Descriptive Analysis of Vitreoretinal Surgery Fellowship Program Directors.

Purpose: To evaluate the demographic, educational, and scholarly characteristics of Association of University Professors of Ophthalmology-accredited vitreoretinal surgery fellowship program directors in the United States and Canada. Methods: Demographic, educational, and scholarly profiles of identified program directors were collated from online public resources. Characteristics were compared by sex, program size, ranking, and affiliation. Results: Eighty-one program directors (mean age [±SD] 54.7 ± 11.0 years) from 78 fellowship programs were identified. The minority were women (14.8%), who were on average 6 years younger than their male counterparts (P = .07). The majority of program directors had an academic affiliation (90.1%), most commonly professor (54.8%). The mean h-index, 5-year h-index, and m-quotient were 20.9 ± 14.9, 5.9 ± 4.4, and 0.82 ± 0.42, respectively. Compared with their counterparts, program directors of both "top 10" and large programs published more manuscripts (P < .05), accrued more citations (P < .05), and had a higher h-index (P < .05). Fellowship programs with female program directors had a significantly larger proportion of female retina faculty (P = .002). Conclusions: The backgrounds of vitreoretinal surgery program directors are diverse. However, women remain underrepresented in this position, highlighting an area with the potential for greater equity in ophthalmology.

Predictors of Ophthalmology Resident Performance From Medical Student Application Materials.

OBJECTIVE: To determine whether elements in ophthalmology residency applications are predictors of future resident performance. DESIGN: This multi-institutional, cross-sectional, observational study retrospectively reviewed the residency application materials of ophthalmology residents who graduated from residency from 2006 through 2018. Resident performance was scored by 2 faculty reviewers in 4 domains (clinical, surgical, academic, and global performance). Correlation between specific elements of the residency application and resident performance was assessed by Spearman correlation coefficients (univariate) and linear regression (multivariate) for continuous variables and logistic regression (multivariate) for categorical variables. SETTING: Seven ophthalmology residency programs in the US. PARTICIPANTS: Ophthalmology residents who graduated from their residency program. RESULTS: High-performing residents were a diverse group, in terms of sex, ethnicity, visa status, and educational background. Residents with United States Medical Licensing Examination Step 1 scores higher than the national average for that year had significantly higher scores in all 4 performance domains than those who scored at or below the mean (all domains P < 0.05). Residents who had honors in at least 4 core clerkships and who were members of Alpha Omega Alpha Medical Honor Society also had higher scores in all 4 performance domains (all domains P ≤ 0.04). Step 1 score (ρ=0.26, P < 0.001) and the difference between Step 1 score and the national average for that year (ρ=0.19, P = 0.009) positively correlated with total resident performance scores. Residents who passed the American Board of Ophthalmology Written Qualifying Examination or Oral Examination on their first attempt had significantly higher Step 1/2 scores (P ≤ 0.005), Ophthalmology Knowledge Assessment Program scores (P = 0.001), and resident performance scores (P ≤ 0.004). CONCLUSIONS: In this new landscape of increasing numbers of applicants to residency programs and changing of the Step 1 score to pass/fail, our findings may help guide selection committees as they holistically review applicants to select exceptional future residents in ophthalmology.

Intravitreal triple therapy with vancomycin, ceftazidime, and moxifloxacin for bacterial endophthalmitis: A Twelve-year experience.

