Crystalline lens changes after selective laser trabeculoplasty in Afro-Caribbean patients with open-angle glaucoma; report 4 of the West Indies Glaucoma Laser Study (WIGLS).

PURPOSE: To characterize changes in nuclear, cortical, and posterior subcapsular lens opacities after selective laser trabeculoplasty (SLT) in Afro-Caribbean eyes with primary open-angle glaucoma (POAG). SETTING: Three clinical practices, Saint Lucia and Dominica. DESIGN: Prospective case series. METHODS: Patients with POAG in the West Indies Glaucoma Laser Study (WIGLS) had 360-degree SLT after medication washout. No antiinflammatory therapy was used after SLT. Nuclear, cortical, and posterior subcapsular lens opacities were graded through dilated pupils using the Lens Opacification Classification System III (LOCS III) at baseline and 12, 24, and 36 months after SLT, with the grader masked to all previous values after baseline assessment. Changes in opacity scores from baseline were evaluated using paired t tests. RESULTS: Seventy-two patients (142 phakic eyes) were evaluated. The mean (±SD) baseline LOCS III opacity scores in right eyes and left eyes, respectively, were 2.44 ± 1.23 and 2.40 ± 1.16 (nuclear), 0.39 ± 1.08 and 0.30 ± 0.85 (cortical), and 0.22 ± 0.59 and 0.15 ± 0.36 (posterior subcapsular). Other than a small improvement in bilateral nuclear opacity scores at 12 months, no statistically or clinically significant changes in any opacity score occurred in either eye up to 36 months postoperatively. Three eyes (2.1%) with preexisting lens opacities had cataract surgery for progressive lens changes at 3 months, 21 months, and 26 months, respectively, after SLT. CONCLUSIONS: Selective laser trabeculoplasty was not associated with clinically significant changes in nuclear, cortical, or posterior subcapsular lens opacities in glaucomatous Afro-Caribbean eyes. The rate of cataract surgery is consistent with reported rates from longitudinal natural history studies in Caribbean and non-Caribbean populations.

West Indies Glaucoma Laser Study (WIGLS)-2: Predictors of Selective Laser Trabeculoplasty Efficacy in Afro-Caribbeans With Glaucoma.

PURPOSE: To identify factors associated with intraocular pressure (IOP) reduction following selective laser trabeculoplasty (SLT) in Afro-Caribbean people with primary open-angle glaucoma (POAG). DESIGN: This was a prospective stepped-wedge study. METHODS: Data were drawn from 72 Afro-Caribbean subjects with POAG participating in the ongoing West Indies Glaucoma Laser Study. Multivariable mixed-model analysis was utilized to develop a predictive model for percent IOP reduction 12 months following SLT. Putative factors (age, sex, site, baseline IOP, prior use of prostaglandin therapy, number of prewashout IOP-lowering medications, central corneal thickness, severity of glaucoma, duration of follow-up, and signs of acute postoperative inflammation) were evaluated in bivariate analysis. Factors significant at P≤0.2 were included in the final model. Right and left eye data were modeled separately. RESULTS: At month 12 following SLT, mean IOP reductions in the West Indies Glaucoma Laser Study were 6.2 to 6.5 mm Hg (29.7% to 31.0%) in right and left eyes. The only factor significant in both eyes (P=0.0005 in right eyes and P<0.0001 in left eyes) was time, with IOP reductions being greatest at month 3 and declining slightly over time through month 12. Vertical cup-disc ratio (P=0.006) and prior prostaglandin therapy (P=0.004) were significant only in right eyes, and central corneal thickness (P=0.014) was significant only in left eyes. Factors significant only unilaterally did not approach significance in fellow eyes, suggesting the possibility that these represent type 1 errors. Site (St. Lucia vs. Dominica) was not a significant factor, establishing generalizability of these treatment outcomes to a broader population of African-derived people. CONCLUSIONS: This analysis did not identify any subject-specific factors consistently predictive of therapeutic response to SLT. Of note, no factors predicted a suboptimal response. These findings favorably position SLT for broad application as primary therapy in African-derived people with POAG.

Postoperative Inflammation After Endoscopic Cyclophotocoagulation: Racial Distribution and Effect on Outcomes.

