Dry Eye Research in 2006: 32 Notable Human Studies

The 2006 picture

What the research shows

The most persuasive 2006 results came from controlled comparisons and better measurement of dry eye signs, but few interventions showed a clear, durable symptom advantage. Population estimates varied greatly with sampling and diagnostic rules, and early biomarker findings remained exploratory.

Treatments and tear conservation

Randomized studies compared drops, supplements, and care around LASIK or contact lens wear. Uncontrolled series examined serum drops, topical steroids, and tear-drainage surgery in selected patients.

1. Cyclosporine improved meibomian gland signs, but not symptoms clearly

   Thirty-three people with symptomatic meibomian gland dysfunction were randomized to twice-daily 0.05% cyclosporine or preservative-free artificial tears for three months; 26 completed follow-up. Gland plugging, several lid findings, and corneal staining improved more with cyclosporine, but the symptom difference was not statistically significant. The small number who completed the trial limits confidence in the clinical benefit.

2. Warm moist air showed promise for meibomian gland dysfunction

   Investigators first tested a ten-minute warm moist-air treatment in 15 people with meibomian gland dysfunction and 20 controls, then compared two weeks of twice-daily use in 10 patients with warm towel compresses in 10 others. Tear breakup time improved in the device group but not the towel group, and lipid-layer thickness increased more with the device. The small comparison, without reported random assignment, cannot establish a durable advantage over standard warm compresses.

3. Serum drops improved some tear measures after LASIK

   A randomized study followed 27 men after LASIK, comparing autologous serum drops with artificial tears for six months. Tear breakup time at six months and rose bengal staining at one and three months favored serum, while dryness ratings, Schirmer readings, and fluorescein staining did not differ clearly. The male-only postoperative sample was small, and the results do not establish benefit for other forms of dry eye.

4. Cyclosporine around LASIK improved refractive accuracy, not reported dryness

   In a double-masked randomized trial, 21 patients who already had dry eye used cyclosporine or preservative-free artificial tears starting a month before LASIK and continuing afterward. Eyes in the cyclosporine group were closer to the intended refractive target at three and six months, but symptom scores and corneal staining did not differ significantly between groups. The small surgical trial should not be read as evidence of broader dry eye symptom relief.

5. A liposomal eyelid spray beat a lipid eye gel in one crossover trial

   A randomized, multicenter crossover study assigned 74 patients with lipid-layer dry eye to six weeks each of a liposomal spray applied to closed eyelids and a triglyceride-containing eye gel, in opposite orders. Tear and lid measurements and patient preference favored the spray during both treatment periods. The comparison used two active products and had no sham spray, so it cannot establish benefit against no treatment.

6. The tear product paired with cyclosporine changed trial outcomes

   Sixty-one patients were randomized to six months of cyclosporine with one of two artificial tears, or to one tear product alone. Cyclosporine paired with Systane improved corneal staining and several reported symptoms more than cyclosporine paired with Refresh Tears, while Schirmer and conjunctival measures showed no clear differences. Multiple product-specific comparisons in a modest trial make the result a question about supportive drops, not a general estimate of cyclosporine benefit.

7. A fatty-acid supplement missed most between-group outcomes

   In a six-month double-masked trial, 71 patients with mild to moderate dry eye received polyunsaturated fatty-acid capsules or placebo. Overall tear tests and patient ratings did not differ significantly between groups, though two selected signs improved. The borderline and mixed findings require a larger confirmatory trial before drawing a treatment conclusion.

8. Umbilical cord serum drops showed promise in an uncontrolled series

   Thirty-one patients with severe dry eye used umbilical cord serum drops for two months while investigators tracked symptoms, tear tests, staining, and conjunctival cells. Symptoms, breakup time, corneal staining, and cell measures improved from baseline, but Schirmer results and corneal sensitivity did not. Without a comparison group, the study cannot separate the drops' effect from other changes over time.

9. A contact lens cyclosporine pilot found better dryness ratings

   Seventeen contact lens wearers with dryness were randomized to cyclosporine or rewetting drops for five weeks, with investigators masked to assignment. Dryness ratings and temporal conjunctival staining favored cyclosporine, but the difference in lens-wearing time was not statistically significant. The sample was too small and follow-up too short to settle whether the treatment improves long-term lens tolerance.

10. One viscous artificial tear reduced staining more over a week

    After an initial paired-eye comfort comparison, patients were randomized to one week of carboxymethylcellulose or a propylene-glycol/polyethylene-glycol lubricant. Inferior corneal and temporal conjunctival staining favored carboxymethylcellulose, and more patients preferred it in the initial comparison. The short, product-specific trial does not show whether either drop has a durable advantage.

