The Pathophysiology, Diagnosis, and Treatment of Dry Eye Disease
Background: Dry eye disease (DED) is common; its prevalence around the world varies from 5% to 34%. Its putative pathogenetic mechanisms include hyperosmolarity of the tear film and inflammation of the ocular surface and lacrimal gland. Dry eye is clinically subdivided into two subtypes: one with decreased tear secretion (aqueous-deficient DED), and one with increased tear evaporation (hyperevaporative DED).
Methods: This review is based on pertinent publications retrieved by a selective PubMed search and on the authors’ own clinical and scientific experience.
Results: The diagnostic evaluation of dry eye disease should include a detailed patient history, thorough split-lamp examination, and additional tests as indicated. Few randomized controlled therapeutic trials for dry eye have been published to date. Artificial tears of various kinds are recommended if the symptoms are mild. Lid hygiene is helpful in the treatment of hyperevaporative dry eye, while collagen or silicon plugs can be used for partial occlusion of the efferent lacrimal ducts to treat severe hyposecretory dry eye. The benefit of long-term topical anti-inflammatory treatment of moderate or severe dry eye disease with corticosteroids or cyclosporine A eye drops has been documented in clinical trials on a high evidence level. Orally administered tetraycycline derivatives and omega-3 or omega-6 fatty acids are also used.
Conclusion: The treatment of dry eye has evolved from tear substitution alone to a rationally based therapeutic algorithm. Current research focuses on pathophysiology, new diagnostic techniques, and novel therapies including secretagogues, topical androgens, and new anti-inflammatory drugs.
Dry eye disease is defined as 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 subacute inflammation of the ocular surface” (1).
The ocular surface (cornea, conjunctiva, accessory lacrimal glands), meibomian glands (specific sebaceous glands of the eyelid margin, which produce the outer lipid film of the tear film), the main lacrimal gland, and the innervation between them form a functional unit. Any or all of these structures may be affected in dry eye disease (2). Recent studies have shown that dry eye is an inflammatory disease that has many features in common with autoimmune disease (2, 3, e1). Stress to the ocular surface (environmental factors, infection, endogenous stress, antigens, genetic factors) is postulated as the pathogenetic triggering mechanism. Proinflammatory cytokines, chemokines, and matrix metalloproteinases lead to the expansion of autoreactive T helper cells which infiltrate the ocular surface and lacrimal gland (2, 3). The result is a vicious circle of damage to the ocular surface and inflammation.
Classification into “dry eye with reduced tear production (aqueous-deficient)” and “dry eye with increased evaporation of the tear film (hyperevaporative)” has proved useful on practical grounds.
Around 10% of patients with dry eye have a solely aqueous-deficient disorder. Hyperevaporative disorders, mostly caused by dysfunction of the meibomian glands, and mixed hyperevaporative/aqueous-deficient forms account for more than 80% of cases (4, e2, e3). Based on this new insight, novel diagnostic procedures and therapeutic approaches have evolved.
After reading this article, the reader should:
- Have learned that dry eye disease is not a minor complaint but a disease that has much in common with autoimmune diseases.
- Understand that the modern diagnostic procedure for dry eye disease requires, in addition to careful history taking and examination, specific tests to distinguish it from other diseases of the ocular surface such as allergies and infections.
- Be able to implement a sophisticated therapeutic regimen in which anti-inflammatory therapy plays an important role.
Around the world, between 5% and 34% of people suffer from dry eye (5, 6, e4–e7); prevalence increases significantly with age. The large differences in prevalence figures are due to variations in study populations, geographical differences and differences in method, and, until the middle of 2007, variations in the definition of the disease. No current prevalence figures exist for Germany. A study dating from 1977 showed that 11.7% of the German population—about 9 million people in all—suffered from symptoms of dry eye (7).
Dry eye impairs functional vision, especially in reading, at the computer, or when driving (9, 10, e10, e11). Reading speed is significantly reduced and correlates with disease severity (9). Tests in a driving simulator have shown significantly reduced reaction time (10). Reduced quality of life in everyday activities and leisure pursuits is reported by 60% of patients—comparable to the decrease in quality of life reported for angina pectoris—while 38% of patients complain of reduced efficiency at work (11, 12, e12).
Dry eye disease is significantly associated with anxiety disorders and depression (11, 13, e13). One large population-based cross-sectional study found manifest depression in 13.7% of patients with dry eye disease, compared with 8.6% of the control group.
Annual treatment costs per patient with dry eye in the USA are US$ 783 (taking account of the fact that patients themselves pay for a large proportion of the artificial tears required). The cost to the health care system is US$ 3.84 million a year (14).
The subjective symptoms in dry eye disease are often nonspecific. They include (1):
- Foreign body sensation
More or less pronounced conjunctival redness and damage to the ocular surface with punctate epithelial erosions (superficial punctate keratitis) are typical in dry eye; temporal conjunctival folds parallel to the lid margin are indicative. The lower tear meniscus is reduced. In addition, there are often signs of meibomian gland dysfunction with thickened eyelid margins and telangiectasia. The meibomian gland orifices are obstructed with a cloudy, granular or solid secretion that can only be expressed by exerting considerable pressure on the lower lid (15). If the meibomian gland dysfunction is associated with inflammation, blepharitis (inflammation of the lid margin) or meibomitis (inflammation of the meibomian glands) is present.
In late stages or in severe forms of the disease, conjunctival scarring or corneal complications can occur. In addition to filamentary keratitis, persistent epithelial defects, ulceration, and even corneal perforation can complicate the course. Severe complications of dry eye disease are rare and are observed in the context of primary or secondary Sjögren's syndrome, graft-versus-host disease, ichthyosis, Stevens–Johnson syndrome, and xerophthalmia (e14–e21). They can result in loss of vision or even functional blindness.
A classification of dry eye based on the severity of symptoms and clinical signs has been established (1) (Table 1).
Unfortunately subjective and objective clinical findings do not always correlate (16, 17). There are patients in considerable discomfort who have no significant clinical signs, and also those with severe dry eye and vision-threatening ocular complications who suffer from only mild symptoms.
