To assess the association between insufficient follow-up and clinical parameters such as disease severity and medication use among glaucoma patients at a metropolitan county hospital.
Two-hundred and six patients with established glaucoma were recruited from San Francisco General Hospital. Subjects were classified based on compliance with recommended follow-up examination intervals over the year preceding commencement of the study, as determined by patient medical records. Glaucoma severity was determined based on the American Academy of Ophthalmology Preferred Practice Patterns guidelines. Multivariate logistic regression analysis was used to assess the relationship between adherence with follow-up visits and disease severity.
After adjustment for the impact of potential confounding variables, subjects with severe glaucomatous disease were found to have been less adherent to their recommended follow-up than those patients with mild or moderate glaucomatous disease (adjusted OR 1.89, 95% CI 1.21-2.94; P = .01). Subjects who were on glaucoma medications were found to be less adherent to follow-up recommendations (adjusted OR 3.29, 95% CI 1.41-7.65, P = .01).
Subjects with poor follow-up adherence were significantly more likely to have severe glaucomatous disease, suggesting that poor follow-up may contribute to disease worsening or, alternatively, those with more severe disease are less inclined to follow up at appropriate intervals.
Glaucoma is one of the leading causes of blindness worldwide. It is estimated that the number of individuals with open-angle glaucoma in the United States will increase by 50% such that 3.36 million adults will have the disease by the year 2020. Multiple clinical trials have demonstrated that pharmacologic lowering of intraocular pressure (IOP) reduces the rate of vision loss in glaucoma patients. Based on these results, one may postulate that improved patient adherence with glaucoma therapy can significantly delay disease progression and vision loss.
Regular patient follow-up is critical for physicians to monitor glaucomatous disease and adjust therapy as needed. The American Academy of Ophthalmology recommends in the Preferred Practice Pattern guidelines at least 2 follow-up visits per year in patients with primary open-angle glaucoma. Lee and associates found that lack of formal education, no use of prescribed glaucoma medications, or belief that follow-up is less important if one uses glaucoma medications were all independent predictors of inconsistent glaucoma follow-up. Other questionnaire-based studies have identified reasons for poor follow-up adherence such as long waiting times, unfamiliarity with necessary treatment duration, and lack of knowledge regarding the permanency of glaucoma-induced vision loss.
Although nonadherence to follow-up recommendations has been found to be directly associated with many risk factors, no adequately powered study has examined the association between follow-up adherence and clinical parameters such as glaucoma severity and medication use.
We conducted a cross-sectional study of individuals with glaucoma to determine if disease severity and use of glaucoma medications were factors associated with follow-up visit adherence at the San Francisco General Hospital (SFGH).
This cross-sectional study enrolled 206 glaucoma patients attending follow-up visits at the SFGH Glaucoma Clinic in San Francisco, California between June 1, 2011 and August 1, 2011. The clinic is located in a hospital that is administered by the county of San Francisco and serves the indigent and underinsured residents of the city of San Francisco. Human subjects approval for this study was obtained from the institutional review boards of the following organizations: SFGH; the University of California, San Francisco; and the Stanford University School of Medicine. Informed written consent was obtained from all participants. Health Insurance Portability and Accountability Act (HIPAA)-compliant consent forms were obtained from all study subjects. The research protocol adhered to the tenets of the Declaration of Helsinki for clinical research.
At SFGH, glaucoma patients are scheduled to attend routine follow-up visits at regular intervals based on disease severity ( Table 1 ). Classification according to these guidelines was based on appointment data gathered from medical records. The electronic medical record revealed all appointment activity whether attended, canceled, or missed. Rescheduled appointments were removed from the record. Only attended appointments were used in our analysis of follow-up adherence. Only approximately 5% of appointments are rescheduled within the department of ophthalmology at SFGH. Patients who did not attend follow-up within 1 month after their scheduled follow-up date were considered to have failed to attend a follow-up visit. We enrolled 83 and 123 subjects with good and poor follow-up, respectively.
|Glaucoma Disease Severity b|
|Follow-up recommendations||Every 5-6 months (approximately 2 visits/year)||Every 4-5 months (approximately 3 visits/year)||Every 3-4 months (approximately 4 visits/year)|
|Good follow-up||≥2 visits, with 5- to 6-month maximum intervals between visits||≥3 visits, with 4- to 5-month maximum intervals between visits||≥3 visits, with 3- to 4-month maximum intervals between visits|
|Poor follow-up||≤1 visit or extended interval between visits||≤2 visits or extended interval between visits||≤2 visits or extended interval between visits|
b Glaucoma disease severity was evaluated based on the American Academy of Ophthalmology Preferred Practice Patterns guidelines for primary open-angle glaucoma (POAG) and POAG suspects. Mild: Characteristic optic nerve abnormalities are consistent with glaucoma, but the visual field is normal. Moderate: Visual field abnormalities exist in 1 hemifield and are not within central 5 degrees of fixation. Severe: Visual field abnormalities exist in both hemifields or visual field loss is within central 5 degrees of fixation.
