Abstract
Purpose:
To examine the ocular surface disease in primary open-angle glaucoma (POAG) patients already on treatment versus POAG patients without treatment.
Methods:
A prospective cohort study was conducted on 120 eyes of 60 POAG patients: 60 treatment-naïve eyes (group I) and 60 eyes already on topical anti-glaucoma medications (AGMs) (group II). All patients had filled out the Ocular Surface Disease Index (OSDI) questionnaire and underwent a comprehensive glaucoma workup. Tear break-up time (TBUT) test, Schirmer’s test (type I), corneal sensitivity, anterior segment-optical coherence tomography (AS-OCT), and corneal and conjunctival staining were done at day 1, 1 month, 3 months, 6 months, and 12 months follow-up.
Results:
On presentation, TBUT, Schirmer’s test, tear meniscus height (TMH), and tear meniscus depth (TMD) were significantly higher in group I compared to group II. No significant difference was noted in OSDI score, corneal sensitivity, and tear meniscus area (TMA) between the groups on presentation. Both, lissamine green and rose bengal staining, had higher grades in group II compared to group I. Worsening of ocular surface disease was noted in both groups on follow-up. OSDI score, TBUT, Schirmer’s test, TMH, and TMD had better values in group I in comparison to group II on follow-up.
Conclusion:
The study has identified glaucoma patients on AGMs to be more affected by dry eye disease (DED) compared to treatment-naive glaucoma patients. We found statistically significant differences in values of TBUT, Schirmer tests, lissamine and rose bengal staining, and AS-OCT parameters at baseline and 3, 6, and 12 months follow-up. OSDI scores showed significant differences at 6 and 12 months of follow-up. We recommend consideration of evaluation and management of DED/ocular surface disease in glaucoma patients on topical AGMs, particularly multiple drugs and doses.
Keywords: AS-OCT, ocular surface disease, OSDI, primary open-angle glaucoma, treatment-naïve
Glaucoma is a common cause of irreversible blindness, especially in Asians.[1,2] Intraocular pressure (IOP) is the only modifiable risk factor to halt visual field progression.[3] IOP can be controlled by either pharmacological agents, laser therapy, or incisional surgery.[4] According to the European Glaucoma Society Guidelines, the first-line approach to control IOP is with medical treatment. A series of large, multicenter, randomized controlled studies showed that IOP-lowering therapy could prevent glaucoma onset from ocular hypertension and prevent further progression in patients with a confirmed diagnosis of glaucoma.[5] Due to the progressive nature of the disease, long-term treatment is required, with many patients using more than one drug to achieve the target IOP.[6]
Long-term anti-glaucoma therapy is not free from side effects. The ocular surface disease is one of the major side effects of topical anti-glaucoma medications (AGMs).[7] Causes of ocular surface disease due to AGMs are thought to be multifactorial. It can be due to either an allergic or a toxic mechanism.[8,9] Allergic responses are rare and common in the early phases of therapy. Hence, toxicity is likely to be the cause of chronic ocular surface disease, which can be due to preservatives in topical AGM or active compounds itself.[10] This not only changes the local ocular environment (altered tear film stability/osmolarity) but also raised the inflammation and fibrosis after surgery.[11,12]
Subjective severity of dry eye disease (DED) can be assessed by various questionnaires available while damage to the ocular surface can be evaluated by a series of objective tests which includes the Schirmer test, TBUT, ocular surface staining, tear meniscus assessment, tear osmolarity assessment, conjunctival impression cytology, and anterior segment-optical coherence tomography (AS-OCT).
Our study tried to evaluate whether dry eye in glaucoma is due to topical AGMs and their preservatives or glaucoma itself being aggravated further by topical AGM. By doing so, we can detect dry eye in glaucoma patients at an early stage which will result in better and more effective management of dry eye as well as an increase in compliance and adherence to glaucoma therapy. This in turn will lead to better long-term management of glaucoma patients with overall improvement in the quality of life of glaucoma patients. In our study, in addition to routinely performed dry eye tests like Schirmer’s test, TBUT, and ocular surface staining, we also included tear meniscus assessment by AS-OCT which has been done in very few studies.[10,13]
Methods
A prospective cohort study was carried out on 120 eyes of 60 patients with primary open-angle glaucoma (POAG) who met the inclusion and exclusion criteria and visited the glaucoma clinic of the eye department from January 2021 to June 2022 in a tertiary care center in western India after obtaining approval by Institutional Ethics Committee.
