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Purpose: To highlight gaps in the professional ethics of ophthalmology. Design: Perspective. Methods: Presentation of problematic cases in ophthalmologic ethics with juxtaposition of ethical, legal, and conscientious viewpoints informed by relevant literature. Results: What is legal, ethical, and conscientious overlap but are not identical. Professional ethical guidelines, when they exist, are stricter than what the law requires, but are silent on several contemporary controversies. Conscientious guidelines can vary from loosest to strictest as they apply to individuals with wide variability. The relationship of ophthalmology to society changes, and ethical guidelines lag for some of the interactions. Conclusion: The rules of ethics for ophthalmology need to be updated and evidence of activity and oversight made public. Failure to do so invites greater external regulation.

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PURPOSE: To review changes in the provision of charity eye care in the past 50 years with hypothesized resulting effects on surgical training and patient outcomes. DESIGN: Perspective. METHODS: Case report, comparison of experience in community and training program settings, and selected literature review. RESULTS: The population to which charity care applies has shrunk as broader insurance coverage has been legislated, but in 2023 remains at approximately 7.3% of the US population. In areas with ophthalmology training programs, house staff supervised by faculty provide most of the charity care. In areas without training programs, a shrinking pool of willing private practitioners provides charity care. Because there is no organized financial support behind provision of charity, nonanecdotal data needed to assess the problem and guide decision making are lacking. CONCLUSIONS: Charity eye care in ophthalmology in 2024 is a patchwork of transient, local efforts that have a few common themes: absent material basis for sustainability, a narrowing base of support by clinicians, transfer of care to training programs, and financial vetting of applicants by nonclinicians. Unless universal health care legislation passes, which would eliminate the issue, suggestions for improvement include broader voluntary participation by private practice ophthalmologists in charity eye care, allocation of charity care spending by nonprofit hospitals to support this effort, and clinician-determined criteria for provision of charitable surgery supported by involved hospital systems.

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BACKGROUND: In eyes with diabetic macular edema, the relative efficacy of administering aflibercept monotherapy as compared with bevacizumab first with a switch to aflibercept if the eye condition does not improve sufficiently (a form of step therapy) is unclear. METHODS: At 54 clinical sites, we randomly assigned eyes in adults who had diabetic macular edema involving the macular center and a visual-acuity letter score of 24 to 69 (on a scale from 0 to 100, with higher scores indicating better visual acuity; Snellen equivalent, 20/320 to 20/50) to receive either 2.0 mg of intravitreous aflibercept or 1.25 mg of intravitreous bevacizumab. The drug was administered at randomization and thereafter according to the prespecified retreatment protocol. Beginning at 12 weeks, eyes in the bevacizumab-first group were switched to aflibercept therapy if protocol-specified criteria were met. The primary outcome was the mean change in visual acuity over the 2-year trial period. Retinal central subfield thickness and visual acuity at 2 years and safety were also assessed. RESULTS: A total of 312 eyes (in 270 adults) underwent randomization; 158 eyes were assigned to receive aflibercept monotherapy and 154 to receive bevacizumab first. Over the 2-year period, 70% of the eyes in the bevacizumab-first group were switched to aflibercept therapy. The mean improvement in visual acuity was 15.0 letters in the aflibercept-monotherapy group and 14.0 letters in the bevacizumab-first group (adjusted difference, 0.8 letters; 95% confidence interval, -0.9 to 2.5; P = 0.37). At 2 years, the mean changes in visual acuity and retinal central subfield thickness were similar in the two groups. Serious adverse events (in 52% of the patients in the aflibercept-monotherapy group and in 36% of those in the bevacizumab-first group) and hospitalizations for adverse events (in 48% and 32%, respectively) were more common in the aflibercept-monotherapy group. CONCLUSIONS: In this trial of treatment of moderate vision loss due to diabetic macular edema involving the center of the macula, we found no evidence of a significant difference in visual outcomes over a 2-year period between aflibercept monotherapy and treatment with bevacizumab first with a switch to aflibercept in the case of suboptimal response. (Funded by the National Institutes of Health; Protocol AC ClinicalTrials.gov number, NCT03321513.).

