Management of dry eye disease: a systematic approach for the primary care physician

Kendrick C Shih 施愷迪，Jimmy SM Lai 黎少明，Alex LK Ng 伍立祺

Summary

Dry eye disease is a common condition of the ocular surface. It is a multifactorial and often chronic problem, present ing with non-specific but very troubling symptoms. It causes considerable impairment to one’s quality of life and poses significant health care costs to society. The diagnosis and classification of dry eye disease requires a careful history and physical examinat ion. Bedside or clinic-based tests may provide additional useful information. A systematic and stepwise approach to treatment, with an emphasis on patient empowerment through lifestyle modification, is recommended as it ensures a logical progression that is easily understandable to the patient. This papers aims to demonstrate that dry eye disease management can be a fulfilling experience for both the primary care physician and the patient.

摘要

乾眼症是一種常見的眼表疾病。它有多種成因，且常屬 慢性。它沒有明顯、但能使人非常煩惱的病徵。對病人 的生活質素有一定影響，並對社會醫療開支構成負擔。 乾眼症的診斷和歸類需從病史、臨床檢查和一些簡單測 試著手。在治療時，會按情況有系統和漸進地，在病人主動在生活習慣上配合進行。本文旨在說明治療乾眼症 可以是一項能令病人和家庭醫生雙方都感滿意的經歷。

lntroduction

Dry eye disease is a common but under-appreciated condition in clinical practice worldwide. It is common in Asian countries, especially in its urban populations. A number of cross-sectional studies in different Asian countries demonstrated that roughly 25-35% of the population suffer from dry eye disease, compared to 5-16% in Western countries.^1-4 Furthermore, its prevalence increases with age^{5, 6}, up to 70% of elderly patients older than 60 years of age was found to be suffering from symptomatic dry eye disease in one study conducted in Japan.⁷ For sufferers, it poses a significant burden on the quality of life, resulting in considerable economic costs to society.⁸ A 2006 healtheconomics study in the United Kingdom estimated that the annual healthcare costs to the public sector for every 1,000 dry eye patients was 1.1 million United States dollars.⁹

The condition may range from mild and episodic to severe and chronic and is often multifactorial in relation to cause.¹⁰ Furthermore, the presenting symptoms of dry eye disease are often non-specific, commonly including complaints of visual impairment, symptoms of ocular surface irritation (grittiness, fatigue, heaviness, burning sensations and photophobia) and paradoxically excessive tearing. It may also be exacerbated by changes in the patient’s environment, lifestyle, health status, systemic disease and medication.¹¹ To further compound the frustrating nature of this condition, the patient’s self-reported symptoms and disease severity often correlate poorly with physical examination findings and investigation results.¹² In fact, results from tests for dry eye disease show low repeatability.¹³ As a result, management of dry eye disease is often perplexing and unsatisfying to the primary care physician. However, it is important to note that there is consistent evidence that treatment, involving both medication and lifestyle modification, is effective in dry eye management.¹¹, ^14-16 This paper aims to demonstrate that a systematic and step-wise approach to dry eye disease management can result in a positive and fulfilling experience for both the primary care practitioner and the patient.

Diagnosis and classification

The definition of dry eye disease has changed over the years, with the most recent international consensus by the Dry Eye Workshop (DEWS) in 2007:

Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.

Thus, the definition is predominantly based on clinical symptoms and simple physical signs. It is important to note the lack of a single questionnaire, physical examination finding or investigation result that can diagnose dry eye disease.¹⁷ Therefore, the diagnosis of dry eye disease is based on the collection of symptoms and signs obtained during a consultation.¹⁸ It can be broadly classified into those with aqueous tear deficiency, excessive tear evaporation or a combination of both. The most common cause of aqueous tear deficiency is lacrimal gland dysfunction secondary to autoimmune disease, termed keratoconjunctivitis sicca. Other less common causes include lacrimal gland deficiency (primary or secondary to systemic disease) and lacrimal duct obstruction.¹⁹ The most common cause of excessive tear evaporation is meibomian gland dysfunction.^{20, 21} This is a prevalent condition of the eyelids where there is a significant change in the consistency and quantity of meibum, causing inflammation of the eyelids and subsequent ocular surface dysfunction. While most cases are idiopathic, it may occasionally be secondary to dermatological conditions like acne rosacea and demodex infestation. In a recent cross-sectional study by Lemp et al, from a sample of 159 patients with confirmed dry eye disease, 14% had aqueous tear deficiency, 50% had evaporative dry eye, and 36% had mixed aqueous tear deficiency and evaporative dry eye.²² We can thus infer that most patients with dry eye disease have some component of excessive evaporative tear loss. This is an important consideration when giving treatment, as patients with evaporative tear loss will rarely improve with prescription of artificial tears alone.

