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A 74-year-old man with a history of multiple squamous cell carcinomas presents with a 5-mm bright pink, dome-shaped papule with overlying vessels at the crown of the scalp. What is your diagnosis?

Radiotherapy (RT) is a modality for cancer management that frequently causes critical injury to tissues adjacent to the targeted cancer site. Acute radiation dermatitis (RD) is one of the most common adverse effects of RT and may lead to secondary infection, disfigurement, and discontinuation of therapy. The authors report the efficacy of a multidisciplinary collaboration between radiation oncology, dermatology, and wound care teams in the management of severe, acute RD. This case report describes the use of noncontact, low-frequency ultrasound (NCLFU)-assisted saline wash therapy leading to accelerated healing of severe RD in an older man treated with RT for scalp squamous cell carcinoma. Although NCLFU-assisted saline wash therapy provides gentle debridement of wound surfaces and has demonstrated efficacy in the management of chronic wounds, the potential role for NCLFU therapy in RD management has not yet been explored.

We analyzed OCT biomarkers of 65 eyes with treatment-naive RVO and ME. While none of the factors analyzed predicted successful treatment discontinuation, early improvements in vision and DRIL were associated with long-term visual outcomes.

Diphencyprone (DPCP) is a hapten that causes a delayed-type hypersensitivity reaction when applied topically. It has clinical uses in the treatment of various conditions such as melanoma metastases, warts, and alopecia areata, but the mechanisms are currently not well understood in humans. To further characterize the immunologic effects of DPCP, the authors performed a proteomic analysis of normal skin of eight healthy volunteers following a single application of DPCP and compared them with placebo-treated skin from the same volunteers. A total of 96 proteins were examined using the Olink immuno-oncology panel at 3 days (peak response), 14 days (partially resolved response), and 120 days (completely resolved response). Our analysis revealed significant upregulation of markers of immune cell activation (interleukin [IL] 8), vascular and tissue remodeling (matrix metallopeptidase 12 [MMP12], nitric oxide synthase 3 [NOS3]), antineoplastic markers (granzyme B [GZMB]), and the Th1 axis (interferon gamma [IFNG], chemokine (C-X-C motif) ligand [CXCL] 9, CXCL10, CXCL11) at days 3 and 14 compared with placebo (p 0.05). In addition, several negative regulators of immune function such as programmed cell death 1 (PD1), programmed cell death ligand 1 (PDL1) (p 0.001), and lymphocyte activation gene 3 (LAG3) (p 0.05) were significantly upregulated at days 3 and 14. This induction of negative regulators may explain the seemingly paradoxical therapeutic benefits of DPCP in autoimmune conditions such as alopecia areata. The current analysis also indicated IL-4 upregulation only at day 3, followed by IL-12 upregulation only at day 14, suggesting a transient Th2 response followed by Th1 polarization. Overall, these data suggest a complex and evolving immunological delayed-type hypersensitivity response to a single application of DPCP over time. Future proteomic studies of samples from patients with melanoma metastases, warts, and alopecia areata treated long term with DPCP are needed to further evaluate its pharmacologic mechanisms.

UNSTRUCTURED Provider opt-out of accepting Medicare insurance is a nationally tracked metric by the Centers for Medicare and Medicaid Services (CMS) for all physicians, including dermatologists. While this usually only consists of a small number of providers, the magnitude of opting-out has varied historically, often tracing changes in systemic healthcare policy, with a spike in mid-2016 and a recent increase in 2022. Here, we explore dermatologist opt-out data since 2001, as reported by CMS, to characterize trends and provide evidence that shifts in provider opt-out may represent a potential indicator of the state of health policy and possible needs for reform.

