Democratizing Health Care in the Metaverse: How Video Games can Monitor Eye Conditions Using the Vision Performance Index: A Pilot Study.

Objective: In a world where digital media is deeply engrained into our everyday lives, there lies an opportunity to leverage interactions with technology for health and wellness. The Vision Performance Index (VPI) leverages natural human-technology interaction to evaluate visual function using visual, cognitive, and motor psychometric data over 5 domains: field of view, accuracy, multitracking, endurance, and detection. The purpose of this study was to describe a novel method of evaluating holistic visual function through video game-derived VPI score data in patients with specific ocular pathology. Design: Prospective comparative analysis. Participants: Patients with dry eye, glaucoma, cataract, diabetic retinopathy (DR), age-related macular degeneration, and healthy individuals. Methods: The Vizzario Inc software development kit was integrated into 2 video game applications, Balloon Pop and Picture Perfect, which allowed for generation of VPI scores. Study participants were instructed to play rounds of each video game, from which a VPI score was compiled. Main Outcome Measures: The primary outcome was VPI overall score in each comparison group. Vision Performance Index component, subcomponent scores, and psychophysical inputs were also compared. Results: Vision Performance Index scores were generated from 93 patients with macular degeneration (n = 10), cataract (n = 10), DR (n = 15), dry eye (n = 15), glaucoma (n = 16), and no ocular disease (n = 27). The VPI overall score was not significantly different across comparison groups. The VPI subcomponent "reaction accuracy" score was significantly greater in DR patients (106 ± 13.2) versus controls (96.9 ± 11.5), P = 0.0220. The VPI subcomponent "color detection" score was significantly lower in patients with DR (96.8 ± 2.5; p=0.0217) and glaucoma (98.5 ± 6.3; P = 0.0093) compared with controls (101 ± 11). Psychophysical measures were statistically significantly different from controls: proportion correct (lower in DR, age-related macular degeneration), contrast errors (higher in cataract, DR), and saturation errors (higher in dry eye). Conclusions: Vision Performance Index scores can be generated from interactions of an ocular disease population with video games. The VPI may offer utility in monitoring select ocular diseases through evaluation of subcomponent and psychophysical input scores; however, future larger-scale studies must evaluate the validity of this tool. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Risk of Stroke, Myocardial Infarction, Deep Vein Thrombosis, Pulmonary Embolism, and Death After Retinal Vein Occlusion.

PURPOSE: To examine rates of stroke, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE), and death in patients after retinal vein occlusion (RVO) compared to controls. DESIGN: Retrospective cohort study. METHODS: An aggregated electronic health records research network, TriNetX, was used to identify patients with diagnosis of RVO and a control group of patients with cataract. Patients were excluded if they had history of stroke, MI, DVT, or PE within 2 years of diagnosis of RVO or cataract. Propensity score matching was performed to control for baseline demographics and medical comorbidities. Main outcomes included relative risk (RR) of death, stroke, MI, DVT, and PE after RVO compared to those in matched controls. RESULTS: A total of 45,304 patients were included in each cohort. There was elevated risk of death in the RVO cohort compared to the control cohort at 1 year (RR = 1.30, P < .01), 5 years (RR = 1.22, P < .01), and 10 years (RR = 1.08, P < .01). There was elevated risk of stroke at 1 year (RR = 1.61, P < .01), 5 years (RR = 1.31, P < .01), and 10 years (RR = 1.18, P < .01). There was elevated risk of MI at 1 year (RR = 1.26, P < .01) and 5 years (RR = 1.13, P < .01), but not at 10 years (RR = 1.06, P = .12). There was mildly elevated risk of DVT at 1 year (RR = 1.65, P < .01) but not at 5 years (RR = 0.94, P = .94) or 10 years (RR = 1.05, P = .37). There was no elevated risk of PE at 1 year (RR = 0.98, P = 0.80), 5 years (RR = 0.95, P = .42), or 10 years (RR = 0.85, P =.40). CONCLUSIONS: There is an increased rate of death, stroke, and MI after RVO compared to those in matched controls. We emphasize the need for long-term systemic evaluation after RVO.

Social Determinants of Health and Perceived Barriers to Care in Diabetic Retinopathy Screening.

