Four-Year Incidence of Open-Angle Glaucoma and Ocular Hypertension: The Los Angeles Latino Eye Study




Purpose


To estimate the 4-year incidence of open-angle glaucoma (OAG) and ocular hypertension (OHT) among adult Latinos 40 years of age and older.


Design


Population-based longitudinal study.


Methods


Comprehensive ophthalmologic examinations including intraocular pressure, visual field testing, and stereoscopic fundus photography were performed at both baseline and the 4-year follow-up examination. Incident OAG at the 4-year follow-up examination was defined as the presence of an open angle and a glaucomatous visual field abnormality or evidence of glaucomatous optic disc damage, or both when not present at baseline. Incident OHT was defined as intraocular pressure of more than 21 mm Hg and the absence of optic disc damage or abnormal visual field results at the 4 year follow-up examination when not present at baseline.


Results


Among the 3939 participants (mean age, 54.7 ± 10.5 years) with complete data for a diagnosis of glaucoma at both baseline and follow-up examination, incident OAG at the 4-year follow-up was identified in 87 persons (4-year incidence rate, 2.3%; 95% confidence interval, 1.8% to 2.8%). Incident OHT at the 4-year follow-up was identified in 124 persons (4-year incidence rate, 3.5%; 95% confidence interval, 2.9% to 4.1%). In participants with OAG in 1 eye, the 4-year risk of OAG developing in the fellow eye was 5 times as high as the risk for those without OAG in either eye at baseline. In participants with OHT in 1 eye, the 4-year risk of OHT developing in the fellow eye was 10 times as high as the risk for those without OHT in either eye at baseline. The incidence rates of OAG and OHT were higher in older Latinos than in younger Latinos.


Conclusions


Incidence of OAG in Latinos is higher than in non-Hispanic whites, but lower than in Afro-Caribbeans. The relatively high rate of incident OAG and OHT underscores the need for community screening programs in this fastest growing segment of the United States population.


Glaucoma is second only to cataract as a cause of blindness worldwide. In contrast to the blindness caused by cataract, glaucoma-related blindness is irreversible. It is estimated that 66.8 million persons in the world have open-angle glaucoma (OAG) and more than 3 million Americans are projected to be affected by this disease by 2020. Given the increasing prevalence of OAG with aging, the demographic shift toward older populations in both developed and developing countries will lead to substantial increases in the incidence of OAG, which undoubtedly will become a challenging public health issue in the upcoming decades.


Numerous population-based studies have reported the prevalence of OAG. Compared with cross-sectional studies, incident studies are more robust in elucidating risk factors for developing OAG and for providing evidence for guidance of clinical management of OAG. However, few studies have documented the incidence of OAG, and no population-based studies have documented the incidence of OAG and ocular hypertension (OHT) in the United States. This lack of studies mainly is the result of the difficulties inherent in conducting a long-term follow-up of a sizable population cohort, given the relatively low frequency of OAG in most populations. To date, all population-based longitudinal studies on OAG were performed outside the United States among persons of African ancestry and among non-Hispanic whites. As far as we are aware, no incidence data on OAG has been reported for Latinos. As the largest and fastest-growing minority in the United States, Latinos have unique demographic, socioeconomic, and ocular health characteristics compared with other racial groups in the United States. Longitudinal studies on OAG in this population to assess the burden of this blinding disease therefore are important for establishing appropriate clinical and public health intervention strategies.


In 2003, we reported the prevalence of OAG and OHT in a population-based sample of Latinos in Los Angeles County, California. The prevalence of OAG among Latinos was similar to that of African Americans, yet much higher than that of non-Hispanic whites. In this article, we describe the incidence rates of OAG and OHT derived from the 4-year follow-up examination of this population. We also describe the longitudinal changes in structural and functional characteristics in eyes in which OAG and OHT develop.


Methods


Study Population


The Los Angeles Latino Eye Study (LALES) is a population-based cohort study of eye disease in self-identified Latinos 40 years of age and older living in 6 census tracts in the city of La Puente, Los Angeles County, California. Latinos (Hispanics, Hispanic Americans, and Latino Americans) are individuals who are born into or descended from a Spanish-speaking community, regardless of race. In the United States, they are a heterogeneous group, with most being of Mexican ancestry (66%). Baseline examination was performed from 2000 through 2003, with a 4-year follow-up examination performed from 2004 through 2008. Details regarding study design, methods, and baseline prevalence data have been reported elsewhere.