PURPOSE: Increasing rates of antibiotic resistance in endophthalmitis have been reported. This study examines outcomes of triple therapy with intravitreal vancomycin, ceftazidime, and moxifloxacin for endophthalmitis. METHODS: Retrospective, consecutive series of all patients treated with abovementioned intravitreal antibiotics from January 2009 to June 2021. Percentages of eyes attaining greater than or equal to 20/200 and 20/50 Snellen visual acuities and adverse events were evaluated. RESULTS: 112 eyes met inclusion criteria. 63 of 112 eyes (56%) achieved a visual acuity of 20/200 during follow-up, with 39 (35%) returning to at least 20/50. In subgroup analysis, 23 of 24 (96%) eyes with post-cataract endophthalmitis obtained ≥ 20/200 acuity and 21 of 24 (88%) obtained ≥ 20/50 acuity during follow-up. There were no cases of macular infarction. CONCLUSIONS: Intravitreal moxifloxacin (160 µg/0.1 mL) was well tolerated as an adjunct to vancomycin and ceftazidime for bacterial endophthalmitis. Use of this novel combination offers several theoretical advantages compared to standard therapy with two antibiotics, including expanded gram-negative coverage and potential synergy, and may be particularly valuable in geographies where the local antibiogram supports empiric use. Further study is merited to verify the safety and efficacy profile.

Inclusion of pregnant and breastfeeding women in nonobstetrical randomized controlled trials.

BACKGROUND: There is an urgent need to prioritize and expedite the inclusion of pregnant and breastfeeding women in research. Characterizing trials that have successfully included these populations could inform the design and execution of future studies. In addition, up-to-date data on their inclusion in clinical research could assist in setting benchmarks, establishing targets, and monitoring progress toward more equitable inclusion. OBJECTIVE: This study aimed to characterize the eligibility and enrollment of pregnant and breastfeeding women in randomized controlled trials evaluating interventions for nonobstetrical conditions experienced by, but not limited to, these populations. STUDY DESIGN: We developed a literature search in collaboration with an information specialist. We included randomized controlled trials published between 2017 and 2019 in the 5 highest-impact general medicine journals and the 3 highest-impact specialty journals in cardiovascular disease, critical care, general infectious diseases, HIV, and psychiatry. We included randomized controlled trials that evaluated screening, diagnosis, prevention, or treatment of nonobstetrical medical conditions. We excluded randomized controlled trials exclusively focused on males, pediatrics, geriatrics, oncology, or postmenopausal women, and publications reporting subgroup, pooled, or follow-up analyses of previously published randomized controlled trials. We screened titles and abstracts independently and in duplicate, with discrepancies resolved by a third reviewer. We entered data into a standardized electronic case report form. We reviewed study protocols, appendices, and trial registries for additional data. RESULTS: Of the 1333 randomized controlled trials, pregnant and breastfeeding women were eligible for 13 (1.0%) and 6 (0.5%), respectively. Pregnancy and breastfeeding eligibility criteria were not addressed in 383 of 1333 (28.7%) and 710 of 1333 (53.3%) randomized controlled trials, respectively. In total, 102 of 937 (10.9%) and 33 of 617 (5.3%) randomized controlled trials that explicitly excluded pregnant and breastfeeding women documented the rationale. Most studies excluding pregnant women (542/937; 57.8%) required at least 1 method of contraception and/or pregnancy testing as part of trial participation for women with reproductive capacity. Among the 13 randomized controlled trials that allowed inclusion of pregnant women, 3 restricted eligibility to specific trimesters. Two randomized controlled trials enrolled pregnant women after the first year of the study following interim review of safety results in nonpregnant participants. Four randomized controlled trials reported the number of pregnant women enrolled, which ranged from 0.7% to 3.4% of the study population. None of the studies reported on pregnancy or perinatal outcomes. Compared with randomized controlled trials that excluded pregnant women, those including them more commonly had an infectious disease focus (12/13 [92.3%] vs 270/937 [28.8%]; p<.0001), including HIV (5/13 [38.5%] vs 96/937 [10.2%]; p=.0079), enrolled participants in sub-Saharan Africa (5/13 [38.5%] vs 111/937 [11.8%]; p=.0143), and had exclusively nonindustry sponsorship (13/13 [100%] vs 559/937 [59.7%]; p=.0025); inclusion varied by study phase, randomization level, and intervention type. CONCLUSION: This study illustrates a major inequity in research involving pregnant and breastfeeding women. As new health challenges arise, including novel pandemics, and the research community mobilizes to develop therapies and innovate in patient care, it is crucial that pregnant and breastfeeding women not be left behind. Greater regulatory support, in the form of explicit requirements and incentives, will be needed to ensure these populations are integrated into the research agenda.

