Purpose
To investigate the relationship between ocular surface disease and glaucoma-related quality of life (QoL), glaucoma severity, and treatment in patients with open-angle glaucoma.
Design
Cross-sectional study.
Methods
setting: Clinical practice. study population: One hundred twenty-four participants—patients with mild (n = 48), moderate (n = 34), or severe (n = 19) glaucoma and 23 controls (glaucoma suspects) not receiving glaucoma treatment—were enrolled. Severity was stratified according to binocular visual field loss. observed procedures: Demographic information, the Ocular Surface Disease Index (OSDI), and Glaucoma Quality of Life-15 (GQL-15) questionnaires were administered. main outcome measures: OSDI score, GQL-15 score, number and type of glaucoma medications, daily dose of benzalkonium chloride (BAK), and visual field indices.
Results
OSDI scores and the number of patients with OSD increased with increasing glaucoma severity ( P < .001 and P < .005). GQL-15 scores reflected decreased QoL with increasing glaucoma severity ( P < .001). These trends were maintained after sub-stratification for age and sex. On univariate regression OSDI was significantly correlated with GQL-15 summary score, glaucoma severity, multiple topical glaucoma medications, worse eye mean deviation and pattern standard deviation, use of topical beta blockers, topical carbonic anhydrase inhibitors, daily dose of BAK, and glaucoma filtration surgery. On multivariate regression GQL-15 summary score (odds ratio [OR] 4.14, 95% confidence interval [CI] 2.59–6.63, P < .001) and a daily dose of BAK greater than 3 (OR 2.47, 95% CI 1.17-5.21, P = .018) were predictive of OSDI score.
Conclusions
OSD is more common in patients with increasing glaucoma severity and is associated with poorer glaucoma-related QoL and higher exposure to BAK.
Assessment of quality of life (QoL) is important in the management of glaucoma patients; it reflects the burden of disease experienced by the patient, it holistically assesses the impact of glaucoma on the individual, and it can be used to monitor progress in patients with glaucoma. Several QoL questionnaires have been validated and correlate closely with clinical indices of glaucoma severity, 1 of which is the Glaucoma Quality of Life-15 (GQL-15). Poorer QoL scores are associated with worse functional status and increased visual morbidity from glaucoma.
Affecting 15% of individuals older than 65, ocular surface disease (OSD) is common. Characterized by symptoms such as grittiness, burning, photophobia, dryness, foreign body sensation, and transient visual disturbance, it results from an inadequate volume and/or quality of tears, resulting in an unstable tear film with ocular surface breakdown. Age, ethnicity, and sex influence OSD: it is more frequent in older subjects and in women. Common ophthalmic conditions that can exacerbate OSD include Meibomian gland dysfunction, blepharitis, lid malposition, trichiasis, keratoconjunctivitis sicca, allergic conjunctivitis, contact lens wear, refractive surgery, corneal exposure, and thyroid eye disease. OSD can cause debilitating symptoms that often impair patients’ work and function. Previous studies using vision-related QoL scores have shown a negative impact of OSD on QoL.
OSD affects up to 59% of patients with glaucoma. This high prevalence may result from both conditions being increasingly common in the elderly; in addition, preservative-containing topical medications, especially those used chronically, can exacerbate or contribute to OSD. Benzalkonium chloride (BAK) in particular reduces the stability of the precorneal tear film, with direct corneal toxicity; this has been shown in vitro and in vivo in animal and human studies. All classes of topical pressure-lowering medications cause ocular surface discomfort, especially topical carbonic anhydrase inhibitors (CAI). Topical medication–related OSD contributes to worse symptoms, poorer adherence, worse surgical outcomes, and reduced QoL in glaucoma patients. Tear cytokines, in particular monocyte chemoattractant protein-1, are elevated in patients on topical medications and are associated with scarring post-trabeculectomy. Bleb dysesthesia, which may follow glaucoma filtration surgery and which occurs more frequently with elevated and exposed blebs, can aggravate OSD symptoms.