Interview and Examination Procedures


All eligible participants from the baseline LALES examination were invited to return for a home interview and a clinical examination. Similar questionnaire and examination procedures were used for both baseline and follow-up studies. Trained ophthalmologists and technicians performed a comprehensive ocular examination using standardized protocols, which included visual field (VF) testing, Goldmann applanation intraocular pressure (IOP) measurement, and simultaneous stereoscopic fundus photography of the optic disc.


Visual Field Evaluation


Detailed descriptions of all OAG and OHT diagnosis-related tests and definitions have been reported previously. In brief, for VF evaluation, a Swedish Interactive Threshold Algorithm Standard C24 was first performed in each eye. If the results were normal, no further tests were conducted. If the results were abnormal or unreliable, the tested eye would undergo a repeat VF test. No VF tests were performed on eyes with visual acuity of light perception or worse at presentation. Next, 2 glaucoma specialists (B.F., B.N.) evaluated the field loss pattern and the congruence among all the repeated VF tests for the eye. Finally, based on an optic disc evaluation, clinical examination data review, and fundus photograph assessment, the glaucoma specialists determined if the field loss was characteristic of glaucoma, compatible with glaucoma, the result of other neurologic or nonglaucomatous cause or artifact, or not determined or not applicable.


Optic Nerve Evaluation


For optic nerve evaluation, simultaneous stereoscopic optic disc photographs were evaluated using a stereoscopic viewer (Asahi Viewer; Pentax, Englewood, Colorado, USA). The 2 glaucoma specialists first determined the photograph quality. If the photograph was gradable, the appearance of the optic disc was characterized in terms of vertical and horizontal cup-to-disc ratio (CDR), CDR asymmetry between fellow eyes, disc and peripapillary nerve fiber layer hemorrhage, peripapillary atrophy (PPA), diffuse thinning of the neural rim, and notching of the neural rim. Finally, the optic disc was classified into the following categories: characteristic of glaucoma, compatible with glaucoma, abnormal but nonglaucomatous (optic disc abnormalities that are not characteristic of or compatible with typical glaucomatous changes, such as changes associated with ischemic optic neuropathy, congenital optic disc pits, laser photocoagulation), normal, or unsure (media opacities precluded an accurate assessment of the optic disc from either disc photographs or on direct ophthalmoscopy). In the absence of clear, high-quality photographs, data from the direct binocular ophthalmoscopic examination of the optic nerve were used.


Diagnosis of Open-Angle Glaucoma and Ocular Hypertension


An expert consensus method was used for OAG diagnosis based on history and clinical examination data. A 3-step process was used to determine the OAG diagnosis. First, 2 glaucoma specialists (B.F., B.N.) evaluated all clinical history and examination data, including VA, Van Herrick test results, gonioscopy results, evaluation of anterior and posterior ocular segments, clinical optic disc and fundus evaluation, optic disc photographs, and VF results. Second, the 2 specialists determined the presence or absence of OAG using specific guidelines. The 2 specialists graded both optic disc photographs and VFs independently and masked to each other. In determining the diagnosis of glaucoma, the specialists classified each eye of each person with particular consideration to the optic disc photographs and VFs. A diagnosis was assigned to each eye if both graders agreed. In the event of disagreement, a third glaucoma specialist (V.C., F.M.) assessed the data. An agreement between 2 of the 3 specialists was used to assign the eye. Additionally, the principal investigator (R.V.) performed a confirmatory review of all cases diagnosed as OAG.


The detailed diagnosis criteria for OAG are described elsewhere. Briefly, based on the presence or absence of optic disc damage, VF defects, or both, as well as the degree of compatibility of these changes with glaucoma, the diagnoses were classified into definite glaucoma or probable glaucoma. Incident OAG was defined as the presence of an open angle and a glaucomatous VF abnormality, evidence of glaucomatous optic disc damage at the 4-year follow-up examination in persons who did not have any evidence of glaucomatous VF abnormality, evidence of glaucomatous optic disc damage at baseline, or a combination thereof. OHT was diagnosed in individuals with an IOP of more than 21 mm Hg (or ≤ 21 mm Hg if the person was using OHT medications or had undergone IOP-lowering laser or incisional surgery in that eye) and in the absence of both optic disc damage and abnormal VF tests results.