PURPOSE: To assess the prevalence of postoperative anterior chamber reaction or persistent anterior uveitis (PAU) by race and its effect on intraocular pressure (IOP) and visual acuity (VA) after combined phacoemulsification and endoscopic cyclophotocoagulation (ECP) in primary open-angle glaucoma. PATIENTS AND METHODS: A retrospective analysis of all patients with primary open-angle glaucoma who underwent combined phacoemulsification cataract extraction with ECP from January 1, 2007 to October 31, 2015. VA, IOP, presence of anterior chamber cells, steroid treatment, and number of IOP lowering drops were analyzed preoperatively and up to 3 months postoperatively. Patients were categorized according to self-reported race. PAU was treated according to severity and presence of symptoms. RESULTS: Two hundred twenty-three eyes met the inclusion criteria. PAU was present in 22.4% of eyes. PAU was significantly correlated with race, particularly African American race. PAU was also associated with a lack of improvement in inflammation at week 1 compared with day 1 postoperatively. However, there was no significant difference in VA, IOP, or reduction of IOP lowering drops in those with or without PAU. When comparing African Americans to whites, PAU and its treatment were not associated with a difference in IOP reduction at 3 months. CONCLUSIONS: PAU is common after combined phacoemulsification and ECP and is significantly correlated with race. Although PAU may require prolonged postoperative treatment, our data does not support poorer VA or IOP outcomes.

West Indies Glaucoma Laser Study (WIGLS): 1. 12-Month Efficacy of Selective Laser Trabeculoplasty in Afro-Caribbeans With Glaucoma.

PURPOSE: To characterize the 12-month intraocular pressure (IOP)-lowering efficacy of selective laser trabeculoplasty (SLT) as sole therapy for primary open-angle glaucoma (POAG) in an Afro-Caribbean population. DESIGN: Stepped-wedge trial. METHODS: Subjects in St. Lucia and Dominica with established POAG were randomized to prompt washout of IOP-lowering medications followed by SLT, 3-month delay followed by washout and SLT, or 6-month delay followed by washout and SLT. Baseline IOP was obtained on 2 different days after washout. Bilateral 360-degree SLT was performed in 1 session. Posttreatment assessments took place 1 hour, 1 week, and 3, 6, 9, and 12 months post-SLT. The main outcome measure was SLT success (defined as IOP ≤ target IOP in both eyes) at 12 months. Target IOP was a 20% or greater reduction in IOP from postwashout baseline. RESULTS: Overall, 72 patients underwent SLT treatment. Mean IOP at enrollment was 15.4 ± 3.6 mm Hg in right eyes and 15.4 ± 3.6 mm Hg in left eyes, which rose to 21.0 ± 3.3 mm Hg and 20.9 ± 3.0 mm Hg, respectively, after washout. Mean IOP at 3, 6, 9, and 12 months ranged from 12.5 mm Hg to 14.5 mm Hg (29.7% to 39.5%; P < .0001 in each eye at each time point). The 12-month success rate was 78%. Transient photophobia and discomfort were common. CONCLUSIONS: SLT monotherapy safely provides significant IOP reduction in Afro-Caribbean eyes with POAG. This treatment can play a significant role in preventing glaucoma vision loss and blindness in people of African descent living in resource-limited regions.

Association of single-nucleotide polymorphisms in non-coding regions of the TLR4 gene with primary open angle glaucoma in a Mexican population.

BACKGROUND: Toll-like receptor 4 (TLR4) non-coding polymorphisms are associated to primary open angle glaucoma (POAG), normal tension glaucoma, and pseudoexfoliation glaucoma. This study was performed to determine whether non-coding single nucleotide polymorphisms (SNPs) in the TLR4 gene contribute to POAG in a Mexican population. MATERIAL AND METHODS: A total of 187 unrelated Mexican patients with POAG and 109 control subjects were included. Allelic, genotypic, and haplotypic diversity was assessed for the non-coding polymorphisms rs11536889, rs1927911, rs12377632, and rs2149356 of the TLR4 gene. Genotyping of target SNPs was performed by 5' exonuclease allelic discrimination assays. RESULTS: Strong linkage disequilibrium was observed among the SNPs (D' > 0.818), which were located in one haplotype block. The rs11536889 polymorphism was not associated to POAG in any case. The frequency of the minor allele of rs2149356 was significantly higher in the glaucoma group, conferring an increased risk of POAG (p = 0.0018, OR = 1.803, 95% CI 1.2556-2.5890) whereas minor allele of rs12377632 was significantly lower, attributing a protective effect (p = 0.0001, OR = 0.6662, 95% CI 0.4753-0.9339). Subjects with genotypes carrying the minor allele of rs1927911 and rs2149356 shown an increased risk for POAG (p = 0.03, OR = 1.78, 95% CI 1.10-2.87, and p < 0.0004, OR =2.62, 95%CI 1.61-4.27 respectively). Finally, we found significant risk haplotypes. The GTT haplotype (constituted by rs1927911, rs12377632, and rs2149356) reached the higher OR (p = 0.0026, OR = 4.70, 95% CI 1.73-12.77). CONCLUSIONS: We have identified intronic TLR4 SNPs as genetic susceptibility alleles for POAG in a Mexican population. Our findings support the association of the TLR4 gene with POAG.