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PURPOSE: To report updated clinical outcomes in subjects undergoing pars plana vitrectomy (PPV) using modern techniques and equipment for the treatment of proliferative diabetic retinopathy-related complications. Pooled analysis of five randomized clinical trials conducted at the same institution and included both study and control subjects from the trials. METHODS: There were 943 subjects who prospectively underwent small-gauge PPV with antivascular endothelial growth factor pretreatment for proliferative diabetic retinopathy-related complications and completed 6-month follow-up. RESULTS: The visual acuity of the study population improved from median 2.00 (interquartile range 1.3, 2.3) at baseline to median 1.00 (interquartile range 0.5, 1.3) at 6 months. One hundred and eighty-four patients (19.5%) achieved 20/50 or better acuity, and 652 patients (69.1%) achieved 20/200 or better acuity at 6 months. The vision improved or remained stable in 901 patients (95.5%), and 11 patients (1.2%) developed no light perception at 6 months. Intraoperative complications occurred in 343 cases (36.4%), and 199 cases (21.1%) experienced a postoperative complication. The most common postoperative complication was vitreous hemorrhage in 124 cases (62.3% of all complications). Unplanned secondary PPV was necessary in 86 cases (9.1%). CONCLUSION: This study reports updated clinical outcomes in patients undergoing PPV for proliferative diabetic retinopathy-related complications which compares favorably with the age before small-gauge PPV and antivascular endothelial growth factor pretreatment.

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PURPOSE: To evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for anti-vascular endothelial growth factor therapy over a 12-week period in patients with neovascular age-related macular degeneration. DESIGN: A phase 2 multicenter randomized double-masked, vehicle-controlled proof-of-concept study. METHODS: Trial includes n = 90 patients with active choroidal neovascularization due to neovascular age-related macular degeneration and under anti-vascular endothelial growth factor treatment. All patients received an intravitreal injection of ranibizumab at baseline and were retreated when there was evidence of disease recurrence (rescue). Patients were randomized 1:1 to receive topical LHA510 or vehicle for 12 weeks. Drops were administered twice a day for 8 weeks and then 3 times a day for the last 4 weeks. MAIN OUTCOME MEASURE: The primary outcome was the number of patients requiring rescue over 84 days of topical dosing. Key secondary outcome measures were time to first rescue, total number of ranibizumab injections, changes in central subfield thickness, and changes of visual acuity from baseline to day 84. RESULTS: The extended per protocol set included 70 patients of whom 25 of 33 patients in the LHA510 group (75.8%) and 25 of 37 patients in the placebo group (67.6%) required rescue by day 84 (P = .8466). Secondary and subgroup analysis did not support evidence of efficacy. Twenty-one of 46 patients administered LHA510 developed a reversible corneal haze that resolved with cessation of treatment and did not recur in patients restarted at once daily frequency. CONCLUSION: In spite of extensive optimization for topical efficacy, LHA510 failed to demonstrate clinical efficacy.

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BACKGROUND: The spread of SARS-CoV-2 in Sub-Saharan Africa is poorly understood and to date has generally been characterised by a lower number of declared cases and deaths as compared to other regions of the world. Paucity of reliable information, with insights largely derived from limited RT-PCR testing in high-risk and urban populations, has been one of the biggest barriers to understanding the course of the pandemic and informed policy-making. Here we estimate seroprevalence of anti-SARS-CoV-2 antibodies in Ethiopia during the first wave of the pandemic. METHODS: We undertook a population-based household seroprevalence serosurvey based on 1856 participants in Ethiopia, in the capital city Addis Ababa, and in Jimma, a middle-sized town in the Oromia region, and its rural surroundings (districts of Seka and Mana), between 22 July and 02 September 2020. We tested one random participant per household for anti-SARS-CoV-2 antibodies using a high specificity rapid diagnostic tests (RDTs) and evaluated population seroprevalence using a Bayesian logistic regression model taking into account test performance as well as age and sex of the participants. FINDINGS: In total, 2304 random households were visited, with 1856 individuals consenting to participate. This produced a sample of 956 participants in Addis Ababa and 900 participants in Jimma. IgG prevalence was estimated at 1.9% (95% CI 0.4-3.7%), and combined IgM/IgG prevalence at 3.5% (95% CI 1.7-5.4%) for Addis Ababa in early August 2020, with higher prevalence in central sub-cities. Prevalence in Jimma town was lower at 0.5% (95% CI 0-1.8%) for IgG and 1.6% (95%CI 0-4.1%) for IgM/IgG, while in rural Jimma IgG prevalence was 0.2% and IgM/IgG 0.4% in early September. INTERPRETATION: More than four months after the first cases were detected in Ethiopia, Addis Ababa displayed a prevalence under 5% and likely as low as 2%, while rural Jimma displayed a prevalence of 0.2%. A 2% seroprevalence figure for the capital translated to a number of cases at least five times larger than those reported for the country as a whole. At the same time, it contrasts with significantly higher seroprevalence figures in large cities in Europe and America only two to three months after the first cases. This population-based seroepidemiological study thus provides evidence of a slower spread of SARS-CoV-2 in the Ethiopian population during the first wave of the pandemic and does not appear to support the notion that lower case numbers were simply a reflection of limited testing and surveillance. FUNDING: Schmidt Family Foundation, Joachim Hertz Foundation, Nespresso, Peet's and Smuckers.