Importance: Regular screening for diabetic retinopathy often is crucial for the health of patients with diabetes. However, many factors may be barriers to regular screening and associated with disparities in screening rates. Objective: To evaluate the associations between visiting an eye care practitioner for diabetic retinopathy screening and factors related to overall health and social determinants of health, including socioeconomic status and health care access and utilization. Design, Setting, and Participants: This retrospective cross-sectional study included adults aged 18 years or older with type 2 diabetes who answered survey questions in the All of Us Research Program, a national multicenter cohort of patients contributing electronic health records and survey data, who were enrolled from May 1, 2018, to July 1, 2022. Exposures: The associations between visiting an eye care practitioner and (1) demographic and socioeconomic factors and (2) responses to the Health Care Access and Utilization, Social Determinants of Health, and Overall Health surveys were investigated using univariable and multivariable logistic regressions. Main Outcome and Measures: The primary outcome was whether patients self-reported visiting an eye care practitioner in the past 12 months. The associations between visiting an eye care practitioner and demographic and socioeconomic factors and responses to the Health Care Access and Utilization, Social Determinants of Health, and Overall Health surveys in All of Us were investigated using univariable and multivariable logistic regression. Results: Of the 11 551 included participants (54.55% cisgender women; mean [SD] age, 64.71 [11.82] years), 7983 (69.11%) self-reported visiting an eye care practitioner in the past year. Individuals who thought practitioner concordance was somewhat or very important were less likely to have seen an eye care practitioner (somewhat important: adjusted odds ratio [AOR], 0.83 [95% CI, 0.74-0.93]; very important: AOR, 0.85 [95% CI, 0.76-0.95]). Compared with financially stable participants, individuals with food or housing insecurity were less likely to visit an eye care practitioner (food insecurity: AOR, 0.75 [95% CI, 0.61-0.91]; housing insecurity: AOR, 0.86 [95% CI, 0.75-0.98]). Individuals who reported fair mental health were less likely to visit an eye care practitioner than were those who reported good mental health (AOR, 0.84; 95% CI, 0.74-0.96). Conclusions and Relevance: This study found that food insecurity, housing insecurity, mental health concerns, and the perceived importance of practitioner concordance were associated with a lower likelihood of receiving eye care. Such findings highlight the self-reported barriers to seeking care and the importance of taking steps to promote health equity.

Risk of Stroke, Myocardial Infarction, and Death After Retinal Artery Occlusion.

