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.

Q Fever-Associated Chorioretinitis.

Coxiella burnetii is the causative agent in Q fever, a zoonotic disease. Ocular manifestations of this disease are extremely rare and have been infrequently reported. In this report, we describe a rare case of chorioretinitis in a patient incompletely treated for Q fever. We highlight the unique ocular manifestation with multimodal imaging, and the importance of a thorough history and prompt and correct treatment of the disease with systemic therapy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:xx-xx.].

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.

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.

Characterizing industry payments to ophthalmologists before and after onset of the COVID-19 pandemic.

Purpose: The COVID-19 pandemic had profound effects on many different aspects of our healthcare system and the relationship between industry and physicians was no exception. The present database study evaluates industry payments to ophthalmologists in order to identify whether there are significant differences in industry payments to ophthalmologists before and after onset of the pandemic. Methods: The Centers for Medicare & Medicaid Services Open Payments Database was queried for all ophthalmologists who received industry payments between 2018 and 2021. Pre-Covid was defined as 2018-2019 while post-Covid was defined as 2020-2021. Payment date, value, type, company making payment, and state of recipient were recorded. The top ten companies and states in terms of payment value were included in analysis. Generalized Estimating Equations (GEE) modeling was used to assess significance. Results: There were 729,263 industry payments to 20,832 ophthalmologists totaling $817,892,867.54 included for analysis in this study. We found that there was a significant increase in the mean value of research payments and a significant decrease in the mean value of general payments after the onset of the pandemic (both p < 0.001). We also report significant changes in industry payments to ophthalmologists based on the company making the payment and the state in which the ophthalmologist practices. Conclusions: Our results suggest that significant differences exist in industry payment patterns to ophthalmologists following onset of the COVID-19 pandemic. Understanding underlying reasons for the observed differences may improve our understanding of the relationship between industry and clinical ophthalmology.

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.

Trends in Workplace-Related Eye Injuries in the United States From 2011 Through 2020.

Purpose: To provide insight into the current scope of workplace-related eye injuries (WREIs) by describing the demographic profiles and causes of WREIs from the years 2011 through 2020. Methods: The US Bureau of Labor Statistics (BLS) dataset on WREIs injuries was used. Descriptive data generated included the frequency of eye injuries, the setting, and demographic data. Results: The BLS reported an estimated 237 590 WREIs in the study timeframe. In that time, the incidence fell from 2.4 to 1.7 per 10 000 workers. These injuries commonly occurred in men (77.1%), White individuals (36.3%), those aged 25 to 34 years (26.9%), and those in the service (23.0%) and production (18.5%) industries. On average, WREIs resulted in a median of 2 missed workdays, with only 5.0% missing more than 1 month of work. Between 2019 and 2020, there was a 15.6% reduction in total WREIs in the US but a 39.3% increase in WREIs among healthcare workers. Conclusions: Men, White individuals, and younger workers might be at increased risk for WREIs. Public health interventions targeted toward improving access to and the quality of protective equipment in these groups and in fields involved in the primary or secondary sectors of industry and healthcare might be the most cost-effective measure to reduce the impact of WREIs on the US workforce.

Assessing the Accuracy and Reliability of AI-Generated Medical Responses: An Evaluation of the Chat-GPT Model.

Background: Natural language processing models such as ChatGPT can generate text-based content and are poised to become a major information source in medicine and beyond. The accuracy and completeness of ChatGPT for medical queries is not known. Methods: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes/no) or descriptive answers. The physicians then graded ChatGPT-generated answers to these questions for accuracy (6-point Likert scale; range 1 - completely incorrect to 6 - completely correct) and completeness (3-point Likert scale; range 1 - incomplete to 3 - complete plus additional context). Scores were summarized with descriptive statistics and compared using Mann-Whitney U or Kruskal-Wallis testing. Results: Across all questions (n=284), median accuracy score was 5.5 (between almost completely and completely correct) with mean score of 4.8 (between mostly and almost completely correct). Median completeness score was 3 (complete and comprehensive) with mean score of 2.5. For questions rated easy, medium, and hard, median accuracy scores were 6, 5.5, and 5 (mean 5.0, 4.7, and 4.6; p=0.05). Accuracy scores for binary and descriptive questions were similar (median 6 vs. 5; mean 4.9 vs. 4.7; p=0.07). Of 36 questions with scores of 1-2, 34 were re-queried/re-graded 8-17 days later with substantial improvement (median 2 vs. 4; p<0.01). Conclusions: ChatGPT generated largely accurate information to diverse medical queries as judged by academic physician specialists although with important limitations. Further research and model development are needed to correct inaccuracies and for validation.

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.

Effectiveness of a Formal Business of Ophthalmology Course for Trainees.

Objective In medical school and residency training, there is little emphasis on the administrative and business aspects of running a clinical practice as either an employee or a business owner. However, by the first day of practice, young ophthalmologists need to have a basic understanding of the business of medicine to be successful in clinical practice and to avoid common pitfalls. Areas such as risk management, negotiation, financial health, lawsuits, marketing, coding, and professionalism are particularly important for practicing ophthalmologists to grasp. We instituted a formal practice management course to increase the early exposure of our trainees to the business aspects of ophthalmology. Methods Ophthalmology trainees engaged in 11, 1-hour sessions over 3 weeks during a practice management course covering 10 of the most relevant business topics for early career ophthalmologists. A precourse needs assessment, and a postcourse satisfaction and outcomes survey were administered. Results Of the 24 trainees who completed the presurvey, 96% of respondents had no previous training in contract negotiation, 88% lacked training in lawsuits, and 88% had no training in liability insurance. 96% had no inpatient coding education, and 88% had no outpatient coding training. Seventeen trainees completed the postsurvey, and statistically significant improvements in confidence ratings were found in all domains including coding, malpractice claims, and building a practice. 88% of trainees reported that the course improved their ability to code, and 100% agreed that the course improved their understanding of lawsuits, ability to negotiate a contract, and their understanding of the business of ophthalmology. Conclusion A formal, targeted business of ophthalmology course improved the knowledge of trainees on essential business concepts. This course can serve as a model for other programs looking to meet this educational need.

Trainee Perspectives of Private Equity's Impact on Ophthalmology.

Objective The accelerated involvement of private equity (PE) in ophthalmology has many potential implications for the future of the field. The aim of this study was to evaluate trainee perspectives on PE's impact on ophthalmology. Methods An electronic survey was sent to trainees via an online ophthalmology research newsletter. The survey assessed for career goals and perspectives on the involvement of PE and its impact across a variety of attributes. Results A total of 41 United States-based respondents responded to the survey, 68% were medical students and 32% were residents or fellows. Seventy-eight percent of respondents reported they would not consider working for a PE-owned practice. There was a negative perceived impact of PE for physician autonomy, long-term physician income, career advancement, and quality of care. There was a positive perceived impact for the number of physician extenders, more referral sources, financial support, bargaining with insurance companies, starting physician salary, and administrative burden. All respondents agreed (76% strongly agree, 24% somewhat agree) that education about practice options and ownership structures is important to include in residency program education, with preferred modalities of small group discussions and on-site learning. Conclusions Trainees broadly perceive PE to negatively impact the practice of ophthalmology. While there were attributes perceived to be positively impacted by PE, these were not felt to be as important as those which may be negatively affected. New modalities for education about practice ownership options are necessary, and small group discussions and on-site learning may be of the highest yield for trainees.

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.