Selective laser trabeculoplasty for the management of open-angle glaucoma in St. Lucia.

OBJECTIVE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) for the treatment of primary open-angle glaucoma in an African-derived population in the developing world. METHODS: Sixty-one subjects from St. Lucia with medically treated primary open-angle glaucoma underwent a 30-day washout, followed by bilateral 360° SLT. Intraocular pressure (IOP) was measured 1 hour; 1 week; and 1, 3, 6, 9, and 12 months after SLT. RESULTS: Mean (SD) IOP with medical therapy was 17.3 (5.0) mm Hg and 17.5 (4.0) mm Hg in the right and left eyes, respectively, and increased to 21.4 (3.6) mm Hg and 21.1 (3.5) mm Hg, respectively, after washout. Both eyes demonstrated a prompt and sustained IOP response to SLT therapy. Intraocular pressure dropped significantly by the first week and remained in the range of 13 to 14 mm Hg without medical therapy through 12 months in patients deemed successful. The mean IOP reductions from baseline ranged from 7.3 to 8.3 mm Hg (34.1%-38.8%) in right eyes and from 7.6 to 8.2 mm Hg (36.0%-38.9%) in left eyes through 12 months. The 12-month Kaplan-Meier survival rate (≥10% IOP reduction from postwashout baseline) was 77.7%, and 93% of successful subjects experienced IOP levels less than with-medication values. Most subjects reported moderate photophobia for 2 to 3 days after SLT; only 1 received anti-inflammatory therapy. Five eyes of 3 subjects had IOP spikes between 5 and 10 mm Hg that resolved without treatment. CONCLUSIONS: The magnitude and duration of IOP reduction are clinically relevant in individuals from St. Lucia of African descent. If repeatable, SLT could be a powerful tool for reducing glaucoma-related blindness in this population.

Association study of multiple gene polymorphisms with the risk of adult-onset primary open-angle glaucoma in a Mexican population.

The aim of this study was to investigate the association of multiple primary open-angle glaucoma (POAG)-risk alleles in a Mexican population for the first time. Genotyping was performed for a total of 26 previously associated alleles located in 11 different genes, including MYOC, CYP1B1, OPTN, IL1A, TNF, OPA1, EDNRA, AGTR2, MTHFR, GSTM1, and GSTT1. The frequencies of these variants were compared in a group of 218 individuals (118 with POAG and 100 adult controls without the disease). Genomic DNA was extracted from blood leukocytes, and genotyping was performed using PCR followed by direct sequencing. GSTM1 and GSTT1 deletion variants were screened by agarose gel analysis. Individual SNP analysis showed that no specific variants conferred an elevated risk for developing POAG. However, the CG genotype for rs5335 polymorphism in EDNRA showed a protective effect against the development of POAG, as it provides an estimated odds ratio of 0.5 (95% CI, 0.3-0.9; p = 0.03). Moreover, one haplotype consisting of rs1056827 and rs100012 in CYP1B1 gene was significantly associated with a protective effect against POAG (p = 0.0045; OR = 0.3; 95% CI, 0.1-0.7). This is the first case-control investigation of POAG-risk alleles in multiple genes in a Latino population. Although our results support that the analyzed variants are not major risk factors for POAG in this ethnic group, they also point toward a protective effect conferred by EDNRA rs5335, as well as by a CYP1B1 haplotype consisting of rs1056827 and rs100012. Our study emphasizes the importance of genotyping ethnic groups with a complex admixture of ancestral populations for contributing to dissecting the genetics of POAG.

