Carolyn Kloek

Regulation of Jak kinases by intracellular leptin receptor sequences.

Leptin signals the status of body energy stores via the leptin receptor (LR), a member of the Type I cytokine receptor family. Type I cytokine receptors mediate intracellular signaling via the activation of associated Jak family tyrosine kinases. Although their COOH-terminal sequences vary, alternatively spliced LR isoforms (LRa–LRd) share common NH2-terminal sequences, including the first 29 intracellular amino acids. The so-called long form LR (LRb) activates Jak-dependent signaling and is required for the physiologic actions of leptin. In this study, we have analyzed Jak activation by intracellular LR sequences under the control of the extracellular erythropoeitin (Epo) (Epo receptor/LRb chimeras). We show that Jak2 is the requisite Jak kinase for signaling by the LRb intracellular domain and confirm the requirement for the Box 1 motif for Jak2 activation. A minimal LRb intracellular domain for Jak2 activation includes intracellular amino acids 31–48. Although the sequence requirements for intracellular amino acids 37–48 are flexible, intracellular amino acids 31–36 of LRb play a critical role in Jak2 activation and contain a loose homology motif found in other Jak2-activating cytokine receptors. The failure of short form sequences to function in Jak2 activation reflects the absence of this motif.

Low Rate of Endophthalmitis in a Large Series of Open Globe Injuries

PURPOSE To determine the percentage of patients in whom endophthalmitis developed after open globe injury. DESIGN Retrospective, noncomparative, consecutive case series. METHODS Charts of all patients (675 in total) treated surgically for open globe injury at the Massachusetts Eye and Ear Infirmary (MEEI) between January 1, 2000 and July 31, 2007 were reviewed. Cases with at least 30 days of follow-up were included in statistical analyses (558 in total). A standardized treatment protocol was used in all cases. Intravenous vancomycin and ceftazidime were started on admission and were stopped after 48 hours. Patients were discharged on topical antibiotics, corticosteroids, and cycloplegia. Surgical repairs were performed by the chief of trauma, a full-time position rotating yearly, who is on call for all open globe trauma. Data collection variables included timing of injury and repair, mechanism of injury, details of surgical repair, and details of follow-up such as duration, presence of complications, and vision. A primary outcome measure of endophthalmitis and secondary outcome measure of risk factors for endophthalmitis were studied. RESULTS During 7.5 years, 675 open globe injuries were treated at MEEI. Of these, 558 had at least 30 days of follow-up (mean, 11 months) and were used in statistical analyses. The overall percentage of endophthalmitis was 0.9% (3 culture-positive cases and 2 culture-negative cases). Four of the 5 cases achieved final acuity of 20/80 or better. Risk factors for endophthalmitis included intraocular foreign body (P = .03; odds ratio, 7.52) and primary intraocular lens placement (P = .05). CONCLUSIONS A standardized protocol including surgical repair by a dedicated eye trauma service and 48 hours of intravenous antibiotics was associated with a posttraumatic endophthalmitis percentage of less than 1%.

Enucleation for open globe injury.

PURPOSE To report the experience of enucleation after open globe at an ophthalmic trauma referral center. DESIGN Retrospective, observational study. METHODS In an ophthalmic trauma referral center the charts of all patients having suffered an open globe injury between January 1, 2000 and June 30, 2007 were reviewed. Variables assessed were age, gender, type of injury (rupture or laceration [penetrating, intraocular foreign body, or perforating]), ocular trauma score, visual acuity, subsequent enucleation, indication for and timing of enucleation, presence of sympathetic ophthalmia, and length of follow-up. RESULTS Among 660 open globe injuries, 55 have undergone enucleation (including 4 eviscerations), 11 primarily and 44 secondarily. Eyes with ruptures were significantly more likely to be enucleated than those with injuries attributable to lacerations (P < .001). The most common reason for secondary enucleation was a blind, painful eye. Two patients (0.3%) developed sympathetic ophthalmia and have maintained good vision in the sympathizing eye. CONCLUSIONS The vast majority of open globes can be repaired without requiring primary enucleation. Secondary enucleation is most commonly carried out for pain. Eyes with no light perception can be closely observed if the patient chooses.