Dry eye symptoms are often non-specific with patients reporting grittiness, fatigue or heaviness, burning sensation and photophobia. These symptoms represent a dysfunctional ocular surface with irritation of the densely innervated cornea and conjunctiva. Furthermore, they may paradoxically complain of excessing tearing, which is a compensatory response of the body to an inadequate tear film and is more commonly seen in evaporative dry eye. As a result of the impaired ocular surface, which is essential to light refraction, patients report transient episodes of blurring of vision, which is usually improved with blinking, rest or after the addition of artificial tears.²³

Physical examination is aided by the use of clinical tools. They can be classified according to the three main aspects of the disease that they measure; lacrimal function, tear stability and ocular surface damage.²⁴

Lacrimal function is commonly measured using the Schirmers Test. This is a simple clinical tool for primary care clinics. The most important is Schirmers Test II, which is conducted under topical anaesthesia, and measures the basal tear secretion of the eyes. The Schirmers Test strips are secured on the lower lid fornices away from the cornea and kept in place for 5 minutes. A reading of less than 5 mm after 5 minutes suggests aqueous tear deficiency. Tear stability and ocular surface damage can both be measured using fluorescein staining. A commercial strip of 2% fluorescein dye is wetted with 0.9% isotonic sodium chloride solution and gently applied to the tarsal conjunctival surface of the lower lid. The patient is then asked to blink a few times to allow diffusion of the fluorescein stain over the entire corneal surface. The eyes are then examined under either a slit lamp or a direct ophthalmoscope using a cobalt blue light. For tear stability, the tear break-up time is measured, which is the interval between a complete blink and the first random dry eye spot noted on the cornea surface. A normal result would be when the tear break-up time exceeds the average inter-blink interval for the patient.²⁵ This is accepted internationally as 10 seconds. For ocular surface damage, this is measured by the intensity and location of punctate epithelial erosions (appearing as green dots) on the corneal surface.²⁶

In addition to assessment of dry eye status, it is important to consider the potential underlying diseases that result in dry eye. A history of contact lens use²⁷, ocular disease (including corneal infections), ocular surgery, especially laser-refractive surgery^{28, 29}, and eyelid abnormalities are important. Physical examination may show evidence of an irregular, scarred corneal surface that results in increased tear evaporation or abnormal eyelid positions. Furthermore, systemic diseases are known to cause or exacerbate dry eye. This is particularly important if aqueous tear deficiency is the predominant cause and there are other symptoms experienced by the patient. Autoimmune diseases like Sjogren’s syndrome, rheumatoid arthritis and systemic lupus erythematosus are commonly associated with keratoconjunctivitis sicca. It is essential to ask about history of dry mouth, and its complications, include halitosis, increased dental caries and changes in dietary habits. It is also important to ask about history of joint aches and pains as well as skin rash. If the conditions are suspected, blood tests for autoimmune markers and a referral to a rheumatologist should be considered. Other conditions to look out for include history of allogenic bonemarrow transplantation, which may result in multi-organ graft-versus-host disease.^{30, 31} One of the most common sites of involvement is the ocular mucosal surface, with sufferers having chronic ocular surface inflammation, destruction of lacrimal glands and ducts, resulting in severe dry eye disease secondary to aqueous tear deficiency. Endocrine conditions like thyroid disorders and diabetes mellitus may also result in dry eye disease.³² Therefore, it is important to ask about recent changes in diet and weight, changes in cold/heat tolerance, polyuria, polydipsia as well as changes in mood. For women, it is important to ask about menstrual status, as dry eye disease is more common after menopause.^{33, 34}

Equally important as checking for history of systemic disease, is taking a complete history of currently-used oral medication. Over-the-counter medication like antihistamines are known to cause dry eye disease, while a number of prescription medications, including hormonal replacement therapy³⁵, anti-hypertensives, anti-depressants, anti-psychotics and medication for movement disorders have dry eye disease as side effects. Although the presence of dry eye disease almost never warrants cessation of systemic medication, understanding its contribution allows the patient a better grasp of his/her current condition.

Treatment

The aim of treatment is to reduce or alleviate symptoms and signs of dry eye disease, maintain and improve visual function and reduce or prevent structural damage to the ocular surface. In order to standardise dry eye management, international consensus groups have been formed to publish guidelines based on the latest technology and evidence. The most recent one is the 2007 International DEWS Report, which provides a step-wise treatment approach to disease management (Figure 3).³⁶ A revised international consensus, DEWS 2, is expected to be published in 2017.³⁷

Education, environmental and dietary modification

All patients with dry eye should be given general advice on environmental modifications.^{11, 16, 38, 39} These include increasing room humidity and avoiding direct exposure to windy areas (which causes the tear film to evaporate). Computer screens should be below eye level so as to minimise the exposed inter-palpebral area and patients should be advised to blink regularly to ensure a re-distribution of an even tear film after each blink. Other factors that could exacerbate dry eyes, such as frequent contact lens wear, or sleep deprivation, should be advised. Systemic medications causing dry eye, such as antihistamines or anti-depressants, should be avoided if possible. For dietary modification, the anti-inflammatory property of Omega-3 fatty acids can improve both aqueous deficient dry eye and Meibomian gland dysfunction (MGD). MGD is a chronic, diffuse abnormality of the Meibomian glands resulting in terminal duct obstruction. This disrupts the lipid layer of the tear film, causing increased evaporation. This is very common in dry eye patient and often co-exist with aqueous deficient dry eye. Patients should be taught to perform daily eyelid warm compression for 10 to 15 minutes followed by a lid hygiene (gentle cleansing of the Meibomian orifices on eyelid margin). Additionally, to further aid patient empowerment, physicians can recommend online self-help and education websites on dry eye disease like www.dryeyezone.com.

