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1.  Estimating Minimally Important Differences for Two Vision-Specific Quality of Life Measures 
Purpose.
To estimate minimally important differences (MIDs) for the Visual Activities Questionnaire (VAQ) and the National Eye Institute-Visual Function Questionnaire (NEI-VFQ).
Methods.
A total of 607 subjects with newly-diagnosed open-angle glaucoma (OAG) was enrolled in the Collaborative Initial Glaucoma Treatment Study (CIGTS) and randomized to initial treatment with medications or surgery. Subjects underwent an ophthalmic examination and telephone-administered quality of life (QOL) interview before randomization and every six months thereafter. The VAQ and NEI-VFQ were used to assess participants' perceptions of their visual function. Clinical measures included the mean deviation (MD) from Humphrey 24-2 full threshold visual field (VF) testing, and best-corrected visual acuity (VA) measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Anchor-based (using MD and VA) and distribution-based methods were used to estimate MIDs.
Results.
Anchor-based cross-sectional analyses at 66 months follow-up found a 10-letter increment in better eye VA corresponded to MIDs of 5.2 units for VAQ and 3.8 units for NEI-VFQ total scores. A 3-dB increment in the better eye MD yielded MIDs of 2.6 and 2.3 units for the same two questionnaires. In longitudinal analyses, MIDs for the VAQ were 3.2 units for a 10-letter change of VA and 3.4 units for a 3-dB change in the MD. Distribution-based MIDs were larger.
Conclusions.
A range of MIDs for the VAQ (2.6–6.5 units) and NEI-VFQ (2.3–3.8 units) was found. Although similar in magnitude, MIDs were sensitive to the MID estimation method, the anchor chosen, and differences between questionnaires. (ClinicalTrials.gov number, NCT00000149.)
Minimally important differences (MIDs) were estimated for two vision-specific quality of life measures, VAQ and NEI-VFQ, using anchor-based cross-sectional, anchor-based longitudinal, and distribution-based methods. Subscale MIDs for VAQ (2.6–6.5 units) and NEI-VFQ (2.3–3.8 units) were found.
doi:10.1167/iovs.13-13683
PMCID: PMC4095718  PMID: 24906863
MID; glaucoma; CIGTS; NEI-VFQ; VAQ
2.  Genome-wide association study and meta-analysis of intraocular pressure 
Human genetics  2013;133(1):41-57.
Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10−8). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.
doi:10.1007/s00439-013-1349-5
PMCID: PMC3982323  PMID: 24002674
3.  Regression Rate of Posterior Uveal Melanomas Following Iodine-125 Plaque Radiotherapy 
Aim:
To characterize the regression rate of posterior uveal melanoma following radioactive iodine-125 (I-125) plaque.
Materials and Methods:
We retrospectively analyzed 95 patients with posterior uveal melanoma who were treated with only radioactive I-125 plaque and had more than 3 years follow-up. All patients were treated with plaque radiotherapy using tumor dose of 85 Gy at the tumor apex, following COMS protocol. Regression rate was assessed with standardized A-scan ultrasonography. Associations with tumor regression were evaluated by means of mixed linear regression modeling.
Results:
Mean decrease in the tumor thickness (% original thickness) at 12, 24, and 36 months after radiotherapy for melanomas <3 mm in thickness was 29%, 38%, and 45%, for melanoma 3-8 mm in thickness was 32%, 44%, and 59%, and for melanoma more than 8 mm in thickness was 52%, 62%, and 68%, respectively. With a doubling of follow-up time (0.5-1 year, or 1-2 years of follow-up from treatment), tumors <3 mm in thickness at treatment showed a 0.5 mm decrease in tumor thickness, whereas melanomas 3-8 mm showed a 1 mm decrease, and melanomas >8 mm showed a 1.7 mm decrease. Uveal melanomas that developed systemic metastasis showed an additional 0.4 mm decrease with a doubling of follow-up time from treatment, compared with those that did not develop metastasis (P = 0.050).
Conclusions:
Posterior uveal melanomas with higher initial thickness show steeper and more reduction in tumor thickness following radioactive I-125 plaque. After the initial phases, the regression curve became similar for tumors with different thicknesses.
doi:10.4103/0974-9233.148358
PMCID: PMC4302463  PMID: 25624683
Uveal Melanoma; Plaque Radiotherapy; Tumor Regression
4.  Identification of Persons with Incident Ocular Diseases Using Health Care Claims Databases 
American journal of ophthalmology  2013;156(6):10.1016/j.ajo.2013.06.035.
Purpose
To assess the extent to which incidence rates calculated for common ocular diseases by using claims data may be overestimated according to the length of the disease-free, look-back period used in the analysis.
Design
Retrospective longitudinal cohort analysis.
Methods
Billing records of 2457 persons continuously enrolled for 11 years in a managed-care network were searched for International Classification of Diseases (ICD-9-CM) diagnoses of cataract, open-angle glaucoma (OAG), nonexudative age-related macular degeneration (ARMD), and nonproliferative diabetic retinopathy (NPDR) at eye-care visits in the first half of 2001, the second half of 2010, and 2011. For each condition, incidence rates calculated by using look-back periods ranging from 0.5 to 9 years were compared with best estimates from a gold-standard period of 9.5 years.
