Dry Eye Research in 2013: 32 Notable Human Studies

The 2013 picture

What the research shows

The strongest 2013 treatment evidence came from randomized comparisons, but even these trials often mixed encouraging secondary findings with short follow-up or negative primary endpoints. The diagnostic and exposure studies helped explain variation among patients while leaving many tests and risk links in need of broader confirmation.

Treatments and clinical trials

Controlled studies investigated anti-inflammatory drugs, lubricants, supplements, and tear conservation. Several found mixed results or involved small, specialized groups.

1. Topical anakinra improved some outcomes, but missed a key staining test

   A 12-week randomized trial assigned 75 patients with dry eye to two concentrations of the interleukin-1 blocker anakinra or vehicle drops. Bilateral corneal-staining clearance occurred in 29% of the 2.5% group versus 7% of the vehicle group, and symptom scores favored anakinra, but the primary comparison of mean corneal-staining change was not statistically significant. This early-phase trial was small, and the higher dose did not show a consistent added benefit.

2. A short omega-3 trial reported better symptoms and tear tests

   Sixty-four patients with dry eye were randomized to omega-3 fatty-acid capsules or placebo for one month. Symptom scores, tear breakup time, and Schirmer readings improved more in the supplement group. The sample and treatment period were small, so the study cannot establish a durable benefit across dry eye types.

3. A mixed fatty-acid supplement improved symptoms, not tear production

   In a six-month randomized trial, 38 postmenopausal women with moderate to severe dry eye received gamma-linolenic and omega-3 fatty acids or placebo. Symptom scores and some ocular-surface inflammation measures favored the supplement, while tear production, breakup time, and staining did not clearly improve. The small, specific population and mixed signs limit any general treatment claim.

4. Rebamipide matched hyaluronate for corneal staining over four weeks

   A multicenter randomized trial compared 2% rebamipide drops with 0.1% sodium hyaluronate in 188 patients. At four weeks, rebamipide met the trial's noninferiority criterion for corneal staining and performed better on conjunctival staining and some discomfort measures; tear production and breakup time were similar. The active-comparator trial provides short-term evidence but does not show longer-term benefit or superiority on every outcome.

5. MIM-D3 missed its primary dry eye endpoints

   A 28-day randomized phase 2 trial assigned 150 dry eye patients to two doses of the nerve-growth-factor mimetic MIM-D3 or vehicle. Prespecified primary staining and symptom endpoints were not met, although some secondary signs and diary symptoms favored treatment. Those secondary results are exploratory and do not override the negative primary findings.

6. Lipid-containing lubricants reduced evaporation in a chamber study

   A randomized crossover study tested three lubricant formulas for two weeks each in 18 people with dry eye and 19 controls, then measured their tears under low-humidity conditions. All three products improved several dry eye measures, while lipid-containing drops reduced evaporation more than the nonlipid formula. The short, product-specific comparisons had no untreated control period, so the broader clinical advantage remains uncertain.

7. Cyclosporine after cataract surgery improved some tear measures

   In 32 people having cataract surgery in both eyes, one eye received 0.05% cyclosporine and the other saline for three months. Tear production and stability favored cyclosporine at later visits, and patients reported less dryness. The paired-eye design was small, and whole-person symptom ratings cannot be assigned cleanly to one treated eye.

8. Tacrolimus helped selected patients with graft-versus-host dry eye

   Fourteen patients with ocular graft-versus-host disease who could not tolerate cyclosporine used topical tacrolimus for three months while continuing other care. Symptoms and several ocular-surface findings improved from baseline. Because this was a selected, uncontrolled group, the changes cannot be attributed to tacrolimus alone.

9. Punctal plugs improved tear tests in Sjögren dry eye

   A randomized comparison assigned 42 patients with primary Sjögren keratoconjunctivitis sicca to punctal plugs or artificial tears; 40 completed three months. Both groups improved on symptoms and surface staining, while plugs produced greater gains in Schirmer readings and tear breakup time. Contrast sensitivity did not differ significantly between groups, and the study was modest in size and duration.

10. Diquafosol improved symptoms in short breakup-time dry eye

    Researchers studied diquafosol drops in a prospective 39-eye series and a separate four-week randomized comparison involving 17 eyes with short tear breakup time. Symptoms and breakup time improved with diquafosol, but fluorescein staining and topographic tear-stability measures did not show clear gains. The randomized component was very small and focused on a particular dry eye pattern.

