Dry Eye Research in 2016: 34 Notable Human Studies

The 2016 picture

What the research shows

The 2016 studies made dry eye's clinical variety clearer: tear inflammation, gland appearance, pain sensitivity, and symptoms did not always agree. Controlled trials identified specific gains and important null results, while early device and biomarker work still needed independent testing. Population figures remain tied to each study's definition and setting.

Treatment studies

Controlled trials offered the clearest treatment comparisons. Smaller device and procedure studies suggested options for selected patients but could not always separate treatment effects from time, extra care, or placebo response.

1. A short steroid course reduced staining after dry-air exposure

   A double-masked trial randomized 41 people with moderate to severe dry eye to fluorometholone 0.1% or lubricant drops for 22 days, then challenged their eyes for two hours in a controlled adverse environment. Corneal staining worsened in about 24% of the steroid group versus 63% of the lubricant group. This small, brief challenge trial cannot establish routine long-term steroid benefit or safety.

2. Two lubricant formulas improved similarly over two months

   A multicenter masked trial randomized 148 people with dry eye to xanthan gum–chondroitin sulfate or polyethylene glycol–propylene glycol drops for 60 days. Symptoms and several tear measures improved in both groups, without a clear between-formula advantage. The active comparison and short duration do not show how much of either group's improvement came from the drops themselves.

3. Cyclosporine improved staining but missed the combined endpoint

   The multicenter SANSIKA trial randomized 246 people with severe dry eye to 0.1% cyclosporine cationic emulsion or its vehicle for six months. Cyclosporine improved average corneal staining and an inflammation marker, but the primary endpoint requiring both substantial staining and symptom improvement was not met, and symptom scores improved similarly in both groups. Instillation pain was more common with cyclosporine, and the result applies to severe keratitis rather than every form of dry eye.

4. A year-long trial clarified lifitegrast tolerability

   The double-masked SONATA study assigned 331 patients to lifitegrast 5% or placebo drops twice daily for 360 days, focusing on safety. No serious ocular treatment-emergent events were reported, but eye irritation and other ocular events were more frequent with lifitegrast. Because safety was the main question, this trial alone does not establish its comparative symptom benefit.

5. Omega-3 capsules improved short-term measures in gland disease

   A 12-week, double-masked trial compared re-esterified omega-3 capsules with a linoleic-acid control in people with dry eye and meibomian gland dysfunction; 105 completed treatment. Tear osmolarity, breakup time, MMP-9 results, and symptom scores improved more in the omega-3 group. The results describe one supplement and comparator over three months and do not settle whether omega-3 helps dry eye more broadly.

6. Hydroxychloroquine did not clearly help Sjögren dry eye

   A double-blind trial randomized 39 people with primary Sjögren's syndrome to hydroxychloroquine or placebo for 12 weeks; 26 completed follow-up. Tear production and corneal staining did not differ significantly, and the symptom-score improvement with treatment was not significant versus placebo. The small completed sample limits precision, but this study did not demonstrate an ocular benefit from the drug.

7. Thermal pulsation performed similarly to warm compresses

   At a Singapore dry-eye clinic, 25 patients received one thermal-pulsation treatment and 25 used warm compresses twice daily for three months. Irritation improved in both groups, with no significant difference in symptoms or tear and gland measures between treatments over follow-up. The modest comparative study did not show that the device was superior to regular warming.

8. Two lubricant formulations had similar staining results

   An investigator-masked multicenter trial randomized 85 patients with moderate to severe dry eye to a preservative-free cationic emulsion or 0.18% sodium hyaluronate for three months. The cationic drop was noninferior for one-month surface staining, while some discomfort and dryness scores favored it. Secondary symptom differences were modest and do not prove broad superiority across dry-eye types.

9. Intense pulsed light showed improvement without a control group

   Investigators reviewed records of 100 patients with evaporative dry eye and meibomian gland dysfunction who received an average of four intense-pulsed-light sessions at two U.S. centers. Symptoms, tear breakup time, and several lid and meibum scores improved after treatment. The retrospective series had no untreated or sham group, so it cannot establish how much change was caused by the light procedure.

10. Punctal plugs relieved symptoms without lowering tear cytokines

    A single-center study inserted lower punctal plugs in 29 people with moderate dry eye and reassessed the worse eye three weeks later. Symptoms and most staining measures improved, but overall tear cytokine and MMP-9 levels did not change significantly. Short follow-up and the absence of a comparison group limit claims about lasting plug benefit or inflammation.

11. Gland probing added short-term gains to steroid drops

    Forty-nine people with obstructive meibomian gland dysfunction were randomly assigned to fluorometholone drops alone or drops plus intraductal gland probing. After one month, the probing group had better meibum grade, lid findings, and tear breakup time; tear production and gland dropout did not improve. The procedure was not sham-controlled, and the study provides only short-term results in patients who had responded poorly to standard care.

