Ophthalmology - Articles in Press

Optic Disc Torsion Direction Predicts the Location of Glaucomatous Damage in Normal-Tension Glaucoma Patients with Myopia - Corrected Proof

Hae-Young L. Park, Kook Lee, Chan Kee Park — 2012-05-16

Objective: To characterize optic disc tilt and torsion in normal-tension glaucoma (NTG) patients with myopia and to evaluate the relationship between optic disc tilt and torsion with the location of visual field (VF) defect. Design: Retrospective, case-control design. Participants: Two hundred twenty-five NTG patients. Methods: Patients were divided into a myopic NTG group (spherical equivalent more than −2.00 diopters [D] or axial length more than 24.0 mm; n = 166) and nonmyopic NTG group (spherical equivalent less than −0.50 D or axial length less than 24.0 mm; n = 59). Disc tilt, which was identified by the tilt ratio, disc torsion, and area of peripapillary atrophy (PPA), was measured from disc photographs. Patients were divided further into superior and inferior defect groups according to the location of the VF defect in the pattern deviation map. Logistic regression analysis was used to determine the relationship between ocular factors, including tilt ratio, torsion degree, and the VF defect location. Main Outcome Measures: Tilt ratio, torsion degree, PPA area, and location of VF defect. Results: Among 225 NTG eyes, 166 (73.8%) were myopic eyes. The myopic NTG group was significantly younger (42.85 years) than the nonmyopic NTG group (60.73 years). Disc tilt (45.8%) and torsion (75.9%) were significantly more prevalent in the myopic NTG group than in the nonmyopic NTG group. Although just short of statistical significance (P = 0.057), PPA area was larger in the myopic NTG group. The VF defect location was significantly different between the 2 groups, with superior defects more prevalent in the myopic NTG group (69.9%; P<0.001). Torsion degree was significantly different in the superior defect group (18.45°) compared with the inferior defect group (−3.81°; P = 0.001). Torsion degree was the only factor related to VF defect location in both univariate (P = 0.001) and multivariate (P = 0.014) logistic regression analyses. Conclusions: Korean NTG patients had a high prevalence of myopia and young age. Optic disc tilt and torsion were highly prevalent in Korean NTG patients with myopia. The direction of the optic disc torsion may predict the location of damage. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Tear Film Aberration Dynamics and Vision-Related Quality of Life in Patients with Dry Eye Disease - Corrected Proof

Alexandre Denoyer, Ghislaine Rabut, Christophe Baudouin — 2012-05-15

Objective: Corneal and ocular wavefront aberrations were recorded together with clinical examination results and patient-reported vision-related quality-of-life evaluation results to define the relevance of dynamic optical analysis of the eye in dry eye disease (DED). Design: Prospective and comparative clinical study. Participants: Forty DED patients and 40 age- and gender-matched control subjects. Methods: Serial measurements of ocular and corneal higher-order aberrations (HOAs) after blink were performed for 10 seconds using the KR-1 aberrometer (Topcon, Clichy, France). Vision-related health-targeted quality of life was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. The clinical examination included tear film assessment (tear film break-up time and Schirmer I test), ocular surface damage assessment with the Oxford and van Bijsterveld indexes, and Meibomian dysfunction grading. Tear osmolarity also was measured. Main Outcome Measures: The time course of HOAs and modulation transfer function (MTF) was compared between groups and was analyzed in comparison with the OSDI and clinical data in DED patients. Results: The root mean square of ocular and corneal total HOAs, particularly third-order aberrations, significantly increased over the 10-second period in DED patients, whereas no change occurred in controls. Analysis of MTF revealed progressive degradation of ocular optical quality resulting from loss of contrast at intermediate and high spatial frequencies in DED patients compared with controls. The progression index for corneal HOAs was correlated with the subjective index of patient-reported visual outcomes and with objective clinical findings of tear film and ocular surface damage. Conclusions: Objective measurement of the time course of HOAs may constitute a new single instrument to evaluate and manage patients with DED because it reliably reflects the completeness of the disease. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Relationship of Cataract and Cataract Extraction to Age-related Macular Degeneration: The Beaver Dam Eye Study - Corrected Proof

2012-05-14

Objective: To examine the associations of cataract and cataract surgery with early and late age-related macular degeneration (AMD) over a 20-year interval. Design: Longitudinal population-based study of age-related eye diseases. Participants: Beaver Dam Eye Study participants. Methods: Persons aged 43 to 86 years participated in the baseline examination in 1988–1990. Participants were followed up at 5-year intervals after the baseline examination. Examinations consisted of ocular examination with lens and fundus photography, medical history, measurements of blood pressure, height, and weight. Values of risk variables were updated, and incidences of early and late AMD were calculated for each 5-year interval. Odds ratios were computed using discrete linear logistic regression modeling with generalized estimating equation methods to account for correlation between the eyes and multiple intervals. Main Outcome Measures: Age-related macular degeneration. Results: After adjusting for age and sex, neither cataract nor cataract surgery was associated with increased odds for developing early AMD. Further adjusting for high-risk gene alleles (CFH and ARMS2) and other possible risk factors did not materially affect the odds ratio (OR). However, cataract surgery was associated with incidence of late AMD (OR 1.93; 95% confidence interval [CI], 1.28–2.90). This OR was not materially altered by further adjusting for high-risk alleles (CFH Y402H, ARMS2) or other risk factors. The OR for late AMD was higher for cataract surgery performed 5 or more years prior compared with less than 5 years prior. Conclusions: These data strongly support the past findings of an association of cataract surgery with late AMD independent of other risk factors, including high-risk genetic status, and suggest the importance of considering these findings when counseling patients regarding cataract surgery. These findings should provide further impetus for the search for measures to prevent or delay the development of age-related cataract. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Predictive Value of Confocal Scanning Laser for the Onset of Visual Field Loss in Glaucoma Suspects - Corrected Proof

2012-05-14

Purpose: To perform a longitudinal multivariate analysis of the ability of Moorfields Regression Analysis (MRA) to predict the onset of glaucoma in a population of patients with suspected glaucoma due to appearance of the optic nerve head. Design: Prospective longitudinal evaluation of a diagnostic test. Participants: Single, randomly selected eye of prospectively recruited patients with suspected glaucoma based on the optic nerve head appearance on stereophotographs and normal baseline visual field results. Methods: The MRA was evaluated at baseline (Heidelberg Retina Tomograph; Heidelberg Engineering, Dossenheim, Germany), and visual field tests were repeated every 6 months. A longitudinal multivariate proportional hazard ratio (HR) analysis was performed, and likelihood ratios and positive and negative predictive values were compared. Main Outcome Measures: Onset of visual field losses. Results: The study included 230 eyes that were followed up during a mean period of 62±14 months, ranging from 4 to 7 years. The predicted HR (for onset of visual field losses) of the MRA temporal-inferior sector outside normal limits was 3.65 (95% confidence interval [CI], 2.32–5.75; P < 0.0001). An MRA temporal-superior sector outside normal limits had an HR of 3.43 (95% CI, 2.21–5.32; P < 0.0001). Conclusions: The temporal-inferior and temporal-superior positions of the MRA are highly predictive for the onset of visual field loss in glaucoma suspects. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association between Genetic Variants Associated with Vertical Cup-to-Disc Ratio and Phenotypic Features of Primary Open-Angle Glaucoma - Corrected Proof

2012-05-14

Purpose: To assess the association between the genetic variants associated with the optic nerve vertical cup-to-disc ratio (VCDR) and the phenotypic features in patients with primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG) and high-tension glaucoma (HTG). Design: Case-control study. Participants and Controls: Japanese patients with NTG (n = 213) and HTG (n = 212) and 191 control subjects without glaucoma. Methods: DNA samples were genotyped for 7 single nucleotide polymorphisms (SNPs) associated with VCDR: rs1063192 (near gene: CDKN2B), rs10483727 (SIX1), rs17146964 (SCYL1), rs1547014 (CHEK2), rs1900004 (ATOH7), rs1926320 (DCLK1), and rs12015126 (RERE). Main Outcome Measures: The VCDR was compared between genotypes, and allele frequency differences were compared between NTG or HTG subjects and control subjects. Demographic and clinical features were compared between alleles in patients with NTG or HTG. Results: There were significant VCDR differences (P = 0.0077 and P = 0.019) between the genotypes for rs1063192 (CDKN2B) and rs1547014 (CHEK2), respectively. There were significant differences in the rs1063192 (CDKN2B) and rs1900004 (ATOH7) allele frequencies between the NTG subjects and control subjects (P = 0.0023 and P = 0.028, respectively) and a significant difference (P = 0.013) in the rs1547014 (CHEK2) allele frequencies between the HTG subjects and control subjects. Ages at diagnosis were significantly different in the NTG subjects with and without the rs10483727 (SIX1) C allele (P = 0.017) or the rs1926320 (DCLK1) T allele (P = 0.040). Likewise, the age at diagnosis was significantly different (P = 0.037) in the HTG subjects with and without the rs12025126 (RERE) T allele. There were no significant associations between the maximum intraocular pressure (IOP) and 7 genotyped SNP alleles in patients with NTG or HTG. Conclusions: The rs1063192 (CDKN2B) and rs1900004 (ATOH7) seem to be non–IOP-related genetic risk factors for NTG, and the rs1547014 (CHEK2) is a genetic risk factor for HTG. Although the rs10483727 (SIX1), rs1926320 (DCLK1), or rs12025126 (RERE) alone may not be sufficient for the development of POAG, the association of these SNPs with a phenotypic feature in patients with NTG or HTG suggests that these loci contribute to the pathogenesis of POAG. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ocular Adverse Events of Systemic Inhibitors of the Epidermal Growth Factor Receptor: Report of 5 Cases - Corrected Proof

2012-05-14

Purpose: To describe the ocular effects associated with the administration of the systemic epidermal growth factor receptor (EGFR) inhibitors panitumumab and erlotinib. Design: Retrospective, noncomparative interventional case series. Participants: Ten eyes of 5 patients in treatment with systemic EGFR inhibitors, 4 patients with erlotinib for end-stage lung carcinoma, and 1 patient with panitumumab for end-stage colorectal cancer. Methods: Data collected from charts included gender, age at presentation, systemic disease, and clinical presentation in each eye. Main Outcome Measures: Demographics on presentation and clinical findings. Results: Multiple epithelial defects were observed in all 10 eyes, corneal melting and thinning were observed in 3 eyes of 2 patients, 2 eyes of 1 patient presented with lower lid ectropion, and 2 eyes of 2 patients presented with corneal perforation, both requiring a penetrating keratoplasty. Conclusions: Severe ocular side effects, including corneal perforation, may be associated with the use of the EGFR inhibitors panitumumab and erlotinib. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Rabbit Intraocular Reactivity to Endotoxin Measured by Slit-Lamp Biomicroscopy and Laser Flare Photometry - Corrected Proof

