Publications by authors named "Susan M Culican"

27 Publications

  • Page 1 of 1

Development of a taxonomy of unprofessional behavior in clinical learning environments using learner-generated critical incidents.

Med Teach 2021 May 11:1-9. Epub 2021 May 11.

Graduate Medical Education, University of Minnesota, Minneapolis, MN, USA.

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.
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http://dx.doi.org/10.1080/0142159X.2021.1918331DOI Listing
May 2021

Assessing the Clinical Requirement of 2.5% Phenylephrine for Diagnostic Pupil Examination.

J Ocul Pharmacol Ther 2021 Jun 8;37(5):284-289. Epub 2021 Mar 8.

Department of Ophthalmology and Visual Neurosciences, University of Minnesota Medical School, Minneapolis, Minnesota, USA.

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. 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. 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;  = 0.57) or constricted pupil size (2.52 ± 0.93 and 3.56 ± 0.96;  = 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,  = 0.67). 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.
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http://dx.doi.org/10.1089/jop.2020.0111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215398PMC
June 2021

Crowdsourced Assessment of Surgical Skill Proficiency in Cataract Surgery.

J Surg Educ 2021 Jul-Aug;78(4):1077-1088. Epub 2021 Feb 25.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri; Graduate Medical Education, University of Minnesota, Minneapolis, Minnesota; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota. Electronic address:

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 = 0.92) and demonstrated excellent predictive modeling when applied to the independent longitudinal dataset (r = 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.
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http://dx.doi.org/10.1016/j.jsurg.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217126PMC
June 2021

Gender Differences in Case Volume Among Ophthalmology Residents.

JAMA Ophthalmol 2019 Sep;137(9):1015-1020

Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical Center, New York, New York.

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.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.2427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646997PMC
September 2019

Probability of Success in the Ophthalmology Residency Match: Three-Year Outcomes Analysis of San Francisco Matching Program Data.

J Acad Ophthalmol 2018 Jan;10(1):e150-e157

Department of Ophthalmology, Flaum Eye Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York.

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%, < 0.001) and applicants on their first attempt (76% vs 29%, < 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.
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http://dx.doi.org/10.1055/s-0038-1673675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335041PMC
January 2018

Child Neurology: Brown-Vialetto-Van Laere syndrome: Dramatic visual recovery after delayed riboflavin therapy.

Neurology 2018 11;91(20):938-941

From the Departments of Neurology (A.K.B., P.T.G.) and Ophthalmology and Visual Sciences (R.N.M., S.M.C.) and Division of Genetics and Genomic Medicine, Department of Pediatrics (M.S.), Washington University School of Medicine, St Louis, MO; and Department of Pediatrics (A.K.B.), King Abdulaziz University, Jeddah, Saudi Arabia.

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http://dx.doi.org/10.1212/WNL.0000000000006498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260193PMC
November 2018

New advances in amblyopia therapy II: .

Br J Ophthalmol 2018 12 5;102(12):1611-1614. Epub 2018 Jun 5.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA

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.
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http://dx.doi.org/10.1136/bjophthalmol-2018-312173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287570PMC
December 2018

New advances in amblyopia therapy I: binocular therapies and pharmacologic augmentation.

Br J Ophthalmol 2018 11 18;102(11):1492-1496. Epub 2018 May 18.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.

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.
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http://dx.doi.org/10.1136/bjophthalmol-2018-312172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241622PMC
November 2018

Assessing the utility of 2.5% phenylephrine for diagnostic pupillary dilation.

Can J Ophthalmol 2017 Aug;52(4):349-354

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO.

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.
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http://dx.doi.org/10.1016/j.jcjo.2017.01.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437774PMC
August 2017

Functional connectivity alterations in a murine model of optic neuritis.

Exp Neurol 2017 09 11;295:18-22. Epub 2017 May 11.

Department of Neurology, Washington University in St. Louis School of Medicine, United States; Department of Pathology & Immunology, Washington University in St. Louis School of Medicine, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.expneurol.2017.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657240PMC
September 2017

Assessing Progression of Resident Proficiency during Ophthalmology Residency Training: Utility of Serial Clinical Skill Evaluations.

J Med Educ Train 2017 9;1(4). Epub 2017 Sep 9.

Department of Ophthalmology and Visual Sciences, Washington University, St Louis, MO, USA.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870798PMC
September 2017

Obtaining Lissamine Green 1% Solution for Clinical Use.

Cornea 2015 Nov;34(11):1523-5

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO.

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.
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http://dx.doi.org/10.1097/ICO.0000000000000588DOI Listing
November 2015

Exome sequencing identifies novel and recurrent mutations in GJA8 and CRYGD associated with inherited cataract.

