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As the field of ophthalmology has evolved in the last several decades, so has the gender distribution of ophthalmologists. We conducted a narrative review to further characterise the status of women in the realm of publication, presentations, editorial positions, grants, academic promotion, and financial compensation. While the proportion of women publishing, presenting, and filling academic and editorial roles has increased over time, it still does not match that of men. Women are more likely to be first authors instead of senior authors, have lower average h-indices, and are awarded fewer grants. The magnitude of some of these differences is smaller when adjusted for women's shorter career duration on average. Despite increased representation of women in ophthalmology, women continue to receive less compensation for the same work. This review highlights that more can be done to improve gender parity in ophthalmology., (© 2024 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: This study aimed to develop an instrument to measure medical trainees' perceptions of justice in clinical learning environments., Method: Between 2019 and 2023, the authors conducted a multiyear, multi-institutional, multiphase study to develop a 16-item justice measure with 4 dimensions: interpersonal, informational, procedural, and distributive. The authors gathered validity evidence based on test content, internal structure, and relationships with other variables across 3 phases. Phase 1 involved drafting items and gathering evidence that items measured intended dimensions. Phase 2 involved analyzing relevance of items for target groups, examining interitem correlations and factor loadings in a preliminary analysis, and obtaining reliability estimates. Phase 3 involved a confirmatory factor analysis and collecting convergent and discriminant validity evidence., Results: In phase 1, 63 of 91 draft items were retained following a content validation exercise gauging how well items measured targeted dimensions (mean [SD] item ratings within dimensions, 4.16 [0.36] to 4.39 [0.34]) on a 5-point Likert scale (with 1 indicating not at all well and 5 indicating extremely well). In phase 2, 30 items were removed due to low factor loadings (i.e., < 0.40), and 4 items per dimension were selected (factor loadings, 0.42-0.89). In phase 3, a confirmatory factor analysis supported the 4-dimension model (χ2 = 610.14, P < .001; comparative fit index = 0.90, Tucker-Lewis Index = 0.87, root mean squared error of approximation = 0.11, standardized root mean squared residual = 0.06), with convergent and discriminant validity evidence showing hypothesized positive correlations with a justice measure (r = 0.93, P < .001), trait positive affect (r = 0.46, P < .001), and emotional stability (r = 0.33, P < .001) and negative correlations with trait negative affect (r = -0.39, P < .001)., Conclusions: Results indicate the measure's potential utility in understanding justice perceptions and designing targeted interventions., (Copyright © 2024 the Association of American Medical Colleges.)

Purpose: To examine whether gender differences exist in medical trainees' (residents' and fellows') evaluations of faculty at a number of clinical departments., Method: The authors conducted a single-institution (University of Minnesota Medical School) retrospective cohort analysis of 5,071 trainee evaluations of 447 faculty (for which trainee and faculty gender information was available) completed between July 1, 2019, and June 30, 2022. The authors developed and employed a 17-item measure of clinical teaching effectiveness, with 4 dimensions: overall teaching effectiveness, role modeling, facilitating knowledge acquisition, and teaching procedures. Using both between- and within-subject samples, they conducted analyses to examine gender differences among the trainees making ratings (rater effects), the faculty receiving ratings (ratee effects), and whether faculty ratings differed by trainee gender (interaction effects)., Results: There was a statistically significant rater effect for the overall teaching effectiveness and facilitating knowledge acquisition dimensions (B = -0.28 and -0.14, 95% CI: [-0.35, -0.21] and [-0.20, -0.09], respectively, P < .001, medium corrected effect sizes between -0.34 and -0.54); female trainees rated male and female faculty lower than male trainees on both dimensions. There also was a statistically significant ratee effect for the overall teaching effectiveness and role modeling dimensions (B = -0.09 and -0.08, 95% CI: [-0.16, -0.02] and [-0.13, -0.04], P = .01 and < .001, respectively, small to medium corrected effect sizes between -0.16 and -0.44); female faculty were rated lower than male faculty on both dimensions. There was not a statistically significant interaction effect., Conclusions: Female trainees rated faculty lower than male trainees and female faculty were rated lower than male faculty on 2 teaching dimensions each. The authors encourage researchers to continue to examine the reasons for the evaluation differences observed and how implicit bias interventions might help to address them., (Copyright © 2023 by the Association of American Medical Colleges.)

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder characterized by deficits in social communication and restricted, repetitive behaviors. It affects approximately 2.2% of children. Both genetic and environmental risk factors have been identified for ASD. Visual comorbidities are relatively common among children with ASD. Between 20 and 44% of ASD children have visually significant refractive error, on-third have strabismus, and one-fifth have amblyopia. In addition, ASD is 30 times more common in children with congenital blindness. It is unknown whether the association of ASD with visual morbidity is causal, comorbid, or contributing. Structural and functional abnormalities have been identified in MRIs of ASD children, and ASD children have been noted to have aberrant eye tracking. ASD children with visually significant refractive errors and poor spectacle compliance (present in 30% of ASD children) offer the opportunity for investigation into how improved visual acuity influences ASD behaviors. In this review, we focus on what is known of the visual system, refractive surgery, and ASD.

