IMPORTANCE Patient perceptions regarding the risks of obtaining in-person ophthalmic care during the coronavirus disease 2019 (COVID-19) pandemic may affect adherence to recommended treatment plans and influence visual outcomes. A deeper understanding of patient perspectives will inform strategies to optimize adherence with vision-preserving therapies.OBJECTIVE To evaluate perceptions of COVID-19 exposure risk and their association with appointment attendance among patients at high risk of both reversible and irreversible vision loss from lapses in care. DESIGN, SETTING, AND PARTICIPANTSThis survey study included a nonvalidated telephone survey designed in April and May of 2020 and a retrospective medical record review conducted in parallel with survey administration from May 22 to August 18, 2020. Participants were recruited from 2 tertiary eye care centers (Emory Eye Center in Atlanta, Georgia, and W.K. Kellogg Eye Center in Ann Arbor, Michigan). The study included a random sample of patients with diagnoses of exudative age-related macular degeneration (AMD) or diabetic retinopathy (DR) who received an intravitreal injection between January 6 and March 13, 2020, and were scheduled for a second injection between March 13 and May 6, 2020.MAIN OUTCOMES AND MEASURES Association between perceptions regarding COVID-19 risks and loss to follow-up. RESULTSOf 1004 eligible patients, 423 (42%) were successfully contacted, and 348 (82%) agreed to participate (participants' mean [SD] age, 75 [12] years; 195 women [56%]; 287 White [82%] patients). Respondents had a mean (SD) of 2.7 (1.1) comorbidities associated with severe COVID-19, and 77 (22%) knew someone with COVID-19. Of all respondents, 163 (47%) were very concerned or moderately concerned about vision loss from missed treatments during the pandemic. Although 208 (60%) believed the COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exposure at the eye clinic was extremely unlikely or unlikely, 49 (14%) believed it was extremely likely or likely. Seventy-eight participants (22%) were lost to follow-up. Concern regarding COVID-19 exposure during clinic visits (odds ratio [OR], 3.9; 95% CI, 1.8-8.4) and diagnosis of DR (vs AMD) (OR, 8.130; 95% CI, were associated with an increase in likelihood of loss to follow-up.CONCLUSIONS AND RELEVANCE Among patients at high risk for vision loss from lapses in care, many expressed concerns regarding the effect of the pandemic on their ability to receive timely care. Survey results suggest that fear of SARS-CoV-2 exposure was associated with a roughly 4-fold increase in the odds of patient loss to follow-up. These results support the potential importance of clearly conveying infection-control measures.
The TRP channels localized to subdomains of the apical membrane, and BaCl2 was only able to dissociate tight junctions when presented to the apical membrane. The data suggest a potential role for TRP channels as sensors of [Ca(2+)] in the subretinal space.
IMPORTANCE Oklahoma is one of the few states where optometrists have surgical privileges to perform laser trabeculoplasty (LTP). Optometrists in other states are lobbying to obtain privileges to perform LTP and other laser procedures. Little is known whether outcomes of patients undergoing this procedure by optometrists are similar to those undergoing LTP by ophthalmologists. OBJECTIVE To compare outcomes of LTPs performed by ophthalmologists with those performed by optometrists to determine whether differences exist in the need for additional LTPs. DESIGN, SETTING, AND PARTICIPANTS This retrospective longitudinal cohort study used a health care claims database containing more than 1000 eyes of Medicare enrollees with glaucoma who underwent LTP in Oklahoma from January 1, 2008, through December 31, 2013. For each procedure, the data specify the type of eye care professional who performed the LTP. The rate of LTPs performed by ophthalmologists that required 1 or more additional LTPs in the same eye was compared with the rate of LTPs performed by optometrists. Regression models determined factors affecting risk of undergoing more than 1 LTP in the same eye. MAIN OUTCOMES AND MEASURES Proportion of enrollees requiring additional LTPs, hazard ratio with 95% CIs of undergoing additional LTPs.
