Purpose:
To determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis.
Design:
Three multicenter, randomized, double-masked, …
Purpose:
To investigate mortality and graft survival in patients undergoing penetrating keratoplasty (PKP) for rheumatoid arthritis–associated corneal ulceration (RACU), Fuchs’ endothelial dystrophy (FED), and pseudophakic bullous keratopathy (PBK).
Design:
Case-control study.
Participants and Controls:
Patients listed on the UK Transplant Registry who had undergone a PKP for RACU, FED, or PBK between January 4, 1999, and January 4, 2006. Comparative standardized mortality ratios (SMRs) and causes of death were obtained from the Office for National Statistics.
Methods:
Outcome data were collected from the UK Ocular Tissue National Transplant database and supplementary questionnaires at transplantation and at 1, 2, and 5 years. Institutional review board approval for the National Health Service Blood and Transplant to undertake the study was obtained.
Main Outcome Measures:
Mortality and graft survival.
Results:
A total of 3665 patients were included: RACU (117), PBK (1701), and FED (1847). Five-year survival of patients with RACU was 42% (95% confidence interval [CI], 26–56) compared with 76% (95% CI, 72–78) for FED and 55% for PBK (95% CI, 50–60; P < 0.01). The SMRs for female and male patients with RACU were 43.5 (95% CI, 19.5–63.3) and 12.2 (95% CI, 7.1–19.5), respectively, in comparison with 1.84 and 1.45 for patients with RA, respectively (P < 0.01). There were no significant differences in the causes of death among patients with RACU, FED, or PBK (P > 0.9), with infection the most common cause. The 5-year graft survival rate was 48% (95% CI, 32–62) for RACU, 59% (95% CI, 56–62) for PBK, and 84% (95% CI, 82–86) for FED (P < 0.01).
Conclusions:
Mortality and ocular morbidity were significantly increased in patients with RACU. Accelerated immunosenescence should be considered in the differential diagnosis of patients presenting with RACU, and a multidisciplinary approach to management is required.
Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Purpose:
To investigate the incidence of significant adverse ocular side effects after intravenous zoledronate infusion for osteopenia.
Design:
Data analysis of a large, prospective, randomized, double-blind, placebo-controlled clinical trial.
Par…
Purpose:
To examine the characteristics of US medical students applying for ophthalmology residency and to determine the predictors of matching.
Design:
A retrospective case series.
Participants:
A total of 3435 medical students from the United States who applied to an ophthalmology residency program from 2003 to 2008 were included.
Methods:
Matched and unmatched applicants were compared and stratified by predictor variables, including United States Medical Licensing Examination (USMLE) Step 1 score, Alpha Omega Alpha (AOA) status, medical school reputation, and medical school geographic region. Differences in proportions were analyzed using the Fisher exact test. Logistic regression was used to determine the predictors of successful matching.
Main Outcome Measures:
Successful matching to an ophthalmology program.
Results:
The majority of applicants (72%, 2486/3435) matched in ophthalmology. In multivariate analysis, AOA membership (odds ratio [OR], 2.6, P<0.0001), USMLE score (OR, 1.6; P<0.0001), presence of an ophthalmology residency at medical school (OR, 1.4; P = 0.01), top 25 medical school (OR, 1.4; P<0.03), top 10 medical school (OR, 1.6; P<0.02), and allopathic degree (OR, 4.0; P<0.0001) were statistically significant predictors of matching. Approximately 60% (1442/2486) of applicants matched to the same geographic region as their medical school. Applicants were more likely to match at a program in the same geographic region as their medical school than would be predicted by chance alone (P<0.0001). In multivariate analysis, higher USMLE score (OR, 0.9; P<0.0001) and top 10 medical school (OR, 0.7; P = 0.027) were statistically significant predictors of matching to outside the geographic region as one’s medical school.
Conclusions:
The majority of applicants applying for an ophthalmology residency position match successfully. Higher performance on quantitative metrics seems to confer an advantage for matching. The majority of applicants match at a residency program within the same geographic region as one’s medical school.
Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Purpose:
To investigate the associations of the C2-CFB-RDBP-SKIV2L region with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV).
Design:
Cross-sectional, case-control association study.
Participants:
…
Purpose:
To investigate the effect of the lateral decubitus position (LDP) on intraocular pressure (IOP) in glaucoma patients with asymmetric visual field loss.
Design:
Prospective, cross-sectional study.
Participants:
Ninety-eight eyes of 49 consecutive bilateral glaucoma patients with asymmetric visual field loss, divided into better eye and worse eye groups for calculation of mean deviation.
Methods:
Intraocular pressure was measured using a Goldmann applanation tonometer and rebound tonometer (Icare PRO; Icare Finland Oy, Helsinki, Finland) in each of the following positions: sitting, supine, right LDP, and left LDP. Visual field was examined using the Humphrey Field Analyzer (HFA II; Carl Zeiss Meditec, Dublin, CA). A questionnaire on the preferred lying position during sleep was administered to each of the patients.
Main Outcome Measures:
The IOPs measured by rebound tonometer for the better and worse eyes in each position were compared using paired t tests. Agreement between the Goldmann applanation tonometry and rebound tonometry results was assessed by a Bland-Altman plot.
Results:
The IOPs of the better and worse eyes in the sitting position showed no significant difference (P<0.476). The IOP of the worse eye was significantly higher than that of the better eye in the supine position (16.8±3.0 mmHg vs. 15.1±1.8 mmHg; P<0.001). The IOPs of the worse and better eyes in their dependent LDP were 19.1±3.0 mmHg and 17.6±2.3 mmHg, respectively (change in IOP, 1.6±2.4 mmHg; P<0.001). Of the enrolled patients, 75.5% preferred the LDP, and 75.7% of these LDP-preferring patients preferred the worse eye dependent-LDP. The Bland-Altman plot comparing the Goldmann applanation tonometry and rebound tonometry readings showed reasonable agreement between the 2 methods (r2<0.001; P = 0.972).
Conclusions:
This study showed that IOP-elevation asymmetry in LDP is associated with asymmetric visual field loss in glaucoma patients. The LDP, habitually preferred by glaucoma patients, also may be associated with asymmetric visual field damage.
Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Objective:
Central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) causes hypoperfusion, high levels of vascular endothelial growth factor (VEGF), macular edema, and loss of vision. Many patients also show areas of complete clos…
Objective:
To determine the diagnostic ability of laminar thickness obtained using enhanced depth imaging (EDI) of the Heidelberg Spectralis optical coherence tomography (OCT) system (Heidelberg Engineering, Heidelberg, Germany) and the factors relat…
Purpose:
To investigate anterior segment parameters in normal Chinese subjects and study factors influencing these parameters, such as age, gender, and laterality.
Design:
A prospective observational case series.
Participants:
A total of 291 normal subjects (582 eyes) were included.
Methods:
The anterior segment data were determined with a dual Scheimpflug analyzer.
Main Outcome Measures:
The corneal thinnest-point thickness (CTPT), corneal thinnest-point distribution (CTPD), central corneal thickness (CCT), corneal thickness (CT) in the central 10 mm diameter, pupil diameter (PD), pupil center distribution (PCD), anterior chamber depth (ACD), and anterior chamber volume (ACV, 8-mm diameter) were measured.
Results:
The mean distance between the thinnest point and the corneal vertex was 0.70±0.32 mm in the right eyes and 0.42±0.25 mm in the left eyes; the thinnest point was located in the inferior temporal region in 71.1% of the right eyes and 55% of the left eyes. The CCT values were thicker than the CTPT values, and they were positively correlated (right eyes r = 0.994, P<0.001; left eyes r = 0.997, P<0.001). The distance between the pupillary center and the corneal vertex was approximately 0.39±0.27 mm in the right eyes and 0.37±0.24 mm in the left eyes. Furthermore, the percentage of pupillary centers located in the superior regions was 72.2% in the right eyes and 73.5% in the left eyes. Age was negatively correlated with the peripheral CT (7–10 mm diameter), PD, ACD, and ACV of both eyes and the mid-peripheral CT (4–7 mm diameter) of the right eye. Laterality correlated with CTPT (P<0.001) and PD (P<0.001), whereas gender correlated with ACD (P<0.001) and ACV (P = 0.009).
