Glaucoma-associated long-term mortality in a rural cohort from India: the Andhra Pradesh Eye Disease Study.

AIM: To evaluate glaucoma-associated mortality in a rural cohort in India. METHODS: The study cohort comprised individuals aged 40 years and above who took part in the Andhra Pradesh Eye Disease Study (APEDS1) during 1996-2000. All participants underwent detailed comprehensive eye examination. Glaucoma was defined using International Society of Geographic and Epidemiologic Ophthalmology criteria. This cohort was followed up after a decade (June 2009 to January 2010; APEDS2). Mortality HR analysis for ocular risk factors was performed using Cox proportional hazards regression after adjusting for sociodemographic, lifestyle and clinical variables. RESULTS: In APEDS1, 2790 individuals aged more than or equal to 40 years were examined. 47.4% were male. Forty-five participants had primary open angle glaucoma (POAG) and 66 had primary angle closure disease (PACD). Ten years later, 1879 (67.3%) were available, 739 (26.5%) had died and 172 (6.2%) had migrated; whereas 22 of the 45 (48.8%) with POAG and 22 of the 66 (33.3%) with PACD had died. In univariate analysis, a higher mortality was associated with POAG (HR 1.9; 95% CI 1.23 to 2.94), pseudoexfoliation (HR 2.79; 95% CI 2.0 to 3.89), myopia (HR 1.78; 95% CI 1.54 to 2.06) and unit increase in cup:disc ratio (HR 4.49; 95% CI 2.64 to 7.64). In multivariable analysis, only cup:disc ratio remained independently associated with mortality (HR 2.5; 95% CI 1.3 to 5.1). The association remained significant when other ocular parameters were included in the model (HR 2.1; 95% CI 1.03 to 4.2). CONCLUSIONS: This is the first longitudinal study to assess the association of glaucoma and mortality in a rural longitudinal cohort in India. Increased cup:disc ratio could be a potential marker for ageing and would need further validation.

Twenty-year outcomes in patients with newly diagnosed glaucoma: mortality and visual function.

BACKGROUND/AIMS: To determine the mortality within 20 years of diagnosis of chronic open-angle glaucoma (COAG) and visual acuity and visual field progression of a cohort followed for 20 years. METHODS: Twenty years following the diagnosis of COAG in 68 of 436 (16%) patients seen in a glaucoma case-finding clinic, visual and mortality outcomes were audited from medical records. Causes of death were obtained from general practitioner records and death certificates. Probability of death was calculated using a Kaplan-Meier survival curve. The visual field of each eye of survivors was graded using a nine-stage severity scale. Visual outcome was analysed at the 20-year follow-up visit. RESULTS: From 68, 14 (21%) were lost to follow-up. In the remaining 54, 20 (37%) were alive 20 years after diagnosis. Of 63% who died, mean age of death was 84 years, most commonly due to vascular disease. Mean age at presentation of those who died was 73.7 years versus 63.2 years for survivors (P=0.001). The median time to death was 16 years. On visual field analysis, nearly half (48.9%) of eyes did not deteriorate, but 28.3% eyes deteriorated by more than two stages. Those who died had worse final visual acuity than survivors (P<0.001). Three who died were registered severely visually impaired mainly from macular disease, but no survivors were registered (P<0.001). CONCLUSION: In this cohort, approximately two-thirds of patients with glaucoma died within 20 years of diagnosis. In most older patients with glaucoma, the overall goal of preventing visual handicap and blindness is achievable 20 years after diagnosis.

Limbus- versus fornix-based trabeculectomy for open-angle glaucoma eyes with prior ocular surgery: the Collaborative Bleb-Related Infection Incidence and Treatment Study.

We compared the surgical successes of limbus- and fornix-based trabeculectomies in open-angle glaucoma (OAG) eyes that had prior ocular surgery in the Collaborative Bleb-Related Infection Incidence and Treatment Study (CBIITS), Japan. From the 1,098 glaucoma eyes in 34 clinical centers in CBIITS, 195 OAG eyes that had undergone previous trabeculectomy and/or lens extraction were included. Limbus- or fornix-based trabeculectomy with mitomycin C were performed. Surgical failure (IOP ≥ 21, 18, or 15 mmHg for criterion A, B or C, respectively; <20% decrease from baseline; reoperation for glaucoma; or loss of light perception vision) was counted. There were 106 and 89 eyes treated with limbus- and fornix-based trabeculectomies, respectively. At 3 years, IOP (mean ± SD) was 12.5 ± 5.9 and 14.1 ± 6.4 mmHg and the cumulative probabilities of failure during 3 years were 30.2% and 50.5% for criterion A, 40.3% and 57.4% for criterion B, and 57.9% and 65.8% for criterion C in the limbus- and the fornix-based group, respectively. Fornix-based incisions were associated with surgical failure in Cox-proportional multivariable analysis for criterion A [relative risk (RR) = 1.96], and B [RR = 1.60]. Limbus-based trabeculectomy had a higher probability of success in OAG eyes with prior ocular surgery.

