Demographic, Comorbid, and Clinical Variables Associated With Pointwise Visual Field Damage in Glaucoma: Data From the AGIS and CIGTS Clinical Trials.

Purpose: To investigate differences across the visual field (VF) in the rate of glaucomatous progression, the likelihood of defect in four disease severity cross-sections, and comparisons of subgroups in each of between 12 demographic, comorbid, and clinical variables. Methods: Two long-term glaucoma clinical trials used Humphrey Field Analyzer 24-2 VFs to calculate pointwise deviations from age-matched normal controls. Slopes of glaucomatous progression over time were calculated per participant using linear mixed models. Pointwise differences between subgroups in slopes and cross-sectional categories were tested, adjusting for multiple comparisons using false discovery rate (FDR) and Q values. Results: Pointwise data were available for 1118 patients who had 15,073 VFs. On average, defects were seen at all VF points. Of the 12 variables, six had average pointwise slopes where Subgroup 1 had significantly faster progression than Subgroup 2 at all or many of the 52 VF points: participants who were older (≥65 vs. younger), 52/52; were male, 13/52; had diabetes, 29/52; had hypertension, 46/52; had a larger cup-to-disc ratio (≥0.7), 36/52; or had larger differences in absolute mean deviation (MD) between eyes (>3 dB), 52/52. Cross-sectional patterns at MD severity of -12 to -6.1 dB showed strong midline effects for gender and other patterns for hypertension, cup-to-disc ratio, absolute difference in MD between eyes, and disc notching. Conclusions: The approach used provides new longitudinal and cross-sectional insights into variation across the VF associated with demographic, comorbid, and clinical variables. Translational Relevance: This exploration and characterization of variable effects in the setting of pointwise VF testing may enable clinicians to anticipate patterns of VF loss based on demographic, comorbid, and clinical associations.

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

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.

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

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.

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

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 (ß = -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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Visual field improvement in the collaborative initial glaucoma treatment study.

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.

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

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.