Dry Eye Research in 2005: 33 Notable Human Studies

The 2005 picture

What the research shows

The 2005 studies reinforced dry eye as a condition involving tear-film stability, surface health, nerves, and visual function. Several treatments had encouraging results in defined groups, but most intervention studies were small or uncontrolled. Observational links and proposed diagnostic markers needed prospective and independent confirmation.

Treatment studies

Trials and clinical series tested ways to replace tears, retain them, or address inflammation and the tear-film lipid layer. Many measured short-term responses in small or selected groups.

1. Serum drops improved signs over a two-week trial

   After a washout period, researchers randomized 20 patients with severe dry eye to autologous serum drops or preservative-free artificial tears for two weeks. Tear breakup time, surface staining, and symptoms improved more in the serum group. The trial included only 37 eyes and was too short to establish long-term benefit or safety.

2. Longer cyclosporine use was assessed for safety

   An open-label extension followed 412 patients from earlier dry-eye trials while they used topical cyclosporine 0.1% for up to three years; mean exposure was about 20 months. Burning and stinging were the most common reported treatment-related problems, and no serious treatment-related adverse events were reported. Without a concurrent control group, the extension gives a limited picture of comparative benefit, and people willing to continue treatment may differ from those who stopped.

3. Collagen and silicone plugs produced similar short-term results

   A randomized study compared collagen and silicone punctal plugs in 24 people with dry eye, using symptoms, tear tests, staining, and tear-drainage imaging. Both groups improved, with no clear difference between plug materials. The small study did not include an untreated comparison group, so it cannot isolate the effect of plugging itself.

4. An omega-6 supplement showed limited benefit in Sjögren's syndrome

   In a double-masked trial, 40 patients with primary Sjögren's syndrome received either linoleic and gamma-linolenic acids or placebo for one month. The supplement group had higher tear prostaglandin E1 levels and improvements in symptoms and surface staining, while other tear measures did not clearly improve. The sample and treatment period were small, and the trial does not establish a benefit for dry eye outside this condition.

5. Lipid-containing drops thickened the tear layer immediately

   In a masked, fellow-eye comparison of 40 people with dry-eye symptoms and a thin tear-film lipid layer, researchers applied two different lubricating drops and measured lipid thickness soon afterward. The lipid-containing Soothe drop produced a much larger immediate increase than Systane. Lipid thickness is a surrogate measure; the study did not show whether symptoms improved or the change lasted.

6. A lubricant briefly improved measured visual acuity

   Researchers gave one carboxymethylcellulose drop to 20 symptomatic and 20 asymptomatic people with dry eye, then repeated distance and near visual-acuity tests. Acuity improved briefly, with the clearest effect around three to four minutes after dosing. There was no no-drop control, and the study did not test sustained visual or symptom benefit.

7. A gel-forming tear improved scores in an uncontrolled study

   A multicenter study enrolled 168 dry-eye patients, used a seven-day run-in with a comparator tear, then asked them to use an HP-guar lubricant four times daily for 28 days; 147 completed treatment. Staining and symptom scores improved during HP-guar use. Because there was no concurrent randomized comparison, the design cannot separate the product's effect from other changes over time.

8. Eyelid warming helped a small post-LASIK group

   Seventeen patients with persistent dryness more than a year after LASIK used eyelid warming four times daily for four weeks after other inflammation and aqueous-tear problems were addressed. Symptoms, tear breakup time, and lipid-layer measures improved. The uncontrolled series combined warming with other care, so the contribution of warming alone is uncertain.

9. Removing conjunctival folds relieved symptoms in selected patients

   Surgeons treated 168 eyes of 131 patients with conjunctivochalasis, including 50 eyes that also had dry eye, and tracked symptoms and surface findings afterward. Most patients with both conditions reported relief of their main symptom, and corneal staining improved. This uncontrolled surgical series applies to people with excess conjunctival folds, not to dry eye in general.

10. Two soft-lens materials similarly relieved contact lens dryness

    A single-center randomized crossover study fitted 40 symptomatic contact-lens wearers with two lens materials, one in each eye, then swapped sides after six weeks. Both materials were associated with less dryness, discomfort, blur, and fluorescein staining than participants’ usual lenses, with no convincing advantage for either test material. The comparison with habitual lenses was not randomized and may reflect a refitting effect.

Symptoms, vision, and clinical course

Several studies looked at how dry eye affects daily life or visual performance, and at symptoms after contact-lens wear or refractive surgery.

