Extensive Macular Atrophy with Pseudodrusen-like appearance: Progression Kinetics and Late-Stage Findings.

PURPOSE: To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP). DESIGN: Retrospective cohort study. PARTICIPANTS: Seventy-eight patients (156 eyes) affected by EMAP. METHODS: We collected data on best-corrected visual acuity, kinetic perimetry, OCT, short-wavelength autofluorescence, and near-infrared autofluorescence findings. Genetic testing for the TIMP3 and C1QTNF5 genes was performed via Sanger sequencing for 58 patients, with no pathogenic variants identified. MAIN OUTCOME MEASURES: The primary outcomes were best-corrected visual acuity at the last examination, visual field at the last examination, and incidence rates and time-to-event curves for blindness with the United States Social Security Administration and World Health Organization (WHO) criteria, foveal involvement, and atrophy enlargement beyond the 30° and 55° field of view. Imaging findings at the last examination were secondary outcomes. RESULTS: At the most recent visit, mean age was 70.9 ± 5.2 years. Using United States criteria, 58.1% of the patients were blind, and 25.8% were blind according to WHO criteria. All eyes showed large central scotomas, which were associated with visual field constriction in 22.2% of eyes. We detected focal openings or large dehiscences of Bruch's membrane (BM) in 25.4% of eyes. Near-infrared autofluorescence showed increased visibility of the choroidal vessels beyond the atrophy in 87.2% of eyes. The incidence rates for blindness were 3.95 per 100 patient-years with United States criteria and 1.54 per 100 patient-years according to WHO criteria. The incidence rates were 22.8 per 100 eye-years for foveal involvement, 12.0 per 100 eye-years for atrophy enlargement beyond 30°, and 6.6 per 100 eye-years for atrophy enlargement beyond 55°. The estimates were not influenced by the age at onset. CONCLUSIONS: We identified characteristic imaging findings, including BM ruptures, in elder patients with EMAP and calculated incidence rates for different functional and anatomic outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Static Perimetry in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) Study: Assessment Through 2 Years.

PURPOSE: To evaluate disease progression using static perimetry (SP) in patients with USH2A-related retinal degeneration, including Usher syndrome type 2 (USH2) and nonsyndromic autosomal recessive retinitis pigmentosa. DESIGN: Prospective, observational cohort study. METHODS: A total of 102 patients with biallelic disease-causing sequence variants in USH2A with baseline best-corrected visual acuity (BCVA) letter score ≥54 were recruited from 16 clinical sites in Europe and North America. SP, BCVA, full-field stimulus thresholds, spectral domain optical coherence tomography macular scans, and fundus-guided mesopic microperimetry were performed at baseline and annually. The main outcome measures were total hill of vision (VTOT), hill of vision in the central 30° (V30), VTOT minus V30 (VPERIPH), and mean sensitivity. RESULTS: The average decline (95% CI) was 2.05 (1.40, 2.70) decibel-steradian (dB-sr)/y for VTOT, 0.48 (0.32, 0.65) dB-sr/y for V30, 1.53 (0.97, 2.08) dB-sr/y for VPERIPH, and 0.55 (0.40, 0.71) dB/y for mean sensitivity. Average percentage decline per year was 8.3 (5.5, 11.1) for VTOT, 5.2 (3.0, 7.4) for V30, 16.0 (9.5, 22.0) for VPERIPH, and 5.1 (3.5, 6.7) for mean sensitivity. Changes from baseline to year 2 in all SP measures were highly correlated (r's ranging from 0.52 [V30 vs VPERIPH] to 0.98 [VTOT vs VPERIPH]). CONCLUSIONS: Quantitative measures of SP declined significantly over 2 years in USH2A-related retinal degeneration. The annual percentage rate of change was greatest for VTOT and VPERIPH, whereas V30 and mean sensitivity changed least, reflecting earlier and more severe peripheral degeneration compared with central loss.

Characteristics associated with barriers to eye care: A cross-sectional survey at a free vision screening event.

