Sudanese Journal of Ophthalmology

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 11  |  Issue : 1  |  Page : 14--18

Dry eye disease and tear dysfunction in patients with type 2 diabetes: A hospital-based study from South India


K Divya, N Dhivya, M Raaja Ganesh, D Sundar 
 Department of Ophthalmology, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India

Correspondence Address:
Dr K Divya
Associate Professor, Department of Ophthalmology, PSG Institute of Medical Sciences and Research, Coimbatore - 641 004, Tamil Nadu
India

Abstract

Purpose: Diabetics are more prone to dry eye disease (DED) and tear film dysfunction. The aim of this study was to assess the frequency of DED and tear film abnormalities in patients with type 2 diabetes compared to healthy controls. Materials and Methods: This was a hospital-based prospective case-control study. One hundred patients with type 2 diabetes and 100 healthy controls were enrolled by consecutive sampling. All study participants completed the Ocular Surface Disease Index (OSDI) questionnaire to score dry eye symptoms. Tear film breakup time (TFBUT), ocular surface staining with fluorescein and Schirmer's test were performed, and results were analyzed. Student's t-test was applied for comparisons between groups. Correlation between variables was detected using Pearson's correlation coefficient. Statistical significance was set at P < 0.05. Results: Dry eye was encountered in 54 among the 100 diabetic patients studied. Age and sex of diabetic patients were not found to affect the dry eye status. Longer duration of diabetes was significantly associated with DED (P = 0.03). Significant differences in OSDI scores, TFBUT, fluorescein staining, and Schirmer's test values were observed between the study groups (P < 0.001). An increased level of glycosylated hemoglobin was significantly associated with abnormal tear function tests. Conclusion: Patients with longer duration of diabetes and poor glycemic control are more predisposed to have abnormalities of the tear film and DED. Apart from conventional therapies, optimal glycemic control should be an important consideration in the management of tear dysfunction in diabetic patients.



How to cite this article:
Divya K, Dhivya N, Ganesh M R, Sundar D. Dry eye disease and tear dysfunction in patients with type 2 diabetes: A hospital-based study from South India.Sudanese J Ophthalmol 2019;11:14-18


How to cite this URL:
Divya K, Dhivya N, Ganesh M R, Sundar D. Dry eye disease and tear dysfunction in patients with type 2 diabetes: A hospital-based study from South India. Sudanese J Ophthalmol [serial online] 2019 [cited 2019 Dec 8 ];11:14-18
Available from: http://www.sjopthal.net/text.asp?2019/11/1/14/268794


Full Text



 Introduction



The prevalence of diabetes mellitus (DM) has increased significantly in the past several decades and the disease continues to remain a global epidemic. Estimates suggest that 439 million people in the world are likely to have DM by 2030 and this increase in number of diabetics is predicted to be disproportionately more in developing countries.[1] The two major potentially blinding complications of diabetes, namely cataract and retinopathy, have been extensively researched in literature. Apart from these, people with diabetes are also prone for ocular surface disease that includes dry eye, persistent epithelial defects, decreased corneal sensation, and tear film dysfunction. Studies have shown an intimate, complex relationship between diabetes, dry eye, and ocular surface abnormalities.[2],[3]

The reported prevalence rates of dry eye in diabetics have been found to vary widely between 27% and 54%.[4],[5] A recent study from a cornea specialty clinic found the overall presence and the severity of dry eye to be similar in the diabetic and nondiabetic groups. However, significant differences were observed between groups with regard to individual diagnostic assessments.[6] Studies on changes in tear function parameters in diabetes have also shown conflicting results.[7],[8] These can be attributed to major differences in the study characteristics of the population, methodologies, and wide array of diagnostic methods used for assessment. Limited data exist on the occurrence of dry eye and ocular surface disease among diabetics in the Indian population.[9]

This prospective study from India sought to study the frequency of dry eye disease (DED) and tear film changes in patients with type 2 diabetes compared to healthy controls.