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PURPOSE: To describe the characteristics of Japanese patients with hydroxychloroquine (HCQ) retinopathy developing within 3 years of treatment outset. STUDY DESIGN: Retrospective case series METHODS: Three patients with HCQ retinopathy developing within 3 years of treatment outset have been identified in Japan since HCQ became available in 2015. Their medical charts, containing optical coherence tomography (OCT), fundus autofluorescence imaging, and visual field tests, were reviewed. RESULTS: The treatment durations and cumulative doses until onset were 29-36 months and 182-326 g, respectively. The first patient had possible pre-existing maculopathy, although the abnormalities were ambiguous. The second and third patients had impaired renal function. The patients did not complain of severe visual disturbance at diagnosis, but visual field loss and disruption of the outer retinal segments consisting of a parafoveal pattern in the first case and a pericentral pattern (localized, 8 or more degrees from the center of the fovea) in the second and third cases were clearly observed on OCT. Even after HCQ discontinuation, their retinopathy showed slight progression on the visual field tests and OCT images. A blood sample was obtained from 1 patient on the day after HCQ discontinuation, and the whole blood level of HCQ was measured using validated liquid chromatography-tandem mass spectrometry. The HCQ level 27 h after the last dose was high, at 2240 ng/mL (suggested threshold > 1733 ng/mL). CONCLUSION: Ophthalmologic screening from the initiation of HCQ treatment detected 3 cases of HCQ retinopathy developing within 3 years of treatment outset, including a patient with a high blood level of HCQ.

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PURPOSE: To quantify the economic incentives associated with the choice of anti-VEGF drugs for retinal diseases. METHODS: An economic model was created based on the distribution of use and number of injections of bevacizumab (B), versus aflibercept or ranibizumab (AR); published Medicare reimbursement rates; published rebates; estimated unreimbursed drug use; estimated use of drug company samples; and published costs-of-drugs. Differential economic incentives associated with the choice of drugs were calculated over a range of distributions of drug use. RESULTS: The splits in drug choice ranged from 92% AR/8% B to 31% AR/69% B, and in annual injection numbers from 2000 to 6000 with a median of 4000 in one 5-person retina service. Assumed values for rebates were 1% for drug company rebate, 1% for group purchasing organization rebate, and 5 for number of unreimbursed injections per year. The differential economic incentive of a 92% AR/8% B split compared to a 31% AR/69% B split for the median annual number of injections was $266, 893. CONCLUSION: Using real-world data, the economic incentive associated with a choice of more expensive anti-VEGF drugs is large. Accounting for unreimbursed drug use and the cost of additional staff required to manage expensive drug inventory does not nullify the incentive. To what degree this financial incentive influences ophthalmologists' choice of drugs is unknown, but not trivial. Financial disclosure of the conflicts of interest in the drugs recommended for treatment should be discussed with patients.

