Review and analysis of history and utilization of panretinal photocoagulation and ranibizumab after publication of protocol S.

PURPOSE OF REVIEW: We describe the history, utilization, and series results of panretinal photocoagulation (PRP) and ranibizumab and provide an analysis of PRP and ranibizumab usage before versus after the publication of the 2-year and 5-year results of the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol S trial. RECENT FINDINGS: Number of ranibizumabs performed began to increase and number of PRPs performed began to decrease in 2016. After publication of the 2-year results, there was significant negative trend in PRP services and significant positive trend in ranibizumab services (both P < 0.001). After publication of the 5-year results, there was significant negative trend in PRP services (P = 0.003). There were significant negative trends (all P < 0.001) in reimbursement factors for PRP from 2013 to 2020: average work RVU (wRVU), nonfacility physical expense RVU, facility PE RVU, malpractice RVU (MP RVU). SUMMARY: Both PRP and ranibizumab have undergone numerous trials comparing their efficacy to other treatment options or no treatment at all. The publication of the 2-year results of Protocol S was associated with an increase in utilization of ranibizumab and decrease in utilization of PRP, with continued decrease after the publication of the 5-year results.

Building a Future for School-Based Menstruation Health and Hygiene (MHH): Evaluating Implementation of a Menstrual Hygiene Management (MHM) Policy in Chicago Public Schools.

Menstrual health and hygiene (MHH) inequities disproportionately impact communities who are marginalized. In 2018, Illinois passed the Learn with Dignity Act (LWDA) requiring schools to provide menstrual products in bathrooms, yet little is known about its impacts. This evaluation examined LWDA implementation across Chicago Public Schools (CPS) and identified barriers, facilitators, and lessons to inform future MHH policy implementations. A qualitative study was conducted by thematically analyzing interviews with CPS staff (n = 36) from October 2020 - September 2021 in partnership with CPS Office of Student Health and Wellness (OSHW). Staff reported inadequate LWDA and MHH education and inconsistent menstrual product availability. Structural, systemic, and cultural implementation barriers hindered student access to products and created inequities based on age, gender, and income. Staff investment and student education were implementation facilitators. Staff awareness of policy implementation protocol, student MHH education, and addressing access inequities are key factors for consideration in future policy implementations. Through the WSCC model, these findings demonstrated the importance of strengthening MHH policies and policy implementation to promote student health, well-being, and educational opportunities.

Coats-Like Presentation of Familial Exudative Vitreoretinopathy Associated With a Novel LRP5 Variant.

This report describes a unique case of a Coats-like presentation of familial exudative vitreoretinopathy in an 11-year-old girl. The patient was originally referred for evaluation of presumed Coats disease and presented with telangiectatic vessels, perivascular exudates, diffuse peripheral exudation, and intraretinal hemorrhages. Clinical and angiographical findings were consistent with familial exudative vitreoretinopathy, while genetic testing identified variants of uncertain significance in two associated genes, LRP5 and ZNF408. In silico analysis predicts the LRP5 variant to be pathogenic. Retinal vasculopathies often have phenotypic overlap, warranting angiographic examination of both eyes and genetic testing to uncover the correct diagnosis and guide proper treatment. [Ophthalmic Surg Lasers Imaging Retina 2024;55:462-466.].

Optical coherence tomography angiography in pediatric ocular cutis marmorata telangiectatica congenita: A case series.

Purpose: To report 2 cases of enlarged foveal avascular zone (FAZ) on optical coherence angiography (OCTA) imaging in pediatric patients with cutis marmorata telangiectatica congenita (CMTC). Observations: A 10-week-old female and a 3-year-old male diagnosed with CMTC presented for retinal examination. Both had peripheral avascularity on fluorescein angiography (FA) and enlargement of the FAZ on OCTA in both eyes. Conclusions and Importance: Pediatric patients with CMTC should undergo ocular evaluation with not only FA, but also OCTA to more robustly evaluate the affected retina in this rare disease.

Compliance with web content accessibility guidelines in ophthalmology social media posts.

