Ophthalmology - Articles in Press

Genetic Polymorphisms in DNA Repair Genes OGG1, APE1, XRCC1, and XPD and the Risk of Age-Related Cataract - Corrected Proof

2012-02-06

Purpose: To analyze the association of the polymorphisms in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP endonuclease-1 (APE1) genes in the base excision repair pathway and xeroderma pigmentosum complementation group D (XPD) in the nucleotide excision repair pathway with the risk of cataract in a Chinese population. Design: Case-control study. Participants: Subjects with cataract (n = 415) or no cataract (n = 386) in the Age Related Eye Disease Ancillary Study. Methods: The study included 415 cataract patients and 386 controls. Genotyping was carried out by the polymerase chain reaction–restriction fragment length polymorphism method. Differences in the frequencies were estimated by the chi-square test, and risk was estimated by using unconditional logistic regression after adjusting for age and gender. Main Outcome Measures: Association of single nucleotide polymorphisms in OGG1-Ser326Cys with the development of age-related cataract. Results: The OGG1 Cys/Cys genotype frequency was significantly higher in cataract patients (P = 0.014; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.171–3.624). The OGG1 Ser/Ser genotype (P = 0.003; OR, 0.647; 95% CI, 0.487–0.860) seems to have a protective role against cataract, and the Cys allele (P<0.001; OR, 1.517; 95% CI, 1.204–1.911) seems to have a deleterious role in the development of cataract. The genotype frequency of the Ser/Ser of OGG1-Ser326Cys was significantly different in the cortical and mixed-type cataract group (P = 0.014; OR, 0.591; 95% CI, 0.391–0.893; and P = 0.035; OR, 0.639; 95% CI, 0.425–0.960; respectively), and the Cys/Cys genotype of OGG1-Ser326Cys was significantly different in the mixed-type cataract group (P = 0.012; OR, 2.610; 95% CI, 1.284–5.306) compared with that of healthy controls. In XRCC1-Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls. Conclusions: Results suggest that the Cys/Cys genotype of the OGG1-Ser326Cys polymorphism may be associated with increased risk of age-related cataract. However, in XRCC1-Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

HORIZON: An Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration - Corrected Proof

2012-02-06

Objective: To evaluate the long-term safety and efficacy of multiple intravitreal ranibizumab injections (Lucentis, Genentech, Inc., South San Francisco, CA) administered at the investigator's discretion in patients with choroidal neovascularization secondary to age-related macular degeneration. Design: An open-label, multicenter, extension study. Participants: Patients who completed the controlled treatment phase of 1 of 3 prospective, randomized, 2-year clinical trials of ranibizumab were eligible for enrollment. Analyses were performed for 3 groups: (1) patients treated with ranibizumab in the initial study (ranibizumab treated-initial; n = 600); (2) patients randomized to control who crossed over to receive ranibizumab (ranibizumab treated-XO; n = 190); and (3) ranibizumab-naïve patients (ranibizumab untreated; n = 63). Methods: Ranibizumab 0.5 mg was administered at the investigator's discretion. Adverse events (AEs) and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) assessments were conducted at study visits every 3 to 6 months. Main Outcome Measures: Incidence and severity of AEs. Results: There was 1 occurrence of mild endophthalmitis per 3552 HORIZON injections in the ranibizumab treated-initial/ranibizumab treated-XO groups. There were no serious AE reports of lens damage, retinal tears, or rhegmatogenous retinal detachments in the study eyes. The proportion of patients with any single postdose intraocular pressure ≥30 mmHg was 9.2%, 6.6%, and 0%, and the proportion of patients with glaucoma was 3.2%, 4.2%, and 3.2% in the ranibizumab treated-initial, ranibizumab treated-XO, and ranibizumab untreated groups, respectively. Cataract AEs were less frequent in the ranibizumab untreated group: 6.3% versus 12.5% and 12.1% in the ranibizumab treated-initial and ranibizumab treated-XO groups, respectively. The proportion of patients with arterial thromboembolic events as defined by the Antiplatelet Trialists' Collaboration was 5.3% in the ranibizumab treated-initial and ranibizumab treated-XO groups, and 3.2% in the ranibizumab untreated group. At month 48 (2 years of HORIZON), the mean change in BCVA (ETDRS letters) relative to the initial study baseline was 2.0 in the ranibizumab treated-initial group versus −11.8 in the pooled ranibizumab treated-XO and ranibizumab untreated groups. Conclusions: Multiple ranibizumab injections were well tolerated for ≥4 years. With less frequent follow-up leading to less treatment, there was an incremental decline of the visual acuity (VA) gains achieved with monthly treatment. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

A Population-based Survey of the Prevalence and Types of Glaucoma in Nepal: The Bhaktapur Glaucoma Study - Corrected Proof

2012-02-02

Objective: To determine the prevalence and types of glaucoma in a Nepalese population. Design: Cross-sectional, population-based survey. Participants: A total of 4800 subjects aged 40 years or older from the Bhaktapur district of Kathmandu valley. Methods: Subjects aged 40 years or older were selected using a cluster sampling procedure and door-to-door enumeration for a population-based, cross-sectional study. All subjects underwent a detailed ocular examination at the base hospital, which included logarithm of minimal angle of resolution visual acuity, refraction, applanation tonometry, gonioscopy, Lens Opacities Classification System II cataract grading, retinal examination, and Swedish Interactive Thresholding Algorithm standard perimetry when indicated. Main Outcome Measures: Diagnosis of glaucoma was based on criteria described by the International Society for Geographic and Epidemiological Ophthalmology. Results: A total of 4003 subjects underwent a comprehensive eye examination (response rate 83.4%), and complete data were available in 3991 subjects. The mean intraocular pressure was 13.3 mmHg (97.5th and 99.5th percentiles, 18 and 20 mmHg, respectively), and the mean vertical cup-to-disc ratio was 0.26 (97.5th and 99.5th percentiles, 0.6 and 0.8 mmHg, respectively). There were 75 subjects with glaucoma, an age- and sex-standardized prevalence of 1.80 (95% confidence interval [CI], 1.68–1.92). Age- and sex-standardized prevalence was 1.24% (95% CI, 1.14–1.34) for primary open-angle glaucoma (POAG), 0.39% (95% CI, 0.34–0.45) for primary angle-closure glaucoma (PACG), and 0.15% (95% CI, 0.07–0.36) for secondary glaucoma. The prevalence of glaucoma increased with an increase in age with no significant difference in gender. Primary angle-closure glaucoma was 3 times more common in women. Nine eyes were blind, and 2 subjects were bilaterally blind from glaucoma. Conclusions: The overall prevalence of glaucoma was 1.9%. Of all glaucoma cases, POAG accounted for 68%, PACG accounted for 22.67%, and secondary glaucoma accounted for 9.33%. Among the subjects with POAG, 96.08% had not been previously diagnosed. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ranibizumab for Macular Edema Due to Retinal Vein Occlusions: Long-term Follow-up in the HORIZON Trial - Corrected Proof

2012-02-02

Purpose: To assess long-term safety and efficacy of intraocular ranibizumab injections in patients with macular edema after retinal vein occlusion (RVO). Design: Open-label extension trial of the 12-month Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety (CRUISE) trials. Participants: We included 304 patients who completed BRAVO and 304 patients who completed CRUISE. Methods: Patients were seen at least every 3 months and given an intraocular injection of 0.5 mg ranibizumab if they met prespecified retreatment criteria. Main Outcome Measures: Primary outcomes were incidence and severity of ocular and nonocular adverse events (AEs). Key efficacy outcomes included mean change from baseline best-corrected visual acuity (BCVA) letter score by Early Treatment Diabetic Retinopathy Study protocol and central foveal thickness. Results: In patients who completed month 12, the mean number of injections (excluding month 12 injection) in the sham/0.5-, 0.3/0.5-, and 0.5-mg groups was 2.0, 2.4, and 2.1 (branch RVO) and 2.9, 3.8, and 3.5 (central RVO), respectively. The incidence of study eye ocular serious AEs (SAEs) and SAEs potentially related to systemic vascular endothelial growth factor inhibition across treatment arms was 2% to 9% and 1% to 6%, respectively. The mean change from baseline BCVA letter score at month 12 in branch RVO patients was 0.9 (sham/0.5 mg), −2.3 (0.3/0.5 mg), and −0.7 (0.5 mg), respectively. The mean change from baseline BCVA at month 12 in central RVO patients was −4.2 (sham/0.5 mg), −5.2 (0.3/0.5 mg), and −4.1 (0.5 mg), respectively. Conclusions: No new safety events were identified with long-term use of ranibizumab; rates of SAEs potentially related to treatment were consistent with prior ranibizumab trials. Reduced follow-up and fewer ranibizumab injections in the second year of treatment were associated with a decline in vision in central RVO patients, but vision in branch RVO patients remained stable. Results suggest that during the second year of ranibizumab treatment of RVO patients, follow-up and injections should be individualized and, on average, central RVO patients may require more frequent follow-up than every 3 months. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Detection of New-Onset Choroidal Neovascularization Using Optical Coherence Tomography: The AMD DOC Study - Corrected Proof

2012-02-01

Purpose: To determine the sensitivity of time domain optical coherence tomography (OCT) in detecting conversion to neovascular age-related macular degeneration (AMD) in eyes at high risk for choroidal neovascularization (CNV), compared with detection using fluorescein angiography (FA) as the gold standard. Design: Prospective, multicenter, observational study. Participants: Individuals aged ≥50 years with nonneovascular AMD at high risk of progressing to CNV in the study eye and evidence of neovascular AMD in the fellow eye. Methods: At study entry and every 3 months through 2 years, participants underwent best-corrected visual acuity, supervised Amsler grid testing, preferential hyperacuity perimetry (PHP) testing, stereoscopic digital fundus photographs with FA, and OCT imaging. A central Reading Center graded all images. Main Outcomes Measures: The sensitivity of OCT in detecting conversion to neovascular AMD by 2 years, using FA as the reference standard. Secondary outcomes included comparison of sensitivity, specificity, positive predictive value, and negative predictive value of OCT, PHP, and supervised Amsler grid relative to FA for detecting incident CNV. Results: A total of 98 participants were enrolled; 87 (89%) of these individuals either completed the 24-month visit or exited the study after developing CNV. Fifteen (17%) study eyes had incident CNV confirmed on FA by the Reading Center. The sensitivity of each modality for detecting CNV was: OCT 0.40 (95% confidence interval [CI], 0.16–0.68), supervised Amsler grid 0.42 (95% CI, 0.15–0.72), and PHP 0.50 (95% CI, 0.23–0.77). Treatment for incident CNV was recommended by the study investigator in 13 study eyes. Sensitivity of the testing modalities for detection of CNV in these 13 eyes was 0.69 (95% CI, 0.39–0.91) for OCT, 0.50 (95% CI, 0.19–0.81) for supervised Amsler grid, and 0.70 (95% CI, 0.35–0.93) for PHP. Specificity of the OCT was higher than that of the Amsler grid and PHP. Conclusions: Time-domain OCT, supervised Amsler grid, and PHP have low to moderate sensitivity for detection of new-onset CNV compared with FA. Optical coherence tomography has greater specificity than Amsler grid or PHP. Among fellow eyes of individuals with unilateral CNV, FA remains the best method to detect new-onset CNV. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Postcataract Surgery Endophthalmitis in the United States: Analysis of the Complete 2003 to 2004 Medicare Database of Cataract Surgeries - Corrected Proof

Lisa Keay, Emily W. Gower, Sandra D. Cassard, James M. Tielsch, Oliver D. Schein — 2012-02-01

