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To highlight the financial incentive to the physician of choosing an intravitreal anti-vascular endothelial growth factor (VEGF)-based strategy for treating non-proliferative and proliferative diabetic retinopathy, and its possible risks to the patient and costs to the health care system.Perspective with retrospective cost and profit analysis.Review and synthesis of selected literature on the treatment of diabetic retinopathy, with interpretation of activity-based and time-based costing of an intravitreal aflibercept strategy for diabetic retinopathy. Data from the DRCR Retina Network Protocols W and AB and PANORAMA trial were used to illustrate the potential financial incentive underlying such a treatment strategy.Physician treatment algorithms for diabetic vitreous hemorrhage and non-proliferative diabetic retinopathy may be influenced by the substantial financial incentives that intravitreal aflibercept strategies present, despite functional equivalence with alternative and less profitable strategies. For example, pursuing an intravitreal aflibercept-based strategy for diabetic vitreous hemorrhage presents a 76% increased profit over pars plana vitrectomy with laser, with equivalent functional outcomes. For non-proliferative diabetic retinopathy, preventative aflibercept injections represent a potential 414% increase in profit over observation and an increased cost of $12,164 to $17,542 over 2 years per patient, with no improvement in visual function. These findings demonstrate that there may be misaligned financial incentives in the management of diabetic retinopathy.While anti-VEGF therapy is a useful tool in the management of proliferative diabetic retinopathy and diabetic macular edema, it is believed that physicians should avoid overreliance on anti-VEGF injections in the treatment of diabetic retinopathy. Retinal specialists should be cognizant of the limitations, costs, and risks of anti-VEGF monotherapy and prophylactic therapy, and of the imperative to avoid bias towards financially remunerative practice patterns when equally effective alternatives exist.

PURPOSE: Over the past two decades, advancements in imaging modalities have significantly evolved the diagnosis and management of retinal diseases. Through these novel platforms, we have developed a deeper understanding of the anatomy of the choroidal vasculature and the choriocapillaris. The recently developed tools such as optical coherence tomography (OCT) and OCT angiography (OCTA) have helped elucidate the pathological mechanisms of several posterior segment diseases. In this review, we have explained the anatomy of the choriocapillaris and its close relationship to the outer retina and retinal pigment epithelium. METHODS: A comprehensive search of medical literature was performed through the Medline/PubMed database using search terms: choriocapillaris, choroid, quantification, biomarkers, diabetic retinopathy, age-related macular degeneration, choroidal blood flow, mean blur rate, flow deficit, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, indocyanine green angiography, OCTA, Doppler imaging, uveitis, choroiditis, white dot syndrome, tubercular serpiginous-like choroiditis, choroidal granuloma, pachychoroid, toxoplasmosis, central serous chorioretinopathy, multifocal choroiditis, choroidal neovascularization, choroidal thickness, choroidal vascularity index, choroidal vascular density, and choroidal blood supply. The search terms were used either independently or combined with choriocapillaris/choroid. RESULTS: The imaging techniques which are used to qualitatively and quantitatively analyze choriocapillaris are described. The pathological alterations in the choriocapillaris in an array of conditions such as diabetes mellitus, age-related macular degeneration, pachychoroid spectrum of diseases, and inflammatory disorders have been comprehensively reviewed. The future directions in the study of choriocapillaris have also been discussed. CONCLUSION: The development of imaging tools such as OCT and OCTA has dramatically improved the assessment of choriocapillaris in health and disease. The choriocapillaris can be delineated from the stromal choroid using the OCT and quantified by manual or automated methods. However, these techniques have inherent limitations due to the lack of an anatomical distinction between the choriocapillaris and the stromal choroid, which can be overcome with the use of predefined segmentation slabs on OCT and OCTA. These segmentation slabs help in standardizing the choriocapillaris imaging and obtain repeatable measurements in various conditions such as diabetic retinopathy, age-related macular degeneration, pachychoroid spectrum, and ocular inflammations. Additionally, Doppler imaging has also been effectively used to evaluate the choroidal blood flow and quantifying the choriocapillaris and establishing its role in the pathogenesis of various retinochoroidal diseases. As tremendous technological advancements such as wide-field and ultra-wide field imaging take place, there will be a significant improvement in the ease and accuracy of quantifying the choriocapillaris.

