The potential of RNA therapeutics in dermatology.

Ribonucleic acid (RNA) therapeutics hold great potential for the advancement of dermatological treatments due to, among other reasons, the possibility of treating previously undruggable targets, high specificity with minimal side effects, and ability to include multiple RNA targets in a single product. Although there have been research relating to RNA therapeutics for decades, there have not been many products translated for clinical use until recently. This may be because of challenges to the application of RNA therapeutics, including the dearth of effective modes of delivery to the target, and rapid degradation of RNA in the human body and environment. This article aims to provide insight on (1) the wide-ranging possibilities of RNA therapeutics in the field of dermatology as well as (2) how key challenges can be addressed, so as to encourage the development of novel dermatological treatments. We also share our experience on how RNA therapeutics have been applied in the management of hypertrophic and keloid scars.

A Case of a Bumpy Retina.

A 77-year-old male had 3 months of progressive vision decline in the left eye. Dilated fundus examination revealed diffuse hyperpigmented lesions involving the macula and superior fundus that corresponded to areas of nodular retinal pigment epithelium thickening on optical coherence tomography. What would you do next?

Efficacy and safety of narrowband ultraviolet B versus combined ultraviolet A/narrowband ultraviolet B phototherapy in the treatment of chronic atopic dermatitis: A randomised double-blind study.

Phototherapy is a useful treatment modality for atopic dermatitis (AD). This is a prospective randomised double-blind study comparing the clinical efficacy of combined ultraviolet-A (UVA)/narrowband ultraviolet-B (NBUVB) versus NBUVB phototherapy in the treatment of chronic AD. Patients with moderate-to-severe AD were randomised to receive either UVA/NBUVB or NBUVB phototherapy twice weekly over 12 weeks. At baseline, weeks 6 and 12, Eczema Area And Severity Index (EASI), itch score and adverse effects were assessed. At baseline and week 12, disease-related quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Nine patients were randomised to receive UVA/NBUVB and 10 received NBUVB. At week 12, both groups showed significant improvement in EASI and itch scores (p < 0.05). Significant improvement in DLQI was seen in the UVA/NBUVB arm (p = 0.009) with a trend towards improvement in the NBUVB arm (p = 0.11). The efficacy of both modalities were comparable, as were reported adverse effects aside from skin dryness which was higher in the NBUVB arm (40% vs. 0%, p = 0.033). Combined UVA/NBUVB and NBUVB phototherapy have comparable clinical efficacy and safety in the treatment of chronic AD. NBUVB may induce greater skin dryness.

Multiple Retinal Emboli and Medial Canthal Swelling Following Injection of Acellular Porcine Urinary Bladder Matrix for Hair Restoration.

Acellular porcine urinary bladder matrix promotes wound healing and is also used to stimulate hair growth. A 64-year-old female presented with acute-onset OD pain and decreased visual acuity after subcutaneous injection of acellular porcine urinary bladder matrix at the hairline. Fundus examination revealed multiple emboli at retinal arcade branch points, and fluorescein angiography demonstrated corresponding areas of peripheral nonperfusion. Two weeks later, external examination revealed new swelling of the right medial canthus without erythema or fluctuance, which was felt to possibly represent recruitment of vessels after occlusion in the facial vasculature. At 1-month follow up, visual acuity of the OD improved with resolution of right medial canthal swelling. Fundus examination was normal with no visible emboli. Herein, the authors present a case of retinal occlusion and medial canthal swelling following injection of acellular porcine urinary bladder matrix for hair restoration, which to the authors knowledge has not been previously reported.

NOVEL OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN SEROUS MACULAR DETACHMENT AFTER PANRETINAL PHOTOCOAGULATION.

PURPOSE: To describe a novel optical coherence tomography finding in a case of macular serous retinal detachment after pars plana vitrectomy and panretinal photocoagulation. METHODS: Retrospective case report. RESULTS: A 52 year old male with diabetes underwent uncomplicated pars plana vitrectomy with panretinal photocoagulation for non-clearing vitreous hemorrhage, Postoperative course was complicated by significantly decreased vision and a macular serous retinal detachment that was characterized on optical coherence tomography by a reticular network of hyperreflective bands in the subretinal space. Fluid and hyperreflective material in the subretinal space resolved by postoperative Week 6 with standard postoperative eye drops. However, persistent ellipsoid zone disruption was seen up to postoperative Week 20. CONCLUSION: Extensive subretinal bands can be seen after panretinal photocoagulation. This novel finding can pose diagnostic and management challenges but may resolve with conservative medical management.

