Dry Eye Research in 2009: 32 Notable Human Studies

The 2009 picture

What the research shows

The 2009 studies combined stronger population estimates with increasingly detailed tear and eyelid measurements. They also showed why a promising biomarker, a symptom score, or a short clinical response should be read in the context of the people studied and the comparison used. Several findings became influential leads, setting up later tests of proposed thresholds and treatment effects in independent samples.

Treatment studies

The year's clinical interventions ranged from a controlled cyclosporine comparison to smaller or open-label studies. Their designs matter when judging apparent benefit.

1. Vitamin A drops and cyclosporine in a three-arm trial

   A randomized study assigned 150 people with dry eye to vitamin A drops, cyclosporine drops, or neither active drug; everyone also used preservative-free artificial tears. After three months, both active groups had better tear breakup, Schirmer results, and conjunctival-cell findings than the tears-only group. The short trial did not establish whether one active treatment was better or whether gains persisted.

2. Cyclosporine for severe trachoma-related dry eye

   A six-month comparison assigned 32 patients with severe trachomatous dry eye to cyclosporine plus preservative-free tears and 32 to vehicle plus tears. The cyclosporine group improved on several symptoms, staining, tear, and conjunctival-cell measures. The report does not clearly establish randomized allocation or masking, and its results apply to a specific cause of severe dryness.

3. More frequent cyclosporine use after inadequate twice-daily response

   A retrospective series identified 22 patients with severe Sjögren-related or graft-versus-host dry eye who had responded inadequately to twice-daily cyclosporine and then used it three or four times daily. About two-thirds reported improvement, with less corneal staining. Because patients were selected for having improved after the change, this design cannot reliably estimate how often higher dosing would help a new patient.

4. An oral antioxidant supplement in a crossover trial

   Twenty-four dry-eye patients took a multi-ingredient antioxidant supplement and placebo during a double-masked randomized crossover study. Tear breakup and Schirmer measures and several symptoms favored the active period after 12 weeks. The small sample and combined ingredients prevent a conclusion about which component mattered or whether benefits would persist.

5. Hydroxypropyl cellulose inserts in an open-label study

   A multicenter study trained 520 adults with dry eye to use slowly dissolving ocular inserts; 418 completed four weeks. Completers reported better symptoms and OSDI scores, but blurred vision prompted some to stop, and adherence was incomplete. The large sample describes usability and change during treatment, while the lack of a comparison group limits claims of efficacy.

6. Artificial tears and contrast sensitivity over two weeks

   Investigators measured contrast sensitivity and optical aberrations in 22 dry-eye patients and ten controls around a single artificial tear dose and after daily use. A fresh drop briefly worsened optical quality, but that immediate disturbance became smaller over two weeks in the dry-eye group. The small nonrandomized comparison suggests adaptation or tear-film improvement, without identifying a best formulation.

Population patterns and related conditions

Large surveys provide more stable frequency estimates than single-clinic samples, but dry-eye definitions and demographics still differ. Surgical and specialty-clinic studies address narrower groups.

7. Dry-eye symptoms in the Beijing Eye Study

   Investigators questioned and examined a random subsample of 1,957 adults aged 40 or older from the population-based Beijing Eye Study. Frequent dry-eye symptoms affected 21%, but tear breakup, staining, Schirmer results, and gland findings did not distinguish symptomatic from asymptomatic people. The symptom definition and older study population limit comparisons with clinically confirmed dry-eye estimates.

8. Dry-eye prevalence among older U.S. men

   A questionnaire survey of men aged 50 or older in two Physicians' Health Studies estimated an age-standardized dry-eye prevalence of 4.34%, defined by prior diagnosis or frequent severe symptoms. The rate rose with age, and several health and medication factors were associated with reports. Participants were male health professionals, and the estimate did not require a uniform eye examination.

9. The Salnes Eye Study in Spain

   A population-based examination of 654 adults aged 40 to 96 in northwestern Spain required both symptoms and at least one abnormal surface or tear test to define dry eye. The weighted prevalence was 11%, rising with age; rosacea was the main factor associated with that combined definition. The stricter definition helps explain why this figure differs from symptom-only surveys.