Diagnostic tests are necessary in order to distinguish between dry eye, infections and allergies, which can present very similar clinically, but require different treatment. If an incorrect clinical diagnosis is made and antiallergic drugs or epitheliotoxic antibiotics are prescribed, dry eye may worsen. The diagnostic tests allow patients to be classified into one of two treatment-based subgroups, “aqueous-deficient” or “hyperevaporative.” Diagnostic guidelines were published in 2007 by the Dry Eye Workshop (1). The suggested sequence of dry eye tests is presented in Box 2.
A comprehensive history is essential, including (e22):
- Time, place, and diurnal variation of symptoms, workplace stress (e.g., VDU work; dry, dusty air; air conditioning)
- Systemic diseases (especially collagen vascular disease, Graves' disease, diabetes mellitus, infections such as hepatitis C and HIV)
- Medication history.
Questionnaires are available for standardized history taking in suspected dry eye disease (e.g., Ocular Surface Disease Index [OSDI] or the Impact of Dry Eye on Everyday Life [IDEEL] questionnaire) (e23, e24).
Examination of the eyelids
Blinking is important to distribute the tear fluid over the ocular surface, and supports secretion from the meibomian glands. The normal blink rate while speaking is extremely variable at 15.5 ± 13.7 blinks/minute. During reading and computer work, the blink rate is significantly reduced, to 5.3 ± 4.5 blinks/minute (e25, e26), which promotes evaporation of tear fluid. A reduced interval between blinks, from about 6 seconds to 2.6 seconds, and incomplete blinking, are typical of patients with dry eye (19).
Lid congruity and lid closure
Lid incongruity (e.g., ectropion, entropion) or insufficient lid closure (e.g., facial nerve palsy) can disturb the integrity of the tear film on the ocular surface and must be surgically corrected.
Detailed examination of the eyelid margin will yield information about its inflammation or any dysfunction of the meibomian glands with associated hyperevaporative disorder. Eyelashes, eyelid margin, and meibomian gland orifices are examined using the slit lamp. Noncontact infrared meibography allows the meibomian glands to be visualized directly (20) (Figure 1a and 1b).
Examination of the conjunctiva
Temporal lid-parallel conjunctival folds (LIPCOFs) in straight gaze are a result of increased friction between the lids and the conjunctiva. They are regarded as an important indicator of dry eye, with a sensitivity of 84.9% and a specificity of up to 90% (21). They can be simply, quickly, and noninvasively identified using the slit lamp. LIPCOFs are classified according to Höh et al. into three grades (22) (Box 3) (Figure 2).
Examination of the ocular surface
The surface of the eye is examined using the slit lamp and vital stains. The usual dyes in clinical practice are fluorescein and lissamine green. Fluorescein stains both the precorneal tear film and epithelial erosions in the conjunctiva and cornea. Lissamine green highlights superficially damaged cells with a defective mucin layer (e27) (Figure 3).
With all dyes, the intensity of staining and the dye distribution pattern are assessed semiquantitatively. Staining in the area of the palpebral fissure is suggestive of dry eye.
Several indices are available for the assessment of staining, such as the van Bijsterveld Index (Figure 4), the Oxford Grading Scale, and the CLEK scheme (1).
Examination of the tear film
Tear film meniscus
The height of the tear film meniscus observed during slit lamp examination can provide clues about the presence of hyposecretory dry eye. The tear film can be objectively measured using optical coherence tomography (e28). Tear meniscus height was 0.2 ± 0.09 mm in patients with dry eye versus 0.5 ± 0.02 mm in patients with healthy eyes (e29). In clinical practice, a tear meniscus below 0.2 mm is regarded as pathological. A foamy tear film is an indicator of an altered lipid layer in patients with meibomian gland dysfunction.
Tear film break-up time
The tear film break-up time (TFBUT) describes the stability of the tear film. It is determined after instillation of unpreserved fluorescein drops without topical anesthesia using a slit lamp with a cobalt blue filter. After a complete blink, the time to the first break-up of the tear film is measured. The normal range lies between 20 and 30 seconds. Values below 10 seconds are definitely pathological (23) (Figure 5a). Tear film break-up time can be assessed noninvasively, without fluorescein, by using videokeratography (Figure 5b).
Tear secretion tests
The Schirmer test measures the secretions of the lacrimal gland. In the Schirmer I test, calibrated filter paper strips (35 × 5 mm) are placed in the conjunctival sac of the temporal third of the lower eyelid and, with the patient's eyes closed, wetting of the strip is measured after 5 minutes (Figure 6). There are large inter- and intraindividual differences, which make the evaluation difficult. However, both the variation range and the absolute values are reduced in aqueous-deficient dry eye, probably because of the reduced reflex tear secretion (1). Values of 5 or less are certainly pathological (1).
The Jones basal secretion test is performed like the Schirmer I test, but after topical anesthesia. Test results are about 40% lower than in Schirmer I (23) and are also subject to marked inter- and intraindividual fluctuations. In theory, this test measures only the basal secretion, without reflex tears.
Other additional investigations
Tear film osmolarity/MMP-9 test
Measuring tear film osmolarity is regarded as an important further test in the diagnosis of dry eye. A portable osmometer suitable for tear film analysis in routine clinical practice is currently under evaluation in clinical trials (e30, e31). A quick test to determine matrix metalloproteinase-9 (MMP-9) in the tear film of patients with dry eye disease is also being currently evaluated in clinical trials (e32). Because of the paucity of data, however, and partially conflicting results, neither of these techniques is yet part of the standard diagnostic repertoire.
Differentiating between aqueous-deficient and hyperevaporative dry eye
Indicators of tear deficiency include a reduced tear meniscus, LIPCOFs, and a low Schirmer I test result. Patients with hyperevaporative dry eye usually show pathological changes to the lid margins, obstructed meibomian gland orifices, and thickened meibomian gland secretion. Tear film break-up time is reduced. Ocular surface damage and elevated tear film osmolarity can occur with both forms.
Diagnosing Sjögren's syndrome
Patients with xerostomia in addition to dry eye must be investigated for the possible presence of Sjögren's syndrome (SS).
The revised criteria of the European–American Consensus Group for the diagnosis of Sjögren's syndrome are summerized in Box 4 (24). If four of the six criteria are fulfilled, a diagnosis of Sjögren's syndrome can be made (24).
If SSA/SSB diagnostic testing is negative, a positive ANA (antinuclear antibody) test or positive rheumatoid factors may be indicative (25).