2012-05-14

Objective: To evaluate the ocular reactivity of the rabbit to an intracameral injection of a dispersive ophthalmic viscosurgical device (OVD) containing various levels of bacterial endotoxin using slit-lamp biomicroscopy and laser flare photometry. Design: Experimental, randomized, masked animal study. Participants: Thirty Dutch-Belted rabbits. Methods: The rabbits were randomized into 6 groups to receive 0.05 ml of a hydroxypropyl methylcellulose-based dispersive OVD to which had been added one of 5 different doses of bacterial endotoxin ranging from 0.02 to 1.4 endotoxin units (EUs) or a vehicle control to both eyes. The eyes were evaluated for anterior segment inflammation at baseline and 3, 6, 9, 24, 48, and 72 hours after injection using slit-lamp biomicroscopy and laser flare photometry. Main Outcome Measures: Corneal clarity and anterior chamber (AC) inflammation. Results: All the corneas remained clear throughout the study. Anterior chamber cells were seen at 6, 9, and 24 hours in 60% to 100% of the eyes intracamerally injected with endotoxin-containing OVD, and the response declined rapidly after 24 hours. A dose-response effect was seen between the concentration of endotoxin and the AC cell response. The aqueous flare response in eyes injected with the 2 highest doses of endotoxin was significantly greater (P<0.05) than that of controls. The amounts of fibrin observed in the AC were random, with no apparent dose-response effect seen. The flare values as obtained by laser flare photometry were consistent with the slit-lamp biomicroscopy flare findings up to grade 3+. However, the increase in laser flare value seemed to level off in eyes with more than 3+ flare. Neither measure of flare correlated with endotoxin level. Conclusions: Among the parameters evaluated in this study, the AC cell response, evaluated by slit-lamp biomicroscopy and graded using a standard grading system, was found to be the most reliable indicator of the amount of endotoxin in the dispersive OVD. The use of laser flare photometry alone does not seem to be useful in detecting an ocular response to endotoxin contamination in OVDs. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Detecting Endotoxin Contamination of Ophthalmic Viscosurgical Devices: Intracameral versus Intravitreal Assays in Rabbits - Corrected Proof

Shelley Y. Buchen, Don Calogero, Gene Hilmantel, Malvina B. Eydelman — 2012-05-14

Objective: To compare the sensitivities of intracameral and intravitreal assays in the rabbit model to determine the relative adequacy of these methods in detecting bacterial endotoxin contamination of ophthalmic viscosurgical devices (OVDs). Design: Experimental, randomized animal study. Participants: Twenty New Zealand white rabbits. Methods: Rabbits were randomized into 4 groups to receive a cohesive or a dispersive OVD via intracameral or intravitreal injection. All 40 treated eyes (10 eyes of 5 animals in each group) received bilateral injection of OVD spiked with bacterial endotoxin at 7.0 endotoxin units/ml. All eyes were evaluated by slit-lamp biomicroscopy for inflammatory response at 3, 6, 9, 24, 48, and 72 hours after exposure. Eyes that received intravitreal injection were also dilated at 24, 48, and 72 hours and were re-examined by slit-lamp biomicroscopy and by indirect ophthalmoscopy. Main Outcome Measures: Conjunctival inflammation, anterior chamber (AC) flare, cells and fibrin, vitreous haze and cells, iridal hyperemia, corneal clouding, lens opacities, and onset times. Results: Intracamerally injected eyes frequently showed conjunctival congestion, AC cells and flare, iridal hyperemia, and fibrin within 6 hours. Up to 80% showed AC cells and flare at 9 hours, and up to 70% showed fibrin at 24 hours. These signs diminished within 48 hours. Fibrin and cells also were seen on the lens surface of most of the eyes. Intravitreally injected eyes showed no signs of inflammation within 24 hours, other than some conjunctival inflammation. After the 24-hour time point, in addition to some conjunctival inflammation, some other signs of inflammation were observed infrequently in the intravitreally injected eyes, including minor vitreous cell reaction in 2 eyes. Although there was 1 dispersive OVD–treated eye with cells and fibrin on the lens capsule at 48 hours, no aqueous cells or flare were seen in the AC of any intravitreally injected eyes at any time during the course of the study. Conclusions: The rabbit intravitreal assay, when limited to 72 hours, does not seem to have adequate sensitivity to detect endotoxin reliably in OVDs. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Rabbit Ocular Reactivity to Bacterial Endotoxin Contained in Aqueous Solution and Ophthalmic Viscosurgical Devices - Corrected Proof

Shelley Y. Buchen, Don Calogero, Gene Hilmantel, Malvina B. Eydelman — 2012-05-14

Objective: To describe the ocular reactivity of the rabbit to bacterial endotoxin contained in an aqueous medium and in a cohesive and a dispersive ophthalmic viscosurgical device (OVD). Design: Experimental, randomized animal study. Participants: Seventy-five New Zealand white rabbits. Methods: This study was performed using 75 rabbits to evaluate the ocular reactivity to bacterial endotoxin contained in Dulbecco's phosphate-buffered saline (DPBS), a cohesive OVD, and a dispersive OVD. For each test material, 25 rabbits were randomized into 5 groups and were exposed to the test material containing 0.75 endotoxin units (EU), 0.25 EU, 0.08 EU, and 0.02 EU of endotoxin or the vehicle control. The rabbits in each group received bilateral intracameral injection of 0.05 ml of the same test material. All eyes were examined by slit-lamp biomicroscopy at baseline, 3, 6, 9, 24, 48, and 72 hours after injection. At 24 and 72 hours, slit-lamp biomicroscopy (and additionally indirect ophthalmoscopy) was performed through dilated pupils. Main Outcome Measures: Corneal clouding, anterior chamber (AC) flare, cells and fibrin, vitreous haze and cells, cells and fibrin on lens surface, lens opacities, and onset time. Results: The inflammation seen after exposure to the 3 endotoxin-spiked materials followed the same general time course. Anterior chamber cells, flare, iris hyperemia, and conjunctival congestion were seen as early as 3 hours. They started to diminish after 6 hours (DPBS eyes) and 9 hours (OVDs) and were not detectable at 48 and 72 hours, respectively. The AC inflammation was more severe in the OVD eyes than in the DPBS eyes. Anterior chamber fibrin was seen in the OVD eyes only, which persisted through 72 hours in many eyes. A trend toward a dose-response relationship was seen for AC cells and flare and the presence of cells and fibrin on the lens surface in all 3 treatment groups in the first 24 hours. Conclusions: Inflammation was seen after intracameral injection of as little as 0.02 and 0.08 EU in OVD and DPBS eyes, respectively. Observed responses to intracamerally injected endotoxin in OVDs were more severe and of longer duration than those in aqueous medium. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Evaluation of Intraocular Reactivity to Organic Contaminants of Ophthalmic Devices in a Rabbit Model - Corrected Proof

2012-05-14

Objective: To evaluate the intraocular reactivity to organic contaminants of ophthalmic devices in the rabbit. Design: Experimental animal study. Participants: Fifty New Zealand white rabbits. Methods: The rabbits were allocated to 10 groups of 5 each to receive 2 different doses of human albumin and nonhuman nucleic acids and their respective vehicle controls, a denatured cohesive ophthalmic viscosurgical device (OVD) and a denatured dispersive OVD and their respective nondenatured controls. All 10 eyes in each treatment group received bilateral intracameral injection of the test materials. All the eyes in the study were examined by slit-lamp biomicroscopy at baseline and 6, 9, 24, 48, and 72 hours. Pachymetry was also performed on eyes exposed to albumin, protein vehicle control, and the OVDs at these time points. Main Outcome Measures: Corneal thickness, grade of corneal clouding, anterior chamber (AC), cells, flare and fibrin, iridal hyperemia, cell and fibrin on lens surface, and onset time. Results: There were no inflammatory signs in any eyes exposed to human albumin. Anterior chamber cells (1+ to 3+) and flare and fibrin (1+ to 2+), along with cells and fibrin on the lens surface, were seen in the eyes exposed to the nucleic acid samples, and they resolved in 24 hours. Mild (mostly 1+) conjunctival congestion, cells, flare, and fibrin were seen in a few eyes exposed to the 2 denatured OVDs and their controls, with the response durations being shorter in the denatured OVD eyes (24 hours) than in the nondenatured OVD eyes (48 hours). Anterior chamber inflammation was generally observed in fewer denatured OVD eyes than in nondenatured OVD eyes, particularly the dispersive OVD eyes. Conclusions: Intracameral injection of human albumin protein did not cause ocular inflammation. Nucleic acid intracamerally injected into rabbit eyes caused acute inflammation that quickly resolved. Cohesive and dispersive OVD denatured by drying and steam sterilization alone did not cause ocular inflammation. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

The Food and Drug Administration's Proactive Toxic Anterior Segment Syndrome Program - Corrected Proof

2012-05-14

Toxic anterior segment syndrome (TASS) is a rare inflammatory condition usually observed within the first 48 hours after uncomplicated anterior segment surgery. Over the decades since its initial description, a number of TASS outbreaks have been reported. For a few of these outbreaks, the inciting factors were identified, but for the majority, the precipitating factors were often postulated but not confirmed. In light of the limitations identified in these outbreak investigations, the Food and Drug Administration's (FDA's) Center for Devices and Radiological Health staff has embarked on a number of activities aimed at mitigating medical device–related TASS outbreaks. Under the FDA-designed Proactive TASS Program (PTP), FDA scientists have conducted animal studies to better explore the inflammatory potential of suspected ophthalmic device contaminants implicated in prior cases of TASS. For contaminants displaying a TASS-like reaction in these animal models, the FDA scientists have developed analytic test methods to measure the level of those contaminants in or on ophthalmic devices. Moreover, FDA researchers have developed methods to better capture the clinical information necessary to assist investigations of potential future outbreaks. Last, the FDA has partnered with the Centers for Disease Control and Prevention to facilitate a potential TASS investigation, including expediting the analysis of potentially contaminated medical devices. The PTP is an example of the FDA proactively developing test methods and disease surveillance methods geared toward protecting the public's health. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Evaluation of Intraocular Reactivity to Metallic and Ethylene Oxide Contaminants of Medical Devices in a Rabbit Model - Corrected Proof

2012-05-14

Objective: To evaluate the intraocular reactivity to metallic and ethylene oxide (EO) contaminants of ophthalmic devices in rabbits. Design: Two experimental animal studies. Participants: Thirty-five New Zealand white rabbits. Methods: A metallic exposure study and an EO exposure study were performed. In the first study, both eyes of 25 rabbits were equally allocated to intracameral injections of alumina 0.2 μg, alumina 20 μg, copper sulfate 0.4 μg, copper sulfate 20 μg, or an aqueous control. In the second study, 10 rabbits were allocated (5 per group) to receive intracamerally an ophthalmic viscosurgical device (OVD) exposed to EO or not exposed to EO (control). All eyes were examined by slit lamp at baseline and 3, 6, 9, 24, 48, and 72 hours after exposure, with dilated indirect ophthalmoscopy being performed at 24 and 72 hours. Tonometry was performed only in the first study. Main Outcome Measures: Grade of corneal clouding, anterior chamber (AC) flare, AC cells, AC fibrin, iridal hyperemia, cell and fibrin on the lens surface, vitreous haze and cells, lens opacities, intraocular pressure, and onset time. Results: For metallic compounds at the study's low doses, mean inflammatory grades were 0.2 or less above the control for all responses at all time points. For the high-dose alumina, mean inflammatory grades peaked at 6 to 9 hours at 0.5 to 0.7 above the control responses for conjunctival congestion, iris hyperemia, AC cells, flare, and fibrin and declined over the remaining time points. For the high-dose copper sulfate, mean inflammatory grades peaked between 3 and 24 hours at 1.2 to 1.8 above the control responses for conjunctival congestion, iris hyperemia, AC cells, flare, fibrin, and corneal clouding, then subsequently declined. The intraocular pressure changes appeared significant for only high-dose copper sulfate, with mean declines of 4.3 to 7.5 mmHg at 6 to 72 hours. No clinically meaningful differences in ocular inflammation were observed between the OVD exposed to EO and the OVD not exposed to EO. Conclusions: Alumina and copper sulfate did not cause clinically meaningful ocular inflammation at the low study levels (levels expected with ophthalmic devices). Ethylene oxide exposure of an OVD was not associated with inflammation. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Annual Changes in Refractive Errors and Ocular Components before and after the Onset of Myopia in Chinese Children - Corrected Proof

