Abstract
Purpose:
The study was conducted to evaluate occurrence of dry eye disease (DED) in type 2 diabetes mellitus (DM) and its association with diabetic retinopathy (DR) in the affected patients in western India.
Methods:
One hundred and five type 2 diabetic patients referred to a tertiary eye care center were consecutively selected. A detailed systemic history was evaluated. DED was assessed by Ocular Surface Disease Index questionnaire, Schirmer’s test, tear breakup time (TBUT), and fluorescein staining of cornea and conjunctiva, graded according to the National Eye Institute workshop grading. All patients underwent detailed fundus evaluation and DR, if present, was graded according to Early Treatment Diabetic Retinopathy (ETDRS) criteria.
Results:
Prevalence of DED in type 2 diabetics was 43.81% (92/210 eyes). The prevalence and severity of DED was found to be more in patients having higher glycosylated hemoglobin levels (P < 0.0001). Prevalence of DED was found to be high in those not taking any treatment (P < 0.0001). A statistically significant association was found between duration of DM and presence of DED (P = 0.02). Among the patients with DED, a majority had proliferative diabetic retinopathy (PDR; 57/92 eyes, 61.96%).
Conclusion:
The study highlights a significant correlation between DED and DM, and hence, examination for DED with fundus examination should be an integral part of the assessment of type 2 diabetics.
Keywords: Diabetic retinopathy, dry eye, type 2 diabetes
Diabetes mellitus (DM) is one of the leading causes of global morbidity and mortality. In India, the burden of DM is increasing steadily, with its prevalence increasing from 7.1% in 2009 to 8.9% in 2019.[1] Currently, 25.2 million adults are estimated to have impaired glucose tolerance, which is estimated to increase to 35.7 million in the year 2045.[1] Apart from the systemic impact of DM, it causes a spectrum of ocular manifestations like diabetic retinopathy (DR), diabetic papillopathy, glaucoma, cataract, and ocular surface diseases.[2] Diabetics are more prone to suffer from dry eye disease (DED) due to peripheral neuropathy, lacrimal gland dysfunction, inflammatory alterations and systemic hyperosmotic disturbances, secondary to hyperglycemia.[3] DED can cause ocular discomfort, blurred vision, and, in severe cases, blindness. It can also interfere with the quality of life (QOL) of the patient, including physical, social, and psychological functioning, with a negative impact on daily activities and workplace productivity.[4,5] However, a timely diagnosis and early management can avoid these complications and prevent blindness. Hence, this study was undertaken to study the occurrence of DED in type 2 diabetic patients and its association with DR.
Methods
In this cross-sectional, prospective, observational study, 105 patients with type 2 DM, including new and follow-up cases referred to a tertiary eye care center of western India, were consecutively selected. Type 2 DM was diagnosed according to the American Diabetes Association (ADA) criteria [Table 1].[6] The study was approved by the institutional ethics committee and was carried out in accordance with the Declaration of Helsinki. An informed consent for participation in the study was taken from all the patients. Patients with active ocular infection, ocular allergies, lid abnormalities like entropion, ectropion, and lagophthalmos, Sjogren’s syndrome, history of ocular trauma of any kind including chemical injury and ocular surgery within last 2 years, history of refractive surgery, contact lens users, and patients using ocular medications within last 3 months were excluded. Patients with secondary diabetes and a history of smoking, patients on medications like beta blockers, diuretics, antihistaminics, anticholinergics, tricyclic anti-depressants, oral contraceptive pills or steroids and patients with systemic/ auto-immune diseases like rheumatoid arthritis, lupus, Grave’s disease and Parkinsonism, which can affect the tear production were also excluded.
Table 1.
American Diabetes Association criteria for diagnosis of diabetes mellitus
| Parameters | Normal glucose tolerance | Pre-diabetes | Diabetes mellitus |
|---|---|---|---|
| FPG | <100 mg/dl | 100-125 mg/dl | ≥126 mg/dl |
| HbA1c | <5.6% | 5.7%-6.4% | ≥6.5% |
| 2 h PG | <140 mg/dl | 140-199 mg/dl | ≥200 mg/dl |
2 h PG=2-h plasma glucose/postprandial bood glucose, FPG=Fasting plasma glucose, HbA1c=Glycosylated hemoglobin
Sociodemographic data like age and gender, followed by a detailed history regarding diabetes – duration, type of treatment, overall control of diabetes (based on fasting and postprandial sugar levels and glycosylated hemoglobin [HbA1c] values) – were recorded. History of presence of any other associated systemic disease was obtained by direct patient interview and review of the available medical records.
