Influence of Anatomic Locations of T1b Melanomas and Patient Age on Outcomes.

BACKGROUND: There are no guidelines on when to more strongly recommend sentinel lymph node biopsy (SLNB) for T1b melanomas. OBJECTIVE: To examine whether anatomic locations of T1b melanomas and patient age influence metastases. METHODS: We conducted a retrospective study using data from two hospitals in Los Angeles County from January 2010 through January 2020. RESULTS: Out of 620 patients with primary melanomas, 566 melanomas were staged based on the American Joint Committee on Cancer 8th edition melanoma staging. Forty-one were T1b, of which 13 were located on the face/ear/scalp and 28 were located elsewhere. T1b melanomas located on the face/ear/scalp had an increased risk of lymph node or distant metastasis compared with other anatomic sites (31% vs 3.6%, P=0.028). For all melanomas, the risk of lymph node or distant metastasis decreased with age of 64 years or greater (P<0.001 and P=0.034). For T1b melanomas, the risk of distant metastasis increased with increasing age (P=0.047). LIMITATIONS: Data were from a single county.  Conclusion: T1b melanomas of the face/ear/scalp demonstrated a higher risk of lymph node or distant metastasis and may help guide the recommendation of SLNB, imaging, and surveillance. Younger patients may be more strongly considered for SLNB and older patients with T1b melanomas may warrant imaging.  J Drugs Dermatol. 2024;23(5):306-310. doi:10.36849/JDD.7667.

Is Blepharoplasty Cost-effective? Utility Analysis of Dermatochalasis and Cost-effectiveness Analysis of Upper Eyelid Blepharoplasty.

PURPOSE: This cross-sectional prospective study measured utility values of upper eyelid dermatochalasis to quantify its impact on quality of life and assess cost-effectiveness of upper blepharoplasty. METHODS: Utility of dermatochalasis was assessed using the standard reference gamble and time trade-off methods, with dual anchor points of perfect eye function and perfect health. The utility value obtained was used to create a Markov model and run a cost-effectiveness analysis of blepharoplasty as a treatment for dermatochalasis while utilizing the societal perspective. RESULTS: One hundred three patients with dermatochalasis recruited from an urban outpatient ophthalmology clinic completed the utility survey. The authors determined utility values for dermatochalasis ranging from 0.74 to 0.92 depending on the measurement method (standard reference gamble/time trade-off) and anchor points. The cost-effectiveness analysis yielded an incremental cost-effectiveness ratio of $3,146 per quality-adjusted life year, well under the conventional willingness-to-pay threshold of $50,000 per quality-adjusted life year. Probabilistic sensitivity analysis with Monte Carlo simulation demonstrated that blepharoplasty would be cost-effective in 88.1% of cases at this willingness-to-pay threshold. CONCLUSIONS: Dermatochalasis has an impact on quality of life that is significantly associated with level of perceived functional impairment. Rising health care costs have underscored the importance of providing value-based treatment to patients, and the results of this study suggest that blepharoplasty is a cost-effective treatment option for symptomatic bilateral upper eyelid dermatochalasis.

Axial length and pharmacologic pupillary dilation in highly myopic patients.

PURPOSE: To determine how high myopia impacts pharmacological pupillary dilation, and to evaluate the relationship between the extent of pharmacologic pupillary dilation and axial length. METHODS: Patients were grouped into high myopes, defined as one or both eyes having a refractive error greater than - 6 diopters, and controls (between - 2 and + 2 diopters). Dilation was achieved with 1 drop each of tropicamide 1% and phenylephrine 2.5%. Pupil size was measured at full and dim light prior to dilation, then 15 and 30 min after dilation. Biometry was measured for each patient. Statistical analyses were performed using the Mann-Whitney-Wilcoxon tests, two-sample Welch's t-tests, and linear mixed effect models and generalized estimating equations models accounting for inter-eye correlation. RESULTS: Forty patients (20 high myopes and 20 controls, 80 eyes total) participated in the study. High myopes had larger pupils at baseline and achieved significantly greater pupillary size (7.08 mm, 95% CI: 6.97 to 7.19 mm) than controls (6.23 mm, 95% CI: 5.94 to 6.52 mm) after 30 min of dilation (P < .0005). Fully dilated pupil size at 30 min was significantly correlated with both refractive error (r = - 0.57, P < .0005) and axial length (r = 0.47, P < .0005). Generalized estimating equations and linear mixed effect models identified other predictive variables of pupil size after dilation including age and white-to-white diameter. CONCLUSIONS: Highly myopic patients dilate to a larger pupillary size compared to other patients. Predicting dilation based on extent of myopia could facilitate intraocular surgery planning and reduce clinic wait times for myopic patients.

Cost-Effectiveness Analysis of Light Adjustable Lens Compared to Monofocal Intraocular Lens in Cataract Surgery.

