Diabetes is associated with a high risk for various comorbidities, including cardiovascular, kidney, and ocular diseases, such as dry eye disease (DED).^1,2,3

Dry eye disease overview
DED is the most common disorder impacting tear production and the ocular surface. It is characterised by a loss of tear film homeostasis and related ocular symptoms. The onset of DED is influenced by tear film instability, hyperosmolarity, ocular surface inflammation, damage, and neurosensory abnormalities.^2,4

Prevalence of DED in individuals living with diabetes

Among individuals living with diabetes, the prevalence of DED is estimated to range between 30% and 38.3%. In these individuals, DED is often caused by peripheral neuropathy, lacrimal gland dysfunction, inflammatory changes, and systemic hyperosmotic disturbances due to hyperglycaemia.^2,3,5

The incidence of DED is particularly high - reaching 67% - among those with type 2 diabetes (T2DM), which constitutes >90% of diabetes cases, especially in those with uncontrolled diabetes (HbA1c >8%) and long-standing diabetes (over 10 years, 68%). Long-standing diabetes can damage the microvasculature of the lacrimal gland, affecting tear production.^1,6,7

A study by Naik et al found that in most diabetic individuals, DED was primarily caused by meibomian gland dysfunction (MGD, 44%) followed by blepharitis (23.7%).⁷

MGD results from the malfunction of the meibomian glands, which secrete oils that prevent tear film evaporation. When these glands are blocked or dysfunctional, the lipid layer of the tear film becomes deficient, leading to increased tear evaporation and dry eye symptoms.⁹

Blepharitis, characterised by inflammation of the eyelid margins, can present as either anterior or posterior inflammation and typically affects both eyes, leading to irritation at the lid margins, flaking, and crusting of the lashes.¹⁰

Impact of DED on quality of life

DED significantly impacts individuals' quality of life (QoL), manifesting in symptoms such as stinging, watering, redness, and irritation of the ocular surface, particularly the cornea. Individuals living with diabetes and DED often experience additional symptoms like itching and burning. These symptoms severely affect QoL, comparable to conditions like angina, hip fractures, or dialysis.^6,8

DED not only impacts the physical well-being of individuals but also their social and psychological functioning. The most significant costs associated with DED are indirect, primarily due to reduced work productivity.¹¹

Psychologically, individuals with DED and diabetes have higher rates of depression and anxiety compared to the general population. In a study assessing the relationship between depression and major ocular diseases, Jonas et al found that DED was the only ocular disorder associated with an increased rate of depression.¹²

Management challenges

Managing DED is complex due to its multifactorial nature, as noted by the Tear Film and Ocular Surface Society. The primary goal of treatment is to restore tear film and ocular surface homeostasis. Treatment often involves multiple therapies targeting different aspects of the condition. Furthermore, the treatment of DED typically requires ongoing management rather than short-term solutions.¹¹

The 2024 American Academy of Ophthalmology (AAO) recommends that individuals with mild DED symptoms undergo a trial of artificial tears once other potential causes of ocular irritation have been ruled out. For mild cases, artificial tears with preservatives may suffice, but for those using them frequently (more than four times a day), preservative-free options are recommended.¹²

For moderate DED, the AAO suggests additional treatments, including topical anti-inflammatories, surgical procedures, other ophthalmic solutions, corticosteroids, oral fatty acid supplements, aqueous nasal spray, or punctal occlusion. Non-invasive options such as eyeglass side shields and moisture chambers can also be beneficial.¹²
For severe DED, the addition of permanent punctal occlusion may be considered. Thermal cautery is generally more effective and cost-efficient than laser cautery for achieving permanent occlusion.¹²

Efficacy of artificial tears

There is strong evidence that artificial tears can relieve dry eye symptoms within a month of regular use, typically applied about four times a day. However, significant improvements in signs of the condition generally take several months.¹³

According to Silverstein et al, most artificial tears target either the lipid or aqueous layer of the tear film. However, a lubricant addressing all layers is needed to effectively manage DED symptoms.¹⁴

Propylene Glycol-HydroxyPropyl Guar (PG-HPG) nanoemulsion lubricant eye drops are designed to address all layers of the tear film, utilising propylene glycol as the main demulcent and featuring a higher concentration of HPG gelling technology compared to previous formulations.¹⁴

These drops also contain a lipid excipient in smaller nano-sized droplets, improving lipid surface coverage and offering a more translucent appearance. They are intended for individuals with dry eye resulting from either lipid or aqueous deficiency and are suitable for individuals with mixed DED.¹⁴

After application, PG-HPG nanoemulsion forms a protective viscoelastic barrier on the eye’s surface. As the pH normalizes and sorbitol dilutes, this barrier strengthens, gradually releasing lipids into the tear film.¹⁴

Dimyristoyl phosphatidylglycerol, an anionic phospholipid in PG-HPG nanoemulsion, migrates to the surface of the tear film, merging with existing lipids to fill gaps caused by MGD and lipid insufficiency. This formulation helps restore the complete tear structure, alleviating symptoms and maintaining a healthier ocular surface.¹⁴

How safe and effective are PG-HPG nano-emulsion artificial tears?

