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Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is a commonly used therapy for numerous retinal diseases. The most commonly used of these medications are bevacizumab, ranibizumab, aflibercept, and brolucizumab. However, intravitreal administration of these agents is also associated with several inflammatory and non-inflammatory adverse events. The three inflammatory adverse events are sterile intraocular inflammation, brolucizumab-associated retinal vasculitis, and post-injection endophthalmitis. This narrative review summarizes the current literature regarding these conditions, including their epidemiology, presentation, management, outcomes, and pathogenesis. The inflammatory adverse events also share a number of overlapping features, which can make them difficult to discern from one another in a clinical context. This review discusses certain distinguishing features of these conditions that may aid providers in discerning between them and establishing the correct diagnosis.

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.

Purpose: To report the practices and outcomes of ophthalmic evaluations for pentosan polysulfate sodium (PPS) maculopathy at a single institution. Methods: This study was conducted on patients of Massachusetts Eye and Ear who had documented PPS exposure and an ophthalmic encounter from 2019 through 2022. The main outcomes were examination components performed and identification of PPS maculopathy. Image analysis confirmed findings. Results: Thirty-seven patients were included. Of the initial encounters, optical coherence tomography (OCT) was documented for 29 (78.4%) patients, fundus autofluorescence (FAF) for 13 (35.1%), and color fundus photography (CFP) for 12 (32.4%). Four cases (10.8%) of PPS maculopathy were observed. Mean (range) duration of exposure was 17 (15–20), and mean (range) cumulative exposure was 2418 (2190–2628) mg. Maculopathy did not occur until after 15 years of exposure and greater than 2000 mg of cumulative exposure. Three cases (8.1%) of PPS maculopathy were evaluated following drug cessation over a mean of 18.3 months. Two cases (5.4%) of PPS maculopathy progression post-cessation over durations of 1.1 and 4.3 years were described. Conclusion: We found inadequate imaging and documentation of OCT, CFP, and FAF to evaluate for toxicity in patients with a history of current or past PPS exposure. This study contributes four cases of PPS maculopathy to the growing literature reporting the phenotypic spectrum of toxicity, including two cases of maculopathy progression following drug cessation. There is a need for evaluations post-cessation due to possible progression of maculopathy, so patients are not treated inappropriately for differential diagnoses. Plain language summary Evaluating for pentosan polysulfate sodium maculopathy We conducted a retrospective study to assess evaluation practices for pentosan polysulfate use. We found that providers may be underutilizing retinal imaging. We found low rates of toxic maculopathy and high mean exposures for the development of maculopathy. Finally, we report two cases of disease progression post-drug cessation.

Proliferative vitreoretinopathy (PVR) is the leading cause of retinal detachment surgery failure. Despite significant advances in vitreoretinal surgery, it still remains without an effective prophylactic or therapeutic medical treatment. After ocular injury or retinal detachment, misplaced retinal cells undergo epithelial to mesenchymal transition (EMT) to form contractile membranes within the eye. We identified Runt-related transcription factor 1 (RUNX1) as a gene highly expressed in surgically-removed human PVR specimens. RUNX1 upregulation was a hallmark of EMT in primary cultures derived from human PVR membranes (C-PVR). The inhibition of RUNX1 reduced proliferation of human C-PVR cells in vitro, and curbed growth of freshly isolated human PVR membranes in an explant assay. We formulated Ro5-3335, a lipophilic small molecule RUNX1 inhibitor, into a nanoemulsion that when administered topically curbed the progression of disease in a novel rabbit model of mild PVR developed using C-PVR cells. Mass spectrometry analysis detected 2.67 ng/mL of Ro5-3335 within the vitreous cavity after treatment. This work shows a critical role for RUNX1 in PVR and supports the feasibility of targeting RUNX1 within the eye for the treatment of an EMT-mediated condition using a topical ophthalmic agent.

Acromegaly is a rare disease that is caused by a growth hormone (GH) secreting pituitary tumor. This is a case of a 62‐year‐old man who presented with hypertrophic cardiomyopathy more than 25 years after surgical remission without other known etiologies of left ventricular hypertrophy. The patient initially presented at age 28 with symptoms of acromegaly and diagnosed himself, while several physicians dismissed the diagnosis. He underwent transsphenoidal surgery associated with long‐term remission. At age 53, he developed palpitations, light headedness, dizziness, and chest tightness, and an echocardiogram demonstrated left ventricular hypertrophy. At age 60, cardiac magnetic resonance imaging (MRI) suggested hypertrophic cardiomyopathy, which continues to be followed. This case raises the question of whether cardiac morphological changes occur in patients with acromegaly who have GH and insulin‐like growth factor‐1 (IGF‐1) levels well controlled. Cardiac MRI is the most accurate imaging modality for assessment of cardiomyopathy. However, more research is needed to inform clinical guidelines on screening for cardiac functional and morphological changes in patients with acromegaly.

