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Objective This study aimed to analyze the effectiveness of the American Academy of Ophthalmology (AAO)'s Leadership Development Program (LDP), report the program's impact on participants in attaining ophthalmic leadership positions, and identify opportunities to improve future LDP programming. Design An open cohort study was performed on AAO LDP graduates by using an online questionnaire and retrospective monitoring. Participants and Methods AAO LDP graduates from 1999 to 2019 participated in the study. A Likert-scale survey was distributed via email. Online responses were submitted anonymously to a team at the Berkeley Haas School of Business for analysis. A separate review of gender demographics and ophthalmic leadership positions held by graduates was performed. Main Outcomes Measures Regression analysis was performed to determine whether survey results supported a meaningful relationship between the measured impact and the AAO LDP program's perceived effectiveness. Ascension into leadership positions of AAO-related organizations at the national, regional, state, and subspecialty level by AAO LDP graduates was collated. Results Of 381 potential respondents, 203 survey responses were returned (53.3%). 158 reported that they are currently holding a leadership position (77.8%). Statistical analyses indicated that the overall value of the program was seen as highly effective (M = 4.6), and that the development programs combined contributed significantly to AAO LDP being judged as effective overall, F (11,191) = 24.79; p Conclusion The AAO LDP has fulfilled its initial goals of effectively developing a large cohort of ophthalmologists interested in and prepared to take on leadership roles across the profession. Development of more specific outcome measures to evaluate the program, as well as direct optimal programming, are needed to further the success of its aims.

Purpose The recent exponential growth in teleophthalmology has been limited in part by the lack of a validated method to measure visual acuity (VA) remotely. We investigated the validity of a self-administered Early Treatment Diabetic Retinopathy Study (ETDRS) home VA test. We hypothesized that a home VA test with a printout ETDRS chart is equivalent to a standard technician-administered VA test in clinic. Design Prospective cohort study. Participants Two hundred nine eyes from 108 patients who had a scheduled in-person outpatient ophthalmology clinic visit at an academic medical center. Methods Enrolled patients were sent a .pdf document consisting of instructions and a printout ETDRS vision chart calibrated for 5 feet. Patients completed the VA test at home before the in-person appointment, where their VA was measured by an ophthalmic technician using a standard ETDRS chart. Survey questions about the ease of testing and barriers to completion were administered. For the bioequivalence test with a 5% nominal level, the 2 1-sided tests procedure was used, and an equivalent 90% confidence interval (CI) was constructed and compared with the prespecified 7-letter equivalence margin. Main Outcome Measures The primary outcome was the mean adjusted letter score difference between the home and clinic tests. Secondary outcomes included the unadjusted letter difference, absolute letter difference, and survey question responses. Results The mean adjusted VA letter score difference was 4.1 letters (90% CI, 3.2–4.9 letters), well within the 7-letter equivalence margin. Average unadjusted VA scores in clinic were 3.9 letters (90% CI, 3.1–4.7 letters) more than scores at home. The absolute difference was 5.2 letters (90% CI, 4.6–5.9 letters). Ninety-eight percent of patients agreed that the home test was easy to perform. Conclusions An ETDRS VA test self-administered at home following a standardized protocol was equivalent to a standard technician-administered VA test in clinic in the examined population.

Importance There is a lack of peer-reviewed literature on leadership development programs (LDP) in ophthalmology. Research into LDP demographics, outcomes, and methodology is needed. Objective The aim of the study is to evaluate the extent to which LDPs targeting ophthalmologists meet the needs of emerging leaders. Design The design type of the study is cross-sectional analysis. Setting This study involves international setting. Participants The participants involved were ophthalmologists at any career level. Methods Routine internet search was used to identify LDPs targeting ophthalmologists. LDPs identified were categorized by the outcome data available into four levels based on prior literature. Participants were assessed using previously validated software for gender (Gender-API, 2020) and race or ethnicity (NamSor, 2020) Results Nine programs were identified which were classified into LDP generations. The first LDP in ophthalmology was the American Academy of Ophthalmology (AAO) LDP, which served as the nidus for the formation of four multinational LDPs, together forming the Global LDP. These LDPs were similar in size and scope; program size ranging from nine to 30 participants; a length of 1 to 2 years; with similar curricular offerings; with funding primarily derived from cost-sharing with a nominating society. The second generation of ophthalmology LDPs in the United States has targeted female scientists or faculty (Women's LDP by ARVO) and academic ophthalmology leaders (Academic LDP by Association of University Professors of Ophthalmology).The AAO's LDP appears increasingly diverse with approximately 13% women at inception, gradually increasing from 40 to 65% women in the last 5 years (n = 389). There has also been a notable increase in ethnic diversity. Conclusion and Relevance AAO LDP is the preeminent leadership training program for ophthalmologists, and it has influenced the creation of a new generation of LDP offerings. There remains a paucity of LDP evaluation metrics and reported outcomes. Newer iterations are successfully targeting academic leadership and attempting to address known disparities in gender and race or ethnicity. Further expansion of LDPs and related research can ensure equity and diversity in the pipeline.

