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PURPOSE: To discuss the challenges and potential improvement strategies of cost-effectiveness analyses performed for therapeutics targeting inherited retinal diseases. DESIGN: Perspective METHODS: Literature review with discussion of current limitations and improvement recommendations. RESULTS: Cost-effectiveness analysis (CEA) performed for inherited retinal diseases (IRD) therapeutics has multiple limitations. First, the available methods used to measure health-related quality of life and health utilities can be inaccurate when used in IRDs. Second, the financial burden to patients and society by vision impairment associated with IRDs has been inadequately studied and includes a variety of expenditures ranging from direct costs of IRD specialty healthcare to indirect expenses associated with daily living activities. Third, our collective understanding is limited in the areas of IRD natural history and health benefits gained from new IRD treatments (e.g. gene therapies). Additionally, the therapeutic effect from a patient perspective and its duration of action is not fully understood. Due to the scarcity of data, CEA for newly approved therapies has relied on assumptions and creations of predictive models for both costs and health benefits for these new therapeutics in order to calculate the incremental cost-effectiveness ratio (ICER). CONCLUSIONS: CEA studies performed for IRD therapeutics have been limited by the currently established health utilities in ophthalmology and the lack of disease-specific information. The assumptions and extrapolations in these studies create substantial uncertainty in ICER results. An improved framework is required for CEA of IRD therapeutics in order to determine the cost-effectiveness of each therapy brought from clinical trials to clinical practice. TABLE OF CONTENTS STATEMENT: Cost-effectiveness analysis (CEA) studies performed for inherited retinal disease (IRD) therapeutics have been limited by the currently established health utilities in ophthalmology which lack disease specific information. The assumptions and extrapolations made in these studies are susceptible to large amounts of uncertainty in incremental cost-effectiveness ratio calculations. An improved framework for CEA of IRD therapeutics would better inform policy makers and other stakeholders, as these therapies progress from preclinical testing to clinical trials, and finally to clinical practice

Objective We sought to construct and validate a patient-reported outcome measure for screening and monitoring vision-related anxiety in patients with inherited retinal degenerations. Design Item-response theory and graded response modeling to quantitatively validate questionnaire items generated from qualitative interviews and patient feedback. Methods Patients at the Kellogg Eye Center (University of Michigan, Ann Arbor, Michigan, USA) with a clinical diagnosis of an inherited retinal degeneration (n = 128) participated in an interviewer-administered questionnaire. The questionnaire consisted of 166 items, 26 of which pertained to concepts of “worry” and “anxiety.” The subset of vision-related anxiety questions was analyzed by a graded response model using the Cai Metropolis–Hastings Robbins–Monro algorithm in the R software mirt package. Item reduction was performed based on item fit, item information, and item discriminability. To assess test–retest variability, 25 participants completed the questionnaire a second time 4 to 16 days later. Results The final questionnaire consisted of 14 items divided into 2 unidimensional domains: rod function anxiety and cone function anxiety. The questionnaire exhibited convergent validity with the Patient Health Questionnaire for symptoms of depression and anxiety. This vision-related anxiety questionnaire has high marginal reliability (0.81 for rod-function anxiety, 0.83 for cone-function anxiety) and exhibits minimal test–retest variability (ρ = 0.81 [0.64-0.91] for rod-function anxiety and ρ = 0.83 [0.68-0.92] for cone-function anxiety). Conclusions The Michigan Vision-Related Anxiety Questionnaire is a psychometrically validated 14-item patient-reported outcome measure to be used as a psychosocial screening and monitoring tool for patients with inherited retinal degenerations. It can be used in therapeutic clinical trials for measuring the benefit of an investigational therapy on a patient's vision-related anxiety.

