Dry Eye Disease: Diagnostic and Treatment Strategies for Primary Care Physicians and Specialists

Dry eye disease (DED) is a multifactorial disorder characterized by a loss of tear film homeostasis due to the development of dysfunction in the ocular structures that produce and regulate its components, including the lacrimal and meibomian glands, the cornea, and the conjunctiva. Pathological changes trigger a vicious cycle of inflammation and damage to the ocular surface, which can impair quality of life and vision (Craig J.P. et al., 2017; Bron A.J. et al., 2017). According to experts, the global prevalence of DSC ranges from 5 to 50% and varies by population (Craig J.P. et al., 2017; Stapleton F. et al., 2017). Associated symptoms include redness of the eyes, dryness, itching, a foreign body sensation, eye fatigue, and visual disturbances (Begley C.G. et al., 2003). The diagnosis is most often based on a combination of a relevant medical history and several clinical diagnostic findings that reveal abnormalities in the tear film or the ocular surface (Wolffsohn J.S. et al., 2014).

Treatment of KSC
Treatment of KSC, which addresses all etiological components, is often long-term and multifaceted; it potentially includes both pharmacological and non-pharmacological interventions. Treatment usually begins with appropriate conservative therapy and, depending on the severity of the disease, progresses to more intensive treatment (Jones L. et al., 2017).

Pharmacological Therapeutic Agents
Many pharmacological agents are used to treat XO, including both topical and systemic medications. Topical agents include moisturizers, corticosteroids, lifegras (an LFA-1 integrin antagonist), and cyclosporine A. Systemic agents for oral use may include antibiotics (azithromycin, tetracyclines), polyunsaturated omega-3 fatty acids, and antioxidants (Jones L. et al., 2017).

Nonpharmacological therapeutic approaches
Nonpharmacological interventions used to treat chronic conjunctivitis include procedural and device-based therapies, as well as lifestyle modifications. General procedural treatments include tear duct occlusion, intense pulsed light therapy, and others (Stonecipher K. et al., 2020). Device-based therapy includes devices for eyelid hygiene, neurostimulation, warm compresses, and others (Kent C., 2018). Changes in environmental conditions and lifestyle can also improve the condition of patients with DAC.

The Role of Primary Care Physicians and Specialists in the Treatment of DSC
Primary care physicians are the first specialists that patients with CTS turn to; they have the opportunity to provide patients with important information about the underlying disease process, which promotes realistic expectations and long-term adherence to treatment (Akpek E.K. et al., 2019). In addition, primary care physicians may be the first to suspect or diagnose CSC, can initiate non-specialized treatment or provide recommendations to help alleviate symptoms and minimize damage to the ocular surface (Verjee M.A. et al., 2020) or refer the patient to an ophthalmologist for further evaluation and specialized treatment.

Psychiatrists
Many psychoactive medications, including antidepressants, antipsychotics, and anxiolytics, contribute to the development and progression of CSO. The mechanisms responsible for this have not been definitively established and likely depend on the class of drug. For example, tricyclic antidepressants cause CTS by inhibiting secretory function in the lacrimal gland and goblet cells. Selective serotonin reuptake inhibitors increase the levels of serotonin and inflammatory mediators in tears, causing dysfunction and damage to ocular surface structures (Rakofsky J.J. et al., 2021; Chhadva P. et al., 2015).
In addition to the fact that psychoactive medications can contribute to the development of OCS, patients with this condition have a higher prevalence of sleep and mood disorders, which, in turn, may require separate treatment (Jones L. et al., 2017; Na K.S. et al., 2015). In 2022, American scientists published the results of a new study in which they concluded that the presence of depression correlates with more severe symptoms of COPD (p=0.006); at the same time, the severity of depression correlates with the severity of COPD manifestations (p<0.001). These results allow us to consider depressive disorder as a comorbid condition during the treatment of patients with COPD (Zhou Y. et al., 2022). Similar results were previously obtained in a study examining the comorbidity of PD and anxiety disorders (Ulusoy M.O. et al., 2019), which underscores the importance of diagnosing PD before initiating psychiatric treatment.

