Publications by authors named "Paul R Lichter"

58 Publications

The Michigan Vision-Related Anxiety Questionnaire: A Psychosocial Outcomes Measure for Inherited Retinal Degenerations.

Am J Ophthalmol 2021 05 9;225:137-146. Epub 2020 Dec 9.

Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, Michigan, USA. Electronic address:

Objective: We sought to construct and validate a patient-reported outcome measure for screening and monitoring vision-related anxiety in patients with inherited retinal degenerations.

Design: Item-response theory and graded response modeling to quantitatively validate questionnaire items generated from qualitative interviews and patient feedback.

Methods: Patients at the Kellogg Eye Center (University of Michigan, Ann Arbor, Michigan, USA) with a clinical diagnosis of an inherited retinal degeneration (n = 128) participated in an interviewer-administered questionnaire. The questionnaire consisted of 166 items, 26 of which pertained to concepts of "worry" and "anxiety." The subset of vision-related anxiety questions was analyzed by a graded response model using the Cai Metropolis-Hastings Robbins-Monro algorithm in the R software mirt package. Item reduction was performed based on item fit, item information, and item discriminability. To assess test-retest variability, 25 participants completed the questionnaire a second time 4 to 16 days later.

Results: The final questionnaire consisted of 14 items divided into 2 unidimensional domains: rod function anxiety and cone function anxiety. The questionnaire exhibited convergent validity with the Patient Health Questionnaire for symptoms of depression and anxiety. This vision-related anxiety questionnaire has high marginal reliability (0.81 for rod-function anxiety, 0.83 for cone-function anxiety) and exhibits minimal test-retest variability (ρ = 0.81 [0.64-0.91] for rod-function anxiety and ρ = 0.83 [0.68-0.92] for cone-function anxiety).

Conclusions: The Michigan Vision-Related Anxiety Questionnaire is a psychometrically validated 14-item patient-reported outcome measure to be used as a psychosocial screening and monitoring tool for patients with inherited retinal degenerations. It can be used in therapeutic clinical trials for measuring the benefit of an investigational therapy on a patient's vision-related anxiety.
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http://dx.doi.org/10.1016/j.ajo.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184579PMC
May 2021

The Association between Medication Adherence and Visual Field Progression in the Collaborative Initial Glaucoma Treatment Study.

Ophthalmology 2020 04 10;127(4):477-483. Epub 2020 Jan 10.

Department of Ophthalmology and Visual Sciences, Medical School, University of Michigan, Ann Arbor, Michigan; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan.

Purpose: To evaluate the relationship between medication adherence and visual field progression in participants randomized to the medication arm of the Collaborative Initial Glaucoma Treatment Study (CIGTS).

Design: The CIGTS was a randomized, multicenter clinical trial comparing initial treatment with topical medications to trabeculectomy for 607 participants with newly diagnosed glaucoma.

Participants: Three hundred seven participants randomized to the medication arm of the CIGTS.

Methods: Participants were followed up at 6-month intervals for up to 10 years. Self-reported medication adherence and visual fields were measured. Medication adherence was assessed by telephone from responses to the question, "Did you happen to miss any dose of your medication yesterday?" The impact of medication adherence on mean deviation (MD) over time was assessed with a linear mixed regression model adjusting for the effects of baseline MD and age, cataract extraction, interactions, and time (through year 8, excluding time after crossover to surgery). Medication adherence was modeled as a cumulative sum of the number of prior visits where a missed dose of medication was reported.

Main Outcome Measure: Mean deviation over time.

Results: Three hundred seven subjects (306 with adherence data) were randomized to treatment with topical medications and followed up for an average of 7.3 years (standard deviation, 2.3 years). One hundred forty-two subjects (46%) reported never missing a dose of medication over all available follow-up, 112 patients (37%) reported missing medication at up to one third of visits, 31 patients (10%) reported missing medication at one third to two thirds of visits, and 21 patients (7%) reported missing medication at more than two thirds of visits. Worse medication adherence was associated with loss of MD over time (P = 0.005). For subjects who reported never missing a dose of medication, the average predicted MD loss over 8 years was 0.62 dB, consistent with age-related loss (95% confidence interval [CI], 0.17-1.06; P = 0.007); subjects who reported missing medication doses at one third of visits had a loss of 1.42 dB (95% CI, 0.86-1.98; P < 0.0001); and subjects who reported missing medication doses at two thirds of visits showed a loss of 2.23 dB (95% CI, 1.19-3.26; P < 0.0001).

Conclusions: This longitudinal assessment demonstrated a statistically and clinically significant association between medication nonadherence and glaucomatous vision loss.
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http://dx.doi.org/10.1016/j.ophtha.2019.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093219PMC
April 2020

Association of a Primary Open-Angle Glaucoma Genetic Risk Score With Earlier Age at Diagnosis.