Purpose: This study aims to characterize the eye-related quality of life of children with neurodevelopmental and ocular disorders at baseline and after refractive surgery., Design: Prospective interventional case series., Methods: We enrolled children and adolescents 5 to 18 of age with neurodevelopmental disorders undergoing refractive surgery (6 for pre-/postsurgical assessment and 14 for baseline analysis). Eye-related quality of life was measured using the Pediatric Eye Questionnaire (PedEyeQ). Baseline levels of adaptive functioning and social behaviors were measured using the Adaptive Behavioral Assessment System (ABAS-3) and Social Responsiveness Scale (SRS-2). We assessed the correlation between baseline PedEyeQ scores, number of ocular comorbidities, magnitude of refractive error, and ABAS-3 and SRS-2 scores., Results: At baseline, 14 patients demonstrated decreased median eye-related quality of life (<60/100) in 5 of 9 PedEyeQ domains, moderate deficiencies in social behaviors (SRS-2 median 71, range 49-90), and low adaptive functioning (ABAS-3 median percentile for age of 0.100). Baseline PedEyeQ scores did not correlate with magnitude of refractive error or adaptive functioning scores but did correlate with number of ocular comorbidities and social behavior scores. Six patients have undergone refractive surgery without complication. Postoperatively, 11 of 11 eyes were within ±1.5 diopters spherical equivalent. Four of 6 patients exhibited clinically significant improvements in PedEyeQ scores after surgery., Conclusions: Even in the presence of significant social and adaptive impairments, quality of life in children with neurodevelopmental disorders is decreased by ocular disorders. Refractive surgery is associated with clinically significant improvements in eye-related quality of life., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To examine postoperative outcomes in pediatric patients undergoing strabismus surgery to determine the potential impact of socioeconomic disparities on ophthalmic outcomes., Methods: This study included 284 children undergoing strabismus surgery at a tertiary institution with at least 11 months of follow-up and no prior strabismus surgery or other neurologic or ophthalmologic conditions. Demographics, insurance, operative parameters, and appointments scheduled/attended were collected via chart review. Ocular alignment was recorded preoperatively and postoperatively at 3, 12, and 24 months. Two-sided t tests and chi-squared analyses were used to compare demographic and operative parameters. Logistic regression was employed to determine predictive factors for ophthalmic outcomes., Results: There was no difference in failure rates between patients with Medicaid and patients with private insurance 24 months postoperatively (45.9% vs 50.5%, respectively, P = .46). Patients with Medicaid were more likely to not follow up postoperatively (28.2% vs 9.6%, respectively, P < .01), whereas patients with private insurance were more likely to complete more than three follow-up appointments in 24 months (21.5% vs 39.0%, respectively, P < .01). Postoperative attendance was linked to Medicaid status ( P < .01) but not travel time, neighborhood income levels, or social deprivation index factors., Conclusions: There was no difference in failure rates between patients with Medicaid and patients with private insurance. Medicaid status was significantly predictive of loss to follow-up. [ J Pediatr Ophthalmol Strabismus . 2022;59(3):156-163.] .

Purpose: To compare visual acuity outcomes and loss to follow-up after initiation of treatment for unilateral amblyopia in children from different socioeconomic backgrounds., Methods: Medical records of children diagnosed as having unilateral amblyopia at an initial encounter between 2015 and 2018 were reviewed. Medicaid and private insurance were used as proxies for socioeconomic status (SES). Data points were collected at the patients' initial, follow-up, and final visits. Visual acuity improvement was the primary outcome variable in patients with at least one follow-up appointment. In a separate analysis, failure to attend a single follow-up appointment was examined for associations with SES, race, sex, and distance traveled to appointments., Results: Seventy-three patients met the inclusion criteria; of these, 28 had Medicaid and 45 had private insurance. Visual acuity improved by 2.86 lines in the Medicaid group and 2.98 lines in the private insurance group ( P = .84). Number of missed appointments and distance traveled did not correlate with visual acuity improvement. In the loss to follow-up subanalysis, 40 of 141 (28.4%) patients with Medicaid and 11 of 107 (10.3%) patients with private insurance failed to attend a single follow-up visit ( P = .001). No association was found between loss to follow-up and race, sex, or distance traveled., Conclusions: Visual acuity outcomes of treatment for amblyopia did not differ between patients with Medicaid and patients with private insurance who followed up. However, patients with Medicaid were much more likely to be immediately lost to follow-up. Measures should be taken by eye care providers and pediatricians to increase follow-up in patients from low SES populations. [ J Pediatr Ophthalmol Strabismus . 2022;59(2):110-117.] .

Purpose: Few studies have examined medical residents' and fellows' (trainees) direct experience of unprofessional behavior in clinical learning environments (CLE). The purpose of this study was to create a taxonomy of unprofessional behavior in CLEs using critical incidents gathered from trainees., Method: In step 1 (data collection), the authors collected 382 critical incidents from trainees at more than a dozen CLEs over a six-year period (2013-2019). In step 2 (model generation), nine subject matter experts (SMEs) sorted the incidents into homogenous clusters and this structure was tested with principal components analysis (PCA). In step 3 (model evaluation), two new groups of SMEs each re-sorted half of the incidents into the PCA-derived categories., Results: A 13-component solution accounted for 62.46% of the variance in the critical incidents collected. The SMEs who re-sorted the critical incidents demonstrated good agreement with each other and with the 13-component PCA solution. The resulting taxonomy included 13 dimensions, with 48.7% of behaviors focused on displays of aggression or discriminatory conduct., Conclusions: Critical incident methodology can provide unique insights into the dimensionality of unprofessional behavior in the CLE. Future research should leverage the taxonomy created to inform professionalism assessment development in the CLE.

