Search

AimsTo characterise and classify the morphological, clinical and tomographic characteristics of focal choroidal excavation (FCE) lesions to determine their prognostic implications.Methods36 eyes with FCE (32 patients) underwent multimodal imaging, including spectral domain optical coherence tomography and fundus autofluorescence. FCE lesions were classified into three subtypes: (1) type 1: myopic (central choroidal thickness: 200 µm, with associated chorioretinal pathology).Results80.6% of eyes were followed longitudinally (26.8±18.8 months). There were 9 type 1 FCEs (myopic), 8 type 2 FCEs (U-shaped, congenital) and 19 type 3 FCEs (V-shaped, secondary). Type 2 FCEs trended towards larger maximum widths (p=0.0563). Type 3 FCEs were associated with central serous chorioretinopathy or pachyvessels (47.4%), but were also seen in pattern dystrophy, geographic atrophy, inactive choroiditis, torpedo maculopathy and adult-onset vitelliform dystrophy. Choroidal neovascular membranes (CNVMs) were more prevalent in type 3 FCE (41.2% compared with 11.1% for type 1 FCE, p=0.251, and 0% for type 2 FCE, p=0.043).ConclusionsThe FCE types, stratified by central choroidal thickness, demonstrated distinct morphological characteristics and associated findings. The classification scheme held prognostic implications as type 3 FCE with V shapes were associated with other chorioretinal conditions and were more likely to develop CNVM.

Inhibition of vascular endothelial growth factor is the mode of action for several approved therapies, including aflibercept, for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Lack of compliance due to the frequent intravitreal dosing requirements may result in inadequately treated disease, leading to irreversible vision impairment. To date, the majority of gene therapy clinical trials providing sustained anti-VEGF levels in the retina have been limited to subretinal injections requiring a vitrectomy. A single intravitreal injection of a gene therapy product could drastically reduce the treatment burden and improve visual outcomes. ADVM-022, an adeno-associated virus vector encoding aflibercept, has been optimized for intravitreal delivery and strong protein expression. Long-term expression and efficacy of ADVM-022-derived aflibercept were evaluated in a laser-induced choroidal neovascularization (CNV) model in non-human primates. Ocular safety was evaluated following long-term suppression of VEGF by clinical scoring (inflammatory parameters) as well as optical coherence tomography (OCT) and electroretinography (ERG). Intravitreal administration of ADVM-022 was well tolerated and resulted in sustained aflibercept levels in ocular tissues. In addition, ADVM-022 administration 13 months before laser-induced CNV prevented the occurrence of clinically relevant CNV lesions, to the same degree as a bolus of aflibercept delivered at the time of laser. These results demonstrate that a single intravitreal administration of ADVM-022 may provide a safe and effective long-term treatment option for nAMD and DME, and may ultimately improve patients' visual outcomes. Clinical trials are currently underway, evaluating safety and efficacy following a single intravitreal injection of ADVM-022.

Purpose: This work reviews ocular, systemic, and demographic factors contributing to presentation of choroidal neovascular membrane (CNVM)–associated macular hemorrhage after the New York City coronavirus disease 2019 (COVID-19) lockdown. Methods: A retrospective, consecutive case series was conducted of all established patients presenting with macular hemorrhage between March 22, 2020, and August 10, 2020. Results: Fourteen patients (mean age 82.2 years) were evaluated. Ten patients had active CNVMs, 1 had an inactive lesion that was last injected 2 years prior, and 3 had new conversions from nonexudative age-related macular degeneration. In the actively treated CNVM group there was a delay in expected follow-up from 50.4 days to 125 days. Eight patients with previously active CNVM (73%) had a history of prior macular hemorrhage. Eight patients (57%) were on some form of antiplatelet or anticoagulation therapy. Twelve patients (86%) had COVID-19–specific risk factors besides age, and all but 1 patient (93%) delayed care without discussion with a physician. Ten patients (71%) had more than 1 week of symptoms prior to presentation. Twelve patients (86%) had signs of CNVM on prior optical coherence tomography. Conclusions: Adequate documentation of potential risks for hemorrhage (particularly prior hemorrhage or presence of subclinical type 1 CNVM), as well as COVID-19–specific risk factors, would aid triage of clinic appointments in future lockdowns. High-risk patients would likely benefit from direct physician communication discussing their individual risk profiles to alleviate anxiety over clinic visits and communicate their risk of severe vision loss.

Purpose To report the impact of COVID-19 on retina practices in three different "hot spot" cities in the United States. Patients and methods The authors assessed data of encounters and intravitreal injections from March 16th to May 8th 2020, at different offices specializing in retina in the United States. All three practices are located in COVID-19 hot spot zones. One practice was in an academic setting, one practice was in a private multispecialty setting, and one practice was a solo private vitreo-retina practice. All practices were focused on emergent/urgent care, and the results were compared to preCOVID-19 weekly averages. Results A significant decrease in the number of encounters and injections was revealed in all three centers involved in this review. There was a decrease of 87% in encounters (156 patients were seen only) and a decrease of 58% (126 patients) in intravitreal injections in Weill Cornell Medical College in NYC and a decline of 59% (569 patients) in encounters and a decrease of 64% (280 patients) of intravitreal injections at the Ophthalmic Consultants of Boston and Tufts University School of Medicine in Boston. The decline at Miami Ocular Oncology & Retina in Miami was 37% (1198 patients) in the encounters and 30% (867 patients) in the injections. Conclusion This manuscript documents a specific example illustrating that COVID-19 has led to a significant decrease in specialized health services. The degree of infection and mortality rate at each hot spot had a direct impact on the practice volume; however, the type of practice setting also played a role.