UNSTRUCTURED N/A

Non-typhoidal

PURPOSE To identify clinical and anatomic factor-associated vision loss in eyes with treatment-naive diabetic macular edema and good initial visual acuity. METHODS Retrospective cohort study after long-term history of eyes with untreated center-involving diabetic macular edema and baseline visual acuity ≥ 20/25 seen at the University of California, Davis Eye Center between March 2007 and March 2018. We collected characteristics including diabetes type, hemoglobin A1c, presence of visual symptoms, visual acuity, and diabetic retinopathy severity; and spectral-domain optical coherence tomography biomarkers including central subfield thickness, intraretinal cyst size, intraretinal hyperreflective foci, disorganization of retinal inner layers, and outer layer disruptions to determine factors associated with vision loss as defined by DRCR Protocol V as threshold for initiating aflibercept therapy. RESULTS Fifty-six eyes (48 patients) with untreated diabetic macular edema and mean baseline visual acuity of logMAR 0.05 ± 0.05 (Snellen 20/22) were followed for an average of 5.1 ± 3.3 years, with a median time to vision loss of 465 days (15 months). Older age (hazard ratio [HR] 1.04/year, P = 0.0195) and eyes with severe NPDR (HR 3.0, P = 0.0353) or proliferative diabetic retinopathy (HR 7.7, P = 0.0008) had a higher risk of a vision loss event. None of the spectral-domain optical coherence tomography biomarkers were associated with vision loss except central subfield thickness (HR 0.98, P = 0.0470) and cyst diameter (HR 1.0, P = 0.0094). CONCLUSION In eyes with diabetic macular edema and good initial vision, those with older age and worse diabetic retinopathy severity should be monitored closely for prompt treatment initiation when vision loss occurs.

Upon completion of this activity, participants will be able to: In support of improving patient care, this activity has been planned and implemented by Medscape, LLC and Springer Nature. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at www.medscape.org/journal/eye; (4) view/print certificate. 1.0 Release date: 19 April 2019 Expiration date: 19 April 2020 Post-test link: https://medscape.org/eye/posttest909693 S.S. has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Allergan, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Heidelberg Pharma GmbH; Novartis Pharmaceuticals Corporation; Optos; Roche. Served as a speaker or a member of a speakers bureau for: Allergan, Inc.; Bayer AG; Novartis Pharmaceuticals Corporation; Optos. Received grants for clinical research from: Allergan, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Optos. L.S.M. has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Genentech, Inc.; IRIDEX Corporation. Served as a speaker or a member of a speakers bureau for: Genentech, Inc.; IRIDEX Corporation. Received grants for clinical research from: Genentech, Inc. S.S.P. has disclosed the following relevant financial relationships: Received grants for clinical research from: Allergan, Inc.; Roche/Novartis Pharmaceuticals Corporation. G.Y. has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Alimera Sciences; Allergan, Inc.; Carl Zeiss Meditec; IRIDEX Corporation. Received grants for clinical research from: Alcon Laboratories, Inc.; IRIDEX Corporation. K-Y.L., T.K., A.Y., L.M., B.P.D-J., A.M. have disclosed no relevant financial relationships. Laurie Barclay has disclosed no relevant financial relationships. To evaluate the long-term progression of idiopathic epiretinal membranes (iERMs) with good baseline visual acuity, and to identify predictors of visual decline. Retrospective case series We reviewed records of 145 eyes with iERM and best-corrected visual acuity (BCVA) of 20/40 or greater at presentation, including BCVA, lens status, and central macular thickness (CMT) at yearly visits; as well as anatomic biomarkers including vitreomacular adhesion, pseudohole, lamellar hole, intraretinal cysts, disorganization of the inner retinal layers (DRIL), and disruption of outer retinal layers. Linear mixed effects and mixed-effects Cox proportional hazards models were used to identify clinical and anatomic predictors of vision change and time to surgery. At presentation, mean BCVA was 0.17 ± 0.10 logMAR units (Snellen 20/30) and mean CMT was 353.3 ± 75.4 μm. After a median follow-up of 3.7 years (range 1–7 years), BCVA declined slowly at 0.012 ± 0.003 logMAR units/year, with phakic eyes declining more rapidly than pseudophakic eyes (0.019 ± 0.003 vs. 0.010 ± 0.004 logMAR units/year). Metamorphopsia, phakic lens status, lamellar hole, and inner nuclear layer cysts were associated with faster visual decline. Cumulative rates of progression to surgery were 2.9, 5.6, 12.2, and 21.1% at years 1–4. Visual symptoms, metamorphopsia, greater CMT, and disruption of outer retinal layers were associated with greater hazard for surgery. Eyes with iERM and visual acuity ≥ 20/40 experience slow visual decline, with 21% of eyes requiring surgery after 4 years. Clinical and anatomic predictors of vision loss may be distinct from factors associated with earlier surgical intervention.