10. Tear-film symptoms among Malay adults in Singapore

    A population survey of 3,280 Malay adults aged 40 to 80 found frequent tear-film symptoms in 6.5%. Smoking and thyroid disease were associated with reports, which also related to difficulty in daily activities. This was a symptom-based result for one population; it should not be equated with clinically confirmed dry-eye prevalence in other settings.

11. Dry eye in a Shanghai district sample

    A cluster-sampled survey examined 1,085 adults in a Shanghai district with questionnaires and tear and surface tests. About 30% met the local diagnostic criteria, with higher frequency in women, older adults, and contact lens wearers. The result adds geographic context, but the criteria and sampling frame differ from other population studies and limit direct comparison of percentages.

12. Dry eye and quality of life during glaucoma treatment

    An observational comparison of 61 treated glaucoma patients and 20 controls found more dry-eye findings among people using multiple glaucoma drops, alongside poorer vision-related quality-of-life scores. More treatment may track more advanced glaucoma as well as greater surface exposure, so this cross-sectional study cannot assign the quality-of-life difference solely to the drops.

13. Dry eye in the first months after cataract surgery

    A prospective study followed 49 cataract-surgery patients, including 14 with preoperative dry eye. Symptoms and tear measures worsened after surgery, and longer operating-microscope light exposure correlated with poorer dry-eye measures. The small study suggests perioperative factors worth testing, but it does not establish that microscope light itself caused the changes.

14. Contact lens wear and meibomian gland loss

    Noncontact meibography compared 121 contact lens wearers with 137 healthy volunteers. Gland dropout scores were higher in wearers and rose with reported duration of lens use. The cross-sectional design cannot determine whether lens wear caused gland loss, and participants may have differed in other ways relevant to the eyelids.

15. Femtosecond versus mechanical LASIK flaps

    Eyes without preoperative dry-eye findings were randomized to femtosecond or mechanical flap creation during LASIK. At one month, the study reported dry eye in 8% of 113 femtosecond-treated eyes and 46% of 70 microkeratome-treated eyes. The striking difference is limited to the studied devices, early follow-up, and eye-level assessment; flap groups also differed in mean thickness.

16. Previously unrecognized Sjögren syndrome in dry-eye care

    A retrospective review of 220 people seen at a dry-eye center found primary Sjögren syndrome in 24; only eight had that diagnosis at presentation. Some patients were recognized during evaluation and others needed salivary gland biopsy after negative initial blood tests. The specialty-clinic sample cannot estimate prevalence among all dry-eye patients, but it highlights a diagnostic gap.

17. Subtle thyroid eye disease presenting as dry eye

    Among 539 referrals for dry-eye evaluation, clinicians retrospectively identified 21 people with thyroid eye disease without the classic signs of prominent eyes or double vision. Localized redness and subtle lid changes raised suspicion. The case series shows one possible explanation for persistent surface inflammation, but its referral setting and imaging-based case identification do not support routine screening rates.

Tests, tear chemistry, and mechanisms

Much of the year's influential work looked for patterns in tears and eyelid glands. Biomarker panels and proposed cutoffs are discoveries to validate, not established replacements for a full clinical assessment.

18. Inflammatory cytokines in dry-eye tears

    A laboratory comparison measured nine inflammatory signals in tears from seven dry-eye patients and seven controls; all were higher in the patient samples. Conjunctival gene results in a still smaller subset moved in the same direction. This frequently cited study supplied an inflammatory lead, but its tiny sample could not validate the signals as diagnostic markers.

19. MMP-9 activity and dry-eye severity

    Tear and conjunctival samples from 46 patients with dysfunctional tear syndrome and 18 controls showed greater matrix metalloproteinase-9 activity in patient tears, with the highest activity in the most severe group. Activity related to symptoms, staining, and some vision measures. The observational comparison made MMP-9 a promising marker but did not by itself define a clinical cutoff.

20. Tear breakup and hyperosmolar discomfort

    Five volunteers rated discomfort as they kept an eye open and after receiving drops of varying salt or sugar concentration. Tear breakup and discomfort followed related time courses; separate cell experiments suggested that brief high osmolarity can trigger stress signaling. The human experiment provides indirect support for a mechanism, not a direct measurement of transient osmolarity in dry-eye patients.