Importance: Patients with retinal artery occlusions (RAOs) are recommended to have emergent stroke workup, although the true risk of death and subsequent vascular events post-RAO is not clear. Objective: To determine short-term and long-term rates of stroke, myocardial infarction (MI), and death in patients after RAO compared with a control cohort. Design, Setting, and Participants: This retrospective cohort study used aggregated electronic health records from January 1, 2003, through April 14, 2023, from TriNetX, a network with data from more than 111 million patients. Patients with RAO and a cataract control group were identified and matched for age, sex, race, and comorbidities, including hypertension, diabetes, hyperlipidemia, and smoking status. Patients were excluded if they had a stroke or MI within 2 years before the diagnosis of RAO or cataract. Exposure: International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis code for RAO or age-related cataract. Main Outcomes and Measures: Rate of death, stroke, and MI at 2 weeks, 30 days, 1 year, 5 years, and 10 years after RAO compared with matched controls. Results: There were a total of 34 874 patients with at least 1 year of follow-up in the RAO cohort. The mean (SD) age at the RAO event was 66 (15.2) years. The rate of death after RAO diagnosis was higher than after cataract diagnosis at 2 weeks (0.14% vs 0.06%; relative risk [RR], 2.45; 95% CI, 1.46-4.12; risk difference [RD], 0.08%; 95% CI, 0.04%-0.13%; P < .001), 30 days (0.29% vs 0.14%; RR, 2.10; 95% CI, 1.49-2.97; RD, 0.15%; 95% CI, 0.08%-0.22%; P < .001), 1 year (3.51% vs 1.99%; RR, 1.78; 95% CI, 1.61-1.94; RD, 1.41%; 95% CI, 1.17%-1.66%; P < .001), 5 years (22.74% vs 17.82%; RR, 1.28; 95% CI, 1.23-1.33; RD, 4.93%; 95% CI, 4.17%-5.68%; P < .001), and 10 years (57.86% vs 55.38%; RR, 1.05; 95% CI, 1.02-1.07; RD, 2.47%; 95% CI, 1.25%-3.69%; P < .001). Risk of stroke after RAO was higher at 2 weeks (1.72% vs 0.08%; RR, 21.43; 95% CI, 14.67-31.29; RD, 1.64%; 95% CI, 1.50%-1.78%; P < .001), 30 days (2.48% vs 0.18%; RR, 14.18; 95% CI, 10.94-18.48; RD, 2.31%; 95% CI, 2.14%-2.47%; P < .001), 1 year (5.89% vs 1.13%; RR, 5.20; 95% CI, 4.67-5.79; RD, 4.64%; 95% CI, 4.37%-4.91%; P < .001), 5 years (10.85% vs 4.86%; RR, 2.24; 95% CI, 2.09-2.40; RD, 6.00%; 95% CI, 5.50%-6.50%; P < .001), and 10 years (14.59% vs 9.18%; RR, 1.59; 95% CI, 1.48-1.70; RD, 5.41%; 95% CI, 4.62%-6.21%; P < .001). Risk of MI after RAO was higher at 2 weeks (0.16% vs 0.06%; RR, 3.00; 95% CI, 1.79-5.04; RD, 0.11%; 95% CI, 0.06%-0.16%; P < .001), 30 days (0.27% vs 0.10%; RR, 2.61; 95% CI, 1.78-3.83; RD, 0.17%; 95% CI, 0.10%-0.23%; P < .001), 1 year (1.66% vs 0.97%; RR, 1.72; 95% CI, 1.51-1.97; RD, 0.59%; 95% CI, 0.42%-0.76%; P < .001), 5 years (6.06% vs 5.00%; RR, 1.21; 95% CI, 1.12-1.31; RD, 1.07%; 95% CI, 0.64%-1.50%; P < .001), and 10 years (10.55% vs 9.43%; RR, 1.12; 95% CI, 1.04-1.21; RD, 1.13%; 95% CI, 0.39%-1.87%; P = .003). Conclusions and Relevance: This study showed an increased risk of death, stroke, and MI in patients with RAO at both short-term and long-term intervals after RAO compared with a matched control population diagnosed with cataract. These findings suggest a potential need for multidisciplinary evaluation and long-term systemic follow-up of patients post-RAO.

Epidemiology of rhegmatogenous retinal detachment in commercially insured myopes in the United States.

Myopia is a known risk factor for rhegmatogenous retinal detachment (RRD). Given global trends of increasing myopia, we aimed to determine the absolute risk (incidence rate) of RRD in non-myopes, myopes and high myopes in the United States over ten years. We performed a retrospective cohort study of 85,476,781 commercially insured patients enrolled in the Merative™ Marketscan® Research Database. The incidence rate of RRD in phakic patients in the United States was 39-fold higher in high myopes than non-myopes (868.83 per 100,000 person-years versus 22.44 per 100,000 person-years) and three-fold higher in myopes than non-myopes (67.51 per 100,000 person-years versus 22.44 per 100,000 person-years). The incidence rate was significantly higher in males in each category (P < 0.01). Combined, the incidence rate of RRD in phakic patients in the United States from 2007 to 2016 was 25.27 RRDs per 100,000 person-years, a rate higher than those in prior published studies in North America, South America, Europe, Asia, and Australia. The absolute risk of myopia and high myopia increased from 2007 to 2016. The risk of RRD in phakic high myopes rose with increasing age. Notably, the magnitude of increased risk of RRD in myopes varied substantially according to the minimum follow-up period in our models and should be accounted for when interpreting data analyses.

Wide-field swept-source optical coherence tomography angiography in the assessment of retinal microvasculature and choroidal thickness in patients with myopia.