Objective: To test whether crowdsourced lay raters can accurately assess cataract surgical skills., Design: Two-armed study: independent cross-sectional and longitudinal cohorts., Setting: Washington University Department of Ophthalmology., Participants and Methods: Sixteen cataract surgeons with varying experience levels submitted cataract surgery videos to be graded by 5 experts and 300+ crowdworkers masked to surgeon experience. Cross-sectional study: 50 videos from surgeons ranging from first-year resident to attending physician, pooled by years of training. Longitudinal study: 28 videos obtained at regular intervals as residents progressed through 180 cases. Surgical skill was graded using the modified Objective Structured Assessment of Technical Skill (mOSATS). Main outcome measures were overall technical performance, reliability indices, and correlation between expert and crowd mean scores., Results: Experts demonstrated high interrater reliability and accurately predicted training level, establishing construct validity for the modified OSATS. Crowd scores were correlated with (r = 0.865, p < 0.0001) but consistently higher than expert scores for first, second, and third-year residents (p < 0.0001, paired t-test). Longer surgery duration negatively correlated with training level (r = -0.855, p < 0.0001) and expert score (r = -0.927, p < 0.0001). The longitudinal dataset reproduced cross-sectional study findings for crowd and expert comparisons. A regression equation transforming crowd score plus video length into expert score was derived from the cross-sectional dataset (r 2  = 0.92) and demonstrated excellent predictive modeling when applied to the independent longitudinal dataset (r 2  = 0.80). A group of student raters who had edited the cataract videos also graded them, producing scores that more closely approximated experts than the crowd., Conclusions: Crowdsourced rankings correlated with expert scores, but were not equivalent; crowd scores overestimated technical competency, especially for novice surgeons. A novel approach of adjusting crowd scores with surgery duration generated a more accurate predictive model for surgical skill. More studies are needed before crowdsourcing can be reliably used for assessing surgical proficiency., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate whether the standard dilating drop regimen consisting of phenylephrine, tropicamide, and proparacaine produces clinically significant improvement in pupil size compared to tropicamide and proparacaine during diagnostic eye examination. Methods: Sixty-three adult patients at Washington University School of Medicine Eye Clinic were enrolled in this prospective, randomized trial. Each patient received one of two dilating drop regimens: phenylephrine + tropicamide + proparacaine (PE+T+PP), which is considered the standard therapy, or tropicamide + proparacaine (T+PP). Main outcome measures were the proportion of pupils able to achieve successful clinical examination without need for additional dilating drops and change in predilation to postdilation pupil size. Comparisons were made using McNemar's test, repeated measures analysis of variance, and Fisher's test to determine whether PE is a necessary component of the standard eye examination. Results: There were no statistically significant differences between the PE+T+PP and T+PE treatment groups in predilation to postdilation changes in average resting pupil size (1.58 ± 0.66 and 2.61 ± 0.79; P  = 0.57) or constricted pupil size (2.52 ± 0.93 and 3.56 ± 0.96; P  = 0.15). There was no statistically significant difference between patients who obtained a successful dilated pupil examination between those receiving PE+T+PP and those receiving T+PP as determined by the examining physicians (Fisher's, P  = 0.67). Conclusion: The addition of phenylephrine to tropicamide and proparacaine did not improve pupillary dilation size or ability to conduct a clinical examination. A single dilating agent using tropicamide should be considered in clinical practice.

Importance: Although almost equal numbers of male and female medical students enter into ophthalmology residency programs, whether they have similar surgical experiences during training is unclear., Objective: To determine differences for cataract surgery and total procedural volume between male and female residents during ophthalmology residency., Design, Setting, Participants: This retrospective, longitudinal analysis of resident case logs from 24 US ophthalmology residency programs spanned July 2005 to June 2017. A total of 1271 residents were included. Data were analyzed from August 12, 2017, through April 4, 2018., Main Outcomes and Measures: Variables analyzed included mean volumes of cataract surgery and total procedures, resident gender, and maternity or paternity leave status., Results: Among the 1271 residents included in the analysis (815 men [64.1%]), being female was associated with performing fewer cataract operations and total procedures. Male residents performed a mean (SD) of 176.7 (66.2) cataract operations, and female residents performed a mean (SD) of 161.7 (56.2) (mean difference, -15.0 [95% CI, -22.2 to -7.8]; P < .001); men performed a mean (SD) of 509.4 (208.6) total procedures and women performed a mean (SD) of 451.3 (158.8) (mean difference, -58.1 [95% CI, -80.2 to -36.0]; P < .001). Eighty-five of 815 male residents (10.4%) and 71 of 456 female residents (15.6%) took parental leave. Male residents who took paternity leave performed a mean of 27.5 (95% CI, 13.3 to 41.6; P < .001) more cataract operations compared with men who did not take leave, but female residents who took maternity leave performed similar numbers of operations as women who did not take leave (mean difference, -2.0 [95% CI, -18.0 to 14.0]; P = .81). From 2005 to 2017, each additional year was associated with a 5.5 (95% CI, 4.4 to 6.7; P < .001) increase in cataract volume and 24.4 (95% CI, 20.9 to 27.8; P < .001) increase in total procedural volume. This increase was not different between genders for cataract procedure volume (β = -1.6 [95% CI, -3.7 to 0.4]; P = .11) but was different for total procedural volume such that the increase in total procedural volume over time for men was greater than that for women (β = -8.0 [95% CI, -14.0 to -2.1]; P = .008)., Conclusions and Relevance: Female residents performed 7.8 to 22.2 fewer cataract operations and 36.0 to 80.2 fewer total procedures compared with their male counterparts from 2005 to 2017, a finding that warrants further exploration to ensure that residents have equivalent surgical training experiences during residency regardless of gender. However, this study included a limited number of programs (24 of 119 [20.2%]). Future research including all ophthalmology residency programs may minimize the selection bias issues present in this study.

