Gene therapy for age-related macular degeneration: potential, feasibility, and pitfalls.

PURPOSE OF REVIEW: The landscape for age-related macular degeneration (AMD) is rapidly changing with addition of biosimilars and now United States Food and Drug Administration (FDA) approved nonneovascular AMD (nnAMD) treatment options. These developments have inspired a burgeoning pipeline of gene therapy approaches focused on similar antivascular endothelial growth factors (VEGF) and complement related pathways. Historic and more recent setbacks in the gene therapy pipeline, including intraocular inflammatory reactions, have raised important concerns for adverse events related to AMD therapeutics both for gene and nongene approaches. The specific clinical profile of these therapeutics approaching later stage clinical trials are complex and under active investigation; however, these options hold promise to disrupt the current landscape and change management paradigms for one of the leading causes of vision loss worldwide. RECENT FINDINGS: This review covers current gene therapy approaches for neovascular AMD (nAMD) and nnAMD. Intravitreal, suprachoroidal, and subretinal delivery routes are discussed with attention to technical procedure, capabilities for transgene delivery to target tissue, immunogenicity, and collateral effects. Suprachoroidal delivery is an emerging approach which may bridge some of the practical drawbacks for intravitreal and subretinal methods, though with less elaborated immunologic profile. In parallel to delivery modification, viral vectors have been cultivated to target specific cells, with promising enhancements in adeno-associated viral (AAV) vectors and persistent interest in alternate viral and nonviral delivery vectors. Ongoing questions such as steroid or immunosuppressive regimen and economic considerations from a payer and societal perspective are discussed. SUMMARY: The present review discusses emerging gene therapy options which could foster new, more durable nAMD and nnAMD therapeutics. These options will need refinement with regards to route, vector, and dosage, and specialists must decipher the specific clinical risk benefit profile for individual patients. Ongoing concerns for immunogenicity or dosage related adverse events could stifle progress, while further vector development and refined delivery techniques have the potential to change the safety and efficacy of currently options in the pipeline.

Ophthalmology Workforce Projections in the United States, 2020 to 2035.

PURPOSE: To analyze ophthalmology workforce supply and demand projections from 2020 to 2035. DESIGN: Observational cohort study using data from the National Center for Health Workforce Analysis (NCHWA). METHODS: Data accessed from the Department of Health and Human Services, Health Resources and Services Administration (HRSA) website were compiled to analyze the workforce supply and demand projections for ophthalmologists from 2020 to 2035. MAIN OUTCOME MEASURES: Projected workforce adequacy over time. RESULTS: From 2020 to 2035, the total ophthalmology supply is projected to decrease by 2650 full-time equivalent (FTE) ophthalmologists (12% decline) and total demand is projected to increase by 5150 FTE ophthalmologists (24% increase), representing a supply and demand mismatch of 30% workforce inadequacy. The level of projected adequacy was markedly different based on rurality by year 2035 with 77% workforce adequacy versus 29% workforce adequacy in metro and nonmetro geographies, respectively. By year 2035, ophthalmology is projected to have the second worst rate of workforce adequacy (70%) of 38 medical and surgical specialties studied. CONCLUSIONS: The HRSA's Health Workforce Simulation Model forecasts a sizeable shortage of ophthalmology supply relative to demand by the year 2035, with substantial geographic disparities. Ophthalmology is one of the medical specialties with the lowest rate of projected workforce adequacy by 2035. Further dedicated workforce supply and demand research for ophthalmology and allied professionals is needed to validate these projections, which may have significant future implications for patients and providers. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Accuracy and Reliability of Chatbot Responses to Physician Questions.