BACKGROUND/AIMS: Pathological myopia (PM) is a leading cause of blindness worldwide. We aimed to evaluate microvascular and chorioretinal changes in different stages of myopia with wide-field (WF) swept-source (SS) optical coherence tomography angiography (OCTA). METHODS: This prospective cross-sectional observational study included 186 eyes of 122 patients who had undergone imaging between November 2018 and October 2020. Vessel density (VD) and vessel skeletonised density (VSD) of superficial capillary plexus, deep capillary plexus and whole retina, as well as foveal avascular zone parameters, retinal thickness (RT) and choroidal thickness (CT), were calculated. RESULTS: This study evaluated 75 eyes of 48 patients with high myopia (HM), 43 eyes of 31 patients with mild to moderate myopia and 68 eyes of 53 age-matched controls. Controlling for age and the presence of systemic hypertension, we found that HM was associated with decrease in VD and VSD in all layers on 12×12 mm² scans. Furthermore, HM was associated with a VD and VSD decrease in every Early Treatment Diabetic Retinopathy Study grid, with a larger decrease temporally (ßVD=-0.39, ßVSD=-10.25, p<0.01). HM was associated with decreased RT and CT. Reduction in RT was outside the macular region, while reduction in CT was in the macular region. CONCLUSION: Using WF SS-OCTA, we identified reduction in microvasculature and structural changes associated with myopia. Decrease in VD and VSD was greater in the temporal quadrant, and reductions in RT and CT were uneven across the retina. Further work may help identify risk factors for the progression of PM and associated vision-threatening complications.

Fall risk in patients with pseudophakic monovision.

OBJECTIVE: Vision changes can precipitate falls in the elderly resulting in significant morbidity and mortality. We hypothesized that pseudophakic monovision and ensuing anisometropia and aniseikonia impact elderly fall risk. This study assessed fall risk in patients with pseudophakic monovision, pseudophakic single vision distance (classic cataract surgery), and cataracts with no surgery. DESIGN: Retrospective single-institution cohort study PARTICIPANTS: Patients with bilateral cataracts diagnosed at 60 years of age or older who underwent bilateral cataract surgery (monovision or single vision distance) or did not undergo any cataract surgery (n = 13 385). Patients with unilateral surgery or a fall prior to cataract diagnosis were excluded. METHODS: Data were obtained from the Stanford Research Repository. Time-to-fall analysis was performed across all 3 groups. Primary outcome was hazard ratio (HR) for fall after second eye cataract surgery or after bilateral cataract diagnosis. RESULTS: Of 13 385 patients (241 pseudophakic monovision, 2809 pseudophakic single vision, 10 335 no surgery), 850 fell after cataract diagnosis. Pseudophakic monovision was not associated with fall risk after controlling for age, sex, and myopia. Pseudophakic single-vision patients had a decreased time to fall compared with no-surgery patients (log rank, p < 0.001). Older age at cataract diagnosis (HR =1.05, 95% confidence interval [CI] 1.04-1.06, p < 0.001) or at time of surgery (HR = 1.05, 95% CI 1.03-1.07, p < 0.001) increased fall risk, as did female sex (HR = 1.29, 95% CI 1.10-1.51, p = 0.002) and preexisting myopia (HR = 1.31, 95% CI 1.01-1.71, p = 0.046) among nonsurgical patients. CONCLUSIONS: Pseudophakic monovision did not impact fall risk, but pseudophakic single vision may increase falls compared with patients without cataract surgery.

Biometric Variations in High Myopia Associated with Different Underlying Ocular and Genetic Conditions.

Purpose: To report different biometric measurements in high myopia associated with different underlying ocular and genetic conditions. Design: Retrospective study. Subjects: Patients with high myopia. Methods: We searched the Stanford Research Repository tool to identify patients with the diagnosis of high myopia who were seen by a single provider at Byers Eye Institute at Stanford from January 2019 to March 2022. We performed a chart review and included eyes that had high myopia and ocular biometric measurements at any time point after January 2019. We divided our cohort into 5 different groups: (1) isolated high myopia (IHM) (control group); (2) retinopathy of prematurity (ROP); (3) familial exudative vitreoretinopathy; (4) Marfan syndrome; and (5) Stickler syndrome. Main Outcome Measures: Biometric measurements. Results: A total of 246 patients (432 eyes) were included as follows: 202 patients (359 eyes) in the IHM group, 17 patients (27 eyes) in the ROP group, 7 patients (12 eyes) in the familial exudative vitreoretinopathy group, 8 patients (14 eyes) in the Marfan group, and 12 patients (20 eyes) in the Stickler group. The ROP group showed significantly shorter axial lengths, shallower anterior chambers, and thicker lenses compared with the IHM group. The Marfan group showed significantly flatter corneas and thicker lenses compared with the IHM group. The Stickler group showed significantly longer axial lengths compared with the IHM group. Conclusions: High myopia is associated with variable biometric measurements according to underlying ocular or genetic conditions. Retinopathy of prematurity-associated high myopia is primarily lenticular, while Stickler syndrome-associated high myopia is axial. Marfan syndrome-associated high myopia is derived from both axial and lenticular mechanisms.