Fan Xiang, Mingguang He, Ian G. Morgan — 2012-05-11

Objective: To examine annual changes in refraction and ocular components around the onset of myopia in Chinese children. Design: Longitudinal study. Participants: Twins aged 7 to 15 years in 2006 from the Guangzhou Twin Registry. Methods: Participants underwent eye examinations annually from 2006 to 2010. Years were defined (+1 or −1) relative to the examination at which the onset of myopia was first identified. Main Outcome Measures: Annual change in spherical equivalent refraction (SER) and ocular biometry. Results: Children who were not myopic at the first examination and myopic in at least 1 subsequent examination from 2006 to 2010 were included in the analysis. Annual change in SER increased slowly from 4 years before the first detection of myopia to 2 years before myopia onset (−0.25 to −0.4 diopter [D]). The rate of progression was the highest during the year of onset (−0.92 D). After the first detection of myopia, the rate of progression decreased to −0.71 D in the following year and kept decreasing. Annual change in axial length showed a similar, but inverse, shape to that of SER. Annual change in lens power did not change significantly around the onset of myopia. Conclusions: Before the onset of myopia, axial elongation and progression accelerate. After a myopic refraction is established, axial elongation and progression decrease. We suggest that the increases before myopia may be due to increased intensity of study and decreased time outdoors. In contrast, the rapid slowing after the onset of myopia may represent an inhibitory effect of myopic defocus on eye growth. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Systematic Review of the Agreement of Tonometers with Goldmann Applanation Tonometry - Corrected Proof

2012-05-11

Objective: To assess the agreement of tonometers available for clinical practice with the Goldmann applanation tonometer (GAT), the most commonly accepted reference device. Design: A systematic review and meta-analysis of directly comparative studies assessing the agreement of 1 or more tonometers with the reference tonometer (GAT). Participants: A total of 11 582 participants (15 525 eyes) were included. Methods: Summary 95% limits of agreement (LoA) were produced for each comparison. Main Outcome Measures: Agreement, recordability, and reliability. Results: A total of 102 studies, including 130 paired comparisons, were included, representing 8 tonometers: dynamic contour tonometer, noncontact tonometer (NCT), ocular response analyzer, Ocuton S, handheld applanation tonometer (HAT), rebound tonometer, transpalpebral tonometer, and Tono-Pen. The agreement (95% limits) seemed to vary across tonometers: 0.2 mmHg (−3.8 to 4.3 mmHg) for the NCT to 2.7 mmHg (−4.1 to 9.6 mmHg) for the Ocuton S. The estimated proportion within 2 mmHg of the GAT ranged from 33% (Ocuton S) to 66% and 59% (NCT and HAT, respectively). Substantial inter- and intraobserver variability were observed for all tonometers. Conclusions: The NCT and HAT seem to achieve a measurement closest to the GAT. However, there was substantial variability in measurements both within and between studies. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prevalence and Risk Factors for Myopic Retinopathy in a Japanese Population: The Hisayama Study - Corrected Proof

2012-05-11

Purpose: To examine the prevalence of myopic retinopathy and its risk factors in a general Japanese population. Design: Population-based, cross-sectional study. Participants: In 2005, a total of 1969 Hisayama residents aged ≥40 years consented to participate in this study. Of these, 1892 subjects with adequate data were enrolled. Methods: Each participant underwent comprehensive physical and eye examinations that included measurements of refractive error, axial lengths, and color fundus photography. Myopic retinopathy was defined as the presence of diffuse chorioretinal atrophy, patchy chorioretinal atrophy, lacquer cracks, or macular atrophy. Main Outcome Measures: Prevalence of myopic retinopathy. Results: Thirty-three participants had myopic retinopathy and the prevalence was 1.7% (2.2% in women and 1.2% in men). The prevalence of myopic retinopathy increased significantly with advancing age. Diffuse chorioretinal atrophy, patchy chorioretinal atrophy, lacquer cracks, and macular atrophy were present in 1.7%, 0.4%, 0.2%, and 0.4% of subjects, respectively. In multivariate analysis, myopic retinopathy was significantly associated with older age (per 1 year: odds ratio [OR], 1.12; 95% confidence interval [CI], 1.07–1.18), female gender (OR, 3.29; 95% CI, 1.09–9.92), and longer axial length (per 1 mm: OR, 4.20; 95% CI, 3.03–5.83). Conclusions: The prevalence of myopic retinopathy was 1.7% in a general Japanese population. Older age, female gender, and longer axial length were significant risk factors for myopic retinopathy. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Visual Acuity, Optical Components, and Macular Abnormalities in Patients with a History of Retinopathy of Prematurity - Corrected Proof

2012-05-11

Purpose: To examine the optical components and spectral-domain optical coherence tomography (OCT) findings in children with a history of retinopathy of prematurity (ROP) and to identify any associations between the OCT findings and the visual acuities of the patients. Design: Prospective, case-controlled study. Participants and Controls: Children who were between 6 and 14 years of age were divided into the following 4 groups: Patients with a history of threshold ROP who had been treated using laser therapy or cryotherapy (group 1), patients with regressed ROP who had not received any treatment (group 2), patients who were born prematurely but who had no history of ROP (group 3), and normal full-term children (group 4). The posterior poles of the eyes of all of the patients seemed to be normal. Methods: Visual acuities, optical components, and macular thicknesses were measured in 4 groups of patients, and comparisons between the groups were made. Macular thicknesses were measured using OCT. Main Outcome Measures: Visual acuity (VA), optical components, and OCT findings. Results: We enrolled 133 patients in the study. Patients in group 1 had significantly thicker foveas than the other patients, as demonstrated by OCT, and this finding was negatively correlated with gestational age. The incidence of abnormal foveal contours among patients in group 1 was significantly higher than among the rest of the patients. Retention of the inner retinal layers was noted in group 1 patients; however, the structure of the outer retina remained intact. Greater degrees of myopic shift and astigmatism, steeper corneal curvatures, shallower anterior chamber depths, and thicker lenses were noted in previously treated ROP patients. These findings corresponded with poor VA and high refractive errors in group 1 patients. Conclusions: Patients with a history of threshold ROP are more likely to show abnormal foveal development and have a poorer visual prognosis than other patient groups despite a fundus with no macular dragging, disc dragging, or retinal detachment. A steeper corneal curvature, shallower anterior chamber, and greater lens thickness are the main changes in the optical components in these patients. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration: One-Year Findings from the IVAN Randomized Trial - Corrected Proof

2012-05-11

Purpose: To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). Design: Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). Participants: People >50 years of age with untreated nAMD in the study eye who read ≥25 letters on the Early Treatment Diabetic Retinopathy Study chart. Methods: We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. Main Outcome Measures: The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. Results: Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab −1.99 letters, 95% confidence interval [CI], −4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous −0.35 letters; 95% CI, −2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001). Conclusions: The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety. Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references.

An Investigation of Enzymatic Detergents as a Potential Cause of Toxic Anterior Segment Syndrome - Corrected Proof

2012-05-11

Objective: To investigate whether enzymatic detergents used in cleaning ophthalmic surgical instruments can cause toxic anterior segment syndrome (TASS)–like responses in a rabbit model. Design: Randomized, investigator-masked, controlled experimental animal study. Participants: Thirty-five New Zealand white rabbits. Methods: The rabbit eyes were randomized into 7 treatment groups to receive intracameral injection of 1 of 3 different doses of Medline Dual Detergent or Enzol Detergent, or sterile limulus amoebocyte lysate reagent Water as a control. The eyes were evaluated for anterior segment inflammation at baseline and at 1, 3, 6, 24, 48, and 72 hours after treatment by slit-lamp biomicroscopy. Main Outcome Measures: Anterior chamber (AC) inflammation, including cells, flare, fibrin, and iris injection; time course of inflammation; and residual detergent levels in luminated instruments. Results: Moderate to marked injection of the iris vessels was seen as early as 1 hour after treatment with the enzymatic detergents in 41 of 60 eyes, with the response being more severe in the Enzol Detergent-exposed eyes. Severe iris hemorrhages were accompanied by blood in the AC in 13 eyes, which usually persisted through 72 hours, with an associated increase in AC cell and flare. Corneal haze was present in 52 of 56 eyes 1 hour after treatment, but was mild and resolved within 24 hours in all but the Enzol 4.5%–exposed eyes. Median AC cell and flare peaked at 6 hours and resolved by 48 hours. Conclusions: Enzymatic detergents caused a severe but unusual response from the iris when injected intracamerally into rabbit eyes. This response has not been reported in humans with TASS. The time course of inflammation was faster (peak at 6 hours) and resolved more quickly (within 48 hours) than TASS. Simulated cleaning and extraction studies indicate that the level of residual detergent to which a patient could be exposed is significantly less than the lowest dose used in this study. Because that low dose caused no significant observations other than injection of the iris vessels, these results do not support residual enzymatic detergents on surgical instruments as a cause for TASS. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Optic Disc Imaging with Spectral-Domain Optical Coherence Tomography: Variability and Agreement Study with Heidelberg Retinal Tomograph - Corrected Proof

2012-05-09

Objective: To evaluate the agreement of optic disc measurements obtained with the Cirrus high-density optical coherence tomography (HD-OCT) and the Heidelberg retina tomograph (HRT) and compare the intervisit, test–retest variability between the instruments. Design: Prospective, cross-sectional study. Participants: Two hundred seven subjects (109 glaucoma and 98 normal subjects). Methods: One eye from each individual was selected randomly for optic disc imaging by the Cirrus HD-OCT and the HRT. Areas of the optic disc and the cup, cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio were compared between the instruments. The OCT measurements were corrected for ocular magnification using the Littman's formula. The measurement agreement was evaluated with the Bland–Altman plots. The intervisit test–retest variability was examined in 17 randomly selected glaucoma patients who underwent optic disc imaging weekly for 8 consecutive weeks. The intraclass correlation coefficients (ICC) and the reproducibility coefficients of the optic disc parameters were computed. Main Outcome Measures: Measurement agreement, reproducibility coefficients, and ICCs of optic disc parameters. Results: The OCT measured smaller optic disc and rim areas and greater cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio than the HRT did (all with P<0.001). There were proportional biases in the Bland–Altman plots between OCT and HRT optic disc measurements except for rim area and cup-to-disc area ratio. The 95% limits of agreement of rim area ranged between –0.28 and 0.88 mm2 before, and between –0.22 and 0.92 mm2 after correction for ocular magnification. Both OCT and HRT showed high test–retest reproducibility with ICCs ≥0.921. Although the reproducibility coefficient of OCT rim area (0.093 mm2; 95% confidence interval [CI], 0.081–0.105 mm2) was significantly smaller than that of the HRT (0.186 mm2; 95% CI, 0.163–0.210 mm2; P = .018), there were no differences in the ICCs between the instruments. Conclusions: Optic disc assessment by spectral-domain OCT and confocal scanning laser ophthalmoscopy demonstrates poor agreement but similarly low test–retest variability. The source of their disagreement and its effects on the detection of progression require further study. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

A Homozygous Frameshift Mutation in LRAT Causes Retinitis Punctata Albescens - Corrected Proof

2012-05-03

Purpose: To determine the genetic defect and to describe the clinical characteristics in patients with retinitis punctata albescens (RPA) and fundus albipunctatus (FAP). Design: Case series/observational study. Participants: We included 13 patients affected by RPA or FAP. Methods: Thirteen patients were collected from 8 families with a retinal dystrophy characterized by tiny, yellow-white dots on funduscopy, typical for FAP or RPA. All patients underwent full ophthalmologic examinations, including visual field assessment. Fundus photography, and electroretinography were performed in 12 patients, and optical coherence tomography and fundus autofluorescence were performed in 4 patients. DNA samples of all patients were screened for mutations in RLBP1 and for mutations in RDH5 in patients who did not carry mutations in RLBP1. DNA samples of 2 sibling pairs of nonconsanguineous families who carried mutations neither in RLBP1 nor in RDH5 were analyzed by genome-wide homozygosity mapping. Sequence analysis was performed of LRAT, a candidate gene in a shared homozygous region. Main Outcome Measures: We assessed DNA sequence variants, best-corrected visual acuity, fundus appearance, visual field measurements, electroretinogram responses, optical coherence tomography, and fundus autofluorescence. Results: A homozygous frameshift mutation was identified in LRAT in 4 patients with RPA. Mutations in RLBP1 were identified in 7 patients with RPA and in 1 patient with FAP and cone dystrophy. One patient had compound heterozygous mutations in RDH5 and suffered from FAP with mild maculopathy. Conclusions: A genetic defect was identified in LRAT as a novel cause of RPA. LRAT is therefore the fourth gene involved in the visual cycle that may cause a white-dot retinopathy. We also revealed that mutations in RLBP1 may lead to FAP with cone dystrophy. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Subfoveal Choroidal Thickness after Ranibizumab Therapy for Neovascular Age-related Macular Degeneration: 12-Month Results - Corrected Proof