This is a cross-sectional exploratory analysis of publicly available Internet data to examine compliance to web content accessibility guidelines (WCAG) on patient education social media posts in ophthalmology. WCAG ensures web content accessibility for those with disabilities (including visual impairment). A total of 100 social media posts were sampled from ten ophthalmology patient education social media pages and ten non-ophthalmology (cardiopulmonary) pages as the comparison group. Three independent graders evaluated the selected posts based on the WCAG 2 checklist by WebAIM, a non-profit affiliated with Utah State University, after its adaptation for social media posts. Validated accessibility standard labels: "0" for not meeting any standards, "1" or "A" for meeting bare minimum accessibility requirements, "2" or "AA" for meeting legal accessibility requirements, or "3" or "AAA" for exceeding accessibility requirements. There was not enough evidence to detect a difference in WCAG scores between ophthalmology and non-ophthalmology posts (p = 0.80). Forty-nine percent of scores for ophthalmology social media posts showed no compliance with any WCAG. The most common reasons that ophthalmology posts failed to meet criteria were due to color and contrast issues (39%). Most ophthalmology social media posts had low WCAG scores, indicating poor compliance to WCAG. Because social media is highly visual, reduced compliance to WCAG may create barriers for low vision individuals to successfully access patient education social media content.

Non-nasal, atypical retinochoroidal coloboma in pediatric patients: Case series and review.

Purpose: To report 2 cases of atypically located, non-nasal colobomas in the pediatric population. Observations: A 3-week-old female neonate with no known past ocular or medical history was diagnosed with temporal iris and chorioretinal coloboma with tractional membranes upon examination under anesthesia and imaging. A 9-year-old female with a history of bilateral sensorineural hearing loss and left mild hydronephrosis presented with a temporal chorioretinal coloboma associated with retinal detachment. Conclusions and importance: Very few cases of atypically located, non-nasal pediatric colobomas have been reported, and they lack a clear cause or mechanism of formation. Continued documentation of their occurrence and research into their formation at a molecular and embryological level are warranted to better understand their pathogenesis.

Review and analysis of history and utilization of pneumatic retinopexy after pneumatic retinopexy versus vitrectomy for the management of primary rhegmatogenous retinal detachment outcomes randomized trial (PIVOT).

PURPOSE OF REVIEW: We describe the history and series results of pneumatic retinopexy (PnR)and provide an analysis of PnR utilization after publication of results of pneumatic retinopexy versus vitrectomy for the management of primary rhegmatogenous retinal detachment outcomes randomized trial (PIVOT). RECENT FINDINGS: No significant trends were found for average number of services ( P  = 0.153) of PnR after the publication of PIVOT results. SUMMARY: PnR is a rhegmatogenous retinal detachment (RRD) repair technique that was first described in the early 1900 s and has evolved over time to become a modern-day, minimally invasive, underutilized treatment option. Other repair techniques for RRD include scleral buckling and pars plana vitrectomy (PPV), which has been compared to the use of PnR in PIVOT. Results of PIVOT concluded that PnR offered superior visual acuity and noninferiority. PnR is underutilized in the United States even after publication of results of PIVOT deemed it a noninferior treatment. Lack of a significant increase in national utilization of PnR could be associated with multifactorial clinician, systems, and financial reasons in the real-world setting.

Compliance with Web Content Accessibility Guidelines in Ophthalmology Social Media Posts.

This is a cross-sectional analysis of publicly available Internet data to examine compliance to Web Content Accessibility Guidelines (WCAG) on patient education social media posts in ophthalmology. WCAG ensures web content accessibility for those with disabilities (including visual impairment). Social media posts were sampled from 10 ophthalmology patient education social media pages and 10 non-ophthalmology (cardiopulmonary) pages as the comparison group. Three independent reviewers graded the selected posts based on the WebAIM© WCAG 2 checklist adapted for social media posts. Validated accessibility standard labels: "0" for not meeting any standards, "1" for meeting bare minimum accessibility requirements, "2" for meeting legal accessibility requirements, or "3" for exceeding accessibility requirements. There were no significant differences between ophthalmology and non-ophthalmology posts in receiving high vs. low WCAG grades. 49% of ratings for ophthalmology social media posts showed no compliance with any WCAG. The most common reasons that ophthalmology posts failed to meet criteria were due to color and contrast issues (38.9%). Most ophthalmology social media posts had low WCAG scores, indicating poor compliance to WCAG. Because social media is highly visual, reduced compliance to WCAG may create barriers for low vision individuals to successfully access patient education social media content.

Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease.