Pseudoexfoliation and mortality: a population-based 30-year follow-up study.

PURPOSE: To study the relationship between pseudoexfoliation (PEX) and all-cause mortality in a population in which PEX is a common finding. METHODS: Survival analyses were performed in a cohort of 760 residents 65-74 years of age, examined in a population survey in the municipality of Tierp, Sweden, 1984-86. To expand the cohort, participants in other studies in Tierp were enrolled. Additionally, people were recruited by means of glaucoma case records established at the Eye Department in Tierp in 1978-2007. In this way, the cohort comprised 1524 subjects, representing more than 21,100 person-years at risk. Information on deaths was obtained from the local population register. RESULTS: By the conclusion of the study, in August 2013, 1280 deaths had been reported. Of these cases, 350 were affected by PEX at baseline. No association between PEX and mortality was found (hazard ratio 1.00; 95% confidence interval 0.88-1.14). CONCLUSION: The results strongly suggest that PEX had no effect on all-cause mortality in the population under study.

Mortality in primary open-angle glaucoma and exfoliative glaucoma.

PURPOSE: To study mortality among unselected Finnish patients with either primary open-angle glaucoma (POAG) or exfoliative glaucoma (EG) after a minimum follow-up of 7 years after enrollment. METHODS: A total of 344 patients with POAG and 155 patients with EG had received free medication for the treatment of glaucoma from the Finnish National Social Insurance Institution (FSII). The FSII operates national health insurance, which is compulsory for all Finnish citizens. To be granted free medication, the patient has to file an application with a certificate from an ophthalmologist. If the predefined criteria for glaucoma specified by the Finnish Parliament are met, full reimbursement for glaucoma medications is granted and the patient is listed in the registry of FSII. We reviewed the records of 519 consecutive patients who had been diagnosed with glaucoma and to whom free medication had been granted between June 2004 and December 2005. Patients with acute glaucoma or secondary glaucoma were excluded. Those with open angles were classified into POAG or EG. The quality of the ophthalmologists' records was high. The Finnish Population Registry, a governmental institute, provided information on those patients who had died before January 2013. RESULTS: At enrollment, the groups with POAG and EG were comparable as regards sex: 66% female with POAG and 68% with EG. The patients with POAG were younger (median 68 years) than those with EG (median 74 years). By January 2013, 59 patients with POAG and 48 with EG had died. At death, the patients with POAG were younger (median 81.8 years) than those with EG (87.9 years). In both groups, the women lived longer than the men, but among patients with POAG, women and men died at a younger age than those with EG. CONCLUSIONS: As has been reported previously, life expectancy of patients with EG was longer when compared to those with POAG. Higher death rate among patients with EG is explained by higher median age at baseline.

Efficacy, safety, and survival rates of IOP-lowering effect of phacoemulsification alone or combined with canaloplasty in glaucoma patients.

PURPOSE: To evaluate efficacy and survival rates of intraocular pressure (IOP)-lowering effect obtained with phacoemulsification (phaco) alone or in combination with canaloplasty (PCP) in patients with open-angle glaucoma (OAG). METHODS: Retrospective chart review of consecutive cases at the Department of Ophthalmology, Indiana University. Visual acuity (VA), IOP, number of medications (Meds), failures, and survival rates of IOP-lowering effect were analyzed. Inclusion criteria were: patients older than 18 years with OAG and cataract. Exclusion criteria were: no light perception vision, prior glaucoma surgery, chronic uveitis, angle-closure glaucoma, and advanced-stage or end-stage OAG. Failure criteria were: IOP>21 mm Hg or <20% reduction, IOP<6 mm Hg, further glaucoma surgeries, and loss of light perception vision. RESULTS: Thirty-seven patients underwent phaco and 32 patients had PCP. Follow-up was 21.8±10.1 versus 18.8±9.6 months for phaco and PCP, respectively (P=0.21). Age (y) (74.7±9.8 vs. 76.1±8.3, P=0.54), sex (P=81), and laser status (P=0.75) were similar between the groups. Preoperatively, mean±SD logMAR VA (0.5±0.7 vs. 0.5±0.5, P=0.77), IOP (16.2±4.6 vs. 18.2±5.1, P=0.13), and Meds (1.4±1.1 vs. 1.3±0.7, P=0.75) were similar for phaco and PCP, respectively. At 24-month phaco (n=17) and PCP (n=11), respectively, mean±SD were: logMAR VA 0.2±0.2 versus 0.4±0.7, P=0.29; IOP 14.1±4.0 versus 12.9±3.8, P=0.43; and Meds 1.5±1.2 versus 0.3±0.5, P=0.005. Rates of successful IOP lowering without medications for phaco versus PCP at 12 months were 34% versus 75%, respectively (P=0.003). CONCLUSIONS: A combination of canaloplasty with phaco results in a decreased number of glaucoma medications and increased survival rate of IOP-lowering effect compared with phaco alone.

