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Purpose To use electronic health record (EHR) time logs to calculate the complete cost profiles of routine pars plana vitrectomy surgery. Design Economic analysis. Participants Patients undergoing elective vitrectomy procedures (Current Procedural Terminology codes 67040, 67041, and 67042) at Vanderbilt University Medical Center in fiscal year 2019. Methods Process flow mapping for routine vitrectomy surgery was used to define the operative episode. De-identified time logs were sourced from an internal perioperative data warehouse to calculate procedure-level durations. The costs of materials and overhead were calculated from internal financial management software. Costs per minute for space, equipment, and personnel were based on internal figures. These inputs were used for a time-driven activity-based costing (TDABC) analysis. Main Outcome Measures Complete cost profile of routine pars plana vitrectomy surgery. Results Cost analysis of routine vitrectomy surgery resulted in a total cost of $7169.79 per patient, which was $2053.85 more than the maximum Medicare reimbursement for the equivalent episode, $5115.93. Vitrectomy cases do not break even unless the case duration is fewer than 26.81 minutes, overhead is reduced by 53.78%, or reimbursement is increased by 40.15%. Reimbursement does not compensate for variable costs alone for cases lasting longer than 55.09 minutes. In the cohort used here, 68% of cases are completely unprofitable, with increasing losses directly proportional to the length of the case. Conclusions This analysis showed that true costs for routine vitrectomy procedures are significantly more than the maximum allowable Medicare reimbursement. Academic ophthalmology departments may benefit from more accurate costing approaches using existing EHR data. These approaches may be informative for policy discussion regarding appropriate reimbursement.

Unstructured Abstract Thirteen of the fifteen most commonly reported procedures in ophthalmology were subject to a statistically significant reduction in inflation-adjusted reimbursement from 2011 to 2020. A sustainable alternative to budget neutrality is critical.

Objective:Evaluation of a mandatory immunization program to increase and sustain high immunization coverage for healthcare personnel (HCP).Design:Descriptive study with before-and-after analysis.Setting:Tertiary-care academic medical center.Participants:Medical center HCP.Methods:A comprehensive mandatory immunization initiative was implemented in 2 phases, starting in July 2014. Key facets of the initiative included a formalized exemption review process, incorporation into institutional quality goals, data feedback, and accountability to support compliance.Results:Both immunization and overall compliance rates with targeted immunizations increased significantly in the years after the implementation period. The influenza immunization rate increased from 80% the year prior to the initiative to >97% for the 3 subsequent influenza seasons (P < .0001). Mumps, measles and varicella vaccination compliance increased from 94% in January 2014 to >99% by January 2017, rubella vaccination compliance increased from 93% to 99.5%, and hepatitis B vaccination compliance from 95% to 99% (P < .0001 for all comparisons). An associated positive effect on TB testing compliance, which was not included in the mandatory program, was also noted; it increased from 76% to 92% over the same period (P < .0001).Conclusions:Thoughtful, step-wise implementation of a mandatory immunization program linked to professional accountability can be successful in increasing immunization rates as well as overall compliance with policy requirements to cover all recommended HCP immunizations.

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 To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Design Retrospective analysis of a prospective cohort study. Participants Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan–Meier analyses and multivariable proportional hazard regressions were performed. Main Outcome Measures Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98–2.82; P Conclusions This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

Purpose To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design Prospective cohort study within a controlled clinical trial. Participants Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures (1) Presence or development of GA; (2) change in the square root of GA area over time. Results At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P Conclusions Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

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: Visit adherence has been shown to play a significant role in patient health outcomes. The effect of missing visits on visual acuity (VA) in individuals with neovascular age-related macular degeneration has yet to be characterized. OBJECTIVE: To quantify the association between patients’ adherence to randomized clinical trial visits and VA in individuals with neovascular age-related macular degeneration based on 4 visit adherence metrics. DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial randomized clinical trial. Individuals with age-related macular degeneration were recruited from 44 clinical centers in the United States between February 2008 and December 2009. The 2-year study protocol required 1 visit every 4 weeks (every 21-35 days for a total of 26 visits) for monthly vs pro re nata treatments of bevacizumab vs ranibizumab. Analysis took place from November 2018 through May 2019. EXPOSURES: Visit adherence was measured in 4 ways: total number of missed visits, average number of days (avg days) between each visit, longest duration in days (max days) between visits, and visit constancy (the tally of 3-month periods with at least 1 visit attended). Average and max days were also categorized as on time (28-35 days), late (36-60 days), and very late (>60 days). MAIN OUTCOMES AND MEASURES: Change in Early Treatment Diabetic Retinopathy Study VA between the baseline and the last visit. Linear multivariate regression models were applied to analyze the association between visit adherence and change in VA, controlling for age, sex, baseline VA, anti–vascular endothelial growth factor drug, number of injections, and dosing regimen. RESULTS: Of 1178 patients, the mean (SD) age was 79.1 (7.3) years, and 727 (61.7%) were women. The mean (SD) number of missed visits was 2.4 (3.1). Overall, 1091 patients (92.6%) had complete visit constancy during the entire study period. Average days were categorized with 1060 patients (90.0%) classified as on time, 108 (9.2%) were late, and 10 (0.8%) were very late. For max days between visits, 197 patients (16.7%) were on time, 773 (65.6%) were late, and 208 (17.7%) were very late. After controlling for covariates, the late (avg days = −6.1; max days = −2.0) and very late (avg days = −12.5; max days = −5.9) groups saw fewer letters in both the avg and max days categories than patients in the on-time group (P

Purpose The introduction of anti–vascular endothelial growth factor (VEGF) agents has stimulated considerable reexamination of treatment strategies for the management of retinopathy of prematurity (ROP). Herein we summarize and review evolving concepts and provide a personal perspective on clinical management today and future directions of treatment. Design Literature review. Methods To synthesize the evolving management concepts for diagnosis and treatment of retinopathy of prematurity and to provide interpretation and perspective on current emerging therapies. Results Although initial treatment strategies focused on ablative therapy for threshold ROP, earlier treatment for type 1 or pre–threshold disease has been found to decrease unfavorable visual and structural outcomes. Vascular endothelial growth factor has emerged as a significant contributor to retinal-vascular diseases in the previous 2 decades. The potential role of anti-VEGF treatment for type 1 ROP has become a focus in recent years, but the protracted recurrence of disease and unknown adverse ocular and systemic effects have caused concern from some clinicians. In addition, the use of telemedicine technologies may provide the ability to screen remote areas with a shortage of ROP providers, thereby reducing the burden of disease. Conclusions The diagnosis and management of ROP has changed over the past 40 years; the role of anti-VEGF therapy remains to be established in current treatment strategies. Screening for initial disease and progression will likely be impacted by the increasing prevalence of telemedicine and relative shortage of clinicians.