Incidence of OAG in this study is presented using 3 different approaches: (1) incidence in the first eye required that both eyes were free of OAG at baseline (participants were at risk of developing OAG in either eye or both eyes at follow-up); (2) incidence of OAG in the second eye required that at baseline only 1 eye had OAG; and (3) incidence of OAG in either eye was obtained by combining incidence of OAG in the first eye and the second eye. Similar approaches are used for presenting incident OHT data.


Data and Statistical Analysis


All clinical and grading data were entered into a central database with internal, automated, quality-control checks. Incidence and progression of OAG and OHT were dichotomized into yes-or-no categories. Comparisons of incidence rates were made across age groups. Age at baseline was categorized into 5 groups: 40 to 49 years, 50 to 59 years, 60 to 69 years, 70 to 79 years, and 80+ years. Demographic and glaucoma-related clinic characteristics between baseline and follow-up examinations were compared using the chi-square test for categorical variables and the Student t test for continuous variables. Associations of incidence rates across age groups were tested by the Mantel-Haenszel trend test. In addition, the crude overall incidence rates were age-adjusted to the LALES study cohort using direct standardization methods. Results also were annualized to enable comparison across other population-based studies. Intergrader and intragrader agreements were assessed in a random sample of eyes using weighted κ statistics. Secondary analyses included: (1) determining the frequency of specific diagnostic criteria for defining OAG; (2) comparing optic disc and clinical characteristics between baseline and follow-up in participants with incident glaucoma or OHT; and (3) using prediction models to estimate the incidence of OAG or OHT in participants without a 4-year follow-up examination. The Statistical Analysis System (version 9.1; SAS Institute, Inc, Cary, North Carolina, USA) was used for statistical analyses, conducted at the P = .05 significance level.




Results


A flowchart assessing the analytical cohort is presented in Figure (Supplemental Material at AJO.com ). Of the 5907 living eligible participants with clinical examination data at baseline, 4538 (76.6%) completed the 4-year follow-up in-clinic examination. The mean ± standard deviation follow-up period was 4.3 ± 0.03 years. The mean ± standard deviation age of participants was 54.7 ± 10.5 years. Sixty percent of follow-up participants were female, and 76% were born outside of the United States. The participants identified their countries of origin as Mexico (n = 2905, 64%), the United States (n = 1607, 24%), El Salvador (n = 238, 5%), Guatemala (n = 113, 2.5%), Nicaragua (n = 58, 1%) and other (n = 157, 3.5%).


Complete and reliable glaucoma data were available for 3939 participants at both baseline and 4-year follow-up. Of the 599 participants who had a clinical examination but were without complete data for glaucoma diagnosis, 398 (66.4%) had ungradable fundus photographs at follow-up, 118 (19.7%) underwent an in-home examination, 48 (8.0%) declined dilation, and 2 (0.3%) were physically unable to comply with the examination. The reason for incomplete data was unknown for 33 (5.5%) participants. Therefore, the analysis cohort for this article comprised the 3939 participants with valid data for OAG diagnosis in at least 1 eye at follow-up.


As shown in Table 1 , compared with nonparticipants and those who were excluded for analysis (n = 1968), participants in this analysis cohort (n = 3939) were older ( P = .002) and were more likely to be married (73.5% vs 70.7%; P = .03), to have health insurance (67.2% vs 56.8%; P < .0001), to have at least 2 systemic comorbidities (41.7% vs 35.2%; P < .0001), and to report a history of systemic hypertension (30.1% vs 26.8%; P = .01). There were no significant differences between these 2 groups in terms of gender distribution, country of origin, employment status, income and education levels, and history of ocular diseases, including cataract, glaucoma, macular degeneration, and diabetic retinopathy ( P > .05). Considering the big sample size of this study, the difference in age and marital status between participants and nonparticipants may not have an obvious impact on the prevalence estimation, despite the statistically significant P values. Nevertheless, the significant differences between the 2 groups for the rate of comorbidities as well as for those with arterial hypertension should be considered when assessing the risk factors of OAG and OHT.