Objective: To estimate endophthalmitis incidence after cataract surgery nationally and at the state level in 2003 and 2004 and to explore risk factors. Design: Analysis of Medicare beneficiary claims data. Participants: We evaluated billed claims for cataract surgery and endophthalmitis diagnosis and treatment for all Medicare fee-for-service beneficiaries in 2003-2004. Methods: Cataract surgeries were identified by procedure codes and merged with demographic information. Cataract annual surgical volume was calculated for all surgeons. Presumed postoperative endophthalmitis cases were identified by International Classification of Diseases-9 Clinical Modification Codes on claims within 42 days after surgery. Endophthalmitis rates and 95% confidence intervals (CI) were calculated at state and national levels. Logistic regression was used to investigate the association between developing endophthalmitis and surgery location and surgeon factors. Main Outcome Measures: Endophthalmitis incidence and risk factors. Results: We included 4006 cases of presumed endophthalmitis, which occurred after 3 280 966 cataract surgeries. The national rate in 2003 was 1.33 per 1000 surgeries (95% CI, 1.27–1.38) and decreased to 1.11 per 1000 (95% CI, 1.06–1.16) in 2004. Males (relative risk [RR], 1.23; 95% CI, 1.15–1.31), older individuals (RR, 1.53; 95% CI, 1.38–1.69; ≥85 compared with 65–74 years), blacks (RR, 1.17; 95% CI, 1.03–1.33), and Native Americans (RR, 1.72; 95% CI, 1.07–2.77) had increased risk of disease. After adjustment, surgeries by surgeons with low annual volume (RR, 3.80; 95% CI, 3.13–4.61 for 1–50 compared with ≥1001 annual surgeries) and less experience (RR, 1.41; 95% CI, 1.25–1.59 for 1–10 compared with ≥30 years), and surgeries performed in 2003 (RR, 1.20; 95% CI, 1.13–1.28) had increased endophthalmitis risk. Conclusions: Endophthalmitis rates are lower than previous yearly US estimates, but remain higher than rates reported from a series of studies from Sweden; patient factors or methodologic differences may contribute to differences across countries. Patient age, gender, and race, and surgeon volume and years of experience are important risk factors. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Comparative Study of Limbal Stem Cell Deficiency Diagnosis Methods: Detection of MUC5AC mRNA and Goblet Cells in Corneal Epithelium - Corrected Proof

2012-01-31

Purpose: To evaluate a limbal stem cell deficiency (LSCD) diagnosis method based on the detection of the MUC5AC transcript by reverse transcription-polymerase chain reaction (RT-PCR) in comparison with the standard diagnostic method based on goblet cell detection by periodic acid-Schiff (PAS)–hematoxylin staining, using samples obtained from corneal epithelium impression cytology (IC). Design: Transversal, comparative case series. Participants: We studied 59 eyes from 43 patients clinically diagnosed with LSCD. Methods: Impression cytology was used to gather cells from corneal and conjunctival epithelium from the same eye. The presence of goblet cells in the cornea was determined by PAS-hematoxylin staining, whereas the presence of the MUC5AC transcript was detected by RT-PCR using a custom-designed primer pair. Main Outcome Measures: Goblet cells in the corneal epithelium were detected by light microscopy, and the MUC5AC transcript was detected as the corresponding PCR amplicon in agarose gels. Results: Our study included 59 corneal samples, together with their respective conjunctival samples for RT-PCR assays. Of these, 47 samples were also available for comparative PAS-hematoxylin staining. The MUC5AC amplicon was detected in 56 of 59 (94.9%) corneal epithelium samples. In contrast, conventional IC staining detected goblet cells in only 17 of 47 (36.2%) samples; these were not found in 27 of 47 (57.4%) samples (negative results), and 3 of 47 (6.4%) showed inconclusive results. Conclusions: The detection of the MUC5AC transcript in corneal epithelium is a more sensitive method to diagnose LSCD than the conventional PAS-hematoxylin method, although a minimum RNA concentration of 1.2 ng/μl is required for negative results to be reliable. Moreover, RT-PCR is a highly specific and more objective technique. Overall, these findings indicate that molecular analysis facilitates a more precise clinical diagnosis of LSCD, thereby reducing the risk of surgical failure. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Enhanced Depth Imaging Optical Coherence Tomography of Choroidal Nevus in 104 Cases - Corrected Proof

2012-01-31

Purpose: To describe the characteristics of choroidal nevus using the enhanced depth imaging (EDI) feature of spectral-domain optical coherence tomography (OCT). Design: Retrospective, observational case series. Participants: One hundred four eyes with choroidal nevus. Methods: Spectral-domain EDI OCT was performed with a Heidelberg Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany) using a custom scan acquisition protocol of up to 13 raster lines of 9-mm scan length with automatic real-time image averaging set at 100 images. The thickness of choroidal nevus was measured by combining Heidelberg's autosegmentation with manual segmentation. Main Outcome Measures: Imaging features and thickness correlation of choroidal nevus by EDI OCT versus standard ultrasonography. Results: Of 104 eyes with choroidal nevus imaged with EDI OCT, 51 (49%) displayed image detail suitable for study. The remaining 53 cases were suboptimal because of statistically identified factors of age older than 60 years (P = 0.027), female gender (P = 0.008), extramacular location of nevus (P<0.001), mean distance from foveola more than 3 mm (P = 0.002), mean distance from optic disc more than 4 mm (P<0.001), and mean maximal basal diameter more than 5 mm (P = 0.006). Of the 51 suitable cases, mean nevus thickness was 685 μm (median, 628 μm; range, 184–1643 μm) by EDI OCT compared with 1500 μm (median, 1500 μm; range, 1000–2700 μm) by ultrasonography. The most common EDI OCT imaging features included partial (59%) or complete (35%) choroidal shadowing deep to the nevus, choriocapillaris thinning overlying the nevus (94%), retinal pigment epithelial (RPE) atrophy (43%), RPE loss (14%), RPE nodularity (8%), photoreceptor loss (43%), inner segment–outer segment junction (IS–OS) irregularity (37%), IS–OS loss (6%), external limiting membrane irregularity (18%), outer nuclear and outer plexiform layer irregularity (8%), and inner nuclear layer irregularity (6%). Overlying subretinal fluid was identified by EDI OCT (16%), ophthalmoscopic examination (8%), and ultrasonographic evaluation (0%). A comparison of pigmented versus nonpigmented nevus showed only 1 significant difference of more intense choroidal shadowing with pigmented nevus (P = 0.046). Conclusions: Imaging of choroidal nevus with EDI OCT enables precise measurement of tumor thickness with comparatively reduced thickness relative to ultrasonography. Using EDI OCT, 94% of choroidal nevi were found to have overlying choriocapillaris thinning. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intraoperative Ultrasonography-Guided Positioning of Iodine 125 Plaque Brachytherapy in the Treatment of Choroidal Melanoma - Corrected Proof

2012-01-31

Purpose: To report intraoperative ultrasonography-guided positioning of iodine 125 (I125) plaques for brachytherapy of choroidal melanoma as a quality improvement measure. Design: Retrospective, single-center, consecutive case-cohort study. Participants: One hundred fifty consecutive patients with choroidal melanoma. Methods: Patients with choroidal melanoma who were treated with I125 plaque brachytherapy from January 2007 through January 2011 with at least 6 months of clinical follow-up were included. Main Outcome Measures: Patient and tumor characteristics at diagnosis were tabulated. The need for plaque repositioning if intraoperative ultrasonography showed the plaque to be either not centered on the tumor or if there was less than 1.0 mm of plaque margin beyond the tumor border was recorded. The rate of local treatment failure and occurrence of distant metastasis were determined. Results: The average interval from surgery to last follow-up was 21.5 months. Fifty-four (36%) of 150 patients required plaque repositioning. Of tumors located in the macula, equator, and periphery, 15 (36.6%), 26 (36.6%), and 13 (34.2%) required repositioning. There was no case of local treatment failure during a mean follow-up of 21.5 months (range, 6–48 months). Clinical evidence of choroidal melanoma metastasis developed in 9 patients. The cumulative 2-year Kaplan-Meier rate of local treatment failure in the cohort was statistically lower compared with the Collaborative Ocular Melanoma Study, which did not require ultrasonography-guided plaque positioning. Conclusions: Intraoperative ultrasonography identified the need to reposition I125 plaques to achieve centration and plaque margin (>1.0 mm) beyond the tumor border in 36% of eyes. Neither tumor size nor tumor location correlated with the need to reposition the plaque. There was no case of local treatment failure during follow-up in this series. Correct plaque position is an essential component of quality outcomes in brachytherapy. Intraoperative ultrasonography reduces geographic errors in placement in eye plaque therapy and may help to reduce local treatment failure in choroidal melanoma. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Clinicopathologic and Molecular Analysis of a Choroidal Pigmented Schwannoma in the Context of a PTEN Hamartoma Tumor Syndrome - Corrected Proof

2012-01-25

Purpose: To report the first case of choroidal schwannoma in a patient affected by PTEN hamartoma tumor syndrome (PHTS) and investigate the molecular involvement of the phosphatase and tensin homolog (PTEN) and neurofibromin 2 (NF2) genes in this rare intraocular tumor. Design: Observational case report. Participant: A 10-year-old girl diagnosed with PHTS. Methods: The enucleated specimen underwent histologic, immunohistochemical, and transmission electronic microscopy. The expression of PTEN and NF2 and their protein products were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. Somatic mutations of PTEN and NF2, as well as allelic loss, were investigated by direct sequencing of DNA extracted from the tumor. PTEN epigenetic silencing was investigated by pyrosequencing. Main Outcome Measures: Histopathologic and molecular characterization of a choroidal pigmented schwannoma. Results: Histopathologic, immunohistochemical, and electron microscopic analysis demonstrated features consistent with a pigmented cellular schwannoma of the choroid. We found no loss of heterozygosity at the genomic level for the PTEN germline mutation and no promoter hypermethylation or other somatic intragenic mutations. However, we observed an approximate 40% reduction of PTEN expression at both the mRNA and the protein level, indicating that the tumor was nonetheless functionally deficient for PTEN. Although DNA sequencing of NF2 failed to identify any pathologic variants, its expression was abolished within the tumor. Conclusions: We report the first description of a pigmented choroidal schwannoma in the context of a PHTS. This rare tumor showed a unique combination of reduction of PTEN and absence of NF2 expression. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Immunocytochemical Diagnosis as Inflammation by Vitrectomy Cell Blocks in Patients with Vitreous Opacity - Corrected Proof

Toshihiko Matsuo, Kouichi Ichimura — 2012-01-25

Purpose: To describe the clinical and cytopathologic characteristics in patients with vitreous opacity of unknown cause or preceding inflammation, diagnosed cytopathologically as inflammation. Design: Retrospective case series. Participants: Forty-three consecutive patients (61 eyes) who underwent vitrectomy for vitreous opacity of unknown cause or preceding inflammation and were diagnosed cytopathologically with inflammation at one institution in 6 years from 2005 to 2010. During the same period, 11 consecutive patients with vitreous opacity of unknown cause were diagnosed cytopathologically with lymphoma (large B-cell lymphoma) and were excluded from the study. Methods: Cell blocks were made by centrifugation of vitrectomy fluid and embedded in paraffin for immunocytochemistry. Main Outcome Measures: Cytopathologic and immunocytochemical diagnosis using vitrectomy cell blocks. Results: Histiocytes (macrophages), small lymphocytes, neutrophils, and eosinophils were predominant cells, with no atypical large cells on hematoxylin–eosin staining. Immunocytochemically, most predominant cells were CD68-positive histiocytes (macrophages), followed by CD3-positive T cells, but CD20- or CD79a-positive B cells were rarely present. Epithelioid cells, positive for CD68, were found in 4 patients with or without an established diagnosis of sarcoidosis, and giant multinucleated cells were found in 2 patients with suspected preceding self-limiting Vogt-Koyanagi-Harada disease, based on the presence of depigmented red fundi. Inflammation was diagnosed in 2 patients with vitreous opacity who had a preceding onset of brain lymphoma or systemic lymphoma. Conclusions: The presence of macrophages, combined with small T lymphocytes, was a major sign in intravitreal inflammation, manifesting as vitreous opacity. A simple technique of cytopathology and immunocytochemistry, using vitrectomy cell blocks, can be performed in most pathology laboratories. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Choroidal Thickness and Volume Mapping by a Six Radial Scan Protocol on Spectral-Domain Optical Coherence Tomography - Corrected Proof

