Dry Eye Research in 2011: 31 Notable Human Studies

The 2011 picture

What the research shows

The 2011 evidence sharpened the picture of dry eye as a tear-film, gland, surface, and visual-function problem. Larger surveys showed substantial burden, while newer tests and biological markers remained sensitive to case definitions and patient selection. Controlled treatments yielded more specific conclusions than early device and surgical series, and clinical benefit did not always follow a laboratory change.

Treatment studies

The year's intervention papers ranged from randomized comparisons to small feasibility series. Their results are most useful when read alongside each study's control group, follow-up period, and choice of outcome.

1. Dexamethasone delivered by ocular iontophoresis

   A double-masked, single-center trial randomized 103 dry-eye patients to two doses of electrically delivered dexamethasone phosphate or a placebo procedure during a controlled drying challenge. Some staining and discomfort measures favored treatment at selected times, but the prespecified primary endpoints were missed. The short challenge model leaves routine, longer-term clinical benefit unproven.

2. Fatty-acid capsules changed a marker more than symptoms

   A three-month, double-masked trial at nine European centers randomized 138 adults with mild to moderate dry eye to placebo or capsules containing omega-3 and omega-6 fats, vitamins, and zinc. Conjunctival HLA-DR expression fell on some analyses in the supplement group, but signs and symptoms did not differ significantly between groups. The formula had several ingredients, and a marker change alone does not establish clinical benefit.

3. A second supplement trial found narrow clinical gains

   In a six-month, double-masked trial, 181 patients already using tear substitutes received either placebo or an omega-3 and omega-6 supplement. Tear breakup time and ocular fatigue improved modestly with supplementation, while most other symptom differences were not statistically clear. The findings apply to this specific formula and do not show broad relief from dry eye.

4. Adding cyclosporine improved surface measures

   Researchers randomized 42 patients with low tear production and unstable tear film to artificial tears alone or tears plus topical cyclosporine for four months. The combination group had better tear tests, surface staining, and conjunctival goblet-cell density at follow-up. This small study emphasized clinical signs and cell counts, so it gives less information about how much patients felt better.

5. Stopping cyclosporine was followed by worsening in a small extension

   After a prior one-year treatment study, patients continuing cyclosporine were randomized to stay on it or switch to artificial tears, while a former tear-only group began cyclosporine. Half of the eight patients switched off cyclosporine had worse severity after another year, compared with none in the other groups. The withdrawal group was very small and the groups differed at the extension's start, limiting a general maintenance recommendation.

6. Once-daily cyclosporine worked for some stable patients

   A randomized study assigned 100 patients whose dry eye had been treated with twice-daily cyclosporine for at least a year either to continue twice daily or reduce to once daily for six months. Most measured outcomes were similar between groups, but seven of 50 patients in the reduced-dose group stopped early because dryness worsened. Results in selected, previously stable patients do not show that a lower dose suits everyone.

7. Heat and pulsating pressure showed promise for blocked glands

   A multicenter feasibility study treated 14 people with obstructive meibomian gland dysfunction using a 12-minute device that heated and compressed the eyelids. Gland secretion, tear breakup, staining, and symptom scores improved from baseline and remained improved through three months. With no sham-treated group, this small pilot cannot establish how much improvement came from the device.

8. Cautery closed puncta after repeated plug loss

   Surgeons used thermal cautery on 70 puncta in 28 patients with severe dry eye whose plugs had repeatedly fallen out. One punctum reopened over three months, while symptoms, surface staining, and several tear measures improved. The uncontrolled series applies to a selected group with plug extrusion and cannot compare cautery with other options.

9. Three artificial tears showed no clear winner

   A month-long study randomized 27 people with dryness linked to computer or contact-lens use to one of three lubricants or no treatment. Symptoms improved in all four groups, and differences between groups were not statistically significant. The small sample cannot establish that the drops were equally effective or that any one outperformed no treatment.

Vision and everyday impact

These studies examined visual performance, symptoms after LASIK, and the effect of dry eye on work and mood.

10. LASIK flap methods produced similar dryness scores

    In a fellow-eye randomized trial, 51 patients received a mechanical-keratome LASIK flap in one eye and a femtosecond-laser flap in the other, then reported dryness for up to a year. Symptoms did not differ significantly between methods. The trial assessed self-reported dryness in this surgical setting and was not large enough to rule out small differences.