Autosomal recessive Stargardt disease (STGD1) is an inherited retinal degenerative disease associated with a mutated ATP-binding cassette, subfamily A, member 4 (ABCA4) gene. STGD1 is the most common form of juvenile macular degeneration with onset in late childhood to early or middle adulthood and causes progressive, irreversible visual impairment and blindness. No effective treatment is currently available. In the present article, we review the most recent updates in clinical trials targeting the management of STGD1, including gene therapy, small molecule therapy, and stem cell therapy. In gene therapy, dual adeno-associated virus and non-viral vectors have been successful in delivering the human ABCA4 gene in preclinical studies. For pharmaceutical therapies ALK-001, deuterated vitamin A shows promise with preliminary data for phase 2 trial, demonstrating a decreased atrophy growth rate after two years. Stem cell therapy using human pluripotent stem cell-derived retinal pigment epithelium cells demonstrated long-term safety three years after implantation and visual acuity improvements in the first two years after initiation of therapy. Many other treatment options have ongoing investigations and clinical trials. While multiple potential interventions have shown promise in attenuating disease progression, further exploration is necessary to demonstrate treatment safety and efficacy.

Do published trial results influence physician prescribing patterns? Intravitreal antivascular endothelial growth factor usage by the United States Ophthalmologists before and after Protocol T study.

PURPOSE OF REVIEW: Clinical trial publications may influence physician prescribing patterns. The Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol T study, published in 2015, examined outcomes of intravitreal antivascular endothelial growth factor (VEGF) medications for treatment of diabetic macular oedema (DME). This study investigates if the Protocol T 1-year results were associated with changes in prescribing patterns. RECENT FINDINGS: Anti-VEGF agents have revolutionized treatment of DME by blocking angiogenesis signalled by VEGF. Three commonly used anti-VEGF agents are on-label aflibercept (Eylea, Regeneron) and ranibizumab (Lucentis, Genentech) and off-label bevacizumab (Avastin, Genentech). SUMMARY: From 2013 to 2018, there was a significant positive trend in the average number of aflibercept injections for any indication ( P  < 0.002). There was no significant trend in the average number of bevacizumab ( P  = 0.09) and ranibizumab ( P  = 0.43) for any indication. The mean proportion of aflibercept injections per provider per year was 0.181, 0.217, 0.311, 0.403, 0.419 and 0.427; each year-by-year comparison was significant (all P  < 0.001), and the largest increase was in 2015, the year of publication of Protocol T 1-year results. These results imply and reinforce that clinical trial publications may have significant effects on ophthalmologist prescribing patterns.

An In Vivo Study on the Development of Bacterial Microbiome on Clear Orthodontic Retainer.

OBJECTIVES: The objective of this study was to see how the bacterial composition changes on clear orthodontic retainer over a 14-day period. METHODS: Saliva and plaque samples collected from a clear retainer surface were obtained from five healthy volunteers receiving retainer treatment. Prior to clear retainer delivery, patients had not been wearing any other appliances. Patients were instructed to wear their clear retainer for the 14-day period, taking them off to eat and to clean them with a soft-bristle toothbrush. The bacterial composition was determined via Illumina MiSeq sequencing of the bacterial 16S rRNA. After bioinformatics processing using the QIIME pipeline, the intra- and intergroup biodiversity of the sample was analyzed. RESULTS: The bacterial composition changed over a 14-day period in the saliva and on the clear retainer. When comparing the different phylum levels between saliva and clear retainer' microbiota, the Firmicutes were significantly increased 1.26-fold (p = 0.0194) and 1.34-fold (p = 0.0123) after 7 and 14 days of retainer treatment when compared to saliva, respectively. The Campylobacteriota were significantly decreased 1.80-fold (p = 0.05) in the clear retainer when compared to saliva at 7 days. At the genus level, several microbiota were significantly increased in relative abundance in the clear retainer after the 14-day period. CONCLUSION: These findings reveal that the presence of a clear retainer in the mouth might lead to enamel changes or periodontal tissue destruction, especially after 14 days of use.

Antipruritic Effect of Topical Acetaminophen Gel in Histaminergic and Non-histaminergic Itch Provocation: A Double-blind, Vehicle-controlled Pilot Study.