Purpose To assess anti-vascular endothelial growth factor (VEGF) management patterns and anatomic and visual acuity (VA) outcomes among patients with neovascular age-related macular degeneration (nAMD) in United States clinical practice. Design Retrospective observational cohort study. Participants Patients (N = 30 106) initiating intravitreal anti-VEGF treatment for nAMD between October 2009 and November 2016. Methods Analysis of longitudinal electronic health records from USRetina. Main Outcome Measures Number of intravitreal injections, OCT examinations, and fluorescein angiography (FA) examinations per study eye during the first 12 months; corrected VA and central retinal thickness (CRT) at 12 months; and number of ophthalmologist visits, stratified by index anti-VEGF agent. Results Over the first 12 months, patients made a mean of 8.1 (range, 1–39) ophthalmologist visits, received a mean of 6.0 (range, 1–27) anti-VEGF injections, and underwent 7.2 OCT and 5.3 FA examinations per study eye. For eyes with paired baseline and 12-month readings, mean CRT declined from 320 to 271 μm (mean change, –48 μm), and mean VA increased from 60.3 to 61.0 approximate Early Treatment Diabetic Retinopathy Study (ETDRS) letters (mean change, +0.6 letters). Twelve months after initiating index treatment with bevacizumab, ranibizumab, and aflibercept, 19.3%, 15.8%, and 15.5% of eyes, respectively, showed greater than 10-letter gain, whereas 13.2%, 14.7%, and 14.4% of eyes, respectively, showed greater than 10-letter loss. Mean change from baseline VA at 12 months increased linearly with cumulative anti-VEGF injection count: +1.79 versus –0.95 approximate ETDRS letters for eyes receiving 7 or more injections versus fewer than 7 injections. Similarly, the magnitude of the reduction from baseline CRT at 12 months tended to increase linearly with increasing number of anti-VEGF injections. Multivariate linear regression analysis, adjusted for covariates, indicated a significant association between cumulative number of anti-VEGF injections and change from baseline in VA at 12 months, with each unit increase producing an estimated gain of 0.37 approximate ETDRS letters. Conclusions This analysis of combined morphologic and functional outcomes of anti-VEGF therapy, the largest conducted to date in nAMD, identified relatively low anti-VEGF injection frequencies, coupled with moderate anatomic and limited VA improvements, in United States clinical practice.

Several standard-of-care therapies for the treatment of retinal disease, including aflibercept, inhibit vascular endothelial growth factor (VEGFA). The main shortcoming of these therapies is potential undertreatment due to a lack of compliance resulting from the need for repeated injections. Gene therapy may provide sustained levels of anti-VEGFA proteins in the retina following a single injection. In this nonhuman primate study, we explored whether ADVM-022, a recombinant adeno-associated virus (AAV) vector designed to express aflibercept, could induce anti-VEGFA protein levels comparable with those observed following a single-bolus intravitreal (IVT) injection of the standard-of-care aflibercept recombinant protein. The results demonstrated that intraocular levels of aflibercept measured at 56 days after a single IVT injection of ADVM-022 were equivalent to those in the aflibercept recombinant protein-injected animals measured 21–32 days post-administration. ADVM-022-injected animals exhibited signs of an initial self-limiting inflammatory response, but overall all doses were well tolerated. ADVM-022 administration did not result in systemic exposure to aflibercept at any dose evaluated. These results demonstrated that a single IVT injection of ADVM-022 resulted in safe and efficacious aflibercept levels in the therapeutic range, suggesting the potential of a gene therapy approach for long-term treatment of retinal disease with anti-VEGF therapy., Graphical Abstract, Current treatments of nAMD require frequent intravitreal injections of VEGF inhibitors. ADVM-022 is a one-time intravitreal gene therapy designed to express aflibercept. Kiss et al. demonstrated a range of ADVM-022 doses in non-human primates that resulted in safe ocular expression of aflibercept in the therapeutic range, without systemic exposure.

Ranibizumab and aflibercept are FDA-approved treatments for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Although these agents differ in cost and labeled dosing, it is unclear whether these differences are reflected in clinical practice.To compare the real-world frequency and cost of ranibizumab and aflibercept injections among treatment-naive and previously treated patients with nAMD and DME.Claims data from MarketScan Research Databases were retrospectively reviewed to identify treatment-naive patients with nAMD who initiated intravitreal ranibizumab or aflibercept between January 1, 2014, and January 1, 2016, and treatment-naive patients with DME who initiated intravitreal ranibizumab or aflibercept between July 29, 2014, and July 1, 2016. Patients who switched to subsequent-line aflibercept or ranibizumab during the study period were eligible to enter previously treated subgroups. Multivariable regression models were derived to compare the per-patient frequency and cost of injections between ranibizumab- and aflibercept-treated patients with nAMD over 12 months (treatment-naive: n = 1,087 and n = 1,578; previously treated: n = 221 and n = 751) and 24 months (treatment-naive: n = 454 and n = 568; previously treated: n = 93 and n = 284) and in patients with DME over 6 months (treatment-naive: n = 507 and n = 681; previously treated: n = 53 and n = 223) and 12 months (treatment-naive: n = 326 and n = 382; previously treated: n = 24 and n = 122).After adjusting for patient demographics and clinical characteristics, per-patient injection frequency and cost were not significantly different between treatment-naive patients with nAMD who received ranibizumab versus aflibercept over 12 months (5.62 vs. 5.54;Although the frequency and cost of ranibizumab and aflibercept injections were generally comparable among patients treated for nAMD, ranibizumab was associated with estimated per-patient-per-year cost savings of $3,500-$4,500 in those treated for DME. Most patients received fewer injections than any FDA-indicated dosing schedule, suggesting potential undertreatment that may result in suboptimal vision outcomes.Study funding was provided by Genentech, a member of the Roche Group. The sponsor participated in the design of the study; collection, analysis, and interpretation of the data; preparation of the manuscript; and the decision to submit the article for publication. Kiss has been a consultant for and received honoraria from Alcon, Alimera, Allergan, BioMarin, Novartis, and Spark; has been on the advisory board for, a consultant for, received honoraria from, and held stock options in Adverum and Regenxbio; has been a consultant for, received honoraria from, and held stock/stock options in Fortress; has been on the advisory board for, a consultant and investigator for, and received grants and honoraria from Genentech and Regeneron; and has been on the advisory board for, a consultant for, and received grants and honoraria from Optos. Malangone-Monaco, Wilson, Varker, Stetsovsky, and Smith are employees of IBM Watson Health, which received funding from Genentech to undertake this study. Garmo is an employee of Genentech. Data reported in this manuscript were presented in part at the Academy of Managed Care Pharmacy (AMCP) Managed Care and Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

The authors describe a case of a previously unreported phenomenon of focal choroidal excavation (FCE) expansion, in absence of inflammation, due to treatment of an associated choroidal neovascular membrane (CNVM). A patient with new type 2 CNVM, treated during 43 months of follow-up with aflibercept, experienced significant expansion of an FCE with conversion from nonconforming to conforming type. FCE is part of the pachychoroid spectrum and the regression of an associated CNVM during aflibercept treatment as seen in the authors' patient may elucidate the pathogenesis of some forms of focal choroidal excavation and their evolution over time. [ Ophthalmic Surg Lasers Imaging Retina . 2020;51:54–57.]