11. Central corneal staining tracked visual instability

    Investigators compared 22 patients with Sjögren-related dry eye, separated by whether central corneal staining was present, with 10 healthy controls. During brief blink-free testing, eyes with central staining had greater losses in functional visual acuity and more optical aberrations. The small cross-sectional study links surface damage with performance but cannot show which change came first.

12. Workers reported more lost productivity with worse symptoms

    An online U.S. survey screened 9,034 panel members and compared work and daily-activity impairment among eligible employed adults with self-reported physician-diagnosed dry eye. Reported productivity loss while working rose from 11% in the mild group to 18% in the moderate group and 35% in the severe group. The volunteer panel and self-reported outcomes may overstate or misclassify burden, and the survey cannot establish causation.

13. Depression tracked symptoms more than tear-test results

    A population-based analysis of 657 older Koreans measured depressive symptoms alongside dry-eye questions, Schirmer testing, and tear breakup time. Depression correlated with reported dryness but not with the two tear-test measures. This paper reexamined the same Yongin cohort used in the year's prevalence study; its cross-sectional design cannot show whether mood preceded or followed eye symptoms.

Tear-film, surface, and meibomian-gland studies

Investigators compared proposed diagnostic measures with symptoms and clinical findings, and examined tear and gland biology. Promising numbers from selected samples still needed testing across broader clinic populations.

14. Tear osmolarity separated severity groups in a multicenter study

    Across 10 sites, researchers tested tear osmolarity and common dry-eye signs in 314 consecutive participants. At a threshold of 312 mOsm/L, osmolarity had 73% sensitivity and 92% specificity against the study's composite severity classification. That classification combined other clinical tests rather than an independent diagnostic gold standard, so the reported accuracy needs that context.

15. A mix of tear stability and conjunctival folds matched symptoms

    In 47 non-contact-lens wearers, researchers compared dry-eye symptom scores with tear tests, lid-wiper staining, and conjunctival-fold grades. Noninvasive tear breakup time combined with nasal folds distinguished those with and without symptoms better than either measure alone in this sample. The small, selected group and same-sample model testing leave the combination's performance in routine clinics uncertain.

16. The OSDI questionnaire's subscales did not hold up well

    Researchers applied Rasch analysis to Ocular Surface Disease Index responses from 172 women with a dry-eye diagnosis or substantial irritation. The full set of questions fit better after response categories were simplified, but the three existing subscales did not reliably separate respondents. This psychometric finding comes from a postmenopausal female sample and does not invalidate every use of the overall questionnaire.

17. A second osmolarity study tested more severe disease

    A single-center study compared tear osmolarity in 133 patients selected for moderate to severe keratoconjunctivitis sicca and 95 healthy controls. Median values were about 320 and 301 mOsm/L, respectively, and the reported test sensitivity and specificity were 87% and 81%. Separating established cases from healthy volunteers cannot show how well the test handles mild or uncertain cases.

18. Tear cytokine patterns differed across dry-eye subtypes

    An antibody-microarray study compared tear inflammatory proteins in 143 people classified as controls, aqueous-deficient dry eye, lipid-layer disease, or both. Several cytokines were elevated in the aqueous-deficient groups, while the lipid-layer-only group resembled controls on this panel. These cross-sectional protein patterns do not prove that inflammation is absent from all evaporative dry eye.

19. Mucin gene expression showed a partly validated signal

    Conjunctival cell samples from 38 dry-eye patients and 43 matched controls showed lower expression of several mucin genes in the patient group. The investigators reproduced the pattern in a separate set of 30 patients and 16 controls; MUC1 performed best among the tested genes. Both samples were small and selected, so the assay was not yet a general clinical screening test.

20. OCT found especially low tear volume in Sjögren dry eye

    Optical coherence tomography measured upper and lower tear menisci in 26 people with Sjögren-related dry eye, 26 with other dry eye, and 26 controls. Tear volume was lowest in the Sjögren group and related to some surface-damage and tear-stability findings. High diagnostic accuracy within these deliberately distinct groups needs confirmation in patients whose diagnosis is uncertain.