MYCOBACTERIUM ABSCESSUS SCLERAL BUCKLE INFECTION.

PURPOSE: To report the successful management of a rare case of Mycobacterium abscessus scleral buckle infection. METHODS: Case report. RESULTS: A 63-year-old woman with a history of sarcoid anterior uveitis and macula-off retinal detachment repaired by scleral buckle and pars plana vitrectomy presented with eye pain, redness, and purulent drainage in the left eye. Slit-lamp examination showed superonasal scleral buckle exposure, purulent conjunctival discharge, corneal edema, nongranulomatous keratic precipitates, and anterior chamber cell and flare. The patient underwent urgent scleral buckle removal. Intraoperatively, an area of scleral thinning without perforation underneath the exposed buckle was discovered and covered with a scleral patch graft, and an amniotic membrane graft was used to cover an area of bare sclera with significant conjunctival scarring and retraction. Cultures grew M. abscessus panresistant except to amikacin. After 6 weeks of fortified amikacin drops and a long taper of topical steroid therapy for persistent postoperative anterior uveitis, the patient's symptoms resolved. CONCLUSION: Mycobacterium is an emerging causative agent of scleral buckle infections. Our report provides insights about the management of such cases.

Granulicatella Adiacens as an Unusual Cause of Microbial Keratitis and Endophthalmitis: A Case Series and Literature Review.

PURPOSE: To report two cases of microbial keratitis and/or endophthalmitis involving Granulicatella adiacens. METHODS: Case series. RESULTS: 24-year-old female with a history of Herpes simplex virus 1 (HSV-1) and Candida parapsilosis keratitis presented with a geographic epithelial defect and infiltrate in the left eye. Cultures were positive for HSV-1 and G. adiacens. Keratitis resolved with topical vancomycin and oral valacyclovir. A 65-year-old female with a history of type II diabetes and failed therapeutic penetrating keratoplasty presented with inferior corneal graft haze and vitreous inflammation of the right eye. Therapeutic penetrating keratoplasty and pars plana vitrectomy were performed, and the corneal button returned positive for G. adiacens. The patient was treated with topical and intravitreal vancomycin as well as topical and systemic steroids. CONCLUSIONS: These cases expand the literature on G. adiacens keratitis and endophthalmitis and corroborate the role of steroid use and prior surgery as paramount risk factors.

The Role of Ultra-Widefield Fundus Imaging and Fluorescein Angiography in Diagnosis and Treatment of Diabetic Retinopathy.

PURPOSE OF REVIEW: Early detection and treatment are important for preventing vision loss from diabetic retinopathy. Historically, the gold standard for grading diabetic retinopathy has been based on 7-field 30-degree color fundus photographs that capture roughly the central third of the retina. Our aim was to review recent literature on the role of ultra-widefield (allowing capture of up to 82% of the retina in one frame) fundus imaging in screening, prognostication, and treatment of diabetic retinopathy. RECENT FINDINGS: Ultra-widefield fundus imaging can capture peripheral retinal lesions outside the traditional 7-field photographs that may correlate with increased risk of diabetic retinopathy progression. The speed and ability to image through undilated pupils make ultra-widefield imaging attractive for tele-ophthalmology screening. Ultra-widefield fluorescein angiography may help guide targeted laser treatment in eyes with proliferative diabetic retinopathy. Ultra-widefield imaging has potential to help shape new diabetic retinopathy screening, staging, and treatment protocols.

Artificial intelligence for improving sickle cell retinopathy diagnosis and management.