Joong Won Shin, Yong Un Shin, Byung Ro Lee — 2012-01-25

Purpose: To report a 6 radial scan protocol, which simply generates a topographic map of choroidal thickness and volume on a commercial spectral-domain optical coherence tomography (SD-OCT) device. We analyzed the features of the resulting choroidal maps in healthy eyes. Design: Prospective, noncomparative case series. Participants: Eighty eyes from 40 healthy volunteers who visited the healthcare clinic of Hanyang University Hospital from December 2010 to February 2011. Methods: All participants underwent a 6 radial scanning protocol using an SD-OCT device. In a single session, the device produces 6 high-resolution averaging B-scan images. For segmentation of the choroid layer, the reference lines of the retinal boundary (internal limiting membrane–retinal pigment epithelium) were adjusted to the choroidal boundary (retinal pigment epithelium–choroid/sclera junction) in each of the 6 radial B-scans. A topographic map of choroidal thickness and volume was automatically generated by built-in software according to the Early Treatment Diabetic Retinopathy Study (ETDRS) layout. A statistical analysis was conducted to compare the choroidal thickness and volume measurements for each ETDRS subfield. Main Outcome Measures: An ETDRS-style topographic map of choroidal thickness and volume. Results: The mean time required for segmentation adjustment was 167.4±15.8 seconds. The mean choroidal thickness of all ETDRS subfields was 285.9±53.0 μm, and the mean total choroidal volume of the entire ETDRS area was 7.72±1.2 mm3. The nasal outer macula area was significantly smaller than any other ETDRS subfield (P<0.05) except for the adjacent superior and inferior outer macula subfields. Refractive error was correlated with choroidal thickness in all ETDRS subfields. Age was also correlated with choroidal thickness for almost all of the ETDRS subfields except for the temporal inner, nasal outer, and temporal outer macula areas. The total choroidal volume was correlated with the refractive error and age. Conclusions: A 6 radial scan protocol, using a commercial SD-OCT device, enables the production of reliable choroidal thickness and volume maps with an ETDRS layout. By using this protocol, more comprehensive choroidal evaluation is possible in clinical practice or research. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Integrating Event- and Trend-Based Analyses to Improve Detection of Glaucomatous Visual Field Progression - Corrected Proof

2012-01-23

Purpose: To present and evaluate a new method of integrating event- and trend-based analyses of visual field progression in glaucoma. Design: Observational cohort study. Participants: The study included 711 eyes of 357 glaucoma patients or suspects followed up for an average of 5.0±2.0 years with an average of 7.7±2.3 standard automated perimetry visual fields. An additional group of 55 eyes of 55 glaucoma patients underwent repeated tests over a short period to test the specificity of the method. Methods: Event-based analysis of progression was performed using the Guided Progression Analysis (GPA; Carl-Zeiss Meditec, Inc., Dublin, CA). Trend-based assessment used the visual field index (VFI). A hierarchical Bayesian model was built to incorporate results from the GPA in the prior distribution for the VFI slopes, allowing the event-based method to influence the inferences made for the trend-based assessment. Main Outcome Measures: The Bayesian method was compared with the conventional ordinary least squares (OLS) regression method of trend-based assessment. Results: Of the 711 eyes followed up over time, 64 (9%) had confirmed progression with GPA. Bayesian slopes of VFI change were able to detect 63 of these eyes (98%). An additional group of 49 eyes (7%) had progression by Bayesian slopes, but not by GPA. Slopes of VFI change calculated by the OLS method were able to identify only 32 of the 64 eyes (50%) with GPA progression. The agreement with GPA was significantly better for the Bayesian compared with the OLS method (κ = 0.68 vs. 0.43, respectively; P<0.001). Eyes progressing only by the Bayesian method had faster rates of change than those progressing only by the OLS method. When applied to the 50 eyes in the stable glaucoma group, both the Bayesian and the OLS methods had a specificity of 96%. Conclusions: A Bayesian hierarchical modeling approach for integrating event- and trend-based assessments of visual field progression performed better than either method used alone. Estimates of rates of change obtained from the Bayesian model had increased precision and may be superior to the conventional OLS method for providing information on the risk of development of functional impairment in the disease. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Infectious Endophthalmitis in Adult Eyes Receiving Boston Type I Keratoprosthesis - Corrected Proof

2012-01-23

Purpose: To report the clinical characteristics of infectious endophthalmitis after Boston type I keratoprosthesis (K-Pro) implantation. Design: Retrospective study. Participants: One hundred forty-one adult eyes receiving a K-Pro at a single institution from May 2004 through July 2008. Methods: A retrospective chart review was performed of all adult eyes receiving a K-Pro at the University of Rochester from May 2004 through July 2008. Those patients identified as having been treated for exogenous bacterial endophthalmitis were reviewed for demographic data, indication for K-Pro, bandage contact lens use, prophylactic antibiotic use, timing and clinical presentation of endophthalmitis, gram stain and culture results of intraocular fluid, timing and presentation of any subsequent episodes of endophthalmitis (recurrent endophthalmitis), and preoperative and postoperative visual acuity through August 2010. Main Outcome Measures: Incidence of endophthalmitis, time to occurrence, recurrence rates, visual outcomes, and risk factors associated with K-Pro endophthalmitis. Results: Ten (7.1%) of 141 eyes of 130 adult patients were diagnosed and treated for bacterial endophthalmitis. Average time to endophthalmitis developing after K-Pro was 9.8 months (standard deviation [SD], 6.2 months; range, 2–25 months). Coagulase-negative staphylococci were identified in 7 eyes. In 7 of the 10 eyes, recurrent endophthalmitis developed that occurred at a mean of 4 months (SD, 3.9 months; range, 1–13 months) after resolution of the initial episode. At each episode of endophthalmitis, no eye was receiving vancomycin ophthalmic drops and most eyes were receiving only fluoroquinolone ophthalmic drops for prophylaxis. Conclusions: Infectious endophthalmitis after K-Pro implantation has a higher incidence, delayed onset, and high risk for recurrence compared with postoperative endophthalmitis associated with more common intraocular procedures such as cataract surgery. The concurrent use of topical vancomycin is recommended because it seems to be important in reducing the incidence and recurrence of endophthalmitis and because fluoroquinolone ophthalmic drops do not seem to be sufficient prophylaxis in these eyes. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Blepharospasm and Apraxia of Eyelid Opening Associated with Anti-Hu Paraneoplastic Antibodies: A Case Report - Corrected Proof

Christina H. Choe, Roberta E. Gausas — 2012-01-19

Purpose: To report a case of blepharospasm associated with anti-Hu paraneoplastic antibodies that was treated successfully with botulinum toxin A. Design: Case report. Participants: A 57-year-old man had altered mental status and a 20-pound weight loss at presentation. Evaluation revealed an occult small-cell lung cancer. Despite initiating appropriate chemotherapy, his mental status worsened and over the course of several weeks, he was unable to open his eyes because of forceful orbicularis contractions. Neuroimaging and cerebrospinal fluid studies found no evidence of intracranial metastases. However, his paraneoplastic panel was positive for anti-Hu antibodies. He was diagnosed with paraneoplastic encephalitis and blepharospasm. Intervention: Intravenous Solu-Medrol (Pharmacia & Upjohn, Co, Bridgewater, NJ) and periocular injections of botulinum toxin A. Main Outcome Measures: Ocular disease control. Results: Intravenous Solu-Medrol improved his mental status, but did not change his ocular symptoms. Subsequent botulinum toxin A injections allowed spontaneous eyelid opening. Conclusions: Although paraneoplastic blepharospasm is rare, it is an important diagnosis to be aware of because paraneoplastic disorders often herald an occult tumor. This is the only case of paraneoplastic blepharospasm that the authors know of that was the result of anti-Hu antibodies as well as the only case that was treated with botulinum toxin A. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Retinal Nerve Fiber Layer Imaging with Spectral-Domain Optical Coherence Tomography: A Prospective Analysis of Age-Related Loss - Corrected Proof

2012-01-19

Objective: To investigate age-related changes of the retinal nerve fiber layer (RNFL) imaged by a spectral-domain optical coherence tomography (OCT). Design: Prospective, cross-sectional, and longitudinal studies. Participants: One hundred normal individuals were recruited for cross-sectional analysis, 35 of whom were randomly selected for longitudinal analysis. Methods: The circumpapillary average and quadrant RNFL thicknesses were measured by the Cirrus HD-OCT. In the longitudinal study, participants were followed at 4-month intervals for a mean of 30 months (range, 24–41 months) for RNFL and visual field measurements. Cross-sectional RNFL data were analyzed with multiple linear regression models with adjustment of spherical error, optic disc area, and signal strength. Longitudinal RNFL measurements were analyzed with linear mixed models with fixed coefficients on follow-up duration, baseline RNFL thickness, spherical error, optic disc area, and signal strength. Factors influencing the rate of change of RNFL measurements were analyzed in the interaction terms with “duration” in the linear mixed models. Main Outcome Measures: Rates of change of average and quadrant RNFL thicknesses. Results: In the cross-sectional analysis, significant negative correlations were found between age and average (−0.33 μm/year; P = 0.011), inferior (−0.45 μm/year; P = 0.037), and temporal (−0.31 μm/year; P = 0.046) RNFL thicknesses. In the longitudinal analysis, the mean rates of change of average, superior, and inferior RNFL thicknesses were −0.52 (95% confidence interval [CI], −0.86 to −0.17), −1.35 (95% CI, −2.05 to −0.65) and −1.25 μm/year (95% CI, −1.78 to −0.71), respectively, after adjusting for baseline RNFL thickness, spherical error, disc area, and signal strength. There was no detectable RNFL reduction in the nasal and temporal quadrants. The only significant factor influencing the rates of change of RNFL measurements was the baseline RNFL thickness. A greater baseline RNFL thickness was associated with a faster rate of change. Conclusions: Progressive, age-related decline of RNFL thickness can be detected with longitudinal OCT imaging. Rate estimates derived from trend analysis for detection of glaucomatous RNFL progression should be interpreted with reference to the normal ranges of age-related reduction, particularly when the baseline RNFL measurement is large. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Clinical Course, Genetic Etiology, and Visual Outcome in Cone and Cone–Rod Dystrophy - Corrected Proof

2012-01-19

Objective: To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone–rod dystrophy (CRD). Design: Clinic-based, longitudinal, multicenter study. Participants: Consecutive probands with CD (N = 98), CRD (N = 83), and affected relatives (N = 41 and N = 17, respectively) from various ophthalmogenetic clinics in The Netherlands, Belgium, and the United Kingdom. Methods: Data on best-corrected Snellen visual acuity, color vision, ophthalmoscopy, fundus photography, Goldmann perimetry, and full-field standard electroretinogram (ERG) from all patients were registered from medical charts over a mean follow-up of 19 years. The ABCA4, CNGB3, KCNV2, PDE6C, and RPGR genes were analyzed by direct sequencing in autosomal recessive (AR) and X-linked (XL), respectively. Genotyping was not undertaken for autosomal-dominant cases. Main Outcome Measures: The 10-year progression of all clinical parameters and cumulative lifetime risk of low vision and legal blindness were assessed. Results: The mean age onset for CD was 16 years (standard deviation, 11), and of CRD 12 years (standard deviation, 11; P = 0.02). The pattern of inheritance was AR in 92% of CD and 90% of CRD. Ten years after diagnosis, 35% of CD and 51% of CRD had a bull's eye maculopathy; 70% of CRD showed absolute peripheral visual field defects and 37% of CD developed rod involvement on ERG. The mean age of legal blindness was 48 (standard error [SE], 3.1) years in CD, and 35 (SE, 1.1; P<0.001) years in CRD. ABCA4 mutations were found in 8 of 90 (9%) of AR-CD, and in 17 of 65 (26%) of AR-CRD. Other mutations were detected in CNGB3 (3/90; 3%), KCNV2 (4/90; 4%), and in PDE6C (1/90; 1%). The RPGR gene was mutated in the 2 XL-CD and in 4 of 5 (80%) of XL-CRD. ABCA4 mutations as well as age of onset <20 years were significantly associated with a faster progression to legal blindness (P<0.001). Conclusions: Although CD had a slightly more favorable clinical course than CRD, both disorders progressed to legal blindness in the majority of patients. Mutations in the ABCA4 gene and early onset of disease were independent prognostic parameters for visual loss. Our data may serve as an aid in counseling patients with progressive cone disorders. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Efficacy and Safety of Long-term Corticosteroid Eye Drops after Penetrating Keratoplasty: A Prospective, Randomized, Clinical Trial - Corrected Proof