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The structure and functions of the choroid have been long acknowledged but the pathophysiology behind various anomalies has been difficult to understand until the advent of optical coherence tomography (OCT). With OCT imaging, choroidal cavitations appear as optically empty spaces between the outer retinal and choroidal layers with attenuation or loss of outer retinal layers. Choroidal cavitations are found in the posterior pole and seen in conditions such as pathologic myopia, north carolina macular dystrophy (NCMD), focal choroidal excavation (FCE), and torpedo maculopathy (TM). To date, these disorders have not been linked. A commonality they all share is malformation of the RPE-photoreceptor-choroid complex. The following report describes the differences and similarities of choroidal cavitation amongst the different retinal disorders and emphasizes the importance of multimodal imaging in the detection and management of potential complications.

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PURPOSE: To describe the rationale for revising the hydroxychloroquine (HCQ) dosing and screening guidelines and to identify the barriers to more effective guidelines in the future. DESIGN: Literature review. METHODS: A PubMed query of studies on HCQ dosing and HCQ retinopathy (HCQR) screening was conducted with a selective review of the English language literature. RESULTS: Three iterations of the American Academy of Ophthalmology HCQ dosing and HCQR screening guidelines have been published without including prescribing physicians on the writing committees. This may contribute to prescribing physicians' low adherence to the guidelines. As ancillary tests have improved, asymptomatic HCQR is being detected earlier, leading to a higher reported prevalence of HCQR and a drop in the ceiling for safe dosing. These trends put stricter constraints on prescribers and their patients, who may have had well-controlled autoimmune disease on HCQ doses that were previously considered to be below the high-risk threshold for HCQR. Indeed, stopping HCQ at the earliest sign of HCQR should be reconsidered; for cases of early HCQR, dose reduction and more intensive monitoring for retinopathy may strike a more appropriate balance between HCQ risk and benefits. A prospective study using the Diabetic Retinopathy Clinical Research Retina Network with standardized collection of data, HCQ blood levels, centralized grading of ancillary tests, and community and academic ophthalmologists would provide a stronger evidence base for future HCQ guidelines. CONCLUSIONS: The HCQ dosing and screening guidelines should be updated and a prospective study of HCQ dosing and HCQR should be initiated with the joint efforts of ophthalmologists and prescribing physicians.

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PURPOSE: To review the current therapeutic options for the management of diabetic retinopathy (DR) and diabetic macular edema (DME) and examine the evidence for integration of laser and pharmacotherapy. METHODS: A review of the PubMed database was performed using the search terms diabetic retinopathy, diabetic macular edema, neovascularization, laser photocoagulation, intravitreal injection, vascular endothelial growth factor (VEGF), vitrectomy, pars plana vitreous surgery, antiangiogenic therapy. With additional cross-referencing, this yielded 835 publications of which 301 were selected based on content and relevance. RESULTS: Many recent studies have evaluated the pharmacological, laser and surgical therapeutic strategies for the treatment and prevention of DR and DME. Several newer diagnostic systems such as optical coherence tomography (OCT), microperimetry, and multifocal electroretinography (mfERG) are also assisting in further refinements in the staging and classification of DR and DME. Pharmacological therapies for both DR and DME include both systemic and ocular agents. Systemic agents that promote intensive glycemic control, control of dyslipidemia and antagonists of the renin-angiotensin system demonstrate beneficial effects for both DR and DME. Ocular therapies include anti-VEGF agents, corticosteroids and nonsteroidal anti-inflammatory drugs. Laser therapy, both as panretinal and focal or grid applications continue to be employed in management of DR and DME. Refinements in laser devices have yielded more tissue-sparing (subthreshold) modes in which many of the benefits of conventional continuous wave (CW) lasers can be obtained without the adverse side effects. Recent attempts to lessen the burden of anti-VEGF injections by integrating laser therapy have met with mixed results. Increasingly, vitreoretinal surgical techniques are employed for less advanced stages of DR and DME. The development and use of smaller gauge instrumentation and advanced anesthesia agents have been associated with a trend toward earlier surgical intervention for diabetic retinopathy. Several novel drug delivery strategies are currently being examined with the goal of decreasing the therapeutic burden of monthly intravitreal injections. These fall into one of the five categories: non-biodegradable polymeric drug delivery systems, biodegradable polymeric drug delivery systems, nanoparticle-based drug delivery systems, ocular injection devices and with sustained release refillable devices. At present, there remains no one single strategy for the management of the particular stages of DR and DME as there are many options that have not been rigorously tested through large, randomized, controlled clinical trials. CONCLUSION: Pharmacotherapy, both ocular and systemic, will be the primary mode of intervention in the management of DR and DME in many cases when cost and treatment burden are less constrained. Conventional laser therapy has become a secondary intervention in these instances, but remains a first-line option when cost and treatment burden are more constrained. Results with subthreshold laser appear promising but will require more rigorous study to establish its role as adjunctive therapy. Evidence to support an optimal integration of the various treatment options is lacking. Central to the widespread adoption of any therapeutic regimen for DR and DME is substantiation of safety, efficacy, and cost-effectiveness by a body of sound clinical trials.

