PSEUDOMONAL CHOROIDAL ABSCESS AFTER ROUTINE PARS PLANA VITRECTOMY IN AN IMMUNOSUPPRESSED PATIENT.

PURPOSE: To describe an unusual case of pseudomonal choroidal abscess which developed after a routine pars plana vitrectomy in an immunosuppressed patient. METHODS: Case report. A 61-year-old woman with a history of rheumatoid arthritis and ulcerative colitis on abatacept underwent pars plana vitrectomy. A few days after the patient's operation, a partially serous choroidal detachment was identified. Her choroidal detachment increased in size despite prednisone therapy, and she was taken to the operating room for repeat vitrectomy and choroidal drainage. Intraoperatively, there was no significant intraocular inflammation, but purulent whitish material was expressed during external choroidal drainage which grew Pseudomonas aeruginosa. RESULTS: The patient was given intravenous antibiotics. Systemic infectious workup was negative for blood and urine cultures. The patient was transitioned to oral antibiotics, but had persistent eye pain after discharge and vision remained at count fingers. A computed tomography orbit scan with contrast showed persistent choroidal abscess, and intravitreal ceftazidime injections were administered. The patient's subjective pain resolved within several days of the first intravitreal injection; repeat ultrasound also showed interval resolution of the choroidal elevation. One year after the resolution of her choroidal abscess, her visual acuity was Snellen 20/250 in the affected eye. CONCLUSION: Isolated choroidal bacterial abscess is a possible, but rare, complication of pars plana vitrectomy. Although visual prognosis is poor, especially for pseudomonal choroidal abscesses, aggressive treatment with timely choroidal drainage, systemic antibiotics, and intravitreal antibiotics may allow recovery of some ambulatory vision.

Refractive accuracy in eyes undergoing combined cataract extraction and Descemet membrane endothelial keratoplasty.

PURPOSE: To evaluate the refractive accuracy of current intraocular lens (IOL) formulas and propose a modification in calculation of corneal power in eyes undergoing combined cataract extraction and Descemet membrane endothelial keratoplasty (DMEK). DESIGN: Retrospective cohort study. METHODS: Patients with Fuchs endothelial corneal dystrophy undergoing uncomplicated combined cataract surgery and DMEK at a single institution were included. The Hoffer Q, SRK/T, Holladay I, Barrett Universal II and Haigis formulas were compared. A modified corneal power was calculated using a thick lens equation based on anterior and posterior corneal radii and corneal thickness from Pentacam imaging. Error calculations were adjusted based on the difference in optical biometry and the modified corneal power. Mean absolute error (MAE) for each formula was compared between the corneal power modification and optical biometry corneal power. RESULTS: In 86 eyes, the mean error ranged from 0.90 D for the Barrett Universal II formula to -0.10 D for the Haigis formula, with 4 of 5 formulas resulting in a mean hyperopic error. The corneal power modification resulted in a significantly lower MAE for the Hoffer Q (0.82 D), Holladay I (0.85 D), SRK/T (0.85 D) and Barrett Universal II (0.90 D) formulas compared with optical biometry corneal power for the Hoffer Q (1.02 D; p<0.005), Holladay I (0.97 D; p<0.005), SRK/T (0.93 D; p<0.01) and Barrett Universal II (1.16 D; p<0.005) formulas. CONCLUSIONS: All formulas except the Haigis formula resulted in a hyperopic error. The corneal power modification significantly reduced error in four out of five IOL formulas.

Parental Leave Policy for Ophthalmology Residents: Results of a Nationwide Cross-Sectional Study of Program Directors.

BACKGROUND: Many residents become parents during residency and the adequacy of parental leave is integrally related to resident wellness. OBJECTIVE: To understand current parental leave policies in ophthalmology residency programs and program director perceptions of the impact of parental leave on trainees. DESIGN: Cross-sectional study. SETTING: Multicenter among all U.S. ophthalmology residency programs. PARTICIPANTS: Ophthalmology residency program directors during the 2017 to 2018 academic year. RESULTS: Sixty-eight percent (82/120) program directors participated in this study. The majority of programs had written maternity leave policies (89%) and partner leave policies (72%). The typical duration of maternity leave taken ranged from 4 to 6 weeks while typical partner leave duration taken ranged from 1 day to 2 weeks. Residents who take leave may need to extend training at 72% of programs. Program directors perceived that parental leave negatively impacts resident scholarly activities and surgical skills and volume. Male program directors, relative to female program directors, perceived that becoming a childbearing parent negatively impacts resident dedication to patient care. Program directors raised concerns including local support and policy, extension of residency, impact on residents, impact on programs, consistency and fairness, and desire for national policy change. CONCLUSIONS: Parental leave practices vary significantly among ophthalmology training programs with residents typically taking less leave than permitted. Program directors are challenged to accommodate parental leave while balancing resident training and wellness for all trainees in their program.