11. Contact-lens wearers reported more dryness

    A clinic survey compared 502 soft contact-lens wearers with 309 nonwearers using questions about dryness and discomfort. Dryness-related symptoms were reported by 43% of wearers and 15% of nonwearers, and asking how often eyes felt dry helped identify symptomatic wearers. The retrospective clinic sample and self-reported outcome do not show that lenses caused each person's symptoms.

12. A dry-eye questionnaire better reflected reported burden

    Researchers surveyed 210 people, including patients with and without Sjögren-related keratoconjunctivitis sicca and controls, using a dry-eye-specific quality-of-life instrument alongside general health questionnaires. The disease-specific instrument separated groups by clinical severity more clearly than the general measures. The cross-sectional comparison did not establish how well the scores detect meaningful change during treatment.

13. Persistent dryness after LASIK differed across two patient groups

    A retrospective study reviewed 932 patients after LASIK and compared dry-eye findings in East Asian and White groups through six months. Persistent dry eye was recorded more often in the East Asian group, which also had less favorable tear measures before surgery. Baseline differences and other unmeasured factors limit conclusions about why the groups differed.

14. Blink-free visual testing exposed a short-term deficit

    Investigators measured visual acuity over 30 seconds without blinking in 13 dry-eye patients and 20 controls. The dry-eye group lost more functional acuity, and scores improved after punctal plugs were placed. The small comparison and uncontrolled before-and-after plug assessment cannot establish a general treatment effect.

15. A larger randomized LASIK study found no hinge-position effect on dryness

    In 106 patients having LASIK in both eyes, surgeons randomly used a nasal hinge in one eye and a superior hinge in the other. Tear breakup time, Schirmer results, and patient-reported dryness did not differ by hinge position through six months. The paired-eye design controls for many patient factors, but the result applies to these flap techniques and does not mean LASIK itself is free of dry-eye risk.

Tear-film, nerve, and diagnostic studies

Researchers tested new ways to observe the ocular surface and tear film. These studies identified useful signals, but most candidate tests had not been validated across independent patient groups.

16. Lid-wiper staining tracked symptoms despite normal standard tests

    Among 100 people with normal tear breakup, Schirmer scores, and corneal staining, researchers compared 50 with dry-eye symptoms and 50 without. Lid-wiper epithelial staining was found in 76% of symptomatic participants and 12% of controls. This selected cross-sectional sample supports further testing of the sign but does not prove it causes symptoms or works as a stand-alone diagnostic test.

17. Corneal sensitivity was lower in a dry-eye group

    Using a gas esthesiometer, researchers compared corneal responses to mechanical, chemical, and temperature stimuli in 44 dry-eye patients and 42 controls. Dry-eye patients generally needed stronger stimuli to detect them, and thresholds tracked surface staining more closely than Schirmer tear volume. The cross-sectional design does not explain whether nerve changes preceded or followed surface disease.

18. Confocal images found altered corneal nerves

    Confocal microscopy compared corneal nerves in 38 patients with aqueous-deficient dry eye, including eight with Sjögren's syndrome, and 30 matched controls. Nerve patterns differed, with greater number and tortuosity in the Sjögren group and more branching in the broader dry-eye group. The small Sjögren subgroup and one-time imaging cannot identify the direction or clinical meaning of the nerve changes.

19. Tear proteins distinguished cases inside one research sample

    A mass-spectrometry study compared tear-protein patterns from 88 patients with dry eye and 71 controls, then built a seven-peptide classification model. The model reached about 90% sensitivity and specificity in the study data. Because it lacked independent external validation, those numbers should not be treated as real-world diagnostic performance.

20. Tear lipocalin was lower with meibomian gland dysfunction

    Investigators compared tear lipocalin levels in 12 patients with obstructive meibomian gland dysfunction, 12 with a seborrheic form, and 12 age-matched controls. Both patient groups had lower levels, which also tracked tear breakup time and surface staining. This small cross-sectional comparison cannot show whether reduced lipocalin contributes to gland disease or follows from it.

21. A tear-protein panel explored Sjögren diagnosis

    Researchers analyzed tears from 31 people with Sjögren's syndrome and 57 controls, including other dry-eye patients, with mass spectrometry. A candidate protein-score approach distinguished primary Sjögren cases with high sensitivity and specificity within this sample. The small, selected groups and lack of outside validation mean the panel remained a research finding.

