Dry Eye Research in 2002: 31 Notable Human Studies

The 2002 picture

What the research shows

The 2002 studies made dry eye more visible as a problem of fluctuating vision, eye-surface inflammation, mucin balance, and eyelid oil as well as tear amount. Controlled trials offered leads for treatment, but many had small samples and only weeks of follow-up. Population and surgical studies identified questions that later work needed to test more directly.

Treatment and care

Several 2002 trials tested approaches still familiar in dry eye care. Most were small or short, and the formulations and patient groups differed, so apparent advantages should not be compared across studies.

1. Cevimeline for Sjögren-related dry eye

   In a 12-week randomized, double-blind trial, people with Sjögren syndrome received placebo or one of two oral cevimeline doses. The 30-mg dose taken three times daily improved reported eye dryness and tear flow relative to placebo. Sweating, nausea, and other systemic effects were reported. The findings apply to Sjögren-related dryness, not necessarily dry eye from other causes.

2. Sodium hyaluronate compared with saline

   An 86-person randomized, double-blind study compared preservative-free sodium hyaluronate drops with saline for three months. Conjunctival impression cytology, its main measure of surface damage, favored hyaluronate. Only 44 participants were included in the protocol-adherent efficacy analysis, which makes the estimate less secure than the original enrollment suggests.

3. Hypotonic versus isotonic hyaluronate in Sjögren syndrome

   Forty patients with Sjögren syndrome used either hypotonic or isotonic 0.4% hyaluronate drops six times daily for 90 days. Both groups improved, while several staining and tear-stability measures favored the hypotonic formulation. Examiners were masked, but the report does not clearly establish randomized allocation, and the sample was small.

4. Castor oil drops for obstructed eyelid oil glands

   In a double-masked crossover trial, 20 people with noninflamed meibomian gland dysfunction used castor oil drops and placebo for two weeks each. Symptoms, tear evaporation, surface staining, and tear breakup time favored the oil formulation. The brief periods leave open whether benefits persist or whether repeated use causes problems.

5. Trehalose drops in moderate to severe dry eye

   A masked 34-person trial compared trehalose in one eye with saline in the other for four weeks. Surface staining improved with both tested trehalose concentrations, and tear breakup time improved with the lower concentration. Treating fellow eyes differently can reduce some person-level differences, but symptoms are harder to assign to one eye and follow-up was short.

6. Hyaluronate versus polyvinyl alcohol drops

   A randomized crossover study at eight UK centers compared four weeks of sodium hyaluronate with four weeks of polyvinyl alcohol in severe dry eye. Among 32 participants completing both periods, burning scores and one staining measure favored hyaluronate. The sample was modest and the study could not establish long-term superiority.

7. Infrared warm compression for meibomian gland dysfunction

   Thirty-seven people with obstructive meibomian gland dysfunction used an infrared warming device for two weeks. Symptoms, tear breakup time, staining, and gland-opening scores improved from baseline. Because this was a single-arm case series, the study cannot separate the device's effect from expectation, other care, or natural variation.

8. Silicone punctal plugs in ocular surface disease

   Researchers reviewed plug placement in 153 patients with several ocular surface conditions; dry eye was the most common indication. Symptoms and staining often improved at about four weeks, but roughly half of all placed plugs were eventually expelled. The retrospective, uncontrolled design and mixed diagnoses limit a dry-eye-specific efficacy conclusion.

9. Surgical punctal occlusion in severe dry eye

   In a prospective series of 11 patients whose severe dry eye persisted despite medical care, 24 of 26 surgically closed puncta remained functionally occluded over a mean two-year follow-up. Seven patients reported symptom improvement. An open punctum was not a reliable stand-in for symptoms or tear-test results, and there was no comparison group.

10. Artificial tears and short-term visual quality

    A nonrandomized comparison measured corneal topography and visual performance before and one minute after artificial tears in 40 dry-eye patients and 20 controls. Patients with visible surface damage showed better surface regularity and contrast sensitivity immediately after drops. The study tested an immediate optical effect, not sustained symptom relief.