BACKGROUND AND OBJECTIVE: To identify factors associated with successful treatment discontinuation in eyes with retinal vein occlusions (RVOs) and macular edema (ME) in real-world settings. PATIENTS AND METHODS: Retrospective study of 214 eyes with RVO and ME with 24-month follow-up at five academic centers. Regression analyses identified factors associated with (1) successful treatment discontinuation for at least 6 months without fluid recurrence and (2) best-corrected visual acuity (BCVA) at 24 months. RESULTS: Forty percent of eyes with branch RVO and 35% with central RVO (CRVO) / hemi-retinal RVO (HRVO) successfully discontinued therapy without fluid recurrence, with median time to discontinuation of 6 and 7 months, respectively. Lower 6-month central subfield thickness was associated with greater likelihood of treatment discontinuation within 24 months for eyes with CRVO/HRVO ( P = .001), whereas better 6-month BCVA was associated with better 24-month BCVA for all RVO subtypes ( P < .001). CONCLUSION: Early anatomic response at 6 months is associated with greater likelihood of stopping treatments. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:84–92.]

PURPOSE: To evaluate the management and long-term outcomes of patients with diabetic macular oedema (DMO) and good initial visual acuity in real-world settings. METHODS: We reviewed 122 eyes of 100 patients with treatment-naive DMO and initial best-corrected visual acuity (BCVA) of 20/25 or better. We assessed clinical characteristics, logMAR BCVA, central subfield thickness (CST), cumulative intravitreal injections and laser treatments at yearly intervals, and characteristics at time of initial treatment. Linear mixed effects models were used to identify predictors of visual outcomes. RESULTS: At presentation, mean BCVA was 0.057 ± 0.048 logMAR (Snellen 20/23) and mean CST was 288 ± 57 μm. After a median follow-up of 3 years, 51% of eyes underwent treatment. More eyes underwent intravitreal injection as initial treatment (54%), but lasers were initiated at an earlier time and at better BCVA. Final BCVA was associated with better BCVA (P

BACKGROUND AND OBJECTIVE: To evaluate the financial sustainability of teleophthalmology screening for diabetic retinopathy (DR) using telehealth billing codes. PATIENTS AND METHODS: The authors performed an Institutional Review Board-approved retrospective review of medical records, billing data, and quality metrics at the University of California Davis Health System from patients screened for DR through an internal medicine-based telemedicine program using CPT codes 92227 or 92228. RESULTS: A total of 290 patients received teleophthalmology screening over a 12-month period, resulting in an increase in the DR screening rate from 49% to 63% ( P < .0001). The average payment per patient was $19.86, with an estimated cost of $41.02 per patient. The projected per-patient incentive bonus was $43.06 with a downstream referral revenue of $39.38 per patient. One hundred seventy-eight clinic visits were eliminated, providing an estimated cost savings of $42.53 per patient. CONCLUSION: Sustainable teleophthalmology screening may be achieved by billing telehealth codes but only with health care incentive bonuses, patient referrals, and by accounting for the projected cost-savings of eliminating office visits. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:S26–S34.]

Purpose To present a perspective on the use of electrotherapeutics in the history of ophthalmology along with the development of novel contemporary ophthalmic instrumentation. Design Perspective study. Methods We reviewed historical journals, articles, and books discussing the use of electricity and electrotherapeutics in ophthalmology. Results Electrotherapeutic applications have been researched and used to treat ocular diseases as far back as the 18th century. By the 20th century, research in electrotherapeutics in ophthalmology had caught the eye of Edward Jackson, the first president of the American Academy of Ophthalmology and Otolaryngology and first editor of the present (third) series American Journal of Ophthalmology. Edward Jackson published an extensive review on this topic and reported a variety of modalities used to treat ocular diseases. Conclusions While many early therapeutic uses of electricity did not produce effective and replicable results, studies on electrical stimulation of the eye provided the foundation for the development of clinically significant vision enhancing and restoring instrumentation.