INTRODUCTION: Social determinants of health can limit access to regular eye care, but their role in ophthalmology is underexamined. The purpose of this study is to assess the relationship between patient characteristics and self-reported barriers to eye care. METHODS: This anonymous, cross-sectional survey was conducted at a two-day free eye clinic event in Pittsburgh, Pennsylvania. Adult patients presenting for vision screening were eligible to participate. Patient characteristics (demographics, health status) and self-reported barriers to eye care were collected. Predictors of barriers to eye care were analyzed using binary logistic regression. RESULTS: Of 269 eligible, consecutive patients approached for survey completion, 183 comprised the volunteer sample. The 183 participants (105 female patients [59%]) had a mean (standard deviation) age of 53 (15) years, and generally self-identified as Black (74, 46%) or White (67, 41%). While a third reported having no health insurance (60, 34%), the remaining two-thirds of participants had public (84, 48%) or private coverage (34, 19%). Three-quarters of respondents reported at least one barrier to receiving regular eye care (136, 76%), most commonly medical costs (89, 50%) and insurance issues (73, 41%). Not having health insurance or vision insurance was strongly associated with reporting at least one barrier to care (OR 5.00, p=0.002, and OR 7.46, p<0.001, respectively). Those with self-reported eye disease were more likely to report transportation difficulties (OR 4.45, p=0.013), and employed participants reported difficulty getting time off work to attend eye exams (OR 7.73, p=0.002). Finally, compared to Black race, White race was associated with a higher likelihood of reporting any barrier to care (OR 2.79, p=0.013). CONCLUSION: Three-quarters of vision screening attendees reported at least one barrier to regular eye care, most commonly medical costs and insurance.

Addressing Social Determinants of Vision Health.

Social determinants of health encompass the quality of an individual's social and physical environment and its effect on health outcomes. Disparities in these social and environmental factors have a significant role in vision health disparities and inequity in eye care. In this review, we discuss how disparities in visual impairment and eye care utilization are affected by each of the five core domains of social determinants of health, namely economic stability (income, employment, and food security), education (education level and health literacy), health care access (insurance and medical costs), neighborhood environment (housing conditions, home ownership, pollution, and crime), and social context (race and racism). Moreover, we describe a framework by which ophthalmologists can take action to address social determinants of vision health. These actionable strategies are guided by recommendations from the National Academies of Sciences, Engineering, and Medicine and have five complementary components to address social needs: awareness (screening for social needs), assistance (connecting patients with social care resources), adjustment (altering clinical care in recognition of social needs), alignment (understanding social assets and collaborating with community organizations), and advocacy (promoting policies to address social needs). Addressing social determinants of health is complex but achievable through collaborative strategies. Ophthalmologists have an important leadership role in addressing eye care disparities by taking action on underlying social determinants of vision health.

Laser Doppler holography of the anterior segment for blood flow imaging, eye tracking, and transparency assessment.

Laser Doppler holography (LDH) is a full-field blood flow imaging technique able to reveal human retinal and choroidal blood flow with high temporal resolution. We here report on using LDH in the anterior segment of the eye without making changes to the instrument. Blood flow in the bulbar conjunctiva and episclera as well as in corneal neovascularization can be effectively imaged. We additionally demonstrate simultaneous holographic imaging of the anterior and posterior segments by simply adapting the numerical propagation distance to the plane of interest. We used this feature to track the movements of the retina and pupil with high temporal resolution. Finally, we show that the light backscattered by the retina can be used for retro-illumination of the anterior segment. Hence digital holography can reveal opacities caused by absorption or diffusion in the cornea and eye lens.

Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) Study: Design and Baseline Characteristics (Report No. 1).

PURPOSE: To describe the study design and characteristics at first visit of participants in the longitudinal Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) study. METHODS: Scotopic microperimetry (sMP) was performed in one designated study eye in a subset of participants with molecularly proven ABCA4-associated Stargardt disease (STGD1) enrolled in a multicenter natural history study (ProgStar). Study visits were every 6 months over a period ranging from 6 to 24 months, and also included fundus autofluorescence (FAF). RESULTS: SMART enrolled 118 participants (118 eyes). At the first visit of SMART, the mean sensitivity in mesopic microperimetry was 11.48 (±5.05; range 0.00-19.88) dB and in sMP 11.25 (±5.26; 0-19.25) dB. For FAF, all eyes had a lesion of decreased autofluorescence (mean lesion size 3.62 [±3.48; 0.10-21.46] mm2), and a total of 76 eyes (65.5%) had a lesion of definitely decreased autofluorescence with a mean lesion size of 3.46 (±3.60; 0.21-21.46) mm2. CONCLUSIONS: Rod function is impaired in STGD1 and can be assessed by sMP. Testing rod function may serve as a potential outcome measure for future clinical treatment trials. This is evaluated in the SMART study.