Importance Drug overdoses have become the number 1 cause of mortality in American adults 50 years and younger. Prescription opioid abuse is a growing concern that has garnered widespread attention among policymakers and the general public. Objective To determine the opioid prescribing patterns among ophthalmologists and elucidate their role in the prescription opioid abuse epidemic. Design, Setting, and Participants In this observational cohort study, beneficiaries and their physicians were analyzed using 2013 to 2015 Medicare Part D Prescriber Data. The Centers for Medicare and Medicaid Services Medicare Part D Prescriber Public Use Files for 2013, 2014, and 2015 were accessed. Analysis began in June 2017. Data were collected and analyzed regarding the prescribing patterns for opioid drugs (eg, number of prescriptions written including refills, number of days’ supply, and prescriber rates) for all participating ophthalmologists. Main Outcomes and Measures The mean number of opioid prescriptions written annually by ophthalmologists; prescriber rates compared with all prescriptions written; and geographic distribution of opioid prescriptions written per ophthalmologist. Results In 2013, 4167 of 19 615 ophthalmologists were women (21.2%). Consistently, most ophthalmologists (88%-89%) wrote 10 opioid prescriptions or fewer annually. Approximately 1% (0.94%-1.03%) of ophthalmologists wrote more than 100 prescriptions per year. On average, ophthalmologists wrote 7 opioid prescriptions per year (134 290 written annually by 19 638 physicians, on average) with a mean supply of 5 days. The 6 states with the highest volume of opioid prescriptions written annually per ophthalmologist were located in the southern United States. Conclusions and Relevance In general, ophthalmologists show discretion in their opioid prescribing patterns. The present opioid abuse epidemic should prompt physicians to consider revisiting their prescribing protocols given the high risk for dependency.

Purpose Inhibiting mechanistic target of rapamycin (mTOR) by pharmacological or genetic approaches can extend lifespan in mammals. The kinase activity of mTOR is controlled by upstream regulatory proteins and its subcellular localization. The purpose of this study was to characterize age-related alterations and functional consequences of mTOR signaling in the postmitotic RPE cells. Methods Activity of mTOR complex 1 (mTORC1) was monitored by measuring phosphorylation status of its downstream effector protein S6, in either cultured human RPE cells or RPE explants prepared from mice at different ages. Subcellular distribution of mTOR was investigated by immunofluorescent staining of RPE culture or flatmount. The signaling of mTORC1 was modulated by either overexpression of a small guanosine triphosphatase, Ras homolog enriched in brain (Rheb), or disruption of the Ragulator complex with small interference RNA targeting p18. The effects of mTOR pathway on degradation of phagocytosed photoreceptor outer segments (POS) were determined by measuring the turnover rate of rhodopsin. Results Aged RPE cells had more lysosome-associated mTOR and had increased response to amino acid stimulation. The lysosome distribution was essential for mTORC1 function, as disruption of the Ragulator complex abolished mTORC1 activation by amino acids. Increased mTORC1 activity caused decreased rate of degradation of internalized POS in the RPE. Conclusions Aging changes the subcellular localization and function of mTOR in the RPE. Increased mTORC1 inhibits POS degradation and may further exacerbate lysosome dysfunction of aged RPE.