Treatment of dry eye disease
Patient education is important and includes the facts that dry eye is a chronic disease, that treatment is long-term and may be slow to take effect. Treatment for dry eye disease involves a step ladder approach corresponding to disease severity and must take into account associated meibomian gland dysfunction, (subclinical) inflammation of the ocular surface, and/or associated systemic disease (16).
The avoidance of aggravating factors such as cigarette smoke, dry heating air, air conditioning, and others is a fundamental part of treatment.
Artificial tears are the mainstay of therapy for all severity grades of dry eye. Although artificial tears are regarded as standard, no large, randomized, controlled studies have been carried out to evaluate the many different kinds of artificial tears available in the market. The licensing of artificial tears, most of which are marketed as CE products, is not based on their clinical effectiveness. Small randomized studies have shown that artificial tears
- Increase tear film stability
- Reduce ocular surface stress
- Improve contrast sensitivity and the optical quality of the surface
- Are able to increase quality of life (e33–e38).
A large number of preparations based on polyvinyl alcohol, povidone, hydroxypropyl guar, cellulose derivatives, and hyaluronic acid are available. Depending on the severity of disease, a whole range of substances from low-viscosity preparations to high-viscosity gels (carbomeres) and ointments can be used (16). As a matter of principle, for ocular surface disorders, products should be recommended that do not contain benzalkonium chloride (an epitheliotoxin) as a preservative (26). For meibomian gland dysfunction, artificial tears containing lipids such as triglycerides, phospholipids, and castor oil are available. In small randomized, controlled trials these led to improved meibomian gland function and increased tear film stability (27, e39–e41).
Eyedrops made from the patient’s own serum (autologous serum eyedrops) are used in a concentration of 20% to 100%. They contain a multitude of epitheliotropic growth factors and anti-inflammatory substances. Autologous serum eyedrops are used particularly in severe cases of dry eye. Their production is regulated by the German Medicines Act and Transfusion Law (28). A randomized, controlled study in patients with severe dry eye disease showed a significant improvement in tear film stability and subjective symptoms but no reduction in surface staining with autologous serum eyedrops compared to preservative-free artificial tears (29).
Even with only moderately severe dry eye, there is an (often subclinical) inflammatory reaction of the ocular surface and the lacrimal gland (2, 3). To break the vicious circle of surface damage and inflammation, anti-inflammatory treatment is required in patients with moderate to severe dry eye disease.
Randomized, controlled clinical studies have shown that unpreserved corticosteroid eyedrops, instilled over a period of 2 to 4 weeks, improve the symptoms and clinical signs of moderate to severe dry eye disease (30, 31). After 2 weeks of treatment, symptoms regressed moderately (43%) or completely (57%). Corneal fluorescein staining reduced significantly. Patient discomfort and clinical signs remained reduced for several weeks after therapy ceased (30, 31). A few patients developed complications with long-term therapy (raised intraocular pressure, cataract), and for this reason corticosteroid eyedrops are recommended only for short-term use (30). A cycle of treatment is also useful for testing patients’ response for long-term anti-inflammatory treatment with cyclosporine A.
Topical cyclosporine A
Cyclosporine A is an immunosuppressant that inhibits the calcineurin–phosphatase pathway by complex formation with cyclophilin, and thus reduces the transcription of T-cell-activating cytokines such as interleukin-2 (IL-2) (e42). Topical application of cyclosporine A leads to increased production of tear fluid, possibly via local release of parasympathetic neurotransmitters (e43). In randomized, controlled clinical trials, treatment with 0.05% eyedrops 2 ×/day led to improvement in keratopathy, increased Schirmer test values, reduced symptoms (blurry vision, ocular dryness, foreign body sensation, and epiphora), and a reduction in the use of artificial tears (32, e44, e45). This clinical improvement was associated with a reduction in inflammatory cells and inflammatory markers on the ocular surface (e46, e47) and an increase in the number of goblet cells in the conjunctiva (e45). Cyclosporine A eyedrops 0.05% are commercially available as a long-term therapeutic agent in the USA. In Germany, cyclosporine A can be prescribed as extemporaneous product from dispensing pharmacies.
Tacrolimus 0.03% eyedrops 1 to 2 ×/day have been successfully used in pilot studies and in small uncontrolled interventional case series in patients with severe dry eye disease. They appear to be as effective as cyclosporine A and are used in patients who cannot tolerate cyclosporine A (e48, e49). Tacrolimus/pimecrolimus skin ointment has been reported as successfully used on the eyelids 1 to 2 ×/day in treatment-resistant blepharokeratoconjunctivitis (e50).
Tetracyclines are bacteriostatic antibiotics with anti-inflammatory effect. They reduce the synthesis and activity of matrix metalloproteinases, the production of interleukin-1 (IL-1) and tumor necrosis factor, collagenase activity, and B-cell activation (e51, e52). Tetracycline analogs have been successfully used in small controlled studies to treat meibomian gland dysfunction and rosacea (33, e53). Dosages varied between 40 and 400 mg/day for doxycycline and between 50 and 100 mg/day for minocycline. Even at low doses, improvements were seen in tear film stability, tear production, and symptoms (33). Because of the significantly higher rate of adverse effects (primarily gastrointestinal and skin problems) at higher dosages, a low dosage for 6 to 12 weeks is recommended (16, 33).
Azithromycin, in addition to its well-known antibiotic effect, also has anti-inflammatory capacities (34). Azithromycin 1% has been successfully used in several small evidence-level-2/3 studies to treat blepharitis and meibomian gland dysfunction (35, e54). In addition to improved meibomian gland function and symptoms, a reduction in bacterial colonization of the eyelid margins and normalization of the meibomian gland secretion lipid profile were found (35, e54).
Omega fatty acids
Omega-3 and omega-6 are essential fatty acids for ocular surface homeostasis. They have to be absorbed from food. Omega-3 fatty acids, especially, work by blocking proinflammatory eicosanoids and reducing cytokines through anti-inflammatory activity (36). In a randomized, controlled clinical study systemic linoleic acid and gamma-linolenic acid given to 26 patients with dry eye disease reduced ocular surface inflammation, surface staining, and symptoms (36). Very recently, omega-3 fatty acid eyedrops have become available, and are currently under investigation.