Jun Shimazaki, Ayumi Iseda, Yoshiyuki Satake, Seika Shimazaki-Den — 2012-01-19

Purpose: Endothelial rejection remains a major cause of graft failure after penetrating keratoplasty (PKP). Topical corticosteroids are the gold standard for preventing rejection; however, protocols for corticosteroid treatment have been diverse. The aim of the present study was to examine the efficacy and safety of long-term use of corticosteroid eye drops after PKP in a randomized, clinical trial. Design: Randomized, nonblinded, clinical trial. Participants: We enrolled 42 patients (21 males and 21 females) with a mean age of 65.3 years who underwent PKP and maintained graft clarity for >1 year with topical steroid eye drops. Intervention: Patients were randomly assigned to 1 of 2 groups: Administration of 0.1% fluorometholone 3 times a day (steroid group) or discontinuation of steroid eye drops (no steroid group). All patients were followed for 12 months. Main Outcome Measures: Proportion of eyes without endothelial rejection and the proportion of eyes with clear grafts and the incidence of local or systemic side effects. Results: Of the initial 42 patients, 4 in the steroid group and 6 in the no steroid group did not complete the trial. Of the patients who completed the trial, 1 patient in the steroid group and 6 in the no steroid group developed endothelial rejection at an average of 5.2±4.5 (mean ± standard deviation) months after study enrollment. The difference in the incidence of rejection between groups was found to be significant by both chi-square (P = 0.027) and Kaplan–Meier analyses (log-rank test, P = 0.032). No difference was observed between the 2 groups in visual acuity, intraocular pressure, epithelial damage, tear-film break-up time, cataract progression, infection, or incidence of systemic side effects. Conclusions: Prolonged use of 0.1% fluorometholone was beneficial for the prevention of rejection after PKP. Because no adverse consequences were noted, we recommend continuing use of the low-dose corticosteroids, even in non–high-risk cases. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Epidemiologic Characteristics of Intraocular Pressure in the Korean and Mongolian Populations: The Healthy Twin and the GENDISCAN Study - Corrected Proof

2012-01-16

Purpose: The purpose of this study was to demonstrate a negative association between intraocular pressure (IOP) and age in 2 Asian populations. In addition, we evaluated genetic and nongenetic factors associated with IOP. Design: Family-based cohort study. Participants: Study subjects >10 years of age from one Korean (The Healthy Twin; n = 1431) and 2 Mongolian populations (The GENDISCAN; n = 859 and 806) with IOP values. Methods: The IOP values were measured with a noncontact tonometer. Each participant received a standard health examination and received questionnaires, which include candidate risk factors on IOP. Mixed models were used to identify risk factors for IOP. Variance-component methods were applied to estimate the heritability of IOP. Main Outcome Measures: The negative trend of IOP with aging and evaluation of impact of genetic and nongenetic components on IOP. Results: The mean ages were 43.6, 34.1, and 36.3 years for the Korean, Orhontuul, and Dashbalbar populations, respectively. The mean IOPs were 14.4 mmHg (95% confidence interval [CI], 14.3–14.6) in the Koreans and 14.1 mmHg (95% CI, 13.9–14.3) and 12.6 mmHg (95% CI, 12.4–12.9) in the Orhontuul and Dashbalbar populations, respectively. In the 3 populations, the IOP decreased as age increased. We replicated an association of systolic blood pressure (SBP) with IOP. In addition, components of the metabolic syndrome (MS), such as plasma glucose, lipid level, and body mass index, showed positive associations with IOP, after adjusting for age and SBP. The IOP also had strong genetic contributions in all populations (heritability, 0.47–0.51). Conclusions: Negative associations between age and IOP were observed in all 3 populations, which cannot be explained by the increasing prevalence of myopia in the younger generation. The different age trend in IOP may in part be responsible for differences in the prevalence of glaucoma subtypes. Our findings suggest that associations between IOP and MS components were independent of established risk factors such as SBP or age. In addition, the importance of inherited risks requires further genetic dissection of IOP determinants for biological understandings of underlying pathophysiology. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Outcomes and Bleb-Related Complications of Trabeculectomy - Corrected Proof

2012-01-16

Purpose: To determine rates of success and complications of trabeculectomy surgery. Design: Case series. Participants: Consecutive patients undergoing trabeculectomy by 2 surgeons between May 2000 and October 2008. Intervention: By using the Wilmer Institute's billing database, we identified all patients at least 12 years of age coded as having undergone trabeculectomy between May 2000 and October 2008 by 1 of 2 glaucoma surgeons and whose surgery was not combined with another operation. From the chart, we abstracted demographic information on the patients and clinical characteristics of the eyes. The Kaplan–Meier product-limit method and Cox proportional hazard models were used to look at success rates and characteristics associated with inadequate intraocular pressure (IOP) reduction. Complications were tabulated. Main Outcome Measures: (1) Success rate of trabeculectomy, as determined by the achievement of each of 4 different IOP goals, with or without IOP-lowering medications; and (2) incidence of surgical complications. Results: During the study period, 797 eyes of 634 persons underwent trabeculectomy without concurrent surgery. The success rates 4 years after surgery, with or without the use of IOP-lowering eye drops, were 70%, 72%, 60%, and 44%, for achievement of target IOP, ≤18 mmHg and ≥20% IOP reduction, ≤15 mmHg and ≥25% reduction, and ≤12 mmHg and ≥30% reduction, respectively. Increased chance of success was associated with European-derived race; use of mitomycin C (MMC); higher concentrations of MMC, when used; and higher preoperative IOP. Age and previous intraocular surgery were not associated with surgical success. Complications included worsening lens opacity in 242 of 443 phakic eyes (55%), loss of ≥3 lines of acuity (Snellen) in 161 eyes (21%), surgery for bleb-related problems in 70 eyes (8.8%), and infection occurring >6 weeks after surgery in 27 eyes (3.4%). A total of 101 eyes of 94 patients had at least 1 subsequent operation for inadequate IOP control. Conclusions: Trabeculectomy surgery performed by 2 experienced glaucoma specialists achieved target IOP at 4 years in 70% of those operated and was associated with progressive cataract and small risks of bleb-related complications. These results are comparable to those reported in smaller series. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Interim Results from the International Trial of Second Sight's Visual Prosthesis - Corrected Proof

2012-01-12

Purpose: This study evaluated the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in blind subjects with severe outer retinal degeneration. Design: Single-arm, prospective, multicenter clinical trial. Participants: Thirty subjects were enrolled in the United States and Europe between June 6, 2007, and August 11, 2009. All subjects were followed up for a minimum of 6 months and up to 2.7 years. Methods: The electronic stimulator and antenna of the implant were sutured onto the sclera using an encircling silicone band. Next, a pars plana vitrectomy was performed, and the electrode array and cable were introduced into the eye via a pars plana sclerotomy. The microelectrode array then was tacked to the epiretinal surface. Main Outcome Measures: The primary safety end points for the trial were the number, severity, and relation of adverse events. Principal performance end points were assessments of visual function as well as performance on orientation and mobility tasks. Results: Subjects performed statistically better with the system on versus off in the following tasks: object localization (96% of subjects), motion discrimination (57%), and discrimination of oriented gratings (23%). The best recorded visual acuity to date is 20/1260. Subjects' mean performance on orientation and mobility tasks was significantly better when the system was on versus off. Seventy percent of the patients did not have any serious adverse events (SAEs). The most common SAE reported was either conjunctival erosion or dehiscence over the extraocular implant and was treated successfully in all subjects except in one, who required explantation of the device without further complications. Conclusions: The long-term safety results of Second Sight's retinal prosthesis system are acceptable, and most subjects with profound visual loss perform better on visual tasks with system than without it. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Multi-Year Follow-up of Fine-Needle Aspiration Biopsy in Choroidal Melanoma - Corrected Proof

Tara A. McCannel, Melinda Y. Chang, Barry L. Burgess — 2012-01-09

Purpose: To report the local and systemic follow-up of patients undergoing transscleral intraoperative fine-needle aspiration biopsy (FNAB) at the time of iodine-125 plaque brachytherapy for the treatment of choroidal melanoma. Design: Retrospective, single-center, consecutive case cohort study. Participants: A total of 170 consecutive patients with choroidal melanoma. Methods: All patients with choroidal melanoma treated with iodine-125 brachytherapy and intraoperative FNAB from January 2005 to January 2010 with at least 1 year of clinical follow-up were included. Main Outcome Measures: Outcomes examined were endophthalmitis, orbital dissemination, local treatment failure, rhegmatogenous retinal detachment, monosomy 3 status, and choroidal melanoma metastasis. Results: A total of 170 consecutive patients with clinical diagnosis of choroidal melanoma, intraoperative FNAB, and post-brachytherapy follow-up of 1 to 6 years (mean, 2.7±1.3 years) were included. For tumors with height of <3.0 mm, 3.0 to 5.0 mm, and >5.0 mm, sufficient biopsy material for fluorescence in situ hybridization (FISH) was obtained in 53%, 68%, and 91%, respectively. During the follow-up period, there was no case of postoperative endophthalmitis, orbital dissemination, or local treatment failure. Three patients developed rhegmatogenous retinal detachment. Fourteen patients developed clinical evidence of metastasis. Of the 14 patients, 8 had monosomy 3 of the primary tumor, 2 had disomy 3, 1 had trisomy 3, and 3 had insufficient material for FISH. The cumulative 5-year Kaplan–Meier metastatic rate was 13%. Conclusions: Transscleral FNAB at the time of iodine-125 plaque brachytherapy was not associated with endophthalmitis, orbital dissemination, or local treatment failure in this series, and post-brachytherapy retinal detachment occurred in 3 eyes. The cumulative Kaplan–Meier 5-year metastatic rate was not statistically different from the rate of 13% reported by the Collaborative Ocular Melanoma Study for tumors of the same size treated by brachytherapy without biopsy. Rhegmatogenous retinal detachment may occur in young patients secondary to posterior vitreous detachment induced by tumor response to radiation, unrelated to FNAB. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Eyes or Subjects: Are Ophthalmic Randomized Controlled Trials Properly Designed and Analyzed? - Corrected Proof

Chun Fan Lee, Andy Chi On Cheng, Daniel Yee Tak Fong — 2012-01-09

Objective: In ophthalmic randomized controlled trials (RCTs), each subject may have 2 potential data points (i.e., eyes) contributing to the clinical trial. Hence, various study designs may arise requiring different statistical tools. This study aimed to assess the appropriateness of study design, statistical tools used, and reporting of results in ophthalmic RCTs. Design: A systematic review of 69 ophthalmic RCTs. Methods: The study design, sample size calculation, statistical analysis, and reporting methodology of all RCTs published in 4 major general clinical ophthalmology journals in 2009 were assessed. Main Outcome Measures: The study design of each article under review is evaluated. Results: The most common study design was a one-eye design (48%). Within this group, only half described the method of selecting the study eye, among which 5 chose the study eye by random selection. In the remaining trials, there were paired-eye design (13%), subject design (19%), and two-eye design (19%). Among the 13 two-eye design studies, 4 allocated both eyes of the subject to the same group, 4 allocated the eyes to different groups, and 4 did not restrict the allocation. None of these studies adjusted for the clustering effect in sample size calculation. Only 5 studies used statistical methods adjusting for nonindependence. Conclusions: There is currently substantial heterogeneity in the quality among published ophthalmic RCTs in terms of proper use of study design, sample size calculation, randomization method, and statistical tools. Future ophthalmic researchers are suggested to consult a statistician and to follow some guidelines such as the CONSORT statement when performing an RCT to improve further the quality of clinical trial. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison of Limbus-Based and Fornix-Based Trabeculectomy: Success, Bleb-Related Complications, and Bleb Morphology - Corrected Proof

2012-01-09

Purpose: To compare the success and complications of trabeculectomy performed with limbus-based and fornix-based conjunctival approaches. Design: Retrospective case series with some prospective data collection. Participants: Consecutive patients undergoing trabeculectomy by 2 surgeons between May 2000 and October 2008. Intervention: We performed limbus-based operations during the first 4 years and fornix-based operations during the last 4 years. We collected data by chart review and by examination at the most recent visit. For each follow-up visit, we defined success as undergoing no further glaucoma procedure and achieving one of our intraocular pressure (IOP) criteria. We used Kaplan–Meier survival analysis, Cox proportional hazards models, and generalized estimating equation (GEE) analysis. During 2009, 439 trabeculectomy sites of 347 patients were quantitatively assessed by the Indiana bleb grading system. Main Outcome Measures: (1) Success rate of trabeculectomy, as determined by the achievement of each of our different IOP goals, with or without IOP-lowering medications; and (2) incidence of surgical complications. Results: During the 4 years after surgery, the success rates of limbus-based and fornix-based trabeculectomy were not statistically different for any of our IOP criteria. Blebs after limbus-based surgery were more likely to be graded as higher and to be avascular (GEE model, both P < 0.0001). Four percent of eyes experienced late-onset bleb leaks within 4 years after both limbus- and fornix-based operations; however, limbus-based cases developed bleb leaks significantly later than did fornix-based cases (2.1 vs. 1.0 years; P=0.002, GEE model). Late bleb-associated infection during the first 4 years after surgery occurred more often in limbus-based operations, although statistical significance was borderline (P=0.054, Cox model). Symptomatic hypotony during all available follow-up was more common with fornix-based operations (P=0.01, GEE model). Eyes undergoing the fornix-based operation had a greater risk of cataract surgery in the 4-year period after surgery (P=0.02, Cox model), and fornix-based cases requiring cataract surgery had the operation earlier than limbus-based cases (P=0.002, GEE model). Conclusions: Success rates are similar between limbus-based and fornix-based trabeculectomy. Limbus-based procedures produce higher, more avascular blebs, with a greater risk of infection. Fornix-based procedures have more symptomatic hypotony and more and earlier cataract development. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intralesional Interferon-α for Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma: Long-term Results - Corrected Proof