prospective pathological study could better describe the in- cidence of this malformation and its clinical correlates. Tina Rutar, MD Susan Huang, MD Michele Bloomer, MD J. Brooks Crawford, MD Author Affiliations: Departments of Ophthalmology (Drs Rutar, Huang, Bloomer, and Crawford) and Pediatrics (Dr Rutar), University of California, San Francisco. Correspondence: Dr Rutar, Department of Ophthalmol- ogy, Division of Pediatric Ophthalmology and Strabis- mus, University of California, San Francisco, 10 Koret Way, K 301, San Francisco, CA 94143-0730 (rutart @vision.ucsf.edu). Financial Disclosure: None reported. 1. Spencer WH. Primary neoplasms of the optic nerve and its sheaths: clinical features and current concepts of pathogenetic mechanisms. Trans Am Oph- thalmol Soc. 1972;70:490-528. 2. Margo CE, Kincaid MC. Angiomatous malformation of the retrolaminar op- tic nerve. J Pediatr Ophthalmol Strabismus. 1988;25(1):37-39. Letter From the DSMC Regarding a Clinical Trial of Lutein in Patients With Retinitis Pigmentosa W e, the members of the Data Safety Monitor- ing Committee (DSMC) for Berson and col- league’s clinical trial of lutein in patients with retinitis pigmentosa who are receiving vitamin A, 1 share many of the concerns Massof and Fishman 2 expressed in their editorial. We served as the DSMC from 2002 through 2009. We reviewed the protocol, the statistical analysis plan, and the emerging data. We were im- pressed by the conduct of the trial, especially the excel- lent patient retention and adherence to the protocol. We reviewed and approved the manuscript before the authors submitted it for publication; however, we note some substantive changes made between the time of our review and the time of publication. For example, the ar- ticle’s new section on “Conclusions” is not consistent with our interpretation of the data, which emphasizes that the trial showed no effect of lutein on the primary outcome. We have carefully evaluated the data from the trial and view that the authors’ conclusion and the section on “Ap- plication to Clinical Practice” overstate the strength of evidence for the use of lutein. We wish to remind the clini- cal community that the evidence adduced for benefit comes from one of several secondary outcomes in a trial in which the primary outcome showed no evidence of benefit (the P value for the effect on Humphrey field ana- lyzer 30-2 field, dB/y was .66). Janet Wittes, PhD Michael B. Gorin, MD, PhD Susan T. Mayne, PhD Cynthia S. McCarthy, DHCE, MA Paul Sternberg Jr, MD Michael Wall, MD Author Affiliations: Statistics Collaborative, Inc, Wash- ington, DC (Dr Wittes); Jules Stein Eye Institute- University of California, Los Angeles (Dr Gorin); De- partment of Epidemiology and Public Health, Yale University, New Haven, Connecticut (Dr Mayne); Pri- vate consultant, Glenshaw, Pennsylvania (Ms McCarthy); Vanderbilt University Medical Center, Nashville, Ten- nessee (Dr Sternberg); and University of Iowa College of Medicine, Iowa City (Dr Wall). Correspondence: Dr Wittes, Statistics Collaborative, Inc, 1625 Massachusetts Ave NW, Ste 600, Washington, DC 20036 (janet@statcollab.com). Financial Disclosure: None reported. 1. Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010;128 2. Massof RW, Fishman GA. How strong is the evidence that nutritional supple- ments slow the progression of retinitis pigmentosa [editorial]? Arch Ophthalmol. In reply The DSMC acknowledges approval of our draft manuscript. The publication 1 contained what we regard as minor adjust- ments requested by the journal, including a “Conclusion” sec- tion in the “Abstract” that restated results. The “Application to Clinical Practice” section was in the draft manuscript ap- proved by the DSMC. Throughout the publication we stated that the treatment effect of lutein was observed only on the secondary endpoint of midperipheral field sensitivity. The DSMC suggests that if significant differences be- tween the treatment groups are not seen with respect to the primary endpoint, then the results of the trial are negative and should have little or no affect on clinical practice. Pre- cedent exists for modifying practice based on results seen with secondary endpoints and subgroup analyses. 2,3 In the Physicians’ Health Study evaluating aspirin, the paucity of cardiovascular deaths led to revision of the primary end- point to include nonfatal myocardial infarction; aspirin was then found effective in preventing primary heart attacks. 2 The Women’s Health Study assessed aspirin’s efficacy in pre- venting heart attack in women older than 45 years. Al- though results of the analysis of the entire study cohort were negative, subgroup analyses showed that aspirin reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction in women older than 65 years. 3 Similarly, results of the lutein trial should not be con- sidered negative simply because the beneficial effect was based on a secondary endpoint. A significant benefit of lutein on preserving midperipheral field sensitivity was observed in randomized comparisons using both parametric (P=.05) and nonparametric analyses (P = .03). Furthermore, observa- tional analyses showed that those with the highest serum lutein level and those with the highest increase in intrareti- nal macular pigment optical density (ie, a measure of in- traretinal lutein) had the least decline in midperipheral field sensitivity (P=.01 and P=.006, respectively). 1 Based on our results, 1,4,5 we reaffirm that most adults with typical retinitis pigmentosa should take 15 000 IU/d of vi- tamin A palmitate. They should avoid high-dose vitamin E supplementation. 4 Adults who start taking vitamin A for the first time should also take 1200 mg/d of docosahexaenoic acid (DHA) for 2 years; after 2 years, they should stop tak- ARCH OPHTHALMOL / VOL 129 (NO. 5), MAY 2011 WWW.ARCHOPHTHALMOL.COM ©2011 American Medical Association. All rights reserved. Downloaded From: http://jamanetwork.com/pdfaccess.ashx?url=/data/journals/ophth/10240/ by a University of California - Los Angeles User on 04/06/2017