Carcinosarcoma, also known as malignant mixed Müllerian tumor (MMMT), includes both malignant epithelial and mesenchymal elements. While the endometrium is the most frequent known site for carcinosarcomas, their development in the fallopian tube is rare condition, only accounting for 0.1 to 0.5% among all gynecological malignancies. Fallopian tube MMMT is associated with an aggressive progression. A total of 94 previous case reports were reviewed and divided, after applying the exclusion criteria, into 2 groups: No evidence of disease (NED) Group including 33 patients reported to be without any residual disease at the end of the follow-up period; death of disease (DOD) Group including 51 patients who died due to the progression of fallopian carcinosarcoma or its complications. The gathered data were statistically analyzed together with a case from our clinical experience: a 65-year-old postmenopausal patient with a final histological diagnosis of fallopian carcinosarcoma staged FIGO IC2, synchronous with a serous endometrial intraepithelial carcinoma. Patient age between 41 and 60 years, symptoms at presentation and computed tomography (CT)/magnetic resonance imaging (MRI) tumor evidence are prognostic factors (P

Purpose To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). Design Retrospective cohort study. Participants Patients with active CMV retinitis evaluated at a tertiary care academic center. Methods Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). Main Outcome Measures The electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including best-corrected visual acuity (BCVA), treatments administered (CMV-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. Results Seven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific CTL therapy included persistent or progressive CMV retinitis (71.4% of patients); CMV UL54 or UL97 antiviral resistance mutations (42.9%); side effects or toxicity from antiviral agents (57.1%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific CTLs, with BCVA stabilizing (4 eyes [40%]) or improving (4 eyes [40%]) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new-onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. Conclusions CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.

Purpose CLN2-associated disease is a hereditary, fatal lysosomal storage disorder characterized by progressive brain and retinal deterioration. Here, we characterize the inner and outer retinal degeneration using automated segmentation software in optical coherence tomography scans, providing an objective, quantifiable metric for monitoring subtle changes previously identified with a validated disease classification scale (the Weill Cornell Batten Scale). Methods This study is a retrospective, single-center cohort review of images from examinations under anesthesia in treatment-naive patients with CLN2-associated disease. Automated segmentation software was used to delineate retinal nerve fiber, ganglion cell layer (GCL), and outer nuclear layer (ONL) thickness measurements in the fovea, parafovea, and perifovea based on age groups (months): 30 to 38, 39 to 45, 46 to 52, 53 to 59, 60 to 66, and 67 or older. Results Twenty-seven eyes from 14 patients were included, with 8 serial images yielding 36 interpretable optical coherence tomography scans. There was a significant difference in parafoveal ONL thickness between 39 to 45 and 46 to 52 months of age (P = 0.032) not seen in other regions or retinal layers. Perifoveal ONL demonstrated a difference in thickness between the 60 to 66 and greater than 67 months age cohorts (P = 0.047). There was strong symmetry between eyes, and high segmentation repeatability. Conclusions Parafoveal ONL thickness represents a sensitive, early age indicator of CLN2-associated degeneration. Outer retinal degeneration is apparent at younger ages than inner retinal changes though in treatment-naive patients all retinal layers showed significant differences between 60 to 66 and more than 67 months of age. Translational relevance This study establishes sensitive, quantitative biomarkers for assessing retinal degeneration in a large cohort natural history study in anticipation of future clinical trials.

Purpose To summarize the results of a consensus meeting aimed at defining terminology for widefield imaging across all retinal imaging methods and to provide recommendations for the nomenclature used to describe related images. Design An international panel with expertise in retinal imaging was assembled to define consensus terminology for widefield imaging and associated terminology. Participants A panel of retina specialists with expertise in retinal imaging. Methods Before the consensus meeting, a set of 7 images acquired with a range of imaging methods and representing both healthy and diseased eyes was circulated to the expert panel for independent assignment of nomenclature for each example. The outputs were assembled and used as the starting point for discussions occurring at a subsequent roundtable meeting. The anatomic location, field of view, and perspective provided by each image example was reviewed. A process of open discussion and negotiation was undertaken until unanimous terminology for widefield imaging was achieved. Main Outcome Measures Definitions of widefield imaging applicable to multiple imaging methods. Results Across a range of different imaging methods, the expert panel identified a lack of uniform terminology being used in recent literature to describe widefield images. The panel recommended the term widefield be limited to images depicting retinal anatomic features beyond the posterior pole, but posterior to the vortex vein ampulla, in all 4 quadrants. The term ultra widefield was recommended to describe images showing retinal anatomic features anterior to the vortex vein ampullae in all 4 quadrants. The definitions were recommended over other device-specific terminology. Conclusions A consistent nomenclature for widefield imaging based on normal anatomic landmarks that is applicable to multiple retinal imaging methods has been proposed by the International Widefield Imaging Study Group. The panel recommends this standardized nomenclature for use in future publications.

Purpose: This article assesses anatomical and visual outcomes after intravitreal antivascular endothelial growth factor (anti-VEGF) treatment in fellow eyes with wet age-related macular degeneration (AMD). Methods: A retrospective chart review was conducted of 349 patients diagnosed with wet AMD between 2005 and 2017 at a single academic institution. Initial diagnosis of unilateral wet AMD and a minimum follow-up time of 1 year after diagnosis were required for inclusion. Individuals were excluded if the initial diagnosis of wet AMD was made at an outside institution, if they had received prior treatment at another institution, or if they had bilateral wet AMD at the time of inclusion. Best-corrected visual acuity, optical coherence tomography (OCT) parameters, and frequency and type of intravitreal anti-VEGF injections were recorded. MedCalc Statistical Software version 17.6 (MedCalc Software) and GraphPad Software (GraphPad Software, Inc) were used for statistical analysis. Results: Of the 349 patients with wet AMD, 192 were included in the study (55%). Of these, 47 (24.5%) developed wet AMD in the fellow eye. The average time to second-eye conversion was 2.6 years, with fellow-eye conversion more likely to occur after 2 years of unilateral disease. On average, patients received 2.16 fewer injections per year in the fellow eye compared with the initially diagnosed eye ( P = .03), and fellow eyes tended to have better OCT results after 12 months of treatment. In addition, compared with ranibizumab and bevacizumab, aflibercept injections appeared to improve visual acuity both in initially diagnosed and fellow eyes. Conclusions: Exudative AMD in the fellow eye has a decreased treatment burden and better visual outcomes compared with the initial eye, which may be attributed to more frequent surveillance and early diagnosis.