2012-01-06

Objective: To report the long-term therapeutic results for patients with conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma who were treated with intralesional injections of interferon-α (IFN-α). Design: Prospective, nonrandomized, interventional case series. Participants: Twenty eyes of 16 patients with histologically proven conjunctival MALT lymphoma in the absence of systemic disease. Methods: Patients were given 1 500 000 international units (IU) of IFN-α (Roferon-A; Roche s.p.a., Milano, Italy) subconjunctivally inside the lesion 3 times weekly for 4 weeks. If there was even a minimal response, a further cycle of 1 000 000 IU 3 times weekly for 4 weeks was administered. Main Outcome Measures: Patients were followed up clinically using slit-lamp examination to determine evidence of tumor disappearance or recurrence. In 10 eyes, an incisional biopsy was performed 6 months after therapy to verify the histologic absence of the lesion. Results: A complete response was obtained in 15 eyes (75%) at the end of first cycle treatment, and in 5 eyes (25%) after further cycles. Seventeen eyes (85%) showed no local recurrence after a median follow-up of 65 months (range, 15–136 months). Three eyes (15%) demonstrated recurrence at variable points after treatment. One patient with stage IIA lymphoma exhibited systemic lymphoma progression. Conclusions: Local immunotherapy with IFN-α seems to be an effective and lasting treatment method and provides an alternative to radiotherapy for conjunctival MALT lymphomas. Very few transient side effects were detected. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison of a New Refractive Multifocal Intraocular Lens with an Inferior Segmental Near Add and a Diffractive Multifocal Intraocular Lens - Corrected Proof

2012-01-04

Purpose: To compare the visual acuity outcomes and ocular optical performance of eyes implanted with a multifocal refractive intraocular lens (IOL) with an inferior segmental near add or a diffractive multifocal IOL. Design: Prospective, comparative, nonrandomized, consecutive case series. Participants: Eighty-three consecutive eyes of 45 patients (age range, 36–82 years) with cataract were divided into 2 groups: group A, 45 eyes implanted with Lentis Mplus LS-312 (Oculentis GmbH, Berlin, Germany); group B, 38 eyes implanted with diffractive IOL Acri.Lisa 366D (Zeiss, Oberkochen, Germany). Methods: All patients underwent phacoemulsification followed by IOL implantation in the capsular bag. Distance corrected, intermediate, and near with the distance correction visual acuity outcomes and contrast sensitivity, intraocular aberrations, and defocus curve were evaluated postoperatively during a 3-month follow-up. Main Outcome Measures: Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected near visual acuity (UNVA), corrected distance near and intermediate visual acuity (CDNVA), contrast sensitivity, intraocular aberrations, and defocus curve. Results: A significant improvement in UDVA, CDVA, and UNVA was observed in both groups after surgery (P≤0.04). Significantly better values of UNVA (P<0.01) and CDNVA (P<0.04) were found in group B. In the defocus curve, significantly better visual acuities were present in eyes in group A for intermediate vision levels of defocus (P≤0.04). Significantly higher amounts of postoperative intraocular primary coma and spherical aberrations were found in group A (P<0.01). In addition, significantly better values were observed in photopic contrast sensitivity for high spatial frequencies in group A (P≤0.04). Conclusions: The Lentis Mplus LS-312 and Acri.Lisa 366D IOLs are able to successfully restore visual function after cataract surgery. The Lentis Mplus LS-312 provided better intermediate vision and contrast sensitivity outcomes than the Acri.Lisa 366D. However, the Acri.Lisa design provided better distance and near visual outcomes and intraocular optical performance parameters. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Quality of Nonmydriatic Digital Fundus Photography Obtained by Nurse Practitioners in the Emergency Department: The FOTO-ED Study - Corrected Proof

2012-01-04

Objective: Nonmydriatic fundus photography by non–ophthalmic-trained personnel has recently been shown to be a potential alternative to direct ophthalmoscopy in the emergency department (ED). We evaluated the reliability of a novel quality rating scale and applied this scale to nonmydriatic fundus photographs taken during routine ED patient encounters to determine factors associated with diminished photograph quality. Design: Prospective, cross-sectional study. Participants: We included 350 patients enrolled in the Fundus photography versus Ophthalmoscopy Trials Outcomes in the Emergency Department study who were photographed by nurse practitioners after <30 minutes of training followed by supervision. Methods: Photographs of both eyes were graded for quality on 2 occasions by 2 neuro-ophthalmologists. Four regions were independently evaluated for quality: Optic disc, macula, and superior and inferior vascular arcades. Quality as a function of the number of photographs taken was evaluated by Kaplan–Meier analysis. Mixed effects ordinal logistic regression was used to evaluate for predictors of image quality while accounting for the repeated measures design. Main Outcome Measures: Overall photographic quality (1–5 scale; 5 best). Results: We evaluated 1734 photographs. Inter- and intraobserver agreements between neuro-ophthalmologists were very good (weighted kappa, 0.84–0.87). Quality of the optic disc area was better than those of other retinal areas (P<0.002). Kaplan–Meier analysis showed that if a high-quality photograph of an eye was not obtained by the third attempt, it was unlikely that one would be obtained at all. A 10-second increase in the interphotograph interval before a total of 40 seconds increased the odds of a 1-unit higher quality rating by 1.81 times (95% confidence interval [CI], 1.68–1.98), and a 10-year increase in age decreased the odds by 0.76 times (95% CI, 0.69–0.85). Black patients had 0.42 times (95% CI, 0.28–0.63) the odds of a 1-unit higher quality rating compared with whites. Conclusions: Our 5-point scale is a reliable measure of nonmydriatic photograph quality. The region of interest, interphotograph interval, and patient age and race are significant predictors of image quality for nonmydriatic photographs taken by nurse practitioners in the ED. Addressing these factors may have a direct impact on the successful implementation of nonmydriatic fundus photography into the ED. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Risk of Corneal Transplant Rejection Significantly Reduced with Descemet's Membrane Endothelial Keratoplasty - Corrected Proof

Arundhati Anshu, Marianne O. Price, Francis W. Price — 2012-01-04

Purpose: To evaluate the relative risk of immunologic rejection episode in patients who underwent Descemet's membrane endothelial keratoplasty (DMEK), Descemet's stripping endothelial keratoplasty (DSEK), and penetrating keratoplasty (PK). Design: Comparative case series. Participants: One hundred forty-one eyes treated with DMEK at Price Vision Group, Indianapolis, Indiana. Methods: The patients in the DMEK group were compared retrospectively with cohorts of DSEK (n = 598) and PK (n = 30) patients treated at the same center, with similar demographics, follow-up duration, and indications for surgery. The postoperative steroid regimen and rejection criteria were identical in the 3 groups. Kaplan–Meier survival analysis, which takes varying length of follow-up into consideration, was performed to determine the cumulative probability of a rejection episode 1 and 2 years after surgery. Proportional hazards analysis was used to determine the relative risk of rejection episodes between the 3 groups. P<0.05 was considered significant and calculated using the log-rank test. Main Outcome Measures: Rejection-free survival and cumulative probability of a rejection episode. Results: The mean recipient age was 66 years (56% females and 94% Caucasian) and median follow-up duration was 13 months (range, 3–40) in the DMEK group. Fuchs' dystrophy was the most common indication for surgery (n = 127; 90%) followed by pseudophakic bullous keratopathy (n = 4; 4%) and regrafts (n = 9; 6.4%). Only 1 patient (0.7%) had a documented rejection episode in the DMEK group compared with 54 (9%) in the DSEK and 5 (17%) in the PK group. The Kaplan–Meier cumulative probability of a rejection episode at 1 and 2 years was 1% and 1%, respectively, for DMEK; 8% and 12%, respectively, for DSEK; and 14% and 18%, respectively, for PK. This was a highly significant difference (P = 0.004). The DMEK eyes had a 15 times lesser risk of experiencing a rejection episode than DSEK eyes (95% confidence limit [CL], 2.0–111; P = 0.008) and 20 times lower risk than PK eyes (95% CL, 2.4–166; P = 0.006). Conclusions: Patients undergoing DMEK had a significantly reduced risk of experiencing a rejection episode within 2 years after surgery compared with DSEK and PK performed for similar indications using the same corticosteroid regimen. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Vitrectomy without Laser Treatment or Gas Tamponade for Macular Detachment Associated with an Optic Disc Pit - Corrected Proof

Akito Hirakata, Makoto Inoue, Tomoyuki Hiraoka, Brooks W. McCuen — 2012-01-04

Purpose: To evaluate the clinical outcomes after vitrectomy, without gas tamponade or laser photocoagulation to the margin of the optic nerve, for the treatment of macular detachment associated with optic disc pits and to characterize retinal manifestations during treatment of optic pit maculopathy using optical coherence tomography (OCT). Design: Noncomparative, retrospective, interventional case series. Participants: Eight consecutive patients (8 to 56 years of age) with unilateral macular detachment associated with optic disc pit. Intervention: Pars plana vitrectomy with induction of a posterior vitreous detachment (PVD) was performed in all eyes. No laser or gas injection was performed in any eye during the original surgery. Patients were followed up for 10 to 46 months (mean, 26 months) after surgery. Main Outcome Measures: Anatomic outcome as determined by OCT and postoperative visual acuities were the main outcome parameters. Fundus autofluorescence (FAF) images were obtained in 4 eyes to document anatomic changes in the macula. Results: Although complete retinal reattachment was achieved in 7 of 8 eyes, up to about 1 year was necessary for the retinal detachment to resolve fully. The 1 eye in which macular detachment failed to resolve completely underwent revision of vitrectomy with a gas tamponade and laser photocoagulation in the peripapillary area. In the early postoperative period, despite persistent macular detachment, the visual acuities improved in 7 eyes. These improved acuities corresponded with remodeling of the photoreceptor outer segments on OCT and the appearance of granular hyperfluorescence on FAF imaging. Conclusions: Vitrectomy with induction of a PVD at the optic disc without gas tamponade or laser photocoagulation seems to be an effective method of managing macular detachment resulting from optic disc pits. The OCT scanning before and after surgery suggests that peripapillary vitreous traction with the passage of fluid into the retina through the pit is the cause of the schisis-like separation seen in optic disc pit maculopathy. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

An Outbreak of Acute Post-Cataract Surgery Pseudomonas sp. Endophthalmitis Caused by Contaminated Hydrophilic Intraocular Lens Solution - Corrected Proof

