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To investigate the distribution of genotypes and natural history of ABCA4 -associated retinal disease in a large cohort of patients seen at a single institution. Retrospective, single-institution cohort review. Patients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4. DNA samples from participants were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing. Charts were reviewed, and clinical data were tabulated. The pathogenic severity of the most common alleles was estimated by studying groups of patients who shared 1 allele. Groups of patients with shared genotypes were reviewed for evidence of modifying factor effects. Age at first uncorrectable vision loss, best-corrected visual acuity, and the area of the I2e isopter of the Goldmann visual field. A total of 460 patients from 390 families demonstrated convincing clinical features of ABCA4 -associated retinal disease. Complete genotypes were identified in 399 patients, and partial genotypes were identified in 61. The median age at first vision loss was 16 years (range, 4–76 years). Two hundred sixty-five families (68%) harbored a unique genotype, and no more than 10 patients shared any single genotype. Review of the patients with shared genotypes revealed evidence of modifying factors that in several cases resulted in a > 15-year difference in age at first vision loss. Two hundred forty-one different alleles were identified among the members of this cohort, and 161 of these (67%) were found in only a single individual. ABCA4 -associated retinal disease ranges from a very severe photoreceptor disease with an onset before 5 years of age to a late-onset retinal pigment epithelium–based condition resembling pattern dystrophy. Modifying factors frequently impact the ABCA4 disease phenotype to a degree that is similar in magnitude to the detectable ABCA4 alleles themselves. It is likely that most patients in any cohort will harbor a unique genotype. The latter observations taken together suggest that patients' clinical findings in most cases will be more useful for predicting their clinical course than their genotype. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Patients with incurable corneal diseases experience visual impairment (VI) despite having a healthy retina and optic pathway. Low-vision aids (LVAs) can optimize the use of remaining vision through magnification and contrast enhancement, but do not harness the full visual capacity because they rely on the optic media. Therefore, we investigated a novel laser eyewear (LEW) technology that bypasses the anterior segment of the eye. Images captured by an integrated camera are projected directly onto the retina using a low-energy laser. The patient is able to view a full-color video, realized as augmented reality. We aimed to evaluate the efficacy of the LEW to enhance the vision of individuals with corneal diseases. Prospective, randomized, crossover clinical trial. We examined the retinal projection glasses in 21 patients (25–69 years) with VI (0.7 logarithm of the minimum angle of resolution [logMAR] or worse) resulting from corneal diseases. Patients with comorbidities that impact vision, such as retinal disorders, were excluded. Standardized measurements of visual acuity (VA) for near vision (NV) and distance vision (DV) were conducted using ETDRS charts with the respective best correction (BC) and then with LEW. In addition reading speed, vision-related quality of life (QoL) and capacity to carry out daily tasks were assessed at an initial visit and at 2 subsequent visits after a home phase with and without the device. Six weeks after last use of the LEW, an ophthalmologic examination including spectral-domain-OCT or full-field-electroretinography was conducted and compared with baseline findings to evaluate the safety of the device. Four patients participated and completed a subsequent 12-month follow-up phase. Improvement of VA using the LEW. Secondary objectives included safety, reading speed, QoL, and usability in daily activities. The mean VA in patients with VI was improved by 0.43 logMAR in DV using the LEW compared with BC (P < 0.0001). Using the ×2 magnification mode of the LEW resulted in an average improvement of 0.66 logMAR compared with BC (P < 0.0001). In NV, an increase of 0.47 logMAR was achieved compared with BC (P < 0.0001). Although only 4 of 21 participants were able to read with BC, 17 of 21 participants were able to read with the LEW. Quality of life significantly improved in the 17 participants who completed all visits. We demonstrated that the retinal projection glasses resulted in enhanced VA for all participants by directly projecting images onto the intact retina. In future, the LEW could represent a new option as an LVA for patients with corneal diseases. No pathological alterations were observed in the safety assessments. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

To describe the largest, most phenotypically and genetically diverse cohort of patients with inherited retinal disease (IRD)-related Coats-like vasculopathy (CLV). Multicenter retrospective cohort study. A total of 67 patients with IRD-related CLV. Review of clinical notes, ophthalmic imaging, and molecular diagnosis from 2 international centers. Visual function, retinal imaging, management, and response to treatment were evaluated and correlated. The prevalence of IRD-related CLV was 0.5%; 54% of patients had isolated retinitis pigmentosa (RP), 21% had early-onset severe retinal dystrophy, and less frequent presentations were syndromic RP, sector RP, cone-rod dystrophy, achromatopsia, PAX6 -related dystrophy, and X-linked retinoschisis. The overall age of patients at CLV diagnosis was 30.7 ± 16.9 years (1–83). Twenty-one patients (31%) had unilateral CLV, and the most common retinal features were telangiectasia, exudates, and exudative retinal detachment (ERD) affecting the inferior and temporal retina. Macular edema/schisis was observed in 26% of the eyes, and ERD was observed in 63% of the eyes. Fifty-four patients (81%) had genetic testing, 40 of whom were molecularly solved. Sixty-six eyes (58%) were observed, 17 eyes (15%) were treated with a single modality, and 30 eyes (27%) had a combined approach. Thirty-five eyes (31%) were "good responders," 42 eyes (37%) were "poor responders," 22 eyes (19%) had low vision at baseline and were only observed, and 12 eyes (11%) did not have longitudinal assessment. Twenty-one observed eyes (62%) responded well versus 14 (33%) treated eyes. Final best-corrected visual acuity was significantly worse than baseline (P = 0.002); 40 patients (60%) lost 15 ETDRS letters or more over follow-up in 1 or both eyes, and 21 patients (31%) progressed to more advanced stages of visual impairment. Inherited retinal disease–related CLV is rare, sporadic, and mostly bilateral; there is no gender predominance, and it can occur in diverse types of IRD at any point of the disease, with a mean onset in the fourth decade of life. Patients with IRD-related CLV who have decreased initial visual acuity, ERD, CLV changes affecting 2 or more retinal quadrants, and CRB1 - retinopathy may be at higher risk of a poor prognosis. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

According to a national claims database, remote retinal imaging utilization in the U.S. increased rapidly from 2011 to 2020, but insurance coverage declined, with disproportionate impact on vulnerable populations including older, Black, and lower-income patients.

PurposeIn a large cohort of molecularly characterized inherited retinal disease (IRD) families, we investigated proportions with disease attributable to causative variants in each gene.DesignRetrospective study of electronic patient records.ParticipantsPatients and relatives managed in the Genetics Service of Moorfields Eye Hospital in whom a molecular diagnosis had been identified.MethodsGenetic screening used a combination of single-gene testing, gene panel testing, whole exome sequencing, and more recently, whole genome sequencing. For this study, genes listed in the Retinal Information Network online resource (https://sph.uth.edu/retnet/) were included. Transcript length was extracted for each gene (Ensembl, release 94).Main outcome measuresWe calculated proportions of families with IRD attributable to variants in each gene in the entire cohort, a cohort younger than 18 years, and a current cohort (at least 1 patient encounter between January 1, 2017, and August 2, 2019). Additionally, we explored correlation between numbers of families and gene transcript length.ResultsWe identified 3195 families with a molecular diagnosis (variants in 135 genes), including 4236 affected individuals. The pediatric cohort comprised 452 individuals from 411 families (66 genes). The current cohort comprised 2614 families (131 genes; 3130 affected individuals). The 20 most frequently implicated genes overall (with prevalence rates per families) were as follows: ABCA4 (20.8%), USH2A (9.1%), RPGR (5.1%), PRPH2 (4.6%), BEST1 (3.9%), RS1 (3.5%), RP1 (3.3%), RHO (3.3%), CHM (2.7%), CRB1 (2.1%), PRPF31 (1.8%), MY07A (1.7%), OPA1 (1.6%), CNGB3 (1.4%), RPE65 (1.2%), EYS (1.2%), GUCY2D (1.2%), PROM1 (1.2%), CNGA3 (1.1%), and RDH12 (1.1%). These accounted for 71.8% of all molecularly diagnosed families. Spearman coefficients for correlation between numbers of families and transcript length were 0.20 (P = 0.025) overall and 0.27 (P = 0.017), -0.17 (P = 0.46), and 0.71 (P = 0.047) for genes in which variants exclusively cause recessive, dominant, or X-linked disease, respectively.ConclusionsOur findings help to quantify the burden of IRD attributable to each gene. More than 70% of families showed pathogenic variants in 1 of 20 genes. Transcript length (relevant to gene delivery strategies) correlated significantly with numbers of affected families (but not for dominant disease).

