Dry Eye Research in 2010: 32 Notable Human Studies

The 2010 picture

What the research shows

The 2010 literature strengthened both treatment comparisons and the language used to measure dry eye, especially through symptom scales and tear osmolarity. It also made a practical point: test abnormalities, patient discomfort, and day-to-day visual difficulty overlap only partly. Patient groups, study design, and follow-up periods gave each result its practical meaning.

Treatment studies

Several studies used randomized comparisons, but their outcomes, patient groups, and treatment periods varied. Short-term improvement in a test or symptom does not establish a lasting benefit for every dry-eye subtype.

1. Azithromycin drops and meibomian gland secretions

   An open-label study followed people with symptomatic meibomian gland dysfunction during topical azithromycin treatment and analyzed expressed gland lipids with infrared spectroscopy. Symptoms and lid findings improved as lipid behavior moved toward the pattern seen in healthier glands. Without an untreated comparison, the study cannot separate a drug effect from time, accompanying care, or measurement variation.

2. Rituximab in primary Sjögren syndrome

   Thirty people with active primary Sjögren syndrome were randomized to rituximab or placebo infusions and followed for 48 weeks. Stimulated saliva flow, the primary outcome, improved more with rituximab; an ocular staining measure improved from baseline within the treated group. The trial was small, and that ocular change was not established as a between-group treatment effect.

3. Cyclosporine versus vehicle in moderate to severe dry eye

   A multicenter, double-masked trial assigned 233 Chinese patients to cyclosporine 0.05% or vehicle twice daily for eight weeks. The combined symptom-and-sign score improved more with cyclosporine, with advantages in dryness, foreign-body sensation, and some staining and Schirmer results. Burning, light sensitivity, tear breakup, and artificial-tear use did not clearly differ, and follow-up was short.

4. Sodium hyaluronate compared with its vehicle

   In a double-masked phase 3 trial, 444 participants used 0.18% sodium hyaluronate drops or their vehicle for two weeks. At day seven, the active drops had modest advantages on the two primary measures: surface staining and overall symptom frequency. The differences sat near the statistical threshold in one analysis, and the brief trial cannot answer how long the benefit lasts.

5. Sea buckthorn oil during the cold season

   One hundred adults with dry-eye symptoms were randomized to oral sea buckthorn oil or placebo for three fall-to-winter months; 86 completed the study. Tear osmolarity rose in both groups but rose less with the oil. Redness and burning results varied between the main and adherence-based analyses, so this trial suggests a possible benefit rather than establishing an effective supplement.

6. An oral adenosine-receptor drug in a phase 2 trial

   A multicenter, double-masked phase 2 study compared oral CF101 with placebo for 12 weeks in moderate to severe dry eye; 68 patients completed treatment. More treated patients cleared or substantially improved corneal staining, and tear breakup and meniscus height also improved. The sample was small and the findings were exploratory; the paper did not establish durable symptom relief or routine clinical use.

7. Cyclosporine and disease course over one year

   A single-center randomized study followed 36 patients using cyclosporine and 22 using artificial tears for 12 months. Disease severity progressed in two cyclosporine users versus seven tear users, and later tear and symptom measures favored cyclosporine. The investigator was masked, but patients received visibly different treatments; the small groups and single center limit the estimate of long-term benefit.

8. Upper versus lower punctal plugs

   In 20 dry-eye patients, researchers placed a temporary collagen plug in one eye's upper punctum and the other eye's lower punctum, then tracked symptoms, staining, tear breakup, and tear-meniscus size for ten days. Both approaches improved several measures, with no clear difference between them. The small, short comparison had no untreated dry-eye eye, so improvement cannot be attributed solely to plug placement.

9. Two lubricant formulations in a masked head-to-head trial

   After a saline run-in, 105 patients in the analyzed population used either a polyethylene glycol and propylene glycol drop with HP-guar or another commercial lubricant for six weeks. The HP-guar formulation reduced corneal and conjunctival staining more at several visits; both groups reported fewer symptoms. This product comparison does not show whether either drop works better than no active treatment.

Who was affected, and how symptoms mattered

These studies broadened the picture beyond tear tests. They also show why prevalence figures and associations must be read alongside each study's definition of dry eye and the population it sampled.

10. Ocular surface symptoms in people using glaucoma drops

    A prospective observational study at ten sites surveyed 630 people using pressure-lowering eye drops for glaucoma or ocular hypertension. Nearly half scored in the mild-to-severe symptom range on the OSDI, and scores increased with the number of medications. Without an untreated comparison or random assignment, the study cannot separate effects of drops from differences in underlying disease or other factors.