Air vs Gas Tamponade During Macular Hole Repair Surgery.

Purpose: This work investigates the visual and anatomical outcomes of full-thickness macular hole (FTMH) repair surgery using air in comparison to gas tamponade. Methods: A retrospective consecutive review of medical records was undertaken of all patients undergoing pars plana vitrectomy for idiopathic FTMH at an academic practice from January 2010 to May 2017. Each operative report was reviewed to investigate the agent used for tamponade at the end of the surgery. Preoperative hole duration and size as measured using optical coherence tomography as well as successful postoperative hole closure were recorded. Use of gas or air was not randomized and was instilled at surgeon discretion. Results: The final analysis included 211 eyes. Gas was used as the tamponade agent in 171 of the 211 eyes; most of these eyes (144 of 171) received sulfur hexafluoride (SF6) and the remainder received perfluoropropane (C3F8). Forty eyes underwent only a complete fluid-air exchange without any gas placement following vitrectomy. There was no statistically significant difference between the 2 groups in mean preoperative macular hole size (P = .43). Nine of the 171 macular holes receiving gas tamponade failed to close (5.3%). One of the 40 macular holes receiving only air failed to close (2.5%). There was no statistically significant difference in hole closure rates between the 2 groups (P = .45). Conclusions: Air served as an equally efficacious internal tamponade agent in comparison to nonexpansile gas following idiopathic FTMH repair surgery.

The Ophthalmology Surgical Competency Assessment Rubric for Panretinal Photocoagulation.

PURPOSE: To develop an internationally valid skill-based rubric that can be used as a global standardized platform for teaching, training, and evaluation of panretinal photocoagulation (PRP) in training programs. DESIGN: A panel of educators and experts in retinal lasers was assembled to develop a standardized objective skill-based rubric. PARTICIPANTS: Sixteen international educators and retina specialists. METHODS: The steps to performing slit-lamp delivery of PRP was described in detail. A group of 6 authors reviewed and agreed on the steps and assigned descriptors to expectation levels of novice, beginner, advanced beginner, and expert according to a modified Dreyfuss model. The tool then was vetted by an international panel of 10 retina specialists who are involved in training ophthalmologists in other countries. MAIN OUTCOME MEASURES: Final version of the tool agreed on by the international review panel. RESULTS: The consecutive steps to performing PRP were outlined and broken down into preparation, procedure, and postoperative care. Descriptive words explaining what to expect from a novice, beginner, advanced beginner, and expert were listed for each step of PRP. Expert comments were incorporated, establishing face and content validity. CONCLUSIONS: This group of authors clearly defined expectations of a trainee at 4 levels of training according to the modified Dreyfus model, and an international panel of retina specialists agreed to its accuracy. This tool, the International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric for Panretinal Photocoagulation, has face and content validity. It can be used globally in training programs both to teach and assess this important comprehensive skill in ophthalmic training.

Scleral Buckle Infection With Pseudallescheria boydii.

Pseudallescheria boydii is a ubiquitous fungus that infects soft tissues and is known to cause ocular disease, including keratitis and endophthalmitis, in rare cases. In immunocompromised hosts, P. boydii can disseminate to or from the eye and other organs with lethal consequences. Postoperative P. boydii infections have, in rare cases, complicated several types of ocular surgeries in immunocompetent patients, but never for a scleral buckle. The authors present the first case of an infected scleral buckle from P. boydii. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:676-678.].

MULTIMODAL IMAGING OF THE RETINA AND CHOROID IN SYSTEMIC AMYLOIDOSIS.