We aimed to characterize the ocular phenotype of patients with ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome and their response to therapy. Single-center observational case study. Eleven patients with a diagnosis of ROSAH syndrome and mutation in ALPK1 were included. Patients with molecularly confirmed ROSAH syndrome underwent ophthalmic evaluation, including visual acuity testing, slit-lamp and dilated examinations, color fundus and autofluorescence imaging, fluorescein angiography, OCT, and electrophysiologic testing. Visual acuity, electrophysiology, fluorescein angiography, and OCT findings. Eleven individuals (6 female and 5 male patients) from 7 families ranging in age from 7.3 to 60.2 years at the time of the initial evaluation were included in this study. Seven patients were followed up for a mean of 2.6 years (range, 0.33–5.0 years). Best-corrected visual acuity at baseline ranged from 20/16 to no light perception. Variable signs or sequelae of intraocular inflammation were observed in 9 patients, including keratic precipitates, band keratopathy, trace to 2+ anterior chamber cells, cystoid macular edema, and retinal vasculitis on fluorescein angiography. Ten patients were observed to show optic disc elevation and demonstrated peripapillary thickening on OCT. Seven patients showed retinal degeneration consistent with a cone–rod dystrophy, with atrophy tending to involve the posterior pole and extending peripherally. One patient with normal electroretinography findings and visual evoked potential was found to have decreased Arden ratio on electro-oculography. Leveraging insights from the largest single-center ROSAH cohort described to date, this study identified 3 main factors as contributing to changes in visual function of patients with ROSAH syndrome: optic nerve involvement; intraocular inflammation, including cystoid macular edema; and retinal degeneration. More work is needed to determine how to arrest the progressive vision loss associated with ROSAH syndrome. Proprietary or commercial disclosure may be found after the references. [ABSTRACT FROM AUTHOR]

To determine whether functional vision and visual function improvements after voretigene neparvovec (VN; Luxturna [Spark Therapeutics, Inc]) administration in patients with biallelic RPE65 mutation-associated inherited retinal disease are maintained at 3 to 4 years and to review safety outcomes. Open-label, randomized, controlled phase 3 trial. Thirty-one individuals were enrolled and randomized 2:1 to intervention (n = 21) or control (n = 10). One participant from each group withdrew before, or at, randomization. Patients in the original intervention (OI) group received bilateral subretinal VN injections. Delayed intervention (DI) patients served as control participants for 1 year then received VN. Change from injection baseline in bilateral performance on the multiluminance mobility test (MLMT), a measure of ambulatory navigation, and change from injection baseline in full-field light sensitivity threshold white light, visual field (VF), and visual acuity (VA). Mean bilateral MLMT change scores at year 4 for OI patients and year 3 for DI patients were 1.7 and 2.4, respectively, with 71% of patients with a year 3 visit able to pass MLMT at the lowest light level. Mean change in full-field light sensitivity threshold white light, averaged over both eyes at year 4 for OI patients and year 3 for DI patients, was −1.90 log 10 (cd.s/m2) and −2.91 log 10 (cd.s/m2), respectively. Mean change in Goldmann kinetic VF III4e sum total degrees, averaged across both eyes, was 197.7 at year 4 for OI patients and 157.9 at year 3 for DI patients. Mean change in VA (Holladay scale), averaged across both eyes, was –0.003 logarithm of the minimum angle of resolution (logMAR) at year 4 for OI patients and −0.06 logMAR at year 3 for DI patients. One OI patient experienced retinal detachment at approximately year 4 that impacted VA for the OI group. No product-related serious adverse events (AEs) occurred, nor did any deleterious immune responses. Improvements in ambulatory navigation, light sensitivity, and VF were consistent in both intervention groups. Overall, improvements were maintained up to 3 to 4 years, with ongoing observation. The safety profile of VN was consistent with vitrectomy and the subretinal injection procedure and was similar between intervention groups, with no product-related serious AEs reported. [ABSTRACT FROM AUTHOR]

ObjectiveTo compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing.DesignProspective, single-center, case control study.ParticipantsFifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration.MethodsParticipants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected.Main outcome measuresWe assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group.ResultsFifty-seven study participants (91.2% female; mean age, 55.7±10.4 years; mean duration of hydroxychloroquine treatment, 15.0±7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (

Ophthalmologic telemedicine programs help to address the growing demand for eye care and lessen healthcare disparities for patients. One example is Technology-Based Eye Care Services (TECS), implemented in the Veteran Affairs Healthcare System in 2015. Accuracy and quality data for TECS both have been reported, and data suggest that although the TECS examination is comparable with an in-person examination, sensitivity for glaucoma and glaucoma suspect detection is less than that for other diseases, such as macular degeneration. Several articles suggest that OCT can improve disease detection for glaucoma. Therefore, this study was undertaken to test the impact of OCT on the accuracy of the TECS protocol. This article reports the data from part II of the TECS Compare trial; results from part I are discussed in a previous article. Prospective comparison between the TECS protocol with OCT versus a face-to-face (FTF) examination for 256 patients. An eligible patient was defined as a patient with no known ocular disease who desired a routine eye examination. Patient underwent the TECS protocol workup and OCT nerve, OCT macula, and FTF examination on the same day. Percent agreement, κ values, sensitivity, and specificity were calculated for nonexpert readers after OCT interpretation of the TECS protocol using the FTF examination as the clinical gold standard. OCT did not improve the diagnostic accuracy of the TECS protocol when compared with an FTF examination. In most cases, OCT had no impact, and in the case of reader 2, OCT actually reduced the κ value from moderate agreement to agreement equal to chance while lowering the percent agreement by 10%. OCT also did not impact inter- or intrareader variability parameters. In this study, OCT did not seem to improve the accuracy of glaucoma or retinal disease detection when added to the standard TECS protocol. In one case, OCT worsened the agreement of the reader compared with the FTF. Further study is necessary to confirm these findings, and results may change if the readers are glaucoma or retina specialists instead of nonexpert OCT readers, comprehensive and anterior segment specialists. [ABSTRACT FROM AUTHOR]

PurposeTo introduce and examine the utility of a retinal imaging technique using high-speed optical coherence tomography (OCT) for creating a more complete retinal structural map to aid in the evaluation of patients with macular pathology.DesignProspective observational case series.ParticipantsFive patients with a variety of macular pathologies.MethodsPatients were imaged with a Fourier-domain high-speed high-resolution OCT system built at our institution. A sweeping serial OCT B-scan of the macula was acquired to create a detailed retinal structural map. The data were then used to make individual clinical observations.ResultsRapid serial OCT B-scans produced detailed macular maps for all 5 patients. Diagnoses of imaged patients included macular hole, lamellar macular hole, regressed macular hole or macular microhole, choroidal neovascular membrane (CNV) from age-related macular degeneration, and CNV from presumed ocular histoplasmosis syndrome. Reconstructed B-scans and C-scans are shown for selected patients to illustrate the additional perspectives gained by obtaining a detailed retinal map.ConclusionsRapid serial Fourier-domain OCT B-scanning can be used to create a detailed retinal structural map. This technique provides additional information that can be missed on single OCT images and provides an accurate way to image large or complex lesions, and allows B-scan and C-scan reconstructions to be made that provide additional perspectives into retinal structures that may be missed using traditional imaging methods.