22. Tear-film optics deteriorated sooner after a blink

    Investigators followed wavefront changes between blinks in 13 dry-eye patients and a normal comparison group. Optical quality began to worsen sooner in the dry-eye group, consistent with earlier tear breakup. The sample was small, and the measured optical signal was not a validated substitute for patient-reported vision problems.

23. An inflammatory marker rose with surface disease severity

    Brush samples from the conjunctiva of patients with mild or moderate dry eye and controls were tested for HLA-DR expression. The marker was higher across sampled regions in moderate disease and in some regions even in mild disease without staining. Each dry-eye severity group had only 16 patients, and the cross-sectional finding does not establish inflammation as the initiating cause.

24. Tear breakup changed optical aberrations

    A study of 120 eyes compared optical aberrations at several points after a blink in normal, dry-eye, and post-LASIK groups. Aberrations rose as the tear film broke up, with an earlier effect in the dry-eye group. This measured an optical mechanism rather than long-term symptoms or a new diagnostic test ready for routine use.

25. Common clinical tests explained little of symptom variation

    Researchers compared symptom questionnaires in 37 moderate dry-eye patients and 52 healthy participants, then assessed tear and surface measures in a subset. Several clinical tests separated the selected groups, but the measured signs left most variation in symptom scores unexplained. The small, deliberately separated sample limits how well the result applies to borderline cases in ordinary clinics.

Population patterns and associated conditions

Larger surveys and clinical comparisons examined dry-eye symptoms and tear measures alongside diet, disease, environment, and vision correction. Their designs primarily show associations.

26. Omega-3 intake was associated with fewer reported cases

    A cross-sectional analysis of 32,470 women compared dietary questionnaire responses with self-reported clinician-diagnosed dry eye. Higher omega-3 intake was associated with modestly lower odds of reported disease, while a high omega-6-to-omega-3 ratio was associated with higher odds. Diet and diagnosis were self-reported, so the study cannot show that changing fat intake prevents dry eye.

27. People with diabetes used ocular lubricants more often

    Health records for more than 159,000 adults older than 50 were used to compare ocular-lubricant use in those with and without diabetes. Use was higher in the diabetes group, at 20.6% versus 13.8%, and poorer glucose control was associated with greater use. A lubricant record is only a proxy for dry eye, and the observational data cannot show that diabetes itself caused the difference.

28. A hospital survey linked dryness with outdoor exposure

    Researchers examined 500 adults at an Indian eye hospital with symptom questions and clinical tests; 18.4% met the study's dry-eye definition. Reported exposure to wind and sunlight was associated with higher odds of dry eye. The hospital sample is not a community prevalence estimate, and the cross-sectional comparisons do not establish exposure as a cause.

29. Dryness symptoms varied by vision-correction method

    A survey of 893 people compared reported dry-eye symptoms among contact-lens wearers, spectacle wearers, and people needing no correction. Symptoms were reported most often by contact-lens wearers, followed by spectacle wearers and then emmetropes. The outcome was a symptom definition, and group differences or self-selection prevent a simple causal interpretation.

30. Dryness was common in a Hispanic optometry-clinic sample

    A Southern California optometry clinic surveyed 463 Hispanic patients about eye dryness. About 44% reported some dryness, while roughly one-quarter reported at least mild symptoms on the study's scale. These are clinic-based symptom reports, not a clinically confirmed population prevalence estimate.

31. Parkinson's disease was linked with less frequent blinking

    Investigators compared 56 people with Parkinson's disease with 36 controls using blink counts and ocular-surface tests. The Parkinson group blinked less often and had more abnormal tear and surface findings. The cross-sectional comparison cannot separate disease effects from treatment, age-related factors, or other differences between the groups.

32. Dry-eye findings did not simply track arthritis activity

    A clinical study tested 72 patients with rheumatoid arthritis for dry-eye signs and Sjögren's syndrome, then compared the eye findings with arthritis activity. Ocular abnormalities were frequent even outside the small Sjögren subgroup, but eye measures did not consistently rise with overall arthritis activity. The modest clinical sample limits estimates of how often these problems occur among all people with rheumatoid arthritis.

33. Sjögren symptoms did not track measured tear production

    A case-control study compared 60 women with primary Sjögren syndrome and 60 age-matched controls using dryness and pain ratings, fatigue and mood questionnaires, blood markers, and Schirmer testing. Reported eye dryness was not correlated with Schirmer scores; in the Sjögren group, age and some disease measures related to tear production. The cross-sectional design cannot establish what drives an individual patient’s symptoms.