The melting point of meibomian lipids is between 28 and 32°C. In patients with meibomian gland dysfunction, the melting point rises to 35°C (e55). The amount of lipid released depends on the temperature of the eyelid. Consistent eyelid hygiene is the basic treatment for meibomian gland dysfunction (37).
Hot compresses, eye lid warming masks or goggles, infrared heaters, and eyelid massage have been investigated in evidence-level-2/3 clinical studies. They led to clinical improvement in eyelid margin morphology with a reduction in blocked meibomian gland excretory ducts, and an increase in tear film stability and lipid layer thickness of the tear film (e56–e59). The effect of a 12-minute one-time automated thermodynamic treatment was compared with conventional eyelid hygiene 2×/day in a randomized clinical observer-masked study. After 1 and 3 months, a significant improvement in symptoms was seen compared to the conventional treatment. The improvement in expressibility of the meibomian secretion was similar for both treatments (e60).
Temporary occlusion of the tear ducts by small collagen or silicone plugs (punctal plugs) is effective in patients with severe aqueous-deficient dry eye disease (38, e61, e62). In a retrospective study, punctal plugs led to an improvement in subjective symptoms in 73.9% of patients, with a significant reduction in surface staining (38). The most frequent ‘complication' is loss of the plug (38, 39). In one prospective observation cohort study, 84.2% of plugs were retained at the end of 3 months, 69.5% after a year, and 55.8% at the end of 2 years (39). Since delayed tear drainage leads to the persistence of toxic and inflammatory factors on the ocular surface, concomitant anti-inflammatory treatment is indicated (e63). Rarely, the plug migrates into the nasolacrimal duct, resulting in inflammation or pyogenic granuloma, conjunctival epithelial erosion, or epiphora (38, 39). Because of the paucity of data, a Cochrane Review dating from 2010 recommended that large, randomized, controlled studies should be carried out to evaluate punctal plugs (40).
For severe ocular surface disorders in dry eye disease, bandage contact lenses and scleral lenses are available (e64). Surgical options such as tarsorrhaphy, amniotic membrane transplantation, and keratoplasty are used in cases of persistent corneal ulceration and perforation (16). Salivary glands have occasionally been transplanted to replace lacrimal glands, but in the long term this led to corneal edema and excessive lacrimation (e65).
To summarize, dry eye is a common disease, the differential diagnosis of which requires
- Careful history taking
- Detailed examination
- A series of diagnostic tests.
Studies show that tear deficiency alone is rarer than hyperevaporative dry eye. Artificial tears, regular eyelid hygiene, and punctal plugs together with anti-inflammatory treatment constitute the established approach to treatment. For patients with only minor symptoms, e.g., when working at a VDU, the primary care physician can try treatment with artificial tears. Patients with persistent moderate to severe clinical symptoms should be referred to an ophthalmologist for diagnosis and treatment.
Conflict of interest statement
Professor Messmer has received consultancy fees, fees for the preparation of scientific continuing education events, reimbursement of conference attendance fees and of travel and accommodation costs, and fees for carrying out clinical trials, from the following firms: Alcon Pharma, Bitop, Bausch & Lomb/Dr. Mann Pharma, Croma Pharma, Oculus Optikgeräte, Pharm-Allergan, Santen, Thea Pharma, and Ursapharm.
Manuscript received on 2 May 2014, revised version accepted on
27 August 2014.
Translated from the original German by Kersti Wagstaff, MA.
Prof. Dr. med. Elisabeth M. Messmer
Augenklinik der Ludwig-Maximilians-Universität
Mathildenstr. 8, 80336 München, Germany
@For eReferences please refer to:
|1.||The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop. Ocul Surf 2007; 5: 75–92. CrossRef|
|2.||Stern ME, Schaumburg CS, Pflugfelder SC: Dry eye as a mucosal autoimmune disease. Int Rev Immunol 2013; 32: 19–41. CrossRef MEDLINE PubMed Central|
|3.||Stevenson W, Chauhan SK, Dana R: Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol 2012; 130: 90–100. CrossRef MEDLINE PubMed Central|
|4.||Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD: Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea 2012; 31: 472–8. CrossRef MEDLINE|
|5.||Chia EM, Mitchell P, Rochtchina E, Lee AJ, Maroun R, Wang JJ: Prevalence and associations of dry eye syndrome in an older population: the Blue Mountains Eye Study. Clin Exp Ophthalmol 2003; 31: 229–32. CrossRef|
|6.||Schaumberg DA, Sullivan DA, Buring JE, Dana MR: Prevalence of dry eye syndrome among US women. Am J Ophthalmol 2003; 136: 318–26. CrossRef|
|7.||Ruprecht KW, Giere W, Wulle KG: Statistical contribution on symptomatic dry eye. Ophthalmologica 1977; 174: 65–74. CrossRef MEDLINE|
|8.||Bron AJ, Tomlinson A, Foulks GN, et al.: Rethinking dry eEye disease: A perspective on clinical implications. Ocul Surf 2014; 12: 1–31. CrossRef MEDLINE|
|9.||Ridder WH 3rd, Zhang Y, Huang JF: Evaluation of reading speed and contrast sensitivity in dry eye disease. Optom Vis Sci 2013; 90: 37–44. CrossRef MEDLINE|
