Reduced Glutathione Level Promotes Epithelial-Mesenchymal Transition in Lens Epithelial Cells via a Wnt/ß-Catenin-Mediated Pathway: Relevance for Cataract Therapy.

The epithelial-mesenchymal transition (EMT) process plays a pivotal role in the pathogenesis of posterior capsular opacification because of remnant lens epithelial cell proliferation, migration, and transformation after cataract surgery. The latter, we hypothesize, may result in posterior capsule wrinkling and opacification because of a profound change in the lens growth environment via a 1000-fold reduction of extracellular glutathione (GSH) levels. To test this hypothesis, we investigated the EMT process in cell culture and GSH biosynthesis deficiency mouse models. Our data indicate a dramatic increase of pro-EMT markers, such as type I collagen, α-smooth muscle actin, vimentin, and fibronectin, under conditions of lens GSH depletion. Further study suggests that decreased GSH triggers the Wnt/ß-catenin signal transduction pathway, independent of transforming growth factor-ß. Equally important, the antioxidants N-acetyl cysteine and GSH ethyl ester could significantly attenuate the EMT signaling stimulated by decreased GSH levels. These findings were further confirmed by mock cataract surgery in both gamma glutamyl-cysteine ligase, catalytic subunit, and gamma glutamyl-cysteine ligase, modifier subunit, knockout mouse models. Remarkably, increased EMT marker expression, ß-catenin activation, and translocation into the nucleus were found in both knockout mice compared with the wild type, and such increased expression could be significantly attenuated by N-acetyl cysteine or GSH ethyl ester treatment. This study, for the first time we believe, links oxidative stress to lens fibrosis and posterior capsular opacification formation via EMT-mediated mechanisms.

Co-management of cataract and glaucoma in the era of minimally invasive glaucoma surgery.

PURPOSE OF REVIEW: This review discusses the options available to be used in conjunction with phacoemulsification cataract surgery to control intraocular pressure. We present a strategy for planning which surgery should be performed based on goals of care. RECENT FINDINGS: New clinical evidence for using the CyPass, Kahook and Xen45 devices has been published recently and is summarized. SUMMARY: Cataract and glaucoma frequently exist together. Because the field of glaucoma surgical care is expanding and cataract surgery is becoming progressively safer, it is important to frequently re-evaluate our treatment paradigms. We review and evaluate current studies and treatment options.

Primary Practice Patterns For The Initial Management of Open Angle Glaucoma.

PRCIS: About 1/4th of survey respondents from an ASCRS database initiate treatment for primary open-angle glaucoma (POAG) with laser trabeculoplasty. Factors impacting physicians' choice of laser versus topical treatment for POAG were explored. PURPOSE: To characterize primary treatment preferences (topical medication vs. laser trabeculoplasty or intracameral sustained release implants) in primary open-angle glaucoma (POAG) patients and determine factors related to primary intervention selection. METHODS: A 33-question survey was distributed to an American Society of Cataract and Refractive Surgery database on treatment choices made by ophthalmologists for POAG. Data collected included country of practice, years of practice, completion of glaucoma fellowship training, type of practice, and preference for first line of treatment of POAG. Multiple logit regression was used to compare the effect of covariates on physicians' choice of either topical medication or laser trabeculoplasty for POAG. RESULTS: A total of 252/19,246 (1.3%) of surveys were returned. Almost three-quarters of respondents utilized topical medication as first line of treatment for POAG (73.6%) while 26.4% preferred to start with laser treatment. Significant variables associated with the selection of laser (vs. drops) are practicing in the U.S. (odds ratio [OR] 2.85, 95% confidence interval [CI] 1.33-6.10), more recent completion of ophthalmology residency (OR 1.95, 95% CI 1.00-3.77), greater volume of minimally invasive glaucoma surgeries (MIGS) (OR 1.68, 95% CI 1.18-2.40), and a glaucoma patient base greater than 25% (OR 2.21, 95% CI 1.09-4.48). CONCLUSIONS: For the first line treatment of POAG, laser trabeculoplasty is more likely to be preferred, over topical drops, by U.S. physicians who are relatively new in practice, who have a larger glaucoma patient base and who perform more MIGS.

Difficult decisions, filtration surgery, and the heartbreak of the numerator.