A validated Ocular Surface Disease Index (OSDI) questionnaire of ocular symptoms related to dry eyes was used and a symptom score was calculated. The OSDI questionnaire is designed to assess the patient’s symptoms and the impact of these symptoms on the daily life of the patient. The overall OSDI score defined the ocular surface as normal (0–12 points) or as having mild (13–22 points), moderate (23–32 points), and severe (33–100 points) disease.[7] The unaided, aided, and pinhole visual acuity using Snellens’s test type was noted. A detailed anterior segment slit-lamp examination was done and the following parameters were recorded: tear meniscus height (TMH), Schirmer’s test 1, tear film breakup time (TBUT), and fluorescein staining of cornea and conjunctiva graded according to the National Eye Institute (NEI) workshop grading.[8] A TMH value, assessed on slit lamp, less than 0.25 mm is suggestive of DED.[8]
To perform the Schirmer’s test, a strip of commercially available pre-sterilized Whatman filter paper no. 41, measuring 5 × 35 mm, was inserted into the lower fornix at the junction of middle and lateral third of the lid margin. The amount of wetting of the paper was recorded in millimeters at the end of 5 min. Any value <10 mm was considered as an indicator of dry eye.[8]
TBUT is defined as the time, in seconds, between the last blink and the appearance of the first random dry spot on the cornea. The lower fornix was stained using a pre-sterilized 2% fluorescein strip. The patient looked straight without blinking while seated on a slit lamp and was observed using a broad beam of cobalt blue light; the time taken for the appearance of first random dark spot was noted. TBUT <10 s was considered as abnormal.[8]
Fluorescein staining of the cornea for NEI workshop grading was done with a pre-sterilized strip of 2% fluorescein inserted in the lower fornix of each eye. After several blinks, ensuring even spread of the stain, the staining pattern was observed under cobalt blue light of the slit lamp. Both corneal and interpalpebral conjunctival staining patterns were recorded and graded according to the NEI workshop grading. The NEI grading scale consists of a grid that divides the corneal area into five sections, each of which is assigned a score between zero and 3 depending on the amount and distribution of the corneal fluorescein staining. The total corneal staining score ranges from 0/15 (absence of corneal epitheliopathy) to 15/15 (severe epitheliopathy).[9]
Patient’s upper and lower lid margins were examined under slit lamp for eyelashes, lid thickening, punctum, and meibomian gland orifices, and meibomian gland dysfunction (MGD) was graded from Grade 0 to Grade 3 as follows: Grade 0- no obstruction, Grade 1- orifices plugged with serous secretion, Grade 2- orifices plugged with toothpaste-like secretions, and Grade 3- blocked glands with no secretion on pressing.[10]
Diagnosis of DED was established by an OSDI score ≥13 with one or more positive clinical findings as follows:
TBUT <10 s or
Ocular surface staining score ≥3 or
Schirmer’s test score ≤10 mm
NEI workshop Grade ≥2
MGD- Grade 2 or 3
A detailed retinal examination was done with an indirect ophthalmoscope and slit-lamp biomicroscopy using 78 D lens after pupillary dilation with 0.5% tropicamide eye drop, and DR, if present, was noted. DR was graded according to Early Treatment Diabetic Retinopathy (ETDRS) classification.[11]
The primary outcome measures included finding
The prevalence of DED in patients with type 2 DM and
The association of DED and DR.
The secondary outcome measures included finding the association between
The duration of DM and DED,
Overall glycemic control (HBA1c level) of the patients and occurrence of DED,
Meibomian gland disease and DED, and
Control of DM and occurrence of DR.
Statistical analysis
The data entry was done in the Microsoft office Excel spreadsheet and subjected to statistical analysis using Statistical Package for the Social Sciences (SPSS) version software version 21 (SPSS Inc., Chicago, IL, USA). Data were analyzed using standard statistical techniques such as tabulation, proportions, percentage, mean, and standard deviation. Categorical variables were analyzed between groups using Chi-square test. P < 0.05 was considered to be statistically significant.