ClinicalTrials.gov was used to assess publication rates among clinical trials in ophthalmology. Approximately one third of diabetic macular edema and age-related macular degeneration clinical trials registered on ClinicalTrials.gov do not result in timely publication of results (within 3 years of study completion).

Intravitreal injections have become the most commonly performed ophthalmic procedure, transforming modern retina practice. Postinjection endophthalmitis, while rare, remains the most feared potential complication. Prophylaxis measures including topical antisepsis, hand hygiene, gloves, masks, and drapes have all been proposed to help prevent postinjection endophthalmitis; however, there remains significant variation in protocol, given the lack of agreement among retina specialists on which steps are crucial to prevent endophthalmitis. With millions of injections performed annually, collating data have helped us better understand risk factors for endophthalmitis after intravitreal injection. We summarize the consensus guidelines for intravitreal injection technique and comprehensively review the literature on prevention of postinjection endophthalmitis.

The Infectious Diseases Society of America recommends ophthalmologic examinations for everyone with positive Candida blood culture results (candidemia) to screen for endophthalmitis, a practice that remains controversial because of multiple concerns for its limited usefulness and potential for harm.To determine guideline efficacy by reconciling discrepancies in the incidence of endophthalmitis and evaluating outcomes of studies assessing ophthalmologic screening for candidemia.PubMed literature searches, including the search terms candidemia, fungemia, chorioretinitis, and endophthalmitis, identified longitudinal studies prior to 2018 of patients who underwent ophthalmologic evaluations in the setting of positive fungal blood culture results regardless of symptoms or clinical status. Additional studies not captured by these queries were found by manually scanning references within the articles captured by the queries. Ambiguous studies of patients with concomitant bacterial or viral infections were excluded.Thirty-eight applicable studies of 7472 patients who underwent ophthalmologic screening for candidemia or fungemia were identified. Criteria were compared with the conventional definition of endophthalmitis based on present (concordant) or absent (discordant) frank vitreous involvement. Concordant (59 of 6693 [0.9%]) and discordant (114 of 779 [14.6%]) endophthalmitis incidence rates differed by 13.8% (95% CI, 11.4%-16.4%; P .001). Visual acuity for each case was recorded verbatim as subjective report provided by each study, when available. None of the concordant endophthalmitis cases reported direct, intraocular, microscopic evidence of Candida or other fungal organisms. Outcomes were available for 19 patients with concordant endophthalmitis; 6 died within 4 weeks of screening. The rate of substantial vision loss was associated (φ = 0.58; 95% CI, 0.01-0.86; P = .046) with additional invasive intervention (3 of 6 [50.0%]) compared with medical management alone (0 of 6).In this systematic review without meta-analysis, inconsistent definitions of endophthalmitis accounted for discrepancies of its incidence and overreporting among patients with candidemia, contributing to bias and resulting in the construction of guidelines. As few as 3 of 7472 patients had potential improvement, while routine examination overall could lead to additional interventions and harm in this population. These findings suggest that indiscriminate screening based on candidemia alone does not appear to be supported by the literature and should be reevaluated for inclusion as a recommendation from the Infectious Diseases Society of America.

Purpose The number of unsolicited patient complaints about a physician has been shown to correlate with increased malpractice risk. Using a large national patient complaint database, we evaluated the number and content of unsolicited patient complaints about ophthalmologists to identify significant risk factors for receiving a complaint. Design Retrospective cohort study. Participants Ophthalmologists, nonophthalmic surgeons, nonophthalmic nonsurgeons. Methods We analyzed 2087 unsolicited or spontaneous complaints reported about 815 ophthalmologists practicing in 24 academic and nonacademic organizations using the Patient Advocacy Reporting System (PARS). Complaints against 5273 nonophthalmic surgeons and 19487 nonophthalmic nonsurgeons during the same period were used for comparison. Complaint type profiles were assigned using a previously validated standardized coding system. We (1) described the distribution of complaints against ophthalmologists; (2) compared the distribution and rates of patient complaints about ophthalmologists with those of nonophthalmic surgeons and nonophthalmic nonsurgeons in the database; (3) analyzed differences in complaint type profiles and quantity of complaints by ophthalmic subspecialty, practice setting, physician gender, medical school type, and graduation date; and (4) identified significant risk factors for high numbers of unsolicited patient complaints after adjusting for other covariates. Main Outcome Measures Unsolicited patient complaints. Results Ophthalmologists had significantly fewer complaints per physician than other nonophthalmic surgeons and nonsurgeons. Sixty-three percent of ophthalmologists had 0 complaints, whereas 10% of ophthalmologists accounted for 61% of all complaints. Ophthalmologists from academic centers, female ophthalmologists, and younger ophthalmologists had significantly more complaints ( P P P Conclusions Ophthalmologists had significantly fewer complaints than nonophthalmic surgeons and nonophthalmic nonsurgeons, and by implication may have a lower malpractice risk as a group. Nevertheless, a small number of ophthalmologists generated a disproportionate number of complaints. Working at an academic center was a significant independent risk factor for having more patient complaints. Further research is needed to clarify the underlying reasons for this association and to identify interventions that may decrease this risk.