11. Topical steroid results were encouraging but uncontrolled

    Thirty patients whose moderate or severe dry eye had not responded to artificial tears used 0.1% fluorometholone drops for one month. Reported symptoms and clinical tests improved from baseline, but no untreated or alternative-treatment group was included. The brief follow-up also cannot establish longer-term steroid safety or effectiveness.

12. Canalicular ligation relieved symptoms in a surgical case series

    Surgeons retrospectively reviewed 59 tear-drainage canalicular ligations in 29 patients with severe dry eye, with an average follow-up of 20 months. Ninety-one percent of patients reported improvement; two later developed troublesome tearing and had the ligation reversed successfully. Without a comparison group or standardized symptom outcome, the benefit estimate is uncertain.

Symptoms, surgery, contact lenses, and visual function

Prospective and cross-sectional studies connected dry eye with refractive surgery, contact lens characteristics, visual quality, and the broader burden of sicca symptoms.

13. Dry eye after LASIK was linked to deeper treatment

    A prospective trial randomized 35 myopic patients to LASIK with either a nasal or superior flap hinge and followed them for six months. Postoperative dry eye, defined by corneal fluorescein staining, was common early on; greater preoperative myopia and deeper laser ablation were associated with higher risk. The study was small, and its staining-based definition does not capture every patient's symptoms.

14. Contact lens dryness tracked tear-film and lens factors

    A cross-sectional study enrolled 415 contact lens wearers and analyzed 360 with usable data, combining self-reported lens-related dryness with tear, lens, and health measurements. Dryness was associated with female sex, higher lens water content, faster tear-film thinning, and higher tear osmolarity, among other factors. Self-reported status and the cross-sectional design prevent a causal claim about any lens feature.

15. Dry eye reduced contrast sensitivity in a case-control study

    Researchers tested contrast sensitivity with and without glare in 33 dry-eye patients and 30 controls. The dry-eye group performed worse across most target sizes, but the extra loss specifically caused by glare differed significantly at only one target size. This small, single-setting comparison measured visual function rather than real-world activities.

16. Sjögren and nonautoimmune sicca patients reported similar burdens

    A prospective cross-sectional study compared 111 people with primary Sjögren syndrome with 65 people who had sicca symptoms but no autoimmune features. Pain, fatigue, dryness, quality of life, and psychological measures were similar between groups, while pain and fatigue tracked quality of life more closely than dryness ratings did. The selected specialty-clinic groups and one-time assessment cannot establish why their symptoms arose.

Questionnaires, tear tests, and ocular-surface biology

Several groups tested faster ways to measure tear changes or examined ocular-surface markers. Most were early validation studies in selected groups rather than ready-made diagnostic standards.

17. Three short questions identified many clinical dry eye cases

    A short dryness, irritation, and diagnosis-history questionnaire was tested within large women's and physicians' cohorts, with longer surveys in selected subsets and clinical examinations in 53 participants. Against the study's tear-test definition, it had 77% sensitivity and 83% specificity, and repeat answers were reasonably consistent. Clinical validation involved only 53 people, so the figures may not transfer to other settings or definitions.

18. The Marx line tracked meibomian gland findings

    Investigators scored the position of a fluorescein-stained line along the lower eyelid in 251 people and compared 15 patients with meibomian gland dysfunction with 15 age-matched controls. Scores rose with age and correlated with gland imaging and secretion findings; the dysfunction group had higher scores. This observational work suggests a quick clinical sign but did not establish diagnostic accuracy in a broad symptomatic population.

19. A five-second strip test reflected tear-meniscus changes

    A prospective study compared strip meniscometry in 50 dry-eye patients and 40 controls alongside tear stability, staining, and Schirmer testing. Strip readings tracked several other measures and changed after punctal occlusion in the patient group. The selected groups and lack of an independent validation sample leave its stand-alone diagnostic value uncertain.

20. Video mapping captured the area of tear-film breakup

    Researchers videotaped prolonged eye opening after fluorescein in 10 people with dry eye and 10 controls, then calculated the area of exposed cornea where the tear film had broken up. The breakup area was larger in the dry-eye group, whereas the between-group differences in conventional breakup time and maximum blink interval were not statistically clear. The sample was small and the prolonged staring task differs from ordinary blinking.

21. CCR5 expression was higher on dry-eye conjunctival cells

    Conjunctival cell samples from 45 patients with aqueous-deficient or evaporative dry eye and 15 controls were analyzed for the inflammatory receptor CCR5. Expression was higher in both dry-eye groups, with a smaller molecular analysis pointing in the same direction. The cross-sectional result identifies an association, not a validated diagnostic marker or proven treatment target.