Monogenic and multifactorial retinal diseases are genetically and clinically diverse conditions that have historically shared an untreatable clinical course. In recent years, the advent of targeted treatments like gene therapy has enabled intraocular delivery of viral vectors, such as adeno-associated viruses and retroviruses, that establish long-term stable protein expression. Despite the innate distinctions between mainly monogenic disorders affecting the retina such as Leber congenital amaurosis (LCA), heterogeneous monogenic conditions like retinitis pigmentosa (RP), and multifactorial diseases such as age-related macular degeneration (AMD), gene therapy has shown great promise as a gene replacement or augmentation strategy to treat or halt these disorders. This review will present an overview of retinal gene therapy and provide a comprehensive analysis of past and current clinical trials for LCA, RP, and AMD. It will discuss the paradigm shift that has occurred in ophthalmic care thanks to the development of gene therapy, as well as its challenges for the future.

Purpose There are limited and conflicting data regarding the impact of comorbid hepatitis C virus (HCV) infection on diabetic retinopathy (DR). This study sought to compare the prevalence and severity of DR among patients with diabetes mellitus (DM) with and without HCV. Patients and methods This was a retrospective, case-control study of patients with DM comparing 120 patients with comorbid HCV and 120 age-matched controls. DR prevalence and several measures of severity were compared between groups. Subgroup analyses were performed among HCV patients with cirrhosis, comorbid HIV, or history of treatment with interferon. Statistical analysis for between-group comparisons utilized both univariate and multivariate analyses. Results Cases and controls exhibited similar baseline characteristics: average hemoglobin A1c, DM duration, and age (p>0.05). Among cases and controls, there was no difference in DR prevalence (35.8% versus 42.5%, respectively, p=0.29) or severity (p>0.05). Within the HCV subgroup, DR severity was reduced in patients with HIV or cirrhosis. However, multivariate analysis identified reduced DM duration in these subgroups as the primary contributor to lesser DR severity, rather than HIV or cirrhosis. Conclusion In this study, comorbid HCV did not modulate the prevalence or severity of DR among patients with DM. These findings may inform clinical monitoring among HCV-positive diabetics undergoing ophthalmic evaluation.

Purpose To determine rates of intraoperative and postoperative systemic and ocular adverse events and establish the value of preoperative medical assessment in patients undergoing surgery for primary rhegmatogenous retinal detachment repair at a single academic center. Patients and methods Retrospective cohort study of 185 patients undergoing surgery for repair of primary rhegmatogenous retinal detachment (RRD) at a single academic center. Medical records were reviewed for medical comorbidities, completion of preoperative medical examination, anesthesia used during surgery, intraoperative adverse medical events, intraoperative ocular complications, and systemic and ocular postoperative complications. The main outcome of interest was the association of comorbidities and preoperative medical evaluation with intraoperative and postoperative complications. Results Approximately 48% of the patients presented with no medical comorbidities of interest. Formal preoperative evaluation by an independent medical provider was completed in 36% of the patients. Overall, intraoperative and postoperative systemic complications (5.7% and 1%, respectively) and intraoperative and postoperative ocular complications (0.5% for both) were uncommon. Patients with a history of chronic heart failure (OR 24.5, P=0.02) or who received general anesthesia (OR 9.56, P

BACKGROUND AND OBJECTIVE: Localized retinal detachment can appear similar to peripheral retinoschisis (RS) based on clinical exam alone. This study utilized ultra-widefield autofluorescence (UAF) to characterize retinal changes in patients with rhegmatogenous retinal detachment (RRD) compared to RS and to help differentiate these two entities in the era of multimodal imaging. PATIENTS AND METHODS: A retrospective review of 282 eyes undergoing diagnostic UAF. Eyes were excluded if the quality of the color photograph or UAF prevented reliable evaluation, or if they contained significant peripheral retinal pathology such as diabetic retinopathy or retinal vein occlusions. Eyes were determined to have RRD or RS based on dilated fundus examination, ultrasound, and optical coherence tomography imaging consistent with the diagnosis. RESULTS: Fifty-three eyes were included; 38 had retinal detachment, and 25 had RS. Eyes were determined to be bullous or not from the color photographs. Based on all UAFs reviewed, images were determined to have granular, normal, hypo-, hyper-, or mixed autofluorescence patterns. The posterior border of the RRD and RS was evaluated separately and determined to have hyper-, hypo-, granular, mixed, or normal autofluorescence. Thirty-three eyes with RRD (86.8%) appeared bullous compared to 12 eyes with RS (48%; P = .002). UAF was considered granular in zero (0%) of RRD eyes and one (4%) RS eye, normal in one RRD eye (2.63%) and 17 (68%) RS eyes, hypoautofluorescent in 27 (71.1%) RRD eyes and four (16%) RS eyes, hyperautofluorescent in one (2.63%) RRD eye and one (4%) RS eye, and mixed in nine (4%) RRD eyes and two (8%) RS eyes ( P < .001). When evaluating the posterior leading edge on UAF, 84.2% (n = 32) of patients with RRD had a hyperautofluorescent leading edge compared to 25% (n = 6) of patients with RS ( P < .001). UAF was homogenous in 65.8% (n = 25) of cases of RRD versus in 92% (n = 23) of cases of RS ( P = .037). CONCLUSIONS: To the authors' knowledge, this is the first study to utilize UAF imaging to differentiate RRD and RS. Findings suggest there are differences between RRD and RS with regards to UAF, UAF of the posterior border, and homogeneity of the area affected. UAF should be considered in the era of multimodal imaging, particularly when clinical exam alone is inadequate to differentiate these two entities. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:550–556.]

Background/objectives This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO). Subjects/methods Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses. Results Oedema duration and oedema extent during the first 52 weeks of ranibizumab treatment showed significant negative associations with BCVA improvement at weeks 52, 104 and 156. Eyes with the most persistent oedema gained (mean) 4.4 (95% CI 0.1─8.7) fewer Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 156 than eyes with the least persistent oedema (P = 0.044). Eyes with the greatest amount of oedema gained (mean) 9.3 (95% CI 4.0─14.5) fewer ETDRS letters at week 156 than eyes with the least amount of oedema (P Conclusions Macular oedema exposure over the first 52 weeks of ranibizumab treatment is a negative prognostic factor for long-term visual acuity improvement in centre-involved DMO.

Ultra-wide-field (UWF) imaging has been used clinically in retina practices for nearly two decades to achieve rapid, single-frame photographic access to the mid- and far-retinal periphery.1–5 These...