Results
In this study, 210 eyes of 105 patients were assessed; 68/105 (64.76%) patients were males and 37/105 (35.24%) were females. The mean age of the participants was 57.89 ± 9.08 years. Best corrected visual acuity of the study population ranged from perception of light (PL) only to 6/6. The mean duration of DM was 6.24 ± 5.79 years. Of the105 patients with DM, 51 were on oral hypoglycemics (OHA), 27 were on insulin, and the remaining 27 were not on any treatment. The overall glycemic control indicated by mean HbA1c was 7.63 ± 1.77. The mean OSDI score was 18.34 ± 11.34. Table 2 shows the mean values of the tests done for DED evaluation, that is, Schirmer’s, TMH, TBUT, and NEI grading, and their association with DED. DED was reported in 43.81% (92/210 eyes) of the participants. It was found to be more prevalent among 19/46 (41.3%) females than 27/46 (58.7%) males, which was not found to be statistically significant (P = 0.3049). Severity of dry eye was not found to be related to gender (P = 0.1744).
Table 2.
Parameters examined in dry eye
| Parameters | Mean value | Dry eye present | Dry eye absent |
|---|---|---|---|
| TMH (mm) | 0.27±0.11 | 0.16±0.06 | 0.35±0.06 |
| Schirmer’s test (s) | 14.1±8.95 | 5.34±3.06 | 18.45±5.03 |
| TBUT (s) | 9.32±4.71 | 4.71±2.75 | 12.92±1.99 |
| NEI workshop grading: Fluorescein staining (stage) corneal | Sub-variable 0 | 0 (0) | 90 (76.27) |
| 1 | 3 (3.26%) | 28 (23.73) | |
| 2 | 34 (36.96%) | 0 (0) | |
| 3 | 34 (36.96%) | 0 (0) | |
| 4 | 21 (22.83%) | 0 (0) | |
| Fluorescein staining (stage) conjunctival | 0 | 0 (0) | 114 (96.61) |
| 1 | 5 (5.43%) | 4 (3.39) | |
| 2 | 37 (40.22%) | 0 (0) | |
| 3 | 38 (41.30%) | 0 (0) | |
| 4 | 12 (13.04%) | 0 (0) |
NEI=National Eye Institute, TBUT=Tear film breakup time, TMH=Tear meniscus height in millimeters (mm)
Presence of DED was higher in the age group 51–60 years (18/46 patients, 39.13%). Severity of DED was not found to be related to age (P = 0.1744). The mean duration of diabetes in those having DED was 7.70 ± 6.33 years, whereas it was 5.10 ± 5.10 years in those not having DED, and the association between duration of DM and presence of DED was statistically significant (P = 0.02) [Fig. 1]. Among type 2 DM patients, prevalence of dry eye was found to be high in those not taking any treatment, followed by those taking insulin (P < 0.0001) [Table 3].
Figure 1.
Scatter plot showing the relation between duration of diabetes mellitus and DED. DED = dry eye disease
Table 3.
Prevalence of dry eye according to the type of treatment in type 2 diabetes mellitus
| Type of treatment | Dry eye present, n (%) | Dry eye absent, n (%) | P |
|---|---|---|---|
| OHA | 16 (31.38) | 35 (68.63) | <0.0001 |
| Insulin | 9 (33.34) | 18 (66.67) | |
| No treatment | 21 (77.78) | 6 (22.23) |
OHA=Oral hypoglycemics, n=Number of patients
Mean OSDI score was 28.91 ± 9.42 in those having dry eye, compared to 10.10 ± 2.03 in those not having dry eye (P < 0.0001). Uncontrolled DM indicated by the HbA1c level was found to have statistically significant association with the OSDI score (P < 0.0001) [Table 4]. Prevalence and severity of DED was found to be more in patients having higher levels of HbA1c levels, which was found to be statistically significant (P < 0.0001) [Table 4]. Of the total 105 patients, 55 (52.3%) had MGD. Of these 55 patients with MGD, 38 (82.61%) had DED (Grade 2/3) and this was found to be statistically significant (P < 0.0001).
Table 4.