Inherited retinal degenerations (IRDs) are a genotypically and phenotypically diverse group of conditions. Great strides have been made toward identifying the genetic basis for these conditions over the last 30 years-more than 270 different genes involved in syndromic and nonsyndromic forms of retinal dystrophies have now been identified. The identification of these genes and the improvement of clinical laboratory techniques have led to the identification of the genetic basis of disease in 56-76% of patients with IRDs through next generation sequencing and copy number variant analysis. Genetic testing is an essential part of clinical care for patients affected with IRDs and is required to confirm the diagnosis, understand the inheritance of the condition, and determine eligibility for gene-specific treatments or clinical trials. Despite the success achieved in determining the genetic cause of these conditions, several challenges remain, which must be considered when providing genetic testing and genetic counseling to patients. For this reason, an integrated team of ophthalmic and genetic clinicians who are familiar with these challenges is necessary to provide optimal comprehensive care to these patients.

To train a deep learning (DL) algorithm to perform fully automated semantic segmentation of multiple autofluorescence lesion types in Stargardt disease.Cross-sectional study with retrospective imaging data.The study included 193 images from 193 eyes of 97 patients with Stargardt disease.Fundus autofluorescence images obtained from patient visits between 2013 and 2020 were annotated with ground-truth labels. Model training and evaluation were performed using fivefold cross-validation.Dice similarity coefficients, intraclass correlation coefficients, and Bland-Altman analyses comparing algorithm-predicted and grader-labeled segmentations.The overall Dice similarity coefficient across all lesion classes was 0.78 (95% confidence interval [CI], 0.69-0.86). Dice coefficients were 0.90 (95% CI, 0.85-0.94) for areas of definitely decreased autofluorescence (DDAF), 0.55 (95% CI, 0.35-0.76) for areas of questionably decreased autofluorescence (QDAF), and 0.88 (95% CI, 0.73-1.00) for areas of abnormal background autofluorescence (ABAF). Intraclass correlation coefficients comparing the ground-truth and automated methods were 0.997 (95% CI, 0.996-0.998) for DDAF, 0.863 (95% CI, 0.823-0.895) for QDAF, and 0.974 (95% CI, 0.966-0.980) for ABAF.A DL algorithm performed accurate segmentation of autofluorescence lesions in Stargardt disease, demonstrating the feasibility of fully automated segmentation as an alternative to manual or semiautomated labeling methods.

BACKGROUND: Several novel treatments of inherited retinal degenerations have undergone phase I/IIa clinical trials with limited sample size, yet investigators must still determine if toxicity or an efficacy signal occurred or if the change was due to test-retest variability (TRV) of the measurement tool. MATERIALS AND METHODS: Synthetic datasets were used to compare three types of TRV estimators under different sample sizes, mean drift, skewness, and number of baseline measurements. RESULTS: Mixed effects models underestimated the standard deviation of measurement error (SDEM); the unbiased change score estimator method (UBS) was more accurate. The fixed effect model had less bias and smaller standard deviation than UBS if >2 baseline measurements. The change score estimator had no bias; other estimators introduced bias for lower variability. With sample size 2 baseline measurements. With non-ideal study parameters, investigators should at least quantify the error estimate present in their data analysis.

Major advances in the study of inherited retinal diseases (IRDs) have placed efforts to develop treatments for these blinding conditions at the forefront of the emerging field of precision medicine. As a result, the growth of clinical trials for IRDs has increased rapidly over the past decade and is expected to further accelerate as more therapeutic possibilities emerge and qualified participants are identified. Although guided by established principles, these specialized trials, requiring analysis of novel outcome measures and endpoints in small patient populations, present multiple challenges relative to study design and ethical considerations. This position paper reviews recent accomplishments and existing challenges in clinical trials for IRDs and presents a set of recommendations aimed at rapidly advancing future progress. The goal is to stimulate discussions among researchers, funding agencies, industry, and policy makers that will further the design, conduct, and analysis of clinical trials needed to accelerate the approval of effective treatments for IRDs, while promoting advocacy and ensuring patient safety.