ImportanceRetinopathy of prematurity (ROP) telemedicine screening programs have been found to be effective, but they rely on widefield digital fundus imaging (WDFI) cameras, which are expensive, making them less accessible in low- to middle-income countries. Cheaper, smartphone-based fundus imaging (SBFI) systems have been described, but these have a narrower field of view (FOV) and have not been tested in a real-world, operational telemedicine setting.ObjectiveTo assess the efficacy of SBFI systems compared with WDFI when used by technicians for ROP screening with both artificial intelligence (AI) and human graders.Design, Setting, and ParticipantsThis prospective cross-sectional comparison study took place as a single-center ROP teleophthalmology program in India from January 2021 to April 2022. Premature infants who met normal ROP screening criteria and enrolled in the teleophthalmology screening program were included. Those who had already been treated for ROP were excluded.ExposuresAll participants had WDFI images and from 1 of 2 SBFI devices, the Make-In-India (MII) Retcam or Keeler Monocular Indirect Ophthalmoscope (MIO) devices. Two masked readers evaluated zone, stage, plus, and vascular severity scores (VSS, from 1-9) in all images. Smartphone images were then stratified by patient into training (70%), validation (10%), and test (20%) data sets and used to train a ResNet18 deep learning architecture for binary classification of normal vs preplus or plus disease, which was then used for patient-level predictions of referral warranted (RW)– and treatment requiring (TR)–ROP.Main Outcome and MeasuresSensitivity and specificity of detection of RW-ROP, and TR-ROP by both human graders and an AI system and area under the receiver operating characteristic curve (AUC) of grader-assigned VSS. Sensitivity and specificity were compared between the 2 SBFI systems using Pearson χ2testing.ResultsA total of 156 infants (312 eyes; mean [SD] gestational age, 33.0 [3.0] weeks; 75 [48%] female) were included with paired examinations. Sensitivity and specificity were not found to be statistically different between the 2 SBFI systems. Human graders were effective with SBFI at detecting TR-ROP with a sensitivity of 100% and specificity of 83.49%. The AUCs with grader-assigned VSS only were 0.95 (95% CI, 0.91-0.99) and 0.96 (95% CI, 0.93-0.99) for RW-ROP and TR-ROP, respectively. For the AI system, the sensitivity of detecting TR-ROP sensitivity was 100% with specificity of 58.6%, and RW-ROP sensitivity was 80.0% with specificity of 59.3%.Conclusions and RelevanceIn this cross-sectional study, 2 different SBFI systems used by technicians in an ROP screening program were highly sensitive for TR-ROP. SBFI systems with AI may be a cost-effective method to improve the global capacity for ROP screening.

Social media support groups can provide accessibility to advice and emotional regarding medical topics, such as retinal detachment repair, but this is almost universally provided by laypersons. We sought to determine how topics related to retinal detachment repair are associated with various emotional responses and the spread of misinformation, as identified through an online social media support group. Retrospective observational study of the largest Facebook support group for retinal detachment from 03/19/2021 to 07/19/2021. Members of the support group that posted during the study period. Comments were coded by content (Pre-procedural, Peri-procedural Post procedural, Repeat procedures) and participant response (Emotional responses, Asking for medical advice, and Misinformation). Associations between content and responses were examined using Pearson’s chi-squared test, two-sample t-test, and linear regression. Posts that included written comments from the study period were analyzed. Negative emotional responses appeared in 30% of posts and positive emotional responses were in 16% of posts. Misinformation was more likely to appear in pre-procedure posts (5.3% versus 1.4%, p = .03). Negative emotional responses trended towards being more common in topics related to repeat procedures (40% vs 28%), although this did not reach statistical significance (p = .06). Surgeons should be aware that patients frequently express negative experiences on this forum, asked for medical advice, even in the post-operative period, and that these posts generated high engagement. Misinformation may be propagated in support groups, though less commonly with regard to post-procedural questions.

Perfluorocarbon liquid (PFCL) is an important adjunct in pars plana vitrectomy (PPV) for complex retinal detachment (RD). Complete removal of PFCL is critical to prevent retinal inflammation and cellular toxicity, but removal is not risk-free. We report a case of a new postoperative onset paracentral visual field defect after PPV with PFCL use for treatment of a macula-on RD. We present pre- and postoperative imaging that suggests a likely perioperative iatrogenic cause. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:644–646.]

Purpose To investigate the underlying reason for the previously observed impact of baseline lesion size, number, and circularity on geographic atrophy (GA) growth rate. Design Retrospective analysis of a multicenter, prospective, randomized controlled trial. Participants Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration. Methods We manually delineated atrophic lesions on color fundus photographs of 318 eyes with GA followed up over at least 2 visits (mean follow-up duration, 5.1 ± 3.0 years). We calculated GA area growth rate for each eye based on the first and last visit. GA perimeter-adjusted growth rate was defined as the ratio between GA area growth rate and mean GA perimeter between the first and last visit for each eye. Main Outcome Measures GA area growth rate, growth rate of the square root of GA area, and GA perimeter-adjusted growth rate. Results GA area growth rate was correlated strongly with mean GA perimeter (r2 = 0.66). GA area growth rate was associated with baseline GA area (r2 = 0.39; P Conclusions The growth rate of GA area is associated strongly with lesion perimeter. This relationship explains the previously observed influences of baseline GA size, lesion number, and circularity on GA growth rate. GA perimeter-adjusted growth rate is uncorrelated with the 3 morphologic factors and may serve as a surrogate outcome measure to monitor GA progression in future studies.