Children with sickle cell hemoglobinopathy (SCH) can demonstrate proliferative retinopathy with vision loss, but lack of consensus exists regarding screening regimens. We sought to determine the prevalence, age at onset, and risk factors associated with sickle cell retinopathy (SCR) to inform development of screening guidelines for asymptomatic children. Retrospective cohort study. Children with SCH over a 4-year period. Prevalences of any retinopathy, nonproliferative retinopathy (NPR), and proliferative retinopathy (PR), determined as proportions of all children examined, were calculated. Subgroup analyses were completed by SCH genotype. Ages at first diagnosis were reported using standard descriptive statistics. The association of potential risk factors with retinopathy were assessed using univariate and multivariate linear and logistic regression. Outcomes were prevalence, age at onset, and type of SCR, based on examination by an ophthalmologist. Markers of SCH severity (number of emergency room or hospital admissions for crises, number of blood transfusions, hydroxyurea therapy, transcranial Doppler–confirmed cerebral vasculopathy), genotype, gender, and race were evaluated as SCR risk factors. Of 398 children (mean age, 9.6±4.6 years; range 0–18 years), 208 (52%) showed sickle cell homozygote (SS) genotype, 113 (28%) showed sickle cell hemoglobin C (SC) genotype, and 77 (19%) showed trait genotype. Forty-eight children (12.1%) demonstrated SCR, 44 of 398 children (11.1%; 95% confidence interval, 8.3%–14.5%) demonstrated NPR, and 9 of 398 children (2.3%; 95% confidence interval, 1.2%–4.2%) demonstrated PR. Prevalence was higher for SC than SS genotype for NPR (21% vs. 9%) and PR (5% vs. 1%); onset for SC genotype was earlier than that for SS genotype for NPR (youngest diagnosis 4.8 vs. 6.1 years) and PR (12.2 vs. 15.4 years). No other risk factors were associated significantly with SCR. Clinical markers of SCH severity assessed were not associated with SCR and are not necessary for screening guidelines. Based on our study and literature review, although screening could begin at age 5 years for NPR, screening of children without ophthalmologic symptoms to identify treatment-requiring PR could begin later, at 9 years of age for SC and 13 years of age for SS. [ABSTRACT FROM AUTHOR]

Purpose To report the incidence of, risk factors for, and characteristics of paracentral acute middle maculopathy (PAMM) after 25-gauge pars plana vitrectomy for proliferative diabetic retinopathy (PDR). Design Retrospective, consecutive, interventional case series. Participants Five hundred thirty eyes of 427 patients who underwent primary vitrectomy for PDR from 2013 through 2016. Methods The patients underwent measurement of best-corrected visual acuity (BCVA), fundus photography, and OCT before and within 2 weeks after vitrectomy. A generalized linear mixed-effects model was used to evaluate risk factors for development of PAMM. Main Outcome Measures The incidence, associated risk factors, and clinical characteristics of PAMM following vitrectomy, including the change in BCVA in eyes with PAMM and the distribution of PAMM as determined by en face OCT. Results Four hundred ninety-six eyes of 395 patients who met the eligibility criteria were evaluated. The incidence of PAMM was 3.8% (15/395) for patients and 3.6% (18/496) for eyes. Multivariate analysis showed the significant risk factors for PAMM development to be younger age (mean age, 49 years in patients and 59 years in control participants; odds ratio [OR] 0.94; 95% confidence interval [CI], 0.89–0.99; P = 0.021) and female gender (66.7% of patients and 31.3% of control participants; OR, 4.48; 95% CI, 1.57–12.6; P = 0.005). The PAMM was distributed on either side of the causative arterioles. In 14 of the 18 eyes (78%), PAMM was located within a 3-mm diameter of the fovea. In 10 eyes (56%), PAMM measured 1 disc diameter or more, and in 5 eyes (28%), PAMM measured one third disc diameter or less. No emboli were found in any eyes; however, multiple segmental arterial constrictions were confirmed during vitrectomy in 1 eye. The BCVA decreased more than 2 lines in 2 eyes (5%). Conclusions Paracentral acute middle maculopathy can develop after pars plana vitrectomy for PDR, especially in patients who are younger and female. Impaired blood flow in arterioles, which leads to tissue hypoxia, was associated with development of PAMM. [ABSTRACT FROM AUTHOR]

Purpose Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments. Design Masked, multicenter, dose de-escalation study. Participants A total of 61 premature infants with type 1 ROP. Methods If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator. Main Outcome Measures Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months. Results Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%–54%) received additional treatment: 3 (5%; 95% CI, 1%–14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%–30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%–30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%–52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%–52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%–55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%–31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions. Conclusions Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment. [ABSTRACT FROM AUTHOR]

Acute retinal arterial ischemia, including vascular transient monocular vision loss (TMVL) and branch (BRAO) and central retinal arterial occlusions (CRAO), are ocular and systemic emergencies requiring immediate diagnosis and treatment. Guidelines recommend the combination of urgent brain magnetic resonance imaging with diffusion-weighted imaging, vascular imaging, and clinical assessment to identify TMVL, BRAO, and CRAO patients at highest risk for recurrent stroke, facilitating early preventive treatments to reduce the risk of subsequent stroke and cardiovascular events. Because the risk of stroke is maximum within the first few days after the onset of visual loss, prompt diagnosis and triage are mandatory. Eye care professionals must make a rapid and accurate diagnosis and recognize the need for timely expert intervention by immediately referring patients with acute retinal arterial ischemia to specialized stroke centers without attempting to perform any further testing themselves. The development of local networks prompting collaboration among optometrists, ophthalmologists, and stroke neurologists should facilitate such evaluations, whether in a rapid-access transient ischemic attack clinic, in an emergency department–observation unit, or with hospitalization, depending on local resources. [ABSTRACT FROM AUTHOR]

Purpose To investigate the relationships between myopic macular retinoschisis (MRS) and posterior staphylomas and to reveal the characteristics of other retinal lesions associated with MRS. Design Retrospective, observational case series. Participants Seven hundred twenty-nine eyes of 420 patients with high myopia, which was defined as myopic refractive error of more than –8.0 diopters or an axial length longer than 26.5 mm. Methods Highly myopic eyes were examined by ultrawide-field (UWF) swept-source (SS) OCT with scan width of up to 23 mm and scan depth of 5 mm. The OCT features of MRS and posterior staphylomas and their spatial relationship were examined in UWF SS OCT images. Main Outcome Measures Associations between MRS and staphylomas. Results In 729 eyes with mean axial length of 30.2±2.1 mm, posterior staphyloma was detected in 482 eyes (66.1%) and MRS was detected in 136 eyes (18.7%). All 136 eyes with an MRS showed outer retinoschisis, and 40 eyes (29.4%) also showed inner retinoschisis. Posterior staphyloma was detected significantly more frequently in eyes with MRS (117/136 [86.0%]) than in eyes without MRS (365/593 [61.6%]; P < 0.001). In all eyes with both staphyloma and outer retinoschisis, the area of the outer retinoschisis was restricted to the area within the staphyloma. In 1 of the 19 eyes with outer retinoschisis but without staphyloma, the outer retinoschisis extended beyond the range of the scanned fundus area. Among the 40 eyes with inner retinoschisis, the inner retinoschisis was located within the region of the outer retinoschisis in 39 eyes (97.5%). In all eyes with inner retinoschisis, retinal lesions causing an inward-directed tractional force were found within the area of the inner retinoschisis. Conclusions In highly myopic eyes, the sites of the MRS and staphylomas were spatially related to each other. Posterior-directed force in association with staphylomas, and an inward-directed force resulting from epiretinal membranes or vitreoretinal attachments, may act as causative factors for MRS. However, the exact mechanisms related to the development of an MRS are probably diverse and complex. [ABSTRACT FROM AUTHOR]