Results
With a 1-year disease-free look-back period, incidence was overestimated by 260% for cataract, 135% for OAG, 209% for ARMD, and 300% for NPDR. Expanding the disease-free “look back” period to three years resulted in a reduction of incidence overestimation to 40% for cataract, 14% for OAG, 45% for AMD, and 100% for NPDR. A 5-year look-back period yielded incidence rates overestimated by<30% for all four conditions.
Conclusions
In our claims-data analysis of four common ocular conditions, a disease-free interval ≤ 1 year insufficiently distinguished newly diagnosed from pre-existing disease, resulting in grossly overestimated incidence rates. Using look-back periods of 3–5 years, depending on the specific diagnosis, yielded considerably more accurate estimates of disease incidence.
doi:10.1016/j.ajo.2013.06.035
PMCID: PMC3836859  PMID: 23972306
5.  Risk of Endophthalmitis and Other Long-Term Complications of Trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS) 
American journal of ophthalmology  2012;155(4):674-680.e1.
Purpose
To report the risk of endophthalmitis and other long-term complications in patients randomized to trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS).
Design
A longitudinal cohort study using data collected from a multicenter, randomized clinical trial.
Methods
Long-term post-operative complications in the 300 patients randomized to trabeculectomy in CIGTS were tabulated. Kaplan-Meier analyses were used to estimate the time-related probability of blebitis, hypotony, and endophthalmitis.
Results
285 patients were included in the final trabeculectomy cohort after accounting for assignment refusal and other early events. Patients were followed for an average of 7.2 years. 163 patients (57%) received 5-fluorouracil (5-FU) intraoperatively. Of the 247 patients with at least 5 years of follow-up, 50 required further treatment for glaucoma. Cataract extraction was performed in 57 patients (20%). Forty patients (14%) required bleb revision at least once. Bleb-related complications included bleb leak (N = 15), blebitis (N = 8), and hypotony (N = 4). Three patients were noted to have endophthalmitis, although the diagnosis in two patients was presumptive. The occurrences of blebitis, hypotony, or endophthalmitis were not significantly associated with 5-FU use. The Kaplan-Meier calculated risks of blebitis and hypotony at 5 years were both 1.5%, while the risk of endophthalmitis was 1.1%.
Conclusions
The potential efficacy of trabeculectomy must be weighed against the long-term risk of complications, especially endophthalmitis, when selecting treatments for patients with open-angle glaucoma. We report a low 5-year risk of endophthalmitis (1.1%) and other bleb-related complications in the trabeculectomy cohort of the CIGTS.
doi:10.1016/j.ajo.2012.10.017
PMCID: PMC3608803  PMID: 23246272
6.  Clinical Characteristics of Newly Diagnosed Primary, Pigmentary, and Pseudoexfoliative Open-Angle Glaucoma in the Collaborative Initial Glaucoma Treatment Study 
The British journal of ophthalmology  2012;96(9):1180-1184.
Background/Aims
Three types of open-angle glaucoma (OAG) – primary, pigmentary, and pseudoexfoliative – are frequently encountered. The aim of this study was to compare demographic, ocular, and systemic medical information collected on people with these three OAG types at diagnosis, and determine if the OAG type affected prognosis.
Methods
Information on 607 participants of the Collaborative Initial Glaucoma Treatment Study was accessed. Descriptive statistics characterized their demographic, ocular, and medical status at diagnosis. Comparisons were made using analysis of variance (ANOVA), and chi-square or Fisher exact tests. Multinomial, mixed, and logistic regression analyses were also performed.
Results
Relative to people with primary OAG, those with pigmentary OAG were younger, more likely to be white, less likely to have a family history of glaucoma, and were more myopic. Those with pseudoexfoliative OAG were older, more likely to be white, more likely to be female, less likely to have bilateral disease, and presented with higher IOP and better VA. The type of glaucoma was not associated with intraocular pressure or visual field progression during follow-up.
Conclusion
Characteristics of newly-diagnosed enrollees differed by the type of OAG. While some of these differences relate to the pathogenesis of OAG type, other differences are noteworthy for further evaluation within population-based samples of subjects with newly-diagnosed OAG.
doi:10.1136/bjophthalmol-2012-301820
PMCID: PMC3480313  PMID: 22773091
Glaucoma; Epidemiology
7.  Filtering data from the collaborative initial glaucoma treatment study for improved identification of glaucoma progression 
Background
Open-angle glaucoma (OAG) is a prevalent, degenerate ocular disease which can lead to blindness without proper clinical management. The tests used to assess disease progression are susceptible to process and measurement noise. The aim of this study was to develop a methodology which accounts for the inherent noise in the data and improve significant disease progression identification.
Methods
Longitudinal observations from the Collaborative Initial Glaucoma Treatment Study (CIGTS) were used to parameterize and validate a Kalman filter model and logistic regression function. The Kalman filter estimates the true value of biomarkers associated with OAG and forecasts future values of these variables. We develop two logistic regression models via generalized estimating equations (GEE) for calculating the probability of experiencing significant OAG progression: one model based on the raw measurements from CIGTS and another model based on the Kalman filter estimates of the CIGTS data. Receiver operating characteristic (ROC) curves and associated area under the ROC curve (AUC) estimates are calculated using cross-fold validation.