To examine the association between geographic atrophy (GA) disease characteristics and mortality risk. We manually delineated color fundus photographs of 209 Age-Related Eye Disease Study (AREDS) participants with GA secondary to age-related macular degeneration to identify total area of atrophy, GA effective radius growth rate, disease laterality, and the presence of foveal center involvement. Associations between GA characteristics and mortality were assessed with Cox proportional hazards models adjusted for health status indicators. During a median follow-up of 6.8 years, 48 (23.0%) participants with GA died. In adjusted models, accounting for age, sex, and health status, participants with total GA area in the highest quartile had a significantly increased risk of all-cause mortality compared to those with total GA area in the lowest quartile (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.32–8.86; P = 0.011). GA effective radius growth rate, bilateral disease, and the presence of foveal center involvement were not significantly associated with mortality. In a multivariable model, including health status indicators and all GA characteristics, total area of atrophy in the highest quartile remained significantly associated with mortality (HR, 4.65; 95% CI, 1.29–16.70; P = 0.019). More extensive GA, as indicated by a greater total area of atrophy, was associated with an increased risk of all-cause mortality in our cohort. The extent of GA may reflect the extent of underlying disease processes that contribute to greater mortality risk, further suggesting that GA may be part of a systemic rather than purely ocular disease process.

Purpose: To report a 4-year-old boy with a large, macula-involving combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) lesion with an associated choroidal neovascular membrane involving the fovea, characterized with multimodal imaging. Methods: Case report. Results: Given the low likelihood of visual improvement with intervention, observation was recommended and the CHRRPE remained stable on follow-up 4 months after presentation. Conclusion: CHRRPE is a rare congenital retinal lesion that is variably pigmented. Awareness of rare complications, such as CNVM, as seen in this pediatric case is paramount.

BackgroundThe macular central 1 mm diameter zone is crucial to patients’ visual acuity, but the long-term natural history of central sparing in eyes with geographic atrophy (GA) is unknown.MethodsWe manually segmented GA in 210 eyes with GA involving central 1 mm diameter zone (mean follow-up=3.8 years) in the Age-Related Eye Disease Study. We measured the residual area in central 1 mm diameter zone and calculated central residual effective radius (CRER) as square root of (residual area/π). A linear mixed-effects model was used to model residual size over time. We added a horizontal translation factor to each data set to account for different durations of GA involving the central zone.ResultsThe decline rate of central residual area was associated with baseline residual area (p=0.008), but a transformation from central residual area to CRER eliminated this relationship (p=0.51). After the introduction of horizontal translation factors to each data set, CRER declined linearly over approximately 13 years (r2=0.80). The growth rate of total GA effective radius was 0.14 mm/year (95% CI 0.12 to 0.15), 3.7-fold higher than the decline rate of CRER (0.038 mm/year, 95% CI 0.034 to 0.042). The decline rate of CRER was 53.3% higher in eyes with than without advanced age-related macular degeneration in the fellow eyes at any visit (p=0.007).ConclusionsCRER in eyes with GA declined linearly over approximately 13 years and may serve as an anatomic endpoint in future clinical trials aiming to preserve the central zone.

Concentric macular rings (CMRs) of Henle's fiber layer (HFL) are an uncommon imaging phenomenon previously associated with foveal hypoplasia and epiretinal membrane. Here, we present a case of a 15-year-old boy with bilateral CMRs, normal visual function, and no ocular pathology. These bilateral findings in the absence of vitreomacular traction, foveal hypoplasia, or any other ocular abnormality suggest that macular rings may occur as a normal but rare variant of HFL architecture. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:353–355.]

PURPOSE: To use empirical data to develop a model of cell loss in choroideremia that predicts the known exponential rate of RPE loss and central, scalloped preservation pattern seen in this disease. METHODS: A computational model of RPE loss was created in Python 3.7, which constructed an array of RPE cells clusters, binarized as either live or atrophic. Two rules were applied to this model: the background effect gave each cell a chance of dying defined by a background function, and the neighbor effect increased the chance of RPE cell death if a neighbor were dead. The known anatomic distribution of rods, RPE, choriocapillaris density, amacrine, ganglion, and cone cells were derived from the literature and applied to this model. Atrophy growth rates were measured over arbitrary time units and fit to the known exponential decay model. The main outcome measures: included topography of atrophy over time and fit of simulated residual RPE area to exponential decay. RESULTS: A background effect alone can simulate exponential decay, but does not simulate the central island preservation seen in choroideremia. An additive neighbor effect alone does not simulate exponential decay. When the neighbor effect multiplies the background effect using the rod density function, our model follows an exponential decay, similar to previous observations. Also, our model predicts a residual island of RPE that resembles the topographic distribution of residual RPE seen in choroideremia. CONCLUSIONS: The pattern of RPE loss in choroideremia can be predicted by applying simple rules. The RPE preservation pattern typically seen in choroideremia may be related to the underlying pattern of rod density. Further studies are needed to validate these findings.

This case series describes the outcomes of cataract extraction with intraocular lens placement in 2 patients.

PURPOSE: To assess the influence of lesion morphology and location on geographic atrophy (GA) growth rate. METHODS: We manually delineated GA on color fundus photographs of 237 eyes in the Age-Related Eye Disease Study. We calculated local border expansion rate (BER) as the linear distance that a point on the GA border traveled over 1 year based on a Euclidean distance map. Eye-specific BER was defined as the mean local BER of all points on the GA border in an eye. The percentage area affected by GA was defined as the GA area divided by the total retinal area in the region. RESULTS: GA enlarged 1.51 ± 1.96 mm2 in area and 0.13 ± 0.11 mm in distance over 1 year. The GA area growth rate (mm2/y) was associated with the baseline GA area (P < 0.001), perimeter (P < 0.001), lesion number (P < 0.001), and circularity index (P < 0.001); in contrast, eye-specific BER (mm/y) was not significantly associated with any of these factors. As the retinal eccentricity increased from 0 to 3.5 mm, the local BER increased from 0.10 to 0.24 mm/y (P < 0.001); in contrast, the percentage of area affected by GA decreased from 49.3% to 2.3%. CONCLUSIONS: Using distance-based measurements allows GA progression evaluation without significant confounding effects from baseline GA morphology. Local GA progression rates increased as a function of retinal eccentricity within the macula which is opposite of the trend for GA distribution, suggesting that GA initiation and enlargement may be mediated by different biological processes.