Purpose To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. Design Cross-sectional meta-analysis. Participants A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9±12.3–82.1±4.2 years) of the European Eye Epidemiology (E3) consortium. Methods We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. Main Outcome Measures Determinants of pRNFLT. Results Mean pRNFLT ranged from 86.8±21.4 μm in the Rotterdam Study I to 104.7±12.5 μm in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (β = –0.38 μm/year; 95% confidence interval [CI], –0.57 to –0.18), higher intraocular pressure (IOP) (β = –0.36 μm/mmHg; 95% CI, –0.56 to –0.15), visual impairment (β = –5.50 μm; 95% CI, –9.37 to –1.64), and history of systemic hypertension (β = –0.54 μm; 95% CI, –1.01 to –0.07) and stroke (β = –1.94 μm; 95% CI, –3.17 to –0.72). A suggestive, albeit nonsignificant, association was observed for dementia (β = –3.11 μm; 95% CI, –6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (β = 1.39 μm/diopter; 95% CI, 1.19–1.59) and smoking (β = 1.53 μm; 95% CI, 1.00–2.06 for current smokers compared with never-smokers). Conclusions In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities. [ABSTRACT FROM AUTHOR]

Purpose To analyze vitreoretinal (VR) complications and treatment outcomes in eyes undergoing modified osteo-odonto-keratoprosthesis (OOKP) surgery. Design Retrospective case series. Participants All patients who underwent modified OOKP (mOOKP) surgery at a tertiary eye-care center from March 2003 to February 2013 were included. Methods Medical records were reviewed for relevant medical history, best-corrected visual acuity (BCVA), slit-lamp examination, ultrasound scan, oral examination findings, and VR complications. Main Outcome Measures The BCVA at the last visit. Optimal anatomic outcome was attached retina with a normal intraocular pressure at the last visit. Results A total of 92 eyes of 90 patients were included. Indications for OOKP included Stevens–Johnson syndrome (n = 53), chemical injury (n = 36), and ocular cicatricial pemphigoid (n = 3). A total of 41 eyes of 39 patients developed VR complications, including vitritis (n = 21), retinal detachment (RD) (n = 12; primary RD = 5), retroprosthetic membrane (RPM) (n = 10; primary RPM = 2), endophthalmitis (n = 8), vitreous hemorrhage (VH) (n = 5; primary VH = 1), serous choroidal detachment (n = 5), hemorrhagic choroidal detachment (n = 2), and leak-related hypotony (n = 1). Mean interval from mOOKP surgery to occurrence of VR complication(s) was 43.8 months (median, 41.9 months; range, 0.2–95.5 months). After treatment of VR complication, visual improvement was seen in 17 eyes (42%) (mean improvement = 1.2 logarithm of the minimum angle of resolution [logMAR]; median, 0.8 logMAR; range, 0.1–2.5 logMAR), visual decline in 7 eyes (14%) (mean decline in BCVA = 0.6 logMAR; median, 0.4 logMAR; range, 0.3–1.8 logMAR), and no change in BCVA in 17 eyes (42%). However, BCVA ≥6/60 was retained in 19 eyes and ≥6/18 was retained in 9 eyes after final VR treatment. Conclusions Vitreoretinal complications constitute a significant cause of visual morbidity in eyes undergoing mOOKP surgery and pose a challenging situation to manage. However, appropriate and timely intervention can achieve encouraging results. [ABSTRACT FROM AUTHOR]

Purpose To describe clinical findings in patients with acute exudative polymorphous vitelliform maculopathy (AEPVM). Design Retrospective, observational, multicenter case series review. Participants Consecutive patients diagnosed with idiopathic AEPVM. Methods Review of clinical charts, multimodal imaging, electrophysiologic findings, and genetic findings in previously unpublished patients and review of the literature. Main Outcome Measures Clinical features of idiopathic AEPVM and differential diagnosis. Results Eighteen patients (age range, 21–74 years) with typical features of AEPVM, including initial localized, serous detachments followed by the development of characteristic yellow-white deposits in the vitelliform space. Over time, this hyperautofluorescent material gravitated within the larger lesions, resulting in typical curvilinear deposits characteristic of later stages. Symptoms and clinical findings lasted from weeks to several years. Some patients showed previously undescribed features such as fluorescein-negative intraretinal cystic changes, choroidal neovascularization, serous retinal elevations mimicking retinal folds, increased choroidal thickness, lack of rapid visual recovery, and recurrence years after complete resolution of initial manifestations. Conclusions Acute exudative polymorphous vitelliform maculopathy can present with a more variable natural course than previously described. Paraneoplastic retinopathy and autosomal recessive bestrophinopathy closely resemble AEPVM, necessitating medical and hereditary evaluation to exclude these clinical possibilities. This series of patients with AEPVM expands the clinical spectrum of the disorder, including demographics, clinical manifestations, imaging features, natural course, and visual prognosis. [ABSTRACT FROM AUTHOR]

Purpose To characterize patients affected by a uniquely severe, rapid-onset chorioretinopathy (ROC) phenotype of ABCA4 disease. Design Comparative cohort study. Participants Sixteen patients were selected from a large clinically diagnosed and genetically confirmed cohort (n = 300) of patients diagnosed with ABCA4 disease. Main Outcome Measures Phenotypic characteristics were assessed on color fundus photographs, short-wavelength autofluorescence (488-nm), and near-infrared autofluorescence (NIR-AF, 787-nm) images. Subfoveal thickness measurements were obtained from enhanced-depth imaging OCT. Generalized retinal function was determined with full-field electroretinogram (ffERG) testing, and lipofuscin accumulation was assessed by quantitative autofluorescence (qAF). Results All patients exhibited advanced disease features, including pigment migration in the macula and retinal vessel attenuation at an early age, and reported a symptomatic onset, on average, at 7.4 years (average for ABCA4 disease is 21.9 years, P < 0.0001). Deterioration of the macula was observed to begin with an intense, homogeneous signal on short-wavelength autofluorescence, which corresponds to an attenuated NIR-AF signal and progresses to a patchy, coalescing pattern of chorioretinal atrophy within the subsequent decade. Measurement of choroidal thickness revealed a more rapid thinning of choriocapillaris with age of Sattler's layer compared with the rate in most other patients with ABCA4 disease ( P < 0.001). Levels of qAF in the macula before atrophy were above both the 95% confidence intervals for healthy individuals and patients with Stargardt disease (STGD1) (>1000 qAF units). Severe attenuation of cone responses and notable decreases in rod responses were detected by ffERG. Sequencing of the ABCA4 gene revealed exclusively deleterious, null mutations, including stop codons; frameshift deletions; variants in canonical splice sites, which completely abolish splicing; and known deleterious missense alleles. Conclusions The ROC phenotype is a unique classification of ABCA4 disease, which is caused by deleterious null biallelic ABCA4 mutations and is characterized by the rapid deterioration of retinal pigment epithelium and photoreceptor layers in the macula and significant choroidal thinning within the first 2 decades of life. [ABSTRACT FROM AUTHOR]