JAMA Ophthalmol 2019 Oct;137(10):1190-1194

Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland.

Importance: Genetic variants associated with primary open-angle glaucoma (POAG) are known to influence disease risk. However, the clinical effect of associated variants individually or in aggregate is not known. Genetic risk scores (GRS) examine the cumulative genetic load by combining individual genetic variants into a single measure, which is assumed to have a larger effect and increased power to detect relevant disease-related associations.

Objective: To investigate if a GRS that comprised 12 POAG genetic risk variants is associated with age at disease diagnosis.

Design, Setting, And Participants: A cross-sectional study included individuals with POAG and controls from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study. A GRS was formulated using 12 variants known to be associated with POAG, and the alleles associated with increasing risk of POAG were aligned in the case-control sets. In case-only analyses, the association of the GRS with age at diagnosis was analyzed as an estimate of disease onset. Results from cohort-specific analyses were combined with meta-analysis. Data collection started in August 2012 for the NEIGHBOR cohort and in July 2008 for the GLAUGEN cohort and were analyzed starting in March 2018.

Main Outcomes And Measures: Association of a 12 single-nucleotide polymorphism POAG GRS with age at diagnosis in individuals with POAG using linear regression.

Results: The GLAUGEN study included 976 individuals with POAG and 1140 controls. The NEIGHBOR study included 2132 individuals with POAG and 2290 controls. For individuals with POAG, the mean (SD) age at diagnosis was 63.6 (9.8) years in the GLAUGEN cohort and 66.0 (13.7) years in the NEIGHBOR cohort. For controls, the mean (SD) age at enrollment was 65.5 (9.2) years in the GLAUGEN cohort and 68.9 (11.4) years in the NEIGHBOR cohort. All study participants were European white. The GRS was strongly associated with POAG risk in case-control analysis (odds ratio per 1-point increase in score = 1.24; 95% CI, 1.21-1.27; P = 3.4 × 10-66). In case-only analyses, each higher GRS unit was associated with a 0.36-year earlier age at diagnosis (β = -0.36; 95% CI, -0.56 to -0.16; P = 4.0 × 10-4). Individuals in the top 5% of the GRS had a mean (SD) age at diagnosis of 5.2 (12.8) years earlier than those in the bottom 5% GRS (61.4 [12.7] vs 66.6 [12.9] years; P = 5.0 × 10-4).

Conclusions And Relevance: A higher dose of POAG risk alleles was associated with an earlier age at glaucoma diagnosis. On average, individuals with POAG with the highest GRS had 5.2-year earlier age at diagnosis of disease. These results suggest that a GRS that comprised genetic variants associated with POAG could help identify patients with risk of earlier disease onset impacting screening and therapeutic strategies.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.3109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707005PMC
October 2019

Characteristics of Industry Payments to Ophthalmologists in the Open Payments Database.

JAMA Ophthalmol 2019 Jul 3. Epub 2019 Jul 3.

Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, Ann Arbor, Michigan.

Importance: An increased awareness of the interactions between the medical industry and health care professionals may lead to lower health care costs and more effective health care practices.

Objective: To assess the characteristics of industry payments made to ophthalmologists between 2013 and 2017.

Design, Setting, And Participants: This analysis included data reported in the June 29, 2018, update of the Centers for Medicare & Medicaid Services Open Payments Database (OPD). The OPD contains public records of industry payments made to physicians and teaching hospitals from August 1, 2013, to December 31, 2017, as reported by the medical industry. All general or research payments distributed to US ophthalmologists and contained in the OPD were included in this study. Data are summarized by practitioner, manufacturer, payment category, and geographic location.

Main Outcomes And Measures: Main outcomes were the distribution, quantity, and value of payments made to ophthalmologists practicing in the United States or US territories. The financial characteristics of payment category, manufacturer, product, and location were also assessed.

Results: This analysis revealed that the OPD showed industry reporting a total of 20 943 ophthalmologists receiving 736 517 payments worth $543 679 603.53 (1.67% of all industry-reported funds in the OPD). The median payment value was $22.44. Most payments were for food and beverages (581 588 [78.96%]), whereas most funds were allocated toward research ($310 142 151.88 [57.05%]) and consulting fees ($73 565 327.71 [13.51%]). The median payout to each ophthalmologist was $637.75 (interquartile range, $167.33-$2065.54). California was the highest-grossing state, receiving $101 135 980.34 (18.60%) of all payments. Fifteen companies were responsible for 87.68% of all funds distributed ($476 719 470.11) and were mostly involved in the production of pharmaceutical agents (anti-vascular endothelial growth factor agents, glaucoma eyedrops, and ocular lubricants) and surgical devices (cataract and glaucoma).