Sickle cell retinopathy is often initially asymptomatic even in proliferative stages, but can progress to cause vision loss due to vitreous haemorrhages or tractional retinal detachments. Challenges with access and adherence to screening dilated fundus examinations, particularly in medically underserved areas where the burden of sickle cell disease is highest, highlight the need for novel approaches to screening for patients with vision-threatening sickle cell retinopathy. This article reviews the existing literature on and suggests future research directions for coupling artificial intelligence with multimodal retinal imaging to expand access to automated, accurate, imaging-based screening for sickle cell retinopathy. Given the variability in retinal specialist practice patterns with regards to monitoring and treatment of sickle cell retinopathy, we also discuss recent progress toward development of machine learning models that can quantitatively track disease progression over time. These artificial intelligence-based applications have great potential for informing evidence-based and resource-efficient clinical diagnosis and management of sickle cell retinopathy.

Pediatric Vitreoretinal Surgery and Integrated Intraoperative Optical Coherence Tomography.

Intraoperative portable handheld and microscope-integrated OCT enhance the pediatric vitreoretinal surgeon's diagnostic abilities during examination under anesthesia and surgery, particularly in children who are challenging to examine preoperatively due to young age or ocular trauma. Improved OCT-guided visualization of vitreoretinal anatomic relationships has the potential to improve surgical safety and efficiency. In retinopathy of prematurity and other pediatric retinal vascular conditions, intraoperative OCT can be critical for distinguishing between retinoschisis and retinal detachment and highlighting abnormalities of the vitreoretinal interface that may contribute to development of tractional retinal detachments. During retinal detachment repair, intraoperative OCT aids identification of subtle retinal breaks, residual subretinal fluid, retained perfluorocarbon, preretinal membranes, and residual hyaloid, among other findings. In macular surgery, intraoperative OCT has demonstrated value in confirming completion or lack thereof of epiretinal and internal limiting membrane peeling and differentiating between lamellar and full-thickness macular holes. OCT-guided subretinal bleb formation and genetic vector delivery are critical to ensuring accurate localization of subretinal gene delivery for inherited retinal degenerations. Research on development of OCT-compatible surgical instruments, real-time three-dimensional volumetric OCT imaging, and integration with intraoperative OCT angiography are anticipated to further increase the utility of intraoperative OCT in pediatric vitreoretinal surgical decision-making.

Presumed Natural History of Combined Hamartoma of the Retina and Retinal Pigment Epithelium.

PURPOSE: To correlate structural changes of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) with patient age. DESIGN: Retrospective study. PARTICIPANTS: Fifty eyes of 49 patients (age range, 1-74 years) with CHRRPE studied at 9 tertiary vitreoretinal institutions. METHODS: We analyzed the clinical findings with respect to lesion topography and pigmentation as well as investigated the OCT findings regarding the thickness, vitreoretinal interface, outer plexiform layer distortion, ellipsoid zone disruption, and retinal pigment epithelium-Bruch's membrane complex involvement of CHRRPE. MAIN OUTCOME MEASURES: Clinical and imaging findings of CHRRPE at different ages. RESULTS: Analysis of 50 CHRRPE patients revealed that younger patients were more likely to demonstrate partial thickness involvement of the retina (P = 0.009) with predominantly inner retinal layer involvement (P = 0.04). The inverse was true for older patients with CHRRPE. In addition, older patients more commonly showed pigmentary changes. Eyes with CHRRPE were more likely to show an increase in central macular thickness independently of tumor location. CONCLUSIONS: Based on these findings, we believe that CHRRPE typically begins in the inner retina and continues toward the outer retina over time, with increase in central macular thickness, despite the location of the tumor.

Deep Learning Detection of Sea Fan Neovascularization From Ultra-Widefield Color Fundus Photographs of Patients With Sickle Cell Hemoglobinopathy.

