A systematic review on prevalence , risk factors , clinical diagnosis and medical management of dry eye disease in the Arab population

Dry eye (DE) is known as a multifactorial disease of the tears and ocular surface that results in symptoms such as discomfort and visual disturbance. In addition, profile tear film (TF) instability with possible damage to the ocular surface, which is characterised by increased osmolarity of the TF and inflammation of the ocular surface, is also observed.1,2 More so, researchers have postulated that DE is a specific pathology caused by diverse aetiologies.3,4 According to Farrand et al.,5 the pathology condition is also termed keratoconjunctivitis sicca (KCS) or dysfunctional tear syndrome (DTS) that results in a significant burden for both patients and ophthalmologists. Previous data have shown that the prevalence of DE ranges from 7% to 33% across the world.6,7 Researchers likewise suggested that the rates of DE vary widely from one population to another because of different definitions, race diversity, types of clinical diagnostic test used, lifestyle, specific regions and age range.8,9,10,11 Therefore, the exact percentage of DE is not accurately estimated worldwide.12 Cases with positive DE signs and clinical symptoms often result in impairment militating against achieving a productive lifestyle, social living and even standard level of education.13,14

Previous studies have reported that the prevalence of DE ranges from 8.7% to 32% in the Middle East. 23,24 However, to the best of our knowledge, the prevalence range of DE in Arab countries is not currently available in the literature. Thus, the present study is the first to perform a systematic review to investigate the prevalence, risk factors, clinical diagnosis, influencing factors and medical management of DE disease specifically in Arab countries within four seasons, namely, less rainfall, cold temperature in winter, hot temperature and high humidity in summer.

Methodology
In this study, all search keywords were carried out with Boolean operators (OR/AND). Main keywords such as prevalence OR incidence OR rate OR frequency OR proportion OR epidemiology OR distribution OR major risk OR influencing factors OR symptoms OR questionnaires OR signs OR clinical tests and DE disease OR syndrome OR disorder were searched on Google Scholar and PubMed databases from June 2017 to June 2020. Furthermore, other search terms included treatment OR management and DTS OR xerophthalmia OR KCS OR keratitis sicca and pharmacologic OR non-pharmacologic approaches and in Arab countries (Saudi Arabia OR Palestine OR Kuwait OR Egypt OR Algeria OR Bahrain) in this investigation (see Figure 1). Admittedly, the information about the prevalence, risk factors, clinical diagnosis and medical management of DE in the Arab population were not available in the Cochrane, KoreaMed and Elsevier databases. This could be one of the limitations of this study. Another possible drawback of this systematic review is that only English language articles published from 2017 to 2020 were selected. The DE started to be referred to as a multifactorial disorder in 2017. 2 However, meta-analysis reports conducted by Jüni et al. 25 and Egger et al. 26 postulated a higher quality of the methodology issues in the English language reviews compared with non-English language publications. The same group of authors also found that English language journals had larger sample sizes and highly reliable outcomes than for other language articles. Case series, case reports and control studies including the TF biochemistry, immunological picture of primary Sjogren's syndrome (SS), homeostasis of the TF, ocular surface inflammation and graft disease were excluded. Then, the following data were extracted from the articles or abstracts that met our inclusion criteria: year of publication, name of first investigator and co-workers, study design, country or area of study, range age or mean age, crude prevalence (%), diagnostic criteria, risk factors and medical management. This enhances and helps to generalise the results of the study and improve internal validity. There were 52 articles and/or abstracts for DE disease in the Arab population in the different databases. However, there were very scarce cohort follow-up reports that aim to identify the treatment of DE disease and variation in the time of measurement of tear break-up time (TBUT) test and tear meniscus height. This is also a limitation of the study. All systematic reviews had a potential drawback, which is the tendency for publishing the manuscript's positive results. This is another limitation of the study. The flow chart of this study is presented in Figure 2.

Ethical consideration
This article followed all ethical standards for research without direct contact with human or animal subjects.
Full abstracts or arƟcles included (56) Case series, case reports and control studies were excluded (2) English abstracts or arƟcles related to systemic lupus erythematosus, Sjögren's syndrome (SS), Non-(SS) and tradiƟonal eye therapies were also excluded (4) Final list of English abstracts or arƟcles included in the current systemaƟc review (52)