Importance Understanding the distribution of patient complaints by physician age may provide insight into common patient concerns characteristic of early, middle, and late stages of careers in ophthalmology. Most previous studies of patient dissatisfaction have not addressed the association with physician age or controlled for other characteristics (eg, practice setting, subspecialty) that may contribute to the likelihood of patient complaints, unsafe care, and lawsuits. Objective To assess the association between ophthalmologist age and the likelihood of generating unsolicited patient complaints (UPCs) among a cohort of ophthalmologists. Design, Setting, and Participants Retrospective cohort study with variable duration of follow-up. The study assessed time to first complaint between 2002 and 2015 in 1342 attending ophthalmologists or neuro-ophthalmologists who had graduated from medical school before 2010 and were affiliated with an organization that participates in Vanderbilt University Medical Center’s Patient Advocacy Reporting System. Participants were stratified into 5 age bands and were followed up from the time of their employment to receipt of their first complaint. Trained coders categorized UPCs into 34 specific types under 6 major categories. Main Outcomes and Measures Time to first recorded complaint. Multivariable Cox proportional hazards model was used to measure the association between time to first complaint and ophthalmologist age after adjustment for predetermined covariates. Results The median physician age was 47 years, with 9% who were 71 years or older. The cohort was 74% male, 90% held MD degrees, and 73% practiced in academic medical centers. The mean follow-up period was 9.8 years. Ophthalmologists older than 70 years had the lowest complaint rate (0.71 per 1000 follow-up days vs 1.41, 1.84, 2.02, and 1.88 in descending order of age band). By 2000 days of follow-up (or within 5.5 years), the youngest group had an estimated UPC risk of 0.523. By 4000 days (>10 years), participants in the older than 70 years age band had an estimated risk of UPC of only 0.364. The 2 youngest age bands were associated with a statistically significant shorter time to first complaint. Compared with those aged 71 years or older, the risk of incurring a UPC for those aged 41 to 50 years was 1.73-fold higher (hazard ratio [HR], 1.73; 95% CI, 1.21-2.46;P = .002). Similarly, participants aged 31 to 40 years had a 2.36 times higher risk of incurring a UPC (HR, 2.36; 95% CI, 1.64-3.40;P Conclusions and Relevance This study suggests that older ophthalmologists are less likely to receive UPCs than younger ones. Although limitations in the study design could affect the interpretation of these conclusions, the findings may have practical implications for patient safety, clinical education, and clinical practice management.

PURPOSE To determine whether preoperative medical testing reduces the risk of postoperative systemic adverse events after vitreoretinal surgery. METHODS Retrospective cohort study at a single academic university hospital involving a total of 2,215 patients undergoing vitreoretinal surgery. Medical charts of 2,215 patients who underwent vitreoretinal surgery between January 2002 and November 2011 at Vanderbilt University were reviewed for baseline comorbidities, preoperative testing, type of anesthesia during surgery, and systemic adverse events occurring within 30 days after surgery. Main outcome measures were the association of baseline characteristics and preoperative testing with postoperative systemic adverse events. RESULTS Approximately a half of patients had electrolyte, renal function, and electrocardiogram evaluation. The most common comorbidities were hypertension (53%), diabetes mellitus (37%), and coronary artery disease (18%). The most common preoperative testing performed was blood glucose (58%). A total of 102 systemic adverse events occurred in 89 of 2,215 patients (4%) within the first 30 days after surgery with the majority (72%) occurring within the first 24 hours. The most common adverse event was bradycardia (34%) followed by desaturation (25%). Patients with a history of coronary artery disease, asthma, chronic renal disease, or receiving general anesthesia had a 2.04 (P = 0.01), 2.18 (P = 0.03), 2.76 (P < 0.01), and 3.72 (P < 0.001) increased odds of developing postoperative systemic adverse events, respectively. Multivariate logistic regression analysis demonstrated no significant correlation between preoperative testing and postoperative adverse events. CONCLUSION Incidence of postoperative systemic adverse events after vitreoretinal surgery was 4% and was significantly increased in patients with coronary artery disease, asthma, chronic renal disease, or receiving general anesthesia. In this series, preoperative testing did not measurably influence rates of postoperative systemic complications.

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.

Importance The frequency of anti–vascular endothelial growth factor (VEGF) injections has grown exponentially with the introduction of bevacizumab, ranibizumab, and most recently aflibercept. The cost associated with these medications has garnered significant national attention, warranting a granular analysis of their use. Objective To analyze trends in anti-VEGF injections for US Medicare Part B beneficiaries from 2012 to 2015. Design, Setting, and Participants This observational cohort study used 2012-2015 data from the Centers for Medicare & Medicaid Services Medicare Part B Provider Utilization Files to analyze trends in intravitreal injections of anti-VEGF medications among Medicare Part B beneficiaries and their health care professionals. Main Outcomes and Measures The primary outcome measure was distribution of and change over time in the number of anti-VEGF injections performed for ranibizumab, aflibercept, and bevacizumab. Results A total of 2 574 124 intravitreal injections were performed by 3348 ophthalmologists in the outpatient setting for Medicare Part B beneficiaries during the 2015 calendar year; 100 ophthalmologists (3.0%) performed the highest volume of intravitreal injections. The total number of intravitreal injections administered in 2015 was 870 843 for aflibercept, 697 412 for ranibizumab, and 1 147 432 for bevacizumab. Ranibizumab injections decreased by 7.1% from 2012 to 2015 and bevacizumab injections decreased by 17.1%. From 2013 to 2015, aflibercept injections increased by 69.4%. The 100 ophthalmologists performing the highest volume of ranibizumab injections, as gauged by number of injections administered, accounted for 31.0% (95% CI, 30.994%-30.997%) of all ranibizumab injections nationally. The 100 ophthalmologists performing the highest volume of aflibercept injections accounted for 17.6% (95% CI, 17.638%-17.641%) of all aflibercept injections and the 100 ophthalmologists performing the highest volume of bevacizumab injections accounted for 19.6% (95% CI, 19.649%-19.653%) of all bevacizumab injections administered nationally to Medicare Part B beneficiaries. The highest number of injections per 1000 Medicare Part B beneficiaries occurred in Nebraska (aflibercept), Tennessee (ranibizumab), and South Dakota (bevacizumab). Conclusions and Relevance A total of 3.0% of ophthalmologists account for 17.6% to 31.0% of the total number of anti-VEGF injections administered nationally in the Medicare Part B population. Overall, bevacizumab and ranibizumab injections have decreased, coinciding with a 69.4% increase in aflibercept injections.

