By 2040, one third of worldwide cases of age-related macular degeneration (AMD) will originate from Asia.1 Although both geographic atrophy (GA) and neovascular AMD (nAMD) can result in irreversible blindness, currently no treatment exists for GA. Thus, understanding the global epidemiologic characterists of GA can better guide allocations of health care resources and future research. To address the limited knowledge regarding the prevalence of GA in the Asian population, Rim et al2 (see page 1371) performed a cross-sectional meta-analysis of 22 population-based studies from the Asian Eye Epidemiology Consortium. A total of 97,213 individuals from 10 Asian countries were included.
Objectives
To evaluate the impact of the novel coronavirus pandemic on practice patterns, clinical behavior, personal health, and emotional/psychological concerns of rhinologists.
Methods
A 15-question survey was sent out to the American Rhinologic Society's (ARS) membership to determine the impact of COVID-19 during the crisis. Demographic factors and practice patterns were collected and evaluated.
Results
There were 224 total respondents out of 835 ARS members queried (26.8% response rate). Study queries were sent in April 2020. Notably, 17.8% reported illness in themselves or their staff and 74.4% noted a psychological/emotional impact. A plurality of rhinologists noted their practice volume and in-office procedure volume has become 20.0% and 0.0% of their prior volumes, respectively. In addition, 96.2% were noted to be using telemedicine in our subspecialty.
Conclusion
In addition to severely impacting volume and the perception of future decreases in patients and revenue, the COVID-19 pandemic has had a physical and emotional impact on rhinologists in ways that need to be further studied. These data include significantly novel and objective information. The COVID-19 crisis also reveals the important role of telemedicine in rhinology. Guidelines regarding personal protective equipment for in-office visits, nasal endoscopy, and other in-office and operating room procedures would be particularly helpful as future waves are expected.
Previously, we and others have shown that the regular intake of green tea polyphenols (GTPs) reduces ultraviolet B (UVB) radiation-induced skin cancer by targeting multiple signaling pathways, including DNA damage, DNA repair, immunosuppression, and inflammation. Here, we determine the effect of GTPs on UVB-induced epigenetic changes, emphasizing DNA hyper-methylation in UV-exposed skin and tumors and their association with miR-29, a key regulator of DNA methyltransferases (DNMTs). Skin cancer was induced in SKH-1 hairless mice following repeated exposures of UVB radiation (180 mJ/cm2, three times/week, 24 weeks) with or without GTPs supplementation (0.2%) in drinking water. Regular intake of GTPs inhibited tumor growth by hindering the cascade of DNA hypermethylation events. GTPs supplementation significantly blocked UVB-induced DNA hypermethylation in the skin (up to 35%; p < 0.0001) and in tumors (up to 50%; p < 0.0001). Experimental results showed that the levels of DNA hypermethylation were higher in GTPs-treated mice than in the control group. The expressions of miR-29a, miR-29b, and miR-29c were markedly decreased in UV-induced skin tumors, and GTPs administration blocked UVB-induced miR-29s depletion. Furthermore, these observations were verified using the in vitro approach in human skin cancer cells (A431) followed by treatment with GTPs or mimics of miR-29c. Increased levels of miR-29 were observed in GTPs-treated A431 cells, resulting in increased TET activity and decreased DNA hypermethylation. In conclusion, UVB-mediated miR-29 depletion promotes DNA hypermethylation and leads to enhanced tumor growth by silencing tumor suppressors. Regular intake of GTPs rescued UVB-induced miR-29 depletion and prevented tumor growth by maintaining reduced DNA hypermethylation and activating tumor suppressors. Our observations suggest that miR-based strategies and regular consumption of GTPs could minimize the risk of UVB-induced skin cancers and contribute to better management of NMSCs.