Importance: Natural language processing tools, such as ChatGPT (generative pretrained transformer, hereafter referred to as chatbot), have the potential to radically enhance the accessibility of medical information for health professionals and patients. Assessing the safety and efficacy of these tools in answering physician-generated questions is critical to determining their suitability in clinical settings, facilitating complex decision-making, and optimizing health care efficiency. Objective: To assess the accuracy and comprehensiveness of chatbot-generated responses to physician-developed medical queries, highlighting the reliability and limitations of artificial intelligence-generated medical information. Design, Setting, and Participants: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes or no) or descriptive answers. The physicians then graded the chatbot-generated answers to these questions for accuracy (6-point Likert scale with 1 being completely incorrect and 6 being completely correct) and completeness (3-point Likert scale, with 1 being incomplete and 3 being complete plus additional context). Scores were summarized with descriptive statistics and compared using the Mann-Whitney U test or the Kruskal-Wallis test. The study (including data analysis) was conducted from January to May 2023. Main Outcomes and Measures: Accuracy, completeness, and consistency over time and between 2 different versions (GPT-3.5 and GPT-4) of chatbot-generated medical responses. Results: Across all questions (n = 284) generated by 33 physicians (31 faculty members and 2 recent graduates from residency or fellowship programs) across 17 specialties, the median accuracy score was 5.5 (IQR, 4.0-6.0) (between almost completely and complete correct) with a mean (SD) score of 4.8 (1.6) (between mostly and almost completely correct). The median completeness score was 3.0 (IQR, 2.0-3.0) (complete and comprehensive) with a mean (SD) score of 2.5 (0.7). For questions rated easy, medium, and hard, the median accuracy scores were 6.0 (IQR, 5.0-6.0), 5.5 (IQR, 5.0-6.0), and 5.0 (IQR, 4.0-6.0), respectively (mean [SD] scores were 5.0 [1.5], 4.7 [1.7], and 4.6 [1.6], respectively; P = .05). Accuracy scores for binary and descriptive questions were similar (median score, 6.0 [IQR, 4.0-6.0] vs 5.0 [IQR, 3.4-6.0]; mean [SD] score, 4.9 [1.6] vs 4.7 [1.6]; P = .07). Of 36 questions with scores of 1.0 to 2.0, 34 were requeried or regraded 8 to 17 days later with substantial improvement (median score 2.0 [IQR, 1.0-3.0] vs 4.0 [IQR, 2.0-5.3]; P < .01). A subset of questions, regardless of initial scores (version 3.5), were regenerated and rescored using version 4 with improvement (mean accuracy [SD] score, 5.2 [1.5] vs 5.7 [0.8]; median score, 6.0 [IQR, 5.0-6.0] for original and 6.0 [IQR, 6.0-6.0] for rescored; P = .002). Conclusions and Relevance: In this cross-sectional study, chatbot generated largely accurate information to diverse medical queries as judged by academic physician specialists with improvement over time, although it had important limitations. Further research and model development are needed to correct inaccuracies and for validation.

Time-driven Activity-based Costing Analysis of Fluorescein Angiography.

PURPOSE: To use electronic health record (EHR) time logs and time-driven activity-based costing (TDABC) to calculate the complete cost profile of office-based fluorescein angiography (FA). DESIGN: Economic analysis. SUBJECTS: Patients undergoing routine FA (Current Procedural Terminology [CPT] 92235) at Vanderbilt Eye Institute in fiscal year 2022. METHODS: Process flow mapping for routine FA was used to define the care episode after manual observation. Deidentified time logs were sourced from the EHR and all manually validated to calculate durations for each stage. The cost of materials was calculated from internal financial figures. Cost per minute for space, equipment, and personnel were based on internal figures. Published fluorescein costs were used for base-case analysis with scenario analysis based on a range of internal figures from pharmacy quotes. These inputs were used for a TDABC analysis. MAIN OUTCOME MEASURES: Time-driven activity-based costing of FA episode of care. Secondary scenario analyses focus on breakeven scenarios for key inputs, including medication costs RESULTS: Cost analysis of office-based FA resulted in an average total cost of $152.95 (nominal) per interpreted study per patient, which was $36.52 more than the maximum Medicare reimbursement for CPT 92235 in Mac Locality for Tennessee 10312 for fiscal year 2022 ($116.43; $76.11 [technical component] and $40.33 [physician component]). The negative contribution margin is strongly influenced by the cost of fluorescein, which comprises 39.8% of the episode costs, excluding overhead. CONCLUSIONS: The current analysis here shows that the recently increased cost of fluorescein has driven up the cost of office-based FA relative to the current maximum allowable Medicare reimbursement, leading to a negative contribution margin and financial loss. Given conservative cost estimates here, it is unlikely for profitability to be achieved without changes in the cost of fluorescein or increased reimbursement. These results may be informative for policy discussion regarding appropriate reimbursement for codes using injectable fluorescein. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effects of Cost Sharing on Ophthalmic Care Utilization in the Affordable Care Act Marketplace.