Diabetic retinopathy (DR) is the leading cause of new-onset blindness in American adults aged 20-74 years old. The number of diabetics living with diagnosed DR increased by 89%, from 4.06 million to 7.69 million, between 2000 and 2010. Projected numbers from the Vision Health Initiative by the CDC predict that the rate of DR will triple by 2050, from 5.5 million people living with DR to 16 million. Screening guidelines aim to detect cases early because the treatments for DR can reduce severe vision loss by up to 94%. However, adherence to these guidelines is quite low. It is estimated that more than half of patients with diabetes may fail to receive necessary screening. Risk factors for non-screening discussed in this study include low health literacy, lack of access to care, pregnancy, physician adherence to guidelines, unique factors present in different minority populations, gender and age disparities, and living in rural regions. This paper also aims to address potential interventions that may improve adherence rates.

Purpose To provide a perspective on the impact of the Comparison of Age-related Macular Degeneration Treatments Trial (CATT) on future clinical practices. Design Interpretation of trial outcomes relative to clinical use of neovascular age-related macular degeneration (AMD) treatments, assessment of the influence of study design and execution on results, and review of unanalyzed safety data in the online supplement. Methods Expert opinion. Results The CATT study supports the selection of either ranibizumab or bevacizumab for treatment of AMD based on factors other than efficacy, such as cost, because monthly administration of bevacizumab was noninferior to the reference treatment of monthly ranibizumab in improving visual acuity at 1 year. Visual acuity results for bevacizumab as needed were inconclusive for noninferiority relative to monthly administration of either drug. The secondary outcome of decrease in thickness at the foveal center as measured by time-domain optical coherence tomography significantly favored the monthly ranibizumab group vs the bevacizumab-as-needed group but is more difficult to interpret as it did not correlate with visual acuity and is less appropriate for a noninferiority design. Bevacizumab groups had a statistically higher observed risk of serious adverse events; however, scrutiny of the online supplements shows similar numbers of cardiac and neurologic events in bevacizumab and ranibizumab users. Information regarding fellow eye treatment with anti-VEGF agents was not given. Conclusions CATT provides the first level I evidence for bevacizumab in a large number of patients with neovascular AMD. The trial supports use of either drug as primary therapy and suggests that modification of monthly dosing regimens is feasible. A difference in cardiovascular safety between the 2 drugs was not apparent on inspection of the supplementary safety data.

Purpose To evaluate the effect of vitrectomy on intraocular pressure (IOP). Methods Retrospective cohort study. Medical records of 101 eyes of 101 patients undergoing nonemergent vitrectomy were reviewed for rates of open-angle glaucoma, increased IOP of >4 mmHg from baseline, change in IOP from baseline, and cataract formation. Preoperative and last measured IOPs were recorded. Baseline risk characteristics including lens status and diabetes were analyzed. Main outcome measures were 1) incidence of open-angle glaucoma; 2) increase in IOP of >4 mmHg; and 3) change in IOP. Results Mean follow-up was 49 months (range, 12-105 months). Mean baseline IOP was 15.3 mmHg, and mean final IOP was 15.8 mmHg (P = 0.3). At the most recent examination, 35 study eyes had a decrease in IOP from baseline, while 14 eyes had no change and 52 eyes had an increase in IOP. Four study eyes were newly diagnosed with ocular hypertension. No study eye developed open-angle glaucoma or required medical, laser, or surgical treatment for glaucoma. Incidence of increased IOP of >4 was 7% at 4 years and 34% at 8 years. Subgroup analysis of 66 patients comparing study eyes with nonvitrectomized fellow eyes demonstrated no significant difference in rates of increased IOP of >4 (P = 0.85). Neither diabetes nor pseudophakia was associated with significantly increased IOP. Conclusion In this series, vitrectomy does not appear to increase IOP even after removal of the crystalline lens.

Background and Objective Chronic idiopathic central serous chorioretinopathy (ICSC) is characterized by persistent, recurrent, and multifocal serous detachments of the neurosensory retina. Our objective is to evaluate the visual and anatomical outcomes of patients who underwent photodynamic therapy (PDT) with Verteporfin for chronic ICSC. Study Design/Materials and Methods A retrospective review of 13 eyes of 12 patients (mean age 55, range 45–66 years) treated with PDT for chronic ICSC between June 2004 and January 2008 was conducted. Two eyes that subsequently developed choroidal neovascularization were excluded. Best corrected visual acuity (BCVA) and clinical examination prior to PDT and at most recent follow-up were recorded. Fluorescein angiography (FA) and optical coherence tomography (OCT) findings prior to and following treatment were reviewed. Results Mean duration of symptoms prior to PDT was 26.7 months (range 3–108 months). Mean follow-up duration was 21.9 months (range 2–42 months). BCVA improved in seven of eleven eyes (mean 1.7 lines, range 1–3 lines), two eyes remained unchanged, and two eyes worsened. Complete resolution of serous detachment was demonstrated in 9 of 11 eyes by FA or OCT and 10 of 11 eyes by clinical examination. One eye showed a reduction in serous detachment by OCT and clinical exam. Three eyes required two treatments for recurrent serous detachment following initial treatment. Conclusion Our data suggest that PDT leads to resolution of serous detachments and visual improvement in patients with chronic ICSC. Further follow-up would be prudent to assess the long-term outcomes and safety in this patient population. Lasers Surg. Med. 40:671–675, 2008. © 2008 Wiley-Liss, Inc.