PURPOSE: To analyze the cost-effectiveness of the Light Adjustable Lens (LAL; RxSight) in comparison to a monofocal intraocular lens (IOL) for individuals undergoing cataract surgery in both eyes. METHODS: A cost-effectiveness analysis was performed using a Markov model that simulated the patient outcomes and costs associated with undergoing cataract surgery with the LAL or monofocal IOL. Cost-effectiveness was determined using the incremental cost-effectiveness ratio (ICER), a measure that quantifies the incremental cost in dollars per quality-adjusted life year (QALY) gained. Treatments with the ICER below the willingness-to-pay threshold (WTP) of $50,000/QALY were considered cost-effective. The model was also evaluated for the impact of uncertainties in parameters using one-way sensitivity and probabilistic sensitivity analyses. RESULTS: The cost-effectiveness analysis showed that the LAL is cost-effective compared to monofocal IOLs in patients undergoing cataract surgery, with ICERs of $9,792/QALY (health care perspective) and $10,072/QALY (societal perspective) both significantly below the WTP. The model was most sensitive to patient age, market cost of the LAL, and proportion of patients with residual astigmatism following cataract surgery. The probabilistic sensitivity analysis showed that cataract surgeries in patients starting at age 65 years were cost-effective in 94% of the simulations at a WTP of $50,000/QALY. CONCLUSIONS: From both health care and societal perspectives, the study shows cataract surgeries performed with the LAL are cost-effective when compared to those performed with a monofocal IOL. More studies are needed to compare the LAL to other premium lenses that also provide patients with excellent visual outcomes at a higher cost. [J Refract Surg. 2023;39(11):777-782.].

Cost-effectiveness analysis of endoscopic dacryocystorhinostomy using Markov modelling.

OBJECTIVE: To determine the cost-effectiveness of endoscopic dacryocystorhinostomy (DCR). METHODS: We constructed a Markov model in which patients with nasolacrimal duct obstruction received endoscopic DCR or no surgery. Incremental cost-effectiveness ratios, 1-way sensitivity analyses, and probabilistic sensitivity analyses were used to evaluate for model sensitivity to multiple model inputs. RESULTS: Endoscopic DCR was found to be cost-effective with an incremental cost-effectiveness ratio of US$2162 per quality-adjusted life-year. The model was most sensitive to the health utility deduction from epiphora. Probabilistic sensitivity analysis found endoscopic DCR to be cost-effective over no surgery 93.7% of the time. CONCLUSIONS: Endoscopic DCR is a cost-effective treatment for patients with epiphora. The model is very sensitive to the negative effect epiphora has on quality of life. With the advancement of health care technology and surgical techniques, the success rates of endoscopic DCR continue to improve and to be an even more efficacious and economical treatment for nasolacrimal duct obstruction.

Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment. METHODS: We conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy. We examined the efficacy and safety of PD-1 therapy, as well as clinical and pathological variables in association with outcomes. Progression-free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated using Kaplan-Meier methodology. Toxicity was graded per Common Terminology Criteria for Adverse Events V.5.0. RESULTS: A total of 29 patients with BCC who were treated with PD-1 inhibition were included for analysis, including 20 (69.0%) with locally advanced and 9 (31.0%) with metastatic disease. The objective response rate was 31.0%, with five partial responses (17.2%), and four complete responses (13.8%). Nine patients had stable disease (31.0%), with a disease control rate of 62.1%. The median DOR was not reached. Median PFS was 12.2 months (95% CI 0.0 to 27.4). Median OS was 32.4 months (95% CI 18.1 to 46.7). Two patients (6.9%) developed grade 3 or higher toxicity, while four patients (13.8%) discontinued PD-1 inhibition because of toxicity. Higher platelets (p=0.022) and any grade toxicity (p=0.024) were significantly associated with disease control rate. CONCLUSIONS: The clinical efficacy of PD-1 inhibition among patients with advanced or metastatic BCC in this real-world cohort were comparable to published trial data. Further investigation of PD-1 inhibition is needed to define its optimal role for patients with this disease.

Five-Year Cost-Effectiveness Modeling of Primary Care-Based, Nonmydriatic Automated Retinal Image Analysis Screening Among Low-Income Patients With Diabetes.

BACKGROUND: Artificial intelligence-based technology systems offer an alternative solution for diabetic retinopathy (DR) screening compared with standard, in-office dilated eye examinations. We performed a cost-effectiveness analysis of Automated Retinal Image Analysis System (ARIAS)-based DR screening in a primary care medicine clinic that serves a low-income patient population. METHODS: A model-based, cost-effectiveness analysis of two DR screening systems was created utilizing data from a recent study comparing adherence rates to follow-up eye care among adults ages 18 or older with a clinical diagnosis of diabetes. In the study, the patients were prescreened with an ARIAS-based, nonmydriatic (undilated), point-of-care tool in the primary care setting and were compared with patients with diabetes who were referred for dilated retinal screening without prescreening, as is the current standard of care. Using a Markov model with microsimulation resulting in a total of 600 000 simulated patient experiences, we calculated the incremental cost-utility ratio (ICUR) of the two screening approaches, with regard to five-year cost-effectiveness of DR screening and treatment of vision-threatening DR. RESULTS: At five years, ARIAS-based screening showed similar utility as the standard of care screening systems. However, ARIAS reduced costs by 23.3%, with an ICUR of $258 721.81 comparing the current practice to ARIAS. CONCLUSIONS: Primary care-based ARIAS DR screening is cost-effective when compared with standard of care screening methods.