Association of HbA1c levels with OSDI score and DED grade in type 2 DM patients
| OSDI score | Overall dry eye grade | Total | P | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||
| No DED | Mild | Moderate | Severe | Absent | Mild | Moderate | Severe | |||
| HbA1c | ||||||||||
| ≤7.0 | 84 | 10 | 4 | 0 | 84 | 10 | 4 | 0 | 98 | <0.0001 |
| 7.1-7.9 | 24 | 6 | 8 | 2 | 24 | 6 | 8 | 2 | 40 | |
| 8.1-8.9 | 8 | 4 | 6 | 0 | 8 | 4 | 6 | 0 | 18 | |
| ≥9.0 | 2 | 12 | 16 | 24 | 2 | 12 | 16 | 24 | 54 | |
| Total | 118 | 32 | 34 | 26 | 118 | 32 | 34 | 26 | 210 | |
DED=Dry eye disease, DM=Diabetes mellitus, HbA1c=Glycated hemoglobin, OSDI=Ocular Surface Disease Index
DR was found in 143/210 eyes (68.09%). DR was seen in 82/92 eyes with DED (89.13%). The presence of uncontrolled type 2 DM was found to be statistically significant with severity of DR (P < 0.0001) [Table 5]. Among those having DR, proliferative diabetic retinopathy (PDR) was noted in 69/210 eyes (32.86%) and this was found to be statistically significant (P < 0.0001) [Table 6]. Also, 57/69 eyes with PDR had associated DED. Severe DED was noted in a majority of eyes (n = 35, 61.4%), moderate DED in 15 eyes (26.3%), and mild DED in seven eyes (12.28%). Hence, DED was found to be more prevalent in patients having PDR (P < 0.0001).
Table 5.
Association between HbA1c levels and DR
| Fundus examination findings | P | |||||
|---|---|---|---|---|---|---|
|
| ||||||
| No DR | Mild NDPR | Moderate NDPR | Severe NDPR | PDR | ||
| HbA1c group | ||||||
| ≤7.0 | 57 | 23 | 7 | 4 | 7 | <0.0001 |
| 7.1-7.9 | 10 | 9 | 3 | 4 | 14 | |
| 8.1-8.9 | 0 | 0 | 6 | 5 | 7 | |
| ≥9.0 | 0 | 0 | 6 | 7 | 41 | |
| Total | 67 | 32 | 22 | 20 | 69 | |
DR=Diabetic retinopathy, HbA1c=Glycated hemoglobin, NPDR=Nonproliferative diabetic retinopathy, PDR=Proliferative diabetic retinopathy
Table 6.
Association between various grades of DR and DED
| Grading of DR | DED present, number of eyes (%) | DED absent, number of eyes (%) | P |
|---|---|---|---|
| DR absent | 10 (10.87) | 57 (48.31) | <0.0001 |
| Mild NPDR | 2 (2.18) | 30 (25.43) | |
| Moderate NPDR | 13 (14.14) | 9 (7.63) | |
| Severe NPDR | 10 (10.87) | 10 (8.48) | |
| PDR | 57 (61.96) | 12 (10.17) | |
| Total | 92/210 eyes (43.8) | 118/210 eyes (56.2) |
DED=Dry eye disease, DR=Diabetic retinopathy, HbA1c=Glycated hemoglobin, NPDR=Nonproliferative diabetic retinopathy, PDR=Proliferative diabetic retinopathy
Discussion
Patients with diabetes are known to have an increased prevalence of DED. Although the association of DED and DM has been previously reported, there are very few studies comparing DED with DR.[12,13] To the best of the authors’ knowledge, no similar study has been reported from western India.