The Ocular Surface Disease Index (OSDI) is a 12-item questionnaire designed to provide a rapid assessment of OSD related to chronic dry eye, its severity, and its impact on the patient’s ability to function. It has been shown to have a high reliability, reproducibility, and validity. It correlates weakly but positively with objective markers of OSD such as tear film break-up time, Schirmer test, and lissamine green surface staining. It has been validated with good sensitivity and specificity to detect normal subjects and patients with a value of <12; scores 12 or greater indicate OSD.
The GQL-15 is a 15-item questionnaire with which patients subjectively evaluate their own ability to perform visually demanding tasks of daily living. The tasks are subdivided into 4 domains: problems with reading/recognizing faces (central/near vision), problems with bumping into/tripping over objects (peripheral vision), problems with darkness/glare, and problems with getting around outside/walking in the street (outdoor mobility). There is high internal reproducibility and consistency of the assessment over time.
Although glaucomatous field loss and OSD each have been shown to contribute to poor QoL in glaucoma patients, the relative impact of each has not been assessed in a combined study. Similarly, while increasing topical medications are associated with poorer OSD-related QoL, it is unknown if a specific class of medication in particular, glaucoma drainage surgery, and/or worsening glaucomatous field loss also influence OSD. Worsening field loss may be associated with OSD as an indirect marker of multiple topical medications; also, it may be additive to OSD as a negative influence on QoL. We investigated the relationship between OSD and QoL in glaucoma patients, specifically whether ocular surface symptoms are associated with glaucoma severity and poorer QoL in glaucoma patients and whether they are associated with the number or type of glaucoma medication used or glaucoma surgery. A greater understanding of the burden of disease caused by OSD will allow clinicians to identify more accurately causes of poor QoL in patients with glaucoma.
Methods
Patients and Study Population
Participants were recruited from patients attending the urban ophthalmic glaucoma subspecialty practice of 1 of the authors (I.G.) and from glaucoma subspecialty clinics in large urban tertiary hospitals.
Informed consent was obtained from each participant. Eligible subjects were prospectively approached during regularly scheduled follow-up visits; those giving consent were enrolled consecutively. The eligibility criteria for the glaucoma group were a diagnosis of chronic open-angle glaucoma (OAG) in 1 or both eyes and the ability to speak, read, and comprehend English fluently. OAG was diagnosed on the basis of characteristic optic disc changes and/or glaucomatous visual field loss demonstrated on the Humphrey visual field analyzer (HFA) (Humphrey Instruments, Inc, Zeiss Humphrey, San Leandro, California, USA) with or without raised intraocular pressure and an open anterior chamber angle on gonioscopy. Patients were required to be on a fixed glaucoma treatment regimen for at least 3 months prior to enrollment. The controls were patients attending the ophthalmic practices with ocular hypertension or those with suspicious optic discs who did not have glaucomatous field loss or sufficient optic nerve changes to be diagnosed with glaucoma; they were not on topical therapy. Patients with any nonglaucomatous condition affecting visual function such as cataract, retinal pathology, symptomatic or uncontrolled systemic disease, nonglaucomatous optic neuropathy and ocular laser treatment or surgery in the previous 3 months were excluded from the study. Patients with significant OSD prior to commencing glaucoma treatment, including those treated with topical cyclosporine, steroids, or punctal plugs within the previous 3 months, were excluded.
Glaucoma patients were stratified by severity of central visual field loss according to the glaucoma staging system (GSS) developed by Nelson and associates. They were classified into 3 groups: “mild” (unilateral loss of less than half of the visual field), “moderate” (unilateral loss of more than half of the visual field, or bilateral loss of less than half of the visual field in each eye), or “severe” (bilateral loss of more than half of the visual field in either eye). This GSS has been shown to correlate strongly with perimetric mean deviation (MD) and pattern standard deviation (PSD).
For the purpose of statistical analysis, participants were stratified into 4 groups: control (ocular hypertension or glaucoma suspect) and mild, moderate, or severe glaucoma. They were then sub-stratified according to age brackets—less than 60, 60–69, 70–79, and 80 or older—and according to sex.