Importance: Adherence to screening for vision-threatening proliferative sickle cell retinopathy is limited among patients with sickle cell hemoglobinopathy despite guidelines recommending dilated fundus examinations beginning in childhood. An automated algorithm for detecting sea fan neovascularization from ultra-widefield color fundus photographs could expand access to rapid retinal evaluations to identify patients at risk of vision loss from proliferative sickle cell retinopathy. Objective: To develop a deep learning system for detecting sea fan neovascularization from ultra-widefield color fundus photographs from patients with sickle cell hemoglobinopathy. Design, Setting, and Participants: In a cross-sectional study conducted at a single-institution, tertiary academic referral center, deidentified, retrospectively collected, ultra-widefield color fundus photographs from 190 adults with sickle cell hemoglobinopathy were independently graded by 2 masked retinal specialists for presence or absence of sea fan neovascularization. A third masked retinal specialist regraded images with discordant or indeterminate grades. Consensus retinal specialist reference standard grades were used to train a convolutional neural network to classify images for presence or absence of sea fan neovascularization. Participants included nondiabetic adults with sickle cell hemoglobinopathy receiving care from a Wilmer Eye Institute retinal specialist; the patients had received no previous laser or surgical treatment for sickle cell retinopathy and underwent imaging with ultra-widefield color fundus photographs between January 1, 2012, and January 30, 2019. Interventions: Deidentified ultra-widefield color fundus photographs were retrospectively collected. Main Outcomes and Measures: Sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network for sea fan detection. Results: A total of 1182 images from 190 patients were included. Of the 190 patients, 101 were women (53.2%), and the mean (SD) age at baseline was 36.2 (12.3) years; 119 patients (62.6%) had hemoglobin SS disease and 46 (24.2%) had hemoglobin SC disease. One hundred seventy-nine patients (94.2%) were of Black or African descent. Images with sea fan neovascularization were obtained in 57 patients (30.0%). The convolutional neural network had an area under the curve of 0.988 (95% CI, 0.969-0.999), with sensitivity of 97.4% (95% CI, 86.5%-99.9%) and specificity of 97.0% (95% CI, 93.5%-98.9%) for detecting sea fan neovascularization from ultra-widefield color fundus photographs. Conclusions and Relevance: This study reports an automated system with high sensitivity and specificity for detecting sea fan neovascularization from ultra-widefield color fundus photographs from patients with sickle cell hemoglobinopathy, with potential applications for improving screening for vision-threatening proliferative sickle cell retinopathy.

Optical coherence tomography imaging of the pediatric retina.

Optical coherence tomography is an increasingly important part of the retinal specialist's and general ophthalmologist's toolkit for diagnosing and managing retinal disease. This review summarizes the unique considerations and available imaging systems with which pediatric ophthalmologists should be familiar when attempting optical coherence tomography in children. Normal developmental changes in foveal and extrafoveal structure and the need for an established pediatric normative database of retinal thicknesses are reviewed. Finally, applications of optical coherence tomography imaging to selected representative pediatric retinal diseases are introduced as examples of how optical coherence tomography in children is furthering the diagnosis and management of vision-threatening retinal diseases.

Epidemiology and Factors Associated with Remission of Pemphigus Vulgaris and Foliaceus in Singapore.

INTRODUCTION: Pemphigus is a chronic, relapsing immunobullous disease. There is limited data on the clinical course and prognostic factors of pemphigus in Asian patients. MATERIALS AND METHODS: We conducted a retrospective cohort study of all newly diagnosed pemphigus vulgaris (PV) and pemphigus foliaceus (PF) patients seen at the National Skin Centre from 1 January 2004 to 31 December 2009. Demographic and clinical data on comorbidities, treatment and remission were recorded. Mortality information was obtained from the National Registry of Diseases. Prognostic endpoint was overall remission at last visit. RESULTS: Sixty- one patients (36 PV and 25 PF) were recruited. Among PV patients, higher initial prednisolone dose (P = 0.017) and the use of azathioprine (P = 0.028) were significantly associated with overall remission at last visit. However, higher desmoglein 1 antibody titres at diagnosis (P = 0.024) and the use of dapsone (P = 0.008) were negatively associated with overall remission at last visit. Among PF patients, only higher desmoglein 1 antibody titre at diagnosis (P = 0.041) was found to be associated with lower overall remission at last visit. There was no mortality during the 3-year follow-up period in both PV and PF. CONCLUSION: Higher initial prednisolone dose and the use of azathioprine in PV desmoglein 1 antibody titre at diagnosis in PV and PF might be prognostic markers for achieving remission. Use of dapsone was associated with lower overall remission in PV, but this might be confounded because dapsone was used as an adjuvant therapy in recalcitrant cases. Owing to study methodology and limitations, further evaluation is needed for better prognostication of pemphigus.