PURPOSE: To determine the distribution and quantity of ophthalmic care consumed on Affordable Care Act (ACA) plans, the demographics of the population utilizing these services, and the relationship between ACA insurance coverage plan tier, cost sharing, and total cost of ophthalmic care consumed. METHODS: This cross-sectional study analyzed ACA individual and small group market claims data from the Wakely Affordable Care Act (WACA) 2018 dataset, which contains detailed claims, enrollment, and premium data from Edge Servers for 3.9 million individual and small group market lives. We identified all enrollees with ophthalmology-specific billing, procedure, and national drug codes. We then analyzed the claims by plan type and calculated the total cost and out-of-pocket (OOP) cost. RESULTS: Among 3.9 million enrollees in the WACA 2018 dataset, 538,169 (13.7%) had claims related to ophthalmology procedures, medications, and/or diagnoses. A total of $203 million was generated in ophthalmology-related claims, with $54 million in general services, $42 million in medications, $20 million in diagnostics and imaging, and $86 million in procedures. Average annual OOP costs were $116 per member, or 30.9% of the total cost, and were lowest for members with platinum plans (16% OOP) and income-driven cost sharing reduction (ICSR) subsidies (17% OOP). Despite stable ocular disease distribution across plan types, beneficiaries with silver ICSR subsidies consumed more total care than any other plan, higher than platinum plan enrollees and almost 1.5× the cost of bronze plan enrollees. CONCLUSIONS: Ophthalmic care for enrollees on ACA plans generated substantial costs in 2018. Plans with higher OOP cost sharing may result in lower utilization of ophthalmic care.

Comparison of Incremental Costs and Medicare Reimbursement for Simple vs Complex Cataract Surgery Using Time-Driven Activity-Based Costing.

Importance: Cataract surgery is one of the most commonly performed surgeries across medicine and an integral part of ophthalmologic care. Complex cataract surgery requires more time and resources than simple cataract surgery, yet it remains unclear whether the incremental reimbursement for complex cataract surgery, compared with simple cataract surgery, offsets the increased costs. Objective: To measure the difference in day-of-surgery costs and net earnings between simple and complex cataract surgery. Design, Setting, and Participants: This study is an economic analysis at a single academic institution using time-driven activity-based costing methodology to determine the operative-day costs of simple and complex cataract surgery. Process flow mapping was used to define the operative episode limited to the day of surgery. Simple and complex cataract surgery cases (Current Procedural Terminology codes 66984 and 66982, respectively) at the University of Michigan Kellogg Eye Center from 2017 to 2021 were included in the analysis. Time estimates were obtained using an internal anesthesia record system. Financial estimates were obtained using a mix of internal sources and prior literature. Supply costs were obtained from the electronic health record. Main Outcomes and Measures: Difference in day-of-surgery costs and net earnings. Results: A total of 16 092 cataract surgeries were included, 13 904 simple and 2188 complex. Time-based day-of-surgery costs for simple and complex cataract surgery were $1486.24 and $2205.83, respectively, with a mean difference of $719.59 (95% CI, $684.09-$755.09; P < .001). Complex cataract surgery required $158.26 more for costs of supplies and materials (95% CI, $117.00-$199.60; P < .001). The total difference in day-of-surgery costs between complex and simple cataract surgery was $877.85. Incremental reimbursement for complex cataract surgery was $231.01; therefore, complex cataract surgery had a negative earnings difference of $646.84 compared with simple cataract surgery. Conclusions and Relevance: This economic analysis suggests that the incremental reimbursement for complex cataract surgery undervalues the resource costs required for the procedure, failing to cover increased costs and accounting for less than 2 minutes of increased operating time. These findings may affect ophthalmologist practice patterns and access to care for certain patients, which may ultimately justify increasing cataract surgery reimbursement.