Measures
Each participant completed both the GQL-15 and OSDI surveys. Demographic information (marital and employment status, education, and ethnicity) and details of current and previous glaucoma treatment were also collected. Snellen visual acuity (VA) was recorded and converted to the logarithm of the minimal angle of resolution (logMAR) for analysis. Achromatic perimetry was performed using the HFA Swedish Interactive Threshold Algorithm standard 24–2 test. Binocular visual field loss was calculated using PROGRESSOR (OBF Laboratories, Malmesbury, England) with point binocular loss defined as threshold <10 dB.
The GQL-15 questionnaire is composed of 15 items, each of which correlates with severity of visual field loss. These are subdivided into 4 aspects of visual disability: 1) central and near vision; 2) peripheral vision; 3) dark adaptation and glare; and 4) outdoor mobility. Each item-level response was coded on a scale of 0 to 5: 0 signifies abstinence from activity for nonvisual reasons, 1 signifies no difficulty, and 5 signifies severe difficulty. The subscale score for each factor was calculated from the average of the scores generated by the item-level responses. The final GQL-15 summary score was out of a total score of 75, with higher scores indicating a poorer glaucoma-related QoL.
The OSDI is based on a 12-item questionnaire assessing symptoms related to chronic dry eye, their severity, and impact on the patient’s ability to function within the last week. Each item is scored from 0 to 4: 0 signifies symptoms none of the time, 1 signifies symptoms some of the time, 2 signifies symptoms half of the time, 3 signifies symptoms most of the time, and 4 signifies symptoms all of the time. The OSDI overall score ranged from 0 to 100, with higher scores indicating worse OSD. A score of 0 to 11.9 was considered normal; 12 or greater was used as a marker of OSD.
Treatment data were recorded for each participant. This included the number and type of topical medication(s), past laser therapy to either eye, and past glaucoma filtration surgery (GFS) to either eye. The number of treatments for each participant was recorded. Combination medications were treated as separate medications for the analysis of types of medication but were treated as 1 product when calculating the total number of topical glaucoma medications used.
Statistical Analysis
Statistical analyses were conducted using Statistical Package for Social Sciences (SPSS, Inc, Chicago, Illinois, USA) for Windows (version 17.0; Microsoft Corporation, Redmond, Washington, USA).
Demographic variables, worse eye VA, MD and PSD, treatment characteristics, OSDI score, and GQL-15 summary and subset scores were compared among the 4 patient groups. Intergroup significance was assessed using the nonparametric Kruskal-Wallis analysis of ranks and analysis of variance for parametric data. Age adjustment of P values was performed using analysis of covariance for parametric data and Kruskal-Wallis analysis on age-stratified nonparametric data.
Worse eye MD, GQL-15, and OSDI scores and the number of patients with OSD were compared across groups divided according to age bracket and sex to identify confounding factors. GQL-15 scores were compared between subjects with and without OSD subdivided according to glaucoma severity groups.
A univariate regression analysis was performed to examine the association between OSDI and the following variables: age, sex, demographic data, GQL-15 score, MD, PSD, VA, glaucoma severity, GFS, the number and type of glaucoma medications used, and daily dose of BAK. Daily dose of BAK was the total number of eye drops administered from topical preparations containing BAK as preservative. All variables were analyzed for correlation using Pearson for parametric and Spearman and Kendall tau-b correlation tests for nonparametric data. Variables with strong (>0.9) correlations were excluded from the regression modeling. Factors predictive of a high OSDI score were then included in a multivariate analysis. The statistical significance of individual regression coefficients was tested using the Wald χ 2 statistic. All variables were assessed for normality and linearity and transformed as required, and analysis of residuals was performed. All tests were 2-tailed, with P value < 0.05 considered significant.