 Materials and Methods



This was a hospital-based cross-sectional study which included 100 patients with type 2 DM. Consecutive patients attending the Ophthalmology Department of a tertiary care center in South India between June 2016 and 2017 were invited to participate. Exclusion criteria included the history of smoking, contact lens wear, past ocular surgery, intake of systemic medications such as antihistamines, tricyclic antidepressants, and other drugs known to cause dry eye. Patients with known ocular or systemic disease that might affect the ocular surface were also excluded from the study. One hundred individuals matched by age were enrolled as a control group. The controls were recruited from individuals attending the department of ophthalmology for routine eye examination and did not have any ocular or systemic disease other than refractive errors. The study protocol was approved by the Institutional Ethics Committee, and the study was conducted according to the principles of the Declaration of Helsinki. Informed consent was obtained from all participants.

For each participant, a detailed ocular and general medical history, including duration of diabetes, medications, and glycosylated hemoglobin (HbA1c) value within the past 3 months was obtained. All study participants completed the Ocular Surface Disease Index (OSDI; Allergan, Inc., Irvine, CA, USA) questionnaire to score dry eye symptoms. The OSDI consists of 12 questions based on symptoms within the past 1 week. The frequency of ocular subjective symptoms (soreness, blurred vision), difficulty with vision-related function (television, visual display unit, driving, and reading) and discomfort due to environmental triggers (low humidity, high wind) are assessed on a Likert scale. The scores range from 0 (least severe) to 100 (most severe).[10]

All participants underwent a general physical and comprehensive ophthalmic examination with slit lamp, including best-corrected visual acuity. Evaluation of the ocular surface and tear film was done by performing the following tests described below in a sequential manner.[11]

Tear film breakup time (TFBUT) was performed by applying a fluorescein strip (Fluostrip/India/Contacareophthalmics and diagnostics) moistening it with a drop of sterile saline, to the lower tarsal conjunctiva without the use of topical anesthesia. The participants were asked to blink several times and then cease blinking until instructed. The tear film was observed under slit lamp with cobalt blue filter. The time interval between the last blink to the appearance of the first random dry spot in the cornea was taken as the TFBUT. The average of three consecutive breakup times was calculated and recorded.

The ocular surface was evaluated by staining the cornea with fluorescein and Oxford grading scheme was used for the recording of staining severity. This scheme has five panels, labeled A to E, with staining represented by punctate dots that increase logarithmically between panels.[12] The appearance of staining on the exposed interpalpebral conjunctiva and cornea is compared with each panel, and the closest match gives the grade. Based on the number of dots seen a grade between 0 and 3 was given for staining on the cornea, nasal, and temporal conjunctiva. The individual scores were added giving a maximum possible total of 9 points. A score of 3 and above was considered to be abnormal.[13]

Schirmer's test was performed without topical anesthesia using standardized Whatman filter paper 41(Tearstrip/India/Contacareophthalmics and diagnostics). The strip was folded at the notch and placed at the junction of the middle and lateral thirds of the lower eyelids and left in place for 5 min. A value of <10 mm wetting in 5 min was considered abnormal.

Due to lack of consensus among the diagnostic criteria for dry eye described in different clinical studies we adopted the following criteria used by Alves et al.: OSDI score >20 and/or Schirmer test <10 mm or TFBUT <6 s and/or ocular surface staining score >3.[14] A diagnosis of DED was made if the participant had at least one positive test according to these criteria. In various clinical studies, authors have adopted different approaches for the diagnosis of dry eye on an ad hoc basis. Several studies have used the positivity of one or more of the tests (tear breakup time [TBUT] or Schirmer or OSDI) for the diagnosis of dry eye.[5],[15],[16] Since there is no uniform set of diagnostic criteria for DED, we considered a diagnosis of dry eye if the patient presented at least one positive test according to these preestablished criteria.

All measurements were performed by the same investigators on the same day under similar testing conditions. Clinical evaluations were done on both eyes, and the mean of the two eyes was used for analysis. To eliminate diurnal variation and possible diagnostic error, all tests were performed in the morning.

Statistical analysis

Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA) version 24. Descriptive statistics was presented as a mean ± standard deviation. The Shapiro–Wilk test was used to test the normality of data distribution. Student's t- test was applied for comparisons between two groups. Correlation between variables was detected using Pearson's correlation coefficient. Statistical significance was set at P < 0.05.

