Paediatric Diabetes and Dry Eye: A Review

Tears spread over the anterior ocular surface forming a protective interface between the epithelium and the external environment.¹ Previously, the tear film was known for comprising of three layers viz. the lipid layer, aqueous layer and the mucin layer. However, recent evidence has shown that the mucin and aqueous layers merge, due to the decreasing gradient of concentration elicited by the mucin layer, giving rise to a single layer known as the mucous-aqueous layer.² The superficial lipid layer comprises of substances secreted by the meibomian glands which aid in providing stability to the tear film by increasing surface tension.³ This protects the tear film against gravity, ensuring optimum ocular protection as well as decreases the rate at which tears evaporate from the surface. Majority of the tear film is comprised of the muco-aqueous layer, which lies below and to an extent is interspersed with the lipid layer.⁴ The aqueous layer is secreted by the lacrimal gland which is found in the superior temporal angle of the orbit, consisting of two parts, the palpebral and orbital lobes. This layer of the tear film consists of electrolytes, to maintain tear osmolarity, ions which are vital for epithelial integrity as well as proteins which are responsible for various actions such as wetting of the ocular surface, reducing surface tension as well as providing protection against infectious agents.⁵ The mucin layer is made up of mucin, immunoglobulins, urea, salts, glucose, leukocytes, cellular debris, and enzymes, primarily secreted by the goblet cells of the conjunctiva. This layer provides lubrication as well as protection to the cornea while anchoring the aqueous tear film to the corneal epithelium. It also helps to prevent desiccation of the ocular surface and infections.⁶

2.1. Diabetes mellitus

Diabetes mellitus (DM) can be defined as a biomedical disorder, resulting from either the inability of insulin to perform its normal functions or a decreased insulin secretion, at times both concurrently.⁷ Consequently, glucose accumulates in the bloodstream and if left untreated, results in various secondary health complications. Loss of weight, frequent urinating, excessive thirst and visual disturbances are among the most frequently reported symptoms of diabetes.⁸ Studies show that in the years, 2016 and 2017, diabetes was listed as being the second most common underlying cause of death in South Africa. Recent statistics showed that the number of people with diabetes globally has risen from 108 000 000 in 1980 to 463 000 000 in 2019. South Africa alone, has seen a rapid escalation in the number of people diagnosed with diabetes, where it has almost tripled from approximately 4.5% in 2010 to 12.7% in 2019.⁹

2.2. Paediatric DM

The detrimental impact of diabetes in children and young adults has been researched quite extensively, yet the prevalence of diabetes as a chronic condition amongst this population 41continues to increase.¹⁰ The diagnosis of diabetes, more specifically type 1 diabetes (T1D), peaks during adolescence with approximately 1 100 000 children below the age of 20 living with T1D globally. It is known to be the second most prevalent chronic condition in children. Providing optimal care for children and adolescents diagnosed with diabetes mellitus demands a multidisciplinary approach comprising of a group of healthcare professionals who acknowledge the skill and expertise of each member.¹¹ Timeous intervention and correct management are vital as the condition is known to lead to a vast number of secondary complications, which include microvascular or cardiovascular disease, blindness, limb amputations¹² and even death.

2.3. Dry eye disease

In recent years, dry eye disease (DED) has fast become a common global concern among the general population. Dry eye syndrome is a generic ocular surface disorder characterized by the loss of homeostasis of the tear film, accompanied by a variety of symptoms, in which tear film hyperosmolarity and instability, inflammation or damage of the ocular surface as well as neurosensory abnormalities may play etiological roles. DED is closely associated with a reduced ability to perform certain activities such as reading, driving, and computer related work, tasks that require visual attention.¹³ Lack of sufficient tears can leave the interpalpebral ocular surface susceptible to damage, affecting the quality of life of these patients.¹⁴

2.4 Pathophysiology of diabetes-related dry eye

Chronically elevated blood glucose levels, peripheral neuropathy, reduced insulin production, and systemic hyperosmotic changes are among the known risk factors for dry eye in diabetic patients. Proliferation of the corneal epithelial cells and acinar lacrimal gland requires insulin. It has been shown that hyperglycemia causes histological changes within the lacrimal gland which indicates the diabetic-induced oxidative stress plays a vital role in the development of dry eye in the diabetic population.¹² Fluctuating glucose and insulin levels have direct and indirect implications on the structure as well as metabolism of the corneal epithelium itself. Hence, hyperglycemia changes the expressions of growth factors and mediators resulting in disruption in cell growth and integrity.¹⁷ These alterations impair tear flow and production, leaving the ocular surface susceptible to many ocular conditions such as, dry eye syndrome. The true pathogenesis however, still remains elusive with a limited number of management approaches made available.¹⁸

2.5. Methods

This integrative search was conducted on online databases such as Google Scholar, ScienceDirect and PubMed with the aim of identifying available evidence in current literature on the prevalence of dry eye in children with diabetes mellitus (type 1/2) as well as to document any ocular surfaces changes in these patients. The guiding question to elaborate the review was: “What scientific knowledge has been produced thus far on the prevalence of dry eye syndrome among children with diabetes?”