2012-01-04

Objective: To report the investigation for the source of infection and the clinical course and treatment response of 11 cases of acute post-cataract surgery endophthalmitis that developed during an outbreak. Design: Retrospective, consecutive, interventional case series. Participants: Eleven patients who developed acute postoperative endophthalmitis after an uneventful cataract surgery with intraocular lens implantation from September 6 to 29, 2010, at a tertiary eye care center in South India. Methods: Aqueous aspirates, vitreous aspirates, and environmental surveillance specimens were sampled. All specimens were subjected to smear and culture. Positive cultures were subjected to antibiotic susceptibility. Genotypic diversity was determined by polymerase chain reaction (PCR) with enterobacterial repetitive intergenic consensus (ERIC) primers of each strain and was used to establish the clonal relationship between clinical and environmental isolates. The clinical patterns were analyzed. Main Outcome Measures: Positive microbiology, molecular diagnostic similarity among the culture positive endophthalmitis cases, and surveillance specimens. Results: Aqueous and vitreous samples showed gram-negative bacilli in the smears of 8 of 11 eyes, and cultures grew Pseudomonas aeruginosa in 5 of 11 eyes. Among the samples from various surveillance specimens cultured, only the hydrophilic acrylic intraocular lenses and their solution grew P. aeruginosa, with antibiotic susceptibility pattern identical to the clinical isolates. The isolates from the patients and the intraocular lens solution revealed matching patterns similar to an American Type Culture Collection (ATCC) strain of P. aeruginosa on ERIC-PCR. The intraocular lenses of the same make were discontinued at our hospital, and the endophthalmitis did not recur. The final visual acuity improved to ≥20/50 in 8 of 11 patients (72.7%). One patient developed retinal detachment, but was treated successfully, and 2 other patients progressed to phthisis bulbi. Conclusions: Positive microbiology and the ERIC-PCR results proved that contamination of hydrophilic intraocular lenses and the preservative solution was the source of infection in this outbreak. Early detection and a planned approach during the outbreak helped us to achieve good visual and anatomic outcomes, even though the offending organism was identified as P. aeruginosa. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Correlation between Clinical Features, Magnetic Resonance Imaging, and Histopathologic Findings in Retinoblastoma: A Prospective Study - Corrected Proof

2012-01-04

Objective: To correlate clinical features with histopathology findings in advanced intraocular retinoblastoma and to determine the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting tumor invasion. Design: Prospective, nonrandomized case series. Participants: We included 75 patients with group E retinoblastoma. Methods: Demographic and clinical features were recorded at presentation. Contrast-enhanced MRI was performed to study tumor characteristics and extent of invasion. Primary enucleation was performed and histopathologic features noted. Statistical analysis was done using the Kruskal–Wallis test to determine correlation between clinical features and histopathology. Sensitivity, specificity, and accuracy of MRI in detecting tumor invasion were determined. Main Outcome Measures: Significant associations between clinical findings at presentation and high-risk histopathology, and correlation between MRI results and histopathologic evidence of tumor invasion. Results: A significant association was found between iris neovascularization and choroidal invasion (P = 0.032), intraocular pressure and optic nerve invasion (P = 0.034), and shallow anterior chamber and iris invasion (P = 0.021). Corneal diameter did not show any significant correlation with high-risk histopathology. On MRI, tumor volume showed a significant association with optic nerve invasion (P = 0.023). The accuracy of MRI in detecting choroidal invasion was 68% (sensitivity, 60%; specificity, 80%). Prelaminar invasion was correctly identified in 9 out of 15 eyes (accuracy, 84%; sensitivity, 60%; specificity, 90%), whereas the accuracy of MRI in detecting postlaminar invasion was 76% (sensitivity, 61.9%; specificity, 81.5%). Ciliary body invasion was correctly identified in 5 out of 7 eyes (accuracy, 93.3%; specificity, 95.6%) and scleral invasion in 5 out of 6 eyes (accuracy, 98.7%; specificity, 100%). Conclusions: As far as we are aware, this is the first prospective study on the correlation of clinical features and MRI findings with histopathologic risk factors in eyes primarily enucleated for retinoblastoma. Neovascularization of iris, intraocular pressure, shallow anterior chamber, and tumor volume correlated well with high-risk histopathology. Because MRI has limitations in reliably predicting microscopic infiltration of the choroid and optic nerve, decision in favor of neoadjuvant chemotherapy on the basis of suspected postlaminar invasion on MRI is not justified in the absence of histopathologic evidence of disease. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Trends in Use of Ancillary Glaucoma Tests for Patients with Open-Angle Glaucoma from 2001 to 2009 - Corrected Proof

Joshua D. Stein, Nidhi Talwar, Alejandra M. LaVerne, Bin Nan, Paul R. Lichter — 2012-01-04

Purpose: To assess trends in the use of ancillary diagnostic tests in the evaluation of patients with open-angle glaucoma (OAG) and glaucoma suspects over the past decade. Design: Retrospective, longitudinal cohort analysis. Participants: A total of 169 917 individuals with OAG and 395 721 individuals with suspected glaucoma aged ≥40 years enrolled in a national United States managed care network between 2001 and 2009. Methods: Claims data were analyzed to assess trends in visual field (VF) testing, fundus photography (FP), and other ocular imaging (OOI) testing for patients with OAG or suspected glaucoma between 2001 and 2009. Repeated-measures logistic regression was performed to identify differences in the odds of undergoing these procedures in 2001, 2005, and 2009 and whether differences exist for patients under the exclusive care of optometrists versus ophthalmologists. Main Outcome Measures: Odds and annual probabilities of undergoing VF testing, FP, and OOI for OAG from 2001 to 2009. Results: For patients with OAG, the odds of undergoing VF testing decreased by 36% from 2001 to 2005, by 12% from 2005 to 2009, and by 44% from 2001 to 2009. By comparison, the odds of having OOI increased by 100% from 2001 to 2005, by 24% from 2005 to 2009, and by 147% from 2001 to 2009. Probabilities of undergoing FP were relatively low (13%–25%) for both provider types and remained fairly steady over the decade. For patients cared for exclusively by optometrists, the probability of VF testing decreased from 66% in 2001 to 44% in 2009. Among those seen exclusively by ophthalmologists, the probability of VF testing decreased from 65% in 2001 to 51% in 2009. The probability of undergoing OOI increased from 26% in 2001 to 47% in 2009 for patients of optometrists and from 30% in 2001 to 46% in 2009 for patients of ophthalmologists. By 2008, patients with OAG receiving care exclusively by optometrists had a higher probability of undergoing OOI than VF testing. Conclusions: From 2001 to 2009, OOI increased dramatically whereas VF testing declined considerably. Because OOI has not been shown to be as effective at detecting OAG or disease progression compared with VF testing, increased reliance on OOI technology, in lieu of VF testing, may be detrimental to patient care. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Optic Disc Margin Anatomy in Patients with Glaucoma and Normal Controls with Spectral Domain Optical Coherence Tomography - Corrected Proof

2012-01-04

Objective: To characterize optic nerve head (ONH) anatomy related to the clinical optic disc margin with spectral domain-optical coherence tomography (SD-OCT). Design: Cross-sectional study. Participants: Patients with open-angle glaucoma with focal, diffuse, and sclerotic optic disc damage, and age-matched normal controls. Methods: High-resolution radial SD-OCT B-scans centered on the ONH were analyzed at each clock hour. For each scan, the border tissue of Elschnig was classified for obliqueness (internally oblique, externally oblique, or nonoblique) and the presence of Bruch's membrane overhanging the border tissue. Optic disc stereophotographs were co-localized to SD-OCT data with customized software. The frequency with which the disc margin identified in stereophotographs coincided with (1) Bruch's membrane opening (BMO), defined as the innermost edge of Bruch's membrane; (2) Bruch's membrane/border tissue, defined as any aspect of either outside BMO or border tissue; or (3) border tissue, defined as any aspect of border tissue alone, in the B-scans was computed at each clock hour. Main Outcome Measures: The SD-OCT structures coinciding with the disc margin in stereophotographs. Results: There were 30 patients (10 with each type of disc damage) and 10 controls, with a median (range) age of 68.1 (42–86) years and 63.5 (42–77) years, respectively. Although 28 patients (93%) had 2 or more border tissue configurations, the most predominant one was internally oblique, primarily superiorly and nasally, frequently with Bruch's membrane overhang. Externally oblique border tissue was less frequent, observed mostly inferiorly and temporally. In controls, there was predominantly internally oblique configuration around the disc. Although the configurations were not statistically different between patients and controls, they were among the 3 glaucoma groups. At most locations, the SD-OCT structure most frequently identified as the disc margin was some aspect of Bruch's membrane and border tissue external to BMO. Bruch's membrane overhang was regionally present in the majority of patients with glaucoma and controls; however, in most cases it was not visible as the disc margin. Conclusions: The clinically perceived disc margin is most likely not the innermost edge of Bruch's membrane detected by SD-OCT. These findings have important implications for the automated detection of the disc margin and estimates of the neuroretinal rim. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Ophthalmology Residency Match Outcomes for 2011 - Corrected Proof

Salman J. Yousuf, Leslie S. Jones — 2012-01-04

Purpose: To determine the match rate and predictors of matching into an ophthalmology residency. Design: Population-based, cross-sectional study. Participants: All 746 candidates who submitted an application for the 2011 ophthalmology residency match. Methods: The Ophthalmology Residency Matching Program applicant database was reviewed to determine applicant characteristics and match outcomes. For US seniors, multivariate regression analysis was performed to determine predictors of matching. Main Outcome Measures: Match rate and predictors of US seniors matching. Results: Rank lists were submitted by 622 applicants, among whom 458 (74%) matched. The match rate was higher for US seniors (83%) than for independent applicants (41%; P < 0.001). US seniors who matched were more likely to be Alpha Omega Alpha medical honor society members (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.16–7.29), to attend medical schools ranked in the top 40 according to National Institutes of Health funding (OR, 2.25; CI, 1.14–4.43), and to have ranked more programs (OR, 1.44; CI, 1.29–1.60). Those ranking 6 to 10 programs had an 80% to 90% chance of matching, and those ranking more than 10 programs had a greater than 90% chance of matching. No clear benefit was observed by ranking additional programs once 11 had already been ranked. Average US Medical Licensing Examination Step 1 scores were 239±14 and 223±18 for applicants who were matched and unmatched, respectively; this difference was significant by univariate analysis (P < 0.001) but not by multivariate regression (P = 0.163). Conclusions: Ophthalmology ranks among the most competitive specialties in medicine. Those most likely to match were US seniors who maintained academic excellence beginning in their preclinical years. A finite relationship exists between ranking a greater number of programs and having a greater chance of matching. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Risk Factors for Cortical, Nuclear, Posterior Subcapsular, and Mixed Lens Opacities: The Los Angeles Latino Eye Study - Corrected Proof

Grace M. Richter, Mina Torres, Farzana Choudhury, Stanley P. Azen, Rohit Varma — 2011-12-26

Purpose: To identify sociodemographic and biological risk factors associated with having cortical, nuclear, posterior subcapsular (PSC), and mixed lens opacities. Design: Population-based, cross-sectional study. Participants: A total of 5945 Latinos aged ≥40 years from 6 census tracts in Los Angeles, California. Methods: Participants underwent an interview and detailed eye examination, including best-corrected visual acuity and slit-lamp assessment of lens opacities using the Lens Opacities Classification System II. Univariate and stepwise logistic regression analyses were used to identify independent risk factors associated with each type of lens opacity. Main Outcome Measures: Odds ratios for sociodemographic and biological risk factors associated with cortical only, nuclear only, PSC only, and mixed lens opacities. Results: Of the 5945 participants with gradable lenses, 468 had cortical only lens opacities, 217 had nuclear only lens opacities, 27 had PSC only opacities, and 364 had mixed lens opacities. Older age, higher hemoglobin A1c, and history of diabetes mellitus were independent risk factors for cortical only lens opacities. Older age, smoking, and myopic refractive error were independent risk factors for nuclear only lens opacities. Higher systolic blood pressure and history of diabetes were independent risk factors for PSC lens opacities. Older age, myopic refractive error, history of diabetes, higher systolic blood pressure, female gender, and presence of large drusen were independent risk factors for mixed lens opacities. Conclusions: The modifiable and non-modifiable risk factors identified in this study provide insight into the mechanisms related to the development of lens opacification. Improved glycemic control, smoking cessation and prevention, and blood pressure control may help to reduce the risk of having lens opacities and their associated vision loss. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Conjunctival Stromal Tumor: Report of 4 Cases - Corrected Proof