|10.||Deschamps N, Ricaud X, Rabut G, Labbe A, Baudouin C, Denoyer A: The impact of dry eye disease on visual performance while driving. Am J Ophthalmol 2013; 156: 184–9. CrossRef MEDLINE|
|11.||Li M, Gong L, Chapin WJ, Zhu M: Assessment of vision-related quality of life in dry eye patients. Invest Ophthalmol Vis Sci 2012; 53: 5722–7. CrossRef MEDLINE|
|12.||Schiffman RM, Walt JG, Jacobsen G, Doyle JJ, Lebovics G, Sumner W: Utility assessment among patients with dry eye disease. Ophthalmology 2003; 110: 1412–9. CrossRef|
|13.||Labbe A, Wang YX, Jie Y, Baudouin C, Jonas JB, Xu L: Dry eye disease, dry eye symptoms and depression: the Beijing Eye Study. Br J Ophthalmol 2013; 97: 1399–403. CrossRef MEDLINE|
|14.||Yu J, Asche CV, Fairchild CJ: The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea 2011; 30: 379–87. CrossRef MEDLINE|
|15.||Foulks GN, Bron AJ: Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf 2003; 1: 107–26. CrossRef|
|16.||Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5: 163–78. CrossRef|
|17.||Sullivan BD, Crews LA, Messmer EM, et al.: Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: clinical implications. Acta Ophthalmol 2014; 92: 161–6. CrossRef MEDLINE|
|18.||Methodologies to diagnose and monitor dry eye disease: Report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5: 108–52. CrossRef|
|19.||Johnston PR, Rodriguez J, Lane KJ, Ousler G, Abelson MB: The interblink interval in normal and dry eye subjects. Clin Ophthalmol 2013; 7: 253–9. CrossRef MEDLINE PubMed Central|
|20.||Arita R, Itoh K, Inoue K, Amano S: Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology 2008; 115: 911–5. CrossRef MEDLINE|
|21.||Nemeth J, Fodor E, Lang Z, et al.: Lid-parallel conjunctival folds (LIPCOF) and dry eye: a multicentre study. Br J Ophthalmol 2012; 96: 1380–5. CrossRef MEDLINE|
|22.||Höh H, Schirra F, Kienecker C, Ruprecht KW: Lid-parallel conjunctival folds are a sure diagnostic sign of dry eye. Ophthalmologe 1995; 92: 802–8. MEDLINE|
|23.||Jacobi C, Cursiefen C: Ophthalmological complications in Sjogren's syndrome. Z Rheumatol 2010; 69: 32–40. CrossRef MEDLINE|
|24.||Vitali C, Bombardieri S, Jonsson R, et al.: Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002; 61: 554–8. CrossRef MEDLINE PubMed Central|
|25.||Liew MS, Zhang M, Kim E, Akpek EK: Prevalence and predictors of Sjogren's syndrome in a prospective cohort of patients with aqueous-deficient dry eye. Br J Ophthalmol 2012; 96: 1498–503. CrossRef MEDLINE|
|26.||Messmer EM: Preservatives in ophthalmology. Ophthalmologe 2012; 109: 1064–70. CrossRef MEDLINE|
|27.||Lee SY, Tong L: Lipid-containing lubricants for dry eye: a systematic review. Optom Vis Sci 2012; 89: 1654–61. CrossRef MEDLINE|
|28.||Geerling G, Unterlauft JD, Kasper K, Schrader S, Opitz A, Hartwig D: Autologous serum and alternative blood products for the treatment of ocular surface disorders. Ophthalmologe 2008; 105: 623–31. CrossRef MEDLINE|
|29.||Celebi AR, Ulusoy C, Mirza GE: The efficacy of autologous serum eye drops for severe dry eye syndrome: a randomized double-blind crossover study. Graefes Arch Clin Exp Ophthalmol 2014; 252: 619–26. CrossRef MEDLINE|
|30.||Marsh P, Pflugfelder SC: Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjogren syndrome. Ophthalmology 1999; 106: 811–6. CrossRef|
|31.||Pflugfelder SC, Maskin SL, Anderson B, et al.: A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance. Am J Ophthalmol 2004; 138: 444–57. CrossRef MEDLINE|
|32.||Sall K, Stevenson OD, Mundorf TK, Reis BL: Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology 2000; 107: 631–9. CrossRef|
|33.||Yoo SE, Lee DC, Chang MH: The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction. Korean J Ophthalmol 2005; 19: 258–63. CrossRef|
|34.||Sadrai Z, Hajrasouliha AR, Chauhan S, Saban DR, Dastjerdi MH, Dana R: Effect of topical azithromycin on corneal innate immune responses. Invest Ophthalmol Vis Sci 2011; 52: 2525–31. CrossRef MEDLINE PubMed Central|
|35.||Foulks GN, Borchman D, Yappert M, Kim SH, McKay JW: Topical azithromycin therapy for meibomian gland dysfunction: clinical response and lipid alterations. Cornea 2010; 29: 781–8. MEDLINE PubMed Central|
|36.||Barabino S, Rolando M, Camicione P, et al.: Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Cornea 2003; 22: 97–101. CrossRef MEDLINE|
|37.||Geerling G, Tauber J, Baudouin C, et al.: The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci 2011; 52: 2050–64. CrossRef MEDLINE PubMed Central|
|38.||Tai MC, Cosar CB, Cohen EJ, Rapuano CJ, Laibson PR: The clinical efficacy of silicone punctal plug therapy. Cornea 2002; 21: 135–9. CrossRef|
|39.||Horwath-Winter J, Thaci A, Gruber A, Boldin I: Long-term retention rates and complications of silicone punctal plugs in dry eye. Am J Ophthalmol 2007; 144: 441–4. CrossRef MEDLINE|
|40.||Ervin AM, Wojciechowski R, Schein O: Punctal occlusion for dry eye syndrome. Cochrane Database Syst Rev 2010: CD006775. MEDLINE PubMed Central|
|e1.||Goyal S, Chauhan SK, El Annan J, et al.: Evidence of corneal lymphangiogenesis in dry eye disease: a potential link to adaptive immunity? Arch Ophthalmol 2010; 128: 819–24. MEDLINE PubMed Central|
|e2.||Heiligenhaus A, Koch JM, Kruse FE, Schwarz C, Waubke TN: Diagnosis and and differentiation of dry eye disorders]. Diagnostik und Differenzierung von Benetzungsstörungen. Der Ophthalmologe 1995; 92: 6–11. MEDLINE|