Results
Table 1 gives the baseline patient characteristics, GQL-15 scores, OSDI scores, and treatment details. A total of 124 participants completed the GQL-15 and the OSDI (23 control subjects, and 48 mild, 34 moderate, and 19 severe glaucoma patients). One patient incompletely answered the surveys and was excluded from analysis. Fifty-seven participants were recruited from the urban ophthalmic glaucoma subspecialty practice of 1 of the authors (I.G.) and 43 and 24 respectively from 2 large urban tertiary referral hospitals.
| Variable | Controls | Patients With Glaucoma | P a | |||
|---|---|---|---|---|---|---|
| Mild | Moderate | Severe | Unadjusted Analysis | Adjusted for Age | ||
| (n = 23) | (n = 48) | (n = 34) | (n = 19) | |||
| Age (years), mean (SD) | 66.1 (12.0) | 70.1 (9.0) | 71.9 (11.7) | 75.4 (13.2) | NS | |
| Sex [no. of patients (%)] | .036 | |||||
| Female | 17 (73.9) | 28 (58.3) | 22 (64.7) | 6 (31.6) | ||
| Male | 6 (26.1) | 20 (41.7) | 12 (35.3) | 13 (68.4) | ||
| Demographic data [no. of patients (%)] | ||||||
| Married/de facto | 15 (65.2) | 32 (66.7) | 12 (35.3) | 11 (57.9) | .029 | |
| Tertiary education | 6 (26.1) | 26 (54.2) | 13 (38.2) | 11 (57.9) | .025 | |
| Retired | 18 (78.3) | 36 (75.0) | 26 (76.5) | 18 (94.7) | NS | |
| White | 18 (78.3) | 40 (83.3) | 34 (100) | 14 (73.7) | .025 | |
| logMAR VA, mean (SD) b | 0.09 (0.17) | 0.089 (0.14) | 0.32 (0.59) | 0.61 (0.79) | <.001 | <.001 |
| HFA MD, mean dB (SD) b | −1.95 (2.6) | −4.74 (3.1) | −13.51 (5.2) | −24.19 (5.3) | <.00001 | <.00001 |
| HFA PSD, mean dB (SD) b | 2.51 (1.5) | 4.17 (3.4) | 9.18 (3.5) | 8.20 (3.0) | <.00001 | <.00001 |
| GQL-15 scores, mean (SD) | ||||||
| Summary score (out of 75) | 21.2 (11.7) | 22.0 (6.9) | 30.9 (11.3) | 36.4 (14.8) | <.00001 | <.00001 |
| Factor 1 (central and near vision) | 2.7 (1.5) | 2.8 (1.3) | 3.9 (1.9) | 4.1 (1.9) | ||
| Factor 2 (peripheral vision) | 8.3 (5.0) | 8.3 (2.7) | 12.1 (5.1) | 14.8 (6.5) | ||
| Factor 3 (glare and dark adaptation) | 8.9 (4.8) | 9.8 (3.9) | 13.1 (5.6) | 15.4 (6.4) | ||
| Factor 4 (outdoor mobility) | 1.3 (0.8) | 1.2 (0.4) | 1.5 (0.8) | 2.2 (1.5) | ||
| OSDI scores, mean (SD) | 5.5 (9.5) | 5.0 (5.1) | 9.8 (6.9) | 13.3 (11.6) | <.001 | <.0001 |
| Patients with OSD [no. of patients (%)] c | 5 (21.7) | 16 (33.3) | 23 (67.6) | 15 (78.9) | <.0001 | NS a [6,8] <.005 a [5,7] |
| Glaucoma treatment [no. of patients (%)] | ||||||
| Prostaglandin analogues | 0 (0) | 40 (83.3) | 27 (79.4) | 14 (73.7) | ||
| Beta blockers | 0 (0) | 22 (45.8) | 18 (52.9) | 16 (84.2) | ||
| Alpha-2 agonists | 0 (0) | 4 (8.3) | 6 (17.6) | 2 (10.5) | ||
| Cholinergics | 0 (0) | 0 (0) | 1 (2.9) | 0 (0) | ||
| Carbonic anhydrase inhibitors | 0 (0) | 8 (16.7) | 10 (29.4) | 7 (36.8) | ||
| Combination topical medications | 0 (0) | 14 (29.2) | 12 (35.3) | 14 (73.7) | ||
| Laser trabeculoplasty | 0 (0) | 4 (8.3) | 6 (17.6) | 3 (15.8) | ||