A Comparative Study of Traditional Scleral Buckling to a New Technique: Guarded Light Pipe with Heads-Up Three-Dimensional Visualization.

Purpose: The guarded light pipe is a recently described alternative endoillumination technique to chandelier illumination. We sought to compare the outcomes of scleral buckling (SB) under indirect ophthalmoscopy (ID) to heads-up three-dimensional visualization with a guarded light pipe (3DGLP). Methods: A retrospective comparative study was performed, including 47 eyes that underwent SB for rhegmatogenous retinal detachment (RRD) repair with either traditional ID (n = 31) or 3DGLP (n = 16). Results: The single surgery anatomic success rate was 87.0% in the ID group and 87.5% in the 3DGLP group. The final anatomic success rate was 100% in both groups. The median (interquartile range) post-operative logMAR was 0.10 (0.0-0.20) in the ID group and 0.08 (0.02-0.69) in the 3DGLP group (p = 0.51). The median operative time was 107 (94-123) minutes in the ID group and 100 (90-111) minutes in the 3DGLP group (p = 0.25). Among eyes that underwent subretinal fluid drainage, the operative time was significantly longer in the ID group compared to the 3DGLP group, 113 (100-135) minutes vs 93 (85-111) minutes (p = 0.035). There were no post-operative complications in the ID group and one complication of self-resolving vitreous hemorrhage associated with a malfunctioning cryoprobe in the 3DGLP group (p = 0.34). There were no cases of post-operative cataract progression in either group. Conclusion: Compared to traditional SB, 3DGLP improves ergonomics and educational value with similar anatomical, visual, intra and post-operative outcomes and may result in shorter operative time in cases requiring subretinal fluid drainage.

Trends in Leadership and Award Recognition Among Women in the American Society of Retina Specialists.

Purpose: This work evaluates trends in achievement of women in the retina field, through an analysis of gender representation in the American Society of Retina Specialists (ASRS). Methods: This retrospective, longitudinal study spans 1983 to 2020. Historical data classified by male or female gender were collected from ASRS's overall membership, board of directors and officers, and recipients of the 4 society awards. The proportion of each benchmark held by women was compared with prior decades since the founding of ASRS using the Fisher's exact test. Results: Women's representation increased from 11% of ASRS members in 2007 to 19.7% in 2020. From 2010 to 2019, women received a higher proportion of society awards (21.1%) compared with membership prior to the start of that decade. In 2020, women were proportionally well represented in board of director positions (21.9%) and held a significantly higher proportion of board positions than in the period 1983 to 1989 (P = .02). From 1983 to 2020, women held 4.3% (1 of 23) of presidencies. Conclusions: Although the number of women in retina is increasing, women remain underrepresented in the leadership of ASRS. Interventions to increase exposure to female mentorship and improve childcare benefits are warranted to engage female ophthalmology trainees in retina and ultimately society leadership.

Higher prevalence of fundus haemorrhages in early-screened (NEST Study) as compared to late-screened (SUNDROP Study) newborn populations.

BACKGROUND/AIMS: To determine whether timing of ophthalmic screening influences prevalence of neonatal fundus haemorrhages. We compared the prevalence of fundus haemorrhages in two populations: term newborns screened early (less than 72 hours) and preterm newborns screened late (4-11 weeks). Additionally, we reviewed the literature on timing and prevalence of newborn haemorrhages. METHODS: Retrospective observational cohort study. Infants who underwent wide-angle ophthalmic digital imaging over one overlapping year in the Newborn Eye Screen Testing (NEST) or Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) programme were included. The PubMed database was filtered to include English-language articles dating back to 1950. Nine articles were selected for review based on inclusion of the prevalence of newborn fundus haemorrhages at multiple time points. RESULTS: A total of 202 patients received early imaging in the NEST cohort and 73 patients received late imaging in the SUNDROP cohort. In the NEST cohort, 20.2% of newborns had haemorrhages. In contrast, we found haemorrhages in only one case or 1.4% of the SUNDROP cohort. Using prevalence data from nine additional studies, we developed a predicted probabilities model of newborn haemorrhages. Per this model, the probability of seeing a haemorrhage if you screen an infant at 1 hour is 18.8%, at 2 weeks is 2.9% and at 1 month is 0.28%. CONCLUSION: We found a significant difference in the prevalence of fundus haemorrhages between the early-screened NEST cohort and the late-screened, preterm SUNDROP cohort. Likely, this difference is due to the transient nature of most newborn haemorrhages.