Surgery, visual function, and quality of life

Prospective surgical cohorts documented transient postoperative symptoms and tear changes. Smaller functional studies and patient reports explored how ocular dryness affects daily activities.

11. Reading speed was slower in a dry eye clinic group

    Investigators compared reading speed and contrast sensitivity in 52 people with dry eye and 20 controls. The dry eye group read more slowly, with greater slowing among those with more severe disease, while contrast sensitivity did not differ significantly. This cross-sectional clinic comparison had a wider age range in the dry eye group and cannot show that treating dryness restores reading speed.

12. Dry eye signs peaked soon after cataract surgery

    A prospective study followed 92 patients after uncomplicated cataract surgery with symptom and tear-film testing. Dry eye findings were most prominent in the first postoperative week and generally lessened by one to three months. The single-center cohort had no nonsurgical comparison group, so it cannot isolate every effect of the procedure.

13. SMILE showed fewer surface changes than LASIK in one cohort

    A prospective six-month study compared 38 patients undergoing small-incision lenticule extraction with 33 undergoing femtosecond LASIK. Both groups had temporary dry eye symptoms and reduced corneal sensitivity, but staining and sensitivity loss were generally less pronounced after SMILE. Treatment was not randomized, leaving room for differences between the surgical groups to affect the comparison.

14. Two LASIK flap methods gave mostly similar dry eye results

    Investigators prospectively followed 87 patients after LASIK with a femtosecond-laser or mechanical-microkeratome flap. Both groups developed temporary worsening in several ocular-surface and sensitivity measures; adjusted tear breakup time favored the femtosecond group, but corneal staining did not clearly differ. Nonrandom assignment and differences in surgical characteristics limit a causal comparison.

15. Dry eye patients missed more targets in a driving simulator

    In a simulator study, 20 people with dry eye were compared with 20 age- and sex-matched controls on target detection and response time. The dry eye group missed more targets and responded more slowly, particularly in simulated complex road situations. A small simulator task cannot establish effects on real-world crash risk.

16. Women reported a greater daily burden from dry eye than men

    A questionnaire study revisited 1,518 women and 581 men with previously identified dry eye from two large U.S. health-professional cohorts. Women reported more severe symptoms, more effects on activities, and greater use of treatments. The analysis relied on self-report, and cohort differences such as age prevent a simple biological explanation for the sex difference.

17. Sjögren symptom burden tracked quality of life differently from other sicca

    A Korean cross-sectional study compared 104 people with primary Sjögren syndrome with 42 who had sicca symptoms without Sjögren syndrome. The Sjögren patient-reported symptom index was associated with poorer health-related quality of life in the Sjögren group, while dry-mouth ratings were more informative in the non-Sjögren group. The study measured associations at one visit and covered systemic sicca as well as eye dryness.

Symptoms, tear tests, and biomarkers

Questionnaires, point-of-care inflammation testing, gland imaging, microscopy, and tear-protein studies offered new ways to characterize dry eye. Most still needed validation outside selected research samples.

18. A Japanese questionnaire measured dry eye's effect on daily life

    Researchers developed the 15-item Dry Eye-Related Quality-of-Life Score questionnaire through several stages and evaluated it in 203 dry eye patients and 21 controls. Its scores showed useful reliability and validity for symptoms and daily impact. The small control group and Japanese development setting mean that performance in other populations requires confirmation.

19. An MMP-9 office test identified inflammation in selected patients

    A masked multicenter study compared a tear MMP-9 point-of-care test with a clinical dry eye classification in 143 patients and 63 controls. Reported sensitivity was 85% and specificity 94%. These figures came from selected groups and a clinical reference definition; MMP-9 indicates ocular-surface inflammation rather than every form of dry eye.

20. Meibomian gland loss tracked a thinner tear lipid layer

    A cross-sectional study compared 30 people with obstructive meibomian gland dysfunction with 25 controls using gland imaging, lipid-layer interferometry, and tear-film tests. Greater gland loss was associated with a thinner lipid layer, and the gland-dysfunction group had shorter tear breakup times. The small observational design cannot show whether gland loss caused the measured tear changes.

21. Confocal imaging found different cell patterns across dry eye types

    Investigators used in vivo corneal confocal microscopy in four groups of 15 people: Sjögren dry eye, non-Sjögren dry eye, meibomian gland dysfunction, and controls. Nerve and inflammatory-cell patterns differed across groups, with prominent changes in some disease subtypes. Fifteen participants per group were not enough to establish dependable diagnostic cutoffs or causal mechanisms.

