Sjögren's Syndrome as a Cause of Dry Eye Syndrome

Introduction

Autoimmune inflammation in Sjögren's syndrome leads to the destruction of salivary and lacrimal glands, resulting in a severe reduction in tear production and development of dry eye syndrome (DES). According to community studies, dry eye syndrome is a very common problem among patients with Sjögren's syndrome, with a prevalence of 5–50%. Among DES patients, individuals with Sjögren's syndrome represent 1–10% according to various studies.

Etiopathogenesis

The etiopathogenesis of DES-related problems is multifactorial, and even in patients with Sjögren's syndrome, numerous intrinsic and extrinsic causes contribute to the development of this syndrome.

Three main types of DES are distinguished from an etiopathogenetic perspective, which are also observed in patients with Sjögren's syndrome:

• The most common is increased tear evaporation causing epithelial damage in the eye, due to Meibomian gland dysfunction.
• Deficient tear production caused by lacrimal gland damage also contributes to the difficulties.
• The third type is the so-called neuropathic dry eye, which has gained increasing attention in recent years. In these patients, the problems are due to nerve dysfunction in the eye surface area (conjunctiva, cornea) or central neurons.

Therapy for dry eye syndrome should therefore not focus solely on local symptoms but also on underlying causes, including environmental factors.

Diagnostic Methods

In the diagnosis of DES in Sjögren's syndrome, classical diagnostic methods to determine dry eye syndrome are used, such as the fluorescein break-up time test, tear osmolarity test, Schirmer's test, and others. However, these tests have several limitations, leading to the current exploration of new methods to clarify the diagnosis of issues associated with Sjögren's syndrome. Such diagnostic procedures include meibography assessing the morphology of Meibomian glands, in vivo confocal microscopy visualizing inflammatory cells, biochemical tear analysis, assessment of tear film proteome, or imaging methods (MRI or ultrasonography) to determine inflammation and gland size. Attention is also given to serological determination of specific antibodies like anti-PSP (parotid secretory protein) or anti-CA6 (carbonic anhydrase).

Current Therapeutic Options

The goal of therapy is to restore ocular surface homeostasis and prevent the return of difficulties. An essential part of any treatment strategy is the use of preservative-free artificial tears, along with education about the adverse effects of environmental factors. According to a recent recommendation by the European League Against Rheumatism (EULAR), therapy for patients with Sjögren's syndrome should begin with artificial tears applied at least twice a day and, if necessary, up to every hour. Preferably, preparations containing methylcellulose or hyaluronic acid should be used.

If there is no improvement, short-term topical application of glucocorticoids (2–4 weeks) and long-term application of cyclosporine A (less frequently tacrolimus), serum eye drops (autologous, allogeneic), and in the last stage, oral administration of muscarinic agonists is recommended. Recently, lifitegrast has been utilized as an alternative to cyclosporine A, with a faster onset of action. Although specific studies for Sjögren's syndrome have not yet been conducted for this drug, the evaluated population included such patients. According to recent recommendations, however, the use of hydroxychloroquine, systemic immunosuppressants, and rituximab is not recommended for dry eye therapy.

Occulusal therapy of the lacrimal ducts also represents a therapeutic option. Substances stimulating tear production, nasal electrostimulation of tear production, mucolytic drops containing acetylcysteine, or lubricants (e.g., lubricin) are among methods currently under research. The standard in evaporative DES therapy is eyelid hygiene and warming.

Conclusion

Dry eye syndrome is a common complication of autoimmune Sjögren's syndrome. Diagnostic options, including differentiation from DES of other etiologies, are currently under intensive research. Essential pillars of therapy include the topical application of preservative-free artificial tears, escalated to topical application of anti-inflammatory agents and potentially other treatment modalities if necessary.

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Source: Vehof J., Utheim T. P., Bootsma H., Hammond C. J. Advances, limitations, and future perspectives in the diagnosis and management of dry eye in Sjögren's syndrome. Clin Exp Rheumatol 2020; 38 Suppl. 126 (4): 301–309.