The treatment of anisometropic or ametropic amblyopia has traditionally enjoyed a high treatment success rate. Early initiation and consistent use of spectacle correction can completely resolve amblyopia in a majority of patients. For those with anisometropic amblyopia that fail to improve with glasses wear alone, patching or atropine penalisation can lead to equalisation of visual acuity. However, successful treatment requires full-time compliance with refractive correction and this can be a challenge for a patient population that often has one eye with good acuity without correction. Other barriers for a select population with high anisometropic  or ametropic amblyopia include rejection of glasses for various reasons including discomfort, behavioural or sensory problems, postural issues and visually significant aniseikonia. When consistent wear of optical correction proves difficult and patching/atropine remains a major obstacle, surgical correction of refractive error has proven success in achieving vision improvement. Acting as a means to achieve spectacle independence or reducing the overall needed refractive correction, refractive surgery can offer a unique treatment option for this patient population. Laser surgery, phakic intraocular lenses and clear lens exchange are three approaches to altering the refractive state of the eye. Each has documented success in improving vision, particularly in populations where glasses wear has not been possible. Surgical correction of refractive error has a risk profile greater than that of more traditional therapies. However, its use in a specific population offers the opportunity for improving visual acuity in children who otherwise have poor outcomes with glasses and patching/atropine alone., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Amblyopia therapy options have traditionally been limited to penalisation of the non-amblyopic eye with either patching or pharmaceutical penalisation. Solid evidence, mostly from the Pediatric Eye Disease Investigator Group, has validated both number of hours a day of patching and days per week of atropine use. The use of glasses alone has also been established as a good first-line therapy for both anisometropic and strabismic amblyopia. Unfortunately, visual acuity equalisation or even improvement is not always attainable with these methods. Additionally, non-compliance with prescribed therapies contributes to treatment failures, with data supporting difficulty adhering to full treatment sessions. Interest in alternative therapies for amblyopia treatment has long been a topic of interest among researchers and clinicians alike. Incorporating new technology with an understanding of the biological basis of amblyopia has led to enthusiasm for binocular treatment of amblyopia. Early work on perceptual learning as well as more recent enthusiasm for iPad-based dichoptic training have each generated interesting and promising data for vision improvement in amblyopes. Use of pharmaceutical augmentation of traditional therapies has also been investigated. Several different drugs with unique mechanisms of action are thought to be able to neurosensitise the brain and enhance responsiveness to amblyopia therapy. No new treatment has emerged from currently available evidence as superior to the traditional therapies in common practice today. But ongoing investigation into the use of both new technology and the understanding of the neural basis of amblyopia promises alternate or perhaps better cures in the future., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To develop a probability model of matching into a US ophthalmology residency program using San Francisco Matching Program (SF Match) data., Design: Retrospective data analysis of de-identified application and matching data., Participants: Registrants for the 2013, 2014, and 2015 ophthalmology residency matches conducted by the SF Match., Methods: Descriptive statistics of candidates, comparison of continuous and categorical variables between matched and nonmatched candidates, and linear regression modeling were performed. A recursive partitioning method was used to create a probability of matching algorithm., Main Outcome Measures: Probability of successfully matching based on quantifiable candidate characteristics., Results: Over the 3-year period, 1,959 individuals submitted an average of 64 applications and received a mean of nine interview invitations. The overall match rate was 71%, with 78% matching at one of their top five choices. Successful matches were more likely to occur in US medical school graduates (78% vs 20%, p < 0.001) and applicants on their first attempt (76% vs 29%, p < 0.001). The association between matching and number of programs applied became negative with > 48 applications. Probability of matching was "high" (> 80%) among US graduates with a step 1 United States Medical Licensing Examination (USMLE)score>243(regardless of number of programs applied to), a step 1 USMLE score of 231 to 243 who applied to at least 30 programs, and first-time applicants with a step 1 score >232. No international medical graduates or repeat applicants had a "high" probability of matching., Conclusions: Although advice must be individualized for each candidate, applicants for ophthalmology residency who fall into a "high" probability of matching group are likely to be successful with applications to 45 or fewer programs. Applying to 80 or more programs should be considered for international medical graduates and/or applicants who are previously unmatched. Modification of the match application data form may allow more detailed analysis of variables such as Alpha Omega Alpha or Gold Humanism Honor Society membership, research activity, and composite evaluation on a standardized letter of recommendation., Competing Interests: Conflict of Interest Dr. Feldon reports personal fees from Association of University Professors of Ophthalmology, outside the submitted work, and is Chair of a Department of Ophthalmology that has a residency training program that could be affected by the information in the article. Dr. Stoner reports support for data analysis from the Association of University Professors of Ophthalmology (AUPO), during the conduct of the study. All the other authors report no conflict of interest.