Results
The logistic regression model developed using Kalman filter estimates as data input achieves higher sensitivity and specificity than the model developed using raw measurements. The mean AUC for the Kalman filter-based model is 0.961 while the mean AUC for the raw measurements model is 0.889. Hence, using the probability function generated via Kalman filter estimates and GEE for logistic regression, we are able to more accurately classify patients and instances as experiencing significant OAG progression.
Conclusion
A Kalman filter approach for estimating the true value of OAG biomarkers resulted in data input which improved the accuracy of a logistic regression classification model compared to a model using raw measurements as input. This methodology accounts for process and measurement noise to enable improved discrimination between progression and nonprogression in chronic diseases.
doi:10.1186/1472-6947-13-137
PMCID: PMC3878032  PMID: 24359562
8.  The Relationship Between Statin Use and Open-Angle Glaucoma 
Ophthalmology  2012;119(10):2074-2081.
Purpose
To determine whether 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) affect the risk of developing open-angle glaucoma (OAG) in persons with hyperlipidemia.
Design
Retrospective longitudinal cohort analysis.
Participants
Individuals age ≥60 with hyperlipidemia enrolled in a national United States managed care network between 2001 and 2009.
Methods
Multivariable Cox regression analyses were performed to assess the relationship between statin use and the development of OAG (from no prior OAG diagnosis), progression from a prior diagnosis of suspected glaucoma to a diagnosis of OAG, and need for medical or surgical interventions for OAG. Regression models were adjusted for sociodemographic factors, medical and ocular comorbidities.
Main Outcome Measures
Hazard ratios (HR) with 95% confidence intervals (CI).
Results
Of the 524,109 individuals with hyperlipidemia, 316,182 (60%) had at least 1 outpatient prescription for statins. The hazard of developing OAG decreased 0.3% (adjusted HR = 0.997, CI (0.994–0.999)) for every additional month of statin consumption. Individuals with hyperlipidemia who took statins continuously for 2 years had an 8% (adjusted HR = 0.922, CI (0.870–0.976) decreased OAG risk relative to those who received no statin therapy. The hazard of progressing from a diagnosis of suspected glaucoma to OAG decreased 0.4% (adjusted HR = 0.996, CI (0.993–0.999)) for every additional month of statin exposure. Individuals who took statins continuously for 2 years had a 9% (adjusted HR = 0.907, CI (0.846–0.973) decreased risk of progressing from suspected glaucoma to OAG relative to those who received no statin therapy. The hazard of requiring medical treatment for OAG decreased 0.4% (adjusted HR = 0.996, CI (0.993–0.998)) for every additional month of statin exposure. No significant differences in need for glaucoma surgery were noted among those with OAG who were and were not taking statins (adjusted HR = 1.002, CI (0.994–1.010)).
Conclusion
Statin use was associated with a significant reduction in the risk of OAG in persons with hyperlipidemia. Given the mounting evidence of statin protection against OAG including both basic science and observational clinical studies, an interventional prospective study might provide additional insights into the role of statins in the prevention of early OAG.
doi:10.1016/j.ophtha.2012.04.029
PMCID: PMC3459293  PMID: 22727176
9.  Prevalence of Corneal Dystrophies in the United States: Estimates from Claims Data 
Knowledge of the prevalence of corneal dystrophies is limited. This report provides prevalence estimates based on claims data obtained from a large U.S. managed-care network. It gives insight to the age, sex, and race distribution of specific corneal dystrophies.
Purpose.
To estimate the prevalence of corneal dystrophies.
Methods.
Records of almost 8 million enrollees in a national managed-care network throughout the United States who had an eye care visit in 2001 to 2009 were searched for a recording of corneal dystrophy on a claim submitted by an ophthalmologist or optometrist from January 1, 2001, through December 31, 2007.
Results.
Unique individuals (n = 27,372) received two or more diagnoses of any type of corneal dystrophy, for an overall corneal dystrophy prevalence rate of 897 per million (106) covered lives. Endothelial and anterior corneal dystrophies accounted for most of the reported dystrophies, and granular corneal dystrophy was the least common, being reported in 167 enrollees. Age, sex, and race variations among the various corneal dystrophies were observed. The mean age of those with macular corneal dystrophy (47.3 years) was 15 years younger than the age of those with endothelial dystrophy (62.9 years), and females were most highly represented (68.5%) among those with lattice corneal dystrophy. Hispanics and blacks were underrepresented relative to enrollees undergoing eye care for reasons other than corneal dystrophy. Keratoplasty was most frequently coded among those with lattice dystrophy.
Conclusions.
Although caveats must be considered in using claims data to estimate prevalence in a population, these data provide an indication of corneal dystrophy's prevalence within insured subjects across the United States. Variations in age, sex, and race, within and between the different types of corneal dystrophies, raise questions that warrant further study.
doi:10.1167/iovs.11-7771
PMCID: PMC3175990  PMID: 21791583
10.  Longitudinal Trends in Resource Utilization in an Incident Cohort of Open Angle Glaucoma Patients 
American journal of ophthalmology  2012;154(3):452-459.e2.