PURPOSE: To present the multimodal imaging findings of four patients with systemic amyloidosis, renal failure, and chorioretinopathy. METHODS: Retrospective analysis of four patients presenting to four institutions with evidence of amyloid induced chorioretinopathy. Fundus photography, autofluorescence, and spectral domain optical coherence tomography findings were studied and are presented. RESULTS: Four patients with biopsy-proven systemic amyloidosis demonstrated progressive chorioretinal degeneration with color fundus photography and autofluorescent imaging. With spectral domain optical coherence tomography analysis, amyloidosis-induced chorioretinopathy was characterized by a widened choriocapillaris band, choroidal infiltration, diffuse photoreceptor dysfunction, and thinning of the outer nuclear layer. CONCLUSION: Multimodal imaging including spectral domain optical coherence tomography analysis in eyes of patients with systemic amyloidosis shows deposition in the choroid. The deposition may cause a secondary toxic and or barrier effect resulting in diffuse retinal pigment epithelium and photoreceptor dysfunction.

Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study: findings at 3 months.

BACKGROUND: The purpose of this paper is to report the 3-month findings of the Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study. METHODS: Eighty eyes of 40 participants undergoing vitrectomy were enrolled. Participants underwent baseline evaluation of the study (surgical) and fellow (control) eye that included: intraocular pressure, central corneal thickness, gonioscopy, cup-to-disc ratio measurement, color fundus and optic disc photography, automated perimetry, and optical coherence tomography of the macula and optic nerve. Evaluation was repeated at 3 months. Main outcome measures were changes in macula and retinal nerve fiber layer (RNFL) thickness and intraocular pressure. RESULTS: All participants completed follow-up. Mean cup-to-disc ratio of study and fellow eyes at baseline was 0.43 ± 0.2 and 0.46 ± 0.2, respectively, and 13% of participants had undiagnosed narrow angles. There was no significant change in intraocular pressure, cup-to-disc ratio, or pattern standard deviation in study eyes compared with baseline or fellow eyes at 3 months. Vision improved in all study eyes at 3 months compared with baseline (P = 0.013), but remained significantly worse than fellow eyes (P < 0.001). Central subfield and temporal peripapillary RNFL thickness were significantly greater in eyes with epiretinal membrane (P < 0.05), and resolution after surgery correlated with visual improvement (P < 0.05). CONCLUSION: The 3-month results do not indicate any increased risk for open-angle glaucoma but suggest that a relatively high percentage of eyes may be at risk of angle closure glaucoma. Temporal RNFL thickness and central subfield were increased in eyes with epiretinal membrane, and resolution correlated with degree of visual recovery.

The role of semaphorins and their receptors in gliomas.

Gliomas are the most common tumor in the central nervous system. High-grade glioblastomas are characterized by their high invasiveness and resistance to radiotherapy, leading to high recurrence rate and short median survival despite radical surgical resection. Characterizations of gliomas at molecular level have revealed aberrations of various growth factor receptors, receptor tyrosine kinases, and tumor suppressor genes that lead to deregulation of multiple signaling pathways, thereby contributing to abnormal proliferation, invasion, and resistance to apoptosis in cancer cells. Recently, accumulating evidence points to the emerging role of axon guidance molecules in glioma progression. Notably, many signaling events harnessed by guidance molecules to regulate cell migration and axon navigation during development are also found to be involved in the modulation of deregulated pathways in gliomas. This paper focused on the signalings triggered by the guidance molecule semaphorins and their receptors plexins and neuropilins, and how their crosstalk with oncogenic pathways in gliomas might modulate cancer progression. The emerging role of semaphorins and plexins as tumor suppressors or oncogenes is also discussed.

Intravitreal bevacizumab as adjunctive treatment for retinopathy of prematurity.