Taizo Yamazaki, Hideki Koizumi, Tetsuya Yamagishi, Shigeru Kinoshita — 2012-05-02

Purpose: To investigate the changes in subfoveal choroidal thickness after intravitreal injections of ranibizumab (IVRs) for neovascular age-related macular degeneration (AMD). Design: Prospective, consecutive, interventional case series. Participants: Eighty eyes (40 affected eyes with neovascular AMD and 40 unaffected fellow eyes) of 40 patients. Methods: Forty eyes with neovascular AMD were treated with 0.5-mg IVRs monthly for 3 months and received additional IVRs as needed over the following 9-month period. Subfoveal choroidal thickness in all 80 eyes was measured by use of enhanced depth imaging optical coherence tomography images before and after starting the IVRs. Main Outcome Measures: Changes in subfoveal choroidal thickness after treatment by IVRs over a 12-month period. Results: Twenty-three eyes (57.5%) were diagnosed with typical neovascular AMD, 16 eyes (40%) were diagnosed with polypoidal choroidal vasculopathy, and 1 eye (2.5%) was diagnosed with retinal angiomatous proliferation. Fifteen eyes (38%) had received some previous treatments for the neovascular lesion before undergoing the IVRs. The mean best-corrected visual acuity of the affected eyes was improved from 0.54 logarithm of the minimum angle of resolution units at baseline to 0.42 at 12 months (P = 0.020). The mean subfoveal choroidal thickness in the affected eyes decreased from 244±62 μm at baseline to 234±66 μm at 1 month (P = 0.013), 226±68 μm at 3 months (P<0.001), 229±67 μm at 6 months (P = 0.002), and 226±66 μm at 12 months (P = 0.002; the change ratio, 93%), whereas that in the unaffected eyes changed from 237±80 μm at baseline to 238±83 μm at 12 months (P = 0.78). In the affected eyes, the change ratio of subfoveal choroidal thickness at 12 months was not correlated with the number of IVRs (mean, 5.8±2.9). Subfoveal choroidal thickness demonstrated a similar trend toward decreasing during the following period independent of the subtypes of neovascular AMD or the treatment histories. Conclusions: Subfoveal choroidal thickness decreased after IVRs in eyes with neovascular AMD. Intravitreal injections of ranibizumab may provide a pharmacologic effect not only on the neovascular lesion but also on the underlying choroid. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Pupil Ruff Atrophy Correlations with Intraocular Pressure and Cup-to-Disc Ratio in a Glaucoma Clinic Population - Corrected Proof

Ghee S. Ang, Tracey Wong, Simon Nicholas, Anthony P. Wells — 2012-05-02

Purpose: To evaluate the correlations between pupil ruff changes and associated gonioscopy findings with intraocular pressure (IOP) and cup-to-disc ratio (CDR). Design: Prospective, observational, comparative study. Participants: A total of 103 patients from a glaucoma clinic population. Patients with pseudoexfoliation, previous intraocular surgery, and IOP-lowering medication were excluded. Methods: Pupillary ruff and associated gonioscopy findings were graded from photographs based on the pupil ruff atrophy (PRA) grading system. Parameters evaluated include pupillary ruff absence and abnormality, pupil edge pigment, and trabecular meshwork pigment. Inter-eye differences were determined and analyzed for correlations with inter-eye differences in IOP and CDR based on Heidelberg Retinal Tomograph II imaging (Heidelberg Engineering, Dossenheim, Germany). Main Outcome Measures: Correlations between inter-eye PRA grading differences and inter-eye IOP and CDR differences. Results: A total of 103 patients were included, with a mean age of 64 years. The average amount of abnormal and missing ruff was 9.5 and 5 clock hours, respectively. Inter-eye IOP asymmetry was significantly associated with asymmetry of amount of abnormal ruff (P = 0.034) and amount of missing ruff (P = 0.022). Inter-eye CDR asymmetry was significantly associated with asymmetry of the amount of missing ruff (P = 0.001) and trabecular meshwork pigmentation (P = 0.006). The eye with the most pupillary ruff loss was 25% more likely to have the greater CDR. Conclusions: Asymmetric pupillary ruff changes were associated with asymmetry in both IOP and CDR. However, the clinical significance of this finding requires further evaluation. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Risk Factors for Conversion to Neovascular Age-related Macular Degeneration Based on Longitudinal Morphologic and Visual Acuity Data - Corrected Proof

Thomas R. Friberg, Richard A. Bilonick, Peter M. Brennen — 2012-05-02

Purpose: To use longitudinal quantitative morphologic and visual acuity (VA) data to investigate the risk of choroidal neovascularization (CNV) event occurrence in eyes with dry age-related macular degeneration (AMD). Design: Prospective observational study. Participants: A total of 513 participants (844 eyes) followed longitudinally in one center enrolled in the Age-Related Eye Disease Study (AREDS) or the Prophylactic Treatment of AMD Study (PTAMD). Methods: We assessed images of previously obtained fundus photographs for the presence of macular pigmentation, drusen area, and drusen distribution (number and size), and fellow eye CNV status at baseline. Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) at each visit and the age of each subject were obtained. We used a longitudinal logistic mixed-effects model with random intercepts fitted to event occurrences to assess risk on a per eye basis. Main Outcome Measures: Odds ratios for CNV event. Results: Thirty-one subjects (6.0%) had events. Only VA changes over time and follow-up interval showed statistically significant effects. Several statistical models that included VA at the previous visit were used. In 2 models, 3 categories of VA were used: ≤75 letters, >75 and ≤85 letters, and >85 letters. Two categories were used for follow-up: ≤3 years versus >3 years or ≤1 year versus >1 year. In the first model with categorization at 3 years, a decrease in acuity from the >85 letter category to ≤75 letters increased the odds of CNV by 16.9 times (P = 0.022). In the model with categorization at 1 year, a decrease in acuity from the >85-letter category to ≤75 letters increased the odds of CNV by 21.4 times (P = 0.0175). Differences between the follow-up intervals were significant (P = 0.043) and indicated a more than 7-fold increase in the odds. Changes in morphologic features of the macula did not show significant effects. Conclusions: A decrease in VA to ≤75 ETDRS letters in an eye with an initial ETDRS baseline acuity of >85 letters increases the likelihood of CNV by approximately 20-fold. This likelihood also increases with aging. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration: Two-Year Results - Corrected Proof

2012-05-02

Objective: To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment. Design: Multicenter, randomized clinical trial. Participants: Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial. Interventions: At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. Main Outcome Measures: Mean change in visual acuity. Results: Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, −1.4 letters; 95% confidence interval [CI], −3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, −2.4 letters; 95% CI, −4.8 to −0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (−2.2 letters; P = 0.03) and a lower proportion without fluid (−19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07−1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF). Conclusions: Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Indications, Outcomes, and Risk Factors for Failure in Tectonic Keratoplasty - Corrected Proof

Marcus Ang, Jodhbir S. Mehta, Chelvin C.A. Sng, Hla Myint Htoon, Donald T.H. Tan — 2012-04-30

Purpose: Outcomes of corneal transplantation for tectonic indications and risk factors for (tectonic and physiologic) graft failure. Design: Retrospective cohort study. Participants: Consecutive patients who underwent keratoplasty for tectonic indications at the Singapore National Eye Centre (SNEC) between January 1, 1991, and December 1, 2009. Methods: Clinical data and donor and recipient characteristics were recorded and analyzed from subjects in the prospective Singapore Corneal Transplant Study. Main Outcome Measures: (1) Tectonic (anatomic) failure defined as recurrence of corneal melt threatening tectonic integrity and requiring additional corneal grafting within 3 months of the primary procedure. (2) Physiologic failure defined as irreversible change in graft clarity preventing recovery in useful vision in grafts initially clear 2 weeks postoperatively. Results: The mean age of the study cohort (n = 362, 193 male and 169 female subjects) was 51.5±20.2 years, with a mean follow-up of 25.8±18.7 months. Patients underwent penetrating keratoplasty (PK) (n = 142, 39.2%), anterior lamellar keratoplasty (ALK) (n = 127, 35.1%), or a peripheral corneoscleral patch graft (n = 93, 25.7%) most commonly for inflammation (n = 68, 18.8%), trauma (n = 66, 18.2%), or infection (n = 66, 18.2%). Risk factors for tectonic failure (18/362 eyes, 5.0%) were severe lid disease (odds ratio [OR], 6.1; 95% confidence interval [CI], 1.7–22.1; P = 0.006), central ALK (OR, 7.5; 95% CI, 1.8–32.4; P = 0.007), and peripheral grafts (OR, 5.7; 95% CI, 1.1–28.3; P = 0.035). Among anatomically successful central grafts (n = 223), the mean physiological graft survival was 96 months (95% CI, 83–110); Kaplan–Meier probabilities for survival at 10 years were 66.8% for ALK and 44.2% for PK. Active corneal inflammation (hazard ratio [HR], 2.5; 95% CI, 1.4–4.4; P = 0.003) and larger donor and recipient graft sizes of ≥9 mm (HR, 17.9; 95% CI, 2.3–140.3; P = 0.006) were risk factors for physiologic graft failure in anatomically successful eyes with central tectonic grafts. Conclusions: Patients with lid disease, central ALK, and peripheral grafts were at higher risk of anatomic failure. For anatomically successful cases with central tectonic grafts, active corneal inflammation and donor size ≥9 mm were risk factors for physiologic failure. In these cases, our results suggest that ALK had better physiologic graft survival outcomes than PK. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Clinical Manifestations of Human Immunodeficiency Virus-Induced Uveitis - Corrected Proof

Paradee Kunavisarut, Wasna Sirirungsi, Kessara Pathanapitoon, Aniki Rothova — 2012-04-30

Purpose: To describe the clinical manifestations of patients with human immunodeficiency virus (HIV)-induced uveitis in Thailand. Design: Prospective cohort study of 6 patients with HIV-induced uveitis. Participants: Six patients (8 eyes) with HIV-induced uveitis who had an extremely high intraocular: plasma HIV-1 RNA ratio. Methods: The clinical manifestations and laboratory findings are reported of 6 consecutive patients with HIV-induced uveitis who had an extremely high intraocular-to-plasma HIV-1 RNA ratio and were diagnosed between July 2009 and May 2011. Main Outcome Measures: Clinical manifestations and laboratory findings. Results: Human immunodeficiency virus-induced uveitis was diagnosed in 4 men and 2 women with an average age of 41 years at presentation. None of the patients were receiving highly active anti-retroviral therapy (HAART) or had clinical or laboratory evidence, or both, of opportunistic infections. The mean plasma load was 218 688 copies/ml (median, 137 500 copies/ml; range, 24 900–540 000 copies/ml), and the mean intraocular HIV load was 20 937 755 copies/ml (median, 7 499 000 copies/ml; range, 2 460 000–89 800 000 copies/ml). The average CD4 cell count was 192 cells/μl (median, 248 cells/μl; range, 5–342 cells/μl). All the patients had decreased vision, and none had conjunctival hyperemia. The anatomic location of uveitis was anterior in all patients, and associated vitreitis was present in 4 patients; none exhibited retinal lesions or scars. Anterior segment inflammation and keratic precipitates were observed in all patients, and none responded to topical corticosteroid therapy. After the administration of HAART, the intraocular inflammation disappeared entirely within several weeks in all of the patients and the intraocular and plasma HIV loads decreased. Conclusions: Human immunodeficiency virus-induced uveitis should be suspected in HAART-naïve, HIV-positive patients or in those in whom this treatment fails and who have anterior uveitis without any retinal lesions and exhibit no response to topical corticosteroids. The concurrent determination of HIV load in the intraocular fluids and plasma may clarify the cause of HIV-associated uveitis.