Overall, the prevalence of dry eye in patients of type 2 DM reported from previous studies is 18%–70%.[14-21] The prevalence of DED in the current study (43.81%) was comparable to a hospital-based study by Sarkar et al.[14] reporting 42% and by Dutta et al.[15] reporting 48.33%. However, it was greater than that reported by community-based studies by Kaiserman et al.[16] and Moss et al.,[17] which reported it to be 20.6% and 13.3%, respectively. The above variation could be due to poor metabolic control of DM in patients admitted in hospital and different diagnostic criteria in different studies, for example, Kaiserman et al.[16] compared the proportion of ocular lubrication consumers among diabetic and nondiabetic patients, while Moss et al.[17] determined dry eye by means of subject self-report. The diagnostic criteria could also vary in hospital-based study, for example, Manaviat et al.[12] (54.3% prevalence), in their hospital-based study, performed Schirmer and TBUT tests and utilized the criterion of only one positive test to establish the diagnosis of dry eye in type 2 diabetics, unlike the present study. Moderate dry eye was found to be most prevalent in our study, in contrast to mild dry eye being the commonest in other studies.[14,22]
In our study, a majority (39%) of patients with DED belonged to 51–60 years age group, which was not found to be statistically significant (P = 0.813); in contrast to other studies where a significant association was found between increase in the prevalence of DED and increase in age.[15-17] In the present study, DED was found to be more prevalent among females than males, which was not found to be statistically significant (P = 0.3049). This is similar to other studies where no association was noticed between gender and DED.[14-17] The female preponderance might be due to sex-specific hormones.[23] A significant association was found between duration of diabetes and presence of dry eye (P = 0.02) in this study, similar to other studies.[12-17,22] A statistically significant association was found between presence of DED and a poor glycemic control, similar to other studies.[14-16]
In the present study, DED in DM was due to tear secretion deficiency and tear film dysfunction, which was associated with low values of TBUT and Schirmer’s test and a high value of fluorescence staining of cornea and conjunctiva.[22] Out of 25.7% patients having HbA1c value ≥9.0, 74% had Schirmer’s value ≤5 in our study, which was similar to other studies, revealing an inverse correlation between the Schirmer’s test score and glycemic control.[15-17] Also, 96% patients having HbA1c level ≥9 had a TBUT value of <10 s, similar to a study done by Dutta et al.[15] in which all the patients with HbA1c levels ≥9 had TBUT <10 s. A higher degree of association was found between DED and MGD, similar to other studies.[24-26] In this study, dry eye was found to be more prevalent and severe in patients having PDR, similar to other studies.[12] However, no significant association of dry eye and DR was reported by Sarkar et al.[14]
The current study has certain limitations. It is a cross-sectional study, and treatment and prognosis of diagnosed cases of dry eye were not included in the study. A control group consisting of those not having type 2 DM was not included in this study.
Conclusion
The current study highlights a significant correlation between DED and duration of type 2 DM and between poor diabetic control and DR. Therefore, examination of DED and DR should be an integral part of the examination of diabetic patients, so as to prevent the adverse complications. Routine clinical screening for DED and DR could potentially allow for a timely and more effective treatment and could contribute to mitigate the DED- and DR-associated reduction in QOL in those with type 2 diabetes.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
- 1.Pradeepa R, Mohan V. Epidemiology of type 2 diabetes in India. Indian J Ophthal. 2021;69:2932–8. doi: 10.4103/ijo.IJO_1627_21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Sayin N, Kara N, Pekel G. Ocular complications of diabetes melitus. World J Diabetes. 2015;8:92–108. doi: 10.4239/wjd.v6.i1.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Zou X, Lu L, Xu Y, Zhu J, He J, Zhang B, et al. Prevalence and clinical characteristics of dry eye disease in community-based type 2 diabetic patients:The Beixinjing eye study. BMC Ophthalmol. 2018;18:117. doi: 10.1186/s12886-018-0781-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Van Tilborg MM, Murphy PJ, Evans KS. Impact of dry eye symptoms and daily activities in a modern office. Optom Vis Sci. 2017;94:688–93. doi: 10.1097/OPX.0000000000001086. [DOI] [PubMed] [Google Scholar]