There is a need for new topical antipruritics that are effective on many types of itch. This study examined the antipruritic efficacy of a new formulation of topical acetaminophen. In vitro skin permeability studies showed that 2.5% and 5% formulations are able to rapidly deliver an adequate amount of the drug into the skin. In a double-blind, vehicle-controlled, randomized study in 17 healthy volunteers, 1%, 2.5% and 5% acetaminophen gels and a vehicle gel were applied to the skin prior to histaminergic and non-histaminergic itch induction and assessment of thermal pain thresholds. The 2.5% and 5% gel formulations significantly reduced the itch intensity time course and the area under the curve for both histamine and cowhage itch. No effect was noted on heat pain thresholds and no adverse effects were observed. These results suggest that topical acetaminophen would be a safe and effective over-the-counter medication for itch.

Risk Prediction of Nosocomial and Posthospital Discharge Infections in Alcohol-Associated Hepatitis.

Alcohol-associated hepatitis (AAH) is a severe form of liver injury with mortality as high as 30%-40% at 90 days. As a result of altered immune function in AAH, bacterial infections are common and are associated with poor outcomes. However, determining the risk and subsequent development of infection in patients with AAH remain challenging. We performed a retrospective study of consecutive patients admitted with a diagnosis of AAH at two independent tertiary centers from 1998 to 2018 (test cohort, n = 286) who developed infections following hospitalization. The diagnosis of AAH was confirmed by manual chart review according to the recent National Institute on Alcohol Abuse and Alcoholism definition. Infections were categorized by location and time of diagnosis as hospital-acquired infection (48 hours after admission until discharge) and posthospital infections (up to 6 months following discharge). The cohort was 66% men, and the median age was 48 (21-83) years. Corticosteroids were used in 32% of all patients with AAH. The overall infection rate was 24%. Of those with infections, 46% were hospital acquired and 54% were acquired after hospitalization. Variables found to be significant risk factors for bacterial infection included the presence of ascites on admission (hazard ratio [HR], 2.06), corticosteroid administration (HR, 1.70), Model for End-Stage Liver Disease (MELD) >23 (HR, 2.61), and white blood cell (WBC) count on admission per point (HR, 1.02). Conclusion: In this multicenter cohort study of patients hospitalized with AAH, MELD score, ascites, WBC count, and use of corticosteroids were identified as significant predictors of the development of bacterial infection. We created a novel predictive equation that may be used to aid in the identification of patients with AAH at high risk of infection.

Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta.

Prurigo nodularis (PN) is a chronic skin dermatosis with hyperkeratotic and intensely pruritic nodules. Managing PN-associated itch is difficult because its aetiology is still unknown. This study aimed to investigate the correlation between itch intensity in PN and the expression of a pruritogenic cytokine interleukin (IL)-31, its receptor complex components IL-31 receptor α (IL-31RA) and oncostatin M receptor ß (OSMRß), and oncostatin M (OSM), which is a ligand of OSMR ß, through immunofluorescence staining examination. Itch intensity in PN was closely correlated with the number of dermal IL-31(+) cells (Spearman's r = 0.551, p < 0.05), dermal IL-31RA(+) cells (r = 0.475, p < 0.05) and dermal OSM(+) cells (r = 0.505, p < 0.05). In addition, the number of dermal OSMRß (+) cells was increased in PN (t test, p < 0.05), despite not being correlated with itch intensity (Spearman's r = 0.375, p > 0.05). Major cellular sources of dermal IL-31 were T cells (27.0% of total IL-31-expressing cells) and macrophages (35.0%), while those of OSM were mainly T cells (49.8%) and mast cells (26.8%). IL-31RA-expressing dermal cells were mostly mast cells (49.3%) and macrophages (36.6%), and OSMRß was mainly expressed by macrophages (51.8%) in the dermis. These findings indicate that IL-31 (mainly from macrophages and T cells) and OSM (principally from T cells and mast cells) stimulate dermal cells expressing IL-31RA and OSMRß (e.g. macrophages), which may further promote itch and inflammation in PN. This complex dermal milieu of cell/cytokine/receptor network can be a therapeutic target for PN-associated itch.

Mechanisms of Itch in Stasis Dermatitis: Significant Role of IL-31 from Macrophages.