12. Omega-3 helped dry-eye measures in a rosacea trial

    A six-month, double-masked trial assigned 130 people with rosacea and dry-eye symptoms to omega-3 capsules or an olive-oil placebo. Symptoms and meibomian gland, tear-breakup, and Schirmer measures improved more in the omega-3 group. The findings concern rosacea-associated symptoms and do not establish the same effect in other causes of dry eye.

Clinical course and everyday impact

These studies followed symptoms after surgery or examined how dry eye relates to chronic pain, work, sleep, and longer-term nerve findings.

13. Chronic pain conditions accompanied greater dry-eye symptoms

    Among 425 Dutch dry-eye clinic patients, those with chronic pain elsewhere reported more ocular symptoms despite similar or milder measured eye signs. The authors saw a related pattern in a 64-person dry-eye subset that reuses the TwinsUK cohort analyzed in earlier years, rather than providing an independent population. Cross-sectional comparisons cannot establish why pain and eye symptoms cluster.

14. Dryness after cataract surgery lasted longer with diabetes

    A prospective study followed 174 patients with diabetes and 474 without it after cataract surgery, excluding people with dry eye beforehand. At one week, study-defined dry eye affected 17.1% and 8.1%, respectively; symptoms and tear stability returned more slowly in the diabetes group but recovered by three months. The groups were not randomized by diabetes status, so other health differences may have contributed.

15. Work impairment tracked symptoms more than clinical signs

    At 10 U.S. eye practices, 158 symptomatic dry-eye patients completed productivity and symptom questionnaires alongside clinical testing. They reported little missed work but substantial reduced performance while working, which correlated more strongly with symptoms than with examination signs. The cross-sectional, self-reported productivity estimates cannot measure each patient's actual output or establish causation.

16. More severe dry eye went with poorer sleep

    Across six eye clinics, investigators compared 301 dry-eye patients with 202 age-matched patients with other irritating ocular-surface conditions. Sleep-quality scores were worse in severe dry eye than in the comparison conditions and rose with dry-eye severity. The clinic-based, cross-sectional design cannot tell whether eye symptoms disrupted sleep or sleep problems worsened symptoms.

17. Corneal nerve differences persisted after LASIK

    A single-visit comparison examined 20 people more than a year after LASIK and 20 healthy controls using tear tests, sensation testing, neuropeptide assays, and corneal nerve imaging. Post-LASIK participants had altered central nerve measures and higher discomfort and tear CGRP levels. With no preoperative measurements, the study cannot identify which differences surgery caused or how nerve findings changed over time.

Testing and tear-film biology

Studies tested clinical grading scales, tear biomarkers, nerve sensitivity, and imaging. Results often depended on the reference group and still needed validation in independent clinics.

18. MMP-9 was positive in fewer than half of confirmed cases

    A prospective study compared a point-of-care tear MMP-9 assay in 47 eyes meeting dry-eye criteria and 54 control eyes. The test was positive in 40.4% of dry-eye eyes and 5.6% of controls, and positivity tracked several surface findings. It identified an inflammatory subset in this sample, but a negative result could not rule out dry eye.

19. Another clinic found no clear symptom pattern by MMP-9 status

    Among 128 symptomatic patients at a Veterans Affairs eye clinic, 39% had a positive point-of-care MMP-9 result in at least one eye. Standard symptom scores and surface signs did not differ significantly between positive and negative groups. This selected, predominantly veteran clinic sample shows that a positive inflammation test need not map neatly onto routine dry-eye measures.

20. Photographic scales improved consistency of gland grading

    Researchers photographed eyelids from 38 patients with meibomian gland dysfunction and 20 controls, then asked experts, general ophthalmologists, and nonphysicians to grade 226 images with new scales. Agreement was generally moderate to good, with stronger repeat ratings among experts. The scales were tested on selected photographs, so consistency during ordinary live examinations still needed confirmation.

21. Tear proteins differed across dry-eye subtypes

    Mass spectrometry compared tears from 80 people divided equally among aqueous-deficient dry eye, evaporative dry eye, combined disease, and healthy controls. Protein patterns differed across groups, and a targeted analysis supported 13 candidate proteins. The exploratory sample was small, and the protein panel was not independently validated as a diagnostic test.

22. Corneal pain sensitivity tracked complaints more than signs

    In 129 Veterans Affairs eye-clinic patients, investigators measured corneal mechanical detection and pain thresholds alongside dry-eye symptoms, ocular pain, and surface signs. Lower thresholds, indicating greater sensitivity, tracked more severe complaints but had little relation to standard ocular signs. The cross-sectional, predominantly older male sample cannot establish why sensitivity and symptoms traveled together.