Purpose To assess the incidence, cumulative rate, and long-term outcomes of infectious and noninfectious endophthalmitis after intravitreal injections (IVTs) of anti-vascular endothelial growth factor (VEGF) agents. Design Database study, prospectively designed. Participants Treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) tracked by the Fight Retinal Blindness! (FRB!) registry that commenced anti-VEGF therapy between January 1, 2006, and November 30, 2016. Methods Cumulative rate of endophthalmitis and survival curves were measured using Cox-proportional hazards models. Locally weighted scatterplot smoothing curves were used to display visual acuity (VA). Main Outcome Measures Incidence and cumulative rate of endophthalmitis, and change in VA 12 months after endophthalmitis. Results Infectious endophthalmitis developed in 18 of 88 150 injections (1/4897 injections [0.020%]; 95% confidence interval [CI], 0.012–0.032) with no difference found between types of anti-VEGF medications ( P = 0.896). The cumulative rate of infectious endophthalmitis per patient was 0.055%, 0.183%, 0.360%, 0.360%, 0.555%, and 0.843% after 10, 20, 30, 40, 50, and 60 IVTs, respectively. However, the “risk” of infectious endophthalmitis did not increase with each successive injection ( P = 0.202). Noninfectious endophthalmitis developed in 11 of 88 150 injections (1/8013 injections [0.012%]; 95% CI, 0.006–0.022). The cumulative rate of noninfectious endophthalmitis per patient was 0.087% and 0.228% after 10 and 20 IVTs, respectively, and then remained stable up to 60 IVTs. The incidence of noninfectious endophthalmitis was higher for bevacizumab (8/9931, 0.081%) compared with ranibizumab (3/54 776, 0.005%; P = 0.005) and aflibercept (0/23 425; P = 0.016), and no differences were observed between ranibizumab and aflibercept ( P = 1.0). The 12-month VA in infectious and noninfectious endophthalmitis was within ±2 lines of before endophthalmitis in 53% and 75% of eyes, respectively; a loss >2 lines was observed in 31% and 25% of eyes, respectively. Conclusions The incidences of infectious and noninfectious endophthalmitis after IVT were low, and the risk did not increase with each successive injection. We found higher rates of noninfectious endophthalmitis with bevacizumab compared with ranibizumab or aflibercept. Three quarters of cases with infectious and two thirds of cases with noninfectious endophthalmitis retained vision within 10 letters of the pre-endophthalmitis level. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the efficacy and safety of ranibizumab 0.5 mg treat-and-extend (T&E) versus monthly regimens in patients with neovascular age-related macular degeneration (nAMD) from the TReat and extEND (TREND) study. Design A 12-month phase 3b visual acuity (VA) assessor-masked, multicenter, randomized, interventional study. Participants Six hundred fifty patients. Methods Treatment-naïve nAMD patients (age, ≥50 years) were randomized 1:1 to receive either a ranibizumab 0.5 mg T&E (n = 323) or monthly (n = 327) regimen. Main Outcomes Measures The primary objective was to show noninferiority of ranibizumab 0.5 mg T&E versus monthly regimen, as assessed by the change in best-corrected VA (BCVA) from baseline to the end of the study. Secondary objectives included change in retinal central subfield thickness (CSFT) from baseline to the end of study, treatment exposure, and safety. Results Overall, 89.8% (T&E) and 90.2% (monthly) of patients completed the study. Patient demographic and baseline characteristics were well balanced between the 2 treatment groups. The T&E regimen was noninferior ( P < 0.001) to the monthly regimen, with a least squares mean BCVA change from baseline of 6.2 versus 8.1 letters to the end of study, respectively. In both treatment groups, most BCVA improvements occurred during the first 6 months and were maintained until the end of the study. The mean change in CSFT from baseline to the end of study was −169.2 μm and −173.3 μm in the T&E and monthly groups, respectively. Fewer injections were required in patients receiving the T&E (8.7) versus monthly (11.1) regimen, with mean number of postbaseline visits of 8.9 and 11.2, respectively. Types and rates of adverse events were comparable between the treatment groups. Conclusions Ranibizumab 0.5 mg administered according to a T&E regimen was statistically noninferior and clinically comparable with a monthly regimen in improving VA from baseline to the end of study. No new safety signals for ranibizumab were identified. [ABSTRACT FROM AUTHOR]

Purpose To investigate the clinical and morphologic characteristics of serous retinal disturbances in patients taking mitogen-activated protein kinase kinase (MEK) inhibitors. Participants A total of 313 fluid foci in 50 eyes of 25 patients receiving MEK inhibitors for treatment of their metastatic cancer, who had evidence of serous retinal detachments confirmed by optical coherence tomography (OCT). Design Single-center, retrospective cohort study. Methods Clinical examination and OCT were used to evaluate MEK inhibitor–associated subretinal fluid. The morphology, distribution, and location of fluid foci were serially evaluated for each eye. Choroidal thickness was measured at each time point (baseline, fluid accumulation, and fluid resolution). Two independent observers performed all measurements. Statistical analysis was used to correlate interobserver findings and compare choroidal thickness and visual acuity at each time point. Main Outcome Measures Comparison of OCT characteristics of retinal abnormalities at baseline to fluid accumulation. Results The majority of patients had fluid foci that were bilateral (92%) and multifocal (77%) and at least 1 focus involving the fovea (83.3%). All fluid foci occurred between the interdigitation zone and an intact retinal pigment epithelium. The 313 fluid foci were classified into 4 morphologies, as follows: 231 (73.8%) dome, 36 (11.5%) caterpillar, 31 (9.9%) wavy, and 15 (4.8%) splitting. Best-corrected visual acuity at fluid resolution was not statistically different from baseline; and no eye lost more than 2 Snellen lines from baseline at the time of fluid accumulation. There was no statistical difference in the choroidal thickness between the different time points (baseline, fluid accumulation, and fluid resolution). A strong positive interobserver correlation was obtained for choroidal thickness measurements (r = 0.97, P < 0.0001) and grading of foci morphology (r = 0.97, P < 0.0001). Conclusion The subretinal fluid foci associated with MEK inhibitors have unique clinical and morphologic characteristics, which can be distinguished from the findings of central serous chorioretinopathy. In this series, MEK inhibitors did not cause irreversible loss of vision or serious eye damage. [ABSTRACT FROM AUTHOR]

Purpose To devise a comprehensive multiplatform genetic testing strategy for inherited retinal disease and to describe its performance in 1000 consecutive families seen by a single clinician. Design Retrospective series. Participants One thousand consecutive families seen by a single clinician. Methods The clinical records of all patients seen by a single retina specialist between January 2010 and June 2016 were reviewed, and all patients who met the clinical criteria for a diagnosis of inherited retinal disease were included in the study. Each patient was assigned to 1 of 62 diagnostic categories, and this clinical diagnosis was used to define the scope and order of the molecular investigations that were performed. The number of nucleotides evaluated in a given subject ranged from 2 to nearly 900 000. Main Outcome Measures Sensitivity and false genotype rate. Results Disease-causing genotypes were identified in 760 families (76%). These genotypes were distributed across 104 different genes. More than 75% of these 104 genes have coding sequences small enough to be packaged efficiently into an adeno-associated virus. Mutations in ABCA4 were the most common cause of disease in this cohort (173 families), whereas mutations in 80 genes caused disease in 5 or fewer families (i.e., 0.5% or less). Disease-causing genotypes were identified in 576 of the families without next-generation sequencing (NGS). This included 23 families with mutations in the repetitive region of RPGR exon 15 that would have been missed by NGS. Whole-exome sequencing of the remaining 424 families revealed mutations in an additional 182 families, and whole-genome sequencing of 4 of the remaining 242 families revealed 2 additional genotypes that were invisible by the other methods. Performing the testing in a clinically focused tiered fashion would be 6.1% more sensitive and 17.7% less expensive and would have a significantly lower average false genotype rate than using whole-exome sequencing to assess more than 300 genes in all patients (7.1% vs. 128%; P < 0.001). Conclusions Genetic testing for inherited retinal disease is now more than 75% sensitive. A clinically directed tiered testing strategy can increase sensitivity and improve statistical significance without increasing cost. [ABSTRACT FROM AUTHOR]