The basis for neuronal dysfunction following inflammatory demyelination of the central nervous system (CNS) remains poorly understood. We characterized the network response to white matter injury in the anterior visual pathway using an experimental model of optic neuritis (ON), as ON is often an early manifestation of immune-mediated CNS demyelination in multiple sclerosis (MS). Optical intrinsic signal imaging was performed before and after the induction of ON in mice to measure changes in cortical network functional connectivity. We observed a greater loss of connectivity between homotopic visual cortices in ON mice compared to controls. Further, decreases in homotopic visual cortex connectivity were associated with visual acuity loss in ON mice. These results demonstrate that network connectivity changes resulting from ON can be modeled in an experimental murine system. Future studies will identify the mechanisms that cause neuronal dysfunction due to white matter injury seen in MS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether the addition of phenylephrine to tropicamide produces any clinically significant change in pupil size during diagnostic eye examination., Methods: Twenty healthy adults at the Washington University School of Medicine Eye Clinic were enrolled in this prospective, nonrandomized, crossover trial. Each had 3 dilating eye drop regimens administered to the left eye on separate days. Tropicamide (T) + proparacaine (PP) + phenylephrine (PE) (T+PP+PE) was considered the standard therapy, to which tropicamide alone (T alone) and tropicamide + proparacaine (T+PP) were compared against. Main outcome measures were postdilation pupil size and proportion of pupils able to achieve adequate clinical pupil dilation of >7 mm. Comparisons were made using Wilcoxon signed-ranked tests and McNemar's test., Results: Mean postdilation pupil size was 7.94 ± 0.78 mm, 7.64 ± 0.78 mm, and 7.48 ± 0.77 mm for T+PP+PE, T+PP, and T alone, respectively. T+PP+PE was statistically superior to T+PP (p = 0.004) and T alone (p < 0.001) with respect to postdilation pupil size. The proportion of pupils able to achieve adequate pupil dilation of >7 mm was 90%, 80%, and 70% for T+PP+PE, T+PP, and T alone, respectively. No statistical difference was observed in each regimen's ability to achieve adequate pupil dilation of >7 mm (T+PP+PE and T+PP: p = 0.47; T+PP+PE and T alone: p = 0.13)., Conclusion: The addition of phenylephrine eye drops to tropicamide produced larger pupil dilation, but the magnitude of benefit was marginal and clinically insignificant in this young, healthy cohort. A single-dilating-agent regimen using tropicamide could be considered in routine clinical practice., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The Accreditation Council for Graduate Medical Education (ACGME) has mandated that residency programs document progression of competency-based outcomes. The Ophthalmic Clinical Evaluation Exercise (OCEX) assesses clinical skills in ophthalmology residents during patient encounters. Although OCEX has been validated for assessing several of the ACGME-mandated competencies, it was unclear whether OCEX can measure the development of proficiency during residency. This study evaluated whether OCEX can discriminate skill levels across years in training., Methods: In 2017, the authors performed a retrospective analysis on modified OCEX evaluations collected for 22 residents over 3 years at 2 residency programs. OCEX subcomponent scores were averaged to generate a mean score for each evaluation, followed by linear regression analysis for mean scores over time for individual residents. One-way ANOVA with repeated measures was used to compare scores aggregated over an academic year between resident classes. The authors also surveyed internal faculty evaluators and nationwide ophthalmology residency program directors on their use of OCEX., Results: Mean OCEX scores for individual residents and resident class averages showed variable trajectories over the course of residency. There was no consistent effect of increasing level of training on scores. Surveys of evaluators and program directors indicated different interpretations of the grading scale anchors and irregular participation by faculty., Conclusion: This dataset suggests that, despite clear behavioral anchors and faculty development on the use of the tool, evaluators still apply inconsistent grading standards that limit the OCEX from accurately monitoring longitudinal development of resident clinical performance in real-world practice.

Purpose: With new compounding pharmacy laws, the only economically feasible approach to using lissamine is through dye-impregnated strips. This research aims to determine the concentration of lissamine that can be obtained using a single commercially available lissamine strip. With the optimal vital staining requiring 1% concentration of lissamine, we sought to obtain this concentration using supplies in an ordinary ophthalmology clinic., Methods: A standard curve was generated using compounded lissamine green 1% solution. Serial dilutions were made with 3 different diluents and measured using a spectrophotometer at a wavelength of 633 μm. Combinations of the number of strips, amount of solvent, and absorption time were performed to obtain a 1% solution. Cost analyses were performed to select the most economical method., Results: Single lissamine strips wetted with any of the diluents produced 0.17% ± 0.05% (95% confidence interval) lissamine solution, a 5-fold weaker concentration than the optimal for vital staining. Combinations of 4 strips in 200 μL (4 drops) for 1 minute and 2 strips in 200 μL for 5 minutes were found to reach concentrations of 1%. Cost analysis showed that the 2 strip/4 drops/5 minutes method costs $0.67 and the 4 strips/4 drops/1 minute method $1.27., Conclusions: Use of a single lissamine strip leads to suboptimal concentrations for vital staining. With only the addition of disposable microcentrifuge tubes to the clinical setting, ophthalmologists can make 1% solutions of lissamine. This solution is both more economical and in compliance with both state and national compounding laws.

Background: Inherited cataract is a clinically important and genetically heterogeneous cause of visual impairment. Typically, it presents at an early age with or without other ocular/systemic signs and lacks clear phenotype-genotype correlation rendering both clinical classification and molecular diagnosis challenging. Here we have utilized trio-based whole exome sequencing to discover mutations in candidate genes underlying autosomal dominant cataract segregating in three nuclear families., Results: In family A, we identified a recurrent heterozygous mutation in exon-2 of the gene encoding γD-crystallin (CRYGD; c.70C > A, p.Pro24Thr) that co-segregated with 'coralliform' lens opacities. Families B and C were found to harbor different novel variants in exon-2 of the gene coding for gap-junction protein α8 (GJA8; c.20T > C, p.Leu7Pro and c.293A > C, p.His98Pro). Each novel variant co-segregated with disease and was predicted in silico to have damaging effects on protein function., Conclusions: Exome sequencing facilitates concurrent mutation-profiling of the burgeoning list of candidate genes for inherited cataract, and the results can provide enhanced clinical diagnosis and genetic counseling for affected families.