Recent developments in imaging technologies now allow the documentation, qualitative and quantitative evaluation of peripheral retinal lesions. As wide field retinal imaging, capturing both the central and peripheral retina up to 200° eccentricity, is becoming readily available the question is: what is it that we gain by imaging the periphery? Based on accumulating evidence it is clear that findings in the periphery do not always associate to those observed in the posterior pole. However, the newly acquired information may provide useful clues to previously unrecognised disease features and may facilitate more accurate disease prognostication. In this review, we explore the anatomy and physiology of the peripheral retina, focusing on how it differs from the posterior pole, recount the history of peripheral retinal imaging, describe various peripheral retinal lesions and evaluate the overall relevance of peripheral retinal findings to different diseases.

This post hoc analysis explores the relationship between early retinal anatomical response and long-term anatomical and visual outcomes with ranibizumab in center-involved diabetic macular edema.Eyes randomized to the ranibizumab plus prompt laser and ranibizumab plus deferred laser treatment arms in the Protocol I study were categorized according to their proportional reduction (20 vs. ≥20%) in central retinal thickness (CRT) after 12 weeks. Adjusted and unadjusted analyses assessed the association between early (Week 12) anatomical response and long-term (Weeks 52 and 156) anatomical and best-corrected visual acuity outcomes.Of 335 study eyes, 118 showed limited (20%) and 217 showed strong (≥20%) CRT reduction at Week 12. In unadjusted and adjusted analyses, limited early CRT response was negatively and significantly associated with strong CRT response at Weeks 52 and 156. Sensitivity analyses indicated that this association was robust and unrelated to any "floor effect." In unadjusted analyses, a strong early CRT response was associated with greater long-term improvement in best-corrected visual acuity; after controlling for confounders, the association lost statistical significance.Early CRT response to ranibizumab is a significant prognostic indicator of medium- to long-term anatomical outcome in center-involved diabetic macular edema.

Objective Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by mutations in the gene encoding for the mitochondrial protein frataxin, is characterized by ataxia and gait instability, immobility, and eventual death. We evaluated corneal confocal microscopy (CCM) quantification of corneal nerve morphology as a novel, noninvasive, in vivo quantitative imaging biomarker for the severity of neurological manifestations in FRDA. Methods Corneal nerve fiber density, branch density, and fiber length were quantified in individuals with FRDA (n = 23) and healthy age-matched controls (n = 14). All individuals underwent genetic testing and a detailed neurological assessment with the Scale for the Assessment and Rating of Ataxia (SARA) and Friedreich's Ataxia Rating Scale (FARS). A subset of individuals with FRDA who were ambulatory underwent quantitative gait assessment. Results CCM demonstrated a significant reduction in nerve fiber density and length in FRDA compared to healthy controls. Importantly, CCM parameters correlated with genotype, SARA and FARS neurological scales, and linear regression modeling of CCM nerve parameter-generated equations that predict the neurologic severity of FRDA. Interpretation Together, the data suggest that CCM quantification of corneal nerve morphology is a rapid, sensitive imaging biomarker for quantifying the severity of neurologic disease in individuals with FRDA. Ann Neurol 2018;84:893-904.

PURPOSE To identify any prognostic associations between preoperative optical coherence tomography findings and postoperative visual outcomes in patients with macula-off rhegmatogenous retinal detachment. METHODS A retrospective, single-center study of patients diagnosed with macula-off rhegmatogenous retinal detachment whom underwent surgical reattachment from 2012 to 2017. Optical coherence tomography images were analyzed by two retina surgeons. Outcome measures included "good" final vision (best-corrected visual acuity of 20/40 or better), "poor" final vision (best-corrected visual acuity of 20/200 or worse), and change in vision (worsened, improved, and improved ≥15 letters) at most recent follow-up. P values were calculated using t tests, analysis of variance, Wilcoxon rank-sum, or Kruskall-Wallis test. RESULTS A total of 49 eyes were included. There was a significant difference in the mean preoperative central retinal thickness between patients who had good final vision and patients who did not (96 μm vs. 161 μm, P = 0.048). In addition, a worse preoperative best-corrected visual acuity and greater subretinal fluid height were associated with vision improvement (P < 0.001). Those with persistent ellipsoid zone disruption postoperatively were less likely to have good final vision (odds ratio = 0.217, 95% confidence interval: 0.057-0.828). CONCLUSION A lower mean preoperative central retinal thickness is associated with good visual prognosis. Eyes with ellipsoid zone disruption postoperatively were less likely to have good final vision. Future studies should include a larger cohort of patients and more optical coherence tomography variables to address the inconsistencies in the current literature.

Purpose: This work aims to evaluate the clinical utility and feasibility of a novel scanning laser ophthalmoscope-based navigated ultra-widefield swept-source optical coherence tomography (UWF SS-OCT) imaging system. Methods: A retrospective, single-center, consecutive case series evaluated patients between September 2019 and October 2020 with UWF SS-OCT (modified Optos P200TxE, Optos PLC) as part of routine retinal care. The logistics of image acquisition, interpretability of images captured, nature of the peripheral abnormality, and clinical utility in management decisions were recorded. Results: Eighty-two eyes from 72 patients were included. Patients were aged 59.4 ± 17.1 years (range, 8-87 years). During imaging, 4.4 series of images were obtained in 4.1 minutes, with 86.4% of the image series deemed to be diagnostic of the peripheral pathology on blinded image review. The most common pathologic findings were chorioretinal scars (18 eyes). In 31 (38%) eyes, these images were meaningful in supporting clinical decision-making with definitive findings. Diagnoses imaged included retinal detachment combined with retinoschisis, retinal hole with overlying vitreous traction and subretinal fluid, vitreous inflammation overlying a peripheral scar, Coats disease, and peripheral retinal traction in sickle cell retinopathy. Conclusions: Navigated UWF SS-OCT imaging was clinically practical and provided high-quality characterization of peripheral retinal lesions for all eyes. Images directly contributed to management plans, including laser, injection or surgical treatment, for a clinically meaningful set of patients (38%). Future studies are needed to further assess the value of this imaging modality and its role in diagnosing, monitoring, and treating peripheral lesions.