BACKGROUND: While laser photocoagulation remains the standard of care in the treatment of advanced retinopathy of prematurity (ROP), regression is not seen in all cases (especially in aggressive posterior disease) following laser alone. We report the results of the use of the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in eyes with ROP at high risk for progression. METHODS: Records of all infants with ROP treated with bevacizumab were reviewed. Bevacizumab was given when conventional laser therapy was not possible in patients with poor pupillary dilation from iris rubeosis, dense vitreous hemorrhage, or increasing vascular activity and vitreoretinal traction despite completed laser therapy. We recorded birth weight, gestational age at birth, severity of ROP, anatomic result, any additional ophthalmic interventions, and early or late adverse systemic effects. RESULTS: Thirteen eyes of 7 infants (median gestational age, 25 weeks; median birth weight, 700 g; follow-up, 9 months [range, 2-17]) were treated with an intravitreal injection of 0.75 mg bevacizumab under sterile conditions by 1 surgeon following detailed discussion with family and attending neonatologists. Injection was not used as monotherapy in any case. Definitive treatment (laser or vitrectomy) was completed successfully within 72 hours of injection. No systemic complication attributable to bevacizumab treatment has been recorded within 2 to 17 months of follow-up. CONCLUSIONS: Treatment with bevacizumab may be used to improve visualization for more definitive laser or surgical treatment and may facilitate disease regression without obvious systemic toxicity. Optimization of dosing, timing, and indications will require additional study.

Photodynamic therapy as treatment of chronic idiopathic central serous chorioretinopathy.

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

Development of a cell transducible RhoA inhibitor TAT-C3 transferase and its encapsulation in biocompatible microspheres to promote survival and enhance regeneration of severed neurons.

PURPOSE: Neurons in post-traumatized mammalian central nervous system show only limited degree of regeneration, which can be attributed to the presence of neurite outgrowth inhibitors in damaged myelin and glial scar, and to the apoptosis of severed central neurons and glial cells during secondary Wallerian degeneration. RhoA GTPase has been implicated as the common denominator in these counter-regeneration events, which shows significant and persistent up-regulation for weeks in injured spinal cord and cerebral infarct after stroke. While the exoenzyme C3 transferase is a potent RhoA inhibitor, its extremely low efficiency of cell entry and degradation in vivo has restricted the therapeutic value. This study aims to circumvent these problems by developing a membrane-permeating form of C3 transferase and a biopolymer-based microsphere depot system for sustainable controlled release of the protein. MATERIALS AND METHODS: A membrane-permeating form of C3 transferase was developed by fusing a Tat (trans-activating transcription factor) transduction domain of human immunodeficiency virus to its amino terminal using standard molecular cloning techniques. After confirming efficient cell entry into epithelial and neuroblastoma cells, the resulting recombinant protein TAT-C3 was encapsulated in biocompatible polymer poly(D,L -lactide-co-glycolide) in the form of microspheres by a water-in-oil-in-water (W/O/W) emulsion method. By blending capped and uncapped form of the polymer at different ratios, TAT-C3 protein release profile was modified to suit the expression pattern of endogenous RhoA during CNS injuries. Bioactivity of TAT-C3 released from microspheres was assessed by RhoA ribosylation assay. RESULTS: In contrast to wild-type C3 transferase, the modified TAT-C3 protein was found to efficiently enter NIH3T3 and N1E-115 neuroblastoma cells as early as 6 hours of incubation. The fusion of TAT sequence to C3 transferase imposed no appreciable effects on its biological activity in promoting neurite outgrowth through RhoA inhibition. Characterization of TAT-C3 encapsulation in various blends of capped/uncapped PLGA polymer revealed the 30:70 formulation to be optimal in attaining a mild initial burst release of 25%, followed by a subsequent average daily release of 2.3% of encapsulated protein over one month, matching the change in RhoA level in severed brain and spinal cord. Importantly, TAT-C3 released from the microspheres remained active up to the first three weeks of incubation. CONCLUSION: Enhanced cell entry of TAT-C3 circumvents the need to administer high dose of the protein to site of injury. The encapsulation of TAT-C3 in different blends of capped/uncapped PLGA microspheres allows adjustment of protein release profile to suit the pattern of RhoA expression in injured CNS.