PURPOSE To present visual acuity (VA) and related findings from patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of subfoveal choroidal neovascularization secondary to age-related macular degeneration (SST Group N Trial). DESIGN Randomized clinical trial. PARTICIPANTS Eligible patients had age-related macular degeneration with subfoveal choroidal neovascularization, some with a classic pattern on fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one eye (study eye) that had received no treatment in the macula. Any contiguous blood had to account for

Purpose To review the clinicopathologic features of eyes enucleated after failed transpupillary thermotherapy. Design Retrospective review. Methods Pathology reports in the L.F. Montgomery Laboratory between 1998 and 2002 were searched for enucleated eyes with choroidal melanoma that had been treated only by transpupillary thermotherapy (TTT) prior to enucleation. The clinical features of the patients, including ultrasonography examination, were reviewed and compared with the pathologic findings. Results Seven eyes from seven patients had been enucleated, representing 8% of eyes treated with TTT at our institute during the period studied. The primary indication for enucleation was tumor growth. The melanomas tended to grow laterally, with minimal if any increase in thickness. Five of the seven eyes histologically demonstrated extrascleral extension, which was detected by ultrasonography prior to enucleation in only one of those eyes. Conclusions Choroidal melanoma may continue to grow along a path of least resistance after TTT. The melanoma may extend laterally in the choroid and through emissary canals. Early extrascleral extension may be difficult to detect by ultrasonography.

Purpose To report the clinicopathologic findings after submacular removal of choroidal neovascular membranes (CNV) treated with verteporfin ocular photodynamic therapy. Design Interventional case series. Methods Retrospective review of eight eyes of eight patients who underwent submacular surgery for CNV after having previously received verteporfin ocular photodynamic therapy for presumed ocular histoplasmosis (one patient), age-related macular degeneration ([AMD] three patients) pathologic myopia (two patients), punctate inner choroiditis (one patient), and idiopathic CNV (one patient). All cases had undergone ocular photodynamic therapy with verteporfin using standard protocols. Six of eight patients suffered a submacular hemorrhage after ocular photodynamic therapy, and two of eight patients refused further ocular photodynamic therapy. All patients subsequently had submacular surgery with removal of the CNV. One membrane was routinely processed, sectioned, and stained with hematoxylin and eosin. Five membranes were stained with toluidine blue for light microscopic examination. Semithin (1.0 μm) sections were cut and stained with uranyl acetate-lead citrate for transmission electron microscopy. Results Choroidal neovascular membranes were removed at 3 days (presumed ocular histoplasmosis), 29 days (punctate inner choroiditis), 63 days (AMD, pathologic myopia), 66 days (AMD), 107 days (pathologic myopia), 116 days (AMD), and 152 days (idiopathic) after verteporfin ocular photodynamic therapy. Histopathologic and ultrastructural examination showed areas of vascular occlusion at 3 days that were not seen at later time points. All specimens had patent CNV. There were signs of vascular damage with extravasated erythrocytes and fibrin, pigment clumping in cells, and inflammatory cells in all but the 3-day specimen. Conclusions This case series presents data only from patients who refused repeat treatment with ocular photodynamic therapy or who developed submacular hemorrhage after initial photodynamic therapy. Histopathologic evaluation of CNV 3 days after verteporfin ocular photodynamic therapy showed partial vascular occlusion that was not present in later specimens. These later specimens demonstrated evidence of vascular damage. Verteporfin ocular photodynamic therapy does not appear to lead to permanent and complete occlusion of the CNV. Thus, treatments that lead to permanent closure of CNV without damage to the retinal pigment epithelium and sensory retina are still needed.

Objective To evaluate the safety and effect on visual acuity of photodynamic therapy with verteporfin (Visudyne, Novartis AG) in patients with subfoveal choroidal neovascularization (CNV) secondary to the ocular histoplasmosis syndrome (OHS). Design Open-label, three-center, noncomparative prospective case series. Participants OHS patients with subfoveal CNV lesions no larger than 5400 μm in greatest linear dimension (GLD) with classic or occult CNV extending under the geometric center of the foveal avascular zone and best-corrected visual acuity letter score of 73 to 34 (approximate Snellen equivalent 20/40–20/200). Methods Twenty-six patients received verteporfin (6 mg/m 2 ) infused IV over 10 minutes. Fifteen minutes after the start of infusion, a laser light at 689 nm delivered 50 J/cm 2 at an intensity of 600 mW/cm 2 over 83 seconds using a spot size with a diameter 1000 μm larger than the GLD of the lesion. At 3-month follow-up examinations, retreatment with the same regimen was applied if angiography showed fluorescein leakage. Safety assessments were also made. Main outcome measures Visual function measurements were the changes from baseline in visual acuity and contrast sensitivity scores and the proportion of patients who, based on best-corrected visual acuity scores, (1) gained 7 or more letters, (2) lost 8 or more letters, and (3) lost 15 or more letters. Results One patient was omitted from the study at the month 3 examination for not meeting the visual acuity eligibility requirements at baseline. By the month 12 examination, but excluding any retreatment at that visit, patients had received an average of 2.9 treatments of a maximum of 4 possible treatments. The month 12 median improvement from baseline in visual acuity of the remaining 25 patients was 7 letters, and median contrast sensitivity improved by 2 letters. Median visual acuity improvement was also 7 letters when three patients, who failed to meet all photographic eligibility requirements at baseline, were excluded. At the month 12 examination, 14 (56%) patients gained 7 or more letters of visual acuity from baseline, whereas 4 (16%) patients lost 8 or more letters, of which 2 (8%) lost 15 or more letters. No serious systemic or ocular adverse events were reported. Conclusions Median visual acuity improved after verteporfin therapy for at least 1 year in a small uncontrolled prospective case series of patients with subfoveal CNV caused by OHS. Verteporfin therapy seemed to be safe and well tolerated in these patients. Two-year data from this study will provide important, additional information on the safety and effect of verteporfin therapy for the treatment of subfoveal CNV secondary to OHS.