Novel and known MYOC exon 3 mutations in an admixed Peruvian primary open-angle glaucoma population.

PURPOSE: The aim of this study was to characterize a representative sample of the Peruvian population suffering open-angle glaucoma (OAG) with respect to the myocilin gene (MYOC) mutations, glaucoma phenotype, and ancestry for future glaucoma risk assessment. METHODS: DNA samples from 414 unrelated Peruvian subjects, including 205 open-angle glaucoma cases (10 juvenile glaucoma [JOAG], 19 normal-tension glaucoma [NTG], and 176 POAG) and 209 randomly sampled controls, were screened for nucleotide changes in MYOC exon 3 by conformational sensitive gel electrophoresis (CSGE) and mutation screening. RESULTS: We identified a probable causative novel MYOC missense mutation, Gly326Ser, in one POAG case and found a consistent genotype-phenotype correlation in eight of his relatives. We also found the known causative MYOC mutation Trp286Arg in one JOAG case and one POAG case. A known causative single base MYOC deletion, T1357, was found in one POAG case. Two previously reported silent polymorphisms, Thr325Thr and Tyr347Tyr, were found in both the case and the control populations. A novel missense variant, Met476Arg, was identified in two unrelated controls. CONCLUSIONS: The screening of exon 3 of MYOC in a representative sample of 205 independent POAG patients from Peru and 209 matched controls identified novel and previously reported mutations (both pathogenic and nonpathogenic) from other global regions. These results reflect the complex admixture of Amerindian and Old World ancestry in urban populations of Latin America, in general, and in Peru, in particular. It will be important to gather information about the ancestral origin of MYOC and other POAG gene mutations to develop screening panels and risk assessment for POAG in Peru.

Central corneal thickness as a predictor of visual field loss in primary open angle glaucoma for a Hispanic population.

BACKGROUND: Primary Open Angle Glaucoma is a multi-factorial disease with a devastating impact on the quality of life of the patient in the moderate and severe stages of the disease. Identifying risk factors for the development of moderate to severe visual field loss may decrease the proportion of patients that experience the severe forms of this disease. PURPOSE: To evaluate whether the central corneal thickness correlates inversely with the severity of visual field loss in Primary Open Angle Glaucoma. METHODS: Retrospective review of 308 charts of patients seen during a six-week period by a glaucoma specialist in his community practice in a large Hispanic area. Patients were classified as normal, ocular hypertensive, and those with Primary Open Angle Glaucoma. Odds ratios and 95% confidence interval were calculated to evaluate risk factors associated to ocular hypertension and Primary Open Angle Glaucoma. Finally, a multivariate polytomous regression model was used to evaluate central corneal thickness as an independent predictor of outcome after adjustment for age and hypertension. Statistical significance was set at p<0.05. RESULTS: Patients with Primary Open Angle Glaucoma show a statistically significant inverse correlation between central corneal thickness and the severity of the visual field damage. CONCLUSION: Thinner corneas could be considered a risk factor for the severity of visual field loss in Primary Open Angle Glaucoma.

Myocilin mt.1 gene promoter single nucleotide polymorphism (-1000C>G) in Brazilian patients with primary open angle glaucoma.

BACKGROUND: The myocilin (MYOC) gene promoter polymorphism -1000C>G (MYOC mt.1) can be associated with faster progression of primary open angle glaucoma (POAG). The purpose of this study was to investigate the MYOC mt.1 in Brazilian patients with POAG and to evaluate its possible role on the phenotype and the severity of the disease. MATERIAL AND METHODS: One hundred sixty-seven POAG patients and 130 normal controls were enrolled. DNA samples were prepared and the MYOC mt.1 polymorphism was screened by real-time polymerase chain reaction (RT-PCR) in an Single-nucleotide polymorphism (SNP) assay. Frequencies of the MYOC mt.1 promoter polymorphism were determined for both groups and compared by Fisher's exact test and Chi-square test with Yate's correction. Intraocular pressure (IOP), cup-to-disc ratio (C/D), number of glaucoma medications, and number of glaucoma surgeries were compared between MYOC mt.1 carriers and non-carriers. RESULTS: MYOC mt.1 genotype frequencies did not differ between POAG and controls (P = 0.420); 14.6% of controls and 16.4% of POAG patients were MYOC mt.1 carriers (CG or GG). Frequencies of the G allele were similar between glaucomatous patients and controls (7.3% and 9.2%, respectively; P = 0.477). Among POAG patients, there were no differences in mean C/D ratio, IOP, number of glaucoma medications, and surgical procedures for IOP control between carries and non-carriers of the MYOC mt.1 promoter polymorphism (p>0.05). CONCLUSION: The G allele of the MYOC mt.1 promoter polymorphism was equally distributed among POAG patients and healthy subjects and it is possibly unrelated to the risk and severity of disease in the Brazilian population.