11. Two lubricants after myopic LASIK

    From a retrospective database of 519 LASIK patients, researchers compared 254 with sufficient follow-up who used carboxymethylcellulose or a hydroxypropyl methylcellulose and dextran lubricant. Early dry-eye symptoms and staining were lower in the carboxymethylcellulose group, but the difference was gone by months three and six. Treatment was not randomized, so other group differences could explain some of the early advantage.

12. Cyclosporine and conjunctival goblet cells

    Investigators took conjunctival biopsies before and after six months of cyclosporine or vehicle treatment in 28 patients with Sjögren or non-Sjögren dry eye, alongside 11 healthy controls. Goblet cell counts rose after cyclosporine, and an epithelial-turnover marker fell in the non-Sjögren group. This small tissue study explored mechanism rather than proving patient-perceived benefit.

Visual function, surgery, and possible risks

These studies connected dry eye with everyday vision, refractive and cataract surgery, medication exposure, and population patterns. Most observed associations rather than testing a preventive intervention.

13. Vision during sustained looking

    A prospective nonrandomized comparison measured acuity after 10 to 20 seconds without blinking in 22 dry-eye patients and eight healthy controls. Functional acuity dropped sharply in the dry-eye groups while remaining stable in controls; corneal surface regularity also worsened. The small groups make the size of the effect uncertain, but the design exposed a limitation of ordinary vision-chart testing.

14. Dry-eye symptoms in a community sample in Indonesia

    Researchers sampled households in five villages and one town in Sumatra and interviewed 1,058 adults. About 27.5% reported at least one frequent dry-eye symptom after age adjustment. Pterygium and current smoking were associated with symptoms, though the cross-sectional survey cannot show that either caused dry eye and symptoms were not the same as an exam-based diagnosis.

15. Preexisting dry eye and LASIK outcomes

    An analysis of 543 LASIK-treated eyes compared patients with definite, probable, or no preoperative dry eye. Vision outcomes and satisfaction were similar across groups, but those with definite dry eye had worse postoperative symptoms, tear measures, and staining. As an observational comparison of eyes rather than randomized treatment groups, it identifies risk without proving how best to prevent it.

16. Dry eye after hyperopic LASIK

    A retrospective 12-month follow-up of 88 people after LASIK for farsightedness found chronic dry-eye symptoms in 32%. Symptoms tracked several tear-film and staining measures and were associated with greater refractive regression. The study had no nonsurgical comparison group, so it cannot assign every later symptom to the procedure.

17. Cataract surgery in patients with dry eye

    A retrospective series examined 25 operated eyes in 23 patients who already had dry eye. Many achieved good final visual acuity, but eight eyes developed superficial punctate keratopathy and eight had an epithelial defect after surgery. The small selected series describes outcomes in this setting; it does not quantify excess risk against patients without dry eye.

18. Isotretinoin and temporary tear-film changes

    Forty patients taking oral isotretinoin for severe acne had eye exams before treatment, during month two, and after stopping. Tear breakup time fell below 10 seconds in half, and 42.5% reported dryness, itching, or contact-lens intolerance; abnormalities had resolved a month after treatment. Without an untreated acne group, the study offers a plausible drug association rather than a controlled risk estimate.

19. Preservatives in glaucoma drops and eye discomfort

    In a prospective survey of 4,107 glaucoma patients, symptoms and ocular-surface signs were more common with preserved than preservative-free drops; reported dry-eye sensation was 23% versus 14%. Some symptoms eased after a switch to preservative-free treatment. Prescribing was not randomized, so the groups may have differed in ways beyond preservatives.

20. Tear-film findings in urban Delhi

    A comparison of 400 symptom-free volunteers found abnormal tear breakup in 24% of Delhi residents versus 5.2% of people living outside the city. The researchers raised air pollution as one possible explanation. Residence also reflects many other exposures, and these test abnormalities did not mean participants had symptomatic dry-eye disease.

Symptoms and diagnostic measures

Questionnaires and tear-film tests can reveal different parts of the dry-eye picture. Their performance depends on the people tested and the reference definition used.