Inclusion criteria: All patients diagnosed with POAG attending the glaucoma clinic outpatient department from June 2021 to June 2022. The diagnosis of POAG was made based on characteristic disc findings, gonioscopic features, and visual field changes.
Exclusion criteria: Patients with a history of cataract/glaucoma surgery or laser procedure within the last 6 months, ocular conditions that can contribute to the occurrence of dry eye such as lid disorders (anterior and posterior blepharitis, ectropion, entropion), contact lens wear, allergic conjunctivitis, chronic conjunctivitis, exposure keratitis, contact dermatitis, and Bell’s palsy, systemic conditions like thyroid, diabetes, lupus, rheumatoid arthritis, scleroderma, Sjögren’s syndrome, vitamin A deficiency, and other factors like smoking; and those with continuous long- term use of ocular or systemic medications (anti-histaminic, anti-depressants, decongestants, beta-blocker drugs, diuretics, and aspirin), disorders decreasing corneal sensitivity, subjects not giving written informed consent and uncooperative patients in whom dry eye assessment cannot be done.
All POAG patients who met the inclusion and exclusion criteria were included in the study and divided into two groups:
Group I: Newly diagnosed patients of POAG not on any treatment from before.
Group II: Patients of POAG already on topical AGMs.
After ensuring that the patient fulfilled our inclusion criteria, the patient was informed about the nature of the study and was given a patient information sheet. The patient was enrolled in the study after obtaining informed written consent. The demographic details of all the participating patients were recorded. A detailed history regarding onset, duration, and progression of symptoms (if any), history of any medical illness or addiction, and family history of glaucoma was taken. Group I patients were started on AGMs and Group II were continued on their medications. All the enrolled patients underwent comprehensive glaucoma workup along with ocular surface examination at day 1, 1 month, 3 months, 6 months, and 12 months follow-up.
All the participants included in the study filled out the Ocular Surface Disease Index (OSDI) questionnaire. The baseline parameters including visual acuity (both unaided and best corrected) using Snellen’s Charts, IOP with Goldmann applanation tonometer, central corneal thickness with the help of autorefractometer, detailed slit-lamp examination, visual fields assessment, dilated fundus examination with +90D lens, and indirect ophthalmoscopy with + 20D lens were performed in each patient.
In addition, the tear break-up time (TBUT) test, Schirmer’s test (type I), corneal sensitivity, tear meniscus assessment by AS-OCT, and staining of the corneal and conjunctival surface were carried out in all the participants for evaluation of ocular surface disease.
The diagnosis of ocular surface disease was based on the OSDI questionnaire (developed by Allergan). It is a disease-specific questionnaire used to quantify the specific impact of dry eye on vision-related quality of life. It includes 12 questions. The responses range from 0 to 4 with 0 indicating none of the time and 4 indicating always; the OSDI score ranges from 0 to 100. The criteria used for the grading was: 0-12 = normal; 13-22 = mild; 23-32 = moderate; and 33-100 = severe. The total OSDI score was calculated by using the formula:
OSDI = Sum of scores for all the questions asked ×25/Total number of questions answered.
Schirmer’s test type 1 was done to test basal and reflex tear secretion by using a Schirmer’s strip. Depending on the wetting of the strip after 5 min, the results of Schirmer’s test were graded as: >10 mm = normal (grade 0); 5-10 mm = mild (grade 1); 3-4 mm = moderate (grade 2); 0-2 mm = severe (grade 3).
The TBUT test was used to determine the stability of the tear film. TBUT is the time interval between the last blink and tear film disruption. TBUT less than 10 s is abnormal and graded as: >10 s = normal (grade 0); 6.1-10 s = fair (grade 1); 3.1-6 s = moderate (grade 2); <3 s = poor (grade 3).
Corneal sensations were checked with the tip of a cotton wisp and the presence of a blink reflex following gentle touch while the patient was asked to view a distant object. They were recorded in all quadrants in a similar manner.