Stasis dermatitis (SD) is a common disease in the elderly population, with pruritus being one of the troublesome symptoms. However, there are few therapeutic modalities available for SD-associated itch because little is known about its pathophysiological mechanism. Therefore, we sought to investigate the mediators of itch in SD using an immunofluorescence study on patient lesions focusing on IL-31. Ex vivo stimulation studies using murine peritoneal macrophages were also used to elucidate the pathological mechanisms of the generation of IL-31. In SD lesions, dermal infiltrating IL-31(+) cells were increased in number compared with the healthy controls, and the majority of IL-31(+) cells were CD68(+) macrophages. The presence of itch in SD was significantly associated with the amount of CD68(+)/IL-31(+) macrophages and CD68(+)/CD163(+) M2 macrophages. The number of CD68(+)/IL-31(+) macrophages was correlated with the number of dermal C-C chemokine receptor type 4(+) T helper type 2 cells, IL-17(+) cells, basophils, substance P(+) cells, and dermal deposition of periostin and hemosiderin. Furthermore, murine peritoneal macrophages expressed an M2 marker arginase-1 and generated IL-31 when stimulated with a combination of substance P, periostin, and red blood cell lysate (representing hemosiderin). IL-31 from macrophages may play a role in itch in SD.

A Systematic Review of Human Trials Using Stem Cell Therapy for Erectile Dysfunction.

INTRODUCTION: Novel therapeutic modalities have been proposed for the treatment and management of erectile dysfunction (ED). Stem cell therapy (SCT) is the injection of mesenchymal stem cells or stromal vascular fractions from adipose and other tissue sources. Although SCT has been studied and reported in multiple rodent trials, few human clinical trials exist. AIM: The aim of this study was to provide a systematic review of SCT for the treatment of ED with an emphasis on data from peer-reviewed human studies. METHODS: A systematic review was performed evaluating SCT for ED in human studies using PubMed-Medline and Scopus databases. Literature search was conducted using key words such as "Clinical Trials of SCT for ED," "Stromal Vascular Fraction Treatment for ED," and "SCT for ED." Systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MAIN OUTCOME MEASURE: The main outcomes measure was the safety and efficacy of SCT for ED in humans. RESULTS: 5 studies specific to SCT for ED treatment were included. A total of 61 patients were included in these phase I and II clinical trials and follow-up periods ranged from 6-62 months. End points of the studies included safety, tolerability, and efficacy of SCT for ED. The majority of the studies demonstrated improvement in erectile function due to SCT in patients, including improvements in penile vascular flow, International Index of Erectile Function-15 items, and Erectile Hardness Scale scores. All of the studies reported that there were no serious adverse events for patients. Limitations of the studies included small cohort sizes, and only 1 contained a sham arm. CONCLUSION: The 5 completed human clinical trials show promise for SCT as a restorative therapy for the treatment of ED. However, although promising, there still exists very limited data for the use of SCT for ED in humans. With the expansion of clinics offering SCT for ED, it is imperative that SCT is investigated further for safety, efficacy, and standardization. Lokeshwar SD, Patel P, Shah SM, et al. A Systematic Review of Human Trials using Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2020;8:122-130.

Pathophysiologic mechanisms of itch in bullous pemphigoid.

BACKGROUND: One of the hallmarks of bullous pemphigoid (BP) is moderate to severe chronic itch. Managing this is difficult because little is known about the mechanisms of itch in BP. OBJECTIVE: We sought to elucidate the pathophysiologic mechanisms of itch in BP. METHODS: The expression of itch mediators in lesions of 24 patients with BP and 6 healthy individuals were examined through immunofluorescence staining. Furthermore, the expression of itch mediators and itch severity was correlated. RESULTS: Itch severity was correlated with eosinophils, substance P, neurokinin 1R, interleukin (IL) 31 receptor A, oncostatin M receptor-ß, IL-13, periostin, and basophils. There was also a trend between itch severity and IL-31 expression. Most of the cells expressing IL-31 or neurokinin 1R were identified as eosinophils. Intraepidermal nerve fiber density was decreased. Other itch mediators, including mast cells, IL-4, thymic stromal lymphopoietin, transient receptor potential vanilloid 1 and ankyrin 1, and protease activated receptor 2 were not significantly correlated with itch severity. LIMITATIONS: The relatively small sample size, the examination of protein expression exclusively through immunofluorescent analysis, and lack of functional assays in patients are the limitations. CONCLUSIONS: Multiple factors are involved in BP-associated itch, including eosinophils, substance P, neurokinin 1R, IL-31, IL-31 receptor A, oncostatin M receptor-ß, IL-13, periostin, and basophils. They could be useful therapeutic targets.