11. The Henan Eye Study at high altitude

    A population survey examined 1,816 Mongolian adults aged 40 or older in a high-altitude Chinese region. About half reported at least one frequent dry-eye symptom, while abnormal breakup, Schirmer, and staining results were less common and related only imperfectly to symptoms. The broad symptom definition and specific environment limit comparisons with prevalence estimates elsewhere.

12. Dry eye and vision-dependent tasks in Singapore

    A population-based study of 3,280 Malay adults related frequent dry-eye symptoms to reported difficulty with reading signs and newspapers, using stairs, watching television, cooking, and night driving. Associations remained after adjustment for age, sex, and presenting vision in adults without visual impairment. The cross-sectional questionnaires show a burden in daily life but cannot establish that dryness caused each difficulty.

13. Screen work and tear secretion

    Investigators studied 1,025 Japanese office workers who used visual displays and found lower Schirmer tear output with longer reported exposure, while tear stability and lipid measures did not show the same relation. A separate rat experiment explored gland changes. The human evidence is cross-sectional, so work habits, environment, and other differences could explain the association.

14. Dry-eye vision changes from morning to evening

    Twenty-one dry-eye patients had visual and surface testing in the morning and evening. By evening, they maintained clear vision for less time between blinks, read more slowly, and had more staining and redness, although reported discomfort did not rise. This small within-person study captures daily variation but cannot show how consistently the pattern appears across larger patient groups.

15. Meibomian gland disease in a dry-eye referral clinic

    A Singapore specialty clinic evaluated 200 dry-eye patients with lid, tear, staining, and symptom measures. Evaporative disease was the most common assigned subtype, and worse meibomian findings related to shorter tear breakup and some visual complaints. The selected clinic population does not provide a community prevalence estimate, and the correlations do not prove gland changes caused the symptoms.

16. Lid-wiper staining in clearly defined dry-eye groups

    A multicenter comparison stained the upper eyelid's wiping surface in 50 patients with definite dry-eye signs and symptoms and 50 asymptomatic controls. Lid-wiper epitheliopathy appeared in 88% of the dry-eye group versus 16% of controls. The separation is striking, but selecting two clearly different groups may overstate how well the sign distinguishes borderline cases in routine care.

17. Quality of life and clinical signs did not align closely

    Across 15 Japanese care sites, 158 patients with dry eye completed vision-related and general quality-of-life surveys alongside standard ocular tests. Patients with Sjögren syndrome had worse tear and staining findings than other patients, yet survey scores were similar, and most sign-to-quality-of-life relationships were weak. The cross-sectional clinic sample underscores the need to ask about experience as well as examine the surface.

Symptom scales and diagnostic tests

The most influential 2010 papers refined how investigators measured change and compared tear-film tests. Proposed cutoffs from one sample remain starting points for validation, especially when patients have mixed causes of discomfort.

18. What counts as a meaningful OSDI change?

    Using 310 patients in an observational treatment registry, researchers compared changes in the Ocular Surface Disease Index with patients' and clinicians' ratings of improvement. The estimated meaningful change was roughly five to seven points for mild or moderate disease and seven to thirteen for severe disease. These anchor-based ranges help interpret scores, though registry participants were mostly women and White, and the estimates need context in other groups.

19. Validation of the five-item Dry Eye Questionnaire

    Across two studies totaling 260 participants, investigators selected five questions about dryness, discomfort, and watery eyes from a longer questionnaire. The resulting DEQ-5 separated self-rated severity levels and established dry-eye, Sjögren, and control groups; the authors proposed screening thresholds. Because items and thresholds were developed in these selected samples, outside validation matters before treating a score as a diagnosis.

20. A multisite comparison of dry-eye severity measures

    Ten U.S. and European sites collected complete osmolarity, staining, tear, gland, and symptom data from 299 adults. Tear osmolarity had the strongest association with the study's composite severity scale, while conventional test thresholds often placed people poorly. The analysis supports a more continuous view of severity, but the ranking and proposed clinical interpretation need validation in independent patients.

21. Tear osmolarity compared with established tests

    A clinic-based comparison measured osmolarity and several standard tests in 105 dry-eye patients and 25 controls. Osmolarity generally rose with assigned severity, but a proposed 305 mOsm/L diagnostic threshold achieved only moderate discrimination. The small control group and cutoffs chosen from the same data limit claims that one reading can settle a diagnosis.