Conclusions And Relevance: Although there is no way to know the veracity of these reports, the findings suggest the financial ophthalmologist-industry relationship is substantial. These relationships may be adding to health care costs and affecting the quality of care, although those associations were not evaluated in this study.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.2456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613310PMC
July 2019

Association of Mandatory Disclosure Policies and Laws With Physician-Industry Financial Relationships.

JAMA Ophthalmol 2019 05;137(5):523-530

W. K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor.

Importance: Beside the goal of increasing transparency to the public, disclosure policies and laws have been established with a goal to also reduce ethically questionable financial relationships between physicians and the medical industry. Data on these relationships should be reviewed to understand the association between these policies and laws and the attainment of reduced relationships.

Objective: To assess whether disclosure policies and laws have been associated with a decrease in financial disclosure reporting by physicians.

Design, Setting, And Participants: This cross-sectional study uses yearly data from 2008 through 2015 from the participants in the American Academy of Ophthalmology's Annual Meeting. Trends in financial disclosures over time were investigated for the association of disclosure policies and laws with potentially beneficial, as well as ethically questionable physician-industry ties. Linear regression models were used to estimate the annual change in financial disclosures and are reported with 95% CIs.

Exposures: Disclosure policies and laws.

Main Outcomes And Measures: The annual aggregate financial disclosures by type (ie, consultant, lecturer, employee, grant support, equity owner, patent holder).

Results: Financial disclosures increased from 3966 in 2008 to 5266 in 2015 (P < .001). The number of disclosures reported in the categories consultant, equity owner, patents, and grant support all increased from 2008 to 2015 (consultant disclosures, 121 [95% CI, 88-155] per year; P < .001; equity owner disclosures, 32 [95% CI, 22-42] per year; P < .001; patent disclosures, 19 [95% CI, 13-26] per year; P < .001; grant support disclosures, 78 [95% CI, 48-107] per year; P < .001), while the employee and lecturer categories did not change significantly. The percentage of financial disclosures in the lecturer category decreased relative to the total (estimate, -1.1% [95% CI, -1.3% to -0.8%] per year; P < .001), owing to the number of financial disclosures for this category remaining stable while most other types increased.

Conclusions And Relevance: Disclosure was not associated with a chilling effect (decrease in financial disclosures associated with potentially beneficial physician-industry ties). Disclosure was associated with a possible disinfecting effect, whereby the percentage of ethically questionable disclosures (ie, lecturers) decreased, although the frequency remained stable. A permissive effect (physicians becoming more inclined to having industry relationships) was also observed. Thus, disclosure rules should be enhanced or alternative approaches to disclosure reconsidered to promote a decrease in ethically questionable relationships.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512261PMC
May 2019

Industry Payments to Physicians and the Public's Right to Know About Them.

Authors:
Paul R Lichter

JAMA Ophthalmol 2018 12;136(12):1381-1382

W. K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor.

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http://dx.doi.org/10.1001/jamaophthalmol.2018.4163DOI Listing
December 2018

Patient-centered and visual quality outcomes of premium cataract surgery: a systematic review.

Eur J Ophthalmol 2017 Jun 24;27(4):387-401. Epub 2017 Apr 24.

Department of Ophthalmology, Kellogg Eye Center, University of Michigan, Ann Arbor, MI - USA.

Purpose: Over 8 million cataract surgeries are performed in the United States and the European Union annually, with many patients choosing to pay out of pocket for premium options including premium intraocular lens implants (IOLs) or laser-assisted cataract surgery (LACS). This report provides a systematic review evaluating patient-centered and visual quality outcomes comparing standard monofocal IOLs to premium cataract surgery options.

Methods: PubMed and EMBASE were searched for publications published between January 1, 1980, and September 18, 2016, on multifocal, accommodative, and toric IOLs, monovision, and LACS, which reported on 1) dysphotopsias, 2) contrast sensitivity, 3) spectacle independence, 4) vision-related quality of life or patient satisfaction, and 5) IOL exchange.

Results: Multifocal lenses achieved higher rates of spectacle independence compared to monofocal lenses but also had higher reported frequency of dysphotopsia and worse contrast sensitivity, especially with low light or glare. Accommodative lenses were not associated with reduced contrast sensitivity or more dysphotopsia but had only modest improvements in spectacle independence compared to monofocal lenses. Studies of monovision did not target a sufficiently myopic outcome in the near-vision eye to achieve the full potential for spectacle independence. Patients reported high levels of overall satisfaction regardless of implanted IOL. No studies correlated patient-reported outcomes with patient expectations.