Advanced age is a major risk factor for a number of vision-threatening eye diseases, including cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD). Although the mechanistic link between aging and AMD remains elusive, age-dependent degeneration of the RPE is a hallmark pathologic change of AMD, especially in the atrophic form.1–3 The RPE is part of the blood-retina barrier and is responsible for nutrient support and metabolism.4 With aging, the RPE monolayer loses cells, whereas the remaining cells are subjected to increased metabolic demand.5,6 Decreased mitochondrial function and compromised antioxidant capacity are evident in the aged RPE.7 The production of neurotrophic and angiogenic factors secreted by the RPE shows age-related changes.8,9 Recently, it has been shown that the RPE/choroid complex becomes immunoreactive with aging10; this may be associated with chronic inflammation and abnormal immune responses under certain genetically susceptible backgrounds such as complement factor H mutation. The molecular mechanisms underlying these age-related changes are largely unknown. The process of aging is determined by a genetically programmed molecular clock and is subjected to regulation by multiple pathways in which TOR-mediated signaling is one of the central players.11,12 TOR is a large serine/threonine protein kinase that integrates upstream signals from nutrients, growth factors, and energy levels to control cell growth and proliferation.13,14 In mammals, mTOR resides in two distinct signaling complexes (mTORC): mTORC1 (mTOR/Raptor/GβL) and mTORC2 (mTOR/Rictor/GβL/SIN1). The rapamycin-sensitive mTORC1 regulates translation and protein synthesis largely through the downstream effector proteins S6K and 4E-BP1.15 The phosphorylation status of these two proteins and substrate S6, further downstream, are commonly used as indicators of mTORC1 activity. In contrast to mTORC1, mTORC2 is resistant to short-term exposure to rapamycin16 and is a principal kinase responsible for the phosphorylation of Akt at Ser473.17–19 Negative regulation of aging by TOR signaling has been firmly established in various invertebrate models.12 Very recently, it has been shown that knocking out S6K increases life span in mice.20 Consistently, reduced mTOR/S6K activity has been observed in mice with extended longevity.21 However, whether mTOR regulates tissue-specific degeneration of the retina has not been well studied. In the present study, we have performed an initial characterization of the mTOR pathway in both immortalized ARPE-19 cells and human RPE cells isolated from donor eye tissues. Our results demonstrate that the RPE cells contain mTOR complexes that can be activated by various upstream stimuli. Cultured primary RPE cells entered replicative senescence after serial passages, and downregulation of mTORC1 signaling relieved senescence-associated phenotypical changes. Furthermore, we found that the response of mTORC1 to nutrient signal was upregulated in the aged RPE cells. Our data indicate that changes in the mTOR-related signaling network will likely contribute to degeneration of the RPE.

The objective of this study was to determine if MTND2*LHON4917G (4917G), a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD). A preliminary study of 393 individuals (293 cases and 100 controls) ascertained at Vanderbilt revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p = 0.11). Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study), we were able to match 560 (280 cases and 280 unaffected) on exact age at examination. This study population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR = 2.16, 95%CI 1.20–3.91, p = 0.01). In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G) appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms.

Purpose To present best-corrected visual acuity (BCVA) findings and other clinical outcomes from eyes of patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of predominantly hemorrhagic subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration. Design Randomized clinical trial (SST Group B Trial). Participants Eligible patients had subfoveal choroidal neovascular lesions greater than 3.5 disk areas (8.9 mm2) composed of at least 50% blood (either blood or CNV underlying the center of the foveal avascular zone) and BCVA of 20/100 to light perception in the study eye. Intervention Patients were assigned randomly at time of enrollment to observation or surgical removal of blood and any associated CNV. Main outcome measure A successful outcome was defined a priori as either improvement in visual acuity (VA), no change in VA, or a decline in VA of no more than 1 line (7 letters) from baseline to the 24-month examination based on an intent-to-treat analysis. Results Of 336 patients enrolled, 168 were assigned to each treatment arm; treatment arms were balanced by baseline characteristics. Of 1501 expected examinations 3 months through 36 months after baseline, 1370 (91%) were performed. Loss of > or =2 lines (> or =8 letters) of VA occurred in 56% of surgery eyes, versus 59% of observation eyes examined at 24 months. Although severe loss of VA was not the primary outcome of interest, surgery more often prevented such loss: 36% in the observation arm versus 21% in the surgery arm at the 24-month examination (chi2 P = 0.004). Of initially phakic eyes, the cumulative percentage that had undergone cataract surgery by 24 months was 44% in the surgery arm, compared with 6% in the observation arm. Twenty-seven eyes (16%) in the surgical arm, compared with 3 eyes (2%) in the observation arm, had a rhegmatogenous retinal detachment (RD). Conclusions Submacular surgery as performed in the SST Group B Trial did not increase the chance of stable or improved VA (the primary outcome of interest) and was associated with a high risk of rhegmatogenous RD, but did reduce the risk of severe VA loss in comparison with observation. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.