Lubricants

Ocular lubricants, or artificial tears (AT), are the first line and mainstay option in treating dry eye.⁴⁰ They are available and can be easily obtained from community pharmacies. The different brands of artificial tears mainly differ in terms of electrolytes composition, choice of viscosity agent and surfactants, osmolarity, and whether preservatives are used or not. No single artificial tears were shown to be superior to the others, and the choice of AT type is mostly based on patient’s preference.^{41, 42} As a general rule, if the patient requires AT more than four times a day, preservative-free preparation should be used as preservatives can exacerbate ocular surface inflammation and cause epithelial toxicity.¹⁵

Artificial tears in gel or ointment form should be used in more advanced cases as they have higher retention time on the ocular surface. However, applying the gel or ointment can cause transient blurring effect and cause inconvenience to patient’s activities of daily living.

Anti-inflammatory agents

From our current understanding, ocular surface inflammation plays a key role in the pathological mechanism of dry eye. Targeting this ocular surface inflammation is essential in the management of dry eye.⁴³ Short-term pulse topical steroid eyedrops could be used.^{44, 45} However, the use of steroid can lead to increased intraocular pressure (IOP), and thus should only be given by ophthalmologists with regular monitoring of the IOP. Topical 0.05% cyclosporine (commercially available as Restasis, Allergen), a Food and Drug Administration approved eyedrops for treating aqueous-deficient dry eye, has been shown in several placebo-controlled randomised controlled trials (RCTs) to be effective in increasing tear production.^46-51 It has a good safety profile, but some patients may experience initial irritation when starting this eyedrops. Topical nonsteroidal anti-inflammatory drug is also effective in reducing dry eye symptoms, but there is risk of corneal epithelial toxicity or even corneal melting, thus it is not commonly used for treating dry eyes.^{52, 53}

Punctal plugs

The use of punctal plugs to retain tears is commonly performed as an office procedure. Two main types of plugs exist, which include an absorbable type usually made of collagen, and a non-absorbable type which usually has a surface collar, neck and a wide base. As the lower punctum drains over 80 to 90% of tears, plugging the lower punctum is usually adequate for alleviating the signs and symptoms of dry eye.^54-56 Side effects of plugs mainly include dislodgement or uncommonly, canaliculitis. In case where dry eye is severe, or frequent replacement of the plugs is required, permanent punctal occlusion with cauterisation could be performed.

Oral medications

The use of oral antibiotic agents, in particularly tetracyclines (such as 100mg doxycycline daily for 2-3 months), should be considered in patients with persistent Meibomian gland dysfunction which is a main cause of evaporative dry eye.^{57, 58} Female patients should be advised on contraception during the treatment period. If tetracyclines are contraindicated or poorly tolerated, macrolides like oral azithromycin could be an alternative for Meibomian gland dysfunctions. Its advantages include shorter treatment duration and better overall clinical response when compared to doxycycline in clinical trials.⁵⁹ The other type of oral medications for dry eye is oral secretagogues.^60-63 These drugs, such as pilocarpine and cevimeline, target the muscarinic cholinergic receptors and can improve dry eye. However, these drugs cause systemic side effects such as excessive sweating and diarrhea, and are rarely prescribed by ophthalmologists in Hong Kong.

Autologous serum eyedrops

Autologous serum eye drops were made using patient’s own serum diluted with balanced-salt solution. This contains epidermal growth factors, fibronectin, and cytokines that are not available in artificial tears, and could improve the dry eye symptoms as well as promoting corneal epithelial healing.^{64, 65} However, due to the need of frequent blood taking and the inconvenience in preparing the eye drops, they are usually reserved for more severe cases with dry eye associated corneal complications such as persistent epithelial defects.

Surgery

The role of surgical intervention is mainly reserved for severe cases with sight-threatening corneal complications, such as in patients with chemical burns, Steven-Johnson Syndrome or other autoimmune diseases affecting the ocular surface. Examples include amniotic membrane transplantation or tarsorrhaphy for corneal ulcerations and perforations.

Conclusion

The DEWS severity grading and treatment suggestions provide a good guideline in the initial management of dry eye. Subsequent follow-ups should follow a stepwise approach based on patient’s response. With the upcoming DEWS 2 international consensus to be published early next year, the approach to dry eye disease management is everevolving with new diagnostic and therapeutic technologies, as well as more evidence from well-designed randomised controlled trials.⁶⁶