In their IOVS article "Rejuvenating Clinician-Scientist Training" (published March 28, 2014), Balamurali Ambati and Judd Cahoon rightly point out the dearth of new clinician-scientists in ophthalmology. Within the context of their suggestions for increasing the number of successful clinician-scientists, they claim that the traditional MD-PhD training programs and K awards have failed to produce individuals who will carry on the important work of clinically relevant research that will improve patients' lives and sight. In this response we present data, including information on the career paths of graduates of the Washington University ophthalmology residency, that call into question the presumed failure of MD-PhD and K award programs and show that, in fact, graduates of these programs are more likely to succeed as clinician-scientists than are their peers who have not trained in such scientifically rigorous environments. We propose that, rather than a failure of early training programs, it may be obstacles that arise later in training and among junior faculty that prevent promising careers from reaching maturity. Funding, one rather large obstacle, takes the form of imbalanced start-up monies, less National Institutes of Health (NIH) funding awarded to young investigators, and study section composition that may work against those with clinically driven questions. We also explore the challenges faced in the culture surrounding residency and fellowship training. We agree with Ambati and Cahoon that there needs to be more innovation in the way training programs are structured, but we believe that the evidence supports supplementing the current model rather than scrapping it and starting over with unproven initiatives. The data on training programs supports the contention that those who have already made substantial investment and commitment to the clinician-scientist pathway through participation in MSTP or K training programs are the most likely to succeed on this career trajectory. To muffle the siren song of private practice and retain those best prepared for the clinician-scientist pathway requires additional investment as their careers mature through protected research time, mentorship, and advocacy., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: Among the options for surgical management of pediatric glaucoma, destruction of the ciliary body reduces aqueous production and, consequently, intraocular pressure (IOP). Compared to more invasive filtering and shunt procedures, cyclodestruction is an attractive option for control of IOP in pediatric glaucomas., Methods: The relative reduction in IOP, duration of effect, and comparable safety and efficacy of transscleral cyclophotocoagulation (TSCP) and endoscopic cyclophotocoagulation (ECP) in pediatric patients with glaucoma was studied in this retrospective chart review., Results: A reduction in IOP of 28.6% and 33.2% with TSCP and ECP, respectively, was found. Eyes treated with ECP underwent an average of 3.24 cyclodestructive procedures; eyes treated with TSCP underwent an average of 2.29 cyclodestructive treatments. These differences were not statistically significant. A final success rate of 67.6% after TSCP and 62% after ECP failed to significantly differ between the two groups. Consequently, two-thirds of the patients were able to avoid penetrating surgery and the associated risks after one or more cyclodestructive procedures., Conclusions: TSCP and ECP are safe, effective, and comparable treatments for pediatric glaucomas. The results suggest that TSCP and ECP may be considered first-line therapy to achieve control of IOP in all forms of pediatric glaucoma. [J Pediatr Ophthalmol Strabismus 2014;51(2):120-127.]., (Copyright 2014, SLACK Incorporated.)

In the outer retina, G protein-coupled receptor (GPCR) signaling mediates phototransduction and synaptic transmission between photoreceptors and ON bipolar cells. In contrast, the functions of modulatory GPCR signaling networks in the inner retina are less well understood. We addressed this question by determining the consequences of augmenting modulatory Gi/o signaling driven by endogenous transmitters. This was done by analyzing the effects of genetically ablating the R7 RGS-binding protein (R7BP), a membrane-targeting protein and positive allosteric modulator of R7-RGS (regulator of the G protein signaling 7) family that deactivates Gi/oα subunits. We found that R7BP is expressed highly in starburst amacrine cells and retinal ganglion cells (RGCs). As indicated by electroretinography and multielectrode array recordings of adult retina, ablation of R7BP preserved outer retina function, but altered the firing rate and latency of ON RGCs driven by rods and cones but not rods alone. In developing retina, R7BP ablation increased the burst duration of glutamatergic waves whereas cholinergic waves were unaffected. This effect on glutamatergic waves did not result in impaired segregation of RGC projections to eye-specific domains of the dorsal lateral geniculate nucleus. R7BP knockout mice exhibited normal spatial contrast sensitivity and visual acuity as assessed by optomotor reflexes. Taken together these findings indicate that R7BP-dependent regulation of R7-RGS proteins shapes specific aspects of light-evoked and spontaneous activity of RGCs in mature and developing retina.

Scleral infantile hemangiomas are rare. We describe a patient who presented at 3 months of age with an enlarging infantile hemangioma on the sclera of the left eye. He had two other hemangiomas on the left eyebrow and chest. Treatment with propranolol resulted in marked improvement of all of his hemangiomas. He did not develop any ocular complications., (© 2012 Wiley Periodicals, Inc.)

Retinal ganglion cells (RGCs) transmit visual information topographically from the eye to the brain, creating a map of visual space in retino-recipient nuclei (retinotopy). This process is affected by retinal activity and by activity-independent molecular cues. Phr1, which encodes a presumed E3 ubiquitin ligase (PHR1), is required presynaptically for proper placement of RGC axons in the lateral geniculate nucleus and the superior colliculus, suggesting that increased levels of PHR1 target proteins may be instructive for retinotopic mapping of retinofugal projections. To identify potential target proteins, we conducted a proteomic analysis of optic nerve to identify differentially abundant proteins in the presence or absence of Phr1 in RGCs. 1D gel electrophoresis identified a specific band in controls that was absent in mutants. Targeted proteomic analysis of this band demonstrated the presence of PHR1. Additionally, we conducted an unbiased proteomic analysis that identified 30 proteins as being significantly different between the two genotypes. One of these, heterogeneous nuclear ribonucleoprotein M (hnRNP-M), regulates antero-posterior patterning in invertebrates and can function as a cell surface adhesion receptor in vertebrates. Thus, we have demonstrated that network analysis of quantitative proteomic data is a useful approach for hypothesis generation and for identifying biologically relevant targets in genetically altered biological models.