AS-OCT was done to assess lower tear meniscus height (L-TMH), lower tear meniscus depth (L-TMD), and lower tear meniscus area (L-TMA). The tear meniscus appears as a triangular shape of a wedge of tear film between the lower lid margin and ocular surface. After obtaining the tear meniscus images, the L-TMH, L-TMD, and TMA were calculated using the Image J software (Java software program developed by the National Institutes of Health, Bethesda, MD; http://imagej.nih.gov/ij/). TMH was measured three times in each photograph, and the mean value was recorded for further analysis. The scan was taken below the corneal vertex, centered on the inferior cornea and lower eyelid. The corneal vertex was determined by the position of specular reflection. The subject was asked to blink normally during the imaging procedure while looking straight at a fixed target within the device. Images were captured within the first second immediately after a blink.
Conjunctival and corneal staining was done using sterile rose bengal and lissamine green paper strips. The strip was applied for 2 min in the lower outer conjunctional cul-de-sac. Then the patient was asked to blink multiple times for a uniform spread of the dye. The examination was done on a slit lamp biomicroscope under white light. Ocular surface damage was graded by using the Oxford grading scheme. The grading chart consisted of a series of panels, labeled A–E, in increasing order of severity, denoting the staining patterns seen in dry eye. These panels were used as a guide to grade the degree of staining seen in the patient. The amount of staining was represented by punctate dots.
All the enrolled patients underwent comprehensive glaucoma evaluations along with ocular surface examination at day 1, 1 month, 3 months, 6 months, and 12 months follow-up.
Data was entered and analyzed using the SPSS (Statistical Package for the Social Sciences) version 25 (IBM SPSS Statistics, Armonk, NY, USA). All nominal variables were described using counts and percentages and analyzed using the Chi-square test or Fischer’s exact test. All continuous variables were described using mean and standard deviation (SD) and analyzed using the independent samples t-test. A P value of less than 0.05 was considered statistically significant.
Results
Our study enrolled 120 eyes of 60 POAG patients: 60 eyes of 30 newly diagnosed, treatment-naive POAG patients (group I) and 60 eyes of 30 POAG patients who were already on topical AGMs (group II). The mean age was comparable between group I (59.00 ± 11.52) and group II (60.3 ± 9.31). There were 18 males and 12 females in group I and 20 males and 10 females in group II (P = 1.00).
The mean visual acuity, cup-disc ratio, and mean deviation on HVF were comparable between the two groups [Table 1]. The mean values of Schirmer’s test and TBUT were significantly more in group II than in group I at baseline (P < 0.0001). There was no significant difference in the mean values of OSDI score between the two groups at baseline (P = 0.511). The mean values of TMH and depth on AS-OCT were significantly higher in group I compared to group II at baseline (P = 0.001 and P = 0.0003, respectively). There was no significant difference in the mean value of the TMA on AS-OCT between the two groups (P = 0.099). In group II, the mean OSDI score was significantly higher in eyes with topical AGMs for >3 years in comparison to those with medications <3 years (P = 0.001) [Table 1].
Table 1.
Baseline characteristics in group I and group II
| Age (years) | Group I (n=60) | Group II (n=60) | P | ||
|---|---|---|---|---|---|
| 40-50 | 10 (16.67%) | 8 (13.33%) | |||
| 51-60 | 8 (13.33%) | 17 (28.33%) | |||
| 61-70 | 22 (36.67%) | 25 (41.67%) | |||
| 71-80 | 20 (33.33%) | 10 (16.67%) | |||
| Mean±SD | 59.00±11.52 | 60.3±9.31 | 0.327 | ||
|
| |||||
| Gender |
Group I (n=60)
|
Group II (n=60)
|
|||
| n | % | n | % | ||
|
| |||||
| Male | 36 | 60.00 | 40 | 66.67 | 0.284 |
| Female | 24 | 40.00 | 20 | 33.37 | |
| Visual acuity | 0.344±0.618 | 0.59±0.998 | 0.107 | ||
| Baseline IOP | 29.66±7.21 | 17.13±6.209 | 0.001 | ||
| Cup-disc ratio | 0.71±0.164 | 0.733±0.176 | 0.46 | ||
| MD | 18.899±2.69 | 19.64±2.41 | 0.114 | ||
| Schirmer’s test-(mm) | 20.2±3.02 | 13.91±3.03 | <0.0001 | ||
| TBUT-(seconds) | 12.1±2.31 | 8.5±1.72 | <0.0001 | ||
| OSDI Questionnaire score | 34.25±9.02 | 35.17±5.98 | 0.511 | ||
| TMH-(microns) | 253.33±8.86 | 248.93±6.95 | 0.001 | ||
| TMD-(microns) | 154.05±5.85 | 149.9±6.30 | 0.0003 | ||
| TMA-(mm2) | 0.025±0.029 | 0.018±0.001 | 0.099 | ||
(CDR: Cup Disc Ratio, MD: Mean Deviation on Humphrey’s Visual Field Analyzer, TBUT: Tear break-up time, OSDI: Ocular surface disease index, TMH: tear meniscus height, TMD: tear meniscus depth, TMA: tear meniscus area)
In group I patients, most of the patients were started on two drugs (32) followed by three drugs (19) whereas in group II, the majority of the participants were on three drugs (24) [Table 2]. In group II, 12 eyes were on one drop, 18 eyes on two drops, and 30 eyes on three drops at baseline [Table 2]. On further subgroup analysis in group II, 24 eyes were on topical AGMs for <3 years and 36 eyes were on topical AGMs for >3 years [Table 2].
