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Since they were first derived more than three decades ago, embryonic stem cells have been proposed as a source of replacement cells in regenerative medicine, but their plasticity and unlimited capacity for self-renewal raises concerns about their safety, including tumour formation ability, potential immune rejection, and the risk of differentiating into unwanted cell types. We report the medium-term to long-term safety of cells derived from human embryonic stem cells (hESC) transplanted into patients. In the USA, two prospective phase 1/2 studies were done to assess the primary endpoints safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium in nine patients with Stargardt's macular dystrophy (age >18 years) and nine with atrophic age-related macular degeneration (age >55 years). Three dose cohorts (50 000, 100 000, and 150 000 cells) were treated for each eye disorder. Transplanted patients were followed up for a median of 22 months by use of serial systemic, ophthalmic, and imaging examinations. The studies are registered with ClinicalTrials.gov, numbers NCT01345006 (Stargardt's macular dystrophy) and NCT01344993 (age-related macular degeneration). There was no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue. Adverse events were associated with vitreoretinal surgery and immunosuppression. 13 (72%) of 18 patients had patches of increasing subretinal pigmentation consistent with transplanted retinal pigment epithelium. Best-corrected visual acuity, monitored as part of the safety protocol, improved in ten eyes, improved or remained the same in seven eyes, and decreased by more than ten letters in one eye, whereas the untreated fellow eyes did not show similar improvements in visual acuity. Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 16–25 points 3–12 months after transplantation in patients with atrophic age-related macular degeneration and 8–20 points in patients with Stargardt's macular dystrophy. The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease. Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of various unmet medical disorders requiring tissue repair or replacement. Advanced Cell Technology.

IntroductionVitreoretinal lymphoma is a rare ocular cancer with high morbidity and mortality despite treatment. Diagnosis by cytopathology is often delayed, and various molecular and image-based investigations have been developed. Diverse treatments are used, but there is a limited medical evidence to differentiate their effectiveness. We designed an international registry that would collect diagnostic, treatment and outcomes data, to establish new evidence for the management of this cancer.Methods and analysisThe International Vitreoretinal B-Cell Lymphoma Registry will accrue data retrospectively for individuals aged 18 years or older, diagnosed with new or recurrent vitreoretinal B-cell lymphoma on or after 1 January 2020. A steering committee of subspecialised ophthalmologists identified 20 key clinical data items that describe patient demographics, tissue involvements, diagnostic testing, ocular and systemic treatments and treatment complications, and visual acuity and survival outcomes. Customised software was designed to permit collection of these data across a single baseline and multiple follow-up forms. The platform collects data without identifiers and at 3 month reporting intervals. Outcomes of the project will include: (1) descriptions of clinical presentations, and diagnostic and therapeutic preferences; (2) associations between clinical presentations, and diagnostics and treatments, and between diagnostics and treatments (assessed by ORs with 95% CIs); and (3) estimations of rates of vision loss, and progression-free and overall survival (assessed by Kaplan-Meier estimates).Ethics and disseminationThe registry has received Australia-wide approval by a national human research ethics committee. Sites located outside Australia are required to seek local human research ethics review. Results generated through the registry will be disseminated primarily by peer-reviewed publications that are expected to inform clinical practice, as well as educational materials.

To report the visual outcomes and complications of scleral fixated intraocular lenses (IOLs) using Gore-Tex suture. The current study is a retrospective noncomparative case series including patients who underwent scleral fixation of IOL (Akreos AO60) using Gore-Tex suture from August 2015 to March 2017 at a university teaching center. Primary outcome measures were visual acuity and complications at last follow-up. The current study included 49 eyes of 48 patients. Mean follow-up duration postsurgery was 6.9 months (range: 0.9-29.4 months). The indications for secondary IOL surgery were dislocated IOL in 16/49 (33%), subluxed IOL in 9/49 (18%), dislocated or subluxed crystalline lens in 9/49 (18%), traumatic cataract in 8/49 (16%), and complicated cataract surgery in 7/49 (14%). Mean best-corrected logMAR visual acuity improved from 1±0.7 (20/200 Snellen equivalent) preoperatively to 0.5±0.5 (20/63 Snellen equivalent) at last follow-up. There were no intraoperative complications noted. Early postoperative complications included significant persistent corneal edema (longer than 1 week) in 4/49 (8.2%), ocular hypertension (intraocular pressure ≥25 mmHg) in 8/49 (16.3%), hypotony (intraocular pressure ≤5 mmHg) in 6/49 (12.2%), cystoid macular edema 3/21 (6.1%), IOL tilt 2/49 (4.1%), hyphema in 2/49 (4.1%), and vitreous hemorrhage in 5/49 (4.8%). There was one case of recurrent retinal detachment. One patient presented with an erosion of the Gore-Tex suture through the conjunctiva resulting in a purulent scleritis 6 months after the initial surgery, and was managed with removal of the IOL, debridement, and cryotherapy. Forty-one of 49 patients completed 3-month follow-up, among which visual acuity improved, deteriorated, or remained same compared to baseline in 27/49 (55.1%), 8/49 (16.3%), and 6/49 (12.2%) eyes, respectively. In the current study, visual acuity outcomes were generally favorable. The complications were largely transient. Significant complications included a suture-related infection, which required removal of the IOL, and a recurrence of a retinal detachment.