Common variants on chromosome 2 and risk of primary open-angle glaucoma in the Afro-Caribbean population of Barbados.

Primary open-angle glaucoma (POAG) is the second leading cause of blindness worldwide. Although a number of genetic loci have shown association or genetic linkage to monogenic forms of POAG, the identified genes and loci do not appear to have a major role in the common POAG phenotype. We seek to identify genetic loci that appear to be major risk factors for POAG in the Afro-Caribbean population of Barbados, West Indies. We performed linkage analyses in 146 multiplex families ascertained through the Barbados Family Study of Glaucoma (BFSG) and identified a strong linkage signal on chromosome 2p (logarithm of odds score = 6.64 at = 0 with marker D2S2156). We subsequently performed case-control analyses using unrelated affected individuals and unaffected controls. A set of SNPs on chromosome 2p was evaluated in two independent groups of BFSG participants, a discovery group (130 POAG cases, 65 controls) and a replication group (122 POAG cases, 65 controls), and a strong association was identified with POAG and rs12994401 in both groups (P < 3.34 E-09 and P < 1.21E-12, respectively). The associated SNPs form a common disease haplotype. In summary, we have identified a locus with a major impact on susceptibility to the common POAG phenotype in an Afro-Caribbean population in Barbados. Our approach illustrates the merit of using an isolated population enriched with common disease variants as an efficient method to identify genetic underpinning of POAG.

Impact of glaucoma, lens opacities, and cataract surgery on visual functioning and related quality of life: the Barbados Eye Studies.

PURPOSE: To determine the relationship of open-angle glaucoma (OAG) and lens opacities to visual functioning and related quality of life (QOL), by using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) in a population of African origin. METHODS: The study included 962 black participants of the Barbados Eye Studies with known glaucoma, prior cataract surgery, visual acuity (VA)

Open-angle glaucoma and mortality: The Barbados Eye Studies.

OBJECTIVE: To evaluate the relationship between open-angle glaucoma (OAG) and mortality in a black population at 9-years' follow-up. DESIGN: Population-based cohort study of 4092 black participants (aged 40-84 years at baseline) in the Barbados Eye Studies. Open-angle glaucoma was defined by visual field defects and optic disc damage, based on standardized examinations and photograph gradings. Ocular hypertension was defined by an intraocular pressure greater than 21 mm Hg or treatment, without OAG damage. Mortality was ascertained from death certificates. Cox proportional hazards regression analyses determined associations with mortality. RESULTS: After 9 years, 764 (19%) participants were deceased. Mortality was unrelated to overall OAG at baseline (n = 300) after adjustment for confounders. However, cardiovascular mortality tended to increase in persons with previously diagnosed/treated OAG (n = 141; relative risk [RR], 1.38, P = .07) and was significantly higher with treatment involving timolol maleate (RR, 1.91, P = .04). Cardiovascular deaths also tended to increase in persons with ocular hypertension at baseline (n = 498; RR, 1.28, P = .06). CONCLUSIONS: In this black population, cardiovascular mortality tended to increase in persons with previously diagnosed/treated OAG and ocular hypertension. The excess mortality associated with timolol maleate treatment of OAG, also found in a white population, warrants further investigation.

Recurrent Myocilin Asn480Lys glaucoma causative mutation arises de novo in a family of Andean descent.