Purpose To create a psychometrically validated patient-reported outcome measure for inherited retinal degenerations. Design Qualitative and quantitative patient-reported outcome (PROs) questionnaire development using item response theory validation. Methods One hundred twenty-eight patients with a diagnosis of an inherited retinal degeneration at the Kellogg Eye Center (University of Michigan) were recruited and administered a 166-item questionnaire comprising 7 expert-defined domains. The questionnaire was re-administered 4-16 days later to a subset of 25 participants to assess test-retest variability. Graded response models were fit by Cai's Metropolis-Hastings Robbins-Monro algorithm using the R (version 3.6.3) package mirt. Model data were fit to assess questionnaire dimensionality, to estimate item information, and to score participants. Poorly functioning items were removed, and the model was refit to create the final questionnaire. Results The psychometrically validated PROs measure was reduced to a 59-item questionnaire measuring 7 unidimesnional domains: central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision, mesopic peripheral vision, and photosensitivity. A total of 39 items were removed because of poor factor loading, low item information, poor person-ability differentiation, or high item-level interdependence. This novel questionnaire produces a reliable domain score for person ability that does not show significant test-retest variability across repeated administration. Conclusions The final PRO questionnaire, known as the Michigan Retinal Degeneration Questionnaire, is psychometrically validated and available for use in the evaluation of patients with inherited retinal degenerations.

OBJECTIVE: To provide a comprehensive review of the ocular manifestations, outcomes, and genetic findings in patients with Coats-like retinitis pigmentosa (RP). DESIGN: Multi-center, retrospective, non-consecutive case series. SUBJECTS: Patients with a diagnosis of RP presenting with Coats-like exudative vitreoretinopathy between January 1, 2008 and October 1, 2019. METHODS: Evaluation of ocular findings at RP diagnosis and at time of presentation of Coats-like exudative vitreoretinopathy, pedigree analysis, genetic testing, retinal imaging, and anatomic outcomes after treatment. MAIN OUTCOME MEASURES: Visual acuity, ophthalmoscopy, optical coherence tomography, fluorescein angiography, and identification of genetic mutations. RESULTS: 9 patients diagnosed with RP and presenting with Coats-like exudative vitreoretinopathy were included. Median age at time of RP diagnosis was 8 years (range, 1 – 22 years), and median age at presentation of Coats-like exudative vitreoretinopathy was 18 years (range 1 – 41 years). 7 patients were female, and 2 were male. The genetic cause of disease was identified in 6 patients. 3 patients presented with Coats-like fundus findings at the time of RP diagnosis. Exudative retinal detachment (ERD) localized to the infratemporal periphery was present in all cases, with bilateral disease observed in 7 patients. In all treated patients, focal laser photocoagulation (LP) was used to treat leaking telangiectasias and to limit further ERD expansion. Cystoid macular edema refractory to carbonic anhydrase inhibitor therapy, and ultimately amenable to treatment with intravitreal anti-vascular endothelial growth factor injection was observed in 4 patients. CONCLUSION: Coats-like vitreoretinopathy is present in up to 5% of all RP patients. The term “Coats-like RP” is colloquially used to describe this disease state which can present at the time of RP diagnosis, or more commonly develops late during the clinical course of patients with longstanding RP. Coats-like RP is distinct from Coats disease in that exudative pathology occurs exclusively in the setting of a coexisting RP diagnosis, is restricted to the infratemporal retina, can affect both eyes, and does not demonstrate a male sex bias. Given the risk of added vision loss posed by exudative vitreoretinopathy in patients with RP, a heightened awareness of this condition is critical in facilitating timely intervention.

PURPOSE: To assess the retinal anatomy and array position in the Argus II Retinal Prosthesis recipients. DESIGN: Prospective, non-comparative cohort study METHODS: Setting: international multicenter study Patients: Argus II recipients enrolled in the Post-Market Surveillance Studies. Procedures: Spectral-domain Optical Coherence Tomography images collected for the Surveillance Studies (NCT01860092 and NCT01490827) were reviewed. Baseline and postoperative macular thickness, electrode-retina distance (gap), optic disc-array overlap, and preretinal membrane presence were recorded at 1, 3, 6, and 12 months. Main Outcome Measures: Axial retinal thickness and axial gap along the array’s long axis (a line between the tack and handle), maximal retinal thickness and maximal gap along a B-scan near the tack, midline, and handle. RESULTS: Thirty-three patients from 16 surgical sites in the United States and Germany were included. Mean axial retinal thickness increased from month 1 through month 12 at each location, but reached statistical significance only at the array midline (p- value=0.007). The rate of maximal thickness increase was highest near the array midline (slope=6.02, p=0.004), compared to the tack (slope=3.60, p

Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration.Retrospective review of children ≤ 17 years old with a mutation-proven retinal dystrophy. Objective clinical disease activity was assessed by a retinal degeneration specialist masked to GVF results. Digital quantification of GVF area was performed.Twenty-nine children (58 eyes), ages 5-16, were identified. GVF area increased with age despite progression in 20 children and clinical stability in nine children. Mean ± standard error increase in GVF area/year was 333 ± 130 mmIn a substantial proportion of children with mutation-proven retinal dystrophies, there is a significant increase in GVF area with age, particularly those12 years, despite progression or stability of disease. These findings suggest that change in GVF area in children with retinal dystrophies can be an unreliable measure of response to treatment and on which to base appropriate counseling about visual impairment.

Purpose To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. Methods This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. Results Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. Conclusion Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

IMPORTANCE: The benefits of no-cost genetic testing initiatives have not been characterized. The no-cost My Retina Tracker Genetic Testing Study (MRT-GTS) research registry for inherited retinal degenerations (IRDs) was launched in 2017 in the US. OBJECTIVE: To investigate the associations of MRT-GTS implementation and patient characteristics with access to genetic testing for IRDs. DESIGN, SETTING, AND PARTICIPANTS: In a cross-sectional design, analysis of new patients evaluated 12 months before (July 1, 2016, to June 13, 2017) and 12 months after (June 14, 2017, to June 30, 2018) MRT-GTS implementation at a single academic referral eye center was conducted. Participants included 369 patients with IRD. Data analysis was conducted from February to June 2020. MAIN OUTCOMES AND MEASURES: Change in rates of successfully obtaining genetic testing, odds ratios (ORs) of association between patient characteristics and obtaining testing, and days elapsed from clinic visit to reporting of results. RESULTS: Among 369 patients (mean [SD] age, 39.5 [20.8] years; 193 [52.3%] women), 144 were evaluated in the pre–MRT-GTS period and 225 in the post–MRT-GTS period. The baseline rate of successfully obtaining testing was 51.4% (95% CI, 42.6%-60.2%). The initiation of MRT-GTS was associated with a 28.9-percentage point increase in testing rate (95% CI, 16.7%-41.1%; P

Purpose The goals of this study were to evaluate the safety of office-based vitreous sampling, and determine the utility of these samples with multiplex cytokine analysis. Methods Vitreous samples were collected from office-based needle aspiration and the rate of adverse events during follow-up was reviewed. The vitreous cytokine concentrations in a subset of patients with diabetic macular edema (DME) were analyzed using a 42 plex-cytokine bead array. These results were compared with vitreous cytokine concentrations in proliferative diabetic retinopathy (PDR) and controls (macular hole, epiretinal membrane, symptomatic vitreous floaters) from pars plana vitrectomy. Results An adequate volume of vitreous fluid (100-200 μL) was obtained in 52 (88%) of 59 office-based sampling attempts. The average length of follow-up was 300 days (range, 42-926 days). There were no complications, including cataract, retinal tear or detachment, and endophthalmitis. Two patients (3%) had posterior vitreous detachments within 3 months. Vitreous cytokine concentrations were measured in 44 patients: 14 controls, 13 with DME, and 17 with PDR. The concentration of ADAM11, CXCL-10, IL-8, and PDGF-A were higher in PDR compared with controls and DME. The concentration of IL-6 was higher in PDR compared with controls, but not compared with DME. Conclusions Office-based vitreous aspiration is safe and yields high-quality samples for multiplex vitreous cytokine analysis. Significant elevations of vitreous cytokines were found in PDR compared with DME and controls, including the novel finding of elevated ADAM11. As such, office-based aspiration is a safe and effective means to identify vitreous factors associated with vitreoretinal disease.