BACKGROUND AND OBJECTIVE: To assess the incidence and outcomes of infectious endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. PATIENTS AND METHODS: Patient records at the Bascom Palmer Eye Institute (BPEI) from January 1, 2005, through December 31, 2014, were reviewed. The largest commercial claims and encounters database in the U.S. (MarketScan) was utilized to calculate the population-based endophthalmitis rate for 2011 to 2013. RESULTS: The population-based rate of endophthalmitis after anti-VEGF injections for 2011 to 2013 was 391/740,757 (0.053%). BPEI’s rate was 20/121,285 (0.016%) during the study period: eight after bevacizumab (0.012%), six after ranibizumab (0.018%), and six after aflibercept (0.031%) injection. Nine BPEI cases (45%) were culture-positive: Streptococcus species (5), coagulase-negative Staphylococcus (3), and non-anthracis Bacillus (1). Final visual acuity varied from 20/25 to no light perception. CONCLUSION: Endophthalmitis after anti-VEGF injection was uncommon in our institution and in the population-based database. Treatment outcomes were variable but generally fared better in the culture-negative cases. [[ Ophthalmic Surg Lasers Imaging Retina . 2015;46:643–648.]

Background: Nephrologists routinely provide end-of-life care for patients with kidney failure (KF) on maintenance dialysis. Involvement of primary care and palliative care physicians may enhance this experience. Objective: The objective was to describe outpatient care patterns in the last year of life and the end-of-life acute care utilization for patients with KF on maintenance dialysis. Design: Retrospective cohort study using population-level health administrative data. Setting & Participants: Outpatient and inpatient care during the last year of life among patients who died between 2017 and 2019, receiving maintenance dialysis in Ontario, Canada. Measurements: The primary exposure is patterns of physician specialties providing outpatient care in the last year of life. Outcomes include outpatient encounters in the last year of life, acute care visitation in the last month of life, and place of death. Methods: We reported the count and percentage of categorical outcomes and the median (interquartile range) for numeric outcomes. We produced time series plots of the mean monthly percentage of encounters to different specialties stratified by physician specialty patterns. We evaluated differences in outcomes by physician specialty patterns using analysis of variance (ANOVA) and Pearson’s chi-square tests (P < .05, two-tailed). Results: Among 6866 patients, the median age at death was 73, 36.1% were female, and 87.8% resided in urban regions. Three patterns emerged: a primary care, nephrology, and palliative care triad (25.5%); a primary care and nephrology dyad (59.3%); and a non-primary care pattern (15.2%). Palliative care involvement is concentrated near death. Of all, 81.4% spent at least 1 day in hospital or emergency department in the last month, but those with primary care, palliative care, and nephrology involvement had the fewest acute care deaths (65.8%). Limitations: Outpatient care patterns were defined using physician billing codes, potentially missing care from other providers. Conclusions: Nephrology and primary care predominantly manage outpatient care in the last year of life for patients with KF on maintenance dialysis, with consistent acute care use across care patterns except for the place of death. Future research should explore associations between patterns of care and end-of-life outcomes to identify the most optimal model of care for patients with KF on maintenance dialysis.