Neurologists
Like tricyclic antidepressants, many medications for Parkinson’s disease, such as levodopa, pramipexole, and benztropine, have anticholinergic effects that cause abnormal tear production and contribute to the development of DCS (Wong J. et al., 2011). On the other hand, the prevalence of DCS among patients with Parkinson’s disease can reach 70% due to lacrimal gland dysfunction and/or ocular surface disorders inherent to the disease’s pathogenesis (Ungureanu L. et al., 2023).
In addition, numerous neurological disorders, including stroke, myasthenia gravis, diabetic neuropathy, neurotrophic keratitis, are associated with tear film abnormalities due to potential disruption of sensory and/or motor innervation of the eyes (Achtsidis V. et al., 2014; Misra S.L. et al., 2014). In studying the relationship between migraine and CTS, researchers from Turkey concluded that patients with this neurological disorder have an increased incidence of CTS (p<0.05), and the intensity of certain types of migraine attacks may increase in the presence of OCS (Koktekir B.E. et al., 2011).

Rheumatologists
Autoimmune disorders, such as Sjögren’s syndrome, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, idiopathic inflammatory myositis, and systemic vasculitides, are known risk factors for SLE; moreover, CS may be one of the first signs of a rheumatic disease (Schargus M. et al., 2015). Approximately 10–95% of patients with immune system disorders experience dry eyes. For example, 38–47% of patients with rheumatoid arthritis (Kemeny-Beke A., et al., 2020), 13.4–39.5% with systemic lupus erythematosus (Dammacco R. et al., 2018), 95% of patients with scleroderma (Mavragani C.P. et al., 2014), and 37–79% with systemic vasculitis (Gomes A. F. et al., 2012).
It is believed that this is caused by the infiltration of immune cells and increased expression of inflammatory cytokines in ocular structures. When the eye becomes a target of the immune response in rheumatic diseases, the ocular immune system is excessively stimulated by relevant immunoregulatory molecules, thereby disrupting the balance of immunoregulatory mechanisms. In addition, chronic inflammation of the ocular surface results from a disruption in the balance between the innate and adaptive immune systems, leading to chronic dry eye (Bron A.J. et al., 2017; Resch M.D. et al., 2015; Wang L. et al., 2021).
Medications used to treat rheumatic conditions, such as nonsteroidal anti-inflammatory drugs and corticosteroids, are also associated with an increased incidence of CSD, and therapy with methotrexate and cyclophosphamide can independently induce or exacerbate symptoms of SCD (Colebatch A.N. et al., 2011; Singh J.A. et al., 2016). For these patients, regular evaluation of the ocular surface should be considered (Punjabi O.S. et al., 2006).

Dermatologists
Chronic facial and ocular rosacea is commonly associated with ocular conditions, including blepharitis and meibomitis, which can lead to dysfunction of the meibomian glands and subsequent atrophy (Karaman Erdur S. et al., 2016). This leads to instability of the tear film, as well as a reduction in tear production. Additionally, patients with rosacea have higher concentrations of pro-inflammatory cytokines on the ocular surface, which typically leads to the development of CRF (Palamar M. et al., 2015). Common dermatological medications can also contribute to a predisposition to DKS. For example, isotretinoin (13-cis-retinoic acid), which is used topically and/or systemically to prevent age-related changes and treat acne vulgaris, can cause blepharitis, meibomian gland dysfunction, and XSO (Aslan Bayhan S. et al., 2016; Ruiz-Lozano R.E. et al., 2020).
Another dermatological condition that may be associated with OCS is atopic dermatitis, which is often accompanied by the development of atopic keratoconjunctivitis, the primary pathogenic mechanism of which is the development of meibomian gland dysfunction, and a shortened tear film break-up time, leading to eye irritation and dryness (Lee S.H. et al., 2019).