|e3.||Tong L, Chaurasia SS, Mehta JS, Beuerman RW: Screening for meibomian gland disease: its relation to dry eye subtypes and symptoms in a tertiary referral clinic in singapore. Invest Ophthalmol Vis Sci 2010; 51: 3449–54. CrossRef MEDLINE|
|e4.||Lin PY, Tsai SY, Cheng CY, et al.: Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology 2003; 110: 1096–101. CrossRef|
|e5.||McCarty CA, Bansal AK, Livingston PM, Stanislavsky YL, Taylor HR: The epidemiology of dry eye in Melbourne, Australia. Ophthalmology 1998; 105: 1114–9. MEDLINE|
|e6.||Moss SE, Klein R, Klein BE: Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol 2000; 118: 1264–8. CrossRef|
|e7.||Schein OD, Hochberg MC, Munoz B, et al.: Dry eye and dry mouth in the elderly: a population-based assessment. Archiv Intern Med 1999; 159: 1359–63. CrossRef|
|e8.||Kim JH, Kim JH, Nam WH, et al.: Oral alcohol administration disturbs tear film and ocular surface. Ophthalmology 2012; 119: 965–71. CrossRef MEDLINE|
|e9.||Thomas J, Jacob GP, Abraham L, Noushad B: The effect of smoking on the ocular surface and the precorneal tear film. Australas Med J 2012; 5: 221–6. CrossRef MEDLINE PubMed Central|
|e10.||Liu Z, Pflugfelder SC: Corneal surface regularity and the effect of artificial tears in aqueous tear deficiency. Ophthalmology 1999; 106: 939–43. CrossRef|
|e11.||Miljanovic B, Dana R, Sullivan DA, Schaumberg DA: Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol 2007; 143: 409–15. CrossRef MEDLINE PubMed Central|
|e12.||Sullivan RM, Cermak JM, Papas AS, Dana MR, Sullivan DA: Economic and quality of life impact of dry eye symptoms in women with Sjogren's syndrome. Adv Exp Med Biol 2002; 506: 1183–8. CrossRef|
|e13.||Paulsen AJ, Cruickshanks KJ, Fischer ME, et al.: Dry eye in the beaver dam offspring study: prevalence, risk factors, and health-related quality of life. Am J Ophthalmol 2014; 157: 799–806. CrossRef MEDLINE|
|e14.||Golubovic S, Parunovic A: Corneal perforation in dry eye patients. Fortschr Ophthalmol 1987; 84: 33–7. MEDLINE|
|e15.||Inagaki E, Ogawa Y, Matsumoto Y, et al.: Four cases of corneal perforation in patients with chronic graft-versus-host disease. Mol Vis 2011; 17: 598–606. MEDLINE PubMed Central|
|e16.||Krachmer JH, Laibson PR: Corneal thinning and perforation in Sjogren's syndrome. Am J Ophthalmol 1974; 78: 917–20. CrossRef|
|e17.||Messmer EM, Hoops JP, Kampik A: Bilateral recurrent calcareous degeneration of the cornea. Cornea 2005; 24: 498–502. CrossRef|
|e18.||Petroutsos G, Paschides CA, Kitsos G, Drosos AA, Psilas K: Sterile corneal ulcers in dry eye. II. Treatment, complications and course. J Fr Ophtalmol 1992; 15: 106–11. MEDLINE|
|e19.||Pfister RR, Murphy GE: Corneal ulceration and perforation associated with Sjogren's syndrome. Archiv Ophthalmol 1980; 98: 89–94. CrossRef|
|e20.||Stevenson W, Shikari H, Saboo US, Amparo F, Dana R: Bilateral corneal ulceration in ocular graft-versus-host disease. Clin Ophthalmol 2013; 7: 2153–8. MEDLINE PubMed Central|
|e21.||Turgut B, Aydemir O, Kaya M, et al.: Spontaneous corneal perforation in a patient with lamellar ichthyosis and dry eye. Clin Ophthalmol 2009; 3: 611–3. CrossRef MEDLINE PubMed Central|
|e22.||Henrich CF, Ramulu PY, Akpek EK: Association of dry eye and inflammatory systemic diseases in a tertiary care-based sample. Cornea 2014; 33: 819–25. CrossRef MEDLINE|
|e23.||Abetz L, Rajagopalan K, Mertzanis P, et al.: Development and validation of the impact of dry eye on everyday life (IDEEL) questionnaire, a patient-reported outcomes (PRO) measure for the assessment of the burden of dry eye on patients. Health Qual Life Outcomes 2011; 9: 111. CrossRef MEDLINE PubMed Central|
|e24.||Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL: Reliability and validity of the Ocular Surface Disease Index. Archiv Ophthalmol 2000; 118: 615–21. CrossRef|
|e25.||Bentivoglio AR, Bressman SB, Cassetta E, et al.: Analysis of blink rate patterns in normal subjects. Mov Disord 1997; 12: 1028–34. CrossRef MEDLINE|
|e26.||Freudenthaler N, Neuf H, Kadner G, Schlote T: Characteristics of spontaneous eyeblink activity during video display terminal use in healthy volunteers. Graefes Arch Clin Exp Ophthalmol 2003; 241: 914–20. CrossRef MEDLINE|
|e27.||Bron AJ, Yokoi N, Gaffney EA, Tiffany JM: A solute gradient in the tear meniscus. I. A hypothesis to explain Marx's line. Ocul Surf 201; 9: 70–91.|
|e28.||Werkmeister RM, Alex A, Kaya S, et al.: Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci 2013; 54: 5578–83. CrossRef MEDLINE|
|e29.||Mainstone JC, Bruce AS, Golding TR: Tear meniscus measurement in the diagnosis of dry eye. Curr Eye Res 1996; 15: 653–61. CrossRef|
|e30.||Lemp MA, Bron AJ, Baudouin C, et al.: Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol 2011; 151: 792–8. CrossRef MEDLINE|
|e31.||Messmer EM, Bulgen M, Kampik A: Hyperosmolarity of the tear film in dry eye syndrome. Dev Ophthalmol 2010; 45: 129–38. CrossRef MEDLINE|
|e32.||Sambursky R, Davitt WF, 3rd, Latkany R, et al.: Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye. JAMA Ophthalmol 2013; 131: 24–8. CrossRef MEDLINE|
|e33.||Barabino S, Rolando M, Nardi M, et al.: The effect of an artificial tear combining hyaluronic acid and tamarind seeds polysaccharide in patients with moderate dry eye syndrome: a new treatment for dry eye. Eur J Ophthalmol 2014; 24: 173–8. CrossRef MEDLINE|