Visual acuity and progression of macular atrophy in patients receiving intravitreal anti-VEGF for age-related macular degeneration.

PURPOSE: Whether intravitreal anti-vascular endothelial growth factors (VEGFs) cause retinal atrophy is still a subject of debate. We reported 13 eyes that received several injections of anti-VEGF for wet age-related macular degeneration (AMD) with good visual acuity despite geographic atrophy on imaging. METHODS: This is a case series study conducted at Byers Eye Institute at Stanford University. Patients of three retina specialists with wet AMD who received six or more intravitreal injection of anti-VEGFs with visual acuity of 20/60 or better and incomplete RPE and outer retina atrophy (iRORA) or complete RPE and outer retinal atrophy (cRORA) were enrolled in this case series. Different imaging modalities were reviewed by three retina specialists comparing the baseline with the most recent exam. RESULTS: About 13 eyes of 10 patients met the selection criteria. Eleven eyes were classified as iRORA and 2 as cRORA. Despite the development of macular atrophy on imaging after an average of 38.1 injections, eyes maintained stable visual acuity. CONCLUSION: The discrepancy between structural and functional findings in this cohort suggests that patients treated by anti-VEGF drugs exhibit divergent clinical outcomes for currently unknown reasons. The authors propose anti-VEGF may affect melanosomes within RPE without disrupting RPE and photoreceptors function completely. This requires further investigation.

Sudden monocular vision loss after sneezing as captured on widefield swept source optical coherence tomography-angiography.

PURPOSE: We report an unusual case of likely combined retinal artery occlusion and retinal vein occlusion following a sneeze. Widefield swept source optical coherence tomography-angiography (WF-SS-OCTA) was used to analyze retinal changes at one-month follow-up. METHODS: The patient reported visual symptoms in his left eye immediately after sneezing five times in a row. Fundus examination showed an embolus along the superior arcade. Stroke workup revealed moderate carotid artery stenosis and a subtherapeutic INR. At one-month follow-up, fundus photography and SS-OCTA were obtained. RESULTS: Fundus photography showed superior retinal whitening and arteriole attenuation, an inferior perifoveal cotton wool spot, and inferotemporal intraretinal hemorrhages. SS-OCTA showed loss of the deep capillary plexus superiorly and inferotemporally, most consistent with combined retinal artery and retinal vein occlusion. CONCLUSION: We report the first case of sneeze-induced combined retinal artery and retinal vein occlusion. The retina is a uniquely accessible window that provides insight into human physiology, and SS-OCTA is a powerful tool that can give further insight into the pathophysiology of an occlusion.

The Utility of Universal Newborn Eye Screening: A Review.

Universal newborn eye screening can identify ocular abnormalities early and help mitigate long-term visual impairment. Traditional neonatal and infant eye screening is administered by neonatologists and pediatricians using the red reflex test. If this test identifies an ocular abnormality, then the patient is examined by an ophthalmologist. Notably, the red reflex test may be unable to detect amblyogenic posterior segment pathology. Recent studies using fundus imaging and telemedicine show reduced cost of human resources and increased sensitivity compared with traditional approaches. In this review, the authors discuss universal newborn eye screening pilot programs with regard to disease prevalence, referral-warranted disease, and cost-effectiveness. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:S6-S16.].

Ocular Penetrance and Safety of the Dopaminergic Prodrug Etilevodopa.