Accuracy of Intraocular Lens Formulas in Eyes With Keratoconus.

PURPOSE: To evaluate the refractive accuracy of current intraocular lens (IOL) formulas in eyes with keratoconus. DESIGN: Retrospective case series. METHODS: Preoperative optical biometry, Pentacam topography, and postoperative outcomes were collected from eyes with keratoconus that had uncomplicated cataract surgery between 2014 and 2018 at a single institution. Exclusion criteria include postoperative best-corrected spectacle visual acuity worse than 20/40, multifocal lens, prior ophthalmic surgeries, and prior ocular trauma. The Hoffer Q, SRK/T, Holladay I, Holladay II, Haigis, and Barrett Universal II formulas were analyzed in each eye stratified by keratoconus severity. RESULTS: A total of 73 eyes were included. All formulas had a positive mean predicted error ranging from 0.10 to 4.38 diopters (D). The Barrett Universal II formula had the lowest median absolute error for stage I (n = 46, 0.445 D) and II (n = 22, 0.445 D) eyes, and the highest percentage of eyes with predicted error within ±0.50 D for both stage I (52%) and II (50%) eyes. In stage III eyes (n = 5), the Haigis formula had the lowest median predicated error (1.90 D) and the highest percentage of eyes with predicted error within ±0.50 D (40%). Corneal power measured by optical biometers was higher than measurements by Pentacam keratometry. CONCLUSIONS: All formulas tend to have a hyperopic surprise. The Barrett Universal II formula was the most accurate for mild to moderate disease. Pentacam keratometry may help avoid hyperopic outcomes.

Author Correction: Reconstruction of cysteine biosynthesis using engineered cysteine-free enzymes.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Ability of Ophthalmology Residents to Self-Assess Their Performance Through Established Milestones.

OBJECTIVES: Accurate self-assessment is an important aspect of practice-based learning and improvement and a critical skill for resident growth. The Accreditation Council for Graduate Medical Education mandates semiannual milestones assessments by a clinical competency committee (CCC) for all ophthalmology residents. There are six core competencies: patient care (PC), medical knowledge, systems-based practice, practice-based learning and improvement, professionalism, and interpersonal communication skills. These competencies are assessed by the milestones rubric, which has detailed behavioral anchors and are also used for trainee self-assessments. This study compares resident self-assessed (SA) and faculty CCC milestones scores. DESIGN: Residents completed milestones self-assessments prior to receiving individual score reports from the CCC. Correlation coefficients were calculated comparing the SA and CCC scores. In addition, statistical models were used to determine predictors of disparities and differences between the SA and CCC scores. SETTING: Wilmer Eye Institute, Johns Hopkins Hospital. PARTICIPANTS: Twenty-one residents in the Wilmer Ophthalmology Residency program from July 2014 to June 2016. RESULTS: Fifty-seven self-assessments were available for the analysis. For each resident's first assessment, SA and CCC scores were strongly correlated (r ≥ 0.6 and p < 0.05) for four milestones, and not correlated for the remaining 20 milestones. In multivariable models, the SA and CCC scores are less disparate for medical knowledge and systems-based practice competencies compared to practice-based learning and improvement. Higher year of training, PC and professionalism competencies were predictive of statistically significant resident overestimation of scores relative to the CCC. In addition, higher CCC scores predicted statistically significant lower SA-CCC disparities and differences. SA-CCC differences did not lower to a significant extent with repeated assessments or modification to the end-of-rotation evaluation forms. CONCLUSIONS: Self-assessments by ophthalmology residents are not well-correlated with faculty assessments, emphasizing the need for improved and frequent timely feedback. Residents have the greatest difficulty self-assessing their professionalism and PC competency. In general, senior residents and underperforming residents have more inaccurate self-assessments.