Conclusions:
The majority of the thinnest corneal points were located in the inferior temporal quadrant, and the pupillary center was located in the superior region of the cornea; both differed substantially from the corneal vertex. The CT increased gradually from the center to the periphery. Age, gender, and laterality correlated with some indexes.
Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Objective:
Neuroretinal rim assessment based on the clinical optic disc margin (DM) lacks a sound anatomic basis for 2 reasons: (1) The DM is not reliable as the outer border of rim tissue because of clinically and photographically invisible extensio…
Objective:
To describe the imaging characteristics of solitary idiopathic choroiditis (SIC).
Design:
Retrospective, observational case series.
Participants:
Ten eyes in 10 patients with SIC.
Methods:
Review of chart, fundus photography, ultraso…
Objective:
To use a novel teaching exercise to encourage students to practice ophthalmoscopy and to measure the learning effect both subjectively and objectively.
Design:
Comparative case series.
Participants:
One hundred thirty-one fourth-year medical students on their 1-week ophthalmology rotations with 89 in the experimental group and 42 in the control group.
Methods:
Those in the experimental group had 1 eye dilated and their optic nerve photographed on the first day. The next day, these students received an unlabeled optic nerve photograph belonging to 1 of their peers (typically 8–10 per group) and were given 3 days to identify the student matching the photograph. The students in the control group were simply encouraged to practice ophthalmoscopy on each other without the use of photographs.
Main Outcome Measures:
Both objective and subjective changes from the beginning to the end of the rotation were measured and compared between the 2 groups.
Results:
In the 89 students who used peer optic nerve photographs, 75 (84.3%) showed improvement in direct ophthalmoscopy skills over the course of the week. In contrast, only 12 (28.6%) of the 42 control students demonstrated an objective improvement (P<0.001). The subjective confidence levels likewise were more improved in the students who took part in the optic nerve photograph exercise.
Conclusions:
These results suggest that the task of matching an unknown optic nerve photograph to the correct eye of a peer leads to increased self-confidence and more proficient use of the direct ophthalmoscope.
Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Purpose:
To estimate retinal ganglion cell (RGC) losses associated with the earliest development of visual field defects in glaucoma.
Design:
Observational cohort study.
Participants:
The study group included 53 eyes of 53 patients with suspected glaucoma who were followed as part of the Diagnostic Innovations in Glaucoma (DIGS) study. These eyes had normal standard automated perimetry (SAP) visual fields at baseline and developed repeatable (3 consecutive) abnormal test results during a median follow-up of 6.7 years. An age-matched control group of 124 eyes of 124 healthy subjects recruited from the general population was included.
Methods:
Estimates of RGC counts were obtained using a previously published model that combines estimates of RGC numbers from SAP sensitivity thresholds and retinal nerve fiber layer (RNFL) thickness measurements with spectral domain optical coherence tomography (SD-OCT). For eyes converting to glaucoma, estimates of RGC counts were obtained at the time (within ±3 months) of the first abnormal visual field, representing the time of earliest detection of visual field losses.
Main Outcome Measures:
Estimates of RGC counts in eyes converting to glaucoma versus healthy eyes.
Results:
The average RGC count estimate in the eyes with early visual field defects was 652057±115829 cells, which was significantly lower than the average of 910 584±142 412 cells found in healthy eyes (P < 0.001). Compared with the average number of RGCs in the healthy group, glaucomatous eyes had an average RGC loss of 28.4%, ranging from 6% to 57%, at the time of the earliest visual field defect on SAP. Retinal ganglion cell counts performed significantly better than the SD-OCT average RNFL thickness parameter in discriminating glaucomatous from healthy eyes with receiver operating characteristic curve areas of 0.95±0.02 versus 0.88±0.03, respectively (P = 0.001).