Background and ObjectivesAlzheimer’s disease (AD) and frontotemporal dementia (FTD) are difficult to reliably differentiate clinically. While their distinct pathologies may be captured by existing diagnostic modalities, these are expensive, time-consuming, and often inaccessible. Dementias are associated with visual dysfunctions, perhaps due to changes in the retina, a developmental outgrowth of the central nervous system. We explore the role of multimodal ocular imaging in the diagnosis of two dementias, AD and FTD.MethodsWe recruited 5 AD participants, 2 FTD participants, and 9 age-matched controls. Each participant underwent comprehensive ophthalmologic examination and imaging (optical coherence tomography (OCT), OCT-angiography (OCTA), wide-field fundus photography, near-infrared imaging, and fundus autofluorescence). Ocular findings were correlated with cerebral amyloid burden, as measured by [11C]PiB PET.ResultsOCT analysis identified a trend toward differences in retinal nerve fiber layer (RNFL) thicknesses among dementia subtypes (p = 0.064). AD eyes had increased RNFL thicknesses compared to FTD (p = 0.046) and control eyes (p = 0.046), and AD RNFL thickness was positively associated with amyloid burden (p = 0.037). OCTA fractal analysis revealed decreased vascular complexity within the retinal superficial vascular complex in AD compared to FTD eyes (p = 0.035). Lastly, fundus autofluorescence demonstrated increased signal intensity in AD eyes compared to control eyes (p = 0.046). However, these findings were not statistically significant following correction for multiple comparisons.DiscussionDespite identifying trends toward differences in retinal layer thicknesses unique to individuals with AD and FTD, our study suggests that changes in retinal thicknesses alone may not serve as reliable biomarkers for distinguishing between dementia subtypes. However, multiple ocular imaging modalities may be considered in conjunction with clinical presentation to aid in diagnosing and monitoring AD and FTD.Trial registrationThe study was prospectively registered on clinicaltrials.gov (NCT03699644) on October 9, 2018.

YouTube.com is a popular, free video platform that parents are increasingly using for medical information. This analysis of pediatric strabismus surgery videos found that many videos lack useful information, and some provide disinformation that may be harmful to pediatric eye care.

This economic evaluation study compares the costs of intravitreal injections of aflibercept, 2 mg, vs pars plana vitrectomy plus panretinal photocoagulation for nonclearing vitreous hemorrhage secondary to proliferative diabetic retinopathy.

BackgroundThe associations of geographic atrophy (GA) progression with systemic health status and medication use are unclear.MethodsWe manually delineated GA in 318 eyes in the Age-Related Eye Disease Study. We calculated GA perimeter-adjusted growth rate as the ratio between GA area growth rate and mean GA perimeter between the first and last visit for each eye (mean follow-up=5.3 years). Patients’ history of systemic health and medications was collected through questionnaires administered at study enrolment. We evaluated the associations between GA perimeter-adjusted growth rate and 27 systemic health factors using univariable and multivariable linear mixed-effects regression models.ResultsIn the univariable model, GA perimeter-adjusted growth rate was associated with GA in the fellow eye at any visit (p=0.002), hypertension history (p=0.03), cholesterol-lowering medication use (pConclusionsGA growth rate may be associated with the fellow eye status, cholesterol-lowering medication use, and diuretic use. These possible associations do not infer causal relationships, and future prospective studies are required to investigate the relationships further.

Amblyopia is the most common cause of preventable visual impairment in children and occurs as a result of unilateral or bilateral impairment in best-corrected visual acuity. Early diagnosis and proper treatment are crucial to prevent poor visual outcomes in adulthood. Advances in technology have provided more objective diagnostic tools, which can now be used by a wide range of healthcare providers. Here, we highlight tools that have gained popularity in the past two decades and compare clinically relevant parameters to guide primary care providers seeking to incorporate instrumental vision screening in pediatric patient care.