Mortality in primary open-angle glaucoma: 'two cupped discs and a funeral'.

PURPOSE: The aim of this study was to investigate the causes of mortality in individuals with open-angle glaucoma (OAG). METHODS: All-cause mortality data from the Registry of Births, Deaths and Marriages for the Australian state of Tasmania, for all people who were at least 40 years of age at the time of death, were classified using International Classification of Diseases-10 guidelines. This information was cross-referenced to identify participants in the Glaucoma Inheritance Study in Tasmania (GIST) who had died. Contingency tables were used for crude analysis and then models were constructed, adjusting for age at death as well as gender. RESULTS: Between 1996 and 2005, a total of 33 879 deaths were recorded. Data were unavailable for 4868 (14.4%) people. The mean age at death for the study sample was 78.4+/-11.5 (range 41-109) years. Of those cases known to have OAG by their participation in GIST (n=2409), full mortality data were available for 741 (92.0%). Following adjustment for the age at death and male gender, the odds ratio for death due to ischaemic heart disease in people with OAG compared to the general population not known to have OAG was significant (OR=1.30, 95% CI: 1.08-1.56; P=0.006). Crude analysis revealed that there were significantly fewer people with OAG who died due to metastatic cancer (P<0.001); however, this did not remain significant following adjustment for age and gender. CONCLUSION: The pathoaetiological relationship between OAG and ischaemic heart disease is unclear and requires further investigation. Increased awareness of the association between cardiovascular disease and OAG is warranted.

Open-angle glaucoma and the risk of stroke development: a 5-year population-based follow-up study.

BACKGROUND AND PURPOSE: Although open-angle glaucoma (OAG) is associated with some of the risk factors of stroke development, there is still no published study addressing whether OAG increases the risk of stroke development. We investigated the risk of stroke development after a diagnosis of OAG. METHODS: Data were retrospectively collected from the Taiwan National Health Insurance Research Database, which is comprised of 1 073 891 random subjects from among Taiwan's 23 million residents. The study cohort comprised all patients with a diagnosis of OAG (International Classification of Diseases, 9th Revision, Clinical Modification code 365.1 to 365.11) in 2001 (n=4032). The comparison cohort was comprised of randomly selected patients (5 for every patient with OAG, n=20 160) matched with the study group in terms of age, gender, geographic location, and comorbid medical disorders. Patients were tracked from their index visits for 5 years. Cox proportional hazard regression was used to compute the 5-year stroke-free survival rate after adjusting for possible confounding factors. RESULTS: Stroke developed in 14.9% of patients with OAG and 9.5% of patients in the comparison cohort during the 5-year follow-up period. Patients with OAG had significantly lower 5-year stroke-free survival rates than patients in the comparison cohort. After adjusting for patients' demographic characteristics and selected comorbidities, patients with OAG were found to have a 1.52-fold (95% CI, 1.40 to 1.72) higher risk of having a stroke than the matched comparison cohort. CONCLUSIONS: Patients with OAG demonstrated a significantly increased risk of stroke development during the 5-year follow-up period.

The association of primary open-angle glaucoma with mortality: a meta-analysis of observational studies.