Conclusions: Studies are needed to thoroughly compare patient-reported outcomes with concomitant patient expectations. In light of the substantial patient costs for premium options, patients and their surgeons will benefit from a better understanding of which surgical options best meet patients' expectations and how those expectations can be impacted by premium versus monofocal-including monovision-options.
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http://dx.doi.org/10.5301/ejo.5000978DOI Listing
June 2017

Binocular Measures of Visual Acuity and Visual Field versus Binocular Approximations.

Ophthalmology 2017 07 10;124(7):1031-1038. Epub 2017 Apr 10.

Department of Health Behavior and Health Education, University of Michigan, Ann Arbor, Michigan.

Purpose: To assess the relationship of binocular visual function tests with binocular approximations using data from the Collaborative Initial Glaucoma Treatment Study (CIGTS).

Design: Case series based on existing data from a clinical trial.

Participants: Six hundred seven patients with newly diagnosed open-angle glaucoma from the CIGTS.

Methods: Monocular visual field (VF) and visual acuity (VA) tests were performed at baseline and every 6 months thereafter. Binocular tests of visual function (Esterman VF score, binocular VA) were added to the CIGTS protocol 3 years into the study. The binocular approximations of binocular visual function were better or worse eye, average eye, better or worse location, and binocular summation or pointwise binocular summation. Associations between binocular tests and binocular approximations to represent binocular visual function were assessed with Pearson's correlations (r), as was the relationship between vision-related quality of life (VR QOL; Visual Activities Questionnaire [VAQ] and the 25-item National Eye Institute Visual Function Questionnaire [NEI VFQ-25]) and binocular tests or binocular approximations of visual function.

Main Outcome Measures: Binocular visual function (VF and VA) and VR QOL.

Results: Five hundred seventy-five patients underwent at least 1 binocular visual function test. The Esterman score was correlated significantly with all binocular approximations of VF, with r values ranging from 0.31 (worse-eye mean deviation [MD]) to 0.42 (better-eye MD; P < 0.0001 for all). Binocular VA showed stronger correlations with binocular approximations, with r values ranging from 0.65 (worse-eye VA) to 0.80 (binocular summation; P < 0.0001 for all). Correlations between the VAQ and Esterman score were stronger in 7 of 9 subscales (r = -0.14 to -0.25; P < 0.05 for all) than correlations with all 7 binocular approximations. In contrast, correlations between the VAQ and binocular VA (r = -0.07 to -0.21) were weaker in all subscales than those with better-eye, average-eye, and binocular summation of VA (r = -0.12 to -0.25), but not different from worse-eye values. These trends also were found in relevant subscales of the NEI VFQ-25.

Conclusions: We found limited benefit in binocular testing of VA in the clinical setting as a means of approximating a patient's reported visual functioning. In contrast, we found some benefit in performing binocular VF testing, because the results correlated more closely with reported functioning than binocular approximations.
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http://dx.doi.org/10.1016/j.ophtha.2017.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483206PMC
July 2017

Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses.

Invest Ophthalmol Vis Sci 2016 Sep;57(11):5046-5052

Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, San Diego, California, United States.

Purpose: Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins.

Methods: We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure.

Results: We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010).

Conclusions: We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important.
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http://dx.doi.org/10.1167/iovs.16-20017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040191PMC
September 2016

Physician-Industry Interactions and Anti-Vascular Endothelial Growth Factor Use Among US Ophthalmologists.

Authors:
Paul R Lichter

JAMA Ophthalmol 2016 08;134(8):903-4

Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor.

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http://dx.doi.org/10.1001/jamaophthalmol.2016.1794DOI Listing
August 2016

Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.

Nat Genet 2016 Feb 11;48(2):189-94. Epub 2016 Jan 11.

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.
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http://dx.doi.org/10.1038/ng.3482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731307PMC
February 2016

Geographic Variation in the Rate and Timing of Cataract Surgery Among US Communities.

JAMA Ophthalmol 2016 Mar;134(3):267-76

Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor2Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor3Department of Health Policy and Management, School of Public Hea.

Importance: Previous studies using data from the 1980s found relatively little geographic variation in cataract surgery rates across the United States. We do not know whether similar patterns hold true today, nor do we know the patient- and community-level factors that might explain any recent geographic variations in the rate and timing of cataract surgery.

Objective: To assess the extent of geographic variation in patient age at initial cataract surgery and the age-standardized cataract surgery rate in a large group of insured US patients with cataracts.

Design, Setting, And Participants: Retrospective cross-sectional study of 1 050 815 beneficiaries older than 40 years of age with cataracts who were enrolled in a nationwide managed-care network during the period from 2001 to 2011. The data analysis was started in 2014 and refined in 2015.