PURPOSE: To report the results of macular hole surgery using indocyanine green to improve visualization and facilitate peeling of the internal limiting membrane. METHODS: A retrospective noncomparative review of a consecutive series of 22 patients (22 eyes) who underwent macular hole repair using indocyanine green to facilitate visualization of the internal limiting membrane was performed. One patient was excluded because of a history of a rhegmatogenous retinal detachment. All patients underwent a three-port pars plana vitrectomy with internal limiting membrane peeling. Indocyanine green (0.1% solution) was used to assist in the visualization of the internal limiting membrane. The main outcome measures were postoperative visual acuity, macular hole status, and postoperative retinal pigment epithelial changes. RESULTS: In 21 eyes, the median preoperative best-corrected visual acuity was 20/200 (range, 20/60 to counting fingers at 5 feet). The median postoperative visual acuity was 20/400 (range, 20/60–1/200) with an average follow-up of 13 weeks. The macular hole was closed in 18 eyes (86%) at the most recent follow-up. Ten eyes were found to have atrophic retinal pigment epithelium changes in the area of the previous macular hole. CONCLUSIONS: Indocyanine green assists in visualization of the internal limiting membrane in macular hole surgery. In our series, 10 eyes had unusual atrophic changes in the retinal pigment epithelium at the site of the previous macular hole, or in the area where the indocyanine green solution would have had direct access to the bare retinal pigment epithelium cells. Although the use of indocyanine green improves visualization and assists with peeling of the internal limiting membrane, the safety and potential toxicity of indocyanine green to the retinal pigment epithelium require further investigation.

To study the results of modern vitrectomy in traction and combined traction-rhegmatogenous retinal detachment involving the macula in cases of ocular toxocariasis.This was a cohort study of patients seen in different institutions in the United States. Ten eyes of 10 patients were studied. Vitrectomy was performed in all eyes, combined with membrane removal, scleral buckle, fluid-gas exchange, silicone oil, or lensectomy in certain cases. The anatomic and visual results of surgery were reviewed.Ten eyes from 10 patients ranging in age from 2 to 33 years (median, 6 years) were reviewed. Follow-up ranged from 3 months to 8 years (median, 2 years). All eyes achieved macular attachment following surgery; vision improved in 5 (50%) eyes, and was unchanged in 5 (50%). Histologic specimens from six eyes were reviewed, and revealed combinations of fibrous tissue, eosinophils, plasma cells, lymphocytes, and giant cells. One specimen revealed an encysted Toxocara canis organism.Inflammation created in response to Toxocara larvae may lead to traction retinal detachment of the macula. Vitreoretinal surgery has a good chance of reattaching the macula and improving vision.

Objective To report the authors' clinical experience with submacular surgery for subfoveal membranes in children and to evaluate the histopathologic findings of membranes in children with various etiologies of choroidal neovascularization. Design Retrospective, noncomparative, interventional case series. Participants Twelve eyes of 12 consecutive children with subfoveal choroidal neovascularization treated by vitrectomy and excision of the choroidal neovascular complex. Intervention Vitrectomy, excision of the choroidal neovascular complex, and air-fluid exchange. Main outcome measures Visual acuity and recurrence of choroidal neovascular membrane. Results Preoperative visual acuities ranged from 20/60 to 20/800 (median, 20/300). Postoperative visual acuities ranged from 20/25 to 20/400 (median, 20/80) after an average follow-up of 20 months (range, 7–62 months). Ten of 12 eyes improved from immediate preoperative visual acuity, and four eyes developed recurrence of neovascular membranes over a mean follow-up of 18 months. Histopathologic examination of six excised membranes showed that the most common components of the membranes were retinal pigment epithelium, fibrocytes, vascular endothelium, and collagen. Conclusion Selected eyes of children with subfoveal neovascular membranes and no evidence of membrane regression may benefit from submacular surgery. The histopathologic findings were similar to adult choroidal neovascularization not associated with age-related macular degeneration.

PURPOSE: Experience is reported with intraoperative pharmacologic lysis of recent submacular hemorrhage with tissue plasminogen activator followed by surgical drainage of the unclotted blood in patients with retinal arterial macroaneurysms. METHODS: Nine eyes (nine patients) with a recent (≤7 days old) submacular hemorrhage involving the center of the fovea secondary to retinal arterial macroaneurysm that were managed with recombinant tissue plasminogen activator–assisted subretinal hemorrhage evacuation, including subretinal injection of tissue plasminogen activator and removal of the liquefied blood. Patients were followed for a mean 18 ± 7 months (range, 7 to 30 months). RESULTS: All nine eyes had improved final corrected visual acuity after surgery, and eight eyes (89%) attained a corrected visual acuity of 20/60 or better (mean, 20/40; range, 20/20 to 20/200). Final corrected visual acuity was limited to 20/200 in one eye. Two eyes developed a cataract that required surgery. CONCLUSIONS: Submacular surgery with tissue plasminogen activator-assisted thrombolysis achieved improved best-corrected visual acuity in eyes with recent submacular hemorrhage involving the center of the fovea associated with retinal arterial macroaneurysm.

To evaluate a tissue sealant (autologous cryoprecipitate activated with bovine thrombin) as an adjuvant in macular hole surgery.Sixty-nine patients with stage 2, 3, or 4 full-thickness macular hole were enrolled consecutively in a prospective pilot study. Anatomic closure of the macular holes with a single operation was the primary outcome. Fifty-eight patients had pre- and postoperative standardized measurements including best refracted visual acuity, reading speed, and contrast sensitivity. Group A patients (45) had primary macular holes; Group B patients (13) had recurrent macular holes or macular holes with "other" retinal pathology. Surgical technique was standardized and membrane dissections were optional.The anatomic closure rate was 80% with a minimum of 6 months follow-up. Mean improvement in visual acuity for Group A (2.9+/-0.4 lines) was significantly better than for Group B (0.8+/-0.5 lines; P = 0.008). Eyes that underwent internal limiting membrane (ILM) dissections had an anatomic closure rate of 96% (23/24), compared with 71% (32/45) in "non-ILM" cases (P = 0.034). Adverse reactions included sterile hypopyon (10%), intraretinal hemorrhage (9%), pigmentary hyperplasia (3%), and retinal detachment (3%).Tissue sealants should be evaluated as an adjuvant in macular hole surgery in a randomized clinical trial. Inflammatory reactions may occur in some patients. Internal limiting membrane dissection may improve anatomic closure rates without adversely affecting the visual acuity.