Purpose To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD). Design Single-center retrospective case series. Participants Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016. Methods Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation. Main Outcome Measures Diagnostic yield and clinical usefulness of genetic testing. Results Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4 , accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion. Conclusions Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology. We propose the introduction of genetic testing early in the diagnostic pathway in children with clinical and/or electrophysiologic findings, suggestive of IRD. [ABSTRACT FROM AUTHOR]

Purpose To test the hypothesis that adjunctive slow-release dexamethasone implant (Ozurdex; Allergan Inc, Irvine, CA) can improve the outcomes of vitreoretinal surgery for established proliferative vitreoretinopathy (PVR). Design A 2-year, single-center, prospective, participant- and surgeon-masked randomized controlled clinical trial (EudraCT No. 2011-004498-96). Participants A total of 140 patients requiring vitrectomy surgery with silicone oil for retinal detachment with established PVR (Grade C) were randomized to standard (control) or study treatment (adjunct) in a 1:1 allocation ratio. Methods Intraoperatively, the adjunct group received an injection of 0.7 mg of slow-release dexamethasone (Ozurdex) at the time of (1) vitrectomy surgery and (2) silicone oil removal. The control group received standard care. Main Outcome Measures Primary outcome measure was the proportion of patients with a stable retinal reattachment with removal of silicone oil without additional vitreoretinal surgical intervention at 6 months. Secondary outcomes included (1) final visual acuity (VA) (median and Early Treatment Diabetic Retinopathy Study [ETDRS] of 55 letters or better); (2) cystoid macular edema (CMO), foveal thickness, and macular volume; (3) development of overt PVR recurrence; (4) complete and posterior retinal reattachment; (5) tractional retinal detachment; (6) hypotony/increased intraocular pressure (IOP); (7) macula pucker/epiretinal membrane; (8) cataract; and (9) quality of life. Results All 140 patients were recruited within 25 months of study commencement; 138 patients had primary outcome data. Primary outcome assessment showed similar results in anatomic success between the 2 groups (49.3% vs. 46.3%, adjunct vs. control; odds ratio, 0.89; 95% confidence interval, 0.46–1.74; P = 0.733). Mean VA at 6 months was 38.3 ETDRS letters and 40.2 letters in the adjunct and control groups, respectively. Secondary anatomic outcomes (complete/posterior reattachment rates and PVR recurrence) were comparable between the 2 groups. At 6 months, fewer adjunct patients had CMO (42.7%) or a foveal thickness of >300 μm (47.6%) compared with controls (67.2% and 67.7%, respectively, P = 0.004, P = 0.023). Conclusions A slow-release dexamethasone implant did not improve the primary anatomic success rate in eyes undergoing vitrectomy surgery with silicone oil for PVR. Further clinical trials are indicated to improve anatomic and visual outcomes in these eyes, but this study suggests that there is a greater reduction in CMO observed at 6 months in vitrectomized eyes treated with slow-release dexamethasone. [ABSTRACT FROM AUTHOR]

Purpose To illustrate the natural history of Leber's hereditary optic neuropathy (LHON). Design Prospective observational case series. Participants The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation. Methods A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged. Main Outcome Measures The main outcome measures were visual acuity, HVF MD, and RNFL thickness. Results Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes. Conclusions Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau. [ABSTRACT FROM AUTHOR]

Topic The purpose of this study was to identify changes in use for vitreoretinal procedures by measuring the number of allowed services using data from the US Medicare Part B Fee-for-Service (FFS) beneficiaries and their providers. Clinical Relevance To analyze vitreoretinal procedural trends, which may indicate standard of care and importance of developing methods of treatments. Methods Medicare Part B National Summary Data Files for calendar years 2000 to 2014 were used to identify the number of allowed services for vitreoretinal procedures and commonly used pharmacologic agents. Linear regression analysis was performed to identify trends in use. Main Outcome Measures To analyze vitreoretinal procedural trends, which may indicate standard of care and importance of developing methods of treatments. Results Vitreoretinal procedures grew 6-fold from 2000 to 2014. Intravitreal injections were the primary driver of growth. A total of 2922 injections were performed in 2000, compared with 2 619 950 injections in 2014 ( P < 0.01). Scleral buckling declined from 6502 procedures in 2000 to 1260 procedures in 2014 ( P < 0.01), whereas vitrectomy use for retinal detachment increased from 13 814 surgeries in 2008 to 19 288 surgeries in 2014 ( P < 0.01). Focal laser treatments declined from 188 351 procedures in 2002 to 83 379 procedures in 2014 ( P < 0.01). Panretinal photocoagulation treatments declined from 109 840 procedures in 2004 to 81 005 procedures in 2014 ( P < 0.01). Conclusions Vitreoretinal practice patterns changed significantly from 2000 to 2014. Intravitreal injections increased by 89 563%. Intravitreal injections accounted for 0.55% of all vitreoretinal procedures in 2000 and increased to 87% in 2014. Scleral buckling sharply declined, and preference for retinal detachment repair shifted further toward vitrectomy with a distribution of 83% vitrectomy, 5% scleral buckling, and 12% pneumatic retinopexy in 2014. Use of laser photocoagulation significantly declined for treatment of macular edema and proliferative retinopathy. Cryotherapy procedures declined across all indications. [ABSTRACT FROM AUTHOR]