PURPOSE: To search for MYOC mutations in Peruvian primary open angle glaucoma (POAG) families. PATIENTS AND METHODS: Two patients from each of the 11 POAG Peruvian families were screened for sequence variants in MYOC coding exons by conformational sensitive gel electrophoresis and sequencing was performed on the samples indicating probable sequence changes. RESULTS: We detected 2 families bearing distortions of conformational sensitive gel electrophoresis indicating mutations. Sequencing of these samples revealed coding sequence changes. A native Andean descent family presented with a MYOC mutation, Asn480Lys (C-->G at nucleotide 1440). This is different from the previously reported C-->A change at nucleotide 1440 that causes Asn480Lys in 2 unrelated French and Dutch families with glaucoma of variable expressivity, and indicates a third independent event. A second family of admixed origin showed the presence of the known Arg76Lys polymorphism. CONCLUSIONS: In the study of MYOC variants in 11 POAG Peruvian families, we have found a family of ethnically admixed origin with polymorphism Arg76Lys and a family of Andean descent bearing a third event of the Asn480Lys, the MYOC mutation that has been reported in the highest number of POAG patients (>80 cases). Analysis of this family could contribute with information about disease manifestation, progression, and treatment response in the context of a distinct genetic background and also climatic, altitude, and socioeconomical conditions.

Risk factors for incident open-angle glaucoma: the Barbados Eye Studies.

PURPOSE: To evaluate risk factors for definite open-angle glaucoma (OAG), based on African-descent participants of the Barbados Eye Studies. DESIGN: Cohort study with 81% to 85% participation over 9 years' follow-up. PARTICIPANTS: We evaluated 3222 persons at risk, 40 to 84 years old, who did not have definite OAG at baseline. METHODS: Participants had standardized study visits at baseline and after 4 and 9 years, with structured interviews, blood pressure (BP), and other measurements. The ophthalmic protocol included automated perimetry, applanation tonometry, fundus photography, and comprehensive ophthalmologic examinations for those referred. Central corneal thickness (CCT) was measured in a subset at the 9-year examination. Incidence was estimated by the product-limit approach; relative risk ratios (RRs) with 95% confidence intervals (CIs) were based on Cox regression models with discrete time. MAIN OUTCOME MEASURE: Nine-year incidence of definite OAG. RESULTS: Over 9 years, 125 persons developed definite OAG (incidence, 4.4%; 95% CI, 3.7-5.2). Baseline factors influencing risk were age (RR, 1.04; 95% CI, 1.02-1.05 per year); family history of glaucoma (RR, 2.4; 95% CI, 1.3-4.6); higher intraocular pressure (IOP) (RR, 1.12; 95% CI, 1.08-1.16 per mmHg); lower systolic BP (RR, 0.91; 95% CI, 0.84-1.00 per 10 mmHg); and lower ocular systolic, diastolic, and mean perfusion pressures (RR, 0.66; 95% CI, 0.54-0.80 per 10 mmHg higher mean perfusion pressure) (RR, 2.6; 95% CI, 1.4-4.6 for low mean perfusion pressure [<40 mmHg]). Thinner CCT was also associated with OAG incidence (odds ratio, 1.41; 95% CI, 1.01-1.96 per 40 mum lower). CONCLUSIONS: This is the first report of risk factors for long-term OAG incidence; it is also based on a sizable number of new cases. Incidence was high in this African-descent population, where the established factors of older age, higher IOP, and family history contributed to risk. Additional predictors were vascular factors, including lower systolic BP, and particularly lower ocular perfusion pressures, which more than doubled risk. Thinner CCT was also a factor. These findings indicate a multifactorial etiology of OAG and suggest that similar risk factors apply across populations. Results are relevant for understanding OAG causation and identifying groups at high risk.

Awareness of incident open-angle glaucoma in a population study: the Barbados Eye Studies.