Main Outcomes And Measures: Median age at initial cataract extraction, age-standardized cataract surgery rate, and time from initial diagnosis to first surgery for patients with cataracts were compared among 306 US communities. Multivariable regression modeling generated hazard ratios (HRs) with 95% CIs identifying factors associated with patients' likelihood of undergoing cataract surgery.

Results: A total of 243 104 patients with cataracts (23.1%) underwent 1 or more surgical procedures (55.1% were female patients). Communities with the youngest and oldest patients at initial surgery differed in age by nearly 20 years (59.9-60.1 years in Lansing, Michigan, and Aurora, Illinois, vs 77.0-79.6 years in Marquette, Michigan; Rochester, New York; and Binghamton, New York). The highest age-standardized cataract surgery rate (37.3% in Lake Charles, Louisiana) was 5-fold higher than the lowest (7.5% in Honolulu, Hawaii). The median time from initial cataract diagnosis to date of first surgery ranged from 17 days (Victoria, Texas) to 367 days (Yakima, Washington). Compared with white patients, black patients had a 15% decreased hazard of surgery (HR, 0.85 [95% CI, 0.83-0.87]), while Latino patients (HR, 1.08 [95% CI, 1.05-1.10]) and Asian patients (HR, 1.09 [95% CI, 1.05-1.12]) had an increased hazard. For every 1° higher latitude, the hazard of surgery decreased by 1% (HR, 0.99 [95% CI, 0.98-0.99]). For every additional optometrist per 100 000 enrollees in a community, the hazard of surgery increased 0.1% (HR, 1.001 [95% CI, 1.001-1.001]).

Conclusions And Relevance: In recent years, patient age at first cataract surgery and the age-standardized surgery rate have varied considerably among some US communities. Future research should explore the extent to which such variations may affect patient outcomes.
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http://dx.doi.org/10.1001/jamaophthalmol.2015.5322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767078PMC
March 2016

Implications of the Sunshine Act--revelations, loopholes, and impact.

Authors:
Paul R Lichter

Ophthalmology 2015 Apr;122(4):653-5

Ann Arbor, Michigan.

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http://dx.doi.org/10.1016/j.ophtha.2014.12.029DOI Listing
April 2015

Payment data and the "me" in Medicare.

Authors:
Paul R Lichter

Ophthalmology 2014 Oct;121(10):1849-51

Ann Arbor, Michigan.

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http://dx.doi.org/10.1016/j.ophtha.2014.07.016DOI Listing
October 2014

Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma.

Hum Genet 2014 Oct 19;133(10):1319-30. Epub 2014 Jul 19.

Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA.

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Using genome-wide association single-nucleotide polymorphism data from the Glaucoma Genes and Environment study and National Eye Institute Glaucoma Human Genetics Collaboration comprising 3,108 cases and 3,430 controls, we assessed biologic pathways as annotated in the KEGG database for association with risk of POAG. After correction for genic overlap among pathways, we found 4 pathways, butanoate metabolism (hsa00650), hematopoietic cell lineage (hsa04640), lysine degradation (hsa00310) and basal transcription factors (hsa03022) related to POAG with permuted p < 0.001. In addition, the human leukocyte antigen (HLA) gene family was significantly associated with POAG (p < 0.001). In the POAG subset with normal-pressure glaucoma (NPG), the butanoate metabolism pathway was also significantly associated (p < 0.001) as well as the MAPK and Hedgehog signaling pathways (hsa04010 and hsa04340), glycosaminoglycan biosynthesis-heparan sulfate pathway (hsa00534) and the phenylalanine, tyrosine and tryptophan biosynthesis pathway (hsa0400). The butanoate metabolism pathway overall, and specifically the aspects of the pathway that contribute to GABA and acetyl-CoA metabolism, was the only pathway significantly associated with both POAG and NPG. Collectively these results implicate GABA and acetyl-CoA metabolism in glaucoma pathogenesis, and suggest new potential therapeutic targets.
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http://dx.doi.org/10.1007/s00439-014-1468-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273559PMC
October 2014

Visual field improvement in the collaborative initial glaucoma treatment study.

Am J Ophthalmol 2014 Jul 12;158(1):96-104.e2. Epub 2014 Apr 12.

Department of Ophthalmology and Visual Sciences, Medical School, University of Michigan, Ann Arbor, Michigan.

Purpose: To evaluate critically visual field (VF) improvement in participants in the Collaborative Initial Glaucoma Treatment Study (CIGTS).

Design: Prospective, comparative case series from a randomized clinical trial comparing trabeculectomy and topical medications in treating open-angle glaucoma (OAG).