Purpose To characterize the first 10 years of intravitreal anti-vascular endothelial growth factor (VEGF) medication use for ophthalmic disease, including bevacizumab, ranibizumab, and aflibercept. Design A retrospective cohort study using administrative claims data from January 1, 2006 to December 31, 2015. Subjects Total of 124 835 patients 18 years of age or over in the United States. Methods OptumLabs Data Warehouse, which includes administrative claims data for over 100 million commercially insured and Medicare Advantage individuals, was used to identify patients receiving intravitreal anti-VEGF injections based on Current Procedural Terminology codes. Main Outcome Measures Total and annual numbers of intravitreal anti-VEGF injections, as well as injections per 1000 enrolled patients per general category of ophthalmic disease, overall and for each available medication. Results There were 959 945 anti-VEGF injections among 124 835 patients from 2006 to 2015. Among all injections, 64.6% were of bevacizumab, 22.0% ranibizumab, and 13.4% aflibercept; 62.7% were performed to treat age-related macular degeneration (AMD), 16.1% to treat diabetic retinal diseases (including 0.9% of all injections that were for proliferative diabetic retinopathy), 8.3% to treat retinal vein occlusions, and 12.9% for all other uses. Use of bevacizumab and ranibizumab for AMD plateaued as of 2011/2012 and decreased thereafter (in 2006, 58.8 and 35.3 injections/1000 AMD patients, respectively; in 2015, 294.4 and 100.7 injections/1000), whereas use of aflibercept increased (1.1 injections/1000 AMD patients in 2011 to 183.0 injections/1000 in 2015). Bevacizumab use increased each year for diabetic retinal disease (2.4 injections/1000 patients with diabetic retinal disease in 2009 to 13.6 per 1000 in 2015) while that of ranibizumab initially increased significantly and then declined after 2014 (0.1 in 2009 to 4.0 in 2015). Aflibercept use increased each year in patients with diabetic retinal diseases and retinal vein occlusions (both <0.1 per 1000 retinal vein occlusion patients in 2011, 5.6 and 140.2 in 2015). Conclusions Intravitreal injections of anti-VEGF medications increased annually from 2006 to 2015. Bevacizumab was the most common medication used, despite its lacking U.S. Food and Drug Administration approval to treat ophthalmic disease, and AMD was the most common condition treated. Ranibizumab use declined after 2014 while both the absolute and relative use of bevacizumab and aflibercept increased. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the specific spectral-domain (SD) optical coherence tomography (OCT) features of retinal astrocytic hamartoma (RAH) and the relationship of these features with tumor size and location. Design Retrospective case series. Participants Forty-seven eyes of 42 patients with RAH. Methods All patients with clinically confirmed RAH were imaged with fundus photography and SD OCT. Main Outcome Measures Precise OCT location of RAH features and the relationship of patient age, visual acuity, tumor size, and tumor location to the presence and size of intralesional optically empty spaces (OESs), appearing as so-called moth-eaten spaces. Results Of 42 patients with RAH, 36 (86%) had unilateral disease and 6 (14%) had bilateral disease. Systemic tuberous sclerosis complex was present in 8 patients (19%). The largest tumor (per eye) demonstrated a mean basal diameter of 3.0 mm (median, 2.0 mm) and a mean thickness of 1.9 mm (median, 1.8 mm). The mean tumor proximity to the foveola was 3.0 mm and that to the optic disc was 1.8 mm. Related features included subretinal fluid (n = 9; 19%), cystoid retinal edema (n = 6; 13%), retinal traction (n = 11; 23%), intralesional cavities (n = 28; 60%), and intralesional calcification (n = 29; 62%). On SD OCT, the tumor epicenter was in the nerve fiber layer (n = 47; 100%), with all other retinal layers appearing thinned or compressed. The tumor showed OESs (n = 43; 91%), representing intralesional calcification or cavitation, and each OES showed a mean diameter of 327 μm (median, 200 μm). When comparing the number of OESs per SD OCT cut through the mass, we found no relationship with patient age, tumor diameter and thickness, distance to the foveola or optic disc, tumor calcification, central macular thickness, or logarithm of the minimum angle of resolution (logMAR) visual acuity. However, a correlation of OES number with OES size ( P = 0.01) and macular tumor location ( P = 0.03) was found. Further analysis demonstrated OES size correlated with tumor basal diameter ( P < 0.01), tumor thickness ( P < 0.01), tumor calcification ( P = 0.01), and logMAR visual acuity ( P = 0.02). Conclusions Retinal astrocytic hamartomas arose in the nerve fiber layer in every case and demonstrated moth-eaten OES, related to intrinsic calcification or cavitation, in 91% of cases. Macular tumors have a greater number of OESs, whereas larger calcified tumors have larger OES diameter. [ABSTRACT FROM AUTHOR]

Purpose To search for a morphologic biomarker to differentiate between pathologic myopia and simple childhood myopia. Design Retrospective case series. Participants The study included children (age ≤15 years) with high myopia (as defined by the Japanese Ministry of Health and Welfare) who attended the High Myopia Clinic between April 1982 and March 1994, had undergone fundus photography, and had a follow-up of 20 years or more. Methods Fundus photographs obtained in childhood and adulthood were examined for presence of pathologic myopia, defined by high myopia (myopic refractive error >8 diopters or axial length ≥26.5 mm) and the presence of stage 2 or higher myopic maculopathy. Main Outcome Measures Myopic maculopathy in childhood. Results The study included 56 eyes of 29 patients with a mean age of 10.2±3.6 years at the initial visit and an age of 36.0±7.6 years at the last visit. Mean axial length was 27.0±1.4 mm at baseline and 29.7±2.0 mm at the last visit. At the last visit, 19 eyes (34%) had tessellated fundus alone, 31 eyes (55%) had diffuse chorioretinal atrophy, 3 eyes (5%) showed patchy chorioretinal atrophy, and 1 eye (2%) had macular atrophy. Thus, 35 eyes (63%) had pathologic myopia in adulthood. Among the 35 eyes, 29 (83%) already had diffuse chorioretinal atrophy at the initial visit in childhood and the remaining 6 eyes (17%) showed tessellated fundus in childhood. The diffuse chorioretinal atrophy seen in childhood was restricted to the area temporal to the peripapillary region. Conclusions The presence of peripapillary diffuse chorioretinal atrophy in children with high axial myopia may be an indicator for the eventual development of advanced myopic chorioretinal atrophy in later life. These features in children may be helpful for differentiating simple childhood myopia from eventual pathologic myopia. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate the outcomes over 12 months in patients with neovascular age-related macular degeneration (nAMD) with insufficient response to ranibizumab who were switched directly to 8-weekly fixed dosing of aflibercept without a loading phase. Design Retrospective interventional study. Participants Consecutive patients with nAMD who were switched from pro re nata (PRN) intravitreal ranibizumab to 8-weekly fixed aflibercept because of persistent disease activity from November 1, 2013, to September 30, 2014, were included. Methods Demographic data, visual acuity (VA), and spectral-domain optical coherence tomography characteristics over time were evaluated to determine the prognostic indicators of final visual outcome at 12 months. Main Outcome Measures The VA, central subfield thickness (CST), presence of macular fluid at month 12 compared with baseline, and the definition of prognostic indicators of final visual outcome at month 12. Results A total of 431 patients (447 eyes) were included in this study. There was no statistically significant difference in VA between baseline and month 12 ( P = 0.79), whereas the CST significantly decreased at month 12 compared with baseline ( P < 0.001). At the 12-month follow-up, 48.3% of eyes had no macular fluid compared with 8.5% at baseline. The mean number of injections at month 12 was 6.8±1.75. Poor prognostic indicators included increasing age, increasing CST, the presence of intraretinal fluid, pigment epithelial detachment, and subfoveal thickening. Conclusions Patients who have not yet “responded” to PRN ranibizumab seem to exhibit retinal dehydration after switching to aflibercept, whereas there was no demonstration of VA benefit. Baseline features at the point of switching can independently predict outcomes. [ABSTRACT FROM AUTHOR]

Purpose To assess the ocular and systemic safety of intravitreal aflibercept injection (IAI) compared with controls in IAI trials in neovascular age-related macular degeneration (nAMD), macular edema following central retinal vein occlusion (MEfCRVO), macular edema following branch retinal vein occlusion (MEfBRVO), and diabetic macular edema (DME). Design Comprehensive review of 10 phase II and III trials of IAI in retinal diseases. Participants Patients were included from IAI trials in nAMD (CLEAR-IT 2 [52 weeks], VIEW 1 [96 weeks], VIEW 2 [96 weeks], VIEW 1 extension [208 weeks]); MEfCRVO (COPERNICUS [100 weeks], GALILEO [76 weeks]); MEfBRVO (VIBRANT [52 weeks]); and DME (DA VINCI [52 weeks], VIVID [100 weeks], VISTA [100 weeks]). Methods Rates were calculated as events/100 person-years at risk (PYR). When applicable, rate ratios (RRs) and 95% confidence intervals (CIs) were provided. Main Outcome Measures Outcomes included rates for intraocular inflammation, endophthalmitis, serious adverse events (SAEs), wound-healing complications, hypertension (HTN), adjudicated Anti-Platelet Trialists' Collaboration (APTC)–defined arterial thromboembolic events (ATEs) (nonfatal myocardial infarction, nonfatal stroke, and vascular death), and death from all causes. Results More than 4000 patients contributed >7000 PYR. For all outcomes, there were no meaningful differences between evaluated adverse event rates for IAI and controls. Overall intraocular inflammation rates were 2.37 (control) and 2.06 (IAI); overall RR was 0.87 (95% CI, 0.61–1.27). Overall endophthalmitis rates were 0.52 (control) and 0.22 (IAI); overall RR was 0.42 (95% CI, 0.18–1.03). Overall SAE rates were 23.09 (control) and 20.80 (IAI); overall RR was 0.90 (95% CI, 0.80–1.02). Overall rates of wound-healing complications were 0.17 (control) and 0.15 (IAI); overall RR was 0.85 (95% CI, 0.24–3.86). Overall HTN rates were 14.87 (control) and 11.27 (IAI), with an overall RR of 0.76 (95% CI, 0.65–0.89); HTN rates were highest in MEfBRVO and lowest in nAMD. For adjudicated APTC-defined ATEs, rates were 2.04 (control) and 2.19 (IAI), with an RR of 1.07 (95% CI, 0.73–1.61). Overall death rates were 1.16 (control) and 1.49 (IAI); overall RR was 1.28 (95% CI, 0.80–2.15). Conclusions Rates of selected ocular and systemic adverse events with IAI were similar to those of controls and similar across disease states in evaluated IAI trials. Intravitreal aflibercept injection was generally well tolerated in the patients evaluated. [ABSTRACT FROM AUTHOR]