Mutations of claudin-19 cause severe ocular deficits that are not easily reconciled with its role in regulating the outer blood retinal barrier. ARPE-19 is a widely used culture model of the retinal pigment epithelium (RPE). ARPE-19 is unique among epithelial cell lines, because it expresses all tight junction proteins except claudin family members. ARPE-19 also loses aspects of the RPE phenotype with cell passage. This study asks whether exogenous expression of the main RPE claudins, claudin-3 and claudin-19, would restore RPE phenotype, and whether these claudins have distinct roles in RPE. An Ussing chamber was used to measure the transepithelial electrical resistance and transepithelial electrical potential. These measurements were used to estimate the permeability co-efficients of ions. The transepithelial diffusion of polyethylene glycols were used to examine the leak pathway of tight junctions. Wound-healing, quantitative RT-PCR and immunoblotting examined diverse aspects of the RPE phenotype. Over-expression of either claudin decreased the permeability of small ions and polyethylene glycol. Both claudins were slightly cation-specific, but claudin-3 was less permeable to large solutes. Claudin expression widely affected gene expression to partially restore RPE phenotype. Claudins redistributed filamentous actin from stress fibers to circumferential bands associated with tight junctions, and made wound-healing more epithelial-like. Both claudins increased the expression of genes related to RPE core functions and increased steady-state levels of phosphorylated-AKT. In conclusion, claudin-3 and claudin-19 formed general permeability barriers and affected cell morphology, proliferation, migration, AKT signaling, and gene expression. When claudins are exogenously expressed, ARPE-19 more closely model native RPE.
IMPORTANCE Medical and surgical interventions for glaucoma are effective only if they are affordable to patients. Little is known about how affordable glaucoma interventions are in developing and developed countries.OBJECTIVE To compare the prices of topical glaucoma medications, laser trabeculoplasty, and trabeculectomy relative with median annual household income (MA-HHI) for countries worldwide.DESIGN, SETTING AND PARTICIPANTS Cross-sectional observational study. For each country, we obtained prices for glaucoma medications, laser trabeculoplasty, and trabeculectomy using government pricing data, drug databases, physician fee schedules, academic publications, and communications with local ophthalmologists. Prices were adjusted for purchasing power parity and inflation to 2016 US dollars, and annual therapy prices were examined relative to the MA-HHI. Interventions costing less than 2.5% of the MA-HHI were considered affordable. MAIN OUTCOMES AND MEASURESDaily cost for topical glaucoma medications, cost of annual therapy with glaucoma medications, laser trabeculoplasty, and trabeculectomy relative to MA-HHI in each country.RESULTS Data were obtained from 38 countries, including 17 developed countries and 21 developing countries, as classified by the World Economic Outlook. We observed considerable variability in intervention prices compared with MA-HHI across the countries and across interventions, ranging from 0.1% to 5% of MA-HHI for timolol, 0.1% to 27% for latanoprost, 0.2% to 17% for laser trabeculoplasty, and 0.3% to 42% for trabeculectomy. Timolol was the most affordable medication in all countries studied and was 2.5% or more of MA-HHI in only 2 countries (5%). The annual cost of latanoprost was 2.5% or more of MA-HHI in 15 countries (41%) (15 developing countries [75%] and no developed countries). The cost of laser trabeculoplasty was 2.5% or more of the MA-HHI in 15 countries (44%) (11 developing countries [65%] and 4 developed countries [24%]). The cost of trabeculectomy was 2.5% or more of the MA-HHI in 28 countries (78%) (18 developing countries [95%] and 10 developed countries [59%]). In 18 countries (53%), laser trabeculoplasty cost less than a 3-year latanoprost supply.CONCLUSIONS AND RELEVANCE For many patients worldwide, the costs of medical, laser, and incisional surgical interventions were 2.5% or more of the MA-HHI. Successfully reducing global blindness from glaucoma requires addressing multiple contributing factors, including making glaucoma interventions more affordable.
Cutaneous squamous cell carcinoma (SCC) is the most prevalent invasive malignancy with metastatic potential. The epidermis is exposed to a variety of environmental DNA-damaging chemicals, principal among which are polyaromatic hydrocarbons (PAH) ubiquitous in the environment, tobacco smoke, and broiled meats. Langerhans cells (LC) comprise a network of dendritic cells situated adjacent to basal, suprabasal, and follicular infundibular keratinocytes that when mutated can give rise to SCC, and LC-intact mice are markedly more susceptible than LC-deficient mice to chemical carcinogenesis provoked by initiation with the model PAH, 7,12-dimethylbenz[a]anthracene (DMBA). LC rapidly internalize and depot DMBA as numerous membrane-independent cytoplasmic foci. Repopulation of LC-deficient mice using fetal liver LC-precursors restores DMBA-induced tumor susceptibility. LC expression of p450 enzyme CYP1B1 is required for maximal rapid induction of DNA-damage within adjacent keratinocytes and their efficient neoplastic transformation; however, effects of tumor progression also attributable to the presence of LC were revealed as CYP1B1-independent. Thus, LC make multifaceted contributions to cutaneous carcinogenesis, including via the handling and metabolism of chemical mutagens. Such findings suggest a cooperative carcinogenesis role for myeloid-derived cells resident within cancer susceptible epithelial tissues principally by influencing early events in malignant transformation.
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