Late infantile Batten disease (CLN2 disease) is a rare, autosomal recessive, neurodegenerative lysosomal storage disease caused by mutations in the CLN2 gene encoding tripeptidyl peptidase 1 (TPP1). We tested intraparenchymal delivery of AAVrh.10hCLN2, a nonhuman serotype rh.10 adeno-associated virus vector encoding human CLN2, in a non-randomized trial consisting of 2 arms assessed over 18 months: an AAVrh.10hCLN2-treated cohort of 8 children with mild to moderate disease, and an untreated, Weill Cornell natural history cohort consisting of 12 children. The treated cohort was also compared to an untreated European natural history cohort of CLN2 disease. The vector was administered through 6 burr holes directly to 12 sites in the brain without immunosuppression. In an additional safety assessment under a separate protocol, 5 children with severe CLN2 disease were treated with AAVrh.10hCLN2. The therapy was associated with a variety of expected adverse events, none causing long-term disability. Induction of systemic anti-AAVrh.10 immunity was mild. Post-therapy, the treated cohort had a 1.3- to 2.6-fold increase in cerebral spinal fluid TPP1. There was a slower loss of grey matter volume in 4 of 7 children by MRI; and a 42.4% and a 47.5% reduction in the rate of decline of motor and language function, compared to the Weill Cornell natural history cohort (p

Purpose of review The neurocutaneous disorders are a genetically and phenotypically diverse group of congenital syndromes characterized by cutaneous, ocular, and central nervous system manifestations. This review provides an overview of the clinical features and retinal findings in selected neurocutaneous disorders. Recent findings Advances in genetics and diagnostic retinal and neuroimaging allow for the recognition of retinal features of common neurocutaneous syndromes and for improved characterization of rarer entities based on previously underdiagnosed or unrecognized retinal findings. Summary Better characterization of the neurocutaneous disorders allows for earlier recognition and the potential for expeditious vision-saving and life-saving treatment.

Mutations in the CLN2 gene lead to a neurodegenerative and blinding lysosomal storage disorder: late infantile neuronal ceroid lipofucinosis, also known as "CLN2 disease." The purpose of the current study was to characterize the evolution of CLN2-associated retinal manifestations using the Weill Cornell Batten Scale (WCBS) and the age association of the retinal degeneration using central subfield thickness (CST) measurements and then correlate these findings with fundus photography and OCT to determine a critical period for retinal intervention.Retrospective, single-center cohort.Eighty-four eyes of 42 treatment-naïve patients with CLN2 disease.Clinical records, fundus photographs, and OCT imaging for patients with CLN2 disease collected during examinations under anesthesia were reviewed. Imaging was categorized per WCBS criteria by 3 masked graders.CLN2-associated retinopathy assessed using WCBS scores, fundus photographs, and OCT imaging, correlated with patient age.Eighty-four eyes of 42 patients had baseline fundus photographs, with baseline OCT in 31 eyes of 16 patients. Fundus photographs were obtained serially for 26 eyes of 13 patients, and serial OCT scans were obtained in 10 eyes of 5 patients. At baseline, bilateral WCBS scores were highly correlated for OCT and fundus photographs (r = 0.96 and 0.82, respectively). Central subfield thickness was negatively correlated with left and right eye WCBS OCT scores (r = -0.92 and -0.83, respectively; P0.001) and fundus photograph scores (r = -0.80 and -0.83, respectively; P0.001). OCT thickness was symmetrical between each eye. Baseline OCT data with age fit using a sigmoid function demonstrated a period of accelerated loss between 48 and 72 months of age.Retinal degeneration associated with CLN2 disease manifests as a progressive, symmetrical decline, which appears to accelerate during a critical period at 48 to 72 months of age, suggesting intervention with retina-specific CLN2 gene therapy should occur ideally before or as early as possible within this critical period. The WCBS is a valuable tool and is highly correlated with the extent of retinal degeneration observed in OCT or fundus photographs; by using the fellow eye as a control, this grading scale can be used to monitor the effect of CLN2 gene therapy in future trials.

Background Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath’s four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18–20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

Inhibition of vascular endothelial growth factor, a key contributor to the choroidal neovascularization associated with wet age-related macular degeneration, is the mode of action of several approved therapies, including aflibercept, which requires frequent intravitreal injections to provide clinical benefit. Lack of compliance with the dosing schedule may result in recurrence of active wet macular degeneration, leading to irreversible vision impairment. Gene therapy providing sustained anti-vascular endothelial growth factor levels in the retina following a single injection could drastically reduce the treatment burden and improve visual outcomes. ADVM-022, an adeno-associated virus vector encoding aflibercept, is optimized for intravitreal delivery and strong protein expression. Here, we report the long-term expression and efficacy of ADVM-022-derived aflibercept in a laser-induced choroidal neovascularization model in non-human primates. Intravitreal administration of ADVM-022 was well tolerated and resulted in sustained aflibercept levels. In addition, ADVM-022 administration 13 months before lasering prevented the occurrence of clinically relevant choroidal neovascularization lesions, similar to animals that received a bolus of intravitreal aflibercept (standard of care) at the time of lesioning. These results demonstrate that a single intravitreal administration of ADVM-022 may provide a safe and effective long-term treatment option for wet macular degeneration and may ultimately improve patients’ visual outcomes., Grishanin et al. (2018) describe preclinical evidence of long-term expression and efficacy of a single intravitreal injection of ADVM-022, a gene-therapy vector encoding aflibercept, an approved anti-VEGFA therapy for wet age-related macular degeneration (wAMD), and which has the potential to alleviate frequent ocular injections required to treat wAMD.

Szilárd Kiss,1 Pravin U Dugel,2,3 Arshad M Khanani,4 Michael S Broder,5 Eunice Chang,5 Gordon H Sun,5 Adam Turpcu6 1Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA; 2Retinal Consultants of Arizona, Phoenix, AZ, USA; 3USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 4Sierra Eye Associates, Reno, NV, USA; 5Partnership for Health Analytic Research, LLC, Beverly Hills, CA, USA; 6Genentech, Inc., South San Francisco, CA, USA Purpose: Intravitreal (IVT) injections of the anti-vascular endothelial growth factor (VEGF) agents aflibercept, bevacizumab, and ranibizumab are commonly prescribed to treat neovascular age-related macular degeneration (nAMD). Studies comparing inflammation rates in large populations of patients receiving these agents and the treatment of ocular inflammation post-IVT anti-VEGF injections are scarce. In this study, we compared rates of endophthalmitis claims (sterile and infectious) following IVT anti-VEGF injections to determine the risk factors associated with developing endophthalmitis, and examined the claims for subsequent treatment. Patients and methods: This retrospective cohort study of USA claims data examined the risk of developing endophthalmitis following IVT injection of aflibercept, bevacizumab, or ranibizumab in patients with nAMD between 11/18/2011 and 5/31/2013. The primary study outcome was occurrence of endophthalmitis within 30 days of a claim for an IVT anti-VEGF injection. Endophthalmitis rates were calculated separately for aflibercept, bevacizumab, and ranibizumab, followed by pairwise comparisons of endophthalmitis frequencies among the 3 treatments. Results: This analysis included 818,558 injections from 156,594 patients with nAMD. The rates (% [n/N]) of endophthalmitis following aflibercept, bevacizumab, and ranibizumab IVT injections were 0.100% (136/135,973), 0.056% (268/481,572), and 0.047% (94/201,013), respectively. In a multivariate analysis, aflibercept was associated with a significantly higher risk of endophthalmitis vs ranibizumab (adjusted odds ratio, 2.19; 95% CI: 1.68–2.85; P