Methods: A total of 607 subjects with newly diagnosed OAG were identified for study. Baseline and follow-up VF tests were obtained and mean deviation (MD) change from baseline over follow-up was analyzed. Clinically substantial change (loss or improvement) was defined as change from baseline of ≥ 3 decibels in MD. Baseline factors were inspected to determine their association with VF improvement in repeated measures regression models.

Results: The percentage of participants showing substantial VF improvement over time was similar to that showing VF loss through 5 years after initial treatment, after which VF loss became more frequent. Measures of better intraocular pressure (IOP) control during treatment were significantly predictive of VF improvement, including a lower mean IOP, a lower minimum IOP, and lower sustained levels of IOP over follow-up. Other predictive factors included female sex (odds ratio [OR] = 1.73), visits 1 year prior to cataract extraction (OR = 0.11), and an interaction between treatment and baseline MD wherein surgically treated subjects with worse baseline VF loss were more likely to show VF improvement.

Conclusions: In the CIGTS, substantial VF loss and improvement were comparable through 5 years of follow-up, after which VF loss became more frequent. Predictive factors for VF improvement included several indicators of better IOP control, which supports the postulate that VF improvement was real.
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http://dx.doi.org/10.1016/j.ajo.2014.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190842PMC
July 2014

Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss.

Ophthalmology 2014 Feb 25;121(2):508-16. Epub 2013 Oct 25.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan.

Purpose: The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further.

Design: Case-control study.

Participants: We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls).

Methods: We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7 × 10(-4) was used to account for multiple comparisons.

Main Outcome Measures: Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss.

Results: We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61 × 10(-7)). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59 × 10(-5)). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07 × 10(-4)), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men.

Conclusions: CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.
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http://dx.doi.org/10.1016/j.ophtha.2013.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937766PMC
February 2014

Genome-wide association study and meta-analysis of intraocular pressure.

Hum Genet 2014 Jan 4;133(1):41-57. Epub 2013 Sep 4.

Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.

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.
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http://dx.doi.org/10.1007/s00439-013-1349-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982323PMC
January 2014

Estrogen pathway polymorphisms in relation to primary open angle glaucoma: an analysis accounting for gender from the United States.

Mol Vis 2013 12;19:1471-81. Epub 2013 Jul 12.

Department of Ophthalmology, Mass Eye & Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.

Purpose: Circulating estrogen levels are relevant in glaucoma phenotypic traits. We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender.

Methods: We included 3,108 POAG cases and 3,430 controls of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation between the SNP panels representative of estrogen metabolism and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm to assess statistical significance relative to the pathways and genes of comparable genetic architecture. These analyses were performed using the meta-analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG overall as well as two subtypes of POAG defined as intraocular pressure (IOP) ≥22 mmHg (high-pressure glaucoma [HPG]) or IOP <22 mmHg (normal pressure glaucoma [NPG]) at diagnosis. We conducted these analyses for each gender separately and then jointly in men and women.

Results: Among women, the estrogen SNP pathway was associated with POAG overall (permuted p=0.006) and HPG (permuted p<0.001) but not NPG (permuted p=0.09). Interestingly, there was no relation between the estrogen SNP pathway and POAG when men were considered alone (permuted p>0.99). Among women, gene-based analyses revealed that the catechol-O-methyltransferase gene showed strong associations with HTG (permuted gene p≤0.001) and NPG (permuted gene p=0.01).

Conclusions: The estrogen SNP pathway was associated with POAG among women.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712669PMC
September 2013

Risk of endophthalmitis and other long-term complications of trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS).

Am J Ophthalmol 2013 Apr 13;155(4):674-680, 680.e1. Epub 2012 Dec 13.

Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan.

Purpose: To report the risk of endophthalmitis and other long-term complications in patients randomized to trabeculectomy in the Collaborative Initial Glaucoma Treatment Study.

Design: A longitudinal cohort study using data collected from a multicenter, randomized clinical trial.

Methods: Long-term postoperative complications in the 300 patients randomized to trabeculectomy in the Collaborative Initial Glaucoma Treatment Study were tabulated. Kaplan-Meier analyses were used to estimate the time-related probabilities of blebitis, hypotony, and endophthalmitis.

Results: Two hundred eighty-five patients were included in the final trabeculectomy cohort after accounting for declining treatment assignment and other early events. Patients were followed up for an average of 7.2 years. One hundred sixty-three patients (57%) received 5-fluorouracil during surgery. 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 2 patients was presumptive. The occurrences of blebitis, hypotony, or endophthalmitis were not significantly associated with 5-fluorouracil use. The Kaplan-Meier calculated risks of blebitis and hypotony at 5 years were both 1.5%, whereas 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 Collaborative Initial Glaucoma Treatment Study.
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http://dx.doi.org/10.1016/j.ajo.2012.10.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608803PMC
April 2013

Racial disparities in the use of ancillary testing to evaluate individuals with open-angle glaucoma.