Silverstein et al assessed how rapidly a single drop of PG-HPG nano-emulsion can relief symptoms. On Day 1, the median reduction in symptom scores was greater than one point across all post-dose time points. Among individuals with a baseline symptom score of six to 10, 67.2% to 77.0% reported a reduction to zero to five within eight hours.¹⁴

The median symptom score for aqueous-deficient dry eye individuals improved from −1 at zero hours to −2.5 at four hours, while evaporative and mixed subtypes showed similar improvements.¹⁴

Furthermore, >80% of individuals reported a soothing sensation lasting throughout the eight-hour evaluation, with median soothing scores consistently around three.¹⁴
Tolerability was high, with >92% of individuals reporting minimal discomfort. Subgroup analyses confirmed these findings across different dry eye subtypes, demonstrating the eye drops' effectiveness and tolerability.¹⁴

Silverstein et al concluded that PG-HPG nanoemulsion consistently reduced the symptoms associated with DED in all individuals, regardless of the disease subtype, thereby providing instant, immediate, and all-day symptom relief.¹⁴

Weisenberger et al evaluated the effects of a single drop of two ocular lubricants - a nanoemulsion and a non-emollient - on tear film lipid layer thickness (LLT) and symptoms of dry eye.¹⁵

The study consisted of two parts: a cross-over comparison measuring LLT and dry eye symptoms at baseline and at intervals up to six hours after instillation, and a one-month observational study assessing LLT and symptoms after daily use of the nanoemulsion drop.¹⁵

In Part 1, a significant increase in average LLT was observed 15 minutes after the instillation of the nanoemulsion drop, particularly in the overall and inferior third of the tear film for subjects with baseline LLT values <50nm. No increase in LLT was found after using the non-emollient drop. Symptoms of dry eye improved for up to six hours following the instillation of both drops.¹⁵

In Part 2, after one month of using the nanoemulsion drop four times daily, individuals reported a statistically and clinically significant improvement in dry eye symptoms.¹⁵

Weisenberger et al concluded that the nanoemulsion eye drop can effectively increase LLT and alleviate dry eye symptoms in individuals with low baseline LLT levels.¹⁵

Managing DED in individuals living with diabetes

The American Diabetes Association (ADA) advises that individuals undergo a dilated eye examination soon after receiving a diabetes diagnosis. Many individuals living with T2DM diabetes may have been living with the condition for years prior to diagnosis, which could result in unnoticed ocular damage. The initial examination should be comprehensive and include pupil dilation. Based on the findings, the physician may recommend follow-up exams every one to two years. If diabetic eye disease is detected, more frequent monitoring may be necessary. The ADA recommends using artificial tears regularly to maintain adequate ocular moisture.^16,17

Conclusion

The efficacy of PG-HPG nanoemulsion artificial tears has been demonstrated across all subtypes of DED. The ADA recommends artificial tears for individuals living with diabetes and DED. As the prevalence of diabetes continues to rise globally, especially in Africa, the need for effective management of associated comorbidities, such as DED, becomes increasingly critical. PG-HPG nanoemulsion offers a comprehensive solution by addressing both lipid and aqueous deficiencies in the tear film, resulting in rapid symptom relief and sustained ocular surface protection. The consistent improvement in tear film lipid layer thickness and significant reduction in dry eye symptoms highlight the potential of PG-HPG nanoemulsion as a valuable therapeutic option for managing DED in individuals living with diabetes, thereby enhancing their QoL and mitigating the ocular complications of diabetes.

References

1. Hossain J, Al-Mamun MS, Islam R. Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused. Health Science Reports, 2024.
2. Yoo TK and Oh E. Diabetes mellitus is associated with dry eye syndrome: a meta-analysis. Int Ophthalmol, 2019.
3. De Freitas GR, Ferraz GAM, Gehlen M, Skare TL. Dry eyes in patients with diabetes mellitus. Prim Care Diabetes, 2021.
4. Golden MI, Meyer JJ, Zeppieri M, et al. Dry Eye Syndrome. [Updated 2024 Feb 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470411/
5. Mansuri F, Bhole PK, Parmar D. Study of dry eye disease in type 2 diabetes mellitus and its association with diabetic retinopathy in Western India. Indian Journal of Ophthalmology, 2023.
6. Yazdani-Ibn-Taz MK, Han MM, Jonuscheit S, et al. Patient-reported severity of dry eye and quality of life in diabetes. Clin Ophthalmol, 2019.
7. Naik K, Magdum R, Ahuja A, et al. Ocular Surface Diseases in Patients with Diabetes. Cureus, 2022.
8. Aljarousha M, Badarudin NE, Che Azemin MZ. Comparison of Dry Eye Parameters between Diabetics and Non-Diabetics in District of Kuantan, Pahang. Malays J Med Sci, 2016.
9. Eberhardt M, Rammohan G. Blepharitis. [Updated 2023 Jan 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459305/
10. Chhadva P, Goldhardt R, Galor A. Meibomian Gland Disease: The Role of Gland Dysfunction in Dry Eye Disease. Ophthalmology, 2017.
11. Craig JP, Nelson JD, Azart T. TFOS DEWS II Report Executive Summary. The Ocular Surface, 2017.
12. Amescua G, Ahmad S, Cheung AY, et al on behalf of the American Academy of Ophthalmology Preferred Practice Pattern Cornea/External Disease Panel Dry Eye Syndrome Preferred Practice Pattern. Ophthalmology, 2024.
13. Semp DA, Beeson D, Sheppard AL, et al. Artificial Tears: A Systematic Review. Clin Optom (Auckl), 2023.
14. 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.
15. Weisenberger KR, Fogt JS, Fogt NF. Comparison of Nanoemulsion and Non-Emollient Artificial Tears on Tear Lipid Layer Thickness and Symptoms. J Optom, 2020.
16. American Diabetes Association. Eye Health Annual Eye Exam. Updated 2024. [Internet]. Available at: https://diabetes.org/sites/default/files/2024-07/ADA24_Annual-Eye-Exam_AA_HEN_IN-7-23-24.pdf
17. American Diabetes Association. Eye Health: Dry Eye with Diabetes. Updated 2024. [Internet]. Available at: https://diabetes.org/sites/default/files/2023-09/EyeHealth_Resource_Dry-Eye_rev-1.pdf