Purpose
To characterize the costs of caring for patients with open-angle glaucoma (OAG) in the United States (US) over time and to identify factors that influence these costs.
Design
Longitudinal cohort study.
Methods
Claims data from 19,927 newly-diagnosed OAG patients enrolled in a large US managed care network were reviewed to identify glaucoma-related charges for all incident OAG patients from 2001–2009. Average glaucoma-related charges for enrollees with OAG were characterized in six month blocks from the date of initial OAG diagnosis through the following 5 years. Factors associated with being an enrollee in the costliest 5% for glaucoma-related charges (accruing ≥$5810 in charges in the first 2 years) were identified using logistic regression.
Results
The costliest 5% of enrollees were responsible for $10,202,871 (24%) of all glaucoma-related charges. By comparison, those whose costs fell within the lower 50% of the cost distribution collectively amassed only $7,986,582 (19%) of all glaucoma-related charges. A spike in glaucoma-related charges occurred in the 6 month period around the time of OAG diagnosis, stabilized by 1 year following diagnosis, and remained relatively constant over time. Risk factors associated with being in the costliest 5% for glaucoma-related care included younger age, Northeastern US state residence, undergoing cataract surgery, and possessing ocular co-morbidities.(p<0.006 for all comparisons).
Conclusions
A small subset of enrollees account for a large proportion of all glaucoma-related charges. Understanding the characteristics of these individuals and finding ways to reduce disease burden and costs associated with their care can result in substantial cost savings.
doi:10.1016/j.ajo.2012.03.032
PMCID: PMC3422396  PMID: 22789564
11.  The Development of a Decision Analytic Model of Changes in Mean Deviation in People with Glaucoma: The COA Model 
Ophthalmology  2012;119(7):1367-1374.
Purpose
To create and validate a statistical model predicting progression of primary open angle glaucoma (POAG) assessed by loss of visual field as measured in mean deviation (MD) using three landmark studies of glaucoma progression and treatment.
Design
A Markov decision analytic model using patient level data described longitudinal MD changes over seven years.
Participants
Patient level data from the Collaborative Initial Glaucoma Treatment Study (CIGTS, n=607), the Ocular Hypertension Treatment Study (OHTS, n=148, only those who developed POAG in the first five years of OHTS) and Advanced Glaucoma Intervention Study (AGIS, n=591), the COA model.
Methods
We developed a Markov model with transition matrices stratified by current MD, age, race and intraocular pressure categories and used a microsimulation approach to estimate change in MD over seven years. Internal validation compared model prediction for seven years to actual MD for COA participants. External validation used a cohort of glaucoma patients drawn from university clinical practices.
Main Outcome Measures
Change in visual field as measured in MD in decibels (dB).
Results
Regressing the actual MD against the predicted produced an R2 of 0.68 for the right eye and 0.63 for the left. The model predicted ending MD for right eyes of 65% of participants and for 63% of left eyes within 3 dB of actual results at seven years. In external validation the model had an R2 of 0.79 in the right eye and 0.77 in the left at five years.
Conclusion
The COA model is a validated tool for clinicians, patients and health policy makers seeking to understand longitudinal changes in mean deviation in people with glaucoma..
doi:10.1016/j.ophtha.2012.01.054
PMCID: PMC3389134  PMID: 22537616
12.  Diffuse lamellar keratitis after laser in situ keratomileusis with femtosecond laser flap creation 
PURPOSE
To identify possible associations with the development of diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK) with femtosecond laser flap creation.
SETTING
University-based academic practice, Ann Arbor, Michigan, USA.
DESIGN
Case-control study.
METHODS
Myopic LASIK was performed between October 2006 and December 2010 using an Intralase 60 kHz femtosecond laser for flap creation. Preoperative clinical characteristics, treatment parameters, and intraoperative and postoperative complications were recorded. Statistical comparisons were made using t, chi-square, and Fisher exact tests and repeated-measures logistic regression to adjust for inter-eye dependency.
RESULTS
The study enrolled 801 eyes (419 patients). Ninety-nine eyes (12.4%) of 70 patients developed DLK; most cases comprised mild flap interface inflammation and were treated with a routine postoperative antiinflammatory regimen. Twenty-two eyes (2.7%) required more than 1 week of antiinflammatory treatment. There was a statistically significant increase in the incidence of DLK with larger flap diameter (P = .0171), higher side-cut energy (P = .0037), and higher raster energy (P = .0033). Patients with DLK were less likely to achieve corrected distance visual acuity of 20/20 or better 1 day postoperatively (P = .0453). The difference in acuity was no longer present at 1 week. There were no significant associations between the incidence of DLK and preoperative refractive error, flap thickness, ablation depth, or other treatment parameters.
CONCLUSIONS
Diffuse lamellar keratitis after LASIK with femtosecond laser flap creation tended to be mild with little effect on visual acuity. Higher energy level for flap creation and larger flap diameter were associated with an increased risk for DLK.
doi:10.1016/j.jcrs.2011.12.030
PMCID: PMC3360807  PMID: 22487775
13.  Glaucoma Associated with Boston Type 1 Keratoprosthesis 
Cornea  2012;31(2):134-139.