All subjects were glaucoma patients treated at SFGH for at least 1 year prior to enrollment. Eligibility criteria included (1) an International Classification of Diseases (ICD-9) diagnosis of primary open-angle glaucoma (POAG), primary angle-closure glaucoma, exfoliative glaucoma, low-tension glaucoma, or glaucoma suspect for more than 1 year; (2) an age of 40 years or older; and (3) the existence of medical record documentation regarding the dates of all glaucoma follow-up visits scheduled and attended over the past 12 months. Baseline demographic factors, comorbidities, history of glaucoma surgery (ie, trabeculectomy), and pharmacy data were retrieved from the patients’ medical records.
The chief of the SFGH Glaucoma Service (S.L.) classified each study subject into 1 of 3 categories of disease severity: mild, moderate, or severe. Patients considered to have “mild” glaucoma were those who had at least 1 eye with (1) a structural abnormality of the optic disc or retinal nerve fiber layer consistent with glaucoma (focal notching of optic disc rim, thinning of the neuroretinal rim with increased cupping of the disc, neuroretinal rim or peripapillary retinal nerve fiber layer hemorrhages) and (2) a normal Humphrey visual field (HVF) examination (ie, not meeting the criteria for a glaucoma defect as defined below). “Moderate” glaucoma was defined by (1) optic nerve abnormalities consistent with glaucoma as detailed above and (2) the presence of a glaucomatous visual field defect that did not cross the horizontal meridian and was not within 5 degrees of fixation. A glaucomatous visual field defect was considered present when a reliable HVF test demonstrated 3 or more abnormal non-edge contiguous points not crossing the horizontal meridian, with a probability of <5% based on comparison with age-matched nonglaucomatous individuals in the pattern deviation plot. Reliable visual fields were those with fixation loss, false-negative, and false-positive values of 33% or less. If a visual field was unreliable, the subject then completed testing during study enrollment to achieve a reliable field. A patient was considered to have “severe” glaucoma if either eye had (1) optic nerve abnormalities consistent with glaucoma as detailed above and (2) visual field abnormalities in both hemifields and/or loss within 5 degrees of fixation in at least 1 hemifield in the worse eye or (3) visual acuity so severely diminished by glaucoma that HVF testing could not be performed (in this latter case, the cup-to-disc ratio was required to be 0.9 or greater). Subjects were required to have at least 1 reliable HVF in both eyes unless they were unable to complete this test because of severe disease. In circumstances when both eyes of the same patient were eligible for the study, the eye with the worse visual field mean deviation was selected. Patients for whom a diagnosis of glaucoma was made, but chart review revealed normal optic nerves and visual fields, did not meet entrance criteria and were excluded from the study.
Medication adherence was assessed using pharmacy data to ascertain the frequency of filled prescriptions and the number of days for which each prescription was filled or refilled. HIPAA-compliant consent forms, which had been obtained from study subjects, were faxed to all pharmacies from which glaucoma medications had been acquired based on information noted in subjects’ medical records. Individuals receiving free medication samples were excluded. However, since it is the policy of the SFGH Medical Center to not provide free samples, none of the recruited subjects had received free samples. Pharmacy dispensing records were traced from the date of the interview to 18 months prior to the recruitment date.
Medication adherence was estimated using the medication possession ratio (MPR) for the 1-year period prior to the subject recruitment date. MPR was calculated as the sum of days of prescription supply dispensed divided by 365 days for each medication used, as calculated in previous studies. Only medications initially prescribed at least 1 year prior to the recruitment date were included in the calculations for the final MPR measure. Patients were classified as “nonadherent” based on an MPR <0.80 and “adherent” based on an MPR >0.80, consistent with the dichotomization of medication adherence in the literature.
Baseline demographic factors and comorbidities were compared between follow-up adherent and nonadherent patients using the χ 2 test for categorical variables and the Student t test for continuous variables. Multivariate logistic regression models were used to assess the adjusted association between disease severity and follow-up adherence. These models were adjusted for demographic characteristics (age, sex, race, education level) and clinical features such as the number of years since the initial diagnosis of glaucoma. According to Table 1 , mild patients were required to have at least 2 visits to be adherent and moderate and severe patients were required to have at least 3 visits to be adherent. The different number of expected follow-up visits was included as a variable and was adjusted for in our multivariate analysis. Effect modification was tested using the Mantel-Haenszel summary odds ratio from stratified tables.
All comparisons were presented as odds ratios (OR) with 95% confidence intervals (CI). P values of less than .05 using 2-sided tests were deemed to represent a statistically significant association. All statistical analyses were conducted using IBM SPSS Statistics statistical software, version 19.0 (SPSS Inc, Chicago, Illinois, USA).
All 226 subjects found to be eligible for the study were offered enrollment, of which 15 chose not to participate on initial contact and another 5 decided to withdraw during the interview. A total of 206 subjects were enrolled, including 123 classified as having poor follow-up and 83 with good follow-up based upon the Preferred Practice Pattern (PPP) guidelines ( Table 1 ).
Table 2 presents demographic characteristics of adherent and nonadherent subjects. The mean age of the study population was 62 years and approximately 60% of subjects were women. Of the 83 subjects classified as having good adherence, 10 (12.0%) were white, 11 (13.3%) were black, 26 (31.3%) were Latino, and 36 (43.4%) were Asian. A majority of the patients were not employed and had some form of government-sponsored health insurance. Of all variables included in the analysis, only disease severity was found to be independently associated with follow-up adherence. Subjects with severe glaucomatous disease were more likely to have been nonadherent with follow-up recommendations relative to those with mild disease (OR 2.68, 95% CI 1.43-5.02, P = .002).
|Characteristic||Follow-up-Adherent Individuals (n = 83)||Follow-up-Nonadherent Individuals (n = 123)||Unadjusted OR for Poor Follow-up Adherence (95% CI)||P Value|
|Age, mean (SD)||62.2 (9.7)||62.4 (9.4)||.90|
|Female||46 (55.4)||78 (63.4)||1 [Reference]||NA|
|Male||37 (44.6)||45 (36.6)||0.72 (0.41-1.27)||.25|
|White||10 (12.0)||14 (11.4)||1 [Reference]||NA|
|Black||11 (13.3)||30 (24.4)||1.95 (0.67-5.66)||.28|
|Latino||26 (31.3)||36 (29.3)||0.99 (0.38-2.57)||>.99|
|Asian||36 (43.4)||43 (35.0)||0.85 (0.34-2.15)||.82|
|Education level a|
|Low||30 (36.1)||42 (34.1)||1 [Reference]||NA|
|Medium||27 (32.5)||38 (30.9)||1.00 (0.51-1.99)||.99|
|High||26 (31.3)||43 (35.0)||1.18 (0.60-2.32)||.63|
|Mild||42 (50.6)||42 (34.1)||1 [Reference]||NA|
|Moderate||16 (19.2)||14 (11.4)||0.88 (0.38-2.02)||.75|
|Severe||25 (30.1)||67 (54.5)||2.68 (1.43-5.02)||.002|
|Years with a glaucoma diagnosis, mean (SD)||5.44 (5.5)||6.12 (6.20)||.42|
|Glaucoma surgical history|
|Laser surgery treatment||13 (15.7)||20 (16.3)||1 [Reference]||NA|
|No interventional treatment||70 (84.3)||103 (83.7)||0.96 (0.45-2.05)||.91|
|No||16 (19.2)||33 (26.8)||1 [Reference]||NA|
|Yes||67 (80.7)||90 (73.2)||1.54 (0.78-3.02)||.21|
|Employed||24 (28.9)||44 (35.8)||1 [Reference]||NA|
|Not working/retired/unemployed/laid off||59 (71.1)||79 (64.2)||0.73 (0.40-1.33)||.31|
|Health insurance status|
|Government coverage (Medicare, MediCal, SF Health Plan)||82 (98.8)||117 (95.1)||1 [Reference]||NA|
|Private||1 (1.2)||4 (3.3)||2.80 (0.31-25.54)||.36|
|No insurance||0 (0)||2 (1.6)||1.13E +09||>.99|
|Size of household, mean (SD), y|
|Single||23 (27.7)||37 (30.1)||1 [Reference]||NA|
|Two||33 (39.8)||31 (25.2)||0.58 (0.29-1.19)||.14|
|Three or more||24 (28.9)||49 (39.8)||1.27 (0.62-2.59)||.51|
|Did not answer||3 (3.6)||6 (4.9)||1.24 (0.28-5.46)||.77|
|Diabetes (yes vs no)||36 (43.3)||52 (42.3)||0.96 (0.55-1.68)||.88|
|Hypertension (yes vs no)||50 (60.2)||71 (57.7)||0.90 (0.51-1.59)||.72|
|Arthritis (yes vs no)||22 (26.5)||27 (22.0)||0.78 (0.41-1.49)||.45|
|Cardiovascular disease (yes vs no)||18 (21.7)||16 (13.0)||0.54 (0.26-1.13)||.10|
|Asthma (yes vs no)||5 (6.0)||8 (6.5)||1.09 (0.34-3.44)||.89|
|Hypercholesteremia (yes vs no)||33 (39.8)||56 (45.5)||1.27 (0.72-2.23)||.41|
Of the 206 subjects enrolled in the study, 157 used topical ocular medications to treat glaucoma. Table 3 compares the clinical characteristics of these subjects classified based on medication adherence. Approximately 50% of patients (76 of 157) were diagnosed with POAG and more than 60% (99 of 157) were prescribed prostaglandin analogue medications. Forty-five percent of patients (70 of 157) received their glaucoma medications for free from insurance coverage. None of our patients received free samples as it is against hospital policy. Patients who were taking 3 medications were significantly more likely to be nonadherent to their medications compared with those taking only 1 medication (OR 2.90, 95% CI 1.08-7.72, P = 0.04). Out-of-pocket cost of medications and the total number of drops per eye per day were not found to be associated with medication adherence.