 Results



The mean age of controls and diabetic patients was 54.7 ± 10.2 and 55.7 ± 9.5 years, respectively. There were 53 females among 100 controls and 45 females among 100 diabetics (P = 0.25). The baseline characteristics of the study participants are shown in [Table 1]. The mean duration of diabetes among diabetics with the dry eye was significantly higher compared to those without dry eye (P = 0.03).{Table 1}

[Table 2] shows the comparison of OSDI, Schirmer test, fluorescein staining, and TFBUT between groups using the Student's t- test. Significant differences in OSDI scores, Schirmer test values, fluorescein staining, and TFBUT were observed between the study groups. OSDI Score was >20 in 32 participants (32%) in the diabetic group. Nineteen percent had OSDI scores between 12 and 20. In the diabetic group, 7 participants (7%) had Schirmer scores <10 mm and 30 (30%) had TBUT <10 s. Ocular surface staining score of >3 was encountered in 51% of the diabetic participants. None of the participants in the control group had abnormal OSDI, Schirmer test, fluorescein staining, or TFBUT.{Table 2}

We evaluated the relationship between HbA1c, duration of diabetes, and ocular surface parameters [Table 3]. The analysis showed significant positive correlation between the duration of diabetes and OSDI scores as well as fluorescein staining of the ocular surface. Although negative, the correlation between duration of diabetes and Schirmer/TFBUT was not statistically significant.{Table 3}

The HbA1c level was found to correlate positively with OSDI scores and ocular surface staining. HbA1c levels correlated negatively with Schirmer values and TFBUT.

 Discussion



The purpose of this clinical study was to assess the frequency of DED and tear film abnormalities in people with diabetes and compare with that of healthy controls. The OSDI scores were higher, and tear film parameters were significantly altered in diabetic patients.

Out of the 100 diabetics studied, 54 were found to have dry eye. Mean age of diabetic individuals with and without dry eye were found to be similar (P = 0.262). Among the 100 patients with diabetes 45 (45%) were females, of which 23 (42.6%) had dry eye and 22 (47.8%) did not have evidence of dry eye (P = 0.600). Hence, there was no statistically significant association between dry eye and age or gender of the diabetic patients. The frequency of dry eye was significantly higher in patients with longer duration of diabetes.

Studies on dry eye in diabetics have revealed wide variation in the prevalence rates due to different diagnostic criteria as well as patient characteristics. Our observations are similar to that of Fuerst et al. who have noted a dry eye prevalence of 54% based on tear osmolarity.[16] Manaviat et al. performed Schirmer and TBUT tests and utilized the criterion of one positive test to diagnose dry eye. Out of the 199 participants studied, 108 (54.3%) were found to have dry eye.[5]

In contrast to these hospital-based studies, a community-based study from Shanghai has reported 17.5% prevalence of definitive DED.[17] Apart from methods used for diagnosis, several other factors such as age, gender, duration of diabetes, and metabolic control have also been reported to affect the prevalence of DED.[18],[19]

Duration of diabetes was found to be significantly associated with dry eye in our study similar to observations of Manaviat et al.[5] Chronic hyperglycemia, diabetic neuropathy, decreased insulin levels, microvasculopathy, and systemic hyperosmotic disturbances in long-standing diabetes lead to dysfunction of the lacrimal functional unit as well as abnormal tear dynamics and DED.[20] However, some studies have found no correlation between DED and duration of diabetes.[4]

Diabetics in this study had significantly higher OSDI scores as compared to the control group. In contrast to our observations, Beckman found the mean OSDI scores to be higher in nondiabetic patients as compared to diabetic patients.[6] This could be attributed to the fact that the mean duration of diabetes in this study was much less (6.9 ± 5.7 years) compared to their study where the mean diabetic duration was 11.1 ± 9 years (range 1–41 years). Long-standing diabetes has been reported to be associated with reduced perception of dry eye symptoms due to impaired corneal sensation and therefore decreased OSDI scores.[16]

We found a significant positive correlation between OSDI scores and duration of diabetes in our study. One possibility for the observed positive correlation is that, as mentioned previously participants with shorter duration of diabetes have normal corneal sensation and therefore, will be aware of dry eye symptoms. Our findings are in agreement with the natural history of DED proposed by Bron et al. This model comprises three stages, namely initiation of DED, reflex compensation, and loss of compensatory response due to sensory nerve impairment.[21]

OSDI scores were found to correlate positively with HbA1c levels in our study. Our observations are in line with previous studies elsewhere, which have shown a positive correlation between OSDI scores and glycemic control.[22],[23]

Although mean Schirmer test scores were in the normal range for both study groups, statistically significant differences were found between the Schirmer values in control and diabetic groups. Our observations are similar to that of Beckman and Yoon et al. who found the values of the Schirmer's test to be >10 mm in both diabetic and nondiabetic patients.[6],[24] In contrast to these findings, the Schirmer values averaged 7.4 ± 0.38 mm in patients with diabetes versus 13.53 ± 0.50 mm in the controls in a series by Dogru et al.[7] Twenty eyes (22.7%) of the diabetic patients in their series had Schirmer test values <5 mm. In our study, only 3% had Schirmer scores <5 mm. Reduced Schirmer scores in people with diabetes compared with nondiabetic participants have been documented in several studies. Some studies have noted a reduction in basal tear secretion, whereas some authors have reported only the reflex tear secretion to be significantly reduced in diabetics.[8],[19],[25]

We found a significant negative correlation between Schirmer test scores and HbA1c levels. Our observations are in line with that of Ozdemir et al. who also found the Schirmer test and TBUT results to be worse in poorly controlled diabetics compared to those with good metabolic control. Kaiserman et al. have reported increasing consumption of ocular lubrication with increased mean annual levels of HbA1c.[18] Poor Schirmer test scores were not related to the duration of diabetes in our study which is in agreement with previous studies.[19]

Significant staining of the ocular surface with fluorescein was noted in diabetic patients in our study. Impaired corneal epithelial barrier function in diabetic patients has been reported by several studies and poor metabolic control, diabetic neuropathy, and advanced retinopathy have been found to correlate with epitheliopathy.[3],[24] Ocular surface staining scores were found to correlate positively with duration of diabetes as well as HbA1c levels in this study. Accumulation of advanced glycation end products (AGE) on the basement membrane of the corneal epithelium has been shown to play a causative role in corneal epithelial disorders of diabetic patients.[26] Since HbA1c is a product of early stage glycation, it correlates well with AGE formation and hence impaired barrier function resulting in staining of the ocular surface.

Significant differences in TFBUT values were noted between diabetic and nondiabetic participants, and lower TFBUT scores were noted in patients with poor glycemic control. These results are comparable to that of Yoon et al. who had evaluated the tear film and ocular surface changes among diabetics from Korea.[24] Ma et al. have reported a significant inverse correlation between serum HbA1c levels and noninvasive TBUT in their study on 80 Chinese participants with type 2 diabetes.[23] These results suggest that poor glycemic control is associated with an unstable tearfilm and ocular surface disease in diabetic patients.

The study has few limitations. We had not performed tear film osmolarity assessment which is an objective test for the diagnosis and follow-up of DED. However, test combination of OSDI/Schirmer test/TFBUT has been shown to have an accuracy of 99.3% for the diagnosis of DED.[14] Sample size and conduct of the study at a single site are other potential limitations of the study. Further studies on large samples with the inclusion of tests such as corneal esthesiometry, tear osmolarity, and other markers of DED will provide valuable insight into the potential mechanisms and treatment options for diabetic DED.

 Conclusion



There are limited data available in the literature about the frequency of dry eye and tear film dysfunction in diabetics from India. With the increasing prevalence of diabetes and its associated complications in India, there is need for more studies from this part of the world. Nearly half of the people with diabetes in this study had features consistent with DED. Patients with longer duration of diabetes and higher HbA1c levels are more predisposed to have abnormalities of tear film and DED. Examination of the ocular surface and testing for DED should be added to the routine screening of diabetes. Apart from conventional therapies such as lubricants, anti-inflammatory agents, and antioxidants optimal glycemic control should be an important consideration in the management of tear dysfunction in diabetic patients.

Acknowledgment

The authors are grateful and would like to acknowledge Dr. Suvetha.K, FAIMER fellow and Associate professor in community medicine, PSG Institute of Medical Sciences and Research, for statistical analysis and guidance in interpretation of results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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