Purpose To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Design Case series. Participants A total of 562 patients diagnosed with IRD. Methods We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Main Outcome Measures Diagnostic yield of genomic testing. Results Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15–45) uplift in diagnostic yield. Conclusions We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. [ABSTRACT FROM AUTHOR]

Purpose To determine whether vitrectomy surgery rates have changed over the past decade and factors affecting the odds of undergoing this procedure. Design Retrospective, longitudinal cohort study. Participants All enrollees 21 years of age or older between 2001 and 2012 in a United States managed care network. Methods Claims data from a managed care network were analyzed to identify all enrollees who underwent 1 vitrectomy or more each year from 2001 through 2012. Rates of vitrectomy per 1000 enrollees were computed each year from 2001 through 2012 for the entire group and separately for patients with and without diabetes mellitus. Multivariate logistic regression assessed factors affecting the odds of undergoing vitrectomy surgery. Main Outcome Measures Annual rates of vitrectomy surgery from 2001 through 2012 and odds ratios (ORs) of undergoing a vitrectomy with 95% confidence intervals (CIs). Results Among the 11 161 907 eligible enrollees, 40 892 (0.4%) underwent vitrectomy over the 12-year period. The average age of those undergoing vitrectomy was 57±13 years. Overall vitrectomy rates increased 31% from 2001 to 2012 (from 1.47 to 1.92 per 1000 patients). During this same period, the vitrectomy rate among persons with diabetes mellitus decreased by 43% (from 5.84 to 3.31 per 1000 patients with diabetes). Women had 24% decreased odds of undergoing vitrectomy (adjusted odds ratio [OR], 0.76; 95% confidence interval [CI], 0.72–0.79). The odds of undergoing a vitrectomy were 17% greater for black persons (adjusted OR, 1.17; 95% CI, 1.07–1.27) and 7% higher for persons with diabetes (adjusted OR, 1.07; 95% CI, 1.01–1.14). Conclusions Overall, we observed an increase in the vitrectomy rates per 1000 enrollees in this large managed care network over the course of the past decade. However, among persons with diabetes mellitus, vitrectomy rates declined substantially over this period. These changes may be explained, in part, by advances in surgical instrumentation and imaging methods to detect retinal diseases changing indications for surgery, improvements in diabetes care, and alternative treatment options for managing retinal conditions. These results may be useful for future planning of manpower needs and highlight the need for aggressive prevention of complications in black persons with diabetes. [ABSTRACT FROM AUTHOR]

Purpose To define the incidence of pseudophakic macular edema (PME) after cataract surgery and to identify contributory risk factors. Design Retrospective database study of electronic medical records (EMRs). Participants A total of 81984 eyes undergoing cataract surgery between December 2010 and December 2014 from 8 independent United Kingdom clinical sites. Methods Structured clinical data mandated by the EMR were anonymized and extracted for each eye undergoing cataract surgery including: perioperative visual acuity, copathologic features, simultaneous surgical procedures, and the presence or absence of a specified list of intraoperative complications. Diabetic status with matched Early Treatment Diabetic Retinopathy Study (ETDRS) grading also was mandated by the EMR. Eyes receiving prophylactic nonsteroidal anti-inflammatory drugs were excluded. Main Outcome Measure Diagnosis of cystoid macular edema or new-onset macular edema in patients with diabetes, recorded by a healthcare professional within 90 days of surgery. Results Baseline incidence of PME in eyes without operative complications, diabetes, or risk factors was 1.17%. Eyes in which PME developed were more likely to be male, older, and to demonstrate risk factors. The relative risk (RR) was increased in eyes with capsule rupture with or without vitreous loss (RR, 2.61; 95% confidence interval [CI], 1.57–4.34), a previous diagnosis of epiretinal membrane (RR, 5.60; 95% CI, 3.45–9.07), uveitis (RR, 2.88; 95% CI, 1.50–5.51), retinal vein occlusion (RR, 4.47; 95% CI, 2.56–5.92), or retinal detachment repair (RR, 3.93; 95% CI, 2.60–5.92). High myopia, age-related macular degeneration, or prostaglandin analog use were not shown to increase risk. Eyes with PME on average had poorer postoperative visual acuity, which persisted to the latest time point assessed, up to 24 weeks. Eyes from patients with diabetes, even in the absence of retinopathy, had an increased RR (RR, 1.80; 95% CI, 1.36–2.36) of new macular edema after surgery. The risk was higher in the presence of any diabetic retinopathy (DR; RR, 6.23; 95% CI, 5.12–7.58) and rose proportionately with increasing severity of DR. Conclusions Pseudophakic macular edema occurs commonly after phacoemulsification cataract surgery, even in the absence of complications and risk factors. This large retrospective study using structured EMR data quantified the RRs of PME and the risk with increasing ETDRS severity of DR. It highlights the need for prophylactic therapy, especially in those groups of eyes with the highest RRs. [ABSTRACT FROM AUTHOR]

Purpose To determine week 52 efficacy and safety outcomes in eyes with macular edema after branch retinal vein occlusion (BRVO) treated with 2 mg intravitreal aflibercept injection (IAI) compared with grid laser. Design VIBRANT was a double-masked, randomized, phase 3 trial. Participants Eyes randomized and treated in VIBRANT were followed to week 52. Methods In the IAI group, eyes received IAI every 4 weeks through week 24 and IAI every 8 weeks through week 48 with rescue grid laser if needed at week 36. In the grid laser group, all eyes received grid laser at baseline and, if prespecified rescue criteria were met, 1 additional laser from week 12 to 20 and IAI every 8 weeks after 3 monthly doses from week 24 onward (the laser/IAI group). Main Outcome Measures The primary outcome measure was percentage of eyes with improvement from baseline best-corrected visual acuity (BCVA) letter score ≥15 at week 24. All outcome measures at week 52 were exploratory, and P values are considered nominal. Results The percentage of eyes with improvement from baseline letter score ≥15 in the IAI and laser/IAI groups was 52.7% versus 26.7% ( P = 0.0003) at week 24 and 57.1% versus 41.1% ( P = 0.0296) at week 52. The corresponding mean change from baseline BCVA letter score was 17.0 versus 6.9 ( P < 0.0001) at week 24 and 17.1 versus 12.2 ( P = 0.0035) at week 52. The mean reduction from baseline central retinal thickness was 280.5 μm versus 128.0 μm ( P < 0.0001) at week 24 and 283.9 μm versus 249.3 μm ( P = 0.0218) at week 52. In the IAI group, 10.6% of eyes received rescue laser at week 36, and in the laser/IAI group, 80.7% received rescue IAI from week 24 to week 48. Traumatic cataract in 1 eye (1.1%) in the IAI group was the only ocular serious adverse event. Conclusions After 6 monthly IAI, injections every 8 weeks maintained control of macular edema and visual benefits through week 52. In the laser group, rescue IAI given from week 24 onward resulted in substantial visual improvements at week 52. [ABSTRACT FROM AUTHOR]