|e34.||Cohen S, Martin A, Sall K: Evaluation of clinical outcomes in patients with dry eye disease using lubricant eye drops containing polyethylene glycol or carboxymethylcellulose. Clin Ophthalmol 2014; 8: 157–64. MEDLINE PubMed Central|
|e35.||Diaz-Valle D, Arriola-Villalobos P, Garcia-Vidal SE, et al.: Effect of lubricating eyedrops on ocular light scattering as a measure of vision quality in patients with dry eye. J Cataract Refract Surg 2012; 38: 1192–7. CrossRef MEDLINE|
|e36.||Doughty MJ: Fluorescein-tear breakup time as an assessment of efficacy of tear replacement therapy in dry eye patients: a systematic review and meta-analysis. Ocul Surf 2014; 12: 100–11. CrossRef MEDLINE|
|e37.||Lee JH, Ahn HS, Kim EK, Kim TI: Efficacy of sodium hyaluronate and carboxymethylcellulose in treating mild to moderate dry eye disease. Cornea 2011; 30: 175–9. CrossRef MEDLINE|
|e38.||Zhang Y, Potvin R, Gong L: A study of the short-term effect of artificial tears on contrast sensitivity in patients with Sjogren's syndrome. Invest Ophthalmol Vis Sci 2013; 54: 7977–82. CrossRef MEDLINE|
|e39.||Craig JP, Purslow C, Murphy PJ, Wolffsohn JS: Effect of a liposomal spray on the pre-ocular tear film. Cont Lens Anterior Eye 2010; 33: 83–7. CrossRef MEDLINE|
|e40.||Goto E, Shimazaki J, Monden Y, et al.: Low-concentration homogenized castor oil eye drops for noninflamed obstructive meibomian gland dysfunction. Ophthalmology 2002; 109: 2030–5. CrossRef MEDLINE|
|e41.||Khanal S, Tomlinson A, Pearce EI, Simmons PA: Effect of an oil-in-water emulsion on the tear physiology of patients with mild to moderate dry eye. Cornea 2007; 26: 175–81. CrossRef MEDLINE|
|e42.||Matsuda S, Koyasu S: Mechanisms of action of cyclosporine. Immunopharmacology 2000; 47: 119–25. CrossRef|
|e43.||Yoshida A, Fujihara T, Nakata K: Cyclosporin A increases tear fluid secretion via release of sensory neurotransmitters and muscarinic pathway in mice. Exp Eye Res 1999; 68: 541–6. CrossRef MEDLINE|
|e44.||Baiza-Duran L, Medrano-Palafox J, Hernandez-Quintela E, Lozano-Alcazar J, Alaniz-de la OJ: A comparative clinical trial of the efficacy of two different aqueous solutions of cyclosporine for the treatment of moderate-to-severe dry eye syndrome. Br J Ophthalmol 2010; 94: 1312–5. CrossRef MEDLINE|
|e45.||Demiryay E, Yaylali V, Cetin EN, Yildirim C: Effects of topical cyclosporine a plus artificial tears versus artificial tears treatment on conjunctival goblet cell density in dysfunctional tear syndrome. Eye Contact Lens 2011; 37: 312–5. CrossRef MEDLINE|
|e46.||Kunert KS, Tisdale AS, Stern ME, Smith JA, Gipson IK: Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. Arch Ophthalmol 2000; 118: 1489–96. CrossRef|
|e47.||Turner K, Pflugfelder SC, Ji Z, et al.: Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion. Cornea 2000; 19: 492–6. CrossRef MEDLINE|
|e48.||Moscovici BK, Holzchuh R, Chiacchio BB, et al.: Clinical treatment of dry eye using 0.03% tacrolimus eye drops. Cornea 2012; 31: 945–9. CrossRef MEDLINE|
|e49.||Sanz-Marco E, Udaondo P, Garcia-Delpech S, Vazquez A, Diaz-Llopis M: Treatment of refractory dry eye associated with graft versus host disease with 0.03% tacrolimus eyedrops. J Ocul Pharmacol Ther 2013; 29: 776–83. CrossRef MEDLINE PubMed Central|
|e50.||Auw-Hadrich C, Reinhard T: [Treatment of chronic blepharokeratoconjunctivitis with local calcineurin inhibitors]. Behandlung der chronischen Blepharokeratokonjunktivitis mit lokalen Kalzineurininhibitoren. Ophthalmologe 2009; 106: 635–8. CrossRef MEDLINE|
|e51.||Kuzin II, Snyder JE, Ugine GD, et al.: Tetracyclines inhibit activated B cell function. Int Immunol 2001; 13: 921–31. CrossRef MEDLINE|
|e52.||Solomon A, Rosenblatt M, Li DQ, et al.: Doxycycline inhibition of interleukin-1 in the corneal epithelium. Invest Ophthalmol Vis Sci 2000; 41: 2544–57. MEDLINE|
|e53.||Shine WE, McCulley JP, Pandya AG: Minocycline effect on meibomian gland lipids in meibomianitis patients. Exp Eye Res 2003; 76: 417–20. CrossRef|
|e54.||Haque RM, Torkildsen GL, Brubaker K, et al.: Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis. Cornea 2010; 29: 871–7. CrossRef MEDLINE|
|e55.||McCulley JP, Shine WE: Meibomian secretions in chronic blepharitis. Adv Exp Med Biol 1998; 438: 319–26. CrossRef|
|e56.||Guillon M, Maissa C, Wong S: Eyelid margin modification associated with eyelid hygiene in anterior blepharitis and meibomian gland dysfunction. Eye Contact Lens 2012; 38: 319–25. CrossRef MEDLINE|
|e57.||Matsumoto Y, Dogru M, Goto E, et al.: Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction. Cornea 2006; 25: 644–50. CrossRef MEDLINE|
|e58.||Olson MC, Korb DR, Greiner JV: Increase in tear film lipid layer thickness following treatment with warm compresses in patients with meibomian gland dysfunction. Eye Contact Lens 2003; 29: 96–9. CrossRef MEDLINE|
|e59.||Purslow C: Evaluation of the ocular tolerance of a novel eyelid-warming device used for meibomian gland dysfunction. Contact Lens Anterior Eye 2013; 36: 226–31. CrossRef MEDLINE|
|e60.||Finis D, Hayajneh J, Konig C, et al.: Evaluation of an automated thermodynamic treatment (LipiFlow®) system for meibomian gland dysfunction: a prospective, randomized, observer-masked trial. Ocul Surf 2014; 12: 146–54. CrossRef MEDLINE|