The Argus II retinal prosthesis (Second Sight Medical Products, Sylmar, CA, USA) is an electronic epiretinal implant designed for use in patients with end-stage retinitis pigmentosa, as well as for other outer retinal degenerative conditions, such as choroideremia, Leber’s congenital amaurosis, Bardet-Biedl syndrome, Usher syndrome and rod–cone disease.1 This device was tested in a clinical trial of 30 subjects in the USA and in Europe to measure the rate of serious adverse events (SAEs) and to assess its effects on functional vision and visual acuity.2–4 Subjects performed better on visual tasks with the device turned on and retained these improvements at 5 years postsurgery.4 Additionally, an acceptable safety profile enabled approval of the device for consumer use by the European regulatory authorities in 2011 (Conformite Europeenne (CE) mark) and by the US Food and Drug Administration (FDA) in 2013 (FDA approval). The implant is composed of an extraocular component, namely, an electronics case and implant coil, as well as an intraocular component involving a 60-electrode array that is tacked over the macula (figure 1). The extraocular and intraocular components are connected by a trans-scleral silicone-coated polyamide electrode cable, and the implantation procedure involves a 5.2 mm pars plana sclerotomy incision to insert the electrode array and the electrode cable into the eye. The sclerotomy is then sutured around the cable and covered by an allograft or autograft material.5 Figure 1 The Argus II retinal prosthesis. Labelled image of the Argus II implant (adapted from Humayun et al 2). As with any system having both intraocular and extraocular components, the trans-scleral electrode cable that traverses the sclerotomy permanently is a high-risk feature of the device, as leakage through the pars plana incision can result in chronic hypotony. The percentages of clinical trial subjects who experienced hypotony were 10.0% at …

© 2015 The Association for Research in Vision and Ophthalmology, Inc. Although rare in the general population, retinal dystrophies occupy a central position in current efforts to develop innovative therapies for blinding diseases. This status derives, in part, from the unique biology, accessibility, and function of the retina, as well as from the synergy between molecular discoveries and transformative advances in functional assessment and retinal imaging. The combination of these factors has fueled remarkable progress in the field, while at the same time creating complex challenges for organizing collective efforts aimed at advancing translational research. The present position paper outlines recent progress in gene therapy and cell therapy for this group of disorders, and presents a set of recommendations for addressing the challenges remaining for the coming decade. It is hoped that the formulation of these recommendations will stimulate discussions among researchers, funding agencies, industry, and policy makers that will accelerate the development of safe and effective treatments for retinal dystrophies and related diseases.

An 85-year-old man with remote thermal sclerostomy and Descemet's stripping automated endothelial keratoplasty (DSAEK) in the right eye presented urgently for pain and blurred vision in that eye. Examination revealed bleb purulence and vitreous cellular aggregates concerning for endophthalmitis. Microscopy of a vitreous sample revealed yeast and pseudohyphae. He developed corneal infiltrates consistent with fungal infection. Therapy included topical, intravitreal, and systemic antifungals voriconazole and amphotericin. Fungal pathogens have very rarely been reported to cause bleb-associated endophthalmitis and should be considered in addition to bacterial pathogens. Vitreous aspiration should be performed in all cases of bleb-related endophthalmitis and include fungal studies. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:691–693.]

We report an unusual phenotype in a child with a clinical diagnosis of recessive Stargardt disease (STGD1) and two pathogenic variants in the ABCA4 gene. Typically, the diagnosis of early-onset STGD1 is challenging because children may present with a variety of fundus changes and a variable rate of progression. At the time of his initial visit, the 6-year-old boy presented with 20/200 OD (right eye) and 20/150 OS (left eye), symmetrical mild foveal atrophy without flecks on fundus exam, and foveal hypoautofluorescence surrounded by a homogeneous hyperautofluorescent background on wide-field fundus autofluorescence. Over 4 years of follow-up, the retinal atrophy continued to progress, resulting in two well-defined and concentric hyperautofluorescent rings: one ring located at the posterior pole and the other located around the peripapillary region. Visual acuity also deteriorated to counting fingers at 4ft OD and 20/500 OS. To the best of our knowledge, this phenotype has not been previously described with the ABCA4 gene.