22. Tear-meniscus height measured by OCT

    Optical coherence tomography measured the tear meniscus in 24 people with definite dry eye and 27 controls. Lower-meniscus height differed between groups, and a proposed cutoff yielded 67% sensitivity and 81% specificity. The noninvasive method was promising, but this small case-control comparison did not establish performance among patients with mixed or uncertain symptoms.

23. Separating meibomian obstruction from low tear production

    Researchers compared 25 people with obstructive meibomian gland dysfunction and 15 with aqueous-deficient dry eye using symptoms, lid findings, meibography, gland secretions, and Schirmer testing. Gland images and secretions differed more than symptoms or tear breakup. A three-score rule reached 68% sensitivity and 80% specificity in these selected groups, leaving substantial room for improved diagnosis.

24. Temporal conjunctival staining as a Sjögren clue

    A retrospective specialty-clinic analysis compared 231 patients with primary Sjögren syndrome and 89 with aqueous-deficient dry eye without Sjögren syndrome. Blood antibodies and salivary biopsy were strongest overall discriminators; among noninvasive ocular findings, rose bengal staining on the outer conjunctiva stood out. The rule was derived from a referral population and cannot replace a full Sjögren evaluation.

25. Tear breakup and loss of visual contrast

    A custom optical setup tracked tear breakup, wavefront quality, and contrast sensitivity while ten soft contact lens wearers delayed blinking. In the four whose central lens surface broke up, optical changes closely tracked declining contrast sensitivity. This small experiment explains a possible route from unstable tears to blurry vision, but it was not a clinical test of dry-eye patients.

Tear-film and ocular-surface biology

Human-sample and imaging studies looked for biological patterns behind symptoms. Most were discovery studies: their associations do not by themselves prove a mechanism or create a ready-to-use diagnostic marker.

26. Confocal imaging of the conjunctiva in Sjögren dry eye

    Researchers used in vivo confocal microscopy in 28 women with Sjögren-related dry eye, seven with non-Sjögren dry eye, and 14 controls. Both dry-eye groups had more inflammatory cells and fewer conjunctival epithelial cells than controls; Sjögren eyes also had more epithelial microcysts. The small, selected groups show a tissue pattern, but do not establish that the scan can diagnose dry-eye subtype in routine care.

27. Inflammatory signals in evaporative dry eye

    Tears from 23 people with mild or moderate evaporative dry eye and nine controls were tested for 15 inflammatory signals. Five were higher in patients, while several signals related to pain, tear stability, or staining. The study showed inflammation beyond severe disease but, with many comparisons and a small sample, could only nominate candidates for further testing.

28. Tear proteins before obvious surface damage

    Researchers compared tear proteins from 60 symptomatic people with evaporative dry eye and unstable tears against 30 controls without symptoms. Lactoferrin, lipocalin-1, and some other proteins were lower, while albumin was higher, even without visible epithelial defects. The cross-sectional result suggests early protein changes but cannot establish which changes precede disease or serve as a reliable test.

29. Tear-meniscus movement during blinking

    Optical coherence tomography followed tear-meniscus size through normal and delayed blinks in 25 people with aqueous-deficient dry eye and 30 controls. Patient menisci were generally smaller and changed less with blinking, suggesting reduced tear-volume dynamics. The laboratory comparison describes physiology, while its specialized patient group and sample size limit diagnostic claims.

30. Age, sex, and the tear-film lipid layer

    A cross-sectional study measured tear breakup and lipid-layer features in 160 adults younger than 45 and 58 older adults. Older participants had shorter noninvasive breakup times and thinner lipid layers; the lipid difference was especially marked among older women. These group patterns offer a possible contributor to age-related dryness, but the study did not follow individuals over time or isolate hormonal causes.

31. Immune cells on the conjunctival surface

    Impression cytology and flow cytometry compared superficial conjunctival cells from dry-eye patients and controls. Patient samples showed more CD14-positive cells, a changed CD4-to-CD8 balance, and higher epithelial HLA-DR, while several other immune-cell counts did not differ. The modest, partly overlapping sample sets and observational design make this a biological lead rather than proof of a single inflammatory pathway.

32. MUC1 mucin in Sjögren and non-Sjögren dry eye

    Tear washings and conjunctival samples from 25 people with Sjögren dry eye, 25 with other aqueous-deficient dry eye, and 26 controls were analyzed for MUC1 protein and gene expression. Soluble MUC1 was highest in Sjögren disease and also elevated in the other dry-eye group. The differences might reflect a surface response to chronic irritation; this comparison cannot show whether MUC1 changes protect the eye or drive disease.