Detection of Clinically Significant Retinopathy of Prematurity Using Wide-angle Digital Retinal Photography: A Report by the American Academy of Ophthalmology - Corrected Proof

2012-04-27

Objective: To evaluate the accuracy of detecting clinically significant retinopathy of prematurity (ROP) using wide-angle digital retinal photography. Methods: Literature searches of PubMed and the Cochrane Library databases were conducted last on December 7, 2010, and yielded 414 unique citations. The authors assessed these 414 citations and marked 82 that potentially met the inclusion criteria. These 82 studies were reviewed in full text; 28 studies met inclusion criteria. The authors extracted from these studies information about study design, interventions, outcomes, and study quality. After data abstraction, 18 were excluded for study deficiencies or because they were superseded by a more recent publication. The methodologist reviewed the remaining 10 studies and assigned ratings of evidence quality; 7 studies were rated level I evidence and 3 studies were rated level III evidence. Results: There is level I evidence from ≥5 studies demonstrating that digital retinal photography has high accuracy for detection of clinically significant ROP. Level III studies have reported high accuracy, without any detectable complications, from real-world operational programs intended to detect clinically significant ROP through remote site interpretation of wide-angle retinal photographs. Conclusions: Wide-angle digital retinal photography has the potential to complement standard ROP care. It may provide advantages through objective documentation of clinical examination findings, improved recognition of disease progression by comparing previous photographs, and the creation of image libraries for education and research. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Comparing Outcome Criteria Performance in Adult Strabismus Surgery - Corrected Proof

Sarah R. Hatt, David A. Leske, Laura Liebermann, Jonathan M. Holmes — 2012-04-27

Purpose: To evaluate the performance of motor, diplopia, and health-related quality of life (HRQOL) criteria when analyzing outcomes of adult strabismus surgery. Design: Cohort study. Participants: We studied 159 adults undergoing 171 strabismus surgeries. Methods: All patients underwent clinical assessment preoperatively and 6 weeks postoperatively, including completion of Adult Strabismus-20 HRQOL questionnaires. Preoperatively, strabismus was classified as either diplopic (n = 117), nondiplopic (n = 38), or atypical diplopic (n = 16). To assess performance of motor, diplopia, and HRQOL criteria, success was defined a priori and applied separately and in combinations. For success: (1) motor criteria, <10 prism diopters by simultaneous prism cover test; (2) diplopia criteria, none or only rare in primary distance and for reading; (3) HRQOL criteria, exceeding previously reported 95% limits of agreement (LOA). Main Outcome Measures: Surgical success rate when applying motor, diplopia, and HRQOL criteria alone and in combinations. Results: Overall, success rates were 90% for motor criteria, 74% for diplopia criteria, and 60% for HRQOL criteria. Combining criteria, the highest success rate was for motor plus diplopia criteria (67%) and the lowest success rate was when combining motor, diplopia, and HRQOL criteria (50%). Conclusions: Applying motor criteria alone yields the highest success rates when evaluating outcomes in adult strabismus surgery, but motor criteria do not fully represent the patient's postoperative status. Combining diplopia criteria with motor criteria provides a more clinically relevant standard for judging the success of adult strabismus surgery. For HRQOL criteria, exceeding 95% LOA at 6 weeks postoperatively seems to be a difficult hurdle to clear for some individual patients, and evaluating change in HRQOL score may be more useful in cohort studies. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

The Development of a Decision Analytic Model of Changes in Mean Deviation in People with Glaucoma: The COA Model - Corrected Proof

2012-04-26

Purpose: To create and validate a statistical model predicting progression of primary open-angle glaucoma (POAG) assessed by loss of visual field as measured in mean deviation (MD) using 3 landmark studies of glaucoma progression and treatment. Design: A Markov decision analytic model using patient level data described longitudinal MD changes over 7 years. Participants: Patient-level data from the Collaborative Initial Glaucoma Treatment Study (n = 607), the Ocular Hypertension Treatment Study (OHTS; n = 148; only those who developed POAG in the first 5 years of OHTS) and Advanced Glaucoma Intervention Study (n = 591), the COA model. Methods: We developed a Markov model with transition matrices stratified by current MD, age, race, and intraocular pressure categories and used a microsimulation approach to estimate change in MD over 7 years. Internal validation compared model prediction for 7 years to actual MD for COA participants. External validation used a cohort of glaucoma patients drawn from university clinical practices. Main Outcome Measures: Change in visual field as measured in MD in decibels (dB). Results: Regressing the actual MD against the predicted produced an R2 of 0.68 for the right eye and 0.63 for the left. The model predicted ending MD for right eyes of 65% of participants and for 63% of left eyes within 3 dB of actual results at 7 years. In external validation the model had an R2 of 0.79 in the right eye and 0.77 in the left at 5 years. Conclusions: The COA model is a validated tool for clinicians, patients, and health policy makers seeking to understand longitudinal changes in MD in people with glaucoma. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Validity of Self-reported Eye Disease and Treatment in a Population-based Study: The Los Angeles Latino Eye Study - Corrected Proof

2012-04-26

Purpose: To examine the validity of self-reported eye disease, including cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), and self-reported surgical treatment for cataract and DR in the Los Angeles Latino Eye Study (LALES). Design: Population-based, cross-sectional study. Participants: A total of 6357 Latinos aged 40+ years from the LALES. Methods: Participants underwent a detailed interview, including survey questions about ocular health, diagnoses, and timing of last eye examination, and a standardized clinical examination. Self-report was compared with examination to determine sensitivity and specificity by length of time since last eye examination. Stepwise logistic regression was used to determine factors associated with inaccurate self-report. Main Outcome Measures: Sensitivity and specificity were calculated for 4 self-reported eye diseases (cataract, AMD, glaucoma, and DR) and for surgical treatment of cataract and DR. Odds ratios (ORs) were determined for factors associated with inaccurate self-report underestimating eye disease and treatment. Results: For each disease, sensitivity and specificity in those who reported their last eye examination as <1 year ago were 36.8% and 92.5% for cataract, 37.7% and 96.3% for glaucoma, 5.1% and 98.9% for AMD, and 25.7% and 94.2% for DR, respectively. Self-report was less accurate with increasing time since last eye examination. Inaccurate self-report was independently associated with better visual acuity (OR, 2.4), <2 comorbidities (OR, 1.7), last eye examination/visit 1 to 5 years ago and ≥5 years ago (OR, 2.3 and 4.9, respectively), and less education (OR, 1.3 for 7–12 years and 1.7 for <7 years). Of 88 participants surgically treated for cataract who reported an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 90.9% and 99.9%, respectively. Of the 31 participants treated for DR (laser/surgery) and reporting an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 19.4% and 99.6%, respectively. Conclusions: Among Latinos, self-reporting of eye disease and surgical history provides a significant underestimate of the disease burden. This may lead to significant misclassification in vision research if self-report alone is used to identify persons with eye disease. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

One-Year Outcomes of the DA VINCI Study of VEGF Trap-Eye in Eyes with Diabetic Macular Edema - Corrected Proof

2012-04-25

Purpose: To compare different doses and dosing regimens of Vascular Endothelial Growth Factor (VEGF) Trap-Eye with laser photocoagulation in eyes with diabetic macular edema (DME). Design: Randomized, double-masked, multicenter, phase 2 clinical trial. Participants: Diabetic patients (n = 221) with center-involved DME. Methods: Participants were assigned randomly to 1 of 5 treatment regimens: VEGF Trap-Eye 0.5 mg every 4 weeks (0.5q4); 2 mg every 4 weeks (2q4); 2 mg every 8 weeks after 3 initial monthly doses (2q8); or 2 mg dosing as needed after 3 initial monthly doses (2PRN), or macular laser photocoagulation. Main Outcome Measures: The change in best-corrected visual acuity (BCVA) at 24 weeks (the primary end point) and at 52 weeks, proportion of eyes that gained 15 letters or more in Early Treatment of Diabetic Retinopathy Study (ETDRS) BCVA, and mean changes in central retinal thickness (CRT) from baseline. Results: As previously reported, mean improvements in BCVA in the VEGF Trap-Eye groups at week 24 were 8.6, 11.4, 8.5, and 10.3 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus 2.5 letters for the laser group (P ≤ 0.0085 versus laser). Mean improvements in BCVA in the VEGF Trap-Eye groups at week 52 were 11.0, 13.1, 9.7, and 12.0 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus −1.3 letters for the laser group (P ≤ 0.0001 versus laser). Proportions of eyes with gains in BCVA of 15 or more ETDRS letters at week 52 in the VEGF Trap-Eye groups were 40.9%, 45.5%, 23.8%, and 42.2% versus 11.4% for laser (P = 0.0031, P = 0.0007, P = 0.1608, and P = 0.0016, respectively, versus laser). Mean reductions in CRT in the VEGF Trap-Eye groups at week 52 were −165.4 μm, −227.4 μm, −187.8 μm, and −180.3 μm versus −58.4 μm for laser (P < 0.0001 versus laser). Vascular Endothelial Growth Factor Trap-Eye generally was well tolerated. The most frequent ocular adverse events with VEGF Trap-Eye were conjunctival hemorrhage, eye pain, ocular hyperemia, and increased intraocular pressure, whereas common systemic adverse events included hypertension, nausea, and congestive heart failure. Conclusions: Significant gains in BCVA from baseline achieved at week 24 were maintained or improved at week 52 in all VEGF Trap-Eye groups. Vascular Endothelial Growth Factor Trap-Eye warrants further investigation for the treatment of DME. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Tofacitinib (CP-690,550), a Janus Kinase Inhibitor for Dry Eye Disease: Results from a Phase 1/2 Trial - Corrected Proof