Table 2.
Distribution of study population according to number and class of anti-glaucoma medications
| Number of drugs | Class of drugs | Group I (n=60) | Group II (n=60) |
|---|---|---|---|
| 1 | Prostaglandin analog | 6 | 6 |
| Beta-blocker | 2 | 6 | |
| Total | 8 | 12 | |
| 2 | PG analog + beta-blocker | 14 | 4 |
| PG analog + alpha agonist | 2 | 0 | |
| Beta-blocker + alpha agonist | 4 | 8 | |
| CA inhibitor + alpha agonist | 12 | 1 | |
| CA inhibitor + beta-blocker | 0 | 4 | |
| CA inhibitor + PG analog | 0 | 1 | |
| Total | 32 | 18 | |
| 3 | Beta-blocker + PG analog + alpha agonist | 10 | 11 |
| CA inhibitor + PG analog + alpha agonist | 4 | 5 | |
| CA inhibitor + beta-blocker + alpha agonist | 5 | 1 | |
| CA inhibitor + PG analog + miotic | 0 | 2 | |
| CA inhibitor + PG analog + beta-blocker | 0 | 5 | |
| Total | 19 | 24 | |
| 4 | Beta-blocker + PG analog + CA inhibitor + alpha agonist | 1 | 4 |
| PG analog + CA inhibitor + alpha agonist + Rho-kinase inhibitor | 0 | 2 | |
| Total | 1 | 6 | |
A significant difference in the staining pattern was noted between the two groups at baseline (P < 0.0001). In group I, 56 (93.33%) eyes showed grade 0, and 4 (6.67%) eyes showed grade 1 with lissamine green staining; and 48 (80%) eyes showed grade 0, and 12 (20%) eyes showed grade 1 with rose bengal staining. In group II, 22 (36.67%) eyes showed grade 0, 34 (56.67%) eyes showed grade 1, and 4 (6.67%) eyes showed grade 2 with lissamine green staining; and 13 (21.67%) eyes showed grade 0, 37 (61.67%) eyes showed grade 1, and 10 (16.67%) eyes showed grade 2 with rose bengal staining [Table 3].
Table 3.