21. A tear-protein panel proposed for dry-eye detection

    Quantitative proteomics compared tears from 56 dry-eye patients and 40 controls, identifying proteins that rose or fell with disease. A four-protein panel performed well within the study's analysis, and most candidate proteins were checked in an independent age-matched set. The results were a strong discovery step, while clinical accuracy in unrelated care populations remained unproven.

22. Proposed criteria for obstructive meibomian gland dysfunction

    Researchers compared 53 patients already diagnosed with obstructive meibomian gland dysfunction with 60 age-matched controls. Symptom, lid-margin, and gland-imaging scores separated the groups, leading to a proposed combined rule. Because the rule was derived from clearly defined cases and controls, it needed testing in less obvious patients before routine diagnostic use.

23. Lipid-layer thickness and reported symptoms

    In 137 routine eye-exam patients, interferometry measured tear lipid-layer thickness after a symptom questionnaire. Thin layers were more common among those with severe symptoms, while thicker layers were more common without symptoms. The relationship supports further study of lipid imaging, but overlapping measurements mean it cannot diagnose an individual from one thickness reading.

24. The chemical makeup of human meibum

    Mass spectrometry of human meibomian secretions identified a detailed range of wax esters and very-long-chain hydroxy fatty-acid compounds. This basic human-sample study improved the chemical map of the tear film's oil source. It did not compare patients with dry eye and controls or test whether any one lipid change predicts symptoms.

25. Tear-meniscus imaging for aqueous-deficient dry eye

    Optical coherence tomography measured upper and lower tear menisci in 48 prescreened patients with aqueous-deficient dry eye and 47 controls. Menisci were smaller in the patient group, and lower-meniscus measurements distinguished the groups well at proposed cutoffs. Selection of clearly affected patients may make performance look better than it would in routine mixed-symptom care.

26. Lipid-layer motion and tear thinning

    Video recordings from 16 healthy volunteers tracked lipid-layer movement between blinks, while tear thinning was measured in 13. The observed lateral flow was too slow to explain most thinning, pointing instead toward evaporation. This physiologic study clarifies a mechanism relevant to dry eye but did not test diseased eyes directly.

27. Tear proteins in contact lens-related dry eye

    Proteomic methods compared tear samples from 11 contact lens wearers reporting dryness and ten lens wearers without it. Several proteins differed, including lower lacritin and lipocalin-related signals in the symptomatic group. The small discovery sample generated candidates rather than a validated explanation or a test ready for lens fitting.

28. Predicting dryness in new contact lens wearers

    Thirty-three new soft contact lens wearers underwent tear and lid tests before a two-month wearing period. Baseline tear breakup time, conjunctival folds, and symptom score together separated those who later reported lens-related dryness in this sample. The prediction rule was built and assessed in the same small group, so its apparent accuracy needs external testing.

29. Tear-meniscus volume in symptomatic lens wearers

    Optical coherence tomography compared three groups of 20: symptomatic contact lens wearers, asymptomatic wearers, and nonwearers. The symptomatic group had smaller tear menisci before and during short lens wear. This association may help explain lens discomfort, though it does not show whether low tear volume preceded the symptoms.

30. Nerve growth factor in contact lens-related dryness

    Investigators compared corneal nerves, sensitivity, and tear proteins in established contact lens wearers with and without dryness and in nonwearers. Lens wearers had lower nerve density than nonwearers, while the symptomatic lens group had higher tear nerve growth factor than asymptomatic wearers. This cross-sectional pattern suggests a nerve response but cannot show whether it caused or followed discomfort.

31. Aqueous-deficient versus evaporative dry eye

    Fifty-six patients classified as aqueous-deficient or evaporative dry eye underwent tests of tear turnover, evaporation, volume, osmolarity, and gland loss. Turnover differed more clearly between the two groups than evaporation, whose values overlapped substantially. Because the clinical labels were the comparison standard, these measurements need further validation before being used to assign subtype alone.

32. A negative result for common tear mucin sugars

    Chemical analysis mapped the main O-linked sugar structures attached to human tear mucins and compared normal tears with non-Sjögren dry-eye tears. The investigators did not find a significant group difference in total O-glycan amount or composition. This useful negative result narrows a proposed mechanism, although different dry-eye subtypes or smaller molecular changes could still matter.