Implications of the presence of private equity in ophthalmology: an academic perspective.

PURPOSE OF REVIEW: Private equity acquisitions of ophthalmology private practices have been steadily increasing over the past decade with far-reaching implications. Ophthalmology departments at academic medical centers are not insulated from the impact of this trend. RECENT FINDINGS: The limited data on this subject in the ophthalmology literature identify the growing number of practice acquisitions. However, the lack of transparency obfuscates a clear understanding of the effect on patients and practice patterns. SUMMARY: Leaders at academic medical centers need to be aware of surrounding practice consolidation because of private equity as this could affect revenue streams and patient referral patterns, accelerating expansion. Trainees are entering an uncertain job marketplace that may create a compelling argument to practice in an academic medical center ophthalmology department.

Potential Cost Savings Associated with a Multiuse Preoperative and Preinjection Eyedrop Protocol.

PURPOSE: To calculate the cost savings associated with a multiuse preoperative and preinjection eyedrop protocol. DESIGN: Economic analysis. PARTICIPANTS: Adults undergoing ophthalmic surgical procedures requiring preoperative dilation and intravitreal injections. METHODS: Economic modeling with scenario analysis was used to derive the value for cost savings secondary to a protocol in which perioperative mydriatic eyedrop bottles are used across multiple patients versus the current protocol in which drop bottles are wasted after single-patient use. Similar analyses were performed for a multiuse povidone-iodine protocol for intravitreal injections. Sensitivity analyses were used to test baseline model assumptions with varying degrees of waste and patient volume. RESULTS: The multiuse mydriatic protocol allowed for a 97.1% reduction in the number of eyedrop bottles required for the single-use protocol (1037 bottles vs. 35 850 bottles). This led to an estimated 5-year cost savings of approximately $240 000 (nominal) per institution (performing an average of 1434 cases/year) in the base case. This savings varied minimally in sensitivity analyses accounting for practical limitations (loss, expiration, or contamination) of multiuse containers, with savings of 97.54% to 95.00% for excess supply ranges from 0% to 100% in the multiuse protocol. Likewise, the cost savings varied minimally in sensitivity analyses for eyedrop sizes, with savings of 99.23% to 96.69% for mydriatic eyedrop sizes of 15 µl per drop to 65 µl per drop, respectively, in the multiuse protocol. Over a 5-year period, for povidone-iodine drops before performing intravitreal injection, the multiuse protocol required 153 bottles compared with 41 954 bottles (99.6% reduction) for the current single-use protocol, resulting in a nominal cost savings of $41 801, which varied minimally in sensitivity analyses. CONCLUSIONS: Multiuse perioperative mydriatic eyedrops are a viable option for cost and environmental waste reduction for ophthalmologic procedures and surgeries requiring dilation. Likewise, multiuse povidone-iodine may allow for large relative cost reduction for in-office procedures. The total potential savings over 5 years was estimated at more than $280 000 before adjusting for inflation.

Annulus-shaped I-125 plaque brachytherapy for conjunctival melanoma.

Purpose: To report successful ring-shaped iodine-125 plaque brachytherapy for conjunctival melanoma. Observations: Eye Physics (EP) plaque brachytherapy, designed with Plaque Simulator software, proved to be an effective treatment modality with some corneal irritation and no recurrence at 12-months post radiation. Conclusion and importance: Management of conjunctival melanoma is complicated by the lack of gold standard adjuvant treatments. I-125 EP plaque brachytherapy represents a viable option for these malignancies. Specifically, ring-shaped plaque geometries allow for targeted radiotherapy.