Objective: To compare the performance on the American Board of Ophthalmology Written Qualifying Examination (WQE) with the performance on step 1 of the United States Medical Licensing Examination (USMLE) and the Ophthalmic Knowledge Assessment Program (OKAP) examination for residents in multiple residency programs., Design: Comparative case series., Participants: Fifteen residency programs with 339 total residents participated in this study. The data were extracted from the 5-year American Board of Ophthalmology report to each participating program in 2009 and included residency graduating classes from 2003 through 2007. Residents were included if data were available for the USMLE, OKAP examination in ophthalmology years 1 through 3, and the WQE score. Residents were excluded if one or more of the test scores were not available., Methods: Two-sample t tests, logistic regression analysis, and receiver operating characteristic (ROC) curves were used to examine the association of the various tests (USMLE, OKAP examination year 1, OKAP examination year 2, OKAP examination year 3, and maximum OKAP examination score) as a predictor for a passing or failing grade on the WQE., Main Outcome Measures: The primary outcome measure of this study was first time pass rate for the WQE., Results: Using ROC analysis, the OKAP examination taken at the third year of ophthalmology residency best predicted performance on the WQE. For the OKAP examination taken during the third year of residency, the probability of passing the WQE was at least 80% for a score of 35 or higher and at least 95% for a score of 72 or higher., Conclusions: The OKAP examination, especially in the third year of residency, can be useful to residents to predict the likelihood of success on the high-stakes WQE examination., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: The purpose of this study was to describe two challenging cases of septic cavernous sinus thrombosis (CST), which presented with vastly different clinical signs and symptoms., Methods: We present two cases of CST with markedly differing clinical presentations, medical comorbidities, and degree of impairment. Initial imaging of each patient failed to show thromboembolic disease., Results: Both patients required multiple imaging procedures to arrive at the correct diagnosis. Each child did respond to treatment once the correct diagnosis was made., Conclusion: CST can have a highly variable clinical presentation, from a subtle sixth nerve palsy to complete ophthalmoplegia and loss of periorbital sensation and corneal reflex. Onset of symptoms may be acute and fulminant or indolent and delayed. The diagnosis is challenging, requiring clinical suspicion and confirmation by imaging. These cases illustrate the importance of retaining clinical suspicion when cranial nerve palsies persist and how valuable rescanning a patient can be.

Spontaneous activity is thought to regulate synaptogenesis in many parts of the developing nervous system. In vivo evidence for this regulation, however, is scarce and comes almost exclusively from experiments in which normal activity was reduced or blocked completely. Thus, whether spontaneous activity itself promotes synaptogenesis or plays a purely permissive role remains uncertain. In addition, how activity influences synapse dynamics to shape connectivity and whether its effects among neurons are uniform or cell-type-dependent is unclear. In mice lacking the cone-rod homeobox gene (Crx), photoreceptors fail to establish normal connections with bipolar cells (BCs). Here, we find that retinal ganglion cells (RGCs) in Crx⁻/⁻ mice become rhythmically hyperactive around the time of eye opening as a result of increased spontaneous glutamate release from BCs. This elevated neurotransmission enhances synaptogenesis between BCs and RGCs, without altering the overall circuit architecture. Using live imaging, we discover that spontaneous activity selectively regulates the rate of synapse formation, not elimination, in this circuit. Reconstructions of the connectivity patterns of three BC types with a shared RGC target further revealed that neurotransmission specifically promotes the formation of multisynaptic appositions from one BC type without affecting the maintenance or elimination of connections from the other two. Although hyperactivity in Crx⁻/⁻ mice persists, synapse numbers do not increase beyond 4 weeks of age, suggesting closure of a critical period for synaptic refinement in the inner retina. Interestingly, despite their hyperactivity, RGC axons maintain normal eye-specific territories and cell-type-specific layers in the dorsal lateral geniculate nucleus.

Biologic agents have dramatically shifted the treatment paradigm for rheumatic disease. Use of these agents can decrease disease burden, allow the patient to be weaned from corticosteroids, and reduce the likelihood of relapse. Eye disease associated with rheumatic conditions may present with a wide range of signs and symptoms. This coexisting pathology should not be overlooked and should be considered a reason for initiation or continuation of biologic therapy. Additionally, many of the ocular manifestations of rheumatic disease respond preferentially to specific targeting molecules. This paper summarizes the available studies on the use, efficacy, and safety of biologic agents in the treatment of ocular manifestations of rheumatic disease.