The authors retrospectively reviewed spectral domain optical coherence tomography (OCT) findings in 10 eyes with macula-involving cytomegalovirus retinitis. Optical coherence tomography findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and in the retina just beyond the leading edge of retinitis., Purpose: To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT). Methods: Subjects were patients with macula-involving CMV retinitis with OCT imaging. The leading edge of retinitis in the macula was identified based on fundus imaging, and OCT findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and just beyond the leading edge of retinitis. Results: Optical coherence tomography imaging of macular CMV retinitis identified vitreous cells in 10 eyes (100%), posterior vitreous detachment in four eyes (40%), broad-based vitreomacular traction in one eye (10%), epiretinal membrane in eight eyes (80%), and lamellar hole–associated epiretinal proliferation associated with an atrophic hole in one eye (10%). Retinal architectural disruption, disruption of inner retinal layers, disruption of the external limiting membrane, and ellipsoid zone abnormalities were noted within the area of retinitis in all eyes and decreased in frequency and severity at and beyond the leading edge of retinitis, although all 10 eyes (100%) exhibited one of these abnormalities, especially outer retinal microabnormalities, beyond the leading edge of retinitis. Conclusion: Microstructural abnormalities were frequently noted on OCT of CMV retinitis, including within the retina beyond the leading edge of retinitis identified by corresponding fundus imaging. Outer retinal abnormalities were noted more frequently than inner retinal abnormalities beyond the leading edge of retinitis. These findings provide insight into the effects of CMV retinitis on retinal microstructure and potentially on vision and highlight the potential utility of OCT for monitoring microprogression of macula-involving CMV retinitis.

The tyrosine kinase inhibitor, JNJ-42756493, is an oral pan-fibroblast growth factor receptor inhibitor being studied as an antineoplastic agent. It is currently the subject of a phase II clinical trial for the treatment of urothelial cancer. We report 2 patients who developed visual disturbance shortly after starting or increasing dosage of this medication and were found to have bilateral foveal detachments on ocular coherence tomography imaging. The first patient discontinued this medication and the retinal lesions resolved with a return to baseline vision within 4 to 6 weeks. After restarting the medication at a lower dose, neither visual disturbance nor retinal lesions recurred. In the second patient, lesions were found to greatly improve shortly after discontinuation of the medication but recurred even on a reduced dose regimen.

CLN2 disease (neuronal ceroid lipofuscinosis type 2) is a rare, autosomal recessive, pediatric-onset, rapidly progressive neurodegenerative lysosomal storage disorder caused by tripeptidyl peptidase 1 (TPP1) enzyme deficiency, and is characterized by language delay, seizures, rapid cognitive and motor decline, blindness, and early death. No management guidelines exist and there is a paucity of published disease-specific evidence to inform clinical practice, which currently draws upon experience from the field of childhood neurodisability. Twenty-four disease experts were surveyed on CLN2 disease management and a subset met to discuss current practice. Management goals and strategies are consistent among experts globally and are guided by the principles of pediatric palliative care. Goals and interventions evolve as the disease progresses, with a shift in focus from maintenance of function early in the disease to maintenance of quality of life. A multidisciplinary approach is critical for optimal patient care. This work represents an initial step toward the development of consensus-based management guidelines for CLN2 disease.

Purpose: To describe cytomegalovirus (CMV) retinitis outcomes in HIV-infected and non–HIV patients at a tertiary care center. Participants: Twenty-six eyes from 20 patients with active CMV retinitis were included in this study. Patients were immunocompromised due to HIV or secondary to immunosuppressive therapy for malignancy and organ transplantation. Methods: This is a retrospective, observational study of patients with newly diagnosed active CMV retinitis. The main outcomes included the incidence of visual acuity loss, the loss of visual acuity to 20/200 or worse, and the loss of 3 lines of vision or more. Secondary outcomes included the identification of risk factors for these visual results and the development of various complications such as retinal detachment (RD) and cataract formation. Results: In all, 51.9% (n = 14) of eyes lost vision from baseline at most recent follow-up and 34.6% (n = 9) lost 3 lines or more of vision, 34.6% (n = 9) of the eyes lost significant vision at most recent follow-up and had a final vision of 20/200 or worse, and 22.73% of phakic eyes underwent cataract surgery, whereas 23.1% (n = 6) of eyes developed RD. Patients presenting with a CD4+ T-cell count 100 cells/µL ( P = .0440). Although not statistically significant, patients who were immunocompromised due to HIV were less likely to lose 3 or more lines of vision ( P = .1881) and less likely to have a final visual acuity of 20/200 or worse ( P = .1881), when compared to patients who were immunocompromised due to other reasons. There was also a nonsignificant trend for eyes affected by a larger area of CMV retinitis at baseline (>25%) to have a final visual acuity of 20/200 or worse when compared to eyes with CMV retinitis involving Conclusions: Our cohort demonstrated that CMV retinitis remains a vision-threatening problem among patients who are immunocompromised due to HIV or other conditions. Immunocompromised patients are still at a significant risk of vision loss and complications from CMV retinitis and should be managed by a multidisciplinary team of physicians. In the immediate future, improved therapies are necessary to achieve immune recovery in patients, particularly for those remaining chronically immunosuppressed.