23. A tear-cytokine model explored ocular graft-versus-host disease

    Researchers measured 15 tear molecules in 22 patients with ocular graft-versus-host disease and 21 healthy participants. A model combining two cytokines with age and sex separated the groups well within this study, with some testing against other dry-eye patients. The small development sample and limited outside validation prevent treating its reported accuracy as established clinical performance.

24. A thicker lipid layer did not always mean healthier glands

    Interferometry measured tear-film lipid thickness in 326 dry-eye patients and 64 controls, alongside gland and surface examinations. Among patients, thicker layers were associated with older age, female sex, hypersecretory meibomian gland dysfunction, and lid inflammation. Lipid thickness alone therefore cannot distinguish normal tear film from every type of gland disease, and the study was cross-sectional.

25. Interferometry patterns helped separate tear-film subtypes

    A single-center study classified tear-film interference patterns in 138 eyes from 76 people with and without dry eye. Ratings were reasonably repeatable and broadly aligned with normal tears, aqueous-deficient dry eye, and meibomian gland dysfunction. The patterns were checked against clinical categories assigned in the same setting, so accuracy in new clinics remained uncertain.

26. A contact-lens symptom score gained a practical threshold

    A daily-disposable lens registry analyzed baseline eight-question dryness scores from 977 soft-lens wearers and tracked scores after refitting. A score of at least 12 best marked highly symptomatic wearers, and about three points was a meaningful change on the scale. Registry data support symptom monitoring but do not prove that the lens refit alone caused improvements.

Population patterns and associated factors

Population samples and clinic comparisons studied where dry-eye symptoms and gland changes were more common. Most were cross-sectional, so they identify associations rather than causes.

27. Ozone and lower humidity correlated with dry eye in Korea

    Researchers linked annual air-quality and weather measures to dry-eye responses from 16,824 people in a South Korean national survey. Higher ozone and lower humidity were associated with more reported dry-eye symptoms and diagnoses; particulate matter measured as PM10 was not. Area-level exposure estimates and the cross-sectional design cannot show that ozone caused an individual's dry eye.

28. Smartphone time was associated with pediatric dry eye

    Researchers examined 916 Korean schoolchildren and asked families about screen time and outdoor activity. Study-defined dry eye affected 6.6%, and longer smartphone use and less outdoor time were associated with it; signs and symptoms improved in affected children after a four-week phone break. The initial comparison and unrandomized break cannot isolate smartphone use as the cause.

29. A Jordanian survey measured widespread dryness symptoms

    A random nonclinical sample of 1,039 Jordanian adults completed an Arabic dry-eye symptom questionnaire. Fifty-nine percent reached the study's symptom threshold, and reports were more frequent with older age and contact-lens wear. The questionnaire did not confirm clinical dry-eye disease, so this is a symptom estimate rather than a diagnostic prevalence figure.

30. Meibomian changes increased with age before discomfort

    A single-visit study examined meibomian glands, tears, and symptoms in 185 adults aged 25 to 66 without known ocular disease. Gland loss and secretion measures generally worsened with age, yet most participants were asymptomatic and gland findings did not track discomfort. The cross-sectional design cannot show when changes began or whether they would progress to symptomatic dry eye.

31. Contact-lens wear went with gland changes

    Researchers compared five matched groups of 20 young adults: never-wearers, current lens wearers with different durations of use, and former wearers. Gland expressibility, dropout, and tear measures differed between never-wearers and the other groups, with little additional change across longer wearing histories. One-time comparisons cannot prove that lens wear caused the changes or that they persist permanently after stopping.

32. Meibum quality mattered in an older veterans' clinic

    An ocular-surface examination of 233 Veterans Affairs eye-clinic patients, mostly older men, found abnormal meibomian findings in 59%. Poor meibum quality, more than lid vascularity, was associated with worse dry-eye symptoms, shorter tear breakup, and more staining. The selected clinic population and cross-sectional design limit population estimates and causal claims.

33. Patients often reported weather-related symptom changes

    Telephone interviews asked 738 people with dry eye or Sjögren's syndrome how seasons and weather affected their symptoms. Almost half said seasons had a strong effect, and wind was the most often reported trigger. Recall and self-selection may shape these reports, and no objective weather exposure or tear-film change was measured.

34. Gland dysfunction was common during glaucoma-drop use

    A cross-sectional study compared 70 people using glaucoma drops for more than a year with 45 healthy controls. Meibomian gland dysfunction was identified in 80% of the treated group, but dry-eye signs and symptom scores did not differ significantly between treated patients with and without gland dysfunction. Glaucoma, medication exposure, and other group differences were not separated experimentally.