Martina C. Herwig, Jill R. Wells, Hans E. Grossniklaus — 2011-12-26

Purpose: To describe the clinical, histopathologic, immunohistochemical, and ultrastructural features of a case series of benign stromal tumors in the bulbar conjunctiva. Design: Observational case series. Participants: Four patients with a conjunctival lesion that were classified histologically as low-grade stromal tumors consisting of spindle-shaped cells with occasional pseudonuclear inclusion and multinucleated cells in a partly myxoid matrix. Methods: Four cases of low-grade conjunctival stromal tumors were retrospectively identified in an ophthalmic pathology laboratory database. Patients' records were analyzed for demographic data, clinical appearance, and the postoperative course. Formalin-fixed, paraffin-embedded specimens were routinely processed and stained with hematoxylin and eosin and periodic acid Schiff. Immunohistochemical stains for vimentin, S100, CD34, smooth muscle actin (SMA), CD68, and factor XIIIa were performed. Transmission electron microscopy (TEM) was performed on 3 of the cases. Main Outcome Measures: Histopathologic evaluation (including immunostains and TEM) and clinical correlation. Results: All 4 tumors occurred in the bulbar conjunctiva of patients between 41 to 53 years of age. None of the patients developed recurrence after excisional biopsy. Histologically, all tumors exhibited spindle-shaped cells with pseudonuclear inclusions and occasional multinuclear cells. Mitotic figures were not observed. The stroma seemed to be myxoid to collagenous. Immunohistochemical stains were positive for CD34, vimentin, and focally for CD68, but were negative for S100 and SMA. Conclusions: We propose to classify these benign lesions, which share distinct histopathologic features, as “conjunctival stromal tumors.” A reactive/inflammatory component needs to be considered in the pathogenesis of this lesion. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

A Twenty-Year Follow-up Study of Trabeculectomy: Risk Factors and Outcomes - Corrected Proof

John Landers, Keith Martin, Nicholas Sarkies, Rupert Bourne, Peter Watson — 2011-12-26

Purpose: This study was undertaken to determine the performance of trabeculectomy surgery over a 20-year period and examine the associations between outcome and risk factors for trabeculectomy failure. Design: Retrospective cohort study. Participants: A total of 234 patients (330 procedures) who had undergone trabeculectomy surgery at Addenbrooke's Hospital, Cambridge, United Kingdom, between January 1988 and December 1990. Methods: Patients were identified through surgical logbooks (n = 521 procedures on 380 patients); after this, a case-note review was undertaken, which identified 234 patients (330 procedures) who had available case notes. Main Outcome Measures: Surgical success was defined as “complete success” while intraocular pressure (IOP) remained <21 mm Hg with no additional medication and as “qualified success” if those requiring additional topical medication were included. Functional success was defined if patients did not progress to legal blindness (visual acuity <3/60 or visual field <10 degrees). Results: After 20 years, 57% were classified as complete success, 88% were classified as qualified success, and 15% had become blind. Those at risk of trabeculectomy failure were younger or had uveitic glaucoma. Those with pseudoexfoliation or aphakia were more likely to progress to blindness. Furthermore, those using 2 or more topical medications or with advanced visual field loss at the time of surgery were more at risk of both trabeculectomy failure and blindness. Conclusions: This study indicates that trabeculectomy survival at 20 years may be approximately 60% with no topical medication and approximately 90% with additional topical medication. Patient age, preoperative topical medication use, glaucoma type, and glaucoma severity will independently influence this outcome. Trabeculectomy surgery is therefore a long-term solution to IOP control. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Age-Related Macular Degeneration and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis - Corrected Proof

2011-12-26

Objective: To determine whether age-related macular degeneration (AMD) is a risk indicator for coronary heart disease (CHD) and cardiovascular disease (CVD) events independent of other known risk factors in a multi-ethnic cohort. Design: Population-based prospective cohort study. Participants: A diverse population sample of 6233 men and women aged 45 to 84 years without known CVD from the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: Participants in the MESA had retinal photographs taken between 2002 and 2003. Photographs were evaluated for AMD. Incident CHD and CVD events were ascertained during clinical follow-up visits for up to 8 years after the retinal images were taken. Main Outcome Measures: Incident CHD and CVD events. Results: Of the 6814 persons at risk of CHD, there were 893 participants with early AMD (13.1%) and 27 patients (0.5%) at baseline. Over a mean follow-up period of 5.4 years, there was no statistically significant difference in incident CHD or CVD between the AMD and non-AMD groups (5.0% vs. 3.9%, P = 0.13 for CHD and 6.6% vs. 5.5%, P = 0.19 for CVD). In Cox regression models adjusting for CVD risk factors, there was no significant relationship between presence of any AMD and any CHD/CVD events (hazard ratio 0.99; 95% confidence interval, 0.74–1.33; P = 0.97). No significant association was found between subgroups of early AMD or late AMD and incident CHD/CVD events. Conclusions: In persons without a history of CVD, AMD was not associated with an increased risk of CHD or CVD. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Corneal Higher-Order Aberrations after Descemet's Membrane Endothelial Keratoplasty - Corrected Proof

2011-12-23

Purpose: We compared corneal higher-order aberrations (HOAs) in eyes after Descemet's membrane endothelial keratoplasty (DMEK), Descemet's stripping automated endothelial keratoplasty (DSAEK), and penetrating keratoplasty (PK), and in a control group that had not undergone surgery. Design: Retrospective analysis of clinical data. Participants: Thirty eyes of 30 patients who had undergone standard DMEK, 20 eyes of 20 patients after DSAEK, 20 eyes of 20 patients after PK, and 20 eyes of 20 controls were analyzed. Methods: In addition to standard postoperative examinations, each participant was analyzed with the Pentacam high-resolution rotating Scheimpflug imaging system (Pentacam HR, Oculus, Wetzlar, Germany). Data were compared between groups. Main Outcome Measures: Visual acuity and HOAs. Results: The mean follow-up was 6.5±1.2 months after DMEK, 22.6±11.8 months after DSAEK, and 103.1±74.2 months after PK. There were no statistically significant differences for the anterior 4.0-mm zones between the DMEK group and the controls or between the DMEK and DSAEK groups. The DMEK procedure compared with PK showed statistically significant differences in all terms for the 4.0-mm zones. All combined Zernike terms for mean posterior aberrations of the central 4.0-mm zones showed statistically significant higher aberrations for DMEK compared with controls. The DMEK procedure compared with DSAEK showed statistically significant lower mean values for all combined Zernike terms, except for coma and coma-like terms in the central 4.0-mm zones of the posterior corneal surface. Compared with PK, DMEK showed statistically significant lower mean values for all combined Zernike terms for the central 4.0-mm zones of the posterior corneal surface, except for spherical aberration (SA) and SA-like terms. Best spectacle-corrected visual acuity (BSCVA) after DMEK was statistically significantly better than after DSAEK (P = 0.001) and PK (P = 0.005). There was no statistically significant difference when BSCVA was compared with controls (P = 0.998). Conclusions: Both DSAEK and PK exhibit increased posterior corneal HOAs even years after surgery. Patients receiving DMEK display only slight changes in posterior corneal HOAs. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Multiple Radial Midpupil Lid Distances: A Simple Method for Lid Contour Analysis - Corrected Proof

Gherusa H. Milbratz, Denny M. Garcia, Fernando C. Guimarães, Antonio A.V. Cruz — 2011-12-23

Purpose: To describe a new computerized method for the analysis of lid contour based on the measurement of multiple radial midpupil lid distances. Design: Evaluation of diagnostic technology. Participants and Controls: Monocular palpebral fissure images of 35 patients with Graves' upper eyelid retraction and of 30 normal subjects. Methods: Custom software was used to measure the conventional midpupil upper lid distance (MPLD) and 12 oblique MPLDs on each 15° across the temporal (105°, 120°, 135°, 150°, 165°, and 180°) and nasal (75°, 60°, 45°, 30°, 15°, and 0°) sectors of the lid fissure. Main Outcome Measures: Mean, standard deviation, 5th and 95th percentiles of the oblique MPLDs obtained for patients and controls. Temporal/nasal MPLD ratios of the same angles with respect to the midline. Results: The MPLDs increased from the vertical midline in both nasal and temporal sectors of the fissure. In the control group the differences between the mean central MPLD (90°) and those up to 30° in the nasal (75° and 60°) and temporal sectors (105° and 120°) were not significant. For greater eccentricities, all temporal and nasal mean MPLDs increased significantly. When the MPLDs of the same angles were compared between groups, the mean values of the Graves' patients differed from control at all angles (F = 4192; P<0.0001). The greatest temporal/nasal asymmetry occurred 60° from the vertical midline. Conclusions: The measurement of radial MPLD is a simple and effective way to characterize lid contour abnormalities. In patients with Graves' upper eyelid retraction, the method demonstrated that the maximum amplitude of the lateral lid flare sign occurred at 60° from the vertical midline. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Congenital Fibrovascular Pupillary Membranes: Clinical and Histopathologic Findings - Corrected Proof

2011-12-23

Purpose: To report the clinical and histopathologic findings associated with congenital fibrovascular pupillary membranes. Design: Case series. Participants: Seven infants were included, 6 with a unilateral congenital pupillary membrane and 1 with classic persistent fetal vasculature (PFV). Methods: Patients underwent a membranectomy, pupilloplasty, or lensectomy. Histopathologic examination was performed on the excised membranes. Main Outcome Measures: Visual acuity and pupil size. Results: Four of the 6 patients with a unilateral congenital pupillary membrane had 1 or more recurrences after a membranectomy and pupilloplasty. The most recent pupil size ranged from 2 to 5 mm in the affected eye. When last tested, the vision in the affected eye was excellent in 4 of the 6 patients. The 2 patients without recurrences of the pupillary membranes underwent multiple iris sphincterotomies at the time of the initial surgery. Histopathologic examination of 2 primary pupillary membranes showed fibrovascular tissue that did not stain for neuron-specific enolase. Smooth muscle actin was only present in vascular walls. In contrast, histopathology of a recurrent pupillary membrane revealed collagenized fibrovascular tissue that was immunoreactive for smooth muscle actin. Finally, histopathology of the retrolenticular membrane excised from an infant with classic PFV was similar to the latter aside from hypercellularity. Conclusions: Congenital fibrovascular pupillary membranes in infants are likely a variant of PFV that may recur if incompletely excised. The risk of these membranes recurring may be reduced by excising as much as the membrane as possible and enlarging the pupil with iris sphincterotomies. A lensectomy should be avoided if possible. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy and Complications of Super-selective Intra-ophthalmic Artery Melphalan for the Treatment of Refractory Retinoblastoma - Corrected Proof

2011-12-23

Purpose: To report the efficacy of super-selective intra-ophthalmic artery melphalan (IAM) for the treatment of refractory retinoblastoma and any associated complications of this treatment. Design: A prospective case series. Participants: Eyes with retinoblastoma that had been treated with systemic chemotherapy or local therapy and had a relapse of their condition. Methods: All patients receiving IAM between May 2009 and September 2010 were included in the study. Intra-ophthalmic artery melphalan was offered to patients who had failed to respond adequately to systemic chemotherapy and local treatment where appropriate or because of a new recurrence of retinoblastoma that could not be treated with local therapies. None of the patients were excluded because of central nervous system abnormalities. Patients received 2 treatments of IAM given 4 weeks apart. All patients received an orthoptic assessment 3 weeks after each treatment and an examination under anesthesia (EUA). A third treatment was given if an unsatisfactory response was observed on EUA after 2 treatments. Main Outcome Measures: The response of the retinoblastoma tumor(s) and any associated local side effects from the treatment. Results: A total of 15 eyes in 14 patients were treated with IAM during the study period. The mean age at the time of IAM was 31.5 months (median 17.3, range 11.2–150.7 months), and the mean follow-up was 8.7 months (3–16.3 months). Tumor control was achieved in 12 eyes (80%), and 12 eyes (80%) had local side effects that included third cranial nerve palsy in 6 (40%), orbital edema in 3 (20%), permanent retinal detachment in 1 (7%), and vitreous hemorrhage in 4 (27%). Seven eyes (47%) developed significant retinal pigment epithelium changes. Conclusions: Intra-ophthalmic artery melphalan is an effective treatment for retinoblastoma, achieving a high level of remission in refractory tumors. It can be associated with significant local side effects that can result in loss of vision and possible amblyogenesis. Clinicians and parents need to consider the benefits and potential local side effects before embarking on treatment. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ocular Mucous Membrane Pemphigoid after Lyell Syndrome: Occasional Finding or Predisposing Event? - Corrected Proof