Economic Evaluation of the Merit-Based Incentive Payment System for Ophthalmologists: Analysis of 2019 Quality Payment Program Data.

Importance: The Merit-Based Incentive Payment System (MIPS) is intended to promote high-value health care through quality-related Medicare payment adjustments. Objective: To assess the economic evaluation of MIPS scoring and reporting on ophthalmologists. Design, Setting, and Participants: In this retrospective, cross-sectional, multicenter economic evaluation conducted from October 10 to November 30, 2021, MIPS performance and related payment adjustments were evaluated using the US Centers for Medicare & Medicaid Service (CMS) public data files for ophthalmologists. Participants were stratified by reporting affiliation. Analysis of variance and summary statistics were used to characterize and compare total and subcategory MIPS scores and adjustments received by participants. Reported CMS methodology and performance year (PY) 2019 payment percentages were used to estimate payment adjustments for the following categories: positive MIPS adjustment plus potential additional adjustment for exceptional performance, positive MIPS adjustment, neutral payment adjustment, negative MIPS payment adjustment, and maximum negative MIPS payment adjustment. Study participants included ophthalmologists registered for Medicare Part B with participation in the Quality Payment Program (QPP) in PY 2019. Main Outcomes and Measures: Proportion of ophthalmologists qualifying for payment adjustments and payment adjustments. Results: For PY 2019, 76.5% of ophthalmologists (13 621) who registered for Medicare participated in the MIPS pathway of the QPP. Ophthalmologists practiced in a predominantly large metropolitan area (12 302; 90.3%). Roughly 99% of participants (11 182) received nonnegative reimbursement adjustments, and 92.6% (10 367) received positive adjustments. Ophthalmologists filing as individuals were less likely to achieve exceptional performance scores compared with those who had a filing category of advanced alternative payment model (APM; odds ratio [OR], 0.0003; 95% CI, 0.00002-0.00481) or group (OR, 0.21013; 95% CI, 0.19020-0.23215). When analyzing participating ophthalmologists with available Medicare payment data (11 193), a total of 8777 (78.4%) achieved exceptional MIPS scores corresponding to mean (SD) adjustments per physician of $244.60 ($217.36) to $4864.78 ($4323.08), or 0.07% ($2 146 835.21 of $3 212 011 252.88) to 1.33% ($42 698 166.89 of $3 212 011 252.88), of the total nondrug Medicare payment. Conclusions and Relevance: Results of this economic evaluation showed that although 78.4% of ophthalmologists received exceptional positive payment adjustments, roughly 84% (798916 of 954615) of all health care professionals nationally achieved this benchmark. Exceptional MIPS was associated with filing as group or APM, resulting in, on average, a relatively small additional payment per participant; this suggests that ophthalmologists who file as individuals should consider an alternative filing approach. Changes in MIPS methodology may disproportionately affect certain ophthalmologists, which warrants further study.

Assessment of retinal manifestations of Parkinson's disease using spectral domain optical coherence tomography: A study in Indian eyes.