Reconstruction of cysteine biosynthesis using engineered cysteine-free enzymes.

Amino acid biosynthesis pathways observed in nature typically require enzymes that are made with the amino acids they produce. For example, Escherichia coli produces cysteine from serine via two enzymes that contain cysteine: serine acetyltransferase (CysE) and O-acetylserine sulfhydrylase (CysK/CysM). To solve this chicken-and-egg problem, we substituted alternate amino acids in CysE, CysK and CysM for cysteine and methionine, which are the only two sulfur-containing proteinogenic amino acids. Using a cysteine-dependent auxotrophic E. coli strain, CysE function was rescued by cysteine-free and methionine-deficient enzymes, and CysM function was rescued by cysteine-free enzymes. CysK function, however, was not rescued in either case. Enzymatic assays showed that the enzymes responsible for rescuing the function in CysE and CysM also retained their activities in vitro. Additionally, substitution of the two highly conserved methionines in CysM decreased but did not eliminate overall activity. Engineering amino acid biosynthetic enzymes to lack the so-produced amino acids can provide insights into, and perhaps eventually fully recapitulate via a synthetic approach, the biogenesis of biotic amino acids.

An overhang-based DNA block shuffling method for creating a customized random library.

We present an overhang-based DNA block shuffling method to create a customized random DNA library with flexible sequence design and length. Our method enables the efficient and seamless assembly of short DNA blocks with dinucleotide overhangs through a simple ligation process. Next generation sequencing analysis of the assembled DNA library revealed that ligation was accurate, directional and unbiased. This straightforward DNA assembly method should fulfill the versatile needs of both in vivo and in vitro functional screening of random peptides and RNA created with a desired amino acid and nucleotide composition, as well as making highly repetitive gene constructs that are difficult to synthesize de novo.

BDNF Pretreatment of Human Embryonic-Derived Neural Stem Cells Improves Cell Survival and Functional Recovery After Transplantation in Hypoxic-Ischemic Stroke.

Intra-arterial neural stem cell (NSC) therapy has the potential to improve long-term outcomes after stroke. Here we evaluate if pretreatment of NSCs with brain-derived neurotrophic factor (BDNF) prior to transplantation improves cell engraftment and functional recovery following hypoxic-ischemic (HI) stroke. Human embryonic-derived NSCs with or without BDNF pretreatment (1 h, 100 ng/ml) were transplanted 3 days after HI stroke. Functional recovery was assessed using the horizontal ladder test. Cell engraftment was evaluated using bioluminescence imaging (BLI) and histological counts of SC121(+) cells. Fluoro-Jade C (FJC) and NeuN stains were used to evaluate neuroprotection. The effect of BDNF on NSCs was analyzed using a migration assay, immunocytochemistry, Luminex proteomic assay, and RT-qPCR.BLI analysis demonstrated significantly higher photon flux in the BDNF-treated NSC group compared to untreated NSC (p = 0.049) and control groups (p = 0.0021) at 1 week after transplantation. Immunohistochemistry confirmed increased transplanted cell survival in the cortex (p = 0.0126) and hippocampus (p = 0.0098) of animals injected with BDNF-treated NSCs compared to untreated NSCs. Behavioral testing revealed that the BDNF-treated NSC group demonstrated increased sensorimotor recovery compared to the untreated NSC and control groups (p < 0.001) over the 1-month period (p < 0.001) following transplantation. A significant improvement in performance was found in the BDNF-treated NSC group compared to the control group at 14, 21, and 28 (p < 0.05) days after transplantation. The cortex and hippocampus of the BDNF-treated NSC group had significantly more SC121(+) NSCs (p = 0.0125, p = 0.0098), fewer FJC(+) neurons (p = 0.0370, p = 0.0285), and a higher percentage of NeuN(+) expression (p = 0.0354) in the cortex compared to the untreated NSC group. BDNF treatment of NSCs resulted in significantly greater migration to SDF-1, secretion of M-CSF, VEGF, and expression of CXCR4, VCAM-1, Thrombospondins 1 and 2, and BDNF. BDNF pretreatment of NSCs results in higher initial NSC engraftment and survival, increased neuroprotection, and greater functional recovery when compared to untreated NSCs.