Cell-mediated killing is an immune response that involves the activation of cells such as phagocytes, natural killer cells (NK), or antigen-specific cytotoxic T-lymphocytes to induce death to pathogenic cells. Enhancing T-cell mediated killing of tumor cells is emerging as a successful therapeutic approach for a variety of cancers. A number of exciting immuno-oncology technologies are being developed, including adoptive cell transfer approaches involving chimeric antigen receptor T- cells (CAR-T), tumor infiltrating lymphocytes (TIL) and natural killer (NK) cells. Biologics and small molecule approaches are also being developed to increase T-cell mediated killing of tumor cells by modulating molecular interactions among immune checkpoints such as PD-1 and CTLA4. While showing great promise, improvements to these therapies are actively being sought, and novel assay technologies aimed at identifying better and safer treatments are needed. Traditional assays for monitoring cell-mediated killing are only capable of homogenous live/dead readouts for an entire sample. Additionally, the gold-standard chromium release assay involves a laborious protocol and radioactive reagents. As an alternative platform for cell-mediated killing studies, IntelliCyt's iQue Screener is a high throughput suspension screening platform based on flow cytometry. The system can identify multiple cell types in suspension and report multiple cell killing readouts, including cell viability and apoptosis in streamlined no wash assay formats. Here we demonstrate two example high throughput flow assays for cell-mediated killing in assay models using NK cells and chimeric antigen receptor (CAR) T-cells. For the NK cell assay, the NK92 cell line was utilized as an effector cell and Jurkat cells were utilized as target cells. By labeling either target or effector cells with a cell encoder dye, both cell populations can be simultaneously monitored. Viability was determined by cell membrane integrity and Caspase 3 activation for both Jurkat and NK92 cells, and compounds that were generally cytotoxic to both NK92 and Jurkat cells could be identified. The specificity of the cell-mediated killing response was demonstrated using known signal transduction inhibitors including sunitinib, U73122, pp2, and wortmannin that would attenuate the NK cell killing activity, at a fixed target to effector cell ratio. In the second assay model using CAR T-cells, the efficacy of different CARs at targeting and killing a B-cell line (NALM-6) was profiled using multiplex assays for both cell endpoints and secreted cytokine endpoints. In addition to cell encoding and live/dead analysis, the secretion of multiple cytokines including inflammatory markers and Granzyme B were evaluated using bead-based ELISA on the same analysis platform. These application examples highlight the robustness and flexibility of the iQue Screener for performing multiplexed screening assays with cells and beads to provide greater contextual value for cell mediated killing studies. Disclosures Luu: IntelliCyt Corp: Employment. Duensing:IntelliCyt Corp: Employment.

The success of immunomodulatory approaches for the treatment of disease has generated tremendous interest in discovery of new immunotherapy based therapeutics. Immunotherapy has the potential of affecting - positively and negatively - the myriad interactions among cells and signaling molecules regulating the immune system, and projects should include high throughput screening campaigns aimed at profiling the effects of compounds on these complex interactions. We describe a no-wash, high throughput screen that provides a multiparameter activity profile for a structure activity relationship (SAR) library of immunomodulatory compounds. Seven known immunomodulatory compounds were used as templates to generate an SAR expansion library of 1438 compounds. The selection utilized a combination of various substructure and similarity search methods combined with the generation of virtual templates. Phytohemagglutinin (PHA) activated PBMCs were treated with the compounds at two doses, 10µM and 50µM. Immunophenotyping was done by α-CD3 and α-CD8 antibodies and differential toxic effects of compounds on the viability of individual cell subsets plus effects on the secretion of three cytokines were used to generate an immunological profile for each compound tested. We demonstrate the combination of a robust SAR expansion system with high throughput, multiplex screening on primary cells to generate activity profiles that can be used for identifying viable therapeutic candidates.