PURPOSE: To assess the retinal manifestations of Parkinson's disease using optical coherence tomography. METHODS: A prospective case-control study comparing 30 eyes from 15 patients with Parkinson's disease and 22 eyes from 11 healthy age-matched controls. Total macular subfield thickness and the thickness of the ganglion cell layer, nerve fiber layer, and peripapillary retinal nerve fiber layer were measured with spectral-domain optical coherence tomography (SD-OCT). RESULTS: The mean age of PD patients was 68.4 years ± 10.64 (range: 46-82) and in the control group was 66.36 ± 5.22 (range: 64-68). The average disease duration in patients with PD was 6.7 ± 2.8 years (range: 2-10 years). The mean best-corrected visual acuity in PD was 20/26 and 20/20 in controls, with P = 0.0059, which was significant. Significant difference was also found in the contrast sensitivity between both groups. Structural differences in the central macular thickness (P = 0.0001), subfield thicknesses in the superior (P = 0.003), inferior (P = 0.001), nasal (P = 0.004), and temporal subfields (P = 0.017) was seen. Severe thinning of the ganglion cell layer was seen in PD patients (P = 0.000) as well as of the nerve fiber layer (P = 0.004). Peripapillary retinal nerve fiber thickness measured showed significant thinning in superotemporal (P = 0.000), superonasal (P = 0.04), inferonasal (P = 0.000), inferotemporal (P = 0.000), nasal (P = 0.000), and temporal quadrants (P = 0.000). CONCLUSION: Visual dysfunction was observed in patients with PD along with structural alterations on OCT, which included macular volumes, ganglion cell layer, and peripapillary retinal nerve fiber layer.

Health Care Price Transparency in Ophthalmology.

IMPORTANCE: Health care price transparency legislation is intended to reduce the ambiguity of hospital charges and the resultant financial stress faced by patients. OBJECTIVE: To evaluate the availability, usability, and variability of standard reported prices for ophthalmologic procedures at academic hospitals. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter economic evaluation study, publicly available price transparency web pages from Association of American Medical Colleges affiliate hospitals were parsed for standard charges and usability metrics. Price transparency data were collected from hospital web pages that met the inclusion criteria. Geographic practice cost indices for work, practice expense, and malpractice were sourced from the Centers for Medicare & Medicaid Services. Data were sourced from February 1 to April 30, 2021. Multiple regression was used to study the geographic influence on standard charges and assess the correlation between standard charges. MAIN OUTCOMES AND MEASURES: Availability and variability of standard prices for Current Procedural Terminology (CPT) codes 66984 (removal of cataract with insertion of lens) and 66821 (removal of recurring cataract in lens capsule using laser). RESULTS: Of 247 hospitals included, 191 (77.3%) provided consumer-friendly shoppable services, most commonly in the form of a price estimator or online tool. For CPT code 66984, 102 hospital (53.4%) provided discount cash pay estimates with a mean (SD) price of $7818.86 ($5407.91). For CPT code 66821, 71 hospital (37.2%) provided discount cash pay estimates with a mean (SD) price of $2041.72 ($2106.44). The top quartile of hospitals, prices wise, listed included prices higher than $10 400 for CPT code 66984 and $2324 for CPT code 66821. Usability issues were noted for 36 hospitals (18.8%), including requirements for personal information or web page navigability barriers. Multiple regression analysis found minimal explanatory value for geographic practice cost indices for cash discount prices for CPT codes 66984 (adjusted R2 = 0.54; 95% CI, 0.41-0.67; P < .001) and 66821 (adjusted R2 = 0.64; 95% CI, 0.51-0.77; P < .001). CONCLUSIONS AND RELEVANCE: Despite recent legislature that codified price transparency requirements, some current standard charges remain ambiguous, with substantial interhospital variability not explained by geographic variability in costs. Given the potential for ambiguous pricing to burden vulnerable, uninsured patients, additional legislation might consider allowing hospitals to defer price estimates or rigorously define standards for actionable cash discount percentages with provisions for displaying relevant benchmark prices.

Chorioretinal Biopsy-Proven Ocular Sarcoidosis in a Patient with a History of B-Cell Lymphoma.

The purpose of this report is to describe biopsy-proven ocular sarcoidosis (OS) in a 67-year-old patient with a history of sarcoidosis and diffuse large B-cell lymphoma (DLBCL). Nonspecific posterior chorioretinal lesions in a patient with prior malignancy necessitated chorioretinal biopsy to rule out metastatic lymphoma. The association between sarcoidosis and malignancy remains unclear and can complicate management of similar patients with nonspecific posterior segment findings. Chorioretinal biopsy may, therefore, be required to rule out malignancy in patients with a leading history.