Purpose To develop a classification system for mechanical injuries of the eye. Methods The Ocular Trauma Classification Group, a committee of 13 ophthalmologists from seven separate institutions, was organized to discuss the standardization of ocular trauma classification. To develop the classification system, the group reviewed trauma classification systems in ophthalmology and general medicine and, in detail, reports on the characteristics and outcomes of eye trauma, then established a classification system based on standard terminology and features of eye injuries at initial examination that have demonstrated prognostic significance. Results This system classifies both open-globe and closed-globe injuries according to four separate variables: type of injury, based on the mechanism of injury; grade of injury, defined by visual acuity in the injured eye at initial examination; pupil, defined as the presence or absence of a relative afferent pupillary defect in the injured eye; and zone of injury, based on the anteroposterior extent of the injury. This system is designed to be used by ophthalmologists and nonophthalmologists who care for patients or conduct research on ocular injuries. An ocular injury is classified during the initial examination or at the time of the primary surgical intervention and does not require extraordinary testing. Conclusions This classification system will categorize ocular injuries at the time of initial examination. It is designed to promote the use of standard terminology and assessment, with applications to clinical management and research studies regarding eye injuries.

Purpose To determine visual acuity outcome after indocyanine green angiography-guided laser photocoagulation of choroidal neovascularization associated with pigment epithelial detachment in eyes with age-related macular degeneration. Methods We retrospectively reviewed pretreatment and posttreatment visual acuity after laser photocoagulation to well-demarcated hyperfluorescent areas seen with indocyanine green angiography adjacent to or within pigment epithelial detachments in 20 eyes of 20 patients with age-related macular degeneration and suspected choroidal neovascularization. Results Visual acuity before and after laser photocoagulation was followed up for 3 to 24 months (median, 9 months). At 3 months after laser photocoagulation, visual acuity had improved 2 or more Snellen lines in two eyes (10%), worsened by 2 or more lines in 10 (50%), and remained unchanged in eight of 20 (40%). By 6 months after laser photocoagulation, visual acuity had improved by 2 or more lines in two eyes (12%), worsened by 2 or more lines in nine (53%), and remained unchanged in six of 17 (35%). At 9 months after laser photocoagulation, visual acuity had improved by 2 or more lines in one eye (9%), worsened by 2 or more lines in nine (82%), and remained unchanged in one of 11 (9%). Conclusions Indocyanine green angiography-guided laser photocoagulation may temporarily stabilize visual acuity in some eyes with choroidal neovascularization associated with pigment epithelial detachments, but final visual acuity decreases with time.

Purpose: The authors determine if specific features of the clinical presentation of acute postoperative endophthalmitis correlate with the microbiologic culture results. Methods: A total of 420 patients who had clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation were evaluated as part of a randomized clinical trial. Results of cultures performed on aqueous and vitreous specimens obtained at presentation were categorized as follows: gram-positive coagulase-negative micrococci, "other" gram-positive, gram-negative, and equivocal/no growth. Results: Eleven features of the initial clinical presentation were associated with significant differences in the microbiologic spectrum ( P Conclusions: The presenting characteristics of acute endophthalmitis after cataract surgery may be helpful in predicting the most likely culture results. Such predictions do not appear sufficiently strong to guide the initial empiric choice of intravitreal antibiotics.

Punctate inner choroidopathyl, multifocal choroiditis2, and multifocal choroiditis associated with progressive subretinal fibrosis3 may all appear quite similar clinically. Patients affected with these conditions, which may represent either variants of single disorder or a spectrum of disease, have a similar profile: they are commonly young myopic females with multiple focal areas of inflammation at the level of the choroid/Bruchs’ membrane/retinal pigment epithelium complex. The aetiology and incidence of these conditions is unknown. Visual outcome in punctate inner choroidopathy is generally good, barring the development of subfoveal choroidal neovascularization (CNV)1.

Purpose: Penetrating ocular trauma resulting from nails can have disastrous visual consequences. Ocular nail gun injuries occur when a nail propelled at high velocity penetrates the globe. The authors report four consecutive patients with ocular injuries resulting from nail guns. Methods: Four patients with ocular nail gun injuries are described: one with scleral penetrating injury, one with corneal penetrating injury, and two with perforating (throughand-through) injuries of the globe. Results: Three of the four patients recovered good visual acuity after surgical intervention. Conclusion: Although dependent on the site of impact, the visual prognosis may be less severe than expected because the nail penetrates the eye at a high velocity such that there are less contusive forces. Adherence to safety precautions involving the use of nail guns as well as the obligatory use of safety glasses should reduce the incidence of these injuries.