21. Surface cooling distinguished a small dry-eye group

    A new thermography device tracked eye-surface temperature for 10 seconds after a blink in 30 dry-eye patients and 30 controls. The dry-eye group cooled more quickly, and the 10-second measure had 83% sensitivity and 80% specificity in this sample. The groups were small and differed in average age, so the device's screening accuracy remained preliminary.

22. Meibum lipids varied with dry-eye severity

    Mass spectrometry measured hundreds of meibum lipid species in 27 Asian patients with dry-eye symptoms and 10 controls. Some lipid species, including O-acyl-omega-hydroxy fatty acids, varied with symptom-based severity. The small cross-sectional study could not tell whether those changes caused tear-film problems or followed them.

23. Meibomian secretions were physically stiffer with gland disease

    Infrared spectroscopy compared human meibum from donors with meibomian gland dysfunction and age-matched donors without dry-eye symptoms. Samples from the dysfunction group had a higher melting-transition temperature and greater lipid order at eye-surface temperature. This laboratory measure suggests a mechanism for poor secretion but does not itself measure patient benefit or prove the direction of the association.

24. Meibomian gland tissue showed altered gene expression

    Researchers isolated meibomian glands from eyelid-surgery specimens of patients with gland dysfunction and age-matched controls, then compared RNA expression. Nearly 400 genes differed, including genes involved in keratinization and cell adhesion. Surgical tissue samples and one-time gene measurements cannot identify which changes initiate disease.

25. Aging glands had fewer dividing cells

    Investigators stained excess eyelid tissue from 36 canthoplasty patients aged 18 to 95 for markers of meibomian cell differentiation, cell cycling, and inflammation. Older glands had fewer actively dividing cells, and inflammatory-cell staining related to gland expression grades. The surgical, cross-sectional sample supports an age-related mechanism but cannot establish progression within individuals.

26. OCT thickness changes were not specific to dry eye

    Spectral-domain OCT measured corneal, limbal, and conjunctival epithelial thickness in 79 participants, including dry-eye patients, controls, and people using glaucoma drops. Both the dry-eye and glaucoma-treatment groups had thinner limbal and thicker bulbar conjunctival epithelium than comparable controls. Because the pattern appeared in more than one condition, it was not a stand-alone dry-eye diagnosis.

Population patterns and associated factors

Surveys and clinical comparisons linked dry-eye measures with age, contact-lens wear, screen work, and other characteristics. Their definitions and source populations matter when interpreting the numbers.

27. A Japanese community survey found symptoms more often in women

    In Koumi, Japan, 2,791 of 3,294 eligible residents aged 40 or older completed a dry-eye and risk-factor questionnaire. A prior diagnosis or frequent severe symptoms was reported by 21.6% of women and 12.5% of men; contact-lens wear was associated with the outcome in both sexes. The definition relied on reported diagnosis or symptoms, and the cross-sectional design cannot show that the associated exposures caused disease.

28. A veterans' clinic study linked dry eye with several diagnoses

    Records from 16,862 patients at two Veterans Affairs eye clinics identified dry eye through both a diagnosis code and treatment record. Cases were more common among women, and conditions including depression, post-traumatic stress disorder, and sleep apnea were associated with greater odds after age and sex adjustment. Eye-clinic patients and record-based case definitions are not a general-population sample, and these associations do not establish causes.

29. Symptoms were common among older Koreans

    A population-based sample of 657 people aged 65 or older in Yongin, South Korea, completed a symptom questionnaire and ocular tests. The adjusted prevalence of symptom-defined dry eye was 33.2%, and about half of symptomatic participants had meibomian gland dysfunction on examination. The result depends on a symptom-based definition and should not be extended to younger people or other populations.

30. Contact lenses and longer screen work traveled with worse tear measures

    A study of office workers compared 69 contact-lens wearers with 102 matched nonwearers and grouped them by whether screen work lasted at least four hours a day. Lens wear and longer screen time coincided with lower tear-meniscus height and higher symptom scores. The nonrandomized comparison cannot separate the effects of lens use, work habits, and other differences between workers.

31. Contact-lens wearers showed gland changes on confocal images

    Laser confocal microscopy compared meibomian glands in 20 contact-lens wearers and 20 age- and sex-matched nonwearers. The wearers had differences in gland structure and secretion appearance alongside worse tear and symptom measures. The small, cross-sectional comparison cannot establish that lens wear produced those changes.