Effects of caffeinated coffee consumption on intraocular pressure, ocular perfusion pressure, and ocular pulse amplitude: a randomized controlled trial

PurposeTo examine the effects of caffeinated coffee consumption on intraocular pressure (IOP), ocular perfusion pressure (OPP), and ocular pulse amplitude (OPA) in those with or at risk for primary open-angle glaucoma (POAG).MethodsWe conducted a prospective, double-masked, crossover, randomized controlled trial with 106 subjects: 22 with high tension POAG, 18 with normal tension POAG, 20 with ocular hypertension, 21 POAG suspects, and 25 healthy participants. Subjects ingested either 237 ml of caffeinated (182 mg caffeine) or decaffeinated (4 mg caffeine) coffee for the first visit and the alternate beverage for the second visit. Blood pressure (BP) and pascal dynamic contour tonometer measurements of IOP, OPA, and heart rate were measured before and at 60 and 90 min after coffee ingestion per visit. OPP was calculated from BP and IOP measurements. Results were analysed using paired t-tests. Multivariable models assessed determinants of IOP, OPP, and OPA changes.ResultsThere were no significant differences in baseline IOP, OPP, and OPA between the caffeinated and decaffeinated visits. After caffeinated as compared with decaffeinated coffee ingestion, mean mm Hg changes (±SD) in IOP, OPP, and OPA were as follows: 0.99 (±1.52, P<0.0001), 1.57 (±6.40, P=0.0129), and 0.23 (±0.52, P<0.0001) at 60 min, respectively; and 1.06 (±1.67, P<0.0001), 1.26 (±6.23, P=0.0398), and 0.18 (±0.52, P=0.0006) at 90 min, respectively. Regression analyses revealed sporadic and inconsistent associations with IOP, OPP, and OPA changes.ConclusionConsuming one cup of caffeinated coffee (182 mg caffeine) statistically increases, but likely does not clinically impact, IOP and OPP in those with or at risk for POAG.

Role of inflammation in orbital cellulitis.

Orbital cellulitis is an inflammatory process that affects the orbital tissue located posterior to the septum with potentially devastating consequences. Bacterial infiltration of the orbital tissues can trigger an intense inflammatory response, with up to 11% of cases resulting in visual loss. As many as 84% of cases of orbital cellulitis result from contiguous sinusitis. There are no lymphatics in the orbit to serve as a conduit for bacterial seeding from the sinuses; rather, septic thrombophlebitis affecting the valveless veins bridging the orbit and the sinuses, as well as bony dehiscences and foramina in the orbital bones, facilitate the spread of infection and inflammation from the sinuses to the orbit. Less commonly, infections located elsewhere in the body hematogenously spread to the orbit. Orbital cellulitis has also been reported after trauma—either secondary to orbital fracture allowing direct communication between the sinuses and the orbit or from penetrating orbital injury—and after dental disease from spread through the maxillary sinus to the orbit.

Achieving Target Refraction after Cataract Surgery

PURPOSE To evaluate the difference between target and actual refraction after phacoemulsification and intraocular lens implantation at an academic teaching institutions Comprehensive Ophthalmology Service. DESIGN Retrospective study. PARTICIPANTS We examined 1275 eye surgeries for this study. METHODS All consecutive cataract surgeries were included if they were performed by an attending or resident surgeon from January through December 2010. Postoperative refractions were compared with preoperative target refractions. Patients were excluded if they did not have a preoperative target refraction documented or if they did not have a recorded postoperative manifest refraction within 90 days. MAIN OUTCOME MEASURES The main outcome measure was percentage of cases achieving a postoperative spherical equivalent ± 1.0 diopter (D) of target spherical equivalent. RESULTS We performed 1368 cataract surgeries from January through December of 2010. Of these, 1275 (93%) had sufficient information for analysis. Of the included cases, 94% (1196 of 1275) achieved ± 1.0 D of target refraction by 90 days after cataract surgery. CONCLUSIONS This paper establishes a new benchmark for a teaching hospital, where 94% of patients achieved within 1.0 D of target refraction after cataract surgery. The refractive outcomes after cataract surgery at this academic teaching institution were higher than average international benchmarks.