Purpose
To evaluate outcomes of the Boston Type 1 keratoprosthesis (KPro) and associated incidence of glaucoma.
Design
Retrospective cohort study.
Participants
All patients who underwent KPro surgery at one institution from 2003-2009 with at least 3 months follow-up.
Methods
Preoperative visual acuity, diagnosis, history of glaucoma, intraoperative and postoperative parameters were recorded. Statistical analysis was performed to identify factors that may influence increase in intraocular pressure (IOP) and glaucoma development or progression after surgery.
Main Outcome Measures
Best corrected visual acuity (BCVA), IOP, postoperative medical and surgical treatments for glaucoma, and KPro retention and complications.
Results
Thirty-six KPro procedures were performed in 30 eyes of 29 patients with mean (± SD) follow-up of 17±19 months (range 3-67 months). The main indication for KPro implantation was corneal graft failure (77%). Primary KPros were performed in 23% of eyes for limbal stem cell deficiency secondary to chemical burns and aniridia, and for herpetic disease. Median preoperative BCVA was hand motions with an overall improvement to 20/330 (range 20/20 to hand motions) at nine months postoperatively; mean BCVA was 20/600 (range 20/40 to NLP) at last follow-up. Twenty eyes (67%) had a preoperative history of glaucoma with eight of those eyes (40%) having undergone prior glaucoma surgery. Twenty-one eyes (70%) underwent concomitant glaucoma surgery. Postoperative increased IOP (22 mmHg or higher) was noted in 15 eyes (50%) while definite glaucoma development or progression was noted in 7 of those 15 eyes (23% of total eyes). Mean BCVA at last follow-up in eyes with glaucoma development or progression was 3/200 compared to 20/563 in the remaining 23 eyes. Six patients (20%) required repeat KPro implantation, and retroprosthetic membranes developed in 23 eyes (77%). No patient developed vitritis or infectious endophthalmitis.
Conclusions
The Boston Type 1 KPro is an effective option for management of eyes with poor prognosis for primary or repeat penetrating keratoplasty. Visual potential is limited by preoperative comorbidities; however, glaucoma development or progression of pre-existing glaucoma is a significant cause of postoperative visual loss. Rigorous perioperative management of elevated IOP is essential for long-term success of KPro surgery.
doi:10.1097/ICO.0b013e31820f7a32
PMCID: PMC3539166  PMID: 22134402
Boston Type 1 Keratoprosthesis; Glaucoma; Keratoplasty
14.  Postoperative endophthalmitis associated with sutured versus unsutured clear corneal cataract incisions 
Aim
To compare the incidence of postoperative endophthalmitis in clear corneal cataract surgeries performed with and without suture closure, antibiotics and povidone iodine.
Setting
Ambulatory surgery facility.
Methods
In a retrospective, consecutive case‐series study, we reviewed the incidence of endophthalmitis in 815 consecutive eyes that underwent cataract surgery by a single surgeon over a 5‐year period (379 unsutured and 436 sutured, 294 without and 521 with antibiotic drops in the immediate postoperative period, and 247 without and 568 with povidone iodine before patching).
Results
There were five cases of culture‐positive postoperative endophthalmitis in the unsutured group and none in the sutured group (p = 0.022). Although patients in these two groups received routine preoperative antibiotic and povidone‐iodine drops, those in whom antibiotic eye drops were not initiated until the day after surgery (p = 0.006) and those who did not receive 5% povidone‐iodine drops immediately after wound closure (p = 0.031), had a higher incidence of endophthalmitis.
Conclusion
Results suggest that by suturing the corneal incisions, by initiating antibiotic eye drops within the first 24 h of surgery and by instilling povidone‐iodine drops after closure, the incidence of endophthalmitis after cataract surgery could possibly be reduced.
doi:10.1136/bjo.2006.109827
PMCID: PMC1955619  PMID: 17510477
15.  In Vivo Confocal Microscopic Evaluation of Corneal Wound Healing after Femtosecond Laser-Assisted Keratoplasty 
Background and Objective
To evaluate corneal wound healing after femtosecond laser-assisted keratoplasty (FLAK) using in vivo confocal microscopy (IVCM).
Study Design
Prospective, interventional, consecutive case series of 17 eyes after mushroom-shaped FLAK. IVCM was performed preoperatively and at 1, 3, 6, and 12 months to assess wound healing.
Results
Mean keratocyte activation grade increased from preoperative levels to 1 month postoperatively in both the central (0.41 ± 0.62 to 1.73 ± 1.03) and peripheral (0.47 ± 0.52 to 1.57 ± 1.09) cornea, then gradually decreased through 12 months. Dendritic cells increased from preoperative to 1 month postoperative in both the central (0.71± 0.83 to 1.33 ± 0.98) and peripheral (0.79 ± 0.70 to 1.42 ± 0.90) cornea, then gradually decreased until 6 months. Stromal reinnervation was 1 month postoperatively in 8 patients (50%). By 12 months, subepithelial nerves were observed centrally in 5 patients (45.5%).