2012-04-23

Objective: To evaluate safety and efficacy of topical ophthalmic tofacitinib (CP-690,550), a novel Janus kinase inhibitor, in treating dry eye disease (DED). Design: A phase 1/2 prospective, randomized, double-masked, multicenter, vehicle- and comparator-controlled trial (NCT00784719). Participants: Patients (n = 327) 18 years of age and older with a DED diagnosis for 6 months or more. Methods: Tofacitinib (0.0003% twice daily, n = 46; 0.001% in both eyes twice daily, n = 47; 0.003% twice daily, n = 48; 0.005% twice daily, n = 48; 0.005% once daily, n = 44) results were compared with those of groups receiving active treatment cyclosporine ophthalmic emulsion 0.05% twice daily (n = 47) and vehicle twice daily (n = 47). Safety and efficacy evaluations were performed at baseline and throughout the 8-week study. Main Outcome Measures: Schirmer wetting, corneal staining, tear film break-up time, conjunctival staining, Ocular Comfort Index (OCI), and Ocular Surface Disease Index (OSDI). Results: All tofacitinib doses were well tolerated, exhibiting better patient-reported ocular tolerability than cyclosporine. For the proportion of patients achieving 10 mm or more Schirmer wetting (without anesthesia) at week 8 (primary end point), greater response rates were observed in the tofacitinib 0.001% twice daily (27.3%), 0.005% twice daily (25.5%), and 0.005% once daily (26.1%) groups versus vehicle (20.0%); however, the differences were not statistically significant. Mean increase in Schirmer wetting (without anesthesia) from baseline was statistically significant (P<0.2, 2-sided) for all tofacitinib doses (1.7–3.1 mm), cyclosporine (3.9 mm), and vehicle (1.4 mm). For corneal staining (total score), significant improvement (reduction) from baseline was observed for all tofacitinib doses (−0.9 to −1.9) and vehicle (−2.0), but not for cyclosporine. The proportion of patients with complete corneal clearing (CCC; 100%) at week 8 was greatest with tofacitinib 0.005% once daily (15.9%) versus vehicle (6.7%). Symptom scores (OCI, OSDI) at week 8 showed significant improvements from baseline for all tofacitinib groups, and tofacitinib demonstrated greater improvements than cyclosporine. The tofacitinib 0.005% once daily group showed significant improvements in both a sign (Schirmer wetting without anesthesia) and symptom (OSDI environmental triggers subscale) versus vehicle and also demonstrated the highest response rate for CCC (16.7%) at week 8. Conclusions: This phase 1/2 study of tofacitinib demonstrated a trend for improving both signs and symptoms of dry eye. All doses of tofacitinib exhibited a reasonable safety profile and were well tolerated by patients with DED. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Risk Factors for Moderate and Severe Microbial Keratitis in Daily Wear Contact Lens Users - Corrected Proof

2012-04-23

Objective: To establish risk factors for moderate and severe microbial keratitis among daily contact lens (CL) wearers in Australia. Design: A prospective, 12-month, population-based, case-control study. Participants: New cases of moderate and severe microbial keratitis in daily wear CL users presenting in Australia over a 12-month period were identified through surveillance of all ophthalmic practitioners. Case detection was augmented by record audits at major ophthalmic centers. Controls were users of daily wear CLs in the community identified using a national telephone survey. Testing: Cases and controls were interviewed by telephone to determine subject demographics and CL wear history. Multiple binary logistic regression was used to determine independent risk factors and univariate population attributable risk percentage (PAR%) was estimated for each risk factor. Main Outcome Measures: Independent risk factors, relative risk (with 95% confidence intervals [CIs]), and PAR%. Results: There were 90 eligible moderate and severe cases related to daily wear of CLs reported during the study period. We identified 1090 community controls using daily wear CLs. Independent risk factors for moderate and severe keratitis while adjusting for age, gender, and lens material type included poor storage case hygiene 6.4× (95% CI, 1.9–21.8; PAR, 49%), infrequent storage case replacement 5.4× (95% CI, 1.5–18.9; PAR, 27%), solution type 7.2× (95% CI, 2.3–22.5; PAR, 35%), occasional overnight lens use (<1 night per week) 6.5× (95% CI, 1.3–31.7; PAR, 23%), high socioeconomic status 4.1× (95% CI, 1.2–14.4; PAR, 31%), and smoking 3.7× (95% CI, 1.1–12.8; PAR, 31%). Conclusions: Moderate and severe microbial keratitis associated with daily use of CLs was independently associated with factors likely to cause contamination of CL storage cases (frequency of storage case replacement, hygiene, and solution type). Other factors included occasional overnight use of CLs, smoking, and socioeconomic class. Disease load may be considerably reduced by attention to modifiable risk factors related to CL storage case practice. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Role of Vascular Endothelial Growth Factor Polymorphisms in the Treatment Success in Patients with Wet Age-related Macular Degeneration - Corrected Proof

2012-04-23

Purpose: Along with environmental risk factors such as smoking, hypertension, and atherosclerosis, genetic susceptibility is a primary contributor to the development and progression of exudative age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a central angiogenic regulator and there has been general agreement now that it is an important trigger for the progression of exudative AMD. In the present study, we tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with exudative AMD. Design: Prospective cohort study. Participants: We included 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally administered bevacizumab in this trial. Methods: All patients were aged >50 years and had angiographically verified exudative AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs833061, rs699947, rs3024997, and rs1005230. At each follow-up visit, visual acuity was reassessed and an ophthalmic examination was carried out. Visual acuity outcome, number of retreatments, and overall time of treatment were analyzed in dependence of the VEGF polymorphisms. Main Outcome Measures: Mean change in visual acuity at the end of the treatment period. Results: The included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment period of 42 to 1182 days. In univariate analysis only the G/G genotypes of rs3024997 and rs2010963 compared with all other 5 single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a significant correlation. Conclusions: The current study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Glaucoma Risk Alleles at CDKN2B-AS1 Are Associated with Lower Intraocular Pressure, Normal-Tension Glaucoma, and Advanced Glaucoma - Corrected Proof

2012-04-23

Purpose: Genetic variation at the 9p21 locus encompassing the CDKN2B-AS1, CDKN2A, and CDKN2B genes has been associated with primary open-angle glaucoma (POAG) in several independent studies. This study aimed to dissect the association further and to determine genotype–phenotype correlations between genetic variation at this locus and a range of glaucoma-related traits in a large cohort of POAG patients. Design: Comparative case series and case-control study. Participants: One thousand four hundred thirty-two POAG patients and 595 unaffected controls recruited from 2 population-based and 2 cross-sectional studies. Methods: Each patient was genotyped at 9 single nucleotide polymorphisms (SNPs) previously associated with POAG at the 9p21 locus. Each SNP was assessed for association with each outcome measure using linear regression under an additive genetic model. Associated traits were explored further including adjustment for relevant covariates. Highest recorded intraocular pressure (IOP) also was analyzed both with and without correction for central corneal thickness (CCT) and was dichotomized into high-tension glaucoma and normal-tension glaucoma (NTG). Main Outcome Measures: Intraocular pressure and vertical cup-to-disc ratio (VCDR). Results: Glaucoma risk alleles at 9p21, particularly, rs7049105 and rs10120688, were associated with the presence of both NTG and advanced POAG. The SNP rs10120688 was associated with greater VCDR after adjustment for covariates (P = 0.003; β = 0.016; standard error, 0.006). In addition, multiple SNPs in the region were associated with reduced IOP, before and after adjustment for CCT. The SNP most significantly associated with IOP was also rs10120688 (P = 0.001; β = −2.135; standard error, 0.634) after adjustment for covariates under an additive model. In a comparison of high-tension versus low-tension glaucoma, this SNP was also the most significantly associated, particularly when IOP was corrected for CCT before classification of the type of glaucoma (P = 0.0009; odds ratio, 0.63; 95% confidence interval, 0.48–0.83). Conclusions: Patients with POAG carrying the glaucoma risk alleles at the 9p21 locus have larger VCDR and lower IOP than POAG patients without these alleles. Carriers of these alleles seem to be predisposed to POAG developing at lower IOP levels and exhibit stronger associations with NTG and advanced glaucoma phenotypes. This may be of relevance when setting target pressures in patients carrying these risk alleles. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Collaborative Ocular Oncology Group Report Number 1: Prospective Validation of a Multi-Gene Prognostic Assay in Uveal Melanoma - Corrected Proof

2012-04-23

Purpose: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). Design: Prospective, multicenter study. Participants: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. Testing: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. Main Outcome Measures: Patients were managed for their primary tumor and monitored for metastasis. Results: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10−14). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. Conclusions: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Treatment of Refractory Uveitis with Adalimumab: A Prospective Multicenter Study of 131 Patients - Corrected Proof

2012-04-23

Objective: To evaluate adalimumab therapy in refractory uveitis. Design: Prospective case series. Participants: A total of 131 patients with refractory uveitis and intolerance or failure to respond to prednisone and at least 1 other systemic immunosuppressive drug participated. Intervention: Patients received a 40 mg adalimumab subcutaneous injection every other week for 6 months. The associated immunosuppressants were tapered after administering 3 adalimumab injections (week 6). Main Outcome Measures: Degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), immunosuppression load (as defined by Nussenblatt et al), visual acuity (logarithm of the minimal angle of resolution [logMAR]), and macular thickness (optical coherence tomography). Results: There were 61 men and 70 women (mean age, 27.3 years). The most common causes were juvenile idiopathic arthritis in 39 patients, pars planitis in 16 patients, and Behçet's disease in 13 patients. Twenty-seven patients had uveitis of idiopathic origin. Inflammation in the anterior chamber was present in 82% of patients and in the vitreous cavity in 59% of patients. Anterior chamber inflammation and vitreous inflammation decreased significantly (P < 0.001) from a mean of 1.51 and 1.03 at baseline to 0.25 and 0.14, respectively, at 6 months. Macular thickness was 296 (102) μ at baseline versus 240 (36) μ at the 6-month visit (P < 0.001). Visual acuity improved by −0.3 logMAR in 32 of 150 eyes (21.3%) and worsened by +0.3 logMAR (−15 letters) in 5 eyes (3.3%). The dose of corticosteroids also decreased from 0.74 (3.50) to 0.20 (0.57) mg/kg/day (P < 0.001). Cystoid macular edema, which was present in 40 eyes at baseline, showed complete resolution in 28 eyes at 6 months. The mean suppression load decreased significantly (8.81 [5.05] vs 5.40 [4.43]; P < 0.001). Six months after the initiation of the study, 111 patients (85%) were able to reduce at least 50% of their baseline immunosuppression load. Only 9 patients (6.9%) had severe relapses during the 6 months of follow-up. Conclusions: Adalimumab seems to be well tolerated and helpful in decreasing inflammatory activity in refractory uveitis and may reduce steroid requirement. Further controlled studies of adalimumab for uveitis are warranted. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Assessment of Macular Choroidal Thickness by Optical Coherence Tomography and Angiographic Changes in Central Serous Chorioretinopathy - Corrected Proof

2012-04-23

Objective: To investigate the relationship between macular choroidal thickness measured by high-penetrating swept-source optical coherence tomography (SS-OCT) and angiographic findings in central serous chorioretinopathy (CSC). Design: Prospective cross-sectional case series. Participants and Controls: Thirty-four patients with CSC (44 eyes) and 17 volunteer subjects (17 normal eyes). Methods: All subjects underwent a comprehensive ophthalmologic and SS-OCT prototype examination. All patients with CSC also underwent simultaneous fluorescein angiography (FA) and indocyanine green angiography (IA). Mean regional choroidal thickness measurements on the Early Treatment Diabetic Retinopathy Study (ETDRS) layout and squared sector grids were obtained by 3-dimensional raster scanning using SS-OCT. Main Outcome Measures: Macular choroidal thickness and angiographic abnormalities. Results: Mean whole macular choroidal thickness in eyes with CSC (total, 329.3±83.0 μm; classic CSC, 326.9±83.1 μm; chronic CSC, 325.4±93.3 μm; and multifocal posterior pigment epitheliopathy, 359.0±15.5 μm) was greater than that in normal eyes (233.0±67.0 μm) (P < 0.001). In unilateral cases, mean whole macular choroidal thickness was greater in eyes with unilateral CSC than in unaffected fellow eyes (P=0.021). There was no significant difference in choroidal thickness between active eyes and resolved eyes in any of the ETDRS sectors. Mean choroidal thickness was greater in areas with leakage on FA than in areas without leakage (P=0.001). Mean choroidal thickness was greater in areas with choroidal vascular hyperpermeability and in areas with punctate hyperfluorescent spots on IA than in unaffected areas (P<0.001 for both). Conclusions: Increased choroidal thickness was observed in the whole macular area of eyes with any of the CSC subtypes. Choroidal thickness was related to leakage from the retinal pigment epithelium, choroidal vascular hyperpermeability, and punctate hyperfluorescent lesions. These findings provide evidence that CSC may be caused by focally increased hydrostatic pressure in the choroid. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Photographic Assessment of Baseline Fundus Morphologic Features in the Comparison of Age-Related Macular Degeneration Treatments Trials - Corrected Proof