OBJECTIVE: To conduct a meta-analysis to estimate the relationship between primary open-angle glaucoma (POAG) and mortality. METHODS: A systematic search of the PubMed, Embase, and Web of Science databases yielded 9 cohort studies with relative risk (RR) estimates for all-cause mortality. The studies were critically reviewed by an expert in the field. The data were extracted and analyzed in a pooled analysis by the random-effects model. Meta-regression to assess for heterogeneity by several covariates and subgroup analysis on cardiovascular mortality were performed. RESULTS: A significant risk was not detected in the final pooled analysis (RR, 1.13; 95% confidence interval [CI], 0.97-1.31) for all-cause mortality. A meta-regression across mean follow-up time, age, and sex was not significant. A meta-regression across diabetes status in 3 of the 9 studies did not demonstrate significant results (P = .94). Subgroup analysis on cardiovascular mortality from 4 of the 9 studies was marginally significant (RR, 1.20; 95% CI, 1.00-1.43; P = .05), but insignificant after removal of a study in which POAG was ascertained by self and proxy report (RR, 1.12; 95% CI, 0.87-1.46). CONCLUSION: This meta-analysis does not demonstrate an association between POAG and all-cause or cardiovascular mortality.

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.

Glaucoma and mortality in the Beijing Eye Study.

PURPOSE: To assess the relationship between glaucoma and mortality in a population-based setting. METHODS: At baseline in 2001, the Beijing Eye Study examined 4356 subjects for glaucoma with a detected glaucoma frequency of 135/4356 or 3.1%. Mean age was 55.9+/-10.4 years (40-101 years). In 2006, all study participants were reinvited for a follow-up examination. RESULTS: Out of the 4356 subjects, 3208 (73.6%) subjects returned for follow-up examination, while 124 (2.8%) subjects were dead, and 1024 (23.5%) subjects did not agree to be re-examined or had moved away. Mortality rate was significantly (P<0.001; odds ratio (OR): 4.72; 95% confidence interval (CI): 2.67, 8.33) higher in the 135 glaucoma subjects (15/135 or 11.1+/-2.7%; 95% CI: 5.8, 16.4) than in the 4221 participants without glaucoma (109/4221 or 2.6+/-0.2%; 95% CI: 2.2, 3.0). In binary logistic regression analysis, mortality was significantly associated with age (P<0.001), gender (P<0.001; OR: 0.44; 95% CI: 0.29, 0.66), level of education (P<0.001; OR: 0.64; 95% CI: 0.55, 0.74), and the presence of glaucoma (P=0.007; OR: 2.30; 95% CI: 1.26, 4.20). If the whole glaucoma group was differentiated into an open-angle glaucoma group and an angle-closure group, mortality was still significantly associated with age (P<0.001), gender (P<0.001), level of education (P<0.001), and with the presence of angle-closure glaucoma (P=0.006; OR: 3.09; 95% CI: 1.49, 10.2), while the association with the presence of open-angle glaucoma was marginally significant (P=0.13; OR: 1.83; 95% CI: 0.84, 4.01). CONCLUSIONS: The data suggest that glaucoma, particularly angle-closure glaucoma, may be associated with an increased rate of mortality in adult Chinese in Greater Beijing.

Ten-year outcomes in newly diagnosed glaucoma patients: mortality and visual function.

OBJECTIVES: To determine the mortality within ten years of diagnosis of chronic open angle glaucoma and the visual field progression amongst survivors of a group of patients who were followed for 10 years. PATIENTS AND METHODS: Of the 436 patients seen in a glaucoma case-finding clinic between July 1994 and December 1995 a diagnosis of chronic open angle glaucoma was made in 65. Ten years after diagnosis the outcome of the 57 patients who were treated at the Oxford Eye Hospital was determined. The causes of death were obtained from the general practitioner records and from the official death certificates. The probability of death was analysed using a Kaplan-Meier survival curve. The visual field of each eye of survivors was graded using a nine-stage severity scale. The visual outcome was analysed at the 10-year follow up visit. FINDINGS: Seventeen patients (29.8%) died during the 10-year period, including nine from cardiovascular disease. The mean (SD) age at presentation of those that died was 76.4 years (9.7) compared with 69.5 years (10.9) for survivors (p = 0.029). Using a nine-stage grading system, 42 eyes (52.5%) did not deteriorate, 30 eyes (37.5%) deteriorated by one stage, seven eyes (8.75%) two stages and one eye (1.25%) three stages over the 10-year period. The average time to first deterioration by one stage was 8.51 years (CI 7.92 to 9.10). The mean (SD) intraocular pressure was 25.6 mmHg (5.8 mmHg) on presentation and 15.7 mmHg (3.0 mmHg) at the end of 10 years. CONCLUSION: Approximately two thirds of patients will still be under care 10 years after presentation. In older, white patients with glaucoma the overall goal of preventing visual handicap is achievable for most patients 10 years after diagnosis.

Open-angle glaucoma and cardiovascular mortality: the Blue Mountains Eye Study.