Conclusions
IVCM after FLAK shows an initial increase in keratocyte activation and dendritic cells that decrease over time. Corneal reinnervation is seen as early as 1 month postoperatively.
doi:10.3928/15428877-20120209-01
PMCID: PMC3535438  PMID: 22329795
17.  Factors Associated with Intraocular Pressure Prior to and during Nine Years of Treatment in the Collaborative Initial Glaucoma Treatment Study 
Ophthalmology  2007;115(6):927-933.
Purpose
To evaluate, both at initial glaucoma diagnosis and during treatment, the role of demographic and clinical factors on intraocular pressure (IOP).
Design
Cohort study of patients enrolled in a randomized clinical trial.
Participants
607 patients with newly diagnosed, open-angle glaucoma (OAG) were enrolled at 14 U.S. centers.
Methods
After randomization to initial surgery or medications, patients were followed at six-month intervals. IOP was measured by Goldmann applanation tonometry. Predictive factors for IOP at baseline and during follow-up were analyzed using linear mixed models.
Main Outcome Measure
IOP at baseline and during follow-up.
Results
The mean baseline IOP was 27.5 mmHg (standard deviation, 5.6 mmHg). Predictive factors for higher baseline IOP included younger age (0.7 mmHg per 10 years), male sex (2.4 mmHg higher than females), pseudoexfoliative glaucoma (5.4 mmHg higher than primary OAG), and pupillary defect (2.2 mmHg higher than those without a defect). During nine years of follow-up, both surgery and medications dramatically reduced IOP from baseline levels, but the extent of IOP reduction was consistently greater in the surgery group. Over follow-up years 2–9, mean IOP was 15.0 vs. 17.2 mmHg for surgery vs. medicine, respectively. Predictive associations with higher IOP during follow-up included higher baseline IOP (P<0.0001), worse baseline visual field (mean deviation; P<0.0001), and lower level of education (P=0.0019). Treatment effect was modified by smoking status: non-smokers treated surgically had lower IOP than smokers treated surgically (14.6 vs. 16.7 mmHg, respectively; P=0.0013). Clinical center effects were significant (P<0.0001) in both the baseline and follow-up models.
Conclusions
In this large cohort of newly diagnosed glaucoma patients, predictors of pre-treatment IOP and IOP measurements over nine years of follow-up were identified. Our findings lend credence to the postulate that sociodemographic, economic, compliance, or other environmental influences play a role in IOP control during treatment.
doi:10.1016/j.ophtha.2007.08.010
PMCID: PMC2758572  PMID: 17964655
19.  Evaluating clinical change and visual function concerns in drivers and non-drivers with glaucoma 
Purpose
To compare drivers and non-drivers, and describe the specific concerns of drivers, among individuals with glaucoma.
Methods
607 newly-diagnosed glaucoma patients from 14 clinical centers of the Collaborative Initial Glaucoma Treatment Study were randomly assigned to initial medicine or surgery and followed every six months for < 5 years. Driving status (drivers vs. non-drivers) as well as patient-reported visual function was determined by the Visual Activities Questionnaire and the National Eye Institute Visual Function Questionnaire. Clinical evaluation included visual field mean deviation (MD) and visual acuity. Statistical comparisons were made using t, Chi-square, and exact tests, regression, and Rasch analyses.
Results
Drivers were more likely than non-drivers to be male, white, married, employed, and have more education, higher income, and fewer co-morbidities. Over 50% of drivers reported at least “some” difficulty performing tasks involving glare, whereas 22% reported at least “some” difficulty with tasks requiring peripheral vision. At 54 months, drivers with moderate/severe bilateral visual field loss (VFL) reported greater difficulty with night driving and tasks involving visual search and visual processing speed than drivers with less bilateral VFL (all p-values <0.05). While those who remained drivers over follow-up had better MD in both eyes than those who became non-drivers due to eyesight, a number of drivers had marked VFL.
Conclusion
Inquiring about specific difficulties with tasks related to glare, visual processing speed, visual search and peripheral vision in driving, especially among patients with substantial bilateral VF damage, will enable physicians to more effectively counsel patients regarding driving.
doi:10.1167/iovs.08-2575
PMCID: PMC3395081  PMID: 19060263
20.  The Relationship Between Components of Metabolic Syndrome and Open-Angle Glaucoma 
Ophthalmology  2011;118(7):1318-1326.
Purpose
To determine whether an association exists between various components of metabolic syndrome (diabetes mellitus (DM), systemic arterial hypertension (HTN), hyperlipidemia, and obesity) and open-angle glaucoma (OAG) in a large, diverse group of individuals throughout the United States.
Design
Longitudinal cohort study.
Participants
All beneficiaries age ≥40 years continuously enrolled in a managed care network who had ≥1 visit to an eye care provider were identified from 2001–2007.
Methods
Billing codes were used to identify individuals with OAG and those with components of metabolic syndrome. Cox regression was used to determine the hazard of developing OAG in enrollees with individual components or combinations of components of metabolic syndrome, with adjustment for sociodemographic factors, systemic medical conditions, and other ocular diseases.
Main Outcome Measures
Hazard of developing OAG.