TABLE 1

Comparison of Sociodemographic and Clinical Characteristics at Baseline between Participants and Nonparticipants in the Los Angeles Latino Eye Study 4-Year Follow-up Study


































































































































































































Characteristics Analysis Cohort (n = 3939) a Nonparticipants or Excluded (n = 1968) b P Value c
No. % No. %
Gender (female) 2355 59.8 1130 57.4 .09
Age group at baseline (y)
Mean age at baseline (± SD) 54.6 ± 10.3 53.7 ± 10.9 .002
40 to 49 1485 37.7 857 43.6
50 to 59 1244 31.6 582 29.6
60 to 69 809 20.5 324 16.5
70 to 79 342 8.7 157 8.0
80+ 59 1.5 48 2.4
Born in the United States 921 23.4 436 22.2 .32
Acculturation (low |<1.9|) d 2640 67.0 1343 68.5 .31
Working status (employed) 1988 50.5 1003 51.0 .70
Education level 12 y or more 1347 34.2 626 31.8 .08
Marital status (married) 2896 73.5 1391 70.7 .03
Annual income > $40 000 491 12.5 247 12.6 .83
Have health insurance 2646 67.2 1117 56.8 <.0001
With 2 or more comorbidities e 1642 41.7 693 35.2 <.0001
Self-reported health status excellent/good 749 19.0 384 19.5 .65
History of hypertension 1184 30.1 527 26.8 .01
History of diabetes mellitus 661 16.8 291 14.8 .06
Self-reported vision status excellent/good 1634 41.5 766 38.9 .08
With any ocular disease 1376 34.9 669 34.0 .45
Glaucoma diagnosed 162 4.3 88 4.5 .74
Self-reported cataract history 388 9.9 169 8.6 .14
Self-reported glaucoma history 107 2.7 52 2.6 .96
Self-reported macular degeneration history 29 0.7 13 0.7 .88
Self-reported diabetic retinopathy history 82 2.1 37 1.9 .95

SD = standard deviation.

a Participants completing the clinical examination at 4-year follow-up.


b Nonparticipants of the follow-up examination participated in the baseline examination, but did not have glaucoma data at follow-up.


c Chi-square test for categorical variables; t test for continuous variables.


d Acculturation was measured using the short-form Cuellar Acculturation Scale.


e Comorbidities refer to the summation of the following medical conditions: arthritis, diabetes mellitus, back pain, hypertension, deafness, asthma, angina, skin cancers, heart disease, stroke, and heart failure.



Four-Year Incidence of Open-Angle Glaucoma and Ocular Hypertension


For the 3939 participants with complete and valid glaucoma diagnosis data, the 4-year incidence of OAG in the first eye (among those without OAG at baseline) was 2.3% (95% confidence interval [CI], 1.8% to 2.9%; Table 2 ). The incidence in the second eye (among those who had OAG in 1 eye at baseline) was approximately 6-fold that in the first eye, with 11 (12.1%) of 91 persons (95% CI, 5.4% to 18.8%) having OAG after 4 years. When combining the incidence in either eye, 98 (2.5%) persons (95% CI, 2.0% to 3.0%) were found to have OAG at the 4-year follow-up examination. After adjusting for the age distribution of this cohort, the overall age-standardized incidence of OAG was 2.5% (95% CI, 1.9% to 3.0%) for the first eye group, 10.9% (95% CI, 4.5% to 17.4%) for the second eye group, and 2.6% (95% CI, 2.1% to 3.2%) for the either eye group. The incidence of OAG was higher in older Latinos than in younger ones. Compared with the incidence of OAG in the youngest age group (40 to 49 years), the incidence of OAG in the oldest group (≥ 80 years) was 14-fold higher in the first eye group, 2.4-fold in the second eye group, and 15-fold higher in the either eye group. No gender difference was found in the incidence of OAG in each group ( P > .05). Of the 87 participants who had incident OAG (iOAG) in the first eye, 23 (26.4%) had bilateral OAG and 64 (73.6%) had unilateral OAG.