T HE REMOVAL OF THE INTERNAL LIMITING MEMbrane (ILM) has been shown to be an effective treatment option in several vitreomacular diseases such as macular holes,1 macular pucker, or macular edema. As the ILM being part of the vitreoretinal interface represents a scaffold for proliferating cells, ILM peeling is currently considered a prophylactic measure against persistent or recurrent macular puckers or macular holes.1 Furthermore, ILM peeling seems to improve postoperative anatomical and functional outcome in macular holes.2 There are only single reports suggesting that ILM peeling correlates with functional deterioration.3 A large prospective study revealed small, paracentral, yet asymptomatic scotomata detected by microperimetry after ILM peeling for macular hole repair.1 This observation may indicate a discrete mechanical trauma to the nerve fiber layer associated with ILM peeling.4 However, the ILM is a very delicate and nearly invisible structure, and its removal represents a challenge for the vitreoretinal surgeon. It is not only difficult to grasp the ILM, but also to determine where the ILM has already been stripped off and where additional peeling might be necessary. Therefore, effort was made to develop a technique to visualize the ILM. One recent approach was the introduction of indocyanine green (ICG) for intraocular application during vitreomacular surgery. A tricarbocyanine dye, indocyanine green (ICG) was initially introduced in 1957. It soon became popular to record dilution curves to measure cardiac output or organ perfusion and was also used for liver function diagnosis. The principal advantages were the confinement to the vascular compartment by binding to plasma proteins and rapid excretion almost exclusively into the bile. Typically, ICG has a maximum peak of absorption at approximately 800 nm. However, it has been shown that the absorption qualities of ICG show significant variations depending on the solvent medium, for example, plasma or water, and the dye concentration. Another influence on the absorption spectrum results from progressive aggregate formation with increasing concentration. In ophthalmology, the main indication is the intravenous application for the imaging of the choroidal circulation by ICG angiography. The intravenous application of the dye has a long history of safety. Additionally, ICG can be used as a vital dye for donor corneal endothelium and to assist capsulorhexis in eyes with mature cataract. In addition, it was observed that ICG may also stain to some degree the vitreous cortex (especially the anterior vitreous base) and the ILM more intensely around the edges of a retinal hole, but no staining around vessels was seen. Recently, ICG was also suggested for photodynamic therapy at the choriocapillaris layer. The first description of ICG staining of the ILM was by Vivian Kim at the American Academy of Ophthalmology in 1999 (poster #349). One of the first reports on ICGassisted ILM peeling was published by Kadonosono and associates in the year 2000.5 It was, furthermore, demonstrated that ICG selectively stains the ILM, as a staining effect could only be achieved when the vitreous cortex or epiretinal tissue was thoroughly removed.6 Additionally, a “negative” staining effect might be useful under special circumstances such as persistent/recurrent holes, where areas of peeled and areas of not removed ILM could be identified during a second surgical approach. Clinical and histopathologic evaluations indicated that the ILM is often unintentionally removed at least in part with the epiretinal cellular layer in macular pucker surgery. However, a complete removal of the ILM reduces reproliferation of epiretinal cells and leads to better functional results.2 Therefore, ICG could be used to assist the removal of tissue (ILM) subsequent to the initial peeling of the visible epiretinal fibrocellular layer. Several published studies have emphasized the obvious advantages of the dye in visualization and easier and more complete removal of the ILM. Consequently, dye-assisted vitrectomy has been received with great enthusiasm. Accepted for publication April 15, 2003. InternetAdvance publication at ajo.com April 22, 2003 From the Ludwig-Maximilians Universitat Munchen, Munchen, Germany (A.K.); and Vanderbilt University Medical Center, Nashville, Tennessee (P.S.). Inquiries to Anselm Kampik, MD, Department of Ophthalmology, Ludwig-Maximilians Universitat Munchen, Mathidenstrasse 8, Munchen, Germany D80336; fax: ( 49) 89-5160-4778.

Several lines of evidence point to a systemic role for oxidative stress in age-related macular degeneration (AMD). Age and smoking are associated with increasing levels of systemic oxidative stress and oral antioxidant supplements have been shown to slow the progression of the disease. In addition, plasma levels of reactive oxygen species and lipid peroxidation products have been closely associated with AMD, and decreased antioxidant enzyme activity has been reported in AMD patients. Polymorphisms in mitochondrial DNA (mtDNA) and in genes coding for antioxidant enzymes have also been linked to AMD. Oxidative stress and inflammatory mediators have been shown to play a role in AMD, although it is unclear whether inflammation is aggravated by oxidative stress or vice versa. As the interaction between inflammation and oxidative stress may be critical to development and progression of AMD, a combination therapy that reduces systemic changes in redox status and controls local inflammation may be able to prevent or at least slow the development of sight-threatening late-stage disease.

In the past several years, we have witnessed a surge of interest in submacular surgery. As the literature on evacuation of subretinal hemor­ rhage and excision of choroidal neovascular membranes continues to grow, an increasing number of retinal surgeons are considering whether to offer such procedures to their pa­ tients. This consideration is tempered by the reality that there are still more questions than answers regarding submacular surgical proce­ dures.

Purpose: The purpose of this study is to assess the benefit of vitreous surgery in preventing full-thickness macular holes in patients with impending (stage 1) macular holes. Methods: A prospective randomized multicenter clinical trial was conducted on patients with full-thickness macular holes in their first eye (stage 3 or 4) and signs and symptoms of stage 1 macular holes in their fellow eye (study eye). The study eye was randomized to vitreous surgery or observation. Outcome was assessed by standardized measurement of visual acuity, detailed clinical examination, fundus photographs, and fluorescein angiography. Results: A full-thickness macular hole developed in 10 (37%) of 27 patients in the vitrectomy group compared with 14 (40%) of 35 patients randomized to observation ( P = 0.81). This difference of 3% has a 95% confidence interval of (-21%,27%). Conclusion: The study was terminated because of low recruitment. The authors were unable to prove (or disprove) the benefit of vitreous surgery in patients with stage 1 macular holes. The authors can state, however, that should a beneficial effect from vitrectomy exist, it would probably be minimal. Considering the cost and morbidity of vitreous surgery, a conservative approach for stage 1 macular hole might be appropriate.

Purpose To determine if short-term Age-Related Eye Disease Study (AREDS) antioxidant and zinc supplementation affects biomarkers of oxidative stress, possibly serving as a predictor of their efficacy. Design Prospective interventional case series. Methods Nineteen subjects, 12 with intermediate or advanced age-related macular degeneration (AMD) (AREDS categories 3 or 4) and 7 non-AMD controls, were admitted to the Vanderbilt General Clinical Research Center and placed on a controlled diet for 7 days. Antioxidant and zinc supplements were stopped 2 weeks prior to study enrollment. Dietary supplementation with 500 mg vitamin C, 400 IU vitamin E, 15 mg β-carotene, 80 mg zinc oxide, and 2 mg cupric oxide per day was instituted on study day 2. Blood was drawn on study days 2 and 7, and plasma concentrations of cysteine (Cys), cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were determined. Results Short-term AREDS supplementation significantly lowered mean plasma levels of CySS in participants on a regulated diet ( P = .034). No significant differences were observed for Cys, GSH, IsoP, or IsoF. There were no significant differences between AMD patients and controls. Conclusions This pilot interventional study shows that a 5-day course of antioxidant and zinc supplements can modify plasma levels of CySS, suggesting that this oxidative stress biomarker could help predict how likely an individual is to benefit from AREDS supplementation. Further, CySS may be useful for the evaluation of new AMD therapies, particularly those hypothesized to affect redox status.

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. 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