Results
Of the 2,182,315 enrollees who met inclusion criteria, 54,558 (2.5%) had OAG. After adjustment for confounding factors, those with DM (hazard ratio (HR)=1.35 [95% confidence interval (CI): 1.21–1.50]) or HTN (HR=1.17 [95% CI: 1.13–1.22]) alone, or in combination, (HR=1.48 [95% CI: 1.39–1.58]) had an increased hazard of developing OAG relative to persons with neither of these conditions. By contrast, persons with hyperlipidemia alone had a 5% decreased hazard of OAG (HR=0.95 [95% CI: 0.91–0.98]). Comorbid hyperlipidemia attenuated the increased hazard between HTN (HR=1.09 [95% CI 1.05–1.12]) or DM (HR=1.13 [95% CI 1.05–1.21]) and OAG.
Conclusion
Given the increasing prevalence of metabolic disorders in the United States, this study furthers our understanding of risk factors associated with OAG and helps identify persons who may be at risk for this condition.
doi:10.1016/j.ophtha.2010.11.022
PMCID: PMC3129406  PMID: 21481477
21.  Differences in Rates of Glaucoma Among Asian Americans Compared With Other Races and Among Individuals of Different Asian Ethnicities 
Ophthalmology  2011;118(6):1031-1037.
Purpose
To determine the incidence and prevalence rates of different glaucoma types among Asian Americans, contrast glaucoma incidence and prevalence rates for Asian Americans with other races, and evaluate the hazard of developing glaucoma among different Asian ethnicities and other races.
Design
Retrospective longitudinal cohort study
Participants
2,259,061 beneficiaries aged ≥40 enrolled in a large, national managed-care network in the United States (US) in 2001–2007
Methods
Incidence and prevalence rates of open-angle glaucoma (OAG), narrow-angle glaucoma (NAG), and normal-tension glaucoma (NTG) were determined for the beneficiaries and stratified by race and Asian ethnicity. Cox regression analyses determined the hazard of developing OAG, NAG, and NTG for Asian Americans compared with other races and among different Asian ethnicities, with adjustment for confounding factors.
Main Outcome Measures
Multivariable hazard of OAG, NAG, and NTG among different races and Asian ethnicities.
Results
The OAG prevalence rate for Asian Americans of 6.52% was similar to that of Latinos (6.40%) and higher than that of non-Hispanic whites (5.59%). The NAG and NTG prevalence rates (3.01% and 0.73%, respectively) were considerably higher among Asian Americans compared with each of the other races. After adjustment for confounding factors, Asian Americans had a 51% increased hazard of OAG (Hazard ratio (HR)=1.51 (95% confidence interval (CI) 1.42–1.60), a 123% increased hazard of NAG (HR=2.23 (95% CI 2.07–2.41), and a 159% increased hazard of NTG (HR=2.59 (95% CI 2.22–3.02) compared with non-Hispanic whites. Vietnamese Americans (HR=3.78, (95% CI 3.19–4.48), Pakistani Americans (HR=2.45, 95% CI 1.50–4.01) and Chinese Americans (HR=2.31, 95% CI 2.06–2.59) had considerably higher hazards of NAG while Japanese Americans (HR=4.37, 95% CI 3.24–5.89) had a substantially higher hazard of NTG, compared with non–Asian Americans.
Conclusions
Given the rapid rise in the number of Asian Americans in the US population, resources need to be devoted to identifying and treating glaucoma among these individuals. Eye-care providers should be aware of the increased hazard of developing OAG, NAG, and NTG among Asian Americans relative to other races. When evaluating Asian Americans, inquiring about ethnicity can provide additional information on risk of specific glaucoma types.
Financial Disclosures
The authors have no proprietary or commercial interest in any materials discussed in this article.
doi:10.1016/j.ophtha.2010.10.024
PMCID: PMC3109193  PMID: 21310489
22.  Can topical ketorolac 0.5% improve the function of Ahmed glaucoma drainage devices? 
Background and Objective
To determine whether postoperative use of topical ketorolac tromethamine 0.5% affects intraocular pressure (IOP) following Ahmed glaucoma drainage device implantation.
Study Design
Patients undergoing Ahmed implantation at the University of Michigan from January 2002-June 2008 were reviewed. Fourteen eyes received ketorolac after surgery; 50 eyes did not. Preoperative and postoperative IOP and glaucoma medications were recorded for both groups; the two-sided Student t-test was used to compare these parameters.
Results
Mean preoperative IOP was similar in the two groups (35.1 ± 11.9 mmHg versus 37.0 ± 12.2 mmHg; p=0.60). At postoperative month 6, the ketorolac eyes following Ahmed implantation had significantly lower IOP compared with the no ketorolac group (13.1 ± 3.7 mmHg versus 19.5 ± 9.3 mmHg respectively; p= 0.0003). There was no difference in the number of glaucoma medications postoperatively between the two groups.
Conclusion
Ketorolac may lead to lower postoperative IOP following Ahmed implantation.
doi:10.3928/15428877-20110324-03
PMCID: PMC3343136  PMID: 21449531
23.  Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma 
PLoS Genetics  2012;8(4):e1002654.
Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63–0.75], p = 1.86×10−18), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21–1.43], p = 3.87×10−11). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50–0.67], p = 1.17×10−12) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53–0.72], p = 8.88×10−10). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41–0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54–1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma.
Author Summary
Loss of vision from glaucoma, a common cause of blindness worldwide, is due to irreversible damage to the optic nerve. Current therapies cannot prevent glaucoma-related optic nerve disease and very little is known about the underlying responsible molecular events. Glaucoma patients affected by the “normal-pressure” subtype of glaucoma (NPG) have increased susceptibility to optic nerve degeneration. Although NPG has a high heritability, common predisposing genetic variants have not been identified. Therefore, we performed a meta-analysis of two independent genome-wide association studies for a common form of glaucoma, primary open angle glaucoma (POAG), followed by NPG subgroup analysis. We found that SNPs in the CDKN2BAS gene region on 9p21 and a highly conserved region with a probable regulatory function on 8q22 were associated with NPG and with optic nerve disease in a second type of glaucoma, exfoliation glaucoma. Both genomic regions are predicted to influence TGF-beta activity, and using whole-genome data we showed that the TGF-beta signaling pathway overall is associated with NPG. These results reveal new insights into the molecular pathogenesis of optic nerve disease in glaucoma and are an important step toward the development of preventative and protective therapies.
doi:10.1371/journal.pgen.1002654
PMCID: PMC3343074  PMID: 22570617
24.  The Effect of Trabeculectomy on Intraocular Pressure of the Untreated Fellow Eye in the Collaborative Initial Glaucoma Treatment Study 
Ophthalmology  2010;117(11):2055-2060.
Purpose
To describe the intraocular pressure (IOP) of the untreated fellow eye following unilateral trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS).
Design
Data collected from a prospective, multicenter, randomized clinical trial
Participants
Three hundred patients with newly diagnosed open-angle glaucoma enrolled at 14 centers in the United States who were randomized to initial trabeculectomy.
Methods
After baseline evaluation and randomization to initial trabeculectomy in the study eye, patients were evaluated at 3 and 6 months, and at 6-month intervals thereafter. The IOP was measured by Goldmann applanation tonometry. All eyes included in the analysis were untreated fellow eyes, and the data were censored for potential IOP lowering events in the fellow eye including trabeculectomy, argon laser trabeculoplasty or cataract extraction. Predictive factors for IOP response in the fellow eye to initial trabeculectomy in the study eye were analyzed using a linear mixed model.
Main Outcome Measure
IOP in the untreated fellow eye during follow up.
Results
While the IOP in the fellow eye was lower than baseline at 3, 6, 12, 18 and 24 months after trabeculectomy in the study eye, this decrease was statistically significant only at month 12 (mean decrease from baseline, 0.73±3.37 mm Hg; P=0.0134). Predictive associations with higher IOP in the fellow eye during follow-up included higher baseline IOP (P<0.0001), lower level of education (P=0.0129), time (p=0.0005) and the presence of other vascular disease (p=0.0069). Patients who ultimately required fellow eye trabeculectomy (p<0.0001) or argon laser trabeculoplasty (p<0.0001) but not cataract extraction (p=0.4597) in the fellow eye had lower IOPs during follow-up after these procedures.
Conclusion
There was no evidence of a substantial effect of trabeculectomy on the untreated fellow eye IOP during follow up. Trabeculectomy does not appear to decrease the mean IOP of the fellow eye, as suggested by some previous studies.
doi:10.1016/j.ophtha.2010.02.016
PMCID: PMC3334525  PMID: 20570363
glaucoma; intraocular pressure; trabeculectomy; fellow eye; contralateral eye
25.  The Effect of Early Post-trabeculectomy Intraocular Pressure Spike in the Collaborative Initial Glaucoma Treatment Study 
Journal of glaucoma  2011;20(4):211-214.
Purpose
To examine effects of early postoperative intraocular pressure (IOP) spike in patients undergoing primary trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS).
Patients and Methods
We identified patients with IOP spike ≥ 5 mmHg above the baseline IOP on postoperative day 1, as well as those without IOP increase. The Mean Deviation (MD), Pattern Standard Deviation (PSD), and Corrected PSD (CPSD) of the visual field (VF) were compared at 6 months and years 1, 2, 3, and 5 after surgery, as was the IOP.
Results
Seventeen of 300 patients (5.7%) had IOP spike. After controlling for baseline VF severity in a generalized linear regression model that addressed change in MD, PSD, and CPSD, or in a logistic regression model for ≥ 3 dB of MD change, comparison between the groups revealed no significant difference at all time points examined (P > .05). Patients with IOP spike had significantly higher mean IOP at years 3 and 5 of follow-up (P ≤ .04).
Conclusions
Among CIGTS patients, early post-trabeculectomy IOP spike ≥ 5 mmHg above baseline IOP was not associated with subsequent VF loss, but was associated with significantly higher IOP during long-term follow-up.
doi:10.1097/IJG.0b013e3181e07947
PMCID: PMC2978773  PMID: 20577103
trabeculectomy; intraocular pressure; spike; visual field; glaucoma

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