96; 95% confidence interval, 0.75-1.23). Limiting analyses to women younger than 75 years with stable intake of lutein plus zeaxanthin, without a history of chronic diseases that are often associated with diet changes, substantially lowered odds ratios (0.57; 95% confidence interval, 0.34-0.95). Exploratory analyses of advanced AMD in 34 participants resulted in protective, but statistically nonsignificant, associations in the overall sample and in women younger than 75 years., Conclusion: Diets rich in lutein plus zeaxanthin may protect against intermediate AMD in healthy women younger than 75 years.

Objectives: To review the frequency and nature of idiopathic macular telangiectasia and to classify the disorders based on new clinical and imaging observations., Methods: A combined retrospective and prospective analysis of newly diagnosed patients seen over a period of 3 years. Patients were identified based on the Gass-Blodi classification and were studied with biomicroscopy, fluorescein angiography, and optical coherence tomography., Results: Ten patients associated with aneurysmal telangiectasia (Gass-Blodi group 1) and 26 patients with perifoveal telangiectasia (Gass-Blodi group 2) were recruited. None with occlusive telangiectasia (Gass-Blodi group 3) were identified. New observations based on clinical, fluorescein angiographic, and optical coherence tomographic findings were made., Conclusions: Our series was similar to that in the Gass-Blodi study in terms of frequency. New observations in groups 1 and 2 have expanded our knowledge of the clinical spectrum of these disorders. A simplified classification termed idiopathic macular telangiectasia with 2 distinct types (type I, or aneurysmal telangiectasia, and type II, or perifoveal telangiectasia) was proposed to produce a better understanding of the entities and to enhance teaching and research. The third type, occlusive telangiectasia, has been omitted from our classification based on its rarity and presence of capillary nonperfusion rather than macular telangiectasia as the primary abnormality.

Objective: To investigate the safety and efficacy of low-dose intravitreal tissue plasminogen activator (tPA) and an expansile gas bubble in displacing submacular hemorrhage in patients with age-related macular degeneration (ARMD)., Patients and Methods: We reviewed retrospectively the medical records of 14 consecutive patients with ARMD from 1 academic center who received low-dose intravitreal tPA (18-50 microg) and expansile gas (0.3-0.4 mL of perfluoropropane) for thrombolysis and displacement of submacular hemorrhage. After the procedure, patients maintained face-down positioning for 1 to 3 days., Main Outcome Measures: Displacement of blood from the fovea, early and final visual acuity, and toxicity of tPA., Results: Submacular blood was completely displaced from the fovea in 10 (71%) of the 14 patients and partially displaced in 3 (21%). In 1 patient, no displacement occurred. Early (<2 months) postoperative visual acuity improved by 2 or more lines in 8 patients (57%). With a mean follow-up of 7.7 months, 2 (15%) of 13 patients maintained 2 or more lines of improvement and 69% (9 patients) maintained preoperative visual acuity. No clinical evidence of retinal toxicity was seen at this low-dose of tPA., Conclusions: Doses of intravitreal tPA ranging from 18 to 50 microg and an expansile gas bubble are safe and effective in displacing submacular hemorrhage in patients with ARMD. Final visual acuity was limited by the underlying presence of end-stage ARMD.

Purpose: To report a case of Purtscher-like retinopathy after administration of retrobulbar anesthesia for an otherwise uncomplicated cataract extraction., Method: Case report., Results: After cataract surgery with retrobulbar anesthesia, the patient followed a typical course of Purtscher-like retinopathy with an initial severe loss of vision followed by a gradual and nearly complete improvement in visual function., Conclusions: Purtscher-like retinopathy is uncommon after administration of retrobulbar anesthesia but had the same clinical course as other causes of this disorder.

Objective: The purpose of the study was to evaluate the occurrence of cataract in young patients after pars plana vitrectomy., Design: The authors reviewed the medical records for previtrectomy and postvitrectomy lens changes in patients younger than 30 years of age at the Kellogg Eye Center, University of Michigan., Participants: Forty-nine patients (50 eyes) younger than 30 years of age (mean age, 23.5 years; range, 5 months-30 years) underwent phakic vitrectomy over a 12-year period., Main Outcome Measures: Cataracts were categorized as posterior subcapsular, nuclear sclerotic, or cortical. Cataracts also were graded as mild (1+), moderate (2+), or severe (3+)., Results: In this series of young patients, vitrectomy was performed for a wide range of ocular conditions, including trauma and complicated retinal detachment. Postvitrectomy cataract developed in 29 patients (60%). Eighteen patients (36%) had visually significant cataract on long-term follow-up (mean follow-up, 29.7 months; range, 6 months-13 years). The most common cataract was posterior subcapsular (57%), followed by nuclear sclerosis (23%), a combination of both (17%), and cortical cataract (3%). Patients with gas-filled eyes had a significantly higher rate of cataract formation than patients with fluid-filled eyes (P < 0.05)., Conclusions: Postvitrectomy cataracts were more common in the authors' series compared with those of previous reports on young patients. Cataracts were most often posterior subcapsular and were significantly associated with the use of intraocular gas. The occurrence of postvitrectomy cataract appears to be higher in patients undergoing vitrectomy for complex ocular conditions, regardless of age.