Purpose: Animal models have demonstrated the role of dopamine in regulating axial elongation, the critical feature of myopia. Because frequent delivery of dopaminergic agents via peribulbar, intravitreal, or intraperitoneal injections is not clinically viable, we sought to evaluate ocular penetration and safety of the topically applied dopaminergic prodrug etilevodopa. Methods: The ocular penetration of dopamine and dopaminergic prodrugs (levodopa and etilevodopa) were quantified using an enzyme-linked immunosorbent assay in enucleated porcine eyes after a single topical administration. The pharmacokinetic profile of the etilevodopa was then assessed in rats. A four-week once-daily application of etilevodopa as a topical eye drop was conducted to establish its safety profile. Results: At 24 hours, the studied prodrugs showed increased dopaminergic derivatives in the vitreous of porcine eyes. Dopamine 0.5% (P = 0.0123) and etilevodopa 10% (p = 0.370) achieved significant vitreous concentrations. Etilevodopa 10% was able to enter the posterior segment of the eye after topical administration in rats with an intravitreal half-life of eight hours after single topical administration. Monthly application of topical etilevodopa showed no alterations in retinal ocular coherence tomography, electroretinography, caspase staining, or TUNEL staining. Conclusions: At similar concentrations, no difference in ocular penetration of levodopa and etilevodopa was observed. However, etilevodopa was highly soluble and able to be applied at higher topical concentrations. Dopamine exhibited both high solubility and enhanced penetration into the vitreous as compared to other dopaminergic prodrugs. Translational Relevance: These findings indicate the potential of topical etilevodopa and dopamine for further study as a therapeutic treatment for myopia.

Statins and the progression of age-related macular degeneration in the United States.

PURPOSE: To study the effect of statin exposure on the progression from non-exudative to exudative age-related macular degeneration (AMD). METHODS: Retrospective cohort study of commercially insured patients diagnosed with non-exudative AMD (n = 231,888) from 2007 to 2015. Time-to-event analysis of the association between exposure to lipid-lowering medications and time from non-exudative AMD to exudative AMD diagnosis was conducted. Outcome measures included progression to exudative AMD, indicated by diagnosis codes for exudative AMD or procedural codes for intravitreal injections. RESULTS: In the year before and after first AMD diagnosis, 11,330 patients were continuously prescribed lipid-lowering medications and 31,627 patients did not take any lipid-lowering medication. Of those taking statins, 21 (1.6%) patients were on very-high-dose lipophilic statins, 644 (47.6%) on high-dose lipophilic statins, and 689 (50.9%) on low-dose lipophilic statins. We found no statistically significant relationship between exposure to low (HR 0.89, 95% CI 0.83 to 1.38) or high-dose lipophilic statins (HR 1.12, 95% CI 0.86 to 1.45) and progression to exudative AMD. No patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD, though this difference was not statistically significant due to the subgroup size (p = .23, log-rank test). CONCLUSIONS: No statistically significant relationship was found between statin exposure and risk of AMD progression. Interestingly, no patients taking very-high-dose lipophilic statins progressed to exudative AMD, a finding that warrants further exploration.

Comparison between wide-field digital imaging system and the red reflex test for universal newborn eye screening in Brazil.

PURPOSE: To compare neonatal eye screening using the red reflex test (RRT) versus the wide-field digital imaging (WFDI) system. METHODS: Prospective cohort study. Newborns (n = 380, 760 eyes) in the Maternity Ward of Irmandade Santa Casa de Misericórdia de São Paulo hospital from May to July 2014 underwent RRT by a paediatrician and WFDI performed by the authors. Wide-field digital imaging (WFDI) images were analysed by the authors. Validity of the paediatrician's RRT was assessed by unweighted kappa [κ] statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: While WFDI showed abnormalities in 130 eyes (17.1%), RRT was only abnormal in 13 eyes (1.7%). Wide-field digital imaging (WFDI) detected treatable retina pathology that RRT missed including hyphema, CMV retinitis, FEVR and a vitreous haemorrhage. The sensitivity of the paediatrician's RRT to detect abnormalities was poor at 0.77% (95% confidence interval, CI, 0.02%-4.21%) with a PPV of only 7.69% (95% CI, 1.08%-38.85%). Overall, there was no agreement between screening modalities (κ = -0.02, 95% CI, -0.05 to 0.01). The number needed to screen to detect ocular abnormalities using WFDI was 5.9 newborns and to detect treatable abnormalities was 76 newborns. CONCLUSION: While RRT detects gross abnormalities that preclude visualization of the retina (i.e. media opacities and very large tumours), only WFDI consistently detects subtle treatable retina and optic nerve pathology. With a higher sensitivity than the current gold standard, universal WFDI allows for early detection and management of potentially blinding ophthalmic disease missed by RRT.