Objective: To evaluate the experiences and preferences of ophthalmology residency applicants and program directors (PDs), with emphasis on the effect of COVID-19 as well as recent changes on the application process.Design: Cross-sectional, online surveyParticipants: All applicants to the Bascom Palmer Eye Institute ophthalmology residency program, and all United States ophthalmology residency PDs, during the 2020-2021 application cycle.Methods: An online survey was distributed to applicants and program directors of the 2020-2021 ophthalmology residency application cycle.Main Outcome Measures: Applicant demographics, application submissions, interview experiences, financial considerations, match results, and suggestions for improvement of the application process.Results: Responses were obtained from 205 applicants (34.9% response rate) and 37 PDs (30.3%). A successful match into an ophthalmology residency was achieved by 144 (83.7%) applicants. Applicants applied to (mean ± SD) 79.7 ± 22.8 ophthalmology residency programs, received 13.1 ± 8.9 invitations to interview, and attended 11.1 ± 5.8 interviews. Most applicants (N = 126; 71.2%) and PDs (N = 22; 78.6%) expressed a preference for in-person interviews over virtual interviews. If given a choice regarding the future direction for interviews, most applicants were unsure (N = 68; 38.4%) or would prefer to hold interviews virtually (N = 62; 35.0%); PDs felt that interviews should go back to being in-person (39.3%) or were unsure (28.6%). Most PDs (N = 21; 72.4%) reported an increased number of applications received by their respective programs this year compared to previous years. While applicants (N = 108; 61.0%) mostly felt that there should not be a cap on the number of applications, 19 (67.9%) PDs supported a limit on application numbers. Applicants spent an average (SD) of $2320.96 ($1172.86) on the application process this year, which is significantly less than 2018-2019 data.Conclusions: The ophthalmology residency application process was especially complex during the COVID-19 pandemic. Although many applicants and PDs were glad that interviews were held virtually this year, they were less certain regarding future years. The virtual format led to a significantly lower financial burden for applicants and may lead some to prefer this format in the future; if a hybrid model is offered for virtual/in-person interviews, these two interview modes should be compared equally.

To examine the association between geographic atrophy (GA) disease characteristics and mortality risk.We manually delineated color fundus photographs of 209 Age-Related Eye Disease Study (AREDS) participants with GA secondary to age-related macular degeneration to identify total area of atrophy, GA effective radius growth rate, disease laterality, and the presence of foveal center involvement. Associations between GA characteristics and mortality were assessed with Cox proportional hazards models adjusted for health status indicators.During a median follow-up of 6.8 years, 48 (23.0%) participants with GA died. In adjusted models, accounting for age, sex, and health status, participants with total GA area in the highest quartile had a significantly increased risk of all-cause mortality compared to those with total GA area in the lowest quartile (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.32-8.86; P = 0.011). GA effective radius growth rate, bilateral disease, and the presence of foveal center involvement were not significantly associated with mortality. In a multivariable model, including health status indicators and all GA characteristics, total area of atrophy in the highest quartile remained significantly associated with mortality (HR, 4.65; 95% CI, 1.29-16.70; P = 0.019).More extensive GA, as indicated by a greater total area of atrophy, was associated with an increased risk of all-cause mortality in our cohort. The extent of GA may reflect the extent of underlying disease processes that contribute to greater mortality risk, further suggesting that GA may be part of a systemic rather than purely ocular disease process.

To investigate the underlying reason for the previously observed impact of baseline lesion size, number, and circularity on geographic atrophy (GA) growth rate.Retrospective analysis of a multicenter, prospective, randomized controlled trial.Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration.We manually delineated atrophic lesions on color fundus photographs of 318 eyes with GA followed up over at least 2 visits (mean follow-up duration, 5.1 ± 3.0 years). We calculated GA area growth rate for each eye based on the first and last visit. GA perimeter-adjusted growth rate was defined as the ratio between GA area growth rate and mean GA perimeter between the first and last visit for each eye.GA area growth rate, growth rate of the square root of GA area, and GA perimeter-adjusted growth rate.GA area growth rate was correlated strongly with mean GA perimeter (rThe growth rate of GA area is associated strongly with lesion perimeter. This relationship explains the previously observed influences of baseline GA size, lesion number, and circularity on GA growth rate. GA perimeter-adjusted growth rate is uncorrelated with the 3 morphologic factors and may serve as a surrogate outcome measure to monitor GA progression in future studies.

Purpose To investigate the topographic distribution of geographic atrophy (GA) and to identify an anatomic endpoint that correlates with visual acuity (VA) in eyes with GA. Design Retrospective analysis of a multicenter, prospective, randomized controlled trial. Participants The Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration. Methods We manually delineated GA on 1654 fundus photographs of 365 eyes. We measured GA areas in 9 subfields on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and correlated them with VA via a mixed-effects model. We determined the optimal diameter for the central zone by varying the diameter from 0 to 10 mm until the highest r2 between GA area in the central zone and VA was achieved. We estimated the VA decline rate over 8 years using a linear mixed model. Main Outcome Measures Geographic atrophy area in macular subfields and VA. Results The percentage of area affected by GA declined as a function of retinal eccentricity. GA area was higher in the temporal than the nasal region (1.30 ± 1.75 mm2 vs. 1.10 ± 1.62 mm2; P = 0.005) and in the superior than the inferior region (1.26 ± 1.73 mm2 vs. 1.03 ± 1.53 mm2; P Conclusions The prevalence of GA varies significantly across different macular regions. Although total GA area was associated poorly with VA, GA area in the central 1-mm diameter zone was correlated significantly with VA and may serve as a surrogate endpoint in clinical trials.