21. The Dry Eye Questionnaire and changes through the day

    A questionnaire study received responses from 62 of 100 mailed patients with aqueous-deficient dry eye and compared them with historical controls. People with Sjögren syndrome generally reported more frequent and intense symptoms, often worsening by evening. The response rate and historical comparison limit how broadly the pattern can be applied.

22. A screening questionnaire for contact-lens dry eye

    Across six North American clinics, 367 contact-lens wearers completed a specialized questionnaire before clinicians recorded their dry-eye assessment. The tool showed moderate discrimination, with an area under the curve of 0.74, and performed better than an older questionnaire in this setting. Its reference was a routine clinical judgment rather than an independent definitive test.

23. Lid-wiper staining in symptomatic contact-lens wearers

    Investigators stained the part of the upper lid that brushes the eye during blinking in 30 symptomatic and 75 asymptomatic soft-lens wearers. Staining appeared in 80% of the symptomatic group versus 13% of the comparison group. The study established an association in contact-lens wearers, but did not show that lid-wiper damage caused their symptoms.

24. Repeatability of a vision-related quality-of-life questionnaire

    Seventy-five dry-eye patients completed the 25-item NEI Visual Function Questionnaire twice. Overall and subscale scores generally showed moderate to high repeatability, while the ocular-pain subscale was less stable. The study examined measurement consistency in one optometry practice, not whether a particular treatment improved quality of life.

25. Fluorescein meniscus time as a tear test

    An open comparison assessed fluorescein meniscus time, tear breakup time, and Schirmer testing in 62 patients with rheumatoid arthritis and dry-eye symptoms plus 51 controls. The new measure flagged more patients as abnormal than Schirmer testing under the study's chosen thresholds. The selected patient group and lack of an independent diagnostic standard limit the claimed sensitivity advantage.

26. High-speed imaging of tear-film buildup

    A preliminary imaging study recorded corneal surface regularity four times a second after blinking in 15 healthy volunteers and seven dry-eye patients. The surface usually became most regular several seconds after a blink, showing that test timing matters. The small dry-eye subgroup leaves diagnostic usefulness unproven.

What the ocular surface studies revealed

Small human tissue and tear studies explored inflammatory and biochemical differences that could help explain dry eye. They were mainly hypothesis-building studies, not clinical tests ready for routine use.

27. Reduced tear MUC5AC in Sjögren syndrome

    Researchers compared tear samples and conjunctival cells from 11 people with Sjögren syndrome and 17 healthy volunteers. Both tear MUC5AC protein and its conjunctival messenger RNA were lower in the Sjögren group, while two other measured mucin transcripts did not differ significantly. The small cross-sectional study supports a possible role for mucin deficiency but cannot establish causation.

28. Inflammatory cells in Sjögren and non-Sjögren dry eye

    Conjunctival biopsies from 15 patients with Sjögren dry eye and 15 with non-Sjögren dry eye showed immune-cell infiltration and markers of activation in both groups, without a clear difference between them. The tissue findings strengthened the case for inflammation in more than one dry-eye subtype. They did not measure whether suppressing those markers would relieve symptoms.

29. A tear enzyme in keratoconjunctivitis sicca

    Tear samples from 20 patients with keratoconjunctivitis sicca contained more group IIA phospholipase A2 than samples from 20 age-matched controls. The authors suggested that reduced aqueous tearing could concentrate the enzyme. This small comparison did not show whether the enzyme itself contributes to disease or can diagnose it reliably.

30. Androgen signaling and eyelid oil composition

    Researchers analyzed meibomian gland secretions from women with complete androgen insensitivity syndrome and age-matched women and men. Several lipid species differed when androgen receptors were dysfunctional, offering human evidence that hormones can influence the tear film's oily layer. The specialized population and biochemical endpoint do not establish a treatment for dry eye.

31. Tear lipids differed in people who could not tolerate contact lenses

    Investigators compared tear-film lipids and related proteins in 14 comfortable soft-lens wearers and 10 whose dryness made regular wear difficult. The intolerant group had more lipid breakdown products, phospholipase activity, and lipocalin in their tears. These small, cross-sectional comparisons suggest a possible tear-film mechanism but cannot establish whether the chemical changes caused intolerance.