Hum Genomics 2014 Nov 18;8:19. Epub 2014 Nov 18.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Ave., Box 8096, St. Louis, Missouri, 63110, USA.

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.
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http://dx.doi.org/10.1186/s40246-014-0019-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240822PMC
November 2014

Retaining clinician-scientists: nature versus nurture.

Invest Ophthalmol Vis Sci 2014 May 27;55(5):3219-22. Epub 2014 May 27.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.

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.
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http://dx.doi.org/10.1167/iovs.14-14605DOI Listing
May 2014

Comparison of the effectiveness and safety of transscleral cyclophotocoagulation and endoscopic cyclophotocoagulation in pediatric glaucoma.

J Pediatr Ophthalmol Strabismus 2014 Mar-Apr;51(2):120-7. Epub 2014 Feb 18.

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.].
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http://dx.doi.org/10.3928/01913913-20140211-01DOI Listing
September 2014

An allosteric regulator of R7-RGS proteins influences light-evoked activity and glutamatergic waves in the inner retina.

PLoS One 2013 9;8(12):e82276. Epub 2013 Dec 9.

Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082276PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857278PMC
October 2014

Identification of potential mediators of retinotopic mapping: a comparative proteomic analysis of optic nerve from WT and Phr1 retinal knockout mice.

J Proteome Res 2012 Nov 23;11(11):5515-26. Epub 2012 Oct 23.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

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.
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http://dx.doi.org/10.1021/pr300767aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510777PMC
November 2012

A multicenter analysis of the ophthalmic knowledge assessment program and American Board of Ophthalmology written qualifying examination performance.

Ophthalmology 2012 Oct 28;119(10):1949-53. Epub 2012 Jul 28.

Department of Ophthalmology, The Methodist Hospital, Houston, Texas, USA.

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.
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http://dx.doi.org/10.1016/j.ophtha.2012.06.010DOI Listing
October 2012

Spontaneous activity promotes synapse formation in a cell-type-dependent manner in the developing retina.

J Neurosci 2012 Apr;32(16):5426-39

Departments of Ophthalmology and Visual Sciences and Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

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.
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http://dx.doi.org/10.1523/JNEUROSCI.0194-12.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353326PMC
April 2012

Scleral hemangioma: case report and response to propranolol.

Pediatr Dermatol 2013 May-Jun;30(3):e16-7. Epub 2012 Apr 4.

Division of Dermatology, Departments of Internal Medicine and Pediatrics Department of Ophthalmology and Visual Sciences, School of Medicine, Washington University and St. Louis Children's Hospital, St. Louis, Missouri, USA.

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.
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http://dx.doi.org/10.1111/j.1525-1470.2012.01754.xDOI Listing
January 2014

Use of biologic agents in ocular manifestations of rheumatic disease.

Int J Rheumatol 2012 15;2012:203819. Epub 2011 Dec 15.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.

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.
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http://dx.doi.org/10.1155/2012/203819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246731PMC
August 2012

Challenging presentations of cavernous sinus thrombophlebitis.

J Ophthalmic Inflamm Infect 2012 Sep 4;2(3):133-6. Epub 2011 Dec 4.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO, 63110, USA,

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.
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http://dx.doi.org/10.1007/s12348-011-0053-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438306PMC
September 2012

Phr1 is required for proper retinocollicular targeting of nasal-dorsal retinal ganglion cells.

Vis Neurosci 2011 Mar 16;28(2):175-81. Epub 2011 Feb 16.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.

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.
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http://dx.doi.org/10.1017/S0952523810000386DOI Listing
March 2011

Nummular keratopathy in a patient with Hyper-IgD Syndrome.

Pediatr Rheumatol Online J 2009 Aug 5;7:14. Epub 2009 Aug 5.

Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, Missouri 63110, USA.

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.
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http://dx.doi.org/10.1186/1546-0096-7-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731058PMC
August 2009

Phr1 regulates retinogeniculate targeting independent of activity and ephrin-A signalling.

Mol Cell Neurosci 2009 Jul 14;41(3):304-12. Epub 2009 Apr 14.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.

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.
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http://dx.doi.org/10.1016/j.mcn.2009.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697264PMC
July 2009

Aicardi-like chorioretinitis and maldevelopment of the corpus callosum in congenital lymphocytic choriomeningitis virus.

J AAPOS 2006 Feb;10(1):58-60

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

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http://dx.doi.org/10.1016/j.jaapos.2005.09.009DOI Listing
February 2006

Repair of cicatricial ectropion in an infant with harlequin ichthyosis using engineered human skin.

Am J Ophthalmol 2002 Sep;134(3):442-3

Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri, USA.

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.
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http://dx.doi.org/10.1016/s0002-9394(02)01567-2DOI Listing
September 2002
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