- 5.Yazdani-Ibn-Taz MK, Han MM, Jonuscheit S, Collier A, Nally JE, Hagan S. Patient reported severity of dry eye and quality of life in diabetes. Clin Ophthalmol. 2019;13:217–24. doi: 10.2147/OPTH.S184173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Harrison TR. Diabetes Mellitus in Harrison's Principles of Internal Medicine. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J, editors. 21st ed. Mcgraw Hill; 2022. [Google Scholar]
- 7.Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the ocular surface disease index. Arch Ophthalmol. 2000;118:615–21. doi: 10.1001/archopht.118.5.615. [DOI] [PubMed] [Google Scholar]
- 8.O'Brien PD, Collum LM. Dry eye:Diagnosis and current treatment strategies. Curr Allergy Asthma Rep. 2004;4:314–9. doi: 10.1007/s11882-004-0077-2. [DOI] [PubMed] [Google Scholar]
- 9.Lemp MA. Report of the national eye institute/industry workshop on clinical trials in dry eyes. CLAO J. 1995;21:221–32. [PubMed] [Google Scholar]
- 10.Bron A, Benjamin L, Snibson G. Meibomian gland disease. Classification and grading of lid changes. Eye (London, England) 1991;5:395–411. doi: 10.1038/eye.1991.65. [DOI] [PubMed] [Google Scholar]
- 11.Solomon SD, Goldberg MF. ETDRS grading of diabetic retinopathy:Still the gold standard? Ophthalmic Res. 2019;62:190–5. doi: 10.1159/000501372. [DOI] [PubMed] [Google Scholar]
- 12.Manaviat MR, Rashidi M, Afkhami-Ardekani M, Shoja MR. Prevalence of dry eye syndrome and diabetic retinopathy in type 2 diabetic patients. BMC Ophthalmol. 2008;8:10. doi: 10.1186/1471-2415-8-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Najafi L, Malek M, Valojerdi AE, Aghili R, Khamseh ME, Fallah AE, et al. Dry eye and its correlation to diabetes microvascular complications in people with type 2 diabetes mellitus. J Diabetes Complications. 2013;27:459–62. doi: 10.1016/j.jdiacomp.2013.04.006. [DOI] [PubMed] [Google Scholar]
- 14.Sarkar KC, Bhattacharyya S, Sarkar P, Maitra A, Mandal R. An observational study on the prevalence of dry eyes in type 2 diabetes mellitus patients and its relation to the duration and severity of disease. J Med Sci Health. 2021;7:68–72. [Google Scholar]
- 15.Dutta SK, Paul G, Paul G. Correlation of dry eye and diabetes mellitus. Indian J Clin Exp Ophthalmol. 2021;7:25–30. [Google Scholar]
- 16.Kaiserman I, Kaiserman N, Nakar S, Vinker S. Dry eye in diabetic patients. Am J Ophthalmol. 2005;139:498–503. doi: 10.1016/j.ajo.2004.10.022. [DOI] [PubMed] [Google Scholar]
- 17.Moss SE, Klein R, Klein BE. Incidence of dry eye in an older population. Arch Ophthalmol. 2004;122:369–73. doi: 10.1001/archopht.122.3.369. [DOI] [PubMed] [Google Scholar]
- 18.Tanushree V, Madhusudhan CN, Hemalatha K, Gowda HT, Acharya AA, Patil S, et al. Prevalence of dry eye in type 2 diabetes mellitus. Int J Sci Stud. 2014;2:119–23. [Google Scholar]
- 19.Seifart U, Strempel I. The dry eye and diabetes mellitus. Ophthalmologe. 1994;91:235–9. [PubMed] [Google Scholar]
- 20.Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, et al. 10-year follow-up of diabetes incidence and weight loss in the diabetes prevention program outcomes study. Lancet. 2009;374:1677–86. doi: 10.1016/S0140-6736(09)61457-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Riordan-Eva, Asbury T, Whitcher JP. Vaughan and Asbury's General Ophthalmology. 16th ed. New York: McGraw-Hill Medical; 2003. pp. 308–10. [Google Scholar]
- 22.Zhang X, Zhao L, Deng S, Sun X, Wang N. Dry eye syndrome in patients with diabetes mellitus:Prevalence, etiology, and clinical characteristics. J Ophthalmol. 2016;2016:8201053. doi: 10.1155/2016/8201053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Matossian C, McDonald M, Donaldson KE, Nichols KK, MacIver S, Gupta PK. Dry eye disease:Consideration for women's health. J Womens Health. 2019;28:502–14. doi: 10.1089/jwh.2018.7041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Sandra Johanna GP, Antonio LA, Andrés GS. Correlation between type 2 diabetes, dry eye and Meibomian glands dysfunction. J Optom. 2019;12:256–62. doi: 10.1016/j.optom.2019.02.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Wu H, Fang X, Luo S, Shang X, Xie Z, Dong N, et al. Meibomian glands and tear film findings in type 2 diabetic patients:A cross-sectional study. Front Med. 2022;9:762493. doi: 10.3389/fmed.2022.762493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Yu T, Shi W-Y, Song A-P, Gao Y, Dang G-F, Ding G. Changes in meibomian glands in patients with type 2 diabetes mellitus. Int J Ophthalmol. 2016;9:1740–4. doi: 10.18240/ijo.2016.12.06. [DOI] [PMC free article] [PubMed] [Google Scholar]