Next generation sequencing (NGS) technology, with the ability to sequence many genomic regions at once, can provide clinicians with increased information, in the form of more mutations detected. Discussions on broad testing technology have largely been focused on incidental findings, or unanticipated results related to diseases beyond the primary indication for testing. By examining multiple genes that could be responsible for the patient's presentation, however, there is also the possibility of unexpected results that are related to the reason genetic testing was ordered. We present a case study where multiple potentially causative mutations were detected using NGS technology. This case raises questions of scientific uncertainty, and has important implications for medical management and secondary studies. Clinicians and genetic counselors should be aware of the potential for increased information to affect one's understanding of genetic risk, and the pre- and post-testing counseling process.

To describe previously unreported clinical characteristics of persistent placoid maculopathy, suggest a pathogenesis of persistent placoid maculopathy using multimodal imaging, and provide evidence supporting high-dose immunosuppression for short-term management.Retrospective case series.The cohort included 3 men with ages ranging from 55 years to 68 years. Persistent placoid maculopathy was bilateral in all 3 patients and characterized by recurrence and choroidal neovascularization in 1 patient. The median time to presentation was 3 months (range, 2-24 months), and follow-up was 8 months (range, 3-24 months). Previously unreported findings of far-peripheral lesions and optic nerve hyperfluorescence on fluorescein angiography were noted in separate individuals. In addition, findings from multimodal imaging supported an inflammatory pathogenesis of the inner choroid and the outer retina. Finally, all patients experienced substantial improvement to structural and functional measures in at least one eye within days to weeks of initiating high-dose corticosteroids (0.75-1 mg/kg/day).Multimodal imaging suggests that persistent placoid maculopathy has an inflammatory pathogenesis that may affect the inner choroid with secondary changes to the retinal pigment epithelium and the outer retina. High-dose corticosteroids may provide short-term benefit.

The Early Treatment Diabetic Retinopathy Study (ETDRS) and other standardized classification schemes have laid a foundation for tremendous advances in the understanding and management of diabetic retinopathy (DR). However, technological advances in optics and image analysis, especially optical coherence tomography (OCT), OCT angiography (OCTa), and ultra-widefield imaging, as well as new discoveries in diabetic retinal neuropathy (DRN), are exposing the limitations of ETDRS and other classification systems to completely characterize retinal changes in diabetes, which we term diabetic retinal disease (DRD). While it may be most straightforward to add axes to existing classification schemes, as diabetic macular edema (DME) was added as an axis to earlier DR classifications, doing so may make these classifications increasingly complicated and thus clinically intractable. Therefore, we propose future research efforts to develop a new, comprehensive, and clinically useful classification system that will identify multimodal biomarkers to reflect the complex pathophysiology of DRD and accelerate the development of therapies to prevent vision-threatening DRD.

PURPOSE. To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2. METHODS. Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA. RESULTS. We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region). CONCLUSIONS. This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration. (Invest Ophthalmol Vis Sci. 2012;53:8232-8237) DOI:10.1167/iovs.12-11025 (Less)

To identify factors associated with best-corrected visual acuity (BCVA) presentation and 2-year outcome in 479 intermediate, posterior, and panuveitic eyes.Cohort study using randomized controlled trial data.Multicenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and at 2 years follow-up used gold-standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and 2-year change in BCVA.Baseline factors significantly associated with reduced BCVA included age ≥50 vs50 years; posterior vs intermediate uveitis; uveitis duration10 vs6 years; anterior chamber (AC) flaregrade 0; cataract; macular thickening; and exudative retinal detachment. Over 2 years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (P = .52) and 10 letters (P.001), respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, resolution of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or10 vs6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening.Intermediate, posterior, and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation.