At the completion of this article, the reader should be able to improve their management of dry eye disease in cases of diabetes, including:
- Define secondary dry eye and its relationship to systemic conditions like diabetes.
Recommend appropriate lubricants and treatment strategies based on tear film deficiencies.- Integrate a preservative-free, multi-dose solution into dry eye management plans for improved patient outcomes.
Megan Zabell
BOptom, MClinOptom
Diabetes increases the risk of dry eye disease (DED), impacting vision and quality of life. MEGAN ZABELL explores the key mechanisms behind diabetes-associated DED, evidence-based management strategies and the pivotal role of the optometrist.
Secondary dry eye – what is it? Secondary dry eye is simply dry eye that has developed as a consequence or complication of an underlying condition.1 This can include iatrogenic dry eye, which is dry eye induced by medication or a medical or surgical procedure. Examples of medications or procedures identified as a risk factor of dry eye include: hormone replacement therapy, refractive surgery, antihistamines, and antidepressant medications.2
Systemic health can also impact the risk of having dry eye disease (DED) – diabetes mellitus is one of the leading systemic risk factors for dry eye disease.3
The interaction between diabetes mellitus and DED is quite a complicated one. Diabetes affects almost one in 10 adults aged 20-79 worldwide,4 causing elevated blood glucose due to insufficient insulin production (Type 1) or insufficient insulin sensitivity (Type 2).
There are a number of key features of diabetes mellitus which contribute towards elevated risk of DED.3 Some of the features of diabetes mellitus that can contribute to this risk include chronic hyperglycaemia, diabetic peripheral neuropathy, decreased insulin levels, microvasculopathy and systemic hyperosmotic disturbances; these can lead to lacrimal unit dysfunction, tear film dysfunction and abnormal tear dynamics, ultimately contributing to DED.3
Management of diabetes mellitus is commonly centred around diet and exercise, glucose monitoring, insulin supplementation and the use of non-insulin antidiabetic medications like metformin. However, evidence suggests that the use of metformin may, itself, increase the risk of diabetes-associated DED.
In a study looking at patients with and without diabetes and the various risk factors for dry eye it was found that among the patients with diabetes, 82.6% of patients with dry eyes (n = 46) were metformin users, compared to only 54% of the group without dry eye (n = 74). This is a statistically significant difference between the groups (p<0.001), indicating that metformin use is a risk factor for DED, above and beyond the pre-existing risk of having diabetes.5 While it is difficult to specify the prevalence of diabetes-related DED (D-DED), a meta-analysis of four case-control studies found that the risk of DED was 30% higher in patients with diabetes as compared to control (patients without diabetes).6
Both DED and diabetes represent a threat to a sufferer’s quality of life (QoL). Patients with Type 2 Diabetes (T2D) have been identified as having inadequate health-related QoL in the following areas: physical function, social functioning, mental health, emotional health, vitality and body pain.7
Similarly, DED markedly undermines patients’ QoL in areas including: physical function, activities of daily living, workplace productivity, social functioning and mental health.8 DED has also been associated with increased self-assessed depression score,9 and patients with DED commonly report anxiety symptoms (37.2%) and disorders (11.4%).10 It has also been demonstrated in the literature that symptoms of DED are associated with reduced QoL in both Type 1 Diabetes (T1D) and T2D, irrespective of whether the patient has diabetic retinopathy.8
There are a number of structural changes that occur to the tear film in diabetes. Peripheral neuropathy and hyperglycaemia have been identified as the leading cause of some of these structural changes.11 Most components of the tear film and ocular structures that are vital to the tear film can be affected by changes that occur during diabetes:
Aqueous changes
• Hyperglycaemia can lead to microvascular damage to the lacrimal gland, and diabetic peripheral neuropathy is associated with impairment of lacrimal innervation, which both contribute to diminished tear production (corneal sensitivity and diminished reflex tearing).11
Mucin changes
• Corneal hypoesthesia can cause decreased mucin production by goblet cells, which leads to reduced tear film stability.11
Lipid changes
• Decreased corneal sensitivity, which reduces the blink rate, leads to the destabilisation of the lipid layer of the tear film and results in increased excess evaporation. Insulin is essential for the desired sebaceous gland activity and is known to induce glandular cell proliferation and lipid secretion. Hyperglycaemia has been shown to contribute to lipolysis in adipocytes. Hyperglycaemia could lead to morphologic changes and a gradual loss of meibomian gland epithelial cells.11
Meibomian gland changes
• Patients with diabetes have been observed to have higher meibomian gland scores, lower meibomian gland expressibility and lid margin abnormalities.12
Epithelial changes
• Diabetes mellitus can cause alterations in the corneal epithelial basal cells and basement membrane, leading to corneal epitheliopathy and adhesion disorders. Loss of corneal nerves in diabetes mellitus leads to reduced neurotrophic support, resulting in accelerated loss and reduced proliferation of epithelial cells. Diabetes mellitus also causes the production of the abnormal basal lamina and inadequate adhesion of epithelial cells to an abnormal basement membrane.11
In the case of patients with diabetes, early diagnosis and effective treatment of DED are essential to avoid the risk of complications.3 Making a diagnosis of DED and forming a management plan can be done as in cases of DED not related to diabetes, one useful resource is the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop II Report (DEWSII).13,14
There is also synchrony in the management strategies applied for both diabetes and DED. Several important elements of diabetes management also support optimal management strategies of DED15,16 – for example, adequate glycaemic control which reduces the risk of microvascular complication in diabetes17 also improves corneal nerve health.15
Adequate systemic hydration is important for patients with diabetes, who may be at greater risk of dehydration,18 and ensuring adequate systemic hydration also supports proper tear production for DED.15 Similarly for patients with diabetes, weight loss improves glycaemic control, reducing the need for glucose-lowering medications19 – a higher body mass index (BMI) has also been linked with metaplasia and goblet cell loss in DED.15
A further important element that links diabetes management and DED management is aiming to maintain optimal insulin levels – while insulin deficiency is a defining feature of diabetes mellitus, adequate insulin mediates healthy epithelial cell metabolism crucial for ocular surface health.15
The management for DED secondary to diabetes follows the same principles as laid out by the four-step management algorithm in TFOS DEWSII,14 with the incorporation of some of the concepts mentioned in the preceding paragraph.
After triaging dry eye symptoms and establishing that the tear film exhibits a loss of homeostasis indicative of DED, the dry eye can then be subtyped into aqueous-deficient dry eye (if the mucoaqueous layer of the tear film in insufficient), evaporative dry eye (if the lipid layer of the tear film is insufficient causing increased evaporation rates), or a mixed type of dry eye that exhibits signs of both subtypes.13 As identified, patients with DED and diabetes may have either (or both) layers of the tear film affected, so the tear film should be carefully assessed when designing a DED management strategy.
If a DED sufferer has insufficiencies in both the lipid and mucoaqueous layers of their tear film, a sensible management strategy would be, among other therapies if needed, recommending an ocular lubricant that supplements both layers of the tear film to avoid the potential burden that needing to use multiple drops could cause.
As identified by TFOS DEWSII it is recommended to use a lipid-containing tear supplement in the case of the DED having an evaporative component,14 something that is supported by clinical evidence.20 In a six-month multicentre, double-masked randomised controlled trial it was found that both lipid-based and non-lipid based tear supplements improved mild-moderate cases of DED, yet the evaporative cases benefited preferentially from lipid-based supplementation.20
A Phase 4, multicentre, open label interventional study investigating the effects of a combination lipid and aqueous lubricating eye drop on symptoms of DED for patients who had evaporative, aqueous deficient, or mixed subtypes of dry eye found that the propylene glycol-hydroxypropyl guar nanoemulsion that is Systane COMPLETE provided immediate and sustained relief of DED symptoms across all subtypes of dry eye.21
Patients with diabetes who attend for eye tests require thorough examination due to the potential ocular complications. One that can’t be neglected among these potential ocular side effects is dry eye – dry eye secondary to diabetes can affect either or both layers of the tear film.
Management recommendations for dry eye secondary to diabetes is equivalent to other dry eyes – one consideration for a tear film that has either or both layers affected could be Systane COMPLETE Lubricant Eye Drops, which has been shown to address the symptoms of evaporative, aqueous deficient, and mixed dry eye for up to eight hours.21 It is available in a multi-dose preservative-free bottle that can be kept for up to three months after opening.
Disclaimer: The author is a paid employee of Alcon Laboratories.
More reading
Aussie researchers lead global study on how dry eye impacts quality-of-life
Optometrists going back to the future on dry eye disease
An Australian ophthalmologist’s take on low light level therapy for dry eye
References
1.Javadi MA, Feizi S. Dry eye syndrome. J Ophthalmic Vis Res. 2011 Jul;6(3):192-8
2. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II Epidemiology Report. Ocul Surf. 2017;15(3):334-365
3. 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
4. International Diabetes Foundation, IDF Diabetes Atlas – 10th edition 2021 [Online]. Available: https://diabetesatlas.org/data/en/world/. [Accessed 19/12/2024]
5. De Freitas GR, Ferraz GAM, Gehlen M, Skare TL. Dry eyes in patients with diabetes mellitus. Prim Care Diabetes. 2021;15(1):184-186
6. Yoo TK, Oh E. Diabetes mellitus is associated with dry eye syndrome: a meta-analysis. Int Ophthalmol. 2019;39(11):2611-2620
7. Zurita-Cruz JN, Manuel-Apolinar L, Arellano-Flores ML, Gutierrez-Gonzalez A, Najera-Ahumada AG, Cisneros-González N. Health and quality of life outcomes impairment of quality of life in type 2 diabetes mellitus: a cross-sectional study. Health Qual Life Outcomes. 2018;16(1):94
8. 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;13:217-224
9. Jonas JB, Wei WB, Xu L, Rietschel M, Streit F, Wang YX. Self-rated depression and eye diseases: The Beijing Eye Study. PLoS One. 2018;13(8):e0202132
10. Ulhaq ZS, Soraya GV, Dewi NA, Wulandari LR. The prevalence of anxiety symptoms and disorders among ophthalmic disease patients. Ther Adv Ophthalmol. 2022;14:25158414221090100
11. Han SB, Yang HK, Hyon JY. Influence of diabetes mellitus on anterior segment of the eye. Clin Interv Aging. 2018;14:53-63
12. Mohamed-Noriega K, González-Arocha CS, Morales-Wong F, et al. Meibomian Gland Dysfunction and Dropout in Diabetic Patients with Non-Proliferative Diabetic Retinopathy. Bioengineering (Basel). 2024;11(9):907
13. Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II Diagnostic Methodology report. Ocul Surf. 2017;15(3):539-574
14. Jones L, Downie LE, Korb D, et al. TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017;15(3):575-628
15. Richdale K, Chao C, Hamilton M. Eye care providers’ emerging roles in early detection of diabetes and management of diabetic changes to the ocular surface: a review. BMJ Open Diabetes Res Care. 2020;8(1):e001094
16. Bron AJ, Willshire C. Tear Osmolarity in the Diagnosis of Systemic Dehydration and Dry Eye Disease. Diagnostics (Basel). 2021;11(3):387
17. American Diabetes Association Professional Practice Committee, “6. Glycemic Targets: Standards of Medical Care in Diabetes-2022,” Diabetes Care, 45, no. Suppl 1, pp. dc22-S006, 2022
18. Mohan V, Kalra S, Zargar AH, Tiwaskar M, Thakor P, Malve H. Diabetes Mellitus and Fluid Imbalance: The Need for Adequate Hydration. J Assoc Physicians India. 2024;72(6S):16-24
19. Horton ES, Silberman C, Davis KL, Berria R. Weight loss, glycemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diabetes Care. 2010;33(8):1759-1765
20. Craig JP, Muntz A, Wang MTM, et al. Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial. Ocul Surf. 2021;20:62-69
21. Silverstein S, Yeu E, Tauber J, et al. Symptom Relief Following a Single Dose of Propylene Glycol-Hydroxypropyl Guar Nanoemulsion in Patients with Dry Eye Disease: A Phase IV, Multicenter Trial. Clin Ophthalmol. 2020;14:3167-3177