| Glaucoma filtration surgery | 0 (0) | 4 (8.3) | 10 (29.4) | 9 (47.4) | ||
| Pharmacotherapy alone | 0 (0) | 42 (87.5) | 24 (70.6) | 9 (47.4) | ||
| Pharmacotherapy and surgery | 0 (0) | 4 (8.3) | 8 (23.5) | 9 (47.4) | ||
| None | 23 (100) | 2 (4.2) | 0 (0) | 1 (5.3) | ||
| No. of topical glaucoma medications, mean (range) | 0 (0) | 1.3 (0–3) | 1.5 (0–3) | 1.3 (0–3) | ||
| Daily BAK dose, mean (range) | 0 (0) | 1.6 (0–5) | 2.2 (0–6) | 2.1 (0–5) | ||
a Two-tailed significance, P < .05: analysis of variance for the natural logarithm of parametric data; Kruskal-Wallis analysis of ranks for nonparametric data. Age adjustment: analysis of covariance with age for parametric data; nonparametric data sub stratified according to age. 5 Age <60; 6 Age 60–69; 7 Age 70–79; 8 Age 80 and older.
The mean and standard deviation of the ages of each group were 66.1 (12.0) for control subjects and 70.1 (9.0) for mild, 71.9 (11.7) for moderate, and 75.4 (13.2) for severe glaucoma patients. Seventy-three participants were women, representing 73.9% (17/23), 58.3% (28/48), 64.7% (22/34), and 31.6% (6/19) of the ocular hypertension, mild, moderate, and severe groups respectively. The variance of sex was significant across the groups, indicating a higher proportion of male subjects with increasing glaucoma severity.
Approximately half the patients were married (ranging from 35.3% (12/34) in the moderate glaucoma group to 66.7% (32/48) in the mild glaucoma group) and had tertiary education (ranging from 26.1% [6/23] in the control group to 57.9% [11/19] in the severe glaucoma group). Most patients were retired (ranging from 78.3% (18/23) in the control group to 94.7% (18/19) in the severe glaucoma group) and white (ranging from 100% (34/34) in the moderate glaucoma group to 73.7% (14/19) in the severe glaucoma group). The variance of many of these factors reached significance, indicating that patients with more severe glaucoma were less likely to be married or white or have tertiary education.
HFA MD and PSD significantly increased with glaucoma severity across all groups. The logMAR VA deteriorated significantly across all groups.
The mean and range of the number of topical glaucoma medications in each group were 0 (0) for control subjects and 1.3 (0–3) for mild, 1.5 (0–3) for moderate, and 1.3 (0–3) for severe glaucoma patients. The mean and range of the daily dose of BAK in each group were 0 (0) for control subjects and 1.6 (0–5) for mild, 2.2 (0–6) for moderate, and 2.1 (0–5) for severe glaucoma patients.
Summary GQL-15 score decreased significantly with increasing glaucoma severity, which was maintained after sub-stratification according to sex and age ( Tables 2 and 3 ). This trend was maintained for each of the 4 sub-factor scores. These findings reflected decreased QoL with increasing glaucoma severity.