Ariana M Levin, Irene Rusu, Anton Orlin, Mrinali P Gupta, Peter Coombs, Donald J D’Amico, Szilárd Kiss Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA Purpose: The aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA) following anti-vascular endothelial growth factor (VEGF) intravitreal injections in patients treated for diabetic retinopathy. Methods: This study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders. Results: Twelve of 16 eyes (75%) or 11 of 15 patients (73.3%) demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF) fluorescein angiography and in the periphery outside the 7SF. Four of 16eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation. Conclusion: In patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA. Keywords: anti-VEGF, diabetes, diabetic retinopathy, ischemia, perfusion, reperfusion

Szilárd Kiss,1 Hitesh S Chandwani,2 Ashley L Cole,2 Vaishali D Patel,2 Orsolya E Lunacsek,3 Pravin U Dugel4 1Department of Ophthalmology, Weill Cornell Medical College, New York, NY, 2Global Health Economics and Outcomes Research, Allergan, Inc., Irvine, CA, 3Global Health Economics and Outcomes Research, Xcenda, LLC, Palm Harbor, FL, 4Retinal Consultants of Arizona and USC Eye Institute, Phoenix, AZ, USA Purpose: To examine the comorbidity profile and update estimates of health care resource utilization for commercially insured, working-age adults with diabetic macular edema (DME) relative to a matched comparison group of diabetic adults without DME. Additional comparisons were made in the subgroup of pseudophakic patients. Patients and methods: A retrospective matched-cohort study of commercially insured diabetic adults aged 18–63 years was conducted using medical and outpatient pharmacy claims (July 1, 2008–June 30, 2013). Outcomes included diabetes-related and ocular comorbidities and health care resource utilization (any health care visit days, outpatient visit days, inpatient visit days, emergency room visits, eye care-related visit days, unique medications) in the 12-month post-index period. Results: All diabetes-related and ocular comorbidities were significantly more prevalent in DME cases versus non-DME controls (P

Purpose To determine rates of intraoperative and postoperative systemic and ocular adverse events and establish the value of preoperative medical assessment in patients undergoing surgery for primary rhegmatogenous retinal detachment repair at a single academic center. Patients and methods Retrospective cohort study of 185 patients undergoing surgery for repair of primary rhegmatogenous retinal detachment (RRD) at a single academic center. Medical records were reviewed for medical comorbidities, completion of preoperative medical examination, anesthesia used during surgery, intraoperative adverse medical events, intraoperative ocular complications, and systemic and ocular postoperative complications. The main outcome of interest was the association of comorbidities and preoperative medical evaluation with intraoperative and postoperative complications. Results Approximately 48% of the patients presented with no medical comorbidities of interest. Formal preoperative evaluation by an independent medical provider was completed in 36% of the patients. Overall, intraoperative and postoperative systemic complications (5.7% and 1%, respectively) and intraoperative and postoperative ocular complications (0.5% for both) were uncommon. Patients with a history of chronic heart failure (OR 24.5, P=0.02) or who received general anesthesia (OR 9.56, P

Purpose To evaluate the long-term safety of vascular endothelial growth factor (VEGF) suppression with sustained aflibercept expression after a single intravitreal injection (IVI) of ADVM-022, an anti-VEGF gene therapy, in non-human primates (NHPs). Methods Non-human primates received bilateral IVI of ADVM-022, a gene therapy vector encoding aflibercept, a standard of care for the treatment of VEGF-based retinal disease. Aflibercept levels from ocular fluids and tissues were measured. Ocular inflammation was assessed by slit lamp biomicroscopy and fundoscopy. The integrity of the retinal structure was analyzed by optical coherence tomography and blue light fundus autofluorescence and electroretinography was performed to determine retinal function. Histologic evaluation of the retina was performed at the longest time point measured (2.5 years after injection). Results Sustained expression of aflibercept was noted out to the last time point evaluated. Mild to moderate inflammatory responses were observed, which trended toward spontaneous resolution without anti-inflammatory treatment. No abnormalities in retinal structure or function were observed, as measured by optical coherence tomography and electroretinography, respectively. RPE integrity was maintained throughout the study; no histologic abnormalities were observed 2.5 years after ADVM-022 IVI. Conclusions In non-human primates, long-term, sustained aflibercept expression and the resulting continuous VEGF suppression by a single IVI of ADVM-022, appears to be safe, with no measurable adverse effects on normal retinal structure and function evaluated out to 2.5 years. Translational relevance Together with the results from previous ADVM-022 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for various VEGF-mediated ophthalmic disorders.

We examined the relationship between glycemic control and urinary tract infections in women with type 1 diabetes mellitus.Women enrolled in the Epidemiology of Diabetes Interventions and Complications study, the observational followup of the Diabetes Control and Complications Trial, were surveyed to assess the rate of physician diagnosed urinary tract infections in the preceding 12 months. The relationship between glycated hemoglobin levels and number of urinary tract infections in the previous 12 months was assessed using a multivariable Poisson regression model.A total of 572 women were evaluated at year 17. Mean age was 50.7 ± 7.2 years, mean body mass index was 28.6 ± 5.9 kg/m(2), mean type 1 diabetes duration was 29.8 ± 5.0 years and mean glycated hemoglobin was 8.0% ± 0.9%. Of these women 86 (15.0%) reported at least 1 physician diagnosed urinary tract infection during the last 12 months. Higher glycated hemoglobin levels were significantly associated with number of urinary tract infections such that for every unit increase (1%) in recent glycated hemoglobin level, there was a 21% (p=0.02) increase in urinary tract infection frequency in the previous 12 months after adjusting for race, hysterectomy status, urinary incontinence, sexual activity in the last 12 months, peripheral and autonomic neuropathy, and nephropathy.The frequency of urinary tract infections increases with poor glycemic control in women with type 1 diabetes. This relationship is independent of other well described predictors of urinary tract infections and suggests that factors directly related to glycemic control may influence the risk of lower urinary tract infections.

Purpose To evaluate the ability to visualize and document posterior segment pathology through the Boston keratoprosthesis (KPro) using the Optos P200Tx ultra-widefield (UWF) scanning laser ophthalmoscope. Methods A retrospective chart review was conducted of patients who underwent Boston Type I keratoprosthesis implantation and who subsequently were imaged with an UWF system. Ultra-widefield images were reviewed to evaluate for vitreoretinal pathology and were compared with the clinical examination. Results In this series of 10 patients (10 eyes), 100% of vitreoretinal pathology found on clinical examination was detectable using the Optos system. In 4 cases (40%), UWF imaging provided superior detection of pathology compared with the clinical examination by imaging through retroprosthetic membranes (3 cases) and by detection of a retinal detachment (one case). In 1 case (10%), B-scan ultrasonography was needed to characterize vitreoretinal pathology that could not be definitively distinguished on UWF imaging and was difficult to detect on clinical examination. Ultra-widefield imaging detected the following vitreoretinal pathologies in KPro eyes: retinal hemorrhage, epiretinal membrane, retinal detachment, proliferative diabetic retinopathy, and choroidal folds. Conclusion Ultra-widefield imaging provides a high-resolution view of the posterior pole and periphery despite the limitations of imaging through the narrow optic of Boston Type I keratoprosthesis, and it may improve visualization through retroprosthetic membranes. Detection and documentation of vitreoretinal complications in the setting of a permanent keratoprosthesis may be enhanced using UWF imaging.