Background/aimsBest-corrected visual acuity (BCVA) is the most common primary endpoint in treatment trials for choroideremia (CHM) but the long-term natural history of BCVA is unclear.MethodsWe searched in seven databases to identify studies that reported BCVA of untreated eyes with CHM. We sought individual-level data and performed segmented regression between BCVA and age. For eyes followed longitudinally, we introduced a horizontal translation factor to each dataset to account for different ages at onset of a rapid BCVA decline.ResultsWe included 1004 eyes from 23 studies. BCVA of the right and left eyes was moderately correlated (r=0.60). BCVA as a function of age followed a 2-phase decline (slow followed by rapid decline), with an estimated transition age of 39.1 years (95% CI 33.5 to 44.7). After the introduction of horizontal translation factors to longitudinal datasets, BCVA followed a 2-phase decline until it reached 0 letters (r2=0.90). The BCVA decline rate was 0.33 letters/year (95% CI −0.38 to 1.05) before 39 years, and 1.23 letters/year (95% CI 0.55 to 1.92) after 39 years (p=0.004).ConclusionBCVA in eyes with CHM follows a 2-phase linear decline with a transition age of approximately 39 years. Future trials enrolling young patients may not be able to use BCVA as a primary or sole endpoint, but rather, may need to employ additional disease biomarkers that change before age 39. BCVA may still have utility as a primary endpoint for patients older than 39 years who have measurable BCVA decline rates.

Purpose To establish a continuous topography of retinal vessel density in normal eyes using optical coherence tomography angiography (OCTA). Methods A retrospective chart review was performed, and 8-mm × 8-mm OCTA images from 22 normal eyes were analyzed. Vessel density was plotted as a continuous function of distance from the foveal center (radial vessel density) and directional meridians (directional vessel density) for the superficial capillary plexus and deep capillary plexus. Results Continuous radial and directional vessel density plots for the superficial and deep capillary plexus were generated. Radial vessel density analysis revealed transition points at 657 microns (95% confidence interval [CI], 619-696) and 950 microns (95% CI, 903-997) from the foveal center for the superficial plexus and deep plexus, respectively. Directional vessel density analysis demonstrated significant vessel density variations in these vascular layers and provided greater detail compared to traditional quadrant analysis. Conclusions There are significant topographic variations of retinal vessel density in normal eyes. Continuous vessel density analysis offers greater sensitivity in detecting topographic vessel density changes compared to traditional methods of analysis. Translational relevance This study establishes a normative continuous vessel density topography that may help elucidate the role of the vascular bed in different chorioretinal diseases.

Purpose To conduct a systematic review and meta-analysis of the natural history of atrophy secondary to choroideremia (CHM). Clinical Relevance A sensitive and reliable anatomic measure to monitor disease progression is needed in treatment trials for CHM. However, the long-term natural history of the residual retinal pigment epithelium (RPE) is unclear, with reported RPE area decline rates varying widely among patients. Methods We searched in 7 literature databases up through July 17, 2019, to identify studies that assessed the residual RPE area in untreated eyes with CHM using fundus autofluorescence (FAF). We sought individual-eye data and investigated the RPE decline pattern using 3 models: the area linear model (ALM), radius linear model (RLM), and area exponential model (AEM), in which the area, radius, and log-transformed area of RPE change linearly with time, respectively. To account for different eyes’ entry times into the studies, we added a horizontal translation factor to each dataset. The RPE decline rate was estimated using a 2-stage random-effects meta-analysis. We assessed the risk of bias using the Quality In Prognosis Studies tool. Results Of 807 articles screened, we included 9 articles containing cross-sectional data (257 eyes) from 6 studies and longitudinal data (229 visits from 68 eyes) from 5 studies. The residual RPE area followed a trend of exponential decay as a function of patient age. After the introduction of horizontal translation factors to longitudinal datasets of individual eyes, the datasets fit along a straight line in the AEM over nearly 60 years (r2 = 0.997). The decline rate of log-transformed RPE area was 0.050 (95% confidence interval, 0.046–0.055) log(mm2)/year and was independent of the baseline RPE area (r = −0.18; P = 0.15) and age (r = 0.06; P = 0.63). In contrast, the decline rates of the area and effective radius of residual RPE strongly correlated with the baseline RPE area (r = 0.90 and 0.61, respectively; P Conclusions The loss of residual RPE area in untreated eyes with CHM follows the AEM over approximately 60 years. Log-transformed residual RPE area measured by FAF can serve as an anatomic endpoint to monitor CHM.

Purpose To evaluate the fractal dimension (Df ) of the choroidal vasculature using widefield indocyanine green (ICG) angiography and correlate it with the stage of age-related macular degeneration (AMD). Methods Widefield ICG angiography performed on 38 eyes was retrospectively analyzed using the FracLac application within the National Institutes of Health ImageJ software to determine regional fractal dimensions in the macular field and widefield. These values were then associated with a diagnosis of no AMD, non-exudative AMD (subdivided into early/intermediate stage vs. advanced stage), or exudative AMD (subdivided into with or without geographic atrophy). The mean values were compared using Wilcoxon's test. Results Early/intermediate non-exudative AMD and exudative AMD without geographic atrophy were found to have statistically significantly lower Df values compared to an absence of AMD when examining the macular field. Exudative AMD with geographic atrophy was found to have a statistically significant lower choroidal fractal dimension compared to no AMD when studied in the widefield. Conclusions Advanced stages of macular degeneration were found to have significantly decreased the fractal dimensions of choroidal vasculature on widefield ICG compared to early/intermediate stages, possibly implying a generalized reduction in complexity and/or vessel caliber of the choroid with advancing stage of AMD. This finding agrees with previous understanding of the development of choriocapillaris atrophy in advanced macular degeneration. Translational Relevance These findings suggest that using automated fractal analysis techniques can aid in differentiating stages of macular degeneration and, with further study, may be used to predict advancement of macular degeneration.