Conjunctival and corneal staining in both the groups at baseline and follow-up visits
| GROUP I (n=60) | ||||||
|---|---|---|---|---|---|---|
| Staining | Grade | Follow-up |
||||
| Baseline | 1 month | 3 months | 6 months | 12 months | ||
|
| ||||||
| n (%) | n (%) | n (%) | n (%) | n (%) | ||
| Lissamine green | 0 | 56 (93.34%) | 55 (91.66%) | 52 (86.666%) | 43 (71.66%) | 24 (40%) |
| I | 4 (6.66%) | 5 (8.33%) | 8 (13.33%) | 17 (28.33%) | 30 (50%) | |
| II | 0 | 0 | 0 | 0 | 6 (10%) | |
| III | 0 | 0 | 0 | 0 | 0 | |
| IV | 0 | 0 | 0 | 0 | 0 | |
| V | 0 | 0 | 0 | 0 | 0 | |
| Rose bengal | 0 | 48 (80%) | 46 (76.66%) | 41 (68.88%) | 37 (61.66%) | 14 (23.33%) |
| I | 12 (20%) | 14 (23.33%) | 19 (31.66%) | 21 (35%) | 35 (58.33%) | |
| II | 0 | 0 | 0 | 2 (3.33%) | 11 (18.33%) | |
| III | 0 | 0 | 0 | 0 | 0 | |
| IV | 0 | 0 | 0 | 0 | 0 | |
| V | 0 | 0 | 0 | 0 | 0 | |
|
| ||||||
| GROUP II (n=60) | ||||||
|
| ||||||
| Lissamine green | 0 | 21 (35%) | 14 (23.33%) | 5 (8.33%) | 0 | 0 |
| I | 35 (58.88%) | 41 (68.33%) | 36 (60%) | 13 (21.67%) | 0 | |
| II | 4 (6.67%) | 5 (8.33%) | 17 (28.33%) | 35 (58.33%) | 30 (50%) | |
| III | 0 | 0 | 2 (3.33%) | 12 (20%) | 27 (45%) | |
| IV | 0 | 0 | 0 | 0 | 7 (11.67%) | |
| V | 0 | 0 | 0 | 0 | 0 | |
| Rose bengal | 0 | 13 (21.67%) | 3 (5%) | 1 (1.67%) | 2 (3.33%) | 0 |
| I | 37 (61.67%) | 41 (68.33%) | 28 (46.67%) | 35 (58.33%) | 0 | |
| II | 10 (16.67%) | 16 (26.67%) | 26 (43.333%) | 23 (38.33%) | 14 (23.33%) | |
| III | 0 | 0 | 5 | 0 | 35 (58.33%) | |
| IV | 0 | 0 | 0 | 0 | 11 (18.33%) | |
| V | 0 | 0 | 0 | 0 | 0 | |
In group I, the mean values of Schirmer’s test and TBUT decreased significantly (P < 0.0001) at each follow-up visit from baseline. The mean OSDI score increased significantly at 6 months (P = 0.006) and 12 months (P = 0.0009) follow-up visits when compared to baseline mean values. In group I, the mean values of TMH decreased significantly at 6 months (P = 0.0001) and 12 months (P < 0.0001) follow-up visit as compared to baseline values. The mean values of TMD decreased significantly at 3 months (P = 0.0079), at 6 months (P < 0.0001), and at 12 months (P < 0.0001) follow-up from baseline [Table 4].
Table 4.
Changes in ocular surface parameters in Group I and Group II on follow-up
| GROUP I (n=60) | ||||||
|---|---|---|---|---|---|---|
| Parameters | Baseline | 1 month | 3 months | 6 months | 12 months | p-value |
| OSDI score | 34.25±9.02 | 35.23±8.55 | 36.81±9.08 | 38.60±7.98 | 39.46±7.64 | 0.0009 |
| Schirmer’s test-(mm) | 20.20±3.02 | 18.77±2.48 | 17.23±2.37 | 15.73±1.84 | 14.25±1.89 | <0.0001 |
| TBUT-(seconds) | 12.10±2.31 | 10.92±1.90 | 9.97±2.11 | 8.55±1.56 | 7.72±1.29 | <0.0001 |
| TMH-(microns) | 253.68±8.87 | 253.22±9.12 | 250.82±9.06 | 247.03±8.97 | 243.52±8.96 | < 0.0001 |
| TMD-(microns) | 154.05±5.85 | 153.33±5.84 | 151.13±5.99 | 148.02±6.14 | 144.53±6.33 | < 0.0001 |
| TMA-(mm2) | 0.025±0.029 | 0.019±0.001 | 0.018±0.001 | 0.018±0.001 | 0.017±0.001 | 0.0348 |
|
| ||||||
| GROUP II (n=60) | ||||||
|
| ||||||
| OSDI score | 35.17±5.98 | 37.79±6.11 | 40.64±5.53 | 44.37±5.32 | 48.56±5.81 | <0.0001 |
| Schirmer’s test-(mm) | 13.91±3.03 | 12.98±2.90 | 11.68±2.46 | 10.21±2.49 | 8.81±2.15 | <0.0001 |
| TBUT-(seconds) | 8.5±1.72 | 7.31±1.65 | 6.43±1.38 | 5.5±1.11 | 4.46±1.08 | <0.0001 |
| TMH-(microns) | 248.93±6.95 | 246.65±7.18 | 243.35±7.27 | 239.71±7.68 | 236.13±7.45 | <0.0001 |
| TMD-(microns) | 149.9±6.30 | 147.68±6.35 | 144.31±6.26 | 140.93±6.13 | 137.46±6.55 | <0.0001 |
| TMA-(mm2) | 0.018±0.001 | 0.018±0.001 | 0.017±0.001 | 0.016±0.001 | 0.016±0.001 | <0.0001 |
OSDI: Ocular surface disease index, TBUT: Tear break-up time, TMH: tear meniscus height, TMD: tear meniscus depth, TMA: tear meniscus area
In group II, mean values of Schirmer’s test and TBUT significantly decreased (P < 0.0001) and the mean value of OSDI score significantly increased on follow-up when compared to baseline mean values. No significant difference was seen in corneal sensitivity on follow-up as compared to baseline. The mean values of TMH, TMD, and TMA significantly decreased on follow-up visits as compared to baseline values [Table 4].