Conclusions:
Glaucomatous eyes with the earliest detectable visual field loss on automated perimetry may already show substantial loss of RGCs. Empirical estimates of RGC counts combining structural and functional tests agreed closely with previous histologic reports on the number of RGCs associated with early visual fields defects on SAP.
Financial Disclosure(s):
Proprietary or commercial disclosure may be found after the references.
Purpose:
To evaluate the efficacy of a novel cyclosporine A (CsA) drug-delivery system (DDS) in the anterior chamber for suppressing the occurrence of rejection and improving the survival of corneal allografts after high-risk keratoplasty.
Design:
Single-center, noncomparative case series.
Participants:
Ninety-two eyes of 92 patients with corneal blindness who required corneal transplantation at Shandong Eye Institute from May 2003 to June 2011.
Methods:
The CsA DDS was implanted into the anterior chamber during high-risk keratoplasty, and subsequent therapeutic effects were evaluated.
Main Outcome Measures:
Occurrence and reversal of graft rejection within 12 months after surgery, long-term survival of corneal grafts (>12 months), biodegradation of the CsA DDS, endothelial cell density by noncontact specular microscopy, and iris status by ultrasound biomicroscopy (UBM).
Results:
At 6 months, the transplantation was scored as success in 81 eyes (88.0%), partial success in 7 eyes (7.6%), and failure in 4 eyes (4.3%). The mean graft survival time was 36.1±17.7 months (range, 12.3–61.6 months). The carrier of the CsA DDS, polylactide-co-glycolide-co-caprolactone, biodegraded completely at 7.6±4.3 months (range, 5–13 months). The density of endothelial cells was 2154±230 cells/mm2 (range, 2067–2319 cells/mm2) immediately after surgery and 2079±156 cells/mm2 (range, 1950–2254 cells/mm2; P > 0.05) at 6 months. No edema of corneal stroma and iris was observed by UBM.
Conclusions:
The CsA DDS implanted in the anterior chamber seems to be effective for the prophylaxis of immune rejection after high-risk keratoplasty without toxicity to the cornea and the iris of patients. It can decrease the rejection episode and prolong the survival time of allografts. The anterior chamber may be a promising drug-delivery target for treatment or prevention of endothelial graft rejection after corneal transplantation.
Financial Disclosure(s):
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Objective:
To compare the efficacy of topical voriconazole and topical natamycin with that of intrastromal voriconazole and topical natamycin in patients with recalcitrant fungal keratitis.
Design:
Randomized clinical trial.
Participants:
Forty e…
Purpose:
To determine the causative pathogens in eyes with bacterial conjunctivitis.
Design:
Evaluation of diagnostic test or technology.
Participants:
Thirteen eyes diagnosed clinically with bacterial conjunctivitis and 12 eyes with normal conju…
Purpose:
To determine the outcome of a reduced amount of medial rectus (MR) muscle recession in esotropes with cerebral palsy (CP) and to compare the surgical response with that of normal controls.
Design:
Retrospective cohort study.
Participants:
Thirty esotropes with CP and 60 age-matched esotropes without CP who underwent a unilateral or bilateral MR muscle recession.
Methods:
The surgical amount of MR muscle recession was reduced by 1 mm per muscle in patients with CP.
Main Outcome Measures:
Success rates, surgical response, cumulative probabilities of success, and factors affecting surgical responses evaluated by generalized linear mixed models.
Results:
In patients with CP, the initial success rate was higher (P = 0.037) and the rate of undercorrection was lower (P = 0.037) compared with patients without CP. At the final visit, success rates were not significantly different between both groups. However, the rate of overcorrection was higher (P = 0.003) compared with patients without CP. The rate of overcorrection per person-year during follow-up was 11% in patients with CP and 2% in patients without CP. Patients with CP showed a greater surgical response than did those without CP, at about 1.3 prism diopters per millimeter of MR muscle recession (P<0.001).
Conclusions:
Even with the reduced amount of recession, esotropes with CP showed a greater surgical response to MR muscle recession than did those without CP, and the incidence of late overcorrection was significantly higher compared with that of patients without CP.
Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Purpose:
To compare the change in lamina cribrosa (LC) displacement in response to intraocular pressure (IOP) lowering in patients with open-angle glaucoma (OAG) using spectral-domain optical coherence tomography (SD-OCT).
Design:
Observational case series.
Participants:
One hundred eyes of 100 patients with OAG in whom IOP at the follow-up examination had decreased by at least 20% compared with the baseline IOP.
Methods:
Serial horizontal B-scan images of the optic nerve head (ONH) were obtained from each eye using enhanced depth imaging SD-OCT. Approximately 65 B-scans covering the optic discs were obtained before and 3 to 6 months after lowering IOP. The baseline and follow-up LC depths (the distance from the Bruch’s membrane opening plane to the level of the anterior LC surface) were measured in B-scan images from each eye.
Main Outcome Measures:
The mean and maximum amount of reductions in LC depth measured in the 7 selected B-scan images.
Results:
Intraocular pressure decreased from 21.2±9.1 to 10.5±2.6 mmHg. The percent of IOP reduction was significantly related to the untreated IOP (P < 0.001). There was a significant decrease in the LC depth at the follow-up examination compared with the baseline value (P < 0.001). The magnitude of LC depth reduction was significantly associated with younger age, higher untreated IOP, higher baseline IOP, and greater percent of IOP reduction (all P < 0.02).
Conclusions:
Reversal of the LC displacement was observed after IOP-lowering treatment in OAG. The degree of LC displacement reversal was related to the amount of IOP lowering.
Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Purpose:
To report the secondary outcomes in the Carotenoids with Coantioxidants in Age-Related Maculopathy trial.
Design:
Randomized double-masked placebo-controlled clinical trial (registered as ISRCTN 94557601).
Participants:
Participants incl…
Purpose:
To assess the mutation spectrum, enzymatic activity, and phenotypic features associated with CYP1B1 genotypes in primary congenital glaucoma (PCG) and nondominant juvenile glaucoma (ndJG).
Design:
CYP1B1 genotyping, segregation analysis, and functional evaluation of mutations in a cohort of patients.
Participants:
A total of 177 probands clinically diagnosed with PCG (161) or ndJG (16).
Methods:
Automatic DNA sequencing of the promoter (−1 to −867) and the 3 CYP1B1 exons. CYP1B1 enzymatic activity was evaluated using an ethoxyresorufin O-deethylation assay in transfected HEK-293T cells.
Main Outcome Measures:
Screening and functional evaluation of CYP1B1 mutations. Glaucoma diagnosis based on slit-lamp examination, measurement of intraocular pressure, gonioscopy, and fundus examination.
Results:
Thirty-one different mutations were identified in 56 PCG and 7 ndJG index cases. To the best of our knowledge, 3 of the identified mutations were novel (−337G>T, F123L, and I399_P400del). Approximately 56% of all mutation carriers were compound heterozygotes, 25% were homozygotes, and both groups inherited glaucoma as an autosomal recessive trait. Nineteen percent of carriers were heterozygotes and showed non-Mendelian segregation. In vitro and inferred functional analysis showed that no less than approximately 74% of the recessive genotypes result in null enzymatic activity. We detected variable expressivity in relation to age of onset and a possible case of incomplete penetrance in 3 of 6 families (50%), with more than 1 affected child or more than 1 subject carrying 2 CYP1B1 mutant alleles. Altogether, these data support that PCG is not a simple monogenic disease. In addition, most patients with PCG carrying null or putative null genotypes showed severe bilateral phenotypes featured by early disease onset, frequently at birth. The mean number of trabeculectomies per eye was significantly higher in carriers than in noncarriers.
Conclusions:
This is the largest analysis of CYP1B1 mutations performed in European patients with PCG to date. Our data show that null CYP1B1 genotypes, and therefore complete absence of CYP1B1 activity, frequently lead to severe phenotypes. Our results support that CYP1B1 glaucoma is not a simple monogenic disease and that CYP1B1 activity levels could influence the phenotype.
Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.