Background: While traditional eye plaque brachytherapy can be used for the treatment of iris melanoma, it faces challenges of poor patient tolerability due to cornea-plaque touch caused by radius of curvature mismatch and potential dosimetric inaccuracy from incomplete coverage. We present novel plaque designs and the first clinical application of the plaques for iris melanoma. Methods: Two dome-shaped plaques (EP2132 and EP1930) were designed to vault above the cornea to treat tumors of the iris and ciliary body. Image-based treatment planning of the first 2 clinical cases using the EP2132 plaque covered the tumor base plus a 2 mm margin and the involved ciliary body with at least 75 Gy to the tumor apex. Results: The tumors decreased in size following treatment. The patients tolerated the treatment well. There was no adverse event associated with the traditional iris plaques, such as decreased vision, pain, corneal edema, glaucoma, or cataract. Conclusion: The novel dome-shaped plaques for the treatment of iris melanoma provide effective dose distribution, improved surgical maneuverability, and increased tolerability for the patient. This plaque model can be used to treat iris melanoma of various sizes, configurations, and locations, including the ciliary body. The need for a customized plaque platform for each patient is minimized.

Objective To evaluate the methodologic quality of 3 primary open-angle glaucoma (POAG) clinical practice guidelines (CPGs). Design The CPGs were assessed with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Participants Four authors (A.M.W., C.M.W., B.K.Y., D.J.W.) performed independent assessments of POAG CPGs. Methods POAG CPGs published by the American Academy of Ophthalmology (AAO), Canadian Ophthalmological Society (COS), and National Institute for Health and Care Excellence (NICE) were appraised using the AGREE II instrument's 6 domains (Scope and Purpose, Stakeholder Involvement, Rigor of Development, Clarity of Presentation, Applicability, and Editorial Independence) and Overall Assessment score summarizing guideline quality across all domains. Results Scores ranged from 28% to 85% for the AAO CPG, 51% to 96% for the COS CPG, and 55% to 97% for the NICE CPG. Intraclass correlation coefficients for the reliability of mean scores for the AAO, COS, and NICE CPGs were 0.89, 0.86, and 0.74; 95% CIs were 0.80 to 0.95, 0.74 to 0.93, and 0.51 to 0.87, respectively. The strongest domains were Scope and Purpose (AAO, COS, NICE) and Clarity of Presentation (COS, NICE). The weakest domains were Stakeholder Involvement (AAO, COS) and Editorial Independence (AAO, COS, NICE). Conclusions Future POAG CPGs can be improved by addressing potential conflicts of interest within the development group, ensuring transparency of guideline development methodology, and involving all relevant stakeholders in guideline development and review.

Purpose This study used the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument to evaluate the methodological quality of clinical practice guidelines (CPG) published by the American Academy of Ophthalmology (AAO), Canadian Ophthalmological Society (COS) and Royal College of Ophthalmologists (RCO) for the management of cataract in adults. Study design An evaluation of the AAO, COS and RCO CPGs using a reliable and validated instrument. Methods Four evaluators independently appraised the three CPGs using the AGREE II Instrument, which covers six domains (Scope and Purpose, Stakeholder Involvement, Rigour of Development, Clarity of Presentation, Applicability and Editorial Independence). The AGREE II includes an Overall Assessment summarising guideline methodological rigour across all domains, using a 7-point scale where perfect adherence equals a score of 7. Results Scores ranged from 36% to 75% for the AAO guideline; 45% to 94% for the COS guideline and 23% to 85% for the RCO guideline. Intraclass correlation coefficients for the reliability of mean scores for the AAO, COS, and RCO were 0.78, 0.74 and 0.80; 95% CIs (0.60 to 0.90), (0.45 to 0.88) and (0.53 to 0.91), respectively. The strongest domains were Scope and Purpose (COS, RCO), Clarity of Presentation (COS, RCO) and Editorial Independence (AAO, COS). The weakest were Stakeholder Involvement (AAO), Applicability (AAO, COS) and Editorial Independence (RCO). Conclusions Cataract surgery practice guidelines can be improved by targeting stakeholder involvement, applicability and editorial independence.

Purpose. To evaluate the methodological quality of age-related macular degeneration (AMD) clinical practice guidelines (CPGs).Methods. AMD CPGs published by the American Academy of Ophthalmology (AAO) and Royal College of Ophthalmologists (RCO) were appraised by independent reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, which comprises six domains (Scope and Purpose, Stakeholder Involvement, Rigor of Development, Clarity of Presentation, Applicability, and Editorial Independence), and an Overall Assessment score summarizing methodological quality across all domains.Results. Average domain scores ranged from 35% to 83% for the AAO CPG and from 17% to 83% for the RCO CPG. Intraclass correlation coefficients for the reliability of mean scores for the AAO and RCO CPGs were 0.74 and 0.88, respectively. The strongest domains were Scope and Purpose and Clarity of Presentation. The weakest were Stakeholder Involvement (AAO) and Editorial Independence (RCO).Conclusions. Future AMD CPGs can be improved by involving all relevant stakeholders in guideline development, ensuring transparency of guideline development and review methodology, improving guideline applicability with respect to economic considerations, and addressing potential conflict of interests within the development group.