Characteristics of Traumatic Cataract Wound Dehiscence

PURPOSE To characterize the clinical course of cataract wound dehiscence. DESIGN Retrospective, comparative case series. METHODS Charts of open globe injuries (848 injuries in 846 patients) treated surgically at the Massachusetts Eye and Ear Infirmary between 2000 and 2009 were retrospectively reviewed. Time from original surgery to wound dehiscence, type of initial surgery, Ocular Trauma Score, age, gender, mechanism of injury, and visual acuity were analyzed. RESULTS Of 846 patients with 848 open globe injuries, 63 experienced cataract wound dehiscence. The majority of these cataract wounds (89%) were extracapsular cataract extraction (ECCE), with only 7 (11%) phacoemulsification wounds. The mean patient age in the wound rupture group was 78.2 years. Female patients comprised the majority (67%) of this subpopulation. The most common mechanisms of injury were fall (65%), blunt trauma (23%), and motor vehicle accident (7%). The median raw ocular trauma score was 47 in wound dehiscence patients. Visual acuity at presentation was light perception in the wound dehiscence group. The best postoperative visual acuity was significantly worse in the wound dehiscence group (hand motion) than in the remaining patients (20/40; P=.0002). When considering the phacoemulsification patients alone, these patients fared much better, with a median postoperative vision of 20/60. CONCLUSIONS Despite recent advances in cataract surgery, wound dehiscence remains a significant source of visual disability, mainly in the geriatric population. Rupture ECCE wound patients have a poor visual prognosis. Fortunately, patients with phacoemulsification site dehiscence appear to regain the majority of their vision after open globe repair.

A Multicenter Analysis of the Ophthalmic Knowledge Assessment Program and American Board of Ophthalmology Written Qualifying Examination Performance

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.

Assessing Resident Cataract Surgery Outcomes Using Medicare Physician Quality Reporting System Measures

OBJECTIVES To assess resident cataract surgery outcomes at an academic teaching institution using 2 Physician Quality Reporting System (PQRS) cataract measures, which are intended to serve as a proxy for quality of surgical care. DESIGN A retrospective review comparing cataract surgery outcomes of resident and attending surgeries using 2 PQRS measures: (1) 20/40 or better best-corrected visual acuity following cataract surgery and (2) complications within 30 days following cataract surgery requiring additional surgical procedures. SETTING An academic ophthalmology center. PARTICIPANTS A total of 2487 surgeries performed at the Massachusetts Eye and Ear Infirmary from January 1, 2011 to December 31, 2012 were included in this study. RESULTS Of all 2487 cataract surgeries, 98.95% achieved a vision of at least 20/40 at or before 90 days, and only 0.64% required a return to the operating room for postoperative complications. Of resident surgeries, 98.9% (1370 of 1385) achieved 20/40 vision at or before 90 days follow-up. Of attending surgeries, 99.0% (1091 of 1102) achieved 20/40 vision at or before 90 days (p = 1.00). There were no statistically significant differences between resident and attending cases regarding postoperative complications needing a return to the operating room (i.e., 0.65%, or 9 of 1385 resident cases vs 0.64%, or 7 of 1102 attending cases; p = 1.00). CONCLUSIONS Using PQRS Medicare cataract surgery criteria, this study establishes new benchmarks for cataract surgery outcomes at a teaching institution and supplemental measure for assessing resident surgical performance. Excellent cataract outcomes were achieved at an academic teaching institution, with results exceeding Medicare thresholds of 50%. There appears to be no significant difference in supervised trainee and attending cataract surgeon outcomes using 2 PQRS measures currently used by Medicare to determine physician reimbursement and quality of care.

Introducing a New Surgical Technology: Controversies in Femtosecond Laser-assisted Cataract Surgery and Impact on Resident Surgical Training

Femtosecond laser-assisted cataract surgery is becoming more widely available as an option for patients considering cataract surgery. Controversies exist around determining the best platform for LCS, the potential global role and cost to the health care system of LCS, as well as the future of LCS in resident surgical training.