Globally, there are nearly three million people living with multiple sclerosis (PLW-MS). Many PLW-MS experience vertigo and have signs of vestibular dysfunction, e.g., low vestibulo–ocular reflex (VOR) gains or the presence of compensatory saccades (CSs), on video head impulse testing (vHIT). We examined whether the vestibular function and compensatory oculomotor behaviors in PLW-MS differed based on the level of MS-related disability. The VOR gain, CS frequency and latency, and gaze position error (GPE) were calculated from the individual traces obtained during six-canal vHIT for 37 PLW-MS (mean age 53.4 ± 12.4 years-old, 28 females) with vertigo and/or an imbalance. The subjects were grouped by their Expanded Disability Status Scale (EDSS) scores: PLW-min-MS (EDSS = 1.0–2.5, n = 8), PLW-mild-MS (EDSS = 3.0–4.5, n = 23), and PLW-moderate-MS (EDSS = 5.0–6.0, n = 6). The between-group differences were assessed with Kruskal–Wallis tests. The VOR gains for most of the canals were higher for PLW-min-MS compared to PLW-mild- and mod-MS, respectively. CS occurred less often in PLW-min-MS versus PLW-mild- and mod-MS, respectively. No clear trend in CS latency was found. The GPE was often lower for PLW-min-MS compared to PLW-mild- and mod-MS, respectively. Thus, our data demonstrate that worse VOR and compensatory oculomotor functions are associated with a greater MS-related disability. PLW-MS may benefit from personalized vestibular physical therapy.
by
Michael S. Ramos;
Lucy T. Xu;
Srinidhi Singuri;
Julio C. Castillo Tafur;
Sruthi Arepalli;
Justis P. Ehlers;
Peter K. Kaiser;
Rishi P. Singh;
Aleksandra V. Rachitskaya;
Sunil K. Srivastava;
Jonathan E. Sears;
Andrew P. Schachat;
Amy S. Babiuch;
Sumit Sharma;
Daniel F. Martin;
Careen Y. Lowder;
Arun D. Singh;
Alex Yuan;
Amy S. Nowacki
Purpose: The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center. Design: Retrospective, institutional review board–approved study. Participants: Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016. Methods: Intravitreal injection. Main Outcome Measures: Complication occurrence within 15 days of injection. Results: From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient's gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications. Conclusions: Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient's gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes.
Purpose: To describe a video-documented assessment of cataract type in the eyes of patients with monocular infantile cataract who were enrolled in the Infant Aphakia Treatment Study.
Methods: The Infant Aphakia Treatment Study is a randomized clinical trial in which the investigators compared intraocular lens (IOL) versus contact lens correction in 114 infants, aged 28 days to <7 months. A total of 83 videos were available for morphological analysis of cataract. Three examiners reviewed all surgical recordings and agreed on the cataract characteristics by using a score sheet to record the lens layer or configuration of the opacity.
Results: Nuclear cataract was present in 45 of 83 eyes (54%). Posterior capsule plaque was observed in 73 eyes (88%). All eyes with fetal nuclear cataract had associated posterior capsule plaque. Cortical cataract without nuclear involvement was seen in 21 eyes (25%). Posterior bowing of the posterior capsule was noted in 4 eyes (5%). Evidence of persistent fetal vasculature (PFV) was present in 18 eyes (22%). PFV was the only finding in 5 eyes but was also seen in combination with nuclear (7 eyes) and cortical cataracts (6 eyes). The entire lens was white in 3 eyes (4%), whereas the lens was partially resorbed in 7 (8%) eyes. Anterior capsule fibrosis was noted in 5 eyes with advanced cataract (1 with total cataract, 4 with partially resorbed lens).
Conclusions: Nuclear opacities were common, but many different cataract types presented in infancy. PFV occurred in isolation or in association with cataract. Posterior capsule plaque was frequently noted, especially when a nuclear cataract was present.