PURPOSE: To evaluate factors related to awareness of incident open-angle glaucoma (OAG) in the Barbados Eye Studies. DESIGN: Cohort study with 81% to 85% response rate over 9 years. PARTICIPANTS: Four thousand three hundred fourteen participants of African descent, 40 to 84 years old at baseline. METHODS: Standardized study visits included an interview on demographic, medical, health care, and other factors; various ophthalmic measurements; fundus photography; and comprehensive ophthalmologic examinations for those referred. MAIN OUTCOME MEASURES: Definite OAG was defined by both visual field and optic disc criteria after ophthalmologic confirmation, regardless of intraocular pressure (IOP). Definite incident participants without prior OAG diagnosis/treatment were considered unaware. Logistic regression analyses evaluated factors associated with OAG unawareness. Results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Over 9 years, 125 participants newly developed definite OAG, of whom 53% were previously unaware. At baseline, the unaware group had significantly lower mean IOP (OR, 0.86; 95% CI, 0.79-0.94) and more hyperopia (OR, 2.69; 95% CI, 1.08-6.69) than those aware. Most unaware and aware participants had > or =2 medical care visits in the previous year (72.7% vs. 83.1%). However, those in the unaware group sought eye care less frequently than those aware (last visit in preceding year, 33.4% vs. 64.4%); these visits were mainly for eyeglasses (71.4% vs. 12.5%), with most having glaucoma tests only during study visits (72.7% vs. 37.3%). The unaware group reported more visits to opticians/optometrists than to private ophthalmologists (OR, 4.20; 95% CI, 1.00-17.66) and fewer visits to a public ophthalmologic clinic (OR, 0.18; 95% CI, 0.04-0.86). CONCLUSIONS: Over half of participants with incident OAG were unaware of their diagnosis. Unawareness was related to lower IOP, hyperopia, and eye care utilization patterns. Although persons in the unaware group had regular visits for medical care, visits for eye care and OAG testing were limited. Unawareness was 4 times more likely when opticians/optometrists were the regular eye care source, compared with private ophthalmologists, and about 80% less likely with a public ophthalmologic source. These findings highlight the high frequency of undiagnosed OAG and importance of comprehensive examinations in disease detection.

Incident open-angle glaucoma and intraocular pressure.

PURPOSE: To evaluate the role of baseline intraocular pressure (b-IOP) as a risk factor for incident open-angle glaucoma (OAG) in participants of African origin from the Barbados Eye Studies. DESIGN: Population-based 9-year cohort study. PARTICIPANTS: Three thousand two hundred twenty-two persons examined during the study period who were free of glaucoma at baseline and at risk of developing OAG during the 9-year follow-up. METHODS: Study protocols were standardized and included ophthalmic and other measurements, automated perimetry, applanation tonometry, fundus photography, and comprehensive ophthalmologic examination for those referred. The product-limit approach was used to estimate incidence. Relationships between b-IOP and incidence were evaluated by adjusted relative risk ratios (RRs) with 95% confidence intervals (CIs), based on Cox regression models. MAIN OUTCOME MEASURE: The 9-year incidence of OAG was based on both visual field and optic disc abnormalities, with ophthalmologic evaluations to exclude other possible causes. RESULTS: The overall 9-year incidence of OAG was 4.4% (95% CI, 3.7%-5.2%), and the mean (standard deviation) b-IOP among persons at risk was 18.0 mmHg (4.1). Among the 125 incident OAG cases, the mean b-IOP was 21.9 mmHg and 46% had b-IOP of >21 mmHg. In contrast, the nonincident group had a mean b-IOP of 17.8 mmHg and only 12% had b-IOP of >21 mmHg. Overall, OAG risk increased by 12% with each 1-mmHg increase in IOP (RR, 1.12; 95% CI, 1.08-1.16). Incidence steadily increased from 1.8% (95% CI, 1.2%-2.7%) for persons with b-IOP of < or =17 mmHg (referent group) to 22.3% (95% CI, 15.8%-31.1%) for those with b-IOP > 25 mmHg, resulting in an adjusted RR of 13.1 (95% CI, 7.1-24.1) among the latter group. The attributable risk for IOP of >25 mmHg was 19%. Using 21 mmHg as a cutoff, the RR was 7.9 (95% CI, 3.8-16.2) and the attributable risk was 37%. CONCLUSIONS: After 9 years' follow-up, the risk of OAG was positively related to IOP levels at baseline. Although persons with b-IOP of >25 mmHg had a 13-fold RR of developing OAG, most cases arose with lower b-IOP. This study thus confirms the role of IOP as an influential risk factor, yet at the same time underscores its limitations in predicting OAG.

Nine-year incidence of open-angle glaucoma in the Barbados Eye Studies.