22. Noninvasive tear breakup agreed weakly with symptom scores

    A study of 99 participants compared noninvasive tear breakup measured by a Keratograph device with the Ocular Surface Disease Index. The relationship was weak and inverse, with a correlation near −0.20. A single instrument measure therefore did not closely reflect how much discomfort patients reported in this sample.

23. Standardized conjunctival sampling supported HLA-DR research

    Researchers tested impression-cytology collection and handling for the inflammatory marker HLA-DR, including comparisons among dry eye patients of differing severity. Their protocol yielded usable cell samples after shipment and storage and showed a severity-related HLA-DR pattern. This methods work did not establish a clinical diagnostic threshold or prove that changing HLA-DR improves symptoms.

24. Tear proteins separated some selected dry eye subtypes

    Two studies analyzed tear proteins from 169 people assigned to control, aqueous-deficient, lipid-deficient, or mixed dry eye groups. A panel of six proteins showed its strongest differences in aqueous-deficient disease, with much less separation for lipid-deficient disease. High classification performance within these selected samples needs independent testing in ordinary clinics.

Associated conditions and environmental stress

Workplace surveys, medical cohorts, and controlled exposure studies linked dry eye findings to screen use, mental health, pain sensitivity, diabetes, autoimmune disease, and dry air. Most observational comparisons cannot establish cause and effect.

25. Dry eye symptoms tracked with sensitivity to pain

    In a cross-sectional study of women in the TwinsUK cohort, researchers compared questionnaire-defined dry eye with heat-pain testing on the forearm. Women reporting dry eye were more sensitive to pain, and greater ocular symptom burden also tracked with greater pain sensitivity in a questionnaire subset. The all-female sample and self-reported eye measures cannot show whether pain sensitivity causes dry eye symptoms or follows them.

26. Long screen hours accompanied more dry eye in office workers

    The Osaka study examined 561 office workers who completed both a questionnaire and an eye examination. Definite or probable dry eye was more common among women than men, and more than eight daily hours of display use was associated with higher odds of dry eye. This cross-sectional workplace sample used a broad case definition and cannot show that screens caused the condition.

27. Depression related more to dry eye symptoms than tear signs

    The population-based Beijing Eye Study compared dry eye measurements with a later depression questionnaire in a large adult cohort. Depression was associated with reported dry eye, while objective tear and surface measures showed little or no corresponding relationship. Different measurement times and the observational design leave the direction and explanation of the association uncertain.

28. Post-traumatic stress and antidepressant use tracked severe dryness symptoms

    Among 248 older male U.S. veterans, researchers compared dry eye symptoms and signs with post-traumatic stress, depression, and medication use. Post-traumatic stress and selective serotonin reuptake inhibitor use were associated with severe symptom reports, but objective tear-test differences were not clear. The cross-sectional, male veteran sample cannot establish medication effects or general-population risk.

29. Dry eye in type 2 diabetes was linked to retinopathy

    Investigators examined 243 people with type 2 diabetes and found dry eye in about 28% under their study definition. Dry eye was associated with diabetic retinopathy but not clearly with neuropathy or nephropathy. The single-time-point clinical sample cannot determine which changes came first or estimate risk for everyone with diabetes.

30. Simulated airplane conditions worsened dry eye measures

    Researchers exposed 20 dry eye patients to a two-hour low-humidity, low-pressure, airflow chamber and compared them with 15 dry eye patients under standard conditions. Symptoms, tear stability, and surface staining worsened under the simulated cabin conditions, alongside changes in tear inflammatory markers. The small controlled simulation cannot quantify symptoms during actual air travel.

31. Baseline tear findings predicted response to a drying challenge

    Fifteen people without dry eye and ten with dry eye underwent a 90-minute low-humidity goggle challenge. Corneal staining increased in both groups, and some baseline tear-meniscus and staining measures related to the response. This small artificial exposure is useful for hypothesis generation, not a validated prediction tool for daily environments.

32. Rheumatoid arthritis with secondary Sjögren showed responsive eye inflammation

    Researchers followed 12 patients with active rheumatoid arthritis and secondary Sjögren syndrome and 12 with rheumatoid arthritis alone, repeating eye exams, confocal imaging, and tear-cytokine tests after systemic arthritis activity was suppressed. Dry eye symptoms, staining, inflammatory-cell density, and selected tear cytokines improved in the secondary Sjögren group, with no comparable pattern in the other group. This very small, nonrandomized before-and-after study cannot isolate the effect of a specific systemic treatment.