The cost-effectiveness of the Argus II retinal prosthesis in Retinitis Pigmentosa patients.

BACKGROUND: Retinitis Pigmentosa (RP) is a hereditary genetic disease causing bilateral retinal degeneration. RP is a leading cause of blindness resulting in incurable visual impairment and drastic reduction in the Quality of life of the patients. Second Sight Medical Products Inc. developed Argus II, a retinal prosthesis system for treating RP. Argus II is the world's first ever-commercial implant intended to restore some vision in the blind patients. The objective of this study was to assess the cost-effectiveness of the Argus® II Retinal Prosthesis System (Argus II) in Retinitis Pigmentosa (RP) patients. METHOD: A multi -state transition Markov model was developed to determine the cost-effectiveness of Argus II versus usual care in RP from the perspective of healthcare payer. A hypothetical cohort of 1000 RP patients aged 46 years followed up over a (lifetime) 25-year time horizon. Health outcomes were expressed as quality adjusted life years (QALYs) and direct healthcare costs expressed in 2012 €. Results are reported as incremental cost per ratios (ICERs) with outcomes and costs discounted at an annual rate of 3.5%. RESULTS: The ICER for Argus II was €14,603/QALY. Taking into account the uncertainty in model inputs the ICER was €14,482/QALY in the probabilistic analysis. In the scenarios of an assumption of no reduction on cost across model visual acuity states or a model time horizon as short as 10 years the ICER increased to €31,890/QALY and €49,769/QALY respectively. CONCLUSION: This economic evaluation shows that Argus II is a cost-effective intervention compared to usual care of the RP patients. The lifetime analysis ICER for Argus II falls below the published societal willingness to pay of EuroZone countries.

Functional and high resolution retinal imaging assessment in a case of ocular siderosis.

PURPOSE: To report new findings in a case of ocular siderosis explored by high resolution angiography and adaptive optics (AO). METHODS: We report data on a 40-year-old man with an intraocular foreign body (IOFB) embedded in the sclera after hammering. RESULTS: Nine months after this accident, the patient presented with full-field electroretinogram (FF-ERG) abnormalities. Subsequent IOFB extraction was performed. One month after the surgery, high resolution angiography showed for the first time small iron particles all over the inner retinal surface. Spreading of these deposits was followed by inflammatory prepapillary new vessels and venous retinal vasculatis, which spontaneously resolved within a few months. ERG responses became slightly electronegative at this time. Clearance of the iron particles was followed over a year with AO and ERG recording. AO revealed an arterial tropism with a decrease in the amount of particles overtime, which may be consistent with macrophagic activity. CONCLUSION: High resolution angiography and AO are new tools, combined with electrophysiology, to better understand ocular siderosis pathophysiology.

Relative frequencies of inherited retinal dystrophies and optic neuropathies in Southern France: assessment of 21-year data management.

PURPOSE: Inherited retinal dystrophies (IRDs) and inherited optic neuropathies (IONs) are rare diseases defined by specific clinical and molecular features. The relative prevalence of these conditions was determined in Southern France. METHODS: Patients recruited from a specialized outpatient clinic over a 21-year period underwent extensive clinical investigations and 107 genes were screened by polymerase chain reaction/sequencing. RESULTS: There were 1957 IRD cases (1481 families) distributed in 70% of pigmentary retinopathy cases (56% non-syndromic, 14% syndromic), 20% maculopathies and 7% stationary conditions. Patients with retinitis pigmentosa were the most frequent (47%) followed by Usher syndrome (10.8%). Among non-syndromic pigmentary retinopathy patients, 84% had rod-cone dystrophy, 8% cone-rod dystrophy and 5% Leber congenital amaurosis. Macular dystrophies were encountered in 398 cases (30% had Stargardt disease and 11% had Best disease). There were 184 ION cases (127 families) distributed in 51% with dominant optic neuropathies, 33% with recessive/sporadic forms and 16% with Leber hereditary optic neuropathy. Positive molecular results were obtained in 417/609 families with IRDs (68.5%) and in 27/58 with IONs (46.5%). The sequencing of 5 genes (ABCA4, USH2A, MYO7A, RPGR and PRPH2) provided a positive molecular result in 48% of 417 families with IRDs. Except for autosomal retinitis pigmentosa, in which less than half the families had positive molecular results, about 75% of families with other forms of retinal conditions had a positive molecular diagnosis. CONCLUSIONS: Although gene discovery considerably improved molecular diagnosis in many subgroups of IRDs and IONs, retinitis pigmentosa, accounting for almost half of IRDs, remains only partly molecularly defined.