Arch Ophthalmol 2012 Dec;130(12):1579-88

Objective: To determine whether racial disparities exist in the use of ancillary testing to evaluate individuals with open-angle glaucoma.

Methods: We identified all enrollees aged 40 years and older in a large US managed care network with retinal or optic nerve conditions that could warrant the use of ancillary testing. Among persons with open-angle glaucoma or glaucoma suspects, we performed repeated-measures multivariable logistic regression to determine the odds and probabilities each year of undergoing visual field testing, fundus photography, and other ocular imaging for black, white, Hispanic, and Asian American men and women and compared the groups.

Results: Among the 797 879 eligible enrollees, 149 018 individuals had open-angle glaucoma. The odds of undergoing visual field testing decreased for all groups from 2001 through 2009, decreasing most for Hispanic men and women (63% and 57%, respectively) (adjusted odds ratio [AOR], 0.37; 95% CI, 0.31-0.43 and AOR, 0.43; 95% CI, 0.37-0.50, respectively) and least (36%) for Asian American men (AOR, 0.64; 95% CI, 0.51-0.80). By comparison, the odds of undergoing other ocular imaging increased for all groups from 2001 through 2009, increasing most (173%) for black men and women (AOR, 2.73; 95% CI, 2.34-3.18 for men and AOR, 2.73; 95% CI, 2.40-3.09 for women) and least (77%) for Hispanic women (AOR, 1.77; 95% CI, 1.49-2.09).

Conclusion: Hispanic men and women had considerably reduced odds of undergoing visual field testing and other ocular imaging compared with other groups during the decade. Although increases in glaucoma testing have been noted in recent years among Hispanic men and women for some types of ancillary tests, efforts should be made to better understand and overcome some of the persistent barriers to monitoring for glaucoma in this group.
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http://dx.doi.org/10.1001/archophthalmol.2012.1325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635134PMC
December 2012

CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States.

Am J Ophthalmol 2013 Feb 27;155(2):342-353.e5. Epub 2012 Oct 27.

Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.

Purpose: To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients.

Design: Retrospective observational case series.

Methods: We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results.

Results: For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95% CI: -0.08, -0.03; P = 6.23E-05) despite having higher intraocular pressure (IOP) (0.70 mm Hg higher per G allele at DNA collection; 95% CI: 0.40, 1.00; P = 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95% CI: 0.02, 0.07; P = 4.74E-04) despite having lower IOP (-0.57 mm Hg per A allele at DNA collection; 95% CI: -0.84, -0.29; P = 6.55E-05).

Conclusion: Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG.
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http://dx.doi.org/10.1016/j.ajo.2012.07.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544983PMC
February 2013

The NEIGHBOR consortium primary open-angle glaucoma genome-wide association study: rationale, study design, and clinical variables.

J Glaucoma 2013 Sep;22(7):517-25

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.

Primary open-angle glaucoma (POAG) is a common disease with complex inheritance. The identification of genes predisposing to POAG is an important step toward the development of novel gene-based methods of diagnosis and treatment. Genome-wide association studies (GWAS) have successfully identified genes contributing to complex traits such as POAG however, such studies frequently require very large sample sizes, and thus, collaborations and consortia have been of critical importance for the GWAS approach. In this report we describe the formation of the NEIGHBOR consortium, the harmonized case control definitions used for a POAG GWAS, the clinical features of the cases and controls, and the rationale for the GWAS study design.
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http://dx.doi.org/10.1097/IJG.0b013e31824d4fd8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485429PMC
September 2013

Clinical characteristics of newly diagnosed primary, pigmentary and pseudoexfoliative open-angle glaucoma in the Collaborative Initial Glaucoma Treatment Study.

Br J Ophthalmol 2012 Sep 6;96(9):1180-4. Epub 2012 Jul 6.

Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, Michigan, USA.

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 the prognosis.

Methods: Information on 607 participants of the Collaborative Initial Glaucoma Treatment Study was accessed. Descriptive statistics characterised their demographic, ocular and medical status at diagnosis. Comparisons were made using analysis of variance and χ(2) or Fisher's 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 women, less likely to have bilateral disease, and presented with higher intraocular pressure (IOP) and better visual acuity. The type of glaucoma was not associated with IOP 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.
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http://dx.doi.org/10.1136/bjophthalmol-2012-301820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480313PMC
September 2012

Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma.

PLoS Genet 2012 26;8(4):e1002654. Epub 2012 Apr 26.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America.

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.
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http://dx.doi.org/10.1371/journal.pgen.1002654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343074PMC
September 2012

Trends in use of ancillary glaucoma tests for patients with open-angle glaucoma from 2001 to 2009.