TABLE 2

Four-Year Incidence of Open-Angle Glaucoma in Participants in the Los Angeles Latino Eye Study
























































































































Age Group (y) Incidence in the First Eye Incidence in the Second Eye Incidence in Either Eye
No. with iOAG No. at Risk % 95% CI No. with iOAG No. at Risk % 95% CI No. with iOAG No. at Risk % 95% CI
40 to 49 15 1465 1.0 0.5 to 1.5 2 12 16.7 0 to 37.8 17 1477 1.2 0.6 to 1.7
50 to 59 17 1210 1.4 0.7 to 2.1 0 19 17 1229 1.4 0.7 to 2.0
60 to 69 31 757 4.1 2.7 to 5.5 5 32 15.6 3.0 to 28.2 36 789 4.6 3.1 to 6.0
70 to 79 17 293 5.8 3.1 to 8.5 2 23 8.7 0 to 20.2 19 316 6.0 3.4 to 8.6
80+ 7 47 14.9 4.7 to 25.1 2 5 40.0 0 to 82.9 9 52 17.3 7.0 to 27.6
Crude overall 87 3772 2.3 1.8 to 2.8 11 91 12.1 5.4 to 18.8 98 3863 2.5 2.0 to 3.0
Age standardized a 2.5 1.9 to 3.0 10.9 4.5 to 17.4 2.6 2.1 to 3.2

CI = confidence interval; OAG = incident open-angle glaucoma.

The 167 participants with glaucoma at baseline are excluded from the analysis cohort.

a Age-standardized incidence rates are adjusted for the Los Angeles Latino Eye Study population.



Incident OHT (iOHT) in the first eye was present at the 4-year follow-up in 124 (3.5%) of 3589 participants (95% CI, 2.9% to 4.1%; Table 3 ). The incidence in the second eye, however, was 31.2% (24/77; 95% CI, 20.8% to 41.5%), approximately 10 times that of the first eye. Combining both eyes, there were 148 (4.0%) of 3666 persons (95% CI, 3.4% to 4.7%) who had OHT at the 4-year follow-up. Similar to OAG, there was a higher incidence of OHT in older Latinos than in younger Latinos ( P < .001, for trend). Compared with the rate of iOHT in the youngest group of Latinos (40 to 49 years), the rate in the oldest group (≥ 80 years) was 3.7 times greater in the first eye group, 2.5 times greater in the second eye group, and 5.8 times greater in either eye group. After adjusting for the age distribution of the LALES cohort, the overall 4-year incidence of OHT was 3.6% (95% CI, 2.3% to 4.2%) for the first eye group, 29% (95% CI, 17.4% to 40.6%) for the second eye group, and 4.2% (95% CI, 3.5% to 4.9%) for the either eye group. No gender differences were found in OHT incidence for either group ( P > .05). Of the 124 participants with iOHT in the first eye, 70 (56.5%) had bilateral iOHT and 54 (43.6%) had unilateral iOHT.



TABLE 3

Four-Year Incidence of Ocular Hypertension in Participants in the Los Angeles Latino Eye Study
























































































































Age Group (y) Incidence in the First Eye Incidence in the Second Eye Incidence in Either Eye
No. with iOAG No. at Risk % 95% CI No. with iOAG No. at Risk % 95% CI No. with iOAG No. at Risk % 95% CI
40 to 49 30 1419 2.1 1.4 to 2.9 3 15 20.0 0 to 40.2 33 1434 2.3 1.5 to 3.1
50 to 59 40 1145 3.5 2.4 to 4.6 6 31 19.4 5.5 to 33.3 46 1176 3.9 2.8 to 5.0
60 to 69 36 715 5.0 3.6 to 6.8 8 15 53.3 28.1 to 78.6 44 730 6.0 4.4 to 7.9
70 to 79 15 271 5.5 2.8 to 8.3 4 10 40.0 9.6 to 70.4 19 281 6.8 3.8 to 9.7
80+ 3 39 7.7 0 to 16.1 3 6 50.0 10.0 to 90.0 6 45 13.3 3.4 to 23.3
Crude overall 124 3589 3.5 2.9 to 4.1 24 77 31.2 20.8 to 41.5 148 3666 4.0 3.4 to 4.7
Age standardized a 3.6 2.3 to 4.2 29.0 17.4 to 40.6 4.2 3.5 to 4.9

CI = confidence interval; iOAG = incident open-angle glaucoma.

a Age-standardized incidence rates are adjusted for the Los Angeles Latino Eye Study population.