One-third of medical students complete medical school without significant exposure to research. This gap in their medical education is significant: research not only exposes medical students to scientific methodology and academic writing, but also encourages them to multi-task, communicate, and critically analyze the scientific literature - valuable skills that will serve them well in their future medical careers. We report herein the proceedings from a student-led symposium that aimed to promote student involvement in research at the Alpert Medical School of Brown University by providing practical information on how to successfully complete a research project.

Prospective survey.To determine the prevalence of use of presurgical psychological screening (PPS) among spine surgeons in the United States, identify factors associated with PPS use, evaluate surgeons' opinions of PPS, and investigate how PPS is applied in clinical practice.The United States Preventive Services Task Force recommends PPS for patients undergoing back surgery. The prevalence of PPS is unknown. Thus, it may be difficult to improve preoperative care for such patients with psychological conditions.An online survey invitation was emailed to 340 spine surgeons. Questions addressed surgeon characteristics (eg, number of years in practice), practice characteristics (eg, practice type), inclusion of integrated rehabilitation and psychological services, and use of PPS. The impact of psychological factors on rehabilitation and recovery was assessed using an 11-point Likert scale (0, no impact; 10, highest impact). We analyzed the 110 (32%) responses with a χ(2) test (significance, P0.05).PPS was used by 37% (41) to screen for depression (100%) or anxiety (85%). PPS use was highest among surgeons with more experience, higher annual volume, and no university affiliation. Among those screening for fear avoidance, use was highest among surgeons more recently entering the field. Surgeons reported a strong belief regarding the impact of psychological factors on pain relief, adherence to therapy, and return to work (mean impact rating,7.0); however, impact on return for follow-up was only moderate (mean rating, 5.8).A minority of surgeons reported using PPS. Surgeons were less likely to use PPS if they had completed residency or begun practice within 14 years, had fewer than 200 cases annually, or were university affiliated. This study highlights the need to advocate for the use of North American Spine Society guidelines regarding the use of PPS.

The Institute of Medicine (IOM) has published a set of eight standards for guideline development groups (GDGs) to derive trustworthy clinical practice guidelines (CPGs). We investigated the adherence of these IOM guidelines to its own standards. The IOM document passed two of its own standards ("GDG-Systematic Review Team Interaction" and "GDG Composition"), only partially passed two others ("Articulation of Recommendation" and "External Review") and failed to pass four ("Establishing Transparency," "Management of Conflict of Interest," "Establishing Evidence Foundations" and "Updating"). The IOM standards for the development of CPGs do not meet their own criteria of trustworthiness. Further study is needed to determine the best methodology to evaluate CPGs.

Dear Editor, Virtual reality (VR) simulation is a promising modality to help ophthalmology residents bridge the gap between the wet lab and the operating room (OR) [1]. However, more widespread implementation of VR simulation in ophthalmology graduate medical education (GME) programs has been limited by concerns about simulator realism fidelity, lack of evidence for surgical skills transfer (VR-to-OR), and startup costs [2]. While current research is focused on addressing simulation fidelity and skills transfer, little has been done to address cost; VR units must be cost effective for VR to become a widespread part of ophthalmology GME [3, 4]. To this end, we investigated potential cost savings of VR training in cataract surgery using the criterion of reduced trainee OR time, one of the only published outcomes of VR-to-OR training [3]. The calculation of cost savings with the use of the VR simulator in residency program is summarized in Table 1. We found that the average US residency program will save $4,980 per year in non-supply costs. In addition, a well-studied VR cataract surgery simulator, the EyeSi (VRmagic, Mannheim, Germany) [1–3], costs approximately $167,000 (pers. comm., VRmagic US Sales representative, 1/07/2013); based on non-supply cost savings, it thus would require an estimated 34 years ($167,070/$4,980) for a typical US residency program to recoup the expense of a VR unit. This analysis has several limitations. First, the cost calculation was based on data from one US Veterans Health Administration (VHA) hospital. While the VHA is the largest provider of health care training in the US, costs in other teaching hospitals may differ. Second, we only evaluated non-supply costs of OR staff salaries, wages, and benefits. These were the only costs that could be readily linked to decreased OR time, as other differences in OR performance have not yet been found. Third, the estimates of savings in OR times were based on one study of 20 residents. Lastly, we only considered savings accrued with VR training in cataract surgery. While a VR training module in vitreoretinal surgery is available at additional cost, US residents only perform an average of 6.5 vitreoretinal procedures as primary surgeon in the course of their training [6]. The low volume of vitreoretinal surgery would be a significant barrier to determining the impact of VR training on resident vitreoretinal surgical outcomes and OR costs. Similarly, low volume would be a barrier for assessing the impact of VR cataract surgery training on other intraocular procedures such as glaucoma surgery. B. K. Young : P. B. Greenberg Division of Ophthalmology, Warren Alpert Medical School of Brown University, Providence, RI, USA