Background Central serous chorioretinopathy (CSC) is marked by serous retinal detachments caused by fluid leakage from the retinal pigment epithelium, often associated with stress, psychiatric disorders and the use of corticosteroids. This study aims to investigate the clinical and systemic characteristics associated with BALAD in patients with CSC, comparing those with and without BALAD to clarify its function as a biomarker of CSC severity and improve diagnostic and treatment approaches. Purpose Compare the clinical characteristics, risk factors, and optical coherence tomography (OCT) findings in patients with Central Serous Chorioretinopathy (CSC) with and without Bacillary Layer Detachment (BALAD), and to identify the distinguishing features and associated conditions of CSC with BALAD. Methods This observational, retrospective, multicenter case–control study collected data from 12 retina centers worldwide on patients with central serous chorioretinopathy (CSC) from December 1, 2022, to April 1, 2023. CSC was defined by serous retinal detachment and fluid leakage through the retinal pigment epithelium. Patients underwent detailed evaluations, including OCT, and were classified as having acute or chronic CSC. Inclusion criteria included a CSC diagnosis with RPE leakage, BALAD confirmed by three authors, age over 18, and a detailed medical history from the 30 days before symptom onset. The study assessed visual acuity, choroidal thickness, psychiatric disorders, corticosteroid use, prior CSC treatments, and hyperreflective material on OCT. Results Thirty-seven patients (40 eyes; mean age, 48.0 ± 11.9 years) had CSC and BALAD and were followed for a mean of 4.92 ± 6.65 months. The control group was comprised of 40 patients with CSC without BALAD (40 eyes; mean age, 48.2 ± 11.9 years). On clinical examination, BALAD was as a circular, yellowish macular lesion. On OCT, BALAD was a detachment of the ellipsoid zone with splitting of the photoreceptor inner segment. BALAD was associated with psychiatric disorders ( p  = 0.014), use of corticosteroids ( p  = 0.004), previous treatment for CSC ( p  = 0.041) and thickened choroid ( p  = 0.036). Conclusions BALAD in CSC differs from a typical CSC due to the presence of a circular, yellowish macular lesion, detachment of the ellipsoid zone, segmentation of the inner segment of the photoreceptor, a thicker choroid, the use of corticosteroids, and generally more aggressive previous treatments. These results suggest that BALAD may serve as a valuable biomarker for the severity of CSC and highlight the influence of inflammation and previous treatments.

Introduction This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts. Methods This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey. Results Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2 , 3.9% mentioned NLRP3 or MEFV , and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams ( p  < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography ( p  > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances ( p  < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 ( p  < 0.01) and interleukin-6 ( p  < 0.01) inhibitors. Conclusions This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network—IUSG unified effort to advance scientific knowledge and clinical practice.

Current data permit only speculations regarding sex differences in the prevalence of infectious uveitis between women and men because uveitis case surveys do not uniformly report gender data. Differences in prevalence that are reported in the literature could relate to simple differences in the number of women and men at risk for infection or to biological differences between men and women. Compared to other types of uveitis, infectious uveitis may be directly related to occupational exposures or sexual behaviors, which differ between women and men, and may mask actual biological differences in susceptibility to ocular manifestations of the infection and its prognosis. In infectious uveitis for which there is no element of sexual transmission and data is available, prevalence of ocular disease is roughly equal between women and men. Women also have a unique relationship with infectious uveitis in their role as mothers. Vertical transmission of infections such as herpes simplex, toxoplasmosis, and cytomegalovirus can produce severe chorioretinitis in neonates.

Background Five of 7 (71%) elderly immunocompetent patients with cytomegalovirus retinitis had retinal arteriolar occlusions versus 2 of 8 (25%) elderly immunocompromised patients and 1 of 19 (5%) younger HIV-infected patients. Compared to HIV-infected patients, elderly patients were more likely to have occlusive events, neovascularization or hemorrhage, and underlying vasculopathy. The purpose of this study is to report the novel finding of extensive retinal arteriolar occlusions and neovascularization in immunocompetent patients with cytomegalovirus retinitis. This is a retrospective observational cohort study of cytomegalovirus retinitis (CMVR) in a university setting. Seven patients were elderly but not immunocompromised, 8 were elderly and iatrogenically immunocompromised, and 16 were HIV-infected. All patients underwent polymerase chain reaction testing of intraocular fluid. Primary outcome measure was visual acuity. Secondary outcome measures were vascular occlusions, ischemic complications, and response to treatment. Results Mean age was 73, 70, and 41 years for immunocompetent, immunocompromised, and HIV-infected patients, respectively. Diabetes and vascular disease were common in the elderly. Vision loss to less than 5/200 occurred in 50% of the immunocompetent elderly patients, and 17% of CMV eyes in immunocompromised and HIV patients. Occlusion of the entire retinal vasculature occurred in 4/7 (57%) of immunocompetent patients despite lack of Zone I involvement, and rubeosis occurred in three, disc neovascularization in one, and vitreous hemorrhage in two patients. Vascular occlusive events were less common in immunocompromised patients and rare in the HIV-infected. Conclusions CMVR in non-HIV-infected elderly patients is associated with retinal arteriolar occlusions. An intact host immune response may increase damage to retinal vessels. Prompt diagnosis may avert catastrophic vision loss.

[[ Ophthalmic Surg Lasers Imaging Retina . 2015;46:396–397.]