22. Tear nucleotides rose with symptoms and mechanical stimulation

    In 97 participants divided among symptom, control, and stimulation groups, investigators measured two diadenosine polyphosphates in collected tears. Levels were higher in symptomatic dry-eye groups and also rose with forced blinking or corneal stimulation. Because normal mechanical activity changed the same molecules, this study alone cannot establish them as specific dry eye biomarkers.

23. Sjögren dry eye showed microscopic conjunctival surface damage

    Conjunctival biopsies from eight patients with Sjögren syndrome and seven controls were examined with electron microscopy. The Sjögren group had fewer and shorter epithelial microvilli, fewer secretory vesicles, and a less visible surface glycocalyx. This very small tissue comparison cannot determine whether those changes cause the dry eye or follow from it.

Prevalence, associated conditions, and environment

Surveys and clinical comparisons examined how dry eye or sicca findings varied with age, location, smoking, autoimmune disease, hormones, and humidity. Sampling and case definitions strongly shaped some estimates.

24. A Bangkok examination sample reported frequent dryness symptoms

    Researchers interviewed and examined 550 adults age 40 or older who came to a Bangkok hospital for annual eye checks. Thirty-four percent reported frequent dry eye symptoms, and meibomian gland disease was associated with symptoms or positive tear tests. Volunteers at one hospital are not a random city sample, and symptoms alone do not equal confirmed disease.

25. Dry eye signs were frequent among selected older Japanese adults

    A study of 113 Japanese pensioners age 60 or older used symptoms, tear tests, staining, and eyelid examination to apply Japanese dry eye criteria. Nearly three-quarters met the study's definition, and meibomian gland changes commonly accompanied tear instability. The small, selected group cannot support a prevalence estimate for all older adults in Japan.

26. Smokers had worse tear-lipid patterns than nonsmokers

    Investigators compared 60 smokers with 34 healthy nonsmokers using ocular-surface tests and tear-lipid imaging. Smokers showed more abnormal lipid-layer spreading, while Schirmer readings and goblet-cell density did not differ significantly. The nonrandomized comparison cannot isolate smoking from other differences between the groups.

27. Sicca in systemic sclerosis often had causes beyond Sjögren syndrome

    A prospective two-center series evaluated 133 patients with systemic sclerosis for dryness and, when indicated, salivary-gland changes. Sixty-eight percent had sicca symptoms, but only 14% met criteria for associated Sjögren syndrome; gland fibrosis was common. This specialty-care study included mouth as well as eye dryness and cannot estimate ocular dry eye prevalence by itself.

28. Sjögren prevalence changed substantially with the criteria used

    A two-phase survey of adult women in Izmir, Turkey combined symptom screening, blood tests, eye and salivary tests, and selected biopsies. Estimated primary Sjögren prevalence was 1.56% under older European criteria and 0.72% under the later US-European criteria. These are estimates of the autoimmune syndrome in women, not the prevalence of dry eye itself.

29. Lower humidity increased tear evaporation in patients and controls

    An evaporometry study compared 18 patients with keratoconjunctivitis sicca and 11 controls under higher and lower relative humidity. Tear evaporation rose sharply when humidity fell in all groups, while between-group evaporation differences were not statistically significant. The controlled measurement did not show how much symptoms would change during ordinary low-humidity exposure.

30. Lower androgen levels were linked specifically to gland-related dry eye

    A prospective case-control study measured circulating androgens in equal-sized groups with gland-related dry eye, nongland dry eye, and no dry eye. Bioavailable testosterone and related hormone measures were lower in the meibomian gland dysfunction group, while the nongland group did not differ clearly from controls. Because hormones and eye findings were measured at one time, the study cannot show that androgen changes caused gland disease.

31. Rheumatoid arthritis patients had more abnormal tear tests

    An Indian hospital study compared 84 adults with rheumatoid arthritis with 84 age- and sex-matched controls. Low Schirmer readings and short tear breakup were more common in the arthritis group, although symptoms did not closely track the tests. The clinic-based cross-sectional comparison does not establish the mechanism or describe risk in the general population.

32. Aging was linked to changes in human meibomian lipids

    Researchers collected meibomian gland secretions from younger and older men and women and analyzed their lipid profiles by chromatography and mass spectrometry. Older participants showed different lipid patterns and more opaque secretions, with some changes varying by sex. The findings offer a plausible route to age-related tear-film problems, but this comparison did not show that the lipid changes caused dry eye.