|e61.||Cohen EJ: Punctal occlusion. Arch Ophthalmol 1999; 117: 389–90. CrossRef|
|e62.||Dursun D, Ertan A, Bilezikci B, Akova YA, Pelit A: Ocular surface changes in keratoconjunctivitis sicca with silicone punctum plug occlusion. Curr Eye Res 2003; 26: 263–9. CrossRef|
|e63.||Roberts CW, Carniglia PE, Brazzo BG: Comparison of topical cyclosporine, punctal occlusion, and a combination for the treatment of dry eye. Cornea 2007; 26: 805–9. CrossRef MEDLINE|
|e64.||Dimit R, Gire A, Pflugfelder SC, Bergmanson JP: Patient ocular conditions and clinical outcomes using a PROSE scleral device. Cont Lens Anterior Eye 2013; 36: 159–63. CrossRef MEDLINE|
|e65.||Geerling G, Collin JR, Dart JK: Ophthalmic experience with submandibular gland transplantation for severe dry eyes. Laryngoscope 2009; 119: 1445–6. CrossRef MEDLINE|
Aggregatibacter actinomycetemcomitans Leukotoxin (LtxA; Leukothera®): Mechanisms of Action and Therapeutic ApplicationsToxins, 201910.3390/toxins11090489
Drug Delivery and Translational Research, 201910.1007/s13346-019-00650-1
The Application of Artificial Neural Networks and Logistic Regression in the Evaluation of Risk for Dry Eye after VitrectomyJournal of Ophthalmology, 202010.1155/2020/1024926
Chronic Autoimmune Epithelitis - Sjogren's Syndrome and Other Autoimmune Diseases of the Exocrine GlandsBook, 201910.5772/intechopen.83821
Naucni casopis urgentne medicine - Halo 194, 201910.5937/Halo1902092S
Deutsches Aerzteblatt Online, 201710.3238/arztebl.2017.0641b
BMC Ophthalmology, 202110.1186/s12886-021-01912-8
Investigative Opthalmology & Visual Science, 201810.1167/iovs.18-24304
Ocular Immunology and Inflammation, 202010.1080/09273948.2020.1757122
Demodex Infection Changes Ocular Surface Microbial Communities, in Which Meibomian Gland Dysfunction May Play a RoleOphthalmology and Therapy, 202110.1007/s40123-021-00356-z
BioMed Research International, 201910.1155/2019/5763658
Frontiers in Physiology, 202010.3389/fphys.2020.01010
Journal of Evolution of Medical and Dental Sciences, 201910.14260/jemds/2019/734
Treatment Satisfaction Among Patients Using Anti-Inflammatory Topical Medications for Dry Eye DiseaseClinical Ophthalmology, 202010.2147/OPTH.S233194
In Vivo Anti-Inflammation Potential of Aster koraiensis Extract for Dry Eye Syndrome by the Protection of Ocular SurfaceNutrients, 202010.3390/nu12113245
A Decade of Effective Dry Eye Disease Management with Systane Ultra (Polyethylene Glycol/Propylene Glycol with Hydroxypropyl Guar) Lubricant Eye DropsClinical Ophthalmology, 202110.2147/OPTH.S294427
The Effect of Sodium Hyaluronate on the Corneal Biomechanics of Patients with Cataract and Dry Eye Before OperationInternational Journal of General Medicine, 202110.2147/IJGM.S297369
Frontiers in Immunology, 202110.3389/fimmu.2021.701951
Indian Journal of Clinical and Experimental Ophthalmology, 202110.18231/j.ijceo.2021.101
Current Eye Research, 201910.1080/02713683.2019.1574834
Pharmaceutical Nanotechnology, 202010.2174/2211738508666200628034227
Deutsches Aerzteblatt Online, 201710.3238/arztebl.2017.00641a
Clinical Ophthalmology, 202110.2147/OPTH.S281666
Development of a Novel In Vitro Immuno-Competent Model of Dry Eye Disease and Its Use to Evaluate the Efficacy of an Ocular Surface ModulatorOcular Immunology and Inflammation, 202110.1080/09273948.2021.1961811
Deutsches Aerzteblatt Online, 201710.3238/arztebl.2017.0302
Journal of Clinical Medicine, 201910.3390/jcm8081227
Ciencia y Tecnología para la Salud Visual y Ocular, 201910.19052/sv.vol17.iss1.3
The Open Ophthalmology Journal, 202110.2174/1874364102115010034
International Journal of Environmental Research and Public Health, 202110.3390/ijerph18052383
Clinical Ophthalmology, 202110.2147/OPTH.S313158
Mucoadhesive Bletilla striata Polysaccharide-Based Artificial Tears to Relieve Symptoms and Inflammation in Rabbit with Dry Eyes SyndromePolymers, 202010.3390/polym12071465
Frontiers in Human Neuroscience, 202010.3389/fnhum.2020.574758
International Journal of Nanomedicine, 202110.2147/IJN.S301717
Trends in the Utilization of Sodium Hyaluronate Eye Drops, Including Disposable and Multiuse Forms, in South Korea: A 14-Year Longitudinal Retrospective Cohort StudyFrontiers in Pharmacology, 202010.3389/fphar.2020.00720
Phase 3 Efficacy (Worse-Eye Analysis) and Long-Term Safety Evaluation of OTX-101 in Patients with Keratoconjunctivitis SiccaClinical Ophthalmology, 202110.2147/OPTH.S279364
Medical Immunology (Russia), 202110.15789/1563-0625-FOO-2036
A Novel Selective 11β-HSD1 Inhibitor, (E)-4-(2-(6-(2,6-Dichloro-4-(Trifluoromethyl)Phenyl)-4-Methyl-1,1-Dioxido-1,2,6-Thiadiazinan-2-yl)Acetamido)Adamantan-1-Carboxamide (KR-67607), Prevents BAC-Induced Dry Eye SyndromeInternational Journal of Molecular Sciences, 202010.3390/ijms21103729
International Journal of Molecular Sciences, 201910.3390/ijms20153755
Analysis of tear inflammatory molecules and clinical correlations in evaporative dry eye disease caused by meibomian gland dysfunctionInternational Ophthalmology, 202010.1007/s10792-020-01489-z
Molecular Biology Reports, 202110.1007/s11033-021-06419-5
Russian Ophthalmological Journal, 202110.21516/2072-0076-2021-14-2-63-68
Effects of Polyunsaturated Fatty Acids on Nonspecific Typical Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Clinical TrialsNutrients, 201910.3390/nu11050942