Disparities in nonmelanoma skin cancer in Hispanic/Latino patients based on Mohs micrographic surgery defect size: A multicenter retrospective study.

BACKGROUND: There is limited literature regarding potential disparities in nonmelanoma skin cancer for patients with skin of color. OBJECTIVE: Use the sizes of Mohs micrographic surgery defects to examine disparities in nonmelanoma skin cancer among Hispanic/Latino patients with a secondary aim to examine the effect of insurance type. METHODS: We conducted a multicenter retrospective study using data from 3 major institutions in Los Angeles County. A total of 3486 Mohs micrographic surgeries of basal cell, squamous cell, and basosquamous cell carcinomas were analyzed. RESULTS: Mohs micrographic surgery defect sizes were 17% larger among Hispanic/Latino patients compared with non-Hispanic White patients. More notably, when comparing defect sizes of squamous cell carcinomas to those of basal cell carcinomas, defects were 80% larger among Hispanic/Latino patients compared to non-Hispanic White patients who had 25% larger defect sizes. Compared to patients with Medicare, patients with health maintenance organization and Medicaid/health maintenance organization had 22% and 52% larger defect sizes, respectively, whereas patients with preferred provider organization, had 10% smaller defect sizes. LIMITATIONS: The data included were from a single county population. CONCLUSION: Disparities regarding nonmelanoma skin cancer exist between patients with skin of color and White patients. Patients and the medical community need to be cognizant that skin cancer can develop in patients regardless of their race and ethnicity.

Immune Complex Formation Is Associated With Loss of Tolerance and an Antibody Response to Both Drug and Target.

AMG 966 is a bi-specific, heteroimmunoglobulin molecule that binds both tumor necrosis factor alpha (TNFα) and TNF-like ligand 1A (TL1A). In a first-in-human clinical study in healthy volunteers, AMG 966 elicited anti-drug antibodies (ADA) in 53 of 54 subjects (98.1%), despite a paucity of T cell epitopes observed in T cell assays. ADA were neutralizing and bound to all domains of AMG 966. Development of ADA correlated with loss of exposure. In vitro studies demonstrated that at certain drug-to-target ratios, AMG 966 forms large immune complexes with TNFα and TL1A, partially restoring the ability of the aglycosylated Fc domain to bind FcγRIa and FcγRIIa, leading to the formation of ADA. In addition to ADA against AMG 966, antibodies to endogenous TNFα were also detected in the sera of subjects dosed with AMG 966. This suggests that the formation of immune complexes between a therapeutic and target can cause loss of tolerance and elicit an antibody response against the target.

PD-1 inhibition therapy for advanced cutaneous squamous cell carcinoma: a retrospective analysis from the University of Southern California.

PURPOSE: Approximately 5% of patients with cutaneous squamous cell carcinoma (CSCC) may develop recurrent or metastatic disease. The management of such cases is challenging and requires multi-disciplinary care. Immunotherapy using PD-1 inhibition was approved to treat unresectable or metastatic CSCC in 2018. Given limited data regarding clinical outcomes outside of published trials, we describe our experience using this therapy. METHODS: We retrospectively reviewed all patients treated with PD-1 inhibition as therapy for locally advanced, regionally metastatic or distant metastatic CSCC at the University of Southern California. Clinicopathological characteristics, treatment data using PD-1 inhibitors, and outcomes were assessed. RESULTS: Among 26 patients treated with PD-1 inhibition, the objective response rate was 42.3%, with 19.2% of patients having partial response and 23.1% having complete response to therapy. The median progression-free survival was 5.4 months. Median tumor mutational burden (TMB) was higher among responders compared to non-responders (60 vs. 9 Mut/Mb, p = 0.04). Primary CSCC tumor location on the head/neck was also associated with response to PD-1 inhibition (p = 0.04). Two patients with mutations affecting mismatch repair deficiency were noted to have complete response to treatment. No other variables were associated with treatment outcomes. CONCLUSION: PD-1 inhibition produces durable responses among patients with advanced or metastatic CSCC. PD-1 inhibition therapy is well tolerated, but patients should be monitored closely for immune-related adverse events, particularly frail or immune-suppressed patients. Further investigation of potential biomarkers to help identify patients who will derive the most benefit from this therapeutic option is needed.