Treating retinal vein occlusions in France, Germany, and Italy: an analysis of treatment patterns, resource consumption, and costs.

PURPOSE: To describe treatment patterns among patients with central or branch retinal vein occlusion (CRVO or BRVO) in France, Germany, and Italy, and to estimate retinal vein occlusion (RVO)-related direct medical costs. METHODS: We used a retrospective chart review to determine 18-month RVO-related resource utilization and calculate 12-month health care costs. Country-specific unit costs (€) were assigned to each resource from the perspective of the health care payer. Costs for France and Germany were based on 2005, and for Italy on 2007 values. RESULTS: Data from a total of 109 BRVO and 119 patients with CRVO were used in the analysis. Laser therapy was the most commonly used intervention in Germany, for both CRVO and patients with BRVO (95%-98% of treatments), while patients in France with either condition had triamcinolone injections most often (63%-67% of treatments). Injections were also administered frequently in Italy and were the most common treatment for CRVO (50%), whereas patients with BRVO used laser therapy most often (41%). Inpatient treatment was most common in Germany (42% of CRVO and 34% of patients with BRVO), and did not occur at all in Italy except for day admissions. Total costs were higher for patients with CRVO in all countries. Most costs in Italy and France were attributable to outpatient treatment. In Germany, hospitalization made up the largest proportion of costs (80%), although more patients used outpatient services. CONCLUSIONS: Approaches to treating BRVO and CRVO vary across European countries. Development of agreed-upon guidelines would support consistency in patient care and reimbursement policy.

Association between visual acuity and medical and non-medical costs in patients with wet age-related macular degeneration in France, Germany and Italy.

INTRODUCTION: Exudative ('wet') age-related macular degeneration (ARMD) is the major cause of blindness in Western developed countries. Treatments aimed at preserving vision are already available and new compounds are under development. Micro-economics information will be pivotal to justifying forthcoming investment. OBJECTIVE: This study sought to investigate the costs of exudative ARMD in patients who were actively treated at ophthalmology referral centres in three European countries: France, Germany and Italy. METHOD: This cross-sectional observational study was conducted in France, Germany and Italy in 2004. The following data were collected: ARMD description, visual acuity (VA), and the medical and non-medical resources used for ARMD in the preceding year. The economic perspective was that of society. ANOVA for cost variables estimated the impact of ARMD per eye, adjusted for sex and age. Both hospital and ambulatory eye centres were included. Patients with exudative ARMD were stratified into four levels of severity using VA thresholds of 20/200 for the worst eye (WE) and 20/40 for the best eye (BE). The main outcome measure was medical and non-medical costs. RESULTS: 360 patients were included (females 60%; mean age 77 years; mean interval since diagnosis 2.3 years). The two groups with the greatest difference in severity of VA loss consisted of BE >or= 20/40, WE >or= 20/200 (27.2% of patients) and BE <20/40, WE <20/200 (25.5% of patients). Total cost was two-thirds medical and one-third non-medical. Total costs increased with ARMD severity and were 1.1-2 times greater for severe disease compared with less severe disease. Average medical costs (2004 values) in France were euro 3714, compared with euro 1810 in Germany and euro 2020 in Italy, and showed slight increases with ARMD severity. Non-medical costs were significantly higher for patients with severe disease and highest in Germany. CONCLUSION: The impact of ARMD on costs was considerable and a positive correlation was found between total costs and ARMD severity. Differences among countries were partly explained by differences in customary care delivery.