All relevant literature documenting tear film changes and the prevalence of dry eye syndrome in children and adolescents living with diabetes, were included and summarised. The final sample comprised of six articles.

2.6. Review

The findings of the search are categorized accordingly and presented along with a short description on tear film osmolarity, tear break-up time, Schirmer, dry eye signs and symptoms, and the prevalence of dry eye syndrome amongst paediatric patients diagnosed with DM.

2.7. Discussion

DM is a set of complex metabolic diseases associated with defects in insulin secretion and/or insulin efficacy, resulting in chronic hyperglycaemia.²⁷ It is known to be one of the most common chronic disorders amongst paediatric patients today.²⁸ According to the International Diabetes Federation, 370 000 000 people globally, were diagnosed with diabetes by the year 2011.This number was predicted to reach approximately 550 000 000 by 2030. Research studies have shown that at least 80% of the diabetic population were from developing countries. By 2017, the total number of children and adolescents, across the world, living with diabetes reached 1 106 500.²⁹ Dry eye disease (DED) is a multifactorial disorder of the preocular surface which is defined by a loss of homeostasis of the tear film.³⁰ The dysfunction may result in one or more both layers of the tear film, namely, the lipid layer and the muco-aqueous layer.⁴ Poor quality of the tear film or a deficiency in tear production, results in the instability of the tear film itself, allowing for excessive evaporation of tears from the surface of the eye. Numerous studies have reported that diabetes is closely linked to an increased risk of developing chronic complications. With regards to the eye itself, patients may develop ocular surface diseases such as dry eye or keratopathy, retinopathy, glaucoma, cataract, refractive abnormalities, all of which could result in a decrease in visual acuity and if not managed effectively, could lead to blindness.²² Tear function may also be reduced in diabetic patients due to either, the impairment of the autonomic nervous system or damage to the lacrimal gland’s microvasculature.30 Anecdotal evidence suggest that older patients are said to be more prone to developing dry eye syndrome mainly due to the anatomy of the eye and the process of aging. However, patients regardless of age with systemic conditions such as diabetes, are at an increased risk and require timeous intervention. By the age of 10, annual ocular screenings are recommended for all patients diagnosed with DM.²⁴

The studies introduced in the present review suggest that diabetes may lead to various ocular surface alterations, even in children. Whilst most literature aimed to merely show certain tear film changes; two studies^22,23 attempted to clinically diagnose dry eye syndrome and showed a higher prevalence in children with diabetes. Therefore, further prospective studies are needed to evaluate the presence of dry eye in children with diabetes, in different geographical locations. In this review, we found that literature on tear film osmolarity in this diabetic population is limited to just one study which showed that tear film osmolarity is generally higher in patients with diabetes. Dry eye may result from an interruption in the flex pathways of tears or a process which affects the lacrimal gland itself, altering the secretion mechanisms. Diabetes presents with a possibility of damage to the lacrimal gland’s microvasculature and along with autonomic neuropathy, the lacrimal gland does not function at its optimum. Diabetic sensory neuropathy, which affects the corneal surface may be the cause of decreased tear secretion.²⁴ Four^22,23,24,25 out of the six studies reviewed, showed that tear break-up time test values were significantly lower among children with DM as compared to the healthy controls.

2.8. Conclusion

Evidence of this review shows that tear film changes among diabetic children may vary. Future studies should assess ocular changes in different parts of the world, as geographics, climate and environment may influence normative tear test values. Due to the limited literature available regarding the prevalence of dry eye and tear osmolarity values in this specific population, it is recommended that more studies are conducted. Poor regulation of insulin and glucose can result in fluctuation of vision as well as place diabetic patients at an increased risk of ocular surface inflammation. With the steady increase in the number of children and adolescents with diabetes, the characteristics and risk factors of dry eye disease in this population has become more valuable and of social significance. Early detection of systemic conditions may allow eye care practitioners to be more proactive in ensuring appropriate referral and intervention which is vital as this can aid in reducing the risk of blindness as well as other diabetes-related morbidities. At present, a large majority of the literature focuses on the prevalence and factors associated with dry eye disease in adults with diabetes, but very few studies have been performed on children with diabetes. Future studies should include the paediatric population, including adolescents to provide a broader understanding on diabetic-related ocular surfaces alterations. Information obtained from these studies will be beneficial to the eye care practitioners around the world, by enhancing physician awareness of dry eye in children.