2011-12-23

Purpose: Ocular mucous membrane pemphigoid (OMMP) is an autoimmune disease involving the eye and characterized by subepithelial detachment resulting from an immunologic reaction against conjunctival basal membrane zone (BMZ) antigens. Lyell syndrome (LS) is a drug-induced, T cell-mediated, cytotoxic reaction involving the mucocutaneous areas. Two patients with LS are presented in whom OMMP developed. Design: Report of 2 cases. Participants: Two male patients, 80 and 60 years old, with persistent corneal ulcerations, corneal melting, and inflammation some months after an LS episode. Methods: Conjunctival biopsy samples were obtained to perform direct immunofluorescence (DIF) and histologic analyses. Indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) also were performed. Main Outcome Measures: Immunodeposit findings on the conjunctival BMZ obtained by DIF and IIF, inflammatory infiltration of the corneoconjunctival samples studied by histologic analysis, and autoantibodies of patient sera directed against BMZ antigens tested by ELISA. Results: Direct immunofluorescence analyses showed immunoglobulin G and complement 3 component deposits along the BMZ in a linear pattern. Histologic analysis revealed the presence of eosinophils, neutrophils, and mast cells with fibrin deposition in the substantia propria of both patients; the data confirmed the clinical suspicion of OMMP. The IIF and ELISA results were negative. Conclusions: Chronic eye surface injury associated with LS may promote autoimmunization against ocular epithelial BMZ antigens, playing a strategic role in the subsequent onset of OMMP. The occurrence of OMMP after LS could be an occasional finding, or conversely, LS could be an underestimated predisposing factor in the development of OMMP. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Retinal Structure, Function, and Molecular Pathologic Features in Gyrate Atrophy - Corrected Proof

2011-12-19

Purpose: To describe phenotypic variability and to report novel mutational data in patients with gyrate atrophy. Design: Retrospective case series. Participants: Seven unrelated patients (10 to 52 years of age) with clinical and biochemical evidence of gyrate atrophy. Methods: Detailed ophthalmologic examination, fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography, and microperimetry testing were performed. The coding region and intron–exon boundaries of ornithine aminotransferase (OAT) were analyzed. OAT mRNA was isolated from peripheral blood leucocytes of 1 patient and analyzed. Main Outcome Measures: OAT mutation status and resultant clinical, structural, and functional characteristics. Results: Funduscopy revealed circular areas of chorioretinal atrophy, and FAF imaging showed sharply demarcated areas of increased or preserved signal in all 7 patients. Spectral-domain optical coherence tomography revealed multiple intraretinal cystic spaces and hyperreflective deposit in the ganglion cell layer of all study subjects. Round tubular, rosette-like structures located in the outer nuclear layer of the retinae of the 4 older patients were observed (termed outer retinal tubulation). Thickening was evident in the foveolae of younger patients, despite the posterior pole appearing relatively preserved. Macular function, assessed by microperimetry, was preserved over areas of normal or increased autofluorescence. However, sensitivity was reduced even in structurally intact parts of the retina. The molecular pathologic features were determined in all study subjects: 9 mutations, 4 novel, were detected in the OAT gene. OAT mRNA was isolated from blood leukocytes, and monoallelic expression of a mutated allele was demonstrated in 1 patient. Conclusions: Fundus autofluorescence imaging can reveal the extent of neurosensory dysfunction in gyrate atrophy patients. Macular edema is a uniform finding; the fovea is relatively thick in early stages of disease and retinal tubulation is present in advanced disease. Analysis of leukocyte RNA complements the high sensitivity of conventional sequencing of genomic DNA for mutation detection in this gene. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Methicillin-Resistant Staphylococcus aureus Ocular Infection: A 10-Year Hospital-Based Study - Corrected Proof

2011-12-16

Purpose: To characterize the patient demographics, clinical features, and antibiotic susceptibility of ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA), including community-associated (CA) and healthcare-associated (HA) isolates. Design:: Retrospective, observational study. Participants:: Patients (n = 519) with culture-proven S. aureus ocular infections seen between January 1, 1999, and December 31, 2008, in Chang Gung Memorial Hospital. Methods:: Data collected included patient demographics and clinical information. Antibiotic susceptibility was verified by disc diffusion method. Main Outcome Measures:: Proportion of MRSA in S. aureus ocular infections and the clinical characteristics, diagnoses, and antibiotic susceptibility patterns of CA-MRSA versus HA-MRSA ocular infections. Results:: We identified 274 patients with MRSA ocular infections, which comprised 181 CA-MRSA and 93 HA-MRSA isolates. The average rate of MRSA in S. aureus infections was 52.8% with a stable trend, whereas the annual ratio of CA-MRSA in ocular MRSA infections averaged 66.1% and tended to increase over the 10-year interval. Patients with ocular CA-MRSA were younger. Lid and lacrimal system disorders were more common, but keratitis, endophthalmitis, and wound infection were less common among CA-MRSA cases than HA-MRSA cases. Both CA-MRSA and HA-MRSA isolates were resistant to clindamycin and erythromycin, but CA-MRSA was more susceptible to sulfamethoxazole/trimethoprim. Conclusions:: Community-associated MRSA is an important pathogen of ocular infections; CA-MRSA and HA-MRSA ocular infections differ demographically and clinically, but both strains were multi-resistant in Chang Gung Memorial Hospital, one of the biggest referral centers in Taiwan. In a country with a high prevalence of MRSA, ophthalmologists should be aware of such epidemiologic information. Financial Disclosure(s):: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Corneal Confocal Microscopy in Patients with Vernal Keratoconjunctivitis - Corrected Proof

2011-12-16

Purpose: To compare corneal morphologic features using in vivo confocal microscopy in vernal keratoconjunctivitis (VKC) patients compared with normal subjects. Design: Prospective, comparative study. Participants: Thirty-two VKC patients (26 males, 6 females; mean age, 17.1 years) and 40 normal subjects (20 males, 20 females; mean age, 19.3 years) were included. Methods: All subjects underwent a full ophthalmologic examination. Confoscan CS4 (Nidek, Gamagori, Japan) images of the central cornea were obtained with a ×40 noncontact lens and Z-ring device. Main Outcome Measures: The superficial and basal epithelium, subbasal nerve plexus, anterior stroma, stromal nerves, and endothelium of the central cornea were studied. Results: The VKC patients had increased diameter, reflectivity, and presence of nuclear activation of superficial epithelial cells; reduced density of the basal membrane; lower density of keratocytes, increased presence of activated keratocytes, and inflammatory cells in the anterior stroma; and lower density and number of fibers, lower number of beadings, and higher grade of tortuosity of fibers in the subbasal nerve plexus. Increased alterations in thickness, deflections, and tortuosity were observed in stromal corneal nerves. An increased number of inflammatory cells in close proximity to the subbasal and stromal nerve fibers also was observed in VKC subjects. Conclusions: Corneal involvement in VKC is associated with alterations of the epithelium and subbasal and stromal corneal nerves. These changes may relate to the tear dysfunction and nonspecific hyperreactivity typical of these patients. Corneal confocal microscopy is a useful tool for studying in vivo pathologic corneal changes in VKC. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Age and Gender Variations in Age-related Macular Degeneration Prevalence in Populations of European Ancestry: A Meta-analysis - Corrected Proof

2011-12-16

Objective: To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study design and time trends. Design: Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases. Participants: Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD). Methods: Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI). Main Outcome Measures: Log odds and prevalence of AMD. Results: There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI, 3.8–4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0–1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1–2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3–7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%–2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%–7.7%) at age 80 and 20% (95% CrI, 14%–27%) at age 90. Conclusions: Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ultra-High Resolution Optical Coherence Tomography for Differentiation of Ocular Surface Squamous Neoplasia and Pterygia - Corrected Proof

2011-12-09

Objective: To assess the use of an ultra–high-resolution (UHR) optical coherence tomography (OCT) as an adjuvant diagnostic tool in distinguishing ocular surface squamous neoplasia (OSSN) and pterygia. Design: Prospective case series. Participants: Thirty-four eyes of 34 patients with conjunctival lesions clinically suspicious for OSSN or pterygia. Methods: All patients were photographed and then imaged with a custom-built UHR OCT device. Subsequently, each patient underwent excisional or incisional biopsy with histopathologic diagnosis. Main Outcome Measures: Comparison of preoperative UHR OCT images and the corresponding histopathologic specimen; comparison of epithelial thickness between the 2 groups as measured by UHR OCT. Results: Preoperative UHR OCT images of OSSN demonstrated similarities to the histopathologic specimens. Both optical and pathologic specimens showed a thickened layer of epithelium, often with an abrupt transition from normal to neoplastic tissue. Likewise, preoperative UHR OCT images of patients with pterygia were well correlated with the histopathologic specimens. As opposed to OSSN, both UHR OCT and pathologic images of pterygia demonstrated a normal thin epithelium, with underlying thickening of the subepithelial mucosal layers. Differences in the measured epithelial thickness on UHR OCT between OSSN and pterygia were statistically significant, with an average epithelial thickness of 346 μm (standard deviation [SD], 167) in OSSN patients and 101 μm (SD, 22) in pterygium patients (P<0.001). By receiver operating characteristic curve, the sensitivity and specificity of UHR OCT for differentiating between OSSN and pterygia was found to be 94% and 100%, respectively, using a cutoff value of 142 μm. Conclusions: Ultra–high-resolution OCT may show promise as a noninvasive diagnostic tool to evaluate ocular surface lesions. In addition to a statistically significant difference in epithelial thickness, a significant degree of morphologic correlation with the histopathologic results demonstrates its potential in evaluating ocular surface squamous neoplasia and pterygia. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Contrast Sensitivity Evaluation in a Population-Based Study in Shahroud, Iran - Corrected Proof

2011-12-07

Purpose: To determine the normal range of contrast sensitivity and its determinants through a population-based study in Shahroud, in northern Iran. Design: Population-based cross-sectional study. Participants: Using random cluster sampling in Shahroud, 6311 people between 40 and 64 years of age were sampled; 5190 (82.24%) responded, and 965 participants were selected randomly for contrast sensitivity testing. Methods: Participants underwent thorough eye examinations, including visual acuity and refraction tests, funduscopy, and slit-lamp examination. Main Outcome Measures: Contrast sensitivity was tested with best correction using the CVS1000 grating charts (VectorVision, Inc., Greenville, OH), and results are reported here in log units. Results: Overall, mean±standard deviation contrast sensitivity in spatial frequencies of 3, 6, 12, and 18 cycles per degree was 1.62±0.19, 1.87±0.22, 1.53±0.28, and 1.09±0.30 log units, respectively. Contrast sensitivity worsened significantly with age and with lower levels of uncorrected visual acuity (P<0.001). Compared with men, contrast sensitivity was worse among women in spatial frequencies of 3 and 6. Contrast sensitivity was significantly worse with myopia of more than 5.0 diopters (P<0.001). There was an inverse correlation between the amount of astigmatism and contrast sensitivity in all spatial frequencies (P<0.001). Contrast sensitivity showed a significant variability among people with normal vision that increased at higher spatial frequencies. Conclusions: The present findings can be used as a reference guide for contrast sensitivity in a general population and for comparison in future studies. Contrast sensitivity declines with age, high myopia, and astigmatism. The wide range variability, even in the presence of normal visual acuity, should be considered when contrast sensitivity is tested. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Validation of Measurement Scales in Ocular Graft-versus-Host Disease - Corrected Proof

2011-12-07

Purpose: To validate measurement scales for rating ocular chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. Candidate scales were recommended for use in clinical trials by the National Institutes of Health (NIH) Chronic GVHD Consensus Conference or have been previously validated in dry eye syndromes. Design: Prospective follow-up study. Participants: Between August 2007 and June 2010, the study enrolled 387 patients with chronic GVHD in a multicenter, prospective, observational cohort. Methods: Using anchor-based methods, we compared clinician or patient-reported changes in eye symptoms (8-point scale) with calculated changes in 5 candidate scales: The NIH eye score, patient-reported global rating of eye symptoms, Lee eye subscale, Ocular Surface Disease Index, and Schirmer test. Change was examined for 333 follow-up visits where both clinician and patient reported eye involvement at the previous visit. Linear mixed models were used to account for within-patient correlation. Main Outcome Measures: An 8-point scale of clinician or patient-reported symptom change was used as an anchor to measure symptom changes at the follow-up visits. Results: In serial evaluations, agreement regarding improvement, stability, or worsening between the clinician and patient was fair (weighted kappa = 0.34). Despite only fair agreement between evaluators, all scales except the Schirmer test correlated with both clinician-reported and patient-reported changes in ocular GVHD activity. Among all scales, changes in the NIH eye scores showed the greatest sensitivity to symptom change reported by clinicians or patients. Conclusions: Our results support the use of the NIH eye score as a sensitive measure of eye symptom changes in clinical trials assessing treatment of chronic GVHD. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.