Prevalence of dry eye
The latest development is a prevalence study of DE in Riyadh district based on a prospective study by utilising the McMonnies' DE questionnaire. 12 A similar study reported that the overall prevalence of DE was 35.9% in cases ≥ 40 years of age (Table 1). Another study, which observed the frequency of DE in the Northern Region of Saudi Arabia, was performed by Alsweilem et al. 19 Their sample consisted of 384 teenagers, which was investigated at 3 months for data collection. The rate of DE in the report was assessed by a predesigned questionnaire. Their results showed that approximately 36.5% of the teenager participants had clinical symptoms. A less recent report that also postulated to determine the prevalence of clinical symptoms associated with risk factors in the King Abdulaziz Specialist Hospital (Taif) was adopted by Alzahrani et al. 20 In that report, the identified risk factors impacting ocular surface disease index (OSDI) included arthritis, hypercholesterolaemia and Lasik surgery. The frequency of DE symptoms in Al-Ahsa, Saudi Arabia was 32.1%, with a higher percentage in subjects > 56 years of age and more predominant in women compared with men, and with the highest percentage amongst smokers and diabetic patients. 23 Likewise, Alharbi and co-workers revealed a higher frequency of DE in coastal population of eastern province, Saudi Arabia (62.4%) compared with the previous clinical report. 23 The same group used the OSDI to assess DE disease. 27 Furthermore, in a cross-sectional study of DE cases in Egypt, the prevalence of DE disease was 6.8%. 28  In a clinical study of an asymptomatic DE in the Lebanese population, with subjects older than 18 years, the prevalence was found to be 36.4%. 35 The symptomatic DE assessment by the OSDI questionnaire was adopted in some studies.

Clinical diagnosis of dry eye
Routinely, dry eye questionnaires (DEQs) are employed for examining the natural history of the disease and in population-based studies. 3 Ocular symptoms are the major concern for patients with DE, 1 which signifies the importance of the application of the appropriately validated

Medical management of dry eye
Dry eye disorder (DED) is reduced in the Arab population by many approaches, such as pharmacologic and nonpharmacologic methods. 16,19,39 There are several pharmacologic methods, which include tear supplementation, tear retention, tear stimulation and anti-inflammatory agents. 40 On the other hand, there are many possible non-pharmacologic approaches regarding the management of DE pathology. These include avoidance of exacerbating factors and eyelid hygiene. 41,42,43 Many tear supplements can be applied to manage the DE syndrome, but the most common treatment of DE in Arab populations includes artificial tears. 44 Asbell 45 found that the use of artificial tears in mild to moderate DE disease was effective. Patients with moderate to severe disease often combine artificial tears with other forms of treatments. 46 The autologous serum tear secreted by the patient has also been used in the management of severe DE syndrome. 47 There are four approaches for tear retention, namely, punctal plugs, moisture spectacles/goggles, therapeutic CLs and tarsorrhaphy. 48,49 Whilst tear stimulation, for instance, oral cholinergic agents such as pilocarpine or cevimeline (used off-label for aqueous-deficient DED). 50,51 Another form of treatment is the use of anti-inflammatory agents. The anti-inflammatory agents can be divided into three main medications, which include topical corticosteroids, oral tetracyclines and topical cyclosporine. 39,52 On the other hand, other therapies such as nutritional supplements (essential fatty acids), mucolytics (topical acetylcysteine, used off-label in DED with filamentary keratitis) and topical vitamin A (off-label and controversial, but possibly useful in severe DED with squamous metaplasia or ocular surface keratinisation) have also been explored. 52,53,54

Discussion
There is high prevalence of DED in the Arab studies compared with other parts of the world. This might be because of the high percentage of rheumatoid arthritis, DM and the use of age-related systemic and topical medications in the elderly population. 21,23,27,31,35 Alzahrani et al. 21 and several other researchers (Sherry et al. 35 ; Shanti et al. 31 ) have reported a significant association between TF harm and increase in age (see Table 2). This may be because of the high percentage of rheumatoid arthritis, DM and the use of age-related systemic and topical medications, which may lead to deterioration of TF intact. 5,12 Furthermore, gender is another factor that has been documented to influence TF profile. 6,7 Arab data found altered rate of tear production in women as compared to men, particularly after  Table 2.
Previous studies on the Arab population found a significant relationship between DE symptoms and positive clinical signs. 17,29,31 This might be attributed to different DE surveys and types of clinical diagnostic tests used. For instance, Shanti et al. 31 reported a strong association between intense symptoms and clinical diagnostic signs, whilst Yasir et al. 12 reported a lack of association between the self-reported symptoms and positive DE signs.

Conclusion
The prevalence of DE in the Arab population varies in reports, from 10% in UAE to 69% in Palestine. Increase in age, gender difference (more in females), wearing of CLs, refractive operation, glaucoma, blepharitis, MGD, pterygium, spring catarrh and allergic conjunctivitis were all known to be related to DE in the Arab population. In addition, topical glaucoma eye drops, biological drugs, arthritis, thyroid disease, hypertension, DM, smoking or passive smoking, computer or smartphone, watching television and continuous reading were also reported to influence the DED prevalence. Furthermore, OSDI is one of the most common tools for the diagnosis of DE syndrome in the Arab population, whilst the most common clinical test used in the Arab reports is the TBUT. Some previous reports have found a lack of association between DE symptoms and signs. However, other studies have found a strong association between them. For treatment, tear supplements can be applied to manage the DE syndrome, and the most common treatment of DE in Arab populations is the use of artificial tears.