2012-04-18

Objective: To describe the methods used for assessment of baseline fundus characteristics from color photography and fluorescein angiography (FA) in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and to describe the relationship between these characteristics and visual acuity. Design: Randomized, masked, multicenter trial. Participants: This investigation included 1185 participants of the CATT study. Methods: Baseline stereoscopic color fundus photographs and FAs of participants in the CATT study were assessed at a central fundus photograph reading center by masked readers. Replicate assessments of random samples of photographs were performed to assess intragrader and intergrader agreements. The association of the lesion characteristics with baseline visual acuity was assessed using analyses of variance and correlation coefficients. Main Outcome Measures: Intragrader and intergrader reproducibility, visual acuity, and lesion characteristics. Results: Intragrader and intergrader reproducibility showed agreements ranging from 75% to 100% and weighted κ values ranging from 0.48 to 1.0 for qualitative determinations. The intraclass correlation coefficients were 0.96 to 0.97 for quantitative measurements of choroidal neovascularization (CNV) area and total area of CNV lesion. The mean visual acuity varied by the type of pathologic features in the foveal center: 64.5 letters (standard error, 0.7 letters) for fluid only, 59.0 letters (standard error, 0.5 letters) for CNV, and 58.7 letters (standard error, 1.3 letters) for hemorrhage (P<0.001). Fibrotic or atrophic scar present in the lesion, but not under the center of the fovea, also was associated with a markedly reduced visual acuity of 48.4 letters (standard error, 2.2 letters; P<0.0001). Although total area of CNV lesion was correlated weakly with visual acuity when all participants were assessed (Spearman correlation coefficient, ρ = −0.16; P<0.001), the correlation was stronger within patients with predominantly classic lesions (ρ = −0.42; P<0.001). Conclusions: These results show that the methodology used for grading CATT fundus images has good reproducibility. As expected, larger total CNV lesion area and pathologic findings such as hemorrhage, fibrosis, and atrophy at baseline are associated with decreased visual acuity. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

International Results with the Boston Type I Keratoprosthesis - Corrected Proof

2012-04-18

Purpose: To determine the indications and outcomes of Boston type 1 keratoprosthesis (Massachusetts Eye and Ear Infirmary, Boston, MA) surgery performed outside of North America and to compare them with those obtained in the United States by the surgeon who trained the international surgeons. Design: Retrospective review of consecutive clinical case series. Participants: One hundred ninety-four patients (223 keratoprosthesis procedures performed in 205 eyes) who received Boston type 1 keratoprosthesis at 11 ophthalmology centers in Armenia, India, Indonesia, Nepal, Philippines, Russia, and Saudi Arabia between May 1, 2006, and July 1, 2011 (international series), and at the Jules Stein Eye Institute between May 1, 2004, and July 1, 2011 (University of California, Los Angeles [UCLA] series). Methods: Data were collected for each procedure regarding the preoperative characteristics of each eye, the surgical procedure(s) performed, and the postoperative outcomes. Statistical analysis was performed to identify significant differences between the international and UCLA series in terms of retention and complications. Main Outcome Measures: Interval visual acuities, keratoprosthesis retention, and significant postoperative complications. Results: In the international series, 113 Boston type I keratoprostheses were implanted in 107 eyes of 100 patients. The most common indication for surgery was corneal graft failure (n = 50; 44%) followed by chemical injury (n = 30; 27%). Although only 2% of eyes had a preoperative corrected distance visual acuity (CDVA) of 20/20 to 20/200, 70%, 68%, and 59% of eyes had a postoperative CDVA of 20/20 to 20/200 at 6 months, 1 year, and 2 years after surgery, respectively. Ninety-one of the 113 keratoprostheses implanted (80.5%) were retained at a mean follow-up of 14.2 months, for a retention failure rate of 22 per 134.6 eye-years (0.163/eye-year). The most common postoperative complications were retroprosthetic membrane formation (27%) and sterile corneal necrosis (18%). The only postoperative complication that was more common in the international series than in the UCLA series was infectious endophthalmitis, which developed in 9% of eyes. Conclusions: Boston keratoprosthesis is a viable means of managing repeat graft failure and ocular chemical injury outside of North America, with similar visual acuity outcomes, retention rates, and incidence rates of postoperative complications to those obtained by North American surgeons. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Fundus Autofluorescence in Polypoidal Choroidal Vasculopathy - Corrected Proof

Tetsuya Yamagishi, Hideki Koizumi, Taizo Yamazaki, Shigeru Kinoshita — 2012-04-18

Purpose: To investigate and compare the characteristics of fundus autofluorescence (FAF) in polypoidal choroidal vasculopathy (PCV) with those in typical neovascular age-related macular degeneration (AMD). Design: Retrospective, observational, consecutive case series. Participants: Ninety-two patients with PCV (92 affected eyes and 86 unaffected fellow eyes) and 31 patients with typical neovascular occult AMD with no classic choroidal neovascularization (31 affected eyes and 24 unaffected fellow eyes). Methods: All study eyes underwent FAF photography with a fundus camera–based system. The incidence and distribution of hypoautofluorescence, that is, the manifestation of retinal pigment epithelium (RPE) damages, were evaluated. Main Outcome Measures: The characteristic FAF findings in PCV. Results: In the affected eyes with PCV, the sites of the neovascular lesions showed 2 distinct FAF patterns: (1) the confluent hypoautofluorescence at the polypoidal lesions and (2) the granular hypoautofluorescence at the branching choroidal vascular networks. The confluent hypoautofluorescence, most of which was surrounded by a hyperautofluorescent ring, was seen in 74 eyes (80.4%) with PCV but was seen in no eyes with typical neovascular AMD (P < 0.001). The granular hypoautofluorescence was seen in 91 eyes (98.9%) with PCV and 27 eyes (87.1%) with typical neovascular AMD (P = 0.014). In addition, the eyes with PCV more frequently showed hypoautofluorescence outside the macular area than those with typical neovascular AMD (P = 0.021). In the unaffected fellow eyes, the hypoautofluorescence was more frequently observed in patients with PCV than in those with typical neovascular AMD, inside the macular area and in the entire FAF image (P = 0.012, P = 0.003, respectively). Conclusions: In eyes with PCV, the polypoidal lesions and the branching choroidal vascular networks appeared to affect the RPE and induce peculiar FAF findings. When compared with the patients with typical neovascular AMD, widespread RPE damage was more frequently observed in the patients with PCV, both in the affected eyes and in the unaffected fellow eyes. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy - Corrected Proof

Ulla Edén, Per Fagerholm, Reza Danyali, Neil Lagali — 2012-04-18

Objective: To document the clinical and morphologic corneal findings in the early stages of congenital aniridic keratopathy in Swedish families. Design: Prospective, observational, comparative case series. Participants: A total of 16 eyes of 16 subjects with congenital aniridic keratopathy and a clear central cornea, and 6 eyes from 6 healthy controls (unaffected relatives). Nine of the 16 eyes with aniridia came from 5 families with a documented familial history of aniridia. Methods: Detailed ophthalmic examinations included best spectacle-corrected visual acuity (BSCVA), tear film production, tear break-up time (BUT), corneal touch sensitivity, intraocular pressure measurement, ultrasound pachymetry, slit-lamp biomicroscopy, and laser scanning in vivo confocal microscopy (IVCM). Main Outcome Measures: Confirmed stage of aniridic keratopathy, clinical parameters of cornea and tear film (visual acuity, sensitivity, corneal thickness, tear production, and BUT), and the morphologic status of corneal epithelium, sub-basal nerves, and limbal palisades of Vogt. Results: In early-stage aniridic keratopathy, BSCVA and tear BUT were reduced relative to controls (P < 0.001 for both), and corneal thickness was increased (P=0.01). Inflammatory dendritic cells were present in the central epithelium in aniridia, with significantly increased density relative to controls (P = 0.001). Discrete focal opacities in the basal epithelial region were present in 5 of 11 aniridia cases with an otherwise clear cornea. Opacities were associated with dendritic cells and harbored structures presumed to be goblet cells. Sub-basal nerves were extremely dense in 3 aniridia cases, and a prominent whorl pattern of nerves and epithelial cells was observed in 1 case. Normal limbal palisade morphology was absent in aniridia but present in controls. Conclusions: Early-stage aniridic keratopathy is characterized by the development of focal opacities in the basal epithelium, altered sub-basal nerves, infiltration of the central epithelium by dendritic cells, tear film instability, and increased corneal thickness and degradation of limbal palisade architecture. These findings may help to elucidate the pathogenesis of aniridic keratopathy. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Keratoplasty for Corneal Endothelial Disease, 2001–2009 - Corrected Proof

2012-04-17

Purpose: To determine the rates of keratoplasty for corneal endothelial disease (CED) from 2001 to 2009 in a large managed care network in the United States, factors that affect which patients undergo this procedure and surgical outcomes. Design: A retrospective review of data from a longitudinal cohort study. Participants: Beneficiaries with CED aged ≥40 years who were receiving eye care during 2001 to 2009. Methods: Rates of keratoplasty for CED were determined at 6-month intervals from January 2001 to December 2009. The mean number of postoperative visits and rates of severe adverse events in the year after keratoplasty surgery were monitored over the course of the decade. Univariable and multivariable logistic regression were performed to identify sociodemographic and other factors associated with undergoing keratoplasty for CED. Main Outcome Measures: Odds of undergoing keratoplasty with 95% confidence intervals, changes in the number of postoperative visits, and rates of adverse events in the year after keratoplasty. Results: Of the 38 648 enrollees who met the inclusion criteria, 2187 underwent ≥1 keratoplasty surgeries from January 2001 to December 2009. After adjustment for confounding factors, individuals with CED had 47% increased odds of undergoing keratoplasty during 2007–2009 relative to 2001–2006. The mean number of postoperative visits to eyecare providers in the year after keratoplasty declined from 12.6 in 2001–2006 to 10.5 in 2007–2008. There was no difference in the proportion of enrollees who developed adverse events after keratoplasty over time. Conclusions: In this analysis of claims data, from 2001 to 2009, a period during which there was an increase in the rate of endothelial keratoplasty, we observed a trend of greater rates of keratoplasty in patients with CED and fewer visits for postoperative care in the later years of the decade compared with the earlier years, along with no change in rates of severe adverse events. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cost-Effectiveness Analysis of Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema - Corrected Proof

Vinay Dewan, Dennis Lambert, Joshua Edler, Steven Kymes, Rajendra S. Apte — 2012-04-16

Objective: Perform a cost-effectiveness analysis of the treatment of diabetic macular edema (DME) with ranibizumab plus prompt or deferred laser versus triamcinolone plus prompt laser. Data for the analysis were drawn from reports of the Diabetic Retinopathy Clinical Research Network (DRCRnet) Protocol I. Design: Computer simulation based on Protocol I data. Analyses were conducted from the payor perspective. Participants: Simulated participants assigned characteristics reflecting those seen in Protocol I. Methods: Markov models were constructed to replicate Protocol I's 104-week outcomes using a microsimulation approach to estimation. Baseline characteristics, visual acuity (VA), treatments, and complications were based on Protocol I data. Costs were identified by literature search. One-way sensitivity analysis was performed, and the results were validated against Protocol I data. Main Outcome Measures: Direct cost of care for 2 years, change in VA from baseline, and incremental cost-effectiveness ratio (ICER) measured as cost per additional letter gained from baseline (Early Treatment of Diabetic Retinopathy Study). Results: For sham plus laser (S+L), ranibizumab plus prompt laser (R+pL), ranibizumab plus deferred laser (R+dL), and triamcinolone plus laser (T+L), effectiveness through 104 weeks was predicted to be 3.46, 7.07, 8.63, and 2.40 letters correct, respectively. The ICER values in terms of dollars per VA letter were $393 (S+L vs. T+L), $5943 (R+pL vs. S+L), and $20 (R+dL vs. R+pL). For pseudophakics, the ICER value for comparison triamcinolone with laser versus ranibizumab with deferred laser was $14 690 per letter gained. No clinically relevant changes in model variables altered outcomes. Internal validation demonstrated good similarity to Protocol I treatment patterns. Conclusions: In treatment of phakic patients with DME, ranibizumab with deferred laser provided an additional 6 letters correct compared with triamcinolone with laser at an additional cost of $19 216 over 2 years. That would indicate that if the gain in VA seen at 2 years is maintained in subsequent years, then the treatment of phakic patients with DME using ranibizumab may meet accepted standards of cost-effectiveness. For pseudophakic patients, first-line treatment with triamcinolone seems to be the most cost-effective option. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Vitamins E and C and Medical Record-Confirmed Age-Related Macular Degeneration in a Randomized Trial of Male Physicians - Corrected Proof