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PURPOSE: The increasing prevalence of obesity over the past 60 years implies the need to reassess the risk of hydroxychloroquine retinopathy (HR) in obese women using the American Academy of Ophthalmology (AAO) 2016 guidelines. DESIGN: Cross-sectional study. PARTICIPANTS: Medical records of 64 patients with HR from the practices of 2 ophthalmologists, 11 of whom were women with body mass index of 30 kg/m2 or more, were reviewed. METHODS: Daily dosing based on real and ideal weight was calculated. MAIN OUTCOME MEASURE: Determine the number (and percentage) of patients given daily dosing according to real-weight and ideal-weight guidelines. RESULTS: In 4 patients (36%), daily dosing was more than 5 mg/kg based on real weight and more than 6.5 mg/kg based on ideal weight. In 4 patients (36%), daily dosing was 5 mg/kg or less based on real weight and 6.5 mg/kg or less based on ideal weight. In 3 patients (27%), daily dosing was 5 mg/kg or less based on real weight and more than 6.5 mg/kg based on ideal weight. No patient had daily dosing of more than 5 mg/kg based on real weight and 6.5 mg/kg or less based on ideal weight. CONCLUSIONS: Twenty-seven percent of cases of hydroxychloroquine retinopathy in obese women had ostensibly safe dosing based on 2016 AAO guidelines. Overdosing of obese women by 2016 AAO guidelines is not rare. Daily dosing based on the older 6.5-mg/kg ideal weight threshold is safer in women with a body mass index of 30 kg/m2 or more.

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PURPOSE: To discuss two striking cases of ophthalmomyiasis interna posterior, in which the larval stage of a botfly is found in the posterior segment. OBSERVATIONS: In the first case, the subretinal maggot is alive and found to be migrating under the retina. The maggot was lasered in the office and killed. In the second case, a dead maggot was discovered in the subretinal space in a child, after it had caused significant subretinal scarring and permanent vision loss. CONCLUSIONS AND IMPORTANCE: Ophthalmomyiasis is a rare condition that can often be unrecognized and result in permanent vision loss. Early diagnosis and photocoagulation of the larva (if alive) can halt progression of vision loss in these cases.

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Importance: Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula (center-involved DME [CI-DME]) with visual acuity impairment (20/32 or worse). The best approach to treating patients with CI-DME and good visual acuity (20/25 or better) is unknown. Objective: To compare vision loss at 2 years among eyes initially managed with aflibercept, laser photocoagulation, or observation. Design, Setting, and Participants: Randomized clinical trial conducted at 91 US and Canadian sites among 702 adults with type 1 or type 2 diabetes. Participants had 1 study eye with CI-DME and visual acuity of 20/25 or better. The first participant was randomized on November 8, 2013, and the final date of follow-up was September 11, 2018. Interventions: Eyes were randomly assigned to 2.0 mg of intravitreous aflibercept (n = 226) as frequently as every 4 weeks, focal/grid laser photocoagulation (n = 240), or observation (n = 236). Aflibercept was required for eyes in the laser photocoagulation or observation groups that had decreased visual acuity from baseline by at least 10 letters (≥ 2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits. Main Outcomes and Measures: The primary outcome was at least a 5-letter visual acuity decrease from baseline at 2 years. Antiplatelet Trialists' Collaboration adverse events (defined as myocardial infarction, stroke, or vascular or unknown death) were reported. Results: Among 702 randomized participants (mean age, 59 years; 38% female [n=264]), 625 of 681 (92% excluding deaths) completed the 2-year visit. For eyes with visual acuity that decreased from baseline, aflibercept was initiated in 25% (60/240) and 34% (80/236) in the laser photocoagulation and observation groups, respectively. At 2 years, the percentage of eyes with at least a 5-letter visual acuity decrease was 16% (33/205), 17% (36/212), and 19% (39/208) in the aflibercept, laser photocoagulation, and observation groups, respectively (aflibercept vs laser photocoagulation risk difference, -2% [95% CI, -9% to 5%]; relative risk, 0.88 [95% CI, 0.57-1.35; P = .79]; aflibercept vs observation risk difference, -3% [95% CI, -11% to 4%]; relative risk, 0.83 [95% CI, 0.55-1.27; P = .79]; laser photocoagulation vs observation risk difference, -1% [95% CI, -9% to 6%]; relative risk, 0.95 [95% CI, 0.64-1.41; P = .79]). Antiplatelet Trialists' Collaboration vascular events occurred in 15 (7%), 13 (5%), and 8 (3%) participants in the aflibercept, laser photocoagulation, and observation groups. Conclusions and Relevance: Among eyes with CI-DME and good visual acuity, there was no significant difference in vision loss at 2 years whether eyes were initially managed with aflibercept or with laser photocoagulation or observation and given aflibercept only if visual acuity worsened. Observation without treatment unless visual acuity worsens may be a reasonable strategy for CI-DME. Trial Registration: ClinicalTrials.gov Identifier: NCT01909791.