Purpose. To study eye movements in a large group of children after the removal of unilateral infantile cataract, and to compare fixation instabilities between treatment groups with or without IOL implantation. Methods. The Infant Aphakia Treatment Study (IATS) is a randomized, multicenter clinical trial comparing IOL to contact lens (CL) treatment with a unilateral infantile cataract in participants who underwent cataract surgery at 1 to 6 months of age. At age 4.5 years, eye movements were recorded in 103 participants, using a high-speed video camera while the child performed a fixation task. The recordings were inspected by masked readers for the presence of fixation instabilities (nystagmus and saccadic oscillations). Results. Overall, fixation instabilities were observed in 50 (60%) of 83 children who had evaluable recordings, with no differences between treatment groups (27 [64%] of 42 in the IOL group, 23 [56%] of 41 in the CL group; P = 0.51). Nystagmus was seen in 38% and saccadic oscillations in 31%, with no differences between treatment groups (P > 0.33). Children without a fixation instability had better visual acuity (P = 0.04). Conclusions. Nystagmus and saccadic oscillations are well-known consequences of infantile cataracts, presumably the result of visual deprivation during the critical period of visual development. After early cataract extraction, successful optical correction may reduce further form deprivation and minimize the incidence of these fixation instabilities. In this study, no differences in the presence of fixation instabilities were found between the two treatment strategies (CL or IOL) for optical correction after cataract removal. (ClinicalTrials.gov number, NCT00212134.)
To determine whether the fellow eye of children who have undergone unilateral cataract extraction in the first year of life are at increased risk of injury and vision loss, the 10.5-year data on 109 of 114 children enrolled in the Infant Aphakia Treatment Study were examined. Based on this limited data, it was estimated that the fellow eye is at greater risk of injury than the operated eye. Our data do not support the risk being higher in children with the worst vision in the treated eye.[Formula presented]
We read with the interest the article by Cao et al. reporting spectacle wear adherence in aphakic children after bilateral cataract surgery. In their series, spectacle adherence was only 31% during the first year of life. Poor spectacle adherence during these formative years when central visual pathways are developing puts these children at risk for life-long visual disability. In contrast, contact lens adherence was much higher during the first year of life among participants in the Infant Aphakia Treatment Study (IATS) a multicenter, longitudinal, randomized clinical trial in the United States, which randomized infants after unilateral cataract surgery to primary intraocular lens (IOL) implantation or aphakia.
Head and neck cancers are among the deadliest cancers, ranked sixth globally in rates of high mortality and poor patient prognoses. The prevalence of head and neck squamous cell carcinoma (HNSCC) is associated with smoking and excessive alcohol consumption. Despite several advances in diagnostic and interventional methods, the morbidity of subjects with HNSCC has remained unchanged over the last 30 years. Epigenetic alterations, such as DNA hypermethylation, are commonly associated with several cancers, including HNSCC. Thus, epigenetic changes are considered promising therapeutic targets for chemoprevention. Here, we investigated the effect of EGCG on DNA hypermethylation and the growth of HNSCC. First, we assessed the expression levels of global DNA methylation in HNSCC cells (FaDu and SCC-1) and observed enhanced methylation levels compared with normal human bronchial epithelial cells (NHBE). Treatment of EGCG to HNSCC cells significantly inhibited global DNA hypermethylation by up to 70–80% after 6 days. Inhibition of DNA hypermethylation in HNSCC cells was confirmed by the conversion of 5-methylcytosine (5-mc) into 5-hydroxy methylcytosine (5hmC). DNA methyltransferases regulate DNA methylation. Next, we checked the effect of EGCG on the expression levels of DNA methyltransferases (DNMTs) and DNMT activity. Treatment of EGCG to HNSCC cells significantly reduced DNMT activity to 60% in SCC-1 and 80% in FaDu cells. The protein levels of DNMT3a and DNMT3b were downregulated in both cell lines after EGCG treatment. EGCG treatment to HNSCC cells reactivated tumor suppressors and caused decreased cell proliferation. Our in vivo study demonstrated that administration of EGCG (0.5%, w/w) as a supplement within an AIN76A diet resulted in inhibition of tumor growth in FaDu xenografts in nude mice (80%; p < 0.01) compared with non-EGCG-treated controls. The growth inhibitory effect of dietary EGCG on the HNSCC xenograft tumors was associated with the inhibition of DNMTs and reactivation of silenced tumor suppressors. Together, our study provides evidence that EGCG acts as a DNA demethylating agent and can reactivate epigenetically silenced tumor suppressors to inhibit the growth of HNSCC cells.