PURPOSE: To evaluate the association between open-angle glaucoma (termed glaucoma) and 9-year mortality in an older population-based cohort. DESIGN: Population-based cohort. PARTICIPANTS: Three thousand six hundred fifty-four persons aged 49 to 97 years (82.4% of the eligible population), residents of the Blue Mountains, west of Sydney, Australia. METHODS: At baseline (1992-1994), glaucoma was diagnosed from congruous typical glaucomatous visual field changes (full-threshold fields) and optic disc cupping (stereo-optic disc photography). Demographic information from baseline participants was matched with the Australian National Death Index data (December 2001) to obtain the number and causes of deaths. Cox proportional hazards regression analysis, controlling for age, male gender, diabetes, hypertension, heart disease, stroke, use of oral beta-blockers, current smoking history, alcohol use, myopia, and nuclear cataract were performed to assess hazard ratios for cardiovascular mortality. Adjustments for all-cause mortality also included history of cancer. MAIN OUTCOME MEASURES: Cardiovascular and all-cause mortality. RESULTS: At baseline, glaucoma was diagnosed in 108 participants (3.0%). Of 873 deaths (23.9%) before January, 2002, 312 people (8.5%) died of cardiovascular events. The age-standardized all-cause mortality was 24.3% in persons with and 23.8% in those without glaucoma, whereas cardiovascular mortality was 14.6% in persons with and 8.4% in those without glaucoma. After multivariate adjustment, those with glaucoma had a nonsignificant increased risk of cardiovascular death (relative risk [RR], 1.46; 95% confidence interval [CI], 0.95-2.23). Increased cardiovascular mortality was observed mainly in glaucoma patients aged <75 years (RR, 2.78; 95% CI, 1.20-6.47). Further stratified analyses showed that cardiovascular mortality was higher among those with previously diagnosed glaucoma (RR, 1.85; 95% CI, 1.12-3.04), particularly in those also treated with topical timolol (RR, 2.14; 95% CI, 1.18-3.89). CONCLUSIONS: Findings from the Blue Mountains Eye Study demonstrate an increased cardiovascular mortality in persons with previously diagnosed glaucoma. There was a suggestion of higher cardiovascular mortality in glaucoma patients using topical timolol that merits further study.

Exfoliative glaucoma and primary open-angle glaucoma: associations with death causes and comorbidity.

PURPOSE: To investigate whether type of glaucoma or use of acetazolamide are associated with main cause of death and comorbidity. MATERIAL AND METHODS: The survival data, including date and cause of death, for 1147 patients with capsular or simple glaucoma who were ultimately hospitalized at the Eye Department, National Hospital, Oslo, between 1961 and 1970, were analysed. Binary logistic regression was carried out to investigate the patterns of death causes and comorbidity in subgroup analyses. RESULTS: Patients with exfoliative glaucoma (XFG) and those with primary open-angle glaucoma (POAG) showed no significant differences in rates of death caused by acute cerebrovascular diseases, cardiac diseases and cancer. Interestingly, we found that chronic cerebral diseases such as senile dementia, cerebral atrophy and chronic cerebral ischaemia (n = 81) were more common in patients with XFG than in those with POAG (p = 0.01) and in the group of acetazolamide users (p = 0.03). Patients with XFG had a higher probability of developing an acute cerebrovascular disease than patients with POAG (n = 228, p = 0.03). CONCLUSION: In this retrospective study, we found that comorbidity with acute cerebrovascular disease and chronic cerebral diseases (senile dementia, cerebral atrophy and chronic cerebral ischaemia) were more common in patients with XFG than in patients with POAG. Prospective data are needed in order to conclude upon the associations found in this study.

Comparison of survival of exfoliative glaucoma patients and primary open-angle glaucoma patients: impact of acetazolamide use.

PURPOSE: To compare the survival rates of patients with exfoliative glaucoma (XFG) and those with primary open-angle glaucoma (POAG), and to establish whether the use of acetazolamide has any influence on survival. METHODS: The survival data, including date and cause of death, for 1147 patients with XFG or POAG who were ultimately hospitalized at the Eye Department, National Hospital, Oslo, between 1961 and 1970, were analysed retrospectively. The Cox proportional hazard model was used in the survival analyses. RESULTS: No statistically significant differences in survival were found between patients with XFG and those with POAG (p = 0.85). As expected, female gender and younger age at diagnosis were associated with longer survival periods. Surprisingly, we found that patients with more recent birth dates had relatively lower survival rates than patients with earlier birth dates; when this was included in the analyses, the use of acetazolamide was found to be associated with reduced survival (n = 492, p = 0.02).