Completion and Reproducibility of Data Collection for Glaucoma Classification


Of the 98 participants with iOAG, 94 (95.9%) underwent an optic disc examination, 83 (84.7%) had gradable optic disc photographs, and 4 (4.1%) had no optic disc data. Two or more VF tests were performed on 54 (55.1%) participants, whereas 39 (39.8%) participants had 1 VF test, and 5 (5.1%) had no VF data ( Table 4 ). The agreement between the 2 glaucoma specialists in estimating glaucoma-related parameters was substantial for vertical CDR (weighted κ, 0.7 [95% CI, 0.5 to 0.8]), horizontal CDR (weighted κ, 0.7 [95% CI, 0.5 to 0.9]), and judgments of abnormal VF tests (weighted κ, 0.9 [95% CI, 0.8 to 1.0]). The agreement between 2 specialists in the diagnosis of OAG and OHT was 89.1% and 75.7%, respectively.



TABLE 4

Completeness of Data for Glaucoma Classification for Participants with Incident Open-Angle Glaucoma in the Los Angeles Latino Eye Study


































Gradable Disc Photographs a Clinical Disc Examination Data Only No Disc Data Total
2 or more visual fields b 49 (50.0) 4 (4.1) 1 (1.0) 54 (55.1)
1 visual field 31 (31.6) 6 (6.1) 2 (2.0) 39 (39.8)
No visual field 3 (3.1) 1 (1.0) 1 (1.0) 5 (5.1)
Total 83 (84.7) 11 (11.2) 4 (4.1) 98 (100)

Data are presented as no. (%).

a Simultaneous stereoscopic optic disc photographs.


b Humphrey C24 Swedish Interactive Threshold Algorithm Standard, full-threshold C24-2, or both.



Criteria for Diagnosis of Open-Angle Glaucoma at Follow-Up Examination


Table 5 details the frequency of cases in each specific diagnostic criterion. Of the 98 participants with iOAG, 55 (56.1%) had at least 1 eye with both VF loss and optic disc damage, regardless of IOP. Of the remaining participants, 14 (14.3%) were diagnosed with OAG in at least 1 eye based on a combination of VF defect and optic disc damage compatible with glaucoma; 29 (29.6%) had at least 1 eye diagnosed with OAG with either VF defect (n = 9 [9.2%]) or optic disc damage (n = 20 [20.4%]) that was characteristic of or compatible with glaucoma.



TABLE 5

Frequency of Specific Diagnostic Criteria for Defining Open-Angle Glaucoma in Los Angeles Latino Eye Study Participants (n = 98)










































Diagnostic Criteria Frequency (n = 98)
No. %
A. Evidence of visual field a and optic disc damage
1. Open angle; 2 or more reliable, abnormal visual field test results with excellent congruence and optic disc damage, both characteristic of glaucoma 16 16.3
2. Open angle; 1 or more abnormal visual field test result(s) and optic disc damage, both characteristic of or compatible with glaucoma 39 39.8
3. End-stage disease with visual acuity of 20/200 or worse, a cup-to-disc ratio of 1.0, and absence of visual field data 1 1.0
4. Combinations of visual field and optic disc abnormalities with fair congruence between fields that are both compatible with glaucoma 14 14.3
B. Evidence of either visual field a or optic disc damage
5. 1 or more abnormal visual field test result(s) that are characteristic of or compatible with glaucoma and no evidence of optic disc damage 9 9.2
6. Characteristic or compatible glaucomatous optic disc damage with no evidence of visual field abnormality 19 19.4

a Humphrey C24 Swedish Interactive Threshold Algorithm Standard, full-threshold C24-2, or both.

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Jan 12, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Four-Year Incidence of Open-Angle Glaucoma and Ocular Hypertension: The Los Angeles Latino Eye Study
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