Ophthalmology 2012 Apr 3;119(4):748-58. Epub 2012 Jan 3.

W.K. Kellogg Eye Center, University of Michigan, Department of Ophthalmology and Visual Sciences, 1000 Wall Street, Ann Arbor, MI 48105, USA.

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.
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http://dx.doi.org/10.1016/j.ophtha.2011.09.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319788PMC
April 2012

GALC deletions increase the risk of primary open-angle glaucoma: the role of Mendelian variants in complex disease.

PLoS One 2011 4;6(11):e27134. Epub 2011 Nov 4.

Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, United States of America.

DNA copy number variants (CNVs) have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG) is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC). This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1.) (p = 0.017, fisher's exact test). It was validated with array comparative genomic hybridization (arrayCGH) and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio) = 3.5, 95% CI -1.1-12.0). Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6-16.4). Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0027134PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208571PMC
March 2012

Intraocular pressure control and long-term visual field loss in the Collaborative Initial Glaucoma Treatment Study.

Ophthalmology 2011 Sep 20;118(9):1766-73. Epub 2011 May 20.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.

Objective: To evaluate the impact of measures of intraocular pressure (IOP) control on progression of visual field (VF) loss during long-term treatment for open-angle glaucoma (OAG).

Design: Longitudinal, randomized clinical trial.

Participants: We included 607 participants with newly diagnosed OAG.

Methods: Study participants were randomly assigned to initial treatment with medications or trabeculectomy, and underwent examination at 6-month intervals. Standardized testing included Goldmann applanation tonometry and Humphrey 24-2 full threshold VFs. Summary measures of IOP control during follow-up included the maximum, mean, standard deviation (SD), range, proportion less than 16, 18, 20, or 22 mmHg, and whether all IOP values were less than each of these 4 cutpoints. Predictive models for VF outcomes were based on the mean deviation (MD) from VF testing, and were adjusted for age, gender, race, baseline VF loss, treatment, and time. Each summary IOP measure was included as a cumulative, time-dependent variable, and its association with subsequent VF loss was assessed from 3 to 9 years postrandomization. Both linear mixed models, to detect shifts in MD levels, and logistic models, to detect elevated odds of substantial worsening (≥3 dB), were used.

Main Outcome Measures: We measured the MD from Humphrey 24-2 full threshold VF tests.

Results: The effect of the summary IOP measures differed between the medicine and surgery groups in models that addressed the continuous MD outcome. After adjustment for baseline risk factors, in the medicine group larger values of 3 IOP control measures-maximum IOP (P = 0.0003), SD of IOP (P = 0.0056), and range of IOP (P<0.0001)-were significantly associated with lower (worse) MD over the 3- to 9-year period. No IOP summary measure was significantly associated with MD over time in the surgery group. The same 3 IOP summary measures were also significantly associated with substantial worsening of MD; however, the effects were similar in both treatment groups. In models predicting inadequate IOP control, consistently significant predictors of higher maximum, SD, and range of IOP included black race, higher baseline IOP, and clinical center.

Conclusions: These results support considering more aggressive treatment when undue elevation or variation in IOP measures is observed.
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http://dx.doi.org/10.1016/j.ophtha.2011.01.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161134PMC
September 2011

Association between the use of glaucoma medications and mortality.

Arch Ophthalmol 2010 Feb;128(2):235-40

Department of Ophthalmology, University of Michigan, 1000 Wall St, Ann Arbor, MI 48105, USA.

Objective: To evaluate the relationship between glaucoma medication use and death.

Methods: This study uses longitudinal data from 2003 to 2007 on persons 40 years and older with glaucoma or suspected glaucoma enrolled in a large managed care network. Cox regression analysis was performed to estimate the hazard of death associated with the use of various glaucoma medication classes and combinations thereof. Multivariable models were adjusted for demographic characteristics and comorbid medical conditions.

Results: Of 21 506 participants with glaucoma or suspected glaucoma, 237 (1.1%) died during the study period. The use of any class of glaucoma medication was associated with a 74% reduced hazard of death (adjusted hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.16-0.40) compared with no glaucoma medication use. This association was observed for use of a single agent alone, such as a topical beta-antagonist (0.44; 0.24-0.83) or a prostaglandin analogue (0.31; 0.18-0.54), and for use of different combinations of drug classes.

Conclusions: After adjustment for potential confounding variables, the use of glaucoma medications was associated with a reduced likelihood of death in this large sample of US adults with glaucoma. Future investigations should explore this association further because these findings may have important clinical implications.
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http://dx.doi.org/10.1001/archophthalmol.2009.378DOI Listing
February 2010
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