2012-04-16

Purpose: To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of the diagnosis of age-related macular degeneration (AMD) in a large-scale randomized trial of male physicians. Design: Randomized, double-masked, placebo-controlled trial. Participants: We included 14 236 apparently healthy United States male physicians aged ≥50 years who did not report a diagnosis of AMD at baseline. Methods: Participants were randomly assigned to receive 400 international units (IU) of vitamin E or placebo on alternate days, and 500 mg of vitamin C or placebo daily. Participants reported new diagnoses of AMD on annual questionnaires and medical record data were collected to confirm the reports. Main Outcome Measures: Incident diagnosis of AMD responsible for a reduction in best-corrected visual acuity to ≤20/30. Results: After 8 years of treatment and follow-up, a total of 193 incident cases of visually significant AMD were documented. There were 96 cases in the vitamin E group and 97 in the placebo group (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.78–1.37). For vitamin C, there were 97 cases in the active group and 96 in the placebo group (HR, 0.99; 95% CI, 0.75–1.31). Conclusions: In a large-scale, randomized trial of United States male physicians, alternate-day use of 400 IU of vitamin E and/or daily use of 500 mg of vitamin C for 8 years had no appreciable beneficial or harmful effect on risk of incident diagnosis of AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Association of Single Nucleotide Polymorphisms of Interleukins-1β, -6, and -12B with Contact Lens Keratitis Susceptibility and Severity - Corrected Proof

2012-04-12

Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in interleukin (IL)-1β, IL-6, and IL-12β are associated with the susceptibility and severity of contact lens-related keratitis. Design: Retrospective, case control study. Participants: One hundred twelve cases of keratitis and 225 controls were recruited from studies conducted at Moorfields Eye Hospital and in Australia during 2003 through 2005. Methods: Buccal swab samples were collected on Whatman FTA cards and were mailed by post for analysis. IL-1β (−31), IL-6 (−174, −572, −597), and IL-12B (3′+1158) genotypes were analyzed with pyrosequencing and analyzed using a regression model for susceptibility (sterile, microbial keratitis, controls) and severity. Statistical significance was set at 0.05. Main Outcome Measures: The relative risk of developing contact lens-related keratitis and more severe forms of the disease based on allele, genotype, and haplotype associations. Results: Carriers of IL-6 SNPs were more likely to experience moderate and severe events compared with those with nonmutated genotypes (−174 heterozygous: odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1–8.3; homozygous: OR, 6.4; 95% CI, 1.4–28.4; −174/−597: OR, 4.1; 95% CI, 1.6–11.0). More severe keratitis and microbial keratitis were less likely to occur in wearers with the nonmutated IL-6 haplotype (severity OR, 0.4 [95% CI, 0.2–0.7]; microbial OR, 0.6 [95% CI, 0.4–0.9]). Wearers carrying an IL-12B SNP had an increased risk of sterile keratitis (OR, 9.7; 95% CI, 1.2–76.9) compared with controls. Conclusions: The IL-6 SNPs are known to reduce protein expression of this cytokine and thus ocular immune defense, and carriers of these SNPs were more likely to experience more severe and microbial keratitis, suggesting that IL-6 decreases the severity and susceptibility of contact lens-related keratitis. Carriers of a functional SNP of IL-12B that is known to increase IL-12 expression and stability are more likely to experience sterile keratitis, suggesting that this is associated with the intense inflammatory reaction that occurs in this condition. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Detection and Time to Treatment of Uveal Melanoma in the United Kingdom: An Evaluation of 2384 Patients - Corrected Proof

Erika M. Damato, Bertil E. Damato — 2012-04-12

Purpose: To determine the mode of detection of uveal melanoma and time to treatment in the United Kingdom. Design: Prospective cohort study. Participants: A total of 2384 patients diagnosed with uveal melanoma at the Liverpool Ocular Oncology Center between 1996 and early 2011. Methods: A questionnaire was completed with every new patient, and the results were correlated with clinical features and treatment. Main Outcome Measures: Tumor detection, practitioner initiating referral, referral pathway, time to treatment, baseline clinical features, and primary ocular treatment. Results: The referral process was initiated by an optometrist, family doctor, or ophthalmologist in 68.0%, 18.2%, and 13.8% of patients, respectively. On referral, 30.2% of patients were asymptomatic. Twenty-three percent of patients reported that their tumor was initially missed; these tended to have a more advanced tumor when they reached our center. The time from referral to treatment had a median of 49 days, exceeding 6 months in 19.8% of patients. This delay was longer in patients who reported that their tumor was missed (median, 92 vs. 40 days; Mann–Whitney, P<0.001). Ophthalmologists delayed the referral process by more than 6 months in 10.9% of patients. Primary enucleation was performed in 33.3% of patients and was more likely in those who reported that their tumor was missed (44.8% vs. 29.8%; chi-square, P<0.001). Conclusions: Many patients with uveal melanoma experience long delays in treatment because their tumor was missed or misdiagnosed. Such patients tend to have a more advanced tumor by the time they reach an oncology center and are more likely to require enucleation. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Acquired Optic Nerve and Peripapillary Pits in Pathologic Myopia - Corrected Proof

2012-04-11

Purpose: To examine the incidence and characteristics of pit-like structures around the optic disc and myopic conus in eyes with high myopia. Design: Prospective, observational case series. Participants: We evaluated 198 eyes of 119 patients with pathologic myopia (spherical equivalent >−8 diopters [D]). We also evaluated 32 eyes of 32 subjects with emmetropia (refractive error ≤±3 D) as controls. Methods: The papillary and peripapillary areas were examined with a prototype swept-source optical coherence tomography (OCT) system with a center wavelength of 1050 nm. We studied the structural characteristics of pit-like changes. Main Outcome Measures: The incidence and characteristics of the optic nerve (ON) pits in eyes with high myopia. Results: Pit-like clefts were found at the outer border of the ON or within the adjacent scleral crescent in 32 of 198 highly myopic eyes (16.2%) but in none of the emmetropic eyes. The eyes with these pits were more myopic, had significantly longer axial lengths, and had significantly larger optic discs than the highly myopic eyes without pits. The pits were located in the optic disc area (optic disc pits) in 11 of 32 eyes and in the area of the conus outside the optic disc (conus pits) in 22 of 32 eyes. One eye had both optic disc pits and conus pits. The optic disc pits existed in the superior or inferior border of the optic disc. All but 1 eye with conus pits had a type IX staphyloma, and the location of the conus pits were present nasal to the scleral ridge or outside the ridge temporal to the nerve. The optic disc pits were associated with discontinuities of the lamina cribrosa, whereas the conus pits appeared to develop from a scleral stretch-associated schisis or to emissary openings for the short posterior ciliary arteries in the sclera. The nerve fiber tissue overlying the pits was discontinuous at the site of the pits. Conclusions: Optic nerve pits are common in highly myopic eyes. The ON pits are barely visible ophthalmoscopically but can be demonstrated by using swept-source OCT. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Prevalence of and Racial Differences in Pterygium: A Multiethnic Population Study in Asians - Corrected Proof

2012-04-11

Purpose: To describe the prevalence and risk factors of pterygium in a multiethnic Asian population and to examine racial differences. Design: Population-based study in Singapore, located 1° north of the equator. Participants: Data were analyzed from 8906 participants from 3 population-based studies of Malays, Indians, and Chinese persons 40 years of age and older conducted between 2004 and 2011. Methods: Standardized slit-lamp examinations were performed by trained study ophthalmologists to examine the anterior segment for evidence of pterygium. Every subject underwent standardized systemic and ocular examinations, interviewer-administered questionnaires, and blood investigations for risk factor assessment. Regression and principle component analysis models were constructed to study the relationship of race and other factors to pterygium. Main Outcome Measures: Any pterygium and severe (grade 3 or opaque) pterygium. Results: The overall prevalence of any pterygium was 10.1% (n = 900), of which severe pterygium was seen in 1.6% (n = 142). The prevalence of any pterygium was more common in Malays (15.5%) than Chinese (7.0%; P<0.001) or Indians (7.0%; P<0.001). Multivariate analysis revealed increasing age (P<0.001), male gender (P<0.001), Malay race (P<0.001), and having a poorer education level (P<0.001) as significant factors for any pterygium. Race contributed significantly to presence of any pterygium (41%; P<0.001) or presence in both eyes (33%; P<0.001) compared with other risk factors. Severe pterygium was associated with outdoor occupation (P = 0.02), but race was not a significant risk factor in multivariate analysis. Conclusions: This population-based study in Asian persons of different races living in the same geographical location at the equator indicated that race is a significant risk factor for pterygium, with Malays having higher prevalence than Indians and Chinese, while controlling for other risk factors. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Risk of Corticosteroid-Induced Hyperglycemia Requiring Medical Therapy among Patients with Inflammatory Eye Diseases - Corrected Proof

2012-04-09

Objective: To identify the incidence and risk factors for corticosteroid-induced hyperglycemia requiring medical therapy among patients with inflammatory eye diseases. Design: Retrospective cohort study. Participants: Patients with ocular inflammation followed at 5 United States tertiary centers that initially were neither diabetic nor taking hypoglycemic medications. Methods: Eligible patients who used oral corticosteroids during follow-up were identified and followed longitudinally for initiation of hypoglycemic medication over 1 year after beginning corticosteroids. The remaining eligible patients were followed for 1 year after their initial visit. Survival analysis was used to calculate the risk of hyperglycemia requiring medical therapy and to identify potential risk factors. Main Outcome Measures: Initiation of hypoglycemic medications. Results: Among 2073 non-diabetic patients treated with oral corticosteroids, 25 (1.21%) initiated hypoglycemic therapy compared with 5 of 2666 patients (0.19%) not treated with oral corticosteroids (relative risk [RR], 4.39; 95% confidence interval [CI], 1.68–11.5). The RR tended to be higher in association with higher initial doses (for initial doses <40 mg of prednisone per day: RR, 3.23; 95% CI, 1.08–9.64; for initial prednisone dose ≥40 mg/d: RR, 5.51; 95% CI, 2.01–15.1). Other risk factors for the initiation of hypoglycemic therapy included older age (RR [per each additional 10 years], 1.46; 95% CI, 1.15–1.85; P = 0.002) and African-American race (RR, 2.94; 95% CI, 1.34–6.43; P = 0.007). Conclusions: These results suggest that the absolute risk of corticosteroid-induced hyperglycemia that is detected and treated with hypoglycemic therapy in the tertiary ocular inflammation setting is low (an excess cumulative risk on the order of 1% within 1 year), although on a relative scale it is approximately 4.4-fold higher than in patients not treated with oral corticosteroids. Older age and African-American race also were risk factors. Physicians who use systemic corticosteroids for ocular inflammatory diseases should be aware of this risk, and should consider surveillance for hyperglycemia among high-risk patients. However, given the low absolute risk, routine laboratory monitoring or referral for monitoring may not be necessary for low-risk patients. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.