Category: Peer-reviewed

Rheumatoid Arthritis–Associated Corneal Ulceration: Mortality and Graft Survival

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.

Investigation of the Human Anterior Segment in Normal Chinese Subjects Using a Dual Scheimpflug Analyzer

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.

Predictors of Matching in an Ophthalmology Residency Program

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.

Effect of Lateral Decubitus Position on Intraocular Pressure in Glaucoma Patients with Asymmetric Visual Field Loss

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.

Combined Depth Imaging Technique on Spectral-Domain Optical Coherence Tomography

Purpose: To describe a technique to obtain combined images of vitreoretinal and choroidal structures using spectral-domain (SD) optical coherence tomography (OCT) and to evaluate applicability in normal eyes and limitations in eyes with cataract.Design: Prospective, observational case series.Methods: Three different foveal scans, including conventional SD OCT, enhanced depth imaging OCT and the novel method called combined depth imaging (CDI) OCT, were obtained in 42 eyes of healthy volunteers and in 26 eyes with cataract using the Heidelberg Spectralis HRA (Heidelberg Engineering). The CDI OCT images were obtained manually using an image modification process that enhances the vitreoretinal interface first and then the choroid, while averaging 100 separate OCT scans. The visualization of the inner border of the preretinal pocket and the outer border of the choroid was graded by independent masked observers for each OCT scan method.Results: The CDI technique was able to create a good-quality combined image of the posterior structures in all the eyes, including eyes with cataract. The agreement between the grading performed by the independent observers was high for both the inner border of the vitreal pocket (κ, 0.86; P < .001) and the outer choroidal border (κ, 0.90; P < .001). CDI OCT was equivalent to conventional SD OCT in visualizing the vitreal pocket (P = .445 for normal eyes, P = .162 for eyes with cataract) and was equivalent to enhanced depth imaging OCT in visualizing the outer choroidal border (P = .660 for normal eyes, P = .329 for eyes with cataract). CDI OCT was superior to conventional SD OCT and enhanced depth imaging OCT in visualizing both of the structures (P < .001).Conclusions: The manual technique of CDI OCT is highly sensitive to visualize posterior vitreoretinal and choroidal structures into a single full-depth image and is not affected by mild to moderate cataract.

Effects of Light Exposure, pH, Osmolarity, and Solvent on the Retinal Pigment Epithelial Toxicity of Vital Dyes

Purpose: To investigate the in vitro effect of pH, osmolarity, solvent, and light interaction on currently used and novel dyes to minimize dye-related retinal toxicity.Design: Laboratory investigation.Methods: Retinal pigment epithelium (RPE) human cells (ARPE-19) were exposed for 10 minutes to different pH solutions (4, 5, 6, 7, 7.5, 8, and 9) and glucose solutions (2.5%, 5.0%, 10%, 20%, 40%, and 50%) with osmolarity from 142 to 2530 mOsm, with and without 0.5 mg/mL trypan blue. R28 cells were also incubated with glucose (150, 310, and 1000 mOsm) and mannitol used as an osmotic control agent in both experiments. Dye-light interaction was assessed by incubating ARPE-19 for 10 minutes with trypan blue, brilliant blue, bromophenol blue, fast green, light green, or indigo carmine (0.05 mg/mL diluted in balanced saline solution) in the presence of high-brightness xenon and mercury vapor light sources.Results: Solutions with nonphysiologic pH, below 7 and above 7.5, proved to be remarkably toxic to RPE cells with or without trypan blue. Also, all glucose solutions were deleterious to RPE (P < .001) even in iso-osmolar range. No harmful effect was found with mannitol solutions. Among the dyes tested, only light green and fast green were toxic to ARPE-19 (P < .001). Light exposure did not increase RPE toxicity either with xenon light or mercury vapor lamp.Conclusions: Solutions containing glucose as a dye solvent or nonphysiologic pH should be used with care in surgical situations where the RPE is exposed. Light exposure under present assay conditions did not increase the RPE toxicity.

The Use of Peer Optic Nerve Photographs for Teaching Direct Ophthalmoscopy

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.

Retinal Ganglion Cell Count Estimates Associated with Early Development of Visual Field Defects in Glaucoma

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.

A Novel Cyclosporine A Drug-Delivery System for Prevention of Human Corneal Rejection after High-risk Keratoplasty: A Clinical Study

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.

Ocular Biometry in the Subtypes of Angle Closure: An Anterior Segment Optical Coherence Tomography Study

Purpose: To evaluate ocular biometric parameters in different subtypes of angle-closure disease in the Iranian population and compare them with normal eyes.Design: Prospective, cross-sectional.Methods: In this clinic-based study, 189 eyes of 154 patients consisting of 40 acute angle-closure glaucoma (AACG) eyes, 40 fellow eyes of AACG, 42 chronic angle-closure glaucoma (CACG) eyes, 40 primary angle-closure suspect (PACS) eyes, and 27 normal eyes underwent complete examination including gonioscopy, A-scan biometry, and anterior segment optical coherence tomography. Only 1 eye of CACG, PACS, and control subjects were selected. Main outcome measures included angle opening distance and trabeculo-iris space area at 500 μm from the scleral spur (AOD500, TISA-500), anterior chamber angle, lens vault, lens thickness, anterior chamber depth (ACD), and lens position.Results: Anterior chamber angle, AOD500, TISA500, ACD, and lens position were less and lens thickness and lens vault were greater in angle-closure than open-angle eyes. ACD was less in AACG than CACG and PACS (P < .001). It was also less in fellow eyes than PACS eyes (P = .04). Lens vault was highest in AACG eyes, followed by fellow eyes, PACS, and CACG. It was significantly more in AACG eyes than CACG and PACS eyes (P < .001 and P = .007, respectively). No difference was observed between AACG and fellow eyes.Conclusions: The anterior segment was crowded in closed-angle compared to open-angle eyes. Higher lens vault may play a role in the development of an acute attack of angle closure.