| Sex | Variable | Controls | Patients With Glaucoma | P a | ||
|---|---|---|---|---|---|---|
| Mild | Moderate | Severe | ||||
| Female | No. patients | 17 | 28 | 22 | 6 | |
| (n = 73) | HFA MD mean dB (SD) b | −1.57 (2.5) | −5.00 (3.4) | −13.56 (5.6) | −21.72 (7.5) | <.00001 |
| GQL-15 summary score mean (SD) (out of 75) | 19.7 (9.5) | 22.8 (7.1) | 32.8 (10.9) | 37.3 (14.5) | <.00001 | |
| OSDI score mean (SD) (out of 48) | 6.5 (10.8) | 4.8 (4.0) | 10.7 (7.5) | 11.0 (4.6) | .01 | |
| No. patients with OSD (%) c | 5 (29.4) | 9 (32.1) | 14 (63.6) | 5 (83.3) | .004 | |
| Male | No. patients | 6 | 20 | 12 | 13 | |
| (n = 51) | HFA MD mean dB (SD) b | −3.05 (3.0) | −4.39 (2.7) | −13.44 (4.8) | −25.33 (3.8) | <.00001 |
| GQL-15 summary score mean (SD) (out of 75) | 25.3 (17.0) | 21.1 (6.7) | 26.6 (11.3) | 35.9 (15.5) | .006 | |
| OSDI score mean (SD) (out of 48) | 2.7 (1.4) | 5.4 (6.4) | 8.5 (5.8) | 14.2 (13.5) | .036 | |
| No. patients with OSD (%) c | 0 (0) | 7 (35.0) | 9 (75.0) | 9 (69.2) | .003 | |
a Two-tailed significance, P < .05: analysis of variance for the natural logarithm of parametric data; Kruskal-Wallis analysis of ranks for nonparametric data.
| Age Bracket | Variable | Controls | Patients With Glaucoma | P a | ||
|---|---|---|---|---|---|---|
| Mild | Moderate | Severe | ||||
| Less than 60 | No. patients | 5 | 10 | 5 | 2 | |
| (n = 22) | HFA MD mean dB (SD) b | −1.47 (4.0) | −4.84 (2.9) | −11.94 (3.9) | −18.33 (6.4) | <.0001 |
| GQL-15 summary score mean (SD) (out of 75) | 18.4 (5.0) | 21 (7.9) | 31.2 (9.8) | 36 (18.4) | .031 | |
| OSDI score mean (SD) (out of 48) | 2.6 (2.4) | 5.9 (7.7) | 9.6 (4.4) | 24.5 (23.3) | .025 | |
| No. patients with OSD (%) c | 0 (0) | 2 (20.0) | 4 (80.0) | 2 (100.0) | .003 | |
| 60-69 | No. patients | 9 | 10 | 7 | 0 | |
| (n = 26) | HFA MD mean dB (SD) b | −1.61 (2.7) | −2.94 (2.9) | −14.07 (5.7) | <.00001 | |
| GQL-15 summary score mean (SD) (out of 75) | 18.44 (3.1) | 26.3 (8.5) | 30 (12.9) | .033 | ||
| OSDI score mean (SD) (out of 48) | 5.3 (7.8) | 6.0 (4.4) | 8 (7.3) | NS | ||
| No. patients with OSD (%) c | 3 (33.3) | 5 (50.0) | 4 (57.1) | NS | ||
| 70–79 | No. patients | 7 | 21 | 12 | 6 | |
| (n = 46) | HFA MD mean dB (SD) b | −2.38 (1.6) | −5.23 (3.2) | −14.02 (5.2) | −23.91 (6.2) | <.00001 |
| GQL-15 summary score mean (SD) (out of 75) | 28.4 (19.6) | 20.6 (5.4) | 31.9 (10.5) | 45.3 (15.0) | .001 | |
| OSDI score mean (SD) (out of 48) | 8.7 (14.9) | 4.6 (4.7) | 11.6 (7.9) | 18.8 (11.2) | .001 | |
| No. patients with OSD (%) c | 2 (28.6) | 7 (33.3) | 9 (75.0) | 6 (100) | .004 | |
| 80 and older | No. patients | 2 | 7 | 10 | 11 | |
| (n = 30) | HFA MD mean dB (SD) b | −3.20 (2.5) | −5.75 (2.9) | −13.31 (6.1) | −25.41 (4.3) | <.00001 |
| GQL-15 summary score mean (SD) (out of 75) | 15 (0) | 21.7 (5.8) | 30 (13.2) | 31.5 (13.2) | NS | |
| OSDI score mean (SD) (out of 48) | 2.0 (1.4) | 3.7 (2.9) | 8.7 (6.5) | 7.5 (6.0) | NS | |
| No. patients with OSD (%) c | 0 (0) | 2 (28.6) | 6 (60) | 7 (63.6) | NS | |
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