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OBJECTIVE: To test whether an educational model involving patients and family members (P/F) in medical error disclosure training for interprofessional clinicians can narrow existing gaps between clinician and P/F views about disclosure. METHOD: Parallel presurveys/postsurveys using Likert scale questions for clinicians and P/F. RESULTS: Baseline surveys were completed by 91% (50/55) of clinicians who attended the workshops and 74% (65/88) of P/F from a hospital patient and family advisory council. P/F's baseline views about disclosure were significantly different from clinicians' in 70% (7/10) of the disclosure expectation items and 100% (3/3) of the disclosure vignette items. For example, compared with clinicians, P/F more strongly agreed that "patients want to know all the details of what happened" and more strongly disagreed that "patients find explanation(s) more confusing than helpful." In the medication error vignette, compared with clinicians, P/F more strongly agreed that the error should be disclosed and that the patient would want to know and more strongly disagreed that disclosure would do more harm than good (all P < 0.05). After the workshop, P/F and clinician views about information sharing, fallibility, truth telling, and threshold for disclosure showed greater concordance, with significant differences remaining in less than half of the expectation items and none of the vignette responses. DISCUSSION: Even with self-selecting clinicians, collaborative learning with P/F highlights important differences in patient and clinician baseline perspectives about medical error disclosure and brings patient and clinicians views closer together.

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BACKGROUND: Cultivating a healthy work environment and upholding patient safety are important priorities in health care. Challenges in workplace communication are common and affect staff well-being and patient outcomes. Previous interventions have focused on organizational issues and work-life balance. OBJECTIVE: To assess the feasibility of monthly interdisciplinary educational rounds that support clinicians' ability to navigate workplace clinical and communication challenges while promoting interprofessional teamwork and self-care. METHODS: The Program to Enhance Relational and Communication Skills rounds are an educational initiative within a large pediatric tertiary care hospital. Participation is voluntary and offered to inter-professional clinicians from 4 critical care units, cardiac catheterization unit, and intermediate care unit. Topics of monthly hour-long sessions are developed collaboratively. Feasibility is assessed by ongoing documentation of attendance. Postintervention questionnaires are used to evaluate the program's value. RESULTS: Between April 2010 and December 2016, a total of 1156 clinicians participated (median, 18 per seminar): 653 nurses (56%), 103 social workers (9%), 102 child life specialists (9%), 32 psychologists (3%), 40 chaplains (3%), 18 physicians (2%), 18 ethicists (2%), and 190 others (16%), including medical interpreters, nursing students, and administrative staff. Ninety-two percent of participants rated their participation as "quite valuable" or "very valuable." Programs of highest interest included child assent, bereavement, social media, and workplace bullying. Evolution into actual clinical practice change remains a challenge for the future. CONCLUSION: Our approach to communication and workplace challenges is relevant, user-friendly, and feasible. Difficult topics are addressed in real time, with clinicians learning interprofessionally.

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