Precise targeting of retinal projections is required for the normal development of topographic maps in the mammalian primary visual system. During development, retinal axons project to and occupy topographically appropriate positions in the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC). Phr1 retinal mutant mice, which display mislocalization of the ipsilateral retinogeniculate projection independent of activity and ephrin-A signaling, were found to have a more global disruption of topographic specificity of retinofugal inputs. The retinocollicular projection lacks local refinement of terminal zones and multiple ectopic termination zones originate from the dorsal-nasal (DN) retinal quadrant. Similarly, in the dLGN, the inputs originating from the contralateral DN retina are poorly refined in the Phr1 mutant. These results show that Phr1 is an essential regulator of retinal ganglion cell projection during both dLGN and SC topographic map development., (Copyright © Cambridge University Press, 2010)

Purpose: To report a case of recurrent nummular keratitis in a pediatric patient with Hyperimmunoglobulinemia D syndrome., Methods: A retrospective chart review., Results: A 14-year-old boy with Hyperimmunoglobulinemia D syndrome (HIDS) presented with photophobia and ocular irritation concomitant with disease exacerbation. He was found on exam to have significant nummular keratitis, which responded to a short course of topical steroids. Despite acute response to local immunosuppression, the patient had several recurrent attacks and eventually developed a large corneal scar and decreased vision. After initiation of infliximab therapy his ocular sequelae improved dramatically and his vision returned to 20/20., Conclusion: One possible form of end-organ damage associated with HIDS is vision threatening nummular keratopathy.

Proper functioning of the mammalian visual system requires that connections between the eyes and their central targets develop precisely. At birth, axons from the two eyes project to broad, overlapping regions of the dorsal-lateral geniculate nucleus (dLGN). In the adult, retinal axons segregate into distinct monocular regions at stereotyped locations within the dLGN. This process is driven by both molecular cues and activity-dependent synaptic competition. Here we demonstrate that Phr1, an evolutionarily conserved regulator of synapse formation and axon guidance, defines a novel molecular pathway required for proper localization of retinogeniculate projections. Following conditional excision of Phr1 in the retina, eye-specific domains within the dLGN are severely disturbed, despite normal spontaneous retinal wave activity and monocular segregation. Although layer placement is dramatically altered, Phr1 mutant retinal axons respond to ephrin-A in vitro. These findings indicate that Phr1 is a key presynaptic regulator of retinogeniculate layer placement independent of activity, segregation, or ephrin-A signaling.

Purpose: To report the use of an Apligraf (Organogenesis, Inc., Canton, Massachusetts, USA) human skin equivalent for repair of cicatricial ectropion in a patient with harlequin ichthyosis., Design: Interventional case report., Methods: A 6-week-old male child with harlequin ichthyosis and severe bilateral upper eyelid cicatricial ectropion underwent repair with Apligraf grafts., Results: After the initial repair with Apligraf grafts, recurrent bilateral upper eyelid ectropion developed, requiring repeat Apligraf grafting at age 61 days. After the second graft, the eyelids remained well positioned until the child's sudden death from respiratory failure at age 6 months., Conclusion: Apligraf human skin equivalent facilitated the repair of cicatricial ectropion in a child with harlequin ichthyosis.

Quantitative fluorescence imaging was used to study the regulation of acetylcholine receptor (AChR) number and density at neuromuscular junctions in living adult mice. At fully functional synapses, AChRs have a half-life of about 14 days. However, 2 hours after neurotransmission was blocked, the half-life of the AChRs was now less than a day; the rate was 25 times faster than before. Most of the lost receptors were not quickly replaced. Direct muscle stimulation or restoration of synaptic transmission inhibited this process. AChRs that were removed from nonfunctional synapses resided for hours in the perijunctional membrane before being locally internalized. Dispersed AChRs could also reaggregate at the junction once neurotransmission was restored. The rapid and reversible alterations in AChR density at the neuromuscular junction in vivo parallel changes thought to occur in the central nervous system at synapses undergoing potentiation and depression.

Nerve terminal withdrawal is accompanied by a loss of acetylcholine receptors (AChRs) at corresponding postsynaptic sites during the process of synapse elimination at developing () and reinnervated adult () neuromuscular junctions. Aside from AChR and nerve terminal loss, however, the molecular and cellular alterations that occur at sites of elimination are unknown. To gain a better understanding of the cascade of events that leads to the disassembly of synaptic sites during the synapse elimination process, we surveyed the distribution of molecular elements of the postsynaptic specialization, the basal lamina, and supporting Schwann cells during the process of synapse elimination that occurs after reinnervation. In addition, quantitative techniques were used to determine the temporal order of disappearance of molecules that were lost relative to the loss of postsynaptic AChRs. We found that the dismantling of the postsynaptic specialization was inhomogeneous, with evidence of rapid dissolution of some aspects of the postsynaptic apparatus and slower loss of others. We also observed a loss of Schwann cell processes from sites of synapse elimination, with a time course similar to that seen for nerve terminal retraction. In contrast, all of the extracellular markers that we examined were lost slowly from sites of synapse loss. We therefore conclude that the synapse elimination process is synapse-wide, removing not only nerve terminals but also Schwann cells and many aspects of the postsynaptic apparatus. The disassembly occurs in a stereotyped sequence with some synaptic elements appearing much more stable than others.

We have developed a technique to measure changes in the amount of fluorescently labeled acetylcholine receptors in living muscles over long time periods. The measurements of fluorescence are made relative to a novel, photolytically stable fluorescence standard (Spectralon) which allows changes in fluorescence to be followed over days, even months. The method compensates for spatial and temporal variations in image brightness due to the light source, microscope, and camera. We use this approach to study the turnover of fluorescently labeled acetylcholine receptors at a single neuromuscular junction in a living mouse by re-imaging the same junction in situ over a period of 3 weeks. In addition we show that the SIT video camera, which is generally considered inadequate for quantitative imaging (in comparison to CCD cameras), is actually a very good quantitative device, especially in situations requiring both fast acquisition and high resolution.