PURPOSE: To determine the 9-year incidence of open-angle glaucoma (OAG) in African-descent participants of the Barbados Eye Studies. DESIGN: Nine-year cohort study with 81% to 85% participation. PARTICIPANTS: Three thousand two hundred twenty-two persons without definite OAG at baseline, at risk of developing OAG at follow-up. METHODS: The standardized protocol included automated perimetry and various ophthalmic measurements, with a comprehensive ophthalmologic examination for those referred. Fundus photographs were evaluated independently by masked graders. Incidence was estimated by the product-limit approach. Relative risk (RR) ratios with 95% confidence intervals (CIs) were based on Cox regression models with discrete time. MAIN OUTCOME MEASURE: Nine-year incidence of definite OAG, based on the development of visual field defects and glaucomatous optic neuropathy, with ophthalmologic confirmation. RESULTS: The 9-year incidence of definite OAG was 4.4% (95% CI, 3.7%-5.2%), or an average of 0.5%/year, based on 125 new cases. Incidence increased greatly with age, from 2.2% at ages 40 to 49 years to 7.9% at ages 70 years or older, and tended to be higher in men than women (4.9% vs. 4.1%; RR, 1.3; 95% CI, 0.9-1.8). More than half (53%) of new cases were undetected, and of these, one third had intraocular pressure of 21 mmHg or less. When 141 persons developing suspected/probable OAG were considered, the total incidence was 9.4% (8.4%-10.6%), averaging approximately 1%/year, also increasing with age, and significantly higher in men than women (10.7% vs. 8.6%; RR, 1.31; 95% CI, 1.02-1.67). CONCLUSIONS: These new data provide a measure of the long-term risk of OAG in an African-descent population, which is markedly higher than in persons of European ancestry. Results confirm the increased risk with age and in men. The incidence data fill a gap in our understanding of OAG risk and have implications for public health policy and planning; they also will allow the study of factors related to the risk of OAG development.

Nine-year changes in intraocular pressure: the Barbados Eye Studies.

OBJECTIVE: To describe temporal changes in intraocular pressure (IOP) and associated risk factors after 9 years of follow-up in a population of African descent. METHODS: Changes in IOP were evaluated in 2298 participants without glaucoma or IOP-lowering treatment at baseline. Risk factor analyses used a multiple regression approach with mixed effects, which accounted for intereye correlation. RESULTS: The mean 9-year change in IOP was small, with relatively large dispersion (mean +/- SD, 0.4 +/- 4.0 mm Hg). Only 6.5% of persons with IOP of 21 mm Hg or less at baseline had elevated IOP greater than 21 mm Hg after 9 years. Mean IOP increases were largest in persons aged 50 to 59 years at baseline (mean +/- SD, 0.9 +/- 4.3 mm Hg), whereas IOP decreased in persons 70 years or older (mean +/- SD, -0.6 +/- 4.2 mm Hg). In multivariate analyses, IOP changes were positively associated with male sex, hypertension, diabetes history, and higher systolic and diastolic blood pressure at baseline, as well as with increases in blood pressure throughout 9 years (P<.05). CONCLUSIONS: After long-term follow-up, minimal changes in IOP were observed in this African-origin population. The consistent relationships of hypertension and diabetes to IOP, a major glaucoma risk factor, underscore the public health importance of controlling these systemic conditions in black populations, where glaucoma incidence is high.

The effect of latanoprost compared with timolol in African-American, Asian, Caucasian, and Mexican open-angle glaucoma or ocular hypertensive patients.

OBJECTIVE: To study the intraocular pressure (IOP) reduction of latanoprost or timolol in a heterogeneous global population. METHODS: A total of 1,389 glaucoma or ocular hypertensive patients treated with 0.005% latanoprost once daily (n = 737) or 0.5% timolol twice daily (n = 652) from eight clinical trials were included. After 3-6 months of treatment, the IOP was analyzed with use of analysis of covariance. RESULTS: Latanoprost or timolol gave statistically significant mean diurnal IOP reduction in the African-American, Asian, Caucasian, and Mexican patients, latanoprost with 7.9 mm Hg and timolol with 6.4 mm Hg. The Asian and Mexican patients showed a larger difference in mean diurnal IOP reduction with use of the two drugs (range 1.8-3.1 mm Hg) than the European and U.S. patients (range 0.6-1.7 mm Hg, p = 0.030). Latanoprost produced similar mean diurnal IOP reduction in patients with and without previous glaucoma treatment other than prostaglandins. CONCLUSION: Latanoprost or timolol statistically significantly reduced the mean diurnal IOP in a heterogenous global population in eight clinical trials. The degree of reduction appeared to be clinically useful. The greatest difference in the mean diurnal IOP-lowering effect of latanoprost or timolol was observed in Mexican and Asian clinical trials.