A 70-year-old man had progressive and severe glaucoma in each eye. He was intolerant to dorzolamide, brimonidine, and netarsudil. Each eye had prior selective laser trabeculoplasty (SLT) as well as phacoemulsification plus minimally invasive glaucoma surgery (MIGS) 6 years before current presentation (iStent [Glaukos Corp.] in the right eye and Cypass [Alcon Laboratories, Inc.] in the left eye). Postoperative acuities were 20/20 and 20/25 in the right and left eyes, respectively. When his left eye progressed with loss of central acuity despite peak intraocular pressures (IOPs) in the middle to upper teens, neuro-ophthalmology consultation was obtained (Figure 1JOURNAL/jcrs/04.03/02158034-202401000-00017/figure1/v/2023-12-22T124801Z/r/image-tiff). That workup included magnetic resonance imaging scan and hematologic screening, but all results were negative, and the neuro-ophthalmic consultant concluded that the vision loss was likely on the basis of glaucoma. Accordingly, a trabeculectomy was performed in the left eye achieving consistent IOPs in the range of 7 to 10 mm Hg without medications, rending the left eye stable since the filtration surgery nearly 2 years previously. The right eye continued to progress both subjectively and objectively, and on recent examination, the IOP measured 20 mm Hg and 09 mm Hg in the right and left eyes, respectively (Figure 2JOURNAL/jcrs/04.03/02158034-202401000-00017/figure2/v/2023-12-22T124801Z/r/image-tiff). Medications included timolol and latanoprostene bunod in the right eye only. Central corneal thickness was 526 µm and 527 µm in the right and left eyes, respectively. The visual acuity now measured 20/25 in the right eye and 20/250 in the left eye. The vertical cup-to-disc ratio was 0.9 in the right eye and 1.0 in the left eye. Gonioscopy revealed a wide open angle in each eye with a patent sclerostomy superiorly in the left eye. The conjunctiva and sclera were healthy and without scarring in the right eye. The bleb in the left eye was diffuse, lightly vascularized, and seidel negative. Axial length (AL) was 26.88 µm in the right eye and 26.77 µm in the left eye. The patient was in good health and was not anticoagulated. An extensive discussion ensued about the best course of action for the right eye. How would you proceed in managing definite progression in this individual's right eye, knowing that he had lost fixation in his left eye at similar pressures?

Fungal panophthalmitis presenting as severe posterior scleritis.

Purpose: To report a highly unusual and fulminant case of infectious fungal panophthalmitis that initially presented as angle closure in the setting of posterior scleritis, culminating in the loss of the affected eye. Observations: A 57-year-old woman with a history of poorly controlled diabetes mellitus and autoimmune disease presented with a unilateral flat anterior chamber, highly elevated intraocular pressure (50-65 mmHg) and severe chemosis of the right eye. Initial VA was NLP in the affected eye. An ultrasound B-scan revealed a very pronounced T-sign and severely thickened posterior sclera and choroid indicative of posterior scleritis. Bloodwork showed elevation of WBC count to 18 K/µL and broad spectrum antibiotics were initiated. However, a comprehensive infectious workup including fungal cultures were persistently negative. After three days of IV NSAIDs and antibiotics, WBC count normalized and pain had mildly improved. After consultation with a multidisciplinary team that included the Glaucoma, Retina/Uveitis, Infectious Disease, Rheumatology and Internal Medicine services, high dose IV methylprednisolone was started. Despite the initial improvement, corneoscleral decompensation and paralimbal perforation of the globe occurred. The eye was enucleated, and pathologic examination revealed a dense focus of budding yeast in the vitreous cavity. Conclusions and importance: Scleritis is a rare entity, with posterior scleritis, infectious scleritis, and fungal scleritis representing increasingly rare subtypes. However, fungal scleritis may be underdiagnosed due to a number of factors including culture negativity, a lack of clinical suspicion, as well as the disease's propensity to masquerade as other pathologies such as angle closure or malignant glaucoma. Fungal scleritis should be considered in cases that present with possible infectious etiology, worsen with systemic corticosteroid treatment, or worsen despite broad-spectrum antibiotic coverage. When treating patients with underlying risk factors such as uncontrolled diabetes mellitus, recent antibiotic use, use of total parenteral nutrition, or immunosuppression, a higher level of suspicion for fungal etiology is also appropriate. In the outpatient setting, fungal eye infections do not always present with critical systemic illness or culture positivity. If there is suspicion for fungal involvement, early aqueous or vitreous tap may improve diagnostic yield.

Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease.

Erythropoiesis-stimulating agents (ESAs) are effective in ameliorating anemia in chronic kidney disease (CKD). A recent trial in diabetic patients with CKD, however, suggested a greater risk of stroke associated with full correction of anemia with ESAs. Using national Veterans Affairs data we performed a case-control study examining the association of incident ESA use with acute stroke in patients with estimated glomerular filtration rate < 60 cm³/min per 1.73 m² and outpatient hemoglobin <12 g/dl. Using diagnosis codes, we identified 2071 acute hospitalized stroke cases and matched them 1:5 with controls without stroke, resulting in 12,426 total patients for analysis. Conditional logistic regression was used to estimate the association of ESA use with stroke, adjusting for potential confounders. After multivariate adjustment, ESA use in 1026 patients was associated with greater odds of stroke (odds ratio 1.30). There was significant interaction between ESA use and cancer, with greater odds of stroke among ESA-treated cancer patients (odds ratio 1.85), but not in ESA-treated patients without cancer (odds ratio 1.07). ESA-treated patients with cancer received a median initial dose 2.5-4 times greater than ESA-treated patients without cancer, but pre-ESA hemoglobin and its rate of change did not differ between these groups. Hence, in a large national sample of anemic patients with CKD, ESA treatment was associated with an increased risk of acute stroke with the greatest effect among patients with cancer.

Application of the Sight Outcomes Research Collaborative Ophthalmology Data Repository for Triaging Patients With Glaucoma and Clinic Appointments During Pandemics Such as COVID-19.

Importance: During the coronavirus disease 2019 (COVID-19) pandemic, eye care professionals caring for patients with sight-threatening diseases, such as glaucoma, have had to determine whether some patient appointments could safely get postponed, weighing the risk that the patient's glaucoma could worsen during the interim vs the morbidity risk of acquiring COVID-19 while seeking ophthalmic care. They also need to prioritize appointment rescheduling during the ramp-up phase (when pandemic-associated service reductions are eased). Objective: To describe a flexible and scalable scoring algorithm for patients with glaucoma that considers glaucoma severity and progression risk vs the presence of high-risk features for morbidity from COVID-19, using information from a large data repository. Design, Setting, and Participants: In this cross-sectional study, patients with upcoming clinic appointments for glaucoma from March 16, 2020, to April 16, 2020, at an academic institution enrolled in the Sight Outcomes Research Collaborative (SOURCE) Ophthalmology Electronic Health Record Data Repository were identified. A risk stratification tool was developed that calculated a glaucoma severity and progression risk score and a COVID-19 morbidity risk score. These scores were summed to determine a total score for each patient. Main Outcomes and Measures: Total scores and percentages of clinic appointments recommended for rescheduling. Results: Among the 1034 patients with upcoming clinic appointments for glaucoma, the mean (SD) age was 66.7 (14.6) years. There were 575 women (55.6%), 733 White individuals (71%), and 160 Black individuals (15.5%). The mean (SD) glaucoma severity and progression risk score was 4.0 (14.4) points, the mean (SD) COVID-19 morbidity risk score was 27.2 (16.1) points, and the mean (SD) total score was 31.2 (21.4) points. During pandemic-associated reductions in services, using total score thresholds of 0, 25, and 50 points would identify 970 appointments (93.8%), 668 appointments (64.6%), and 275 appointments (26.6%), respectively, for postponement and rescheduling. The algorithm-generated total scores also helped prioritize appointment rescheduling during the ramp-up phase. Conclusions and Relevance: A tool that considers the risk of underlying ophthalmic disease progression from delayed care receipt and the morbidity risk from COVID-19 exposure was developed and implemented, facilitating the triage of upcoming ophthalmic appointments. Comparable approaches for other ophthalmic and nonophthalmic care during the COVID-19 pandemic and similar crises may be created using this methodology.

Treat to Target in Psoriatic Arthritis.

A treat-to-target approach to psoriatic arthritis has emerged as a topic of interest following successful application of this treatment paradigm to rheumatoid arthritis. In psoriatic arthritis, this has been examined in one randomized trial to date showing benefits of a tight control treatment strategy over standard care. Nonetheless, international treatment recommendations have called for clinicians to aim for a target of remission or low disease activity, although little or no consensus exists on how to measure these targets. An ideal measure to define a treatment target should be able to address all the disease domains and preferences pertinent to an individual patient.