On comparing the ocular surface parameters between Group I and Group II on follow-up, a significant difference was found in the change in values of Schirmer’s and TBUT, along with AS-OCT parameters of TMH and TMD at 6 months and 12 months follow-up visits [Table 5].
Table 5.
Comparison of ocular surface parameters at 6 months and 12 months follow-up between the two groups
| Ocular surface parameters | Group I (n=60) | Group II (n=60) | P |
|---|---|---|---|
| 6 months follow-up | |||
| Schirmer’s Test-(mm) | 15.7±1.84 | 10.22±2.5 | <0.0001 |
| TBUT-(seconds) | 8.55±1.56 | 5.5±1.11 | <0.0001 |
| OSDI Questionnaire score | 38.6±7.98 | 44.3795±5.32 | <0.0001 |
| TMH-(microns) | 247.03±8.97 | 239.71±7.68 | <0.0001 |
| TMD-(microns) | 148.02±6.14 | 140.93±6.13 | <0.0001 |
| TMA-(mm2) | 0.018±0.001 | 0.016±0.001 | 0.265 |
| 12 months follow-up | |||
| Schirmer’s Test-(mm) | 14.25±1.89 | 8.82±2.15 | <0.0001 |
| TBUT-(seconds) | 7.72±1.29 | 4.47±1.081 | <0.0001 |
| OSDI Questionnaire score | 39.46±7.6 | 48.57±5.8 | <0.0001 |
| TMH-(microns) | 243.52±8.96 | 236.13±7.45 | <0.0001 |
| TMD-(microns) | 144.53±6.33 | 137.46±6.55 | <0.0001 |
| TMA-(mm2) | 0.017±0.001 | 0.016±0.001 | 0.377 |
OSDI: Ocular surface disease index, TBUT: Tear break-up time, TMH: tear meniscus height, TMD: tear meniscus depth, TMA: tear meniscus area
Discussion
Dry eye is one of the major complications of AGMs which has a negative impact on the management of glaucoma patients. Many studies previously had established the role of topical AMGs in the effective management of POAG.[5,6] Anti-glaucoma medical treatment is a lifelong therapy; hence, it exposes the ocular surface to the harmful effects of topical IOP-lowering medications. In our study, we enrolled 120 eyes of 60 POAG patients, out of which 60 eyes were treatment-naïve while 60 were on topical AGM. We assessed the difference in various ocular surface parameters between the two study groups.