Background: Idiopathic juxtafoveolar retinal telangiectasis may cause visual loss. The treatment of this disease is controversial., Methods: The authors reviewed the records of 140 patients with idiopathic juxtafoveolar telangiectasis. A classification scheme based on biomicroscopic and fluorescein angiographic findings is presented. In addition, the effect of photocoagulation on the natural history of the disorder is evaluated., Findings: Patients are categorized into three groups. Group 1 comprises 39 male patients with nonfamilial, easily visible telangiectasis and intraretinal exudation. The telangiectasis is unilateral in 94% of patients. The telangiectasia in this group is probably of developmental origin (Coats syndrome). Group 2 comprises 94 patients with occult juxtafoveolar telangiectasis, minimal exudation, superficial retinal crystalline deposits, and right-angle venules. Late in the course of the disease, foveolar atrophy, intraretinal pigment plaques, and subretinal neovascularization develop. The telangiectasis is acquired during middle age and is bilateral in 98% of patients. Group 3 comprises seven patients with bilateral easily visible telangiectasis, minimal exudation, and capillary occlusion. All of these patients had systemic disease, which was probably related to their eye disease., Conclusion: Slow visual loss beginning in adulthood characterizes most of these patients. The telangiectasis appears to be caused primarily by retinal capillary leakage in group 1, capillary diffusion abnormalities in group 2, and capillary occlusion in group 3. Photocoagulation is probably beneficial for patients in group 1 and not for patients in group 2, at least before their development of subretinal neovascularization.

We studied the ability of standardized echography to correctly diagnose a retinal tear in patients with opaque ocular media due to vitreous hemorrhage. Records were studied of 42 patients with spontaneous vitreous hemorrhage and no ophthalmoscopic view of fundus details. Of these 42 patients, 11 had an echographic diagnosis of probable retinal tear and no retinal detachment. In 10 (91%) of 11 cases, the presence and location of the tears that were diagnosed echographically were confirmed on clinical follow-up. In one patient, an area of peripheral neovascularization was mistaken for a tear. Echography failed to identify one retinal tear that was later detected on clinical examination. Therefore, we have found standardized echography to be a reliable tool in identifying retinal breaks.

The authors reviewed the medical records of 36 patients in whom the nucleus or nuclear fragments were retained in the eye after cataract surgery. In 4 patients, there was no further surgery, and visual acuity deteriorated to counting fingers or worse (mean follow-up time, 14 months). Thirty-two patients underwent vitrectomy to remove the retained, unencapsulated nuclear material. Sixty percent (6 of 10) of patients in whom vitrectomy was performed after 3 weeks had chronic glaucoma on long-term follow-up, whereas this complication developed in only 18% (4 of 22) of patients in whom vitrectomy was performed in less than 3 weeks. Sixty-three percent (21 of 32) of vitrectomy patients had final visual acuity of 20/200 or better after removal of the retained nuclear fragments. The causes of the poorest visual outcome (less than 20/200) included 1 or more of the following: corneal decompensation, chronic inflammation, chronic glaucoma with optic atrophy, and retinal detachment.

Severe bilateral visual loss attributable to multiple retinal arteriolar occlusions occurred in four young women within 24 hours after childbirth. In two patients, labor was complicated by preeclampsia requiring cesarean section. One patient was suffering from pancreatitis. None had connective tissue disease or antecedent trauma. Ophthalmoscopy and fluorescein angiography revealed evidence of multiple superficial peripapillary and macular patches of ischemic retinal whitening simulating Purtscher's retinopathy. By 8 weeks, the white patches were resolving in all eyes and visual acuity had significantly improved in three of the four patients. The pathogenesis of this disorder is unknown but may involve arteriolar obstruction by complement-induced leukoemboli formed during parturition.

Trachoma is a chlamydial disease that affects millions of people each year, particularly in developing countries. In the chronic phase, inflammation causes scarring of the conjunctiva followed by dry eye which can result in blindness. Trachoma may cause dryness of the eye by decreasing mucus production and aqueous secretions. Conjunctival impression cytology was carried out to determine the goblet cell population among patients with trachoma. We performed impression cytology on 32 patients with inactive trachoma and 31 age and sex matched controls. Impression cytology showed that the nasal conjunctiva contains the greatest number of goblet cells. Trachoma patients with severe scarring had significantly less goblet cell counts than those with mild scarring (p less than 0.05). In the group of ten patients with severe trachoma and keratinization, there was marked reduction or absence of goblet cells. Trachoma appears to initiate a viscious cycle of conjunctival scarring, mucus deficiency, and chronic conjunctival inflammation.