Obstetricians and Gynecologists
CSO is most often associated with hormonal changes characteristic of postmenopausal status. In one study, the overall prevalence of CSO in postmenopausal women was 73%. Tear film instability was observed in 35% of patients, and aqueous deficiency in 18.18%; however, most women had a mixed type of pathology. The severity of DSO increased with the patient’s age and the duration of menopause (Maurya R.P. et al., 2019). Early diagnosis and treatment of DSO in postmenopausal women can improve quality of life and reduce the risk of vision loss associated with dry eyes. Therefore, an ophthalmological eye examination should be an integral part of care for postmenopausal women.
Although both low and high estrogen levels are associated with DSO symptoms, low androgen levels are a more significant etiological factor. Postmenopausal hormone therapy with estrogen or estrogen plus progestin has shown limited benefit for DGS symptoms and may even lead to progression of meibomian gland dysfunction, a reduction in tear film break-up time, and decreased tear flow. However, systemic or topical androgen therapy has demonstrated promising results in improving dry eye symptoms (Intira S. et al., 2016).
The association between hormone therapy and an increased incidence of DKS has been observed by researchers in numerous studies (Gomes J.A.P. et al., 2017; Chia E.M. et al., 2003). They noted that hormone replacement therapy (HRT) is associated with an increased risk of developing DSC in postmenopausal women and reported that this risk increases with the duration of HRT (Schaumberg D.A. et al., 2001). The use of hormonal contraceptives also contributes to the development of OCS; an increased risk is observed with regular use and with a higher number of contraceptives used (He B. et al., 2022). The mechanism underlying this association is currently unknown.
The development of CSC in pregnant women is a pressing issue. During pregnancy, the interaction between hormonal, metabolic, hemodynamic, vascular, and immunological factors affects the ocular system and causes changes that are usually temporary. It is believed that DKS may be caused by both hormone-dependent mechanisms and direct damage to lacrimal acinar cells due to pregnancy-induced increased immune reactivity. In previous studies, researchers observed that the prevalence of CSO increases significantly from the second to the third trimester of pregnancy and returns to lower levels 6 weeks after delivery (Nwachukwu N.Z. et al., 2019).

Pediatricians
The prevalence of HSO in pediatric patients is likely underestimated due to a lack of epidemiological data, difficulties in interpreting symptoms, and the tendency of clinicians to associate HSO solely with congenital or autoimmune disorders (Villani E. et al., 2020). Diagnosing HSO is challenging in the pediatric population due to difficulties in identifying symptoms, the lack of validated diagnostic criteria and reference data, and the absence of tests specifically designed for children.
Each year, there is growing evidence that the use of tablets and smartphones among children of various age groups significantly increases their risk of developing HSO. For example, researchers from Korea, while assessing the time children spend in front of screens and outdoors, found that the average daily duration of smartphone use was higher, and the average duration of outdoor activity was lower in the CSD group compared to the control group. After discontinuing smartphone use for 4 weeks in the OSD group, both subjective symptoms and objective signs improved (Moon J.H. et al., 2016). Japanese researchers obtained similar results after evaluating data from >7,000 schoolchildren (Mineshita Y. et al., 2021).
The fundamentals of initial treatment for OCS in children are the same as in adults; including patient education and/or caregiver education, environmental and/or lifestyle modifications, dietary adjustments, eyelid hygiene and/or warm compresses, as well as the use of eye lubricants (Alves M. et al., 2008).

Conclusions

• Primary care physicians, as well as many clinical specialists, play an important role in the management of DKS by establishing the diagnosis and, likely, prescribing non-specialized treatment, as well as referring patients to ophthalmologists for evaluation and initiation of long-term therapy.
• Successful treatment of AMD often involves the use of several pharmacological and/or non-pharmacological treatments, as well as environmental and lifestyle modifications.
• Primary care physicians and clinical specialists should carefully review their treatment protocols for patients at risk of or with existing DSE; whenever possible, they should use medications with less impact on the ocular surface to minimize damage.

Based on materials from: Sheppard J., Lee B.S., Periman L.M. Dry eye disease: identification and therapeutic strategies for primary care clinicians and clinical specialists. Ann Med. 2023 Dec;55(1):241-252.

Reference from “ZU”

One of the first-line treatments for dry eye syndrome is artificial tears—over-the-counter topical agents that lubricate and moisturize the eyes. They may be based on cellulose, hyaluronic acid, carbomers, or polyvinyl alcohol. Highly effective are preparations containing hyaluronic acid, which has mucomimetic, mucoadhesive, and viscoelastic properties, thereby improving the stability of the tear film and ensuring comfort on the eye’s surface.
The domestic pharmaceutical market offers two products manufactured by Kyiv Vitamin Plant JSC that can be used topically for dry eye syndrome: the ophthalmic solution Gilays and the ophthalmic isotonic ointment Gilays Kea. Both products contain hyaluronic acid; its moisturizing and protective properties help alleviate irritation, dryness, burning, and the sensation of a foreign object in the eyes caused by environmental factors (wind, sun, dry air, salt water, smoke, excessively bright light, air conditioning, heating), prolonged computer use, or in cases of eye surgery, conjunctivitis, or frequent or prolonged use of contact lenses. Prepared by Yulia Kotikovich

Prepared by Yulia Kotikovich