In our study, the value of the Schirmer test was significantly lower in group 2 as compared to group 1 at baseline (P < 0.001). At 1 year follow-up, Schirmer’s test values deteriorated significantly in both the groups (P < 0.0001). This was in concordance with the study done by Kamath et al.[14] In group II, eyes on ≥3 topical AMG per day at baseline had significantly lower Schirmer’s test values (P < 0.0001) as compared to eyes on <3 AMG per day. This was in contrast to a study done by Ramli et al. in which no increase in Schirmer test value was seen as the number of eye drops increased.[15] In group II, Schirmer test values did not show any significant difference depending upon the duration of treatment. This is contradictory to a study done by Pai et al., who found lower Schirmer test values in eyes with the duration of treatment ≥5 years.[16]
We found significantly lower TBUT values in group II as compared to group I at baseline (P < 0.0001). Similar to Schirmer test values, the TBUT values also reduced significantly (P < 0.0001) at follow-up visits in both groups. TBUT values at baseline were poorer in eyes on ≥3 AMG per day and with duration of treatment ≥3 years. This was in correspondence with the few studies done earlier.[17] In the study done by Pérez-Bartolomé et al., no significant difference was noted in NI-TBUT between the AGM group and controls.[18]
The difference in OSDI score was not statistically significant between the two groups in our study at baseline. A significant difference was observed between the two groups on follow-up (P < 0.001). Similarly, Went et al. and Cvenkel et al. also found no significant difference in OSDI scores between treated and untreated glaucoma patients.[17,19] This could be due to the fact that in our study region, factors like high temperature and windy climate were more prevalent, which can lead to higher OSDI scores in both groups. We excluded symptomatic dry eye patients, or patients already on treatment for dry eye, except for age and gender matching. The older age of the patients themselves might be contributory for higher scores. OSDI score significantly increased at 1-year follow-up in both groups. A study done by Pérez et al. found lower OSDI scores with the use of preservative-free eye drops. Studies done by Ramli et al. and Lajmi et al. found that Banzalkonium Chloride (BAK) was the major factor associated with higher OSDI scores.[15,18,20] Ramli et al. found a significantly higher OSDI score in the glaucoma group as compared to controls along with rates of abnormal OSDI nearly three times more in subjects who were on BAK containing anti-glaucoma drops but they found no correlation in increased differences in OSDI results and the number of eye drops.[15]
The difference in corneal sensations at baseline between the groups did not show any statistically significant difference (P = 1.00). Also, on 1-year follow-up, corneal sensations showed no significant reduction in both groups. This was in contrast to the study done by Went et al. who found lower corneal sensitivity in patients on preserved AGMs as compared to untreated patients.[19] A possible explanation for this could be the qualitative nature of the method we used to assess corneal sensitivity.
In our study, we found a significantly higher (P < 0.0001) mean values of TMH and TMD in group I as compared to group II at baseline. At 1 year follow-up, in group I, the mean values of THM and TMD reduced significantly (P < 0.05) as compared to baseline values. In group II, at 1-year follow-up, the mean values of TMH, TMD, and TMA reduced significantly (P = 0.0001) when compared to baseline. Wong et al. measured TMH by taking three measurements near the center of the lower meniscus with pre-calibrated digital imaging and then averaging them and found that TMH was significantly poorer in treated eyes as compared to fellow eye (P = 0.03) but the long-term effects on tear meniscus were not assessed by them since that was a cross-sectional study.[20] A study done by Agnifili et al. compared tear meniscus parameters in medically controlled glaucoma patients, patients with evaporative dry eye, and healthy controls, and found similar results as our study.[13]
Grades of ocular surface staining by both lissamine green and rose bengal stains were significantly (P < 0.0001) lower in group I as compared to group II. At 1 year follow-up, grades of both lissamine green and rose bengal ocular surface staining increased in both groups. Studies done by Pérez et al. and Ramli et al. also found similar results as our study but they used fluorescein dye to stain the ocular surface.[15,18] In our study, we used lissamine green and rose bengal stains because these dyes are poorly seen within the tear film; hence, do not obscure the staining pattern. Also, because they do not diffuse into the substantia propria of the conjunctiva, the staining pattern is retained for a longer duration at high contrast. Lajmi et al.[20] used fluorescein and lissamine green dyes and found that a statistically lower incidence of superficial punctate keratitis (SPK) and corneal and conjunctival staining in the lissamine green test (P < 0.001) was associated with a fixed combination of anti-glaucoma eye drops.[13]
In our study, on comparing both the groups on follow-up, OSDI scores were significantly lower in group I in comparison to group II, whereas, TBUT, Schirmer’s test, TMH, and TMD were significantly higher in group I in comparison to group II. This could be due to the initiation of preservative-/BAK-free medications in group I patients. The shorter duration of treatment in group I patients is also contributing to this variation. Although only eight patients were started on a single medication in group I as most of the patients were having moderate to severe glaucoma.
Conclusion
The study has identified glaucoma patients on AGMs to be more affected by DED compared to treatment-naive glaucoma patients. We found statistically significant differences in values of TBUT, Schirmer tests, Lissamine and rose bengal staining, and AS-OCT parameters at baseline and 3, 6, and 12 months follow-up. OSDI scores showed significant differences at 6 and 12 months of follow-up. We recommend consideration of evaluation and management of DED/ocular surface disease in glaucoma patients on topical AGMs, particularly multiple drugs and doses.
Financial support and sponsorship:
Nil.
Conflicts of interest:
There are no conflicts of interest.
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