Background Biomarker”, a merged word of “biological marker”, refers to a broad subcategory of medical signs that objectively indicate the state of health, and well-being of an individual. Biomarkers hold great promise for personalized medicine as information gained from diagnostic or progression markers can be used to tailor treatment to the individual for highly effective intervention in the disease process. Optical coherence tomography (OCT) has proved useful in identifying various biomarkers in ocular and systemic diseases. Main body Spectral domain optical coherence tomography imaging-based biomarkers provide a valuable tool for detecting the earlier stages of the disease, tracking progression, and monitoring treatment response. The aim of this review article is to analyze various OCT based imaging biomarkers and their potential to be considered as surrogate endpoints for diabetic retinopathy, age related macular degeneration, retinitis pigmentosa and vitreomacular interface disorder. These OCT based surrogate markers have been classified as retinal structural alterations (macular central subfield thickness and cube average thickness); retinal ultrastructural alterations (disruption of external limiting membrane and ellipsoid zone, thinning of retinal nerve fiber layer and ganglion cell layer); intraretinal microangiopathic changes; choroidal surrogate endpoints; and vitreoretinal interface endpoints. Conclusion OCT technology is changing very quickly and throughout this review there are some of the multiple possibilities that OCT based imaging biomarkers will be more useful in the near future for diagnosis, prognosticating disease progression and as endpoint in clinical trials.

BACKGROUND AND OBJECTIVE: To compare efficacy of monthly treatment with bevacizumab or ranibizumab for macular edema due to retinal vein occlusion. PATIENTS AND METHODS: Randomized, multicenter, comparative trial (Randomized, multicenter, comparative trial ( ClinicalTrials.gov identifier: NCT01428388). Participants were randomized 1:1 to receive monthly treatment with bevacizumab or ranibizumab. The primary outcome was change in central foveal thickness at 6 months compared to baseline. RESULTS: The trial randomized 98 patients to treatment with bevacizumab or ranibizumab. At 6 months, there were no differences in change in central foveal thickness between groups (bevacizumab: mean reduction of 212.6 µm, 95% confidence interval [CI], −288.3 to −137.0; ranibizumab: mean reduction of 243.8 µm, 95% CI, −309.6 to −178.0; The trial randomized 98 patients to treatment with bevacizumab or ranibizumab. At 6 months, there were no differences in change in central foveal thickness between groups (bevacizumab: mean reduction of 212.6 µm, 95% confidence interval [CI], −288.3 to −137.0; ranibizumab: mean reduction of 243.8 µm, 95% CI, −309.6 to −178.0; P = .72, analysis of variance [ANOVA]). Both groups showed similar functional outcomes (bevacizumab: 0.33 logMAR gain, 95% CI, −0.47 to −0.18; ranibizumab: 0.34 logMAR gain, 95% CI, −0.45 to −0.23; P = .38, ANOVA). CONCLUSION: In the treatment of retinal vein occlusion, bevacizumab and ranibizumab have similar effects on reducing macular thickness and improving visual acuity. [[ Ophthalmic Surg Lasers Imaging Retina . 2015;46:844–850.]

Retinal venous occlusive events are a rare complication of arteriovenous malformations of the retina found in Wyburn-Mason syndrome. The authors present a case of a 28-year-old man diagnosed with Wyburn-Mason syndrome and cutaneous reactive angiomatosis, a reactive angioproliferative disorder induced by vascular occlusion. He developed a central retinal vein occlusion complicated by macular edema and received treatment with intravitreal bevacizumab, which led to resolution of the edema. To the best of the authors’ knowledge, this is the first report of an anti– vascular endothelial growth factor agent employed as an effective treatment for macular edema in the setting of Wyburn-Mason syndrome. The association between Wyburn-Mason syndrome and cutaneous reactive angiomatosis is also a novel finding. [[ Ophthalmic Surg Lasers Imaging Retina . 2015;46:760–762.]