Dry Eye Research in 2007: 32 Notable Human Studies

The 2007 picture

What the research shows

In 2007, researchers examined both dry eye’s effect on everyday visual tasks and changes in the tear film, surface cells, and corneal nerves. No single office test captured the full picture. Treatment comparisons offered clues for specific formulations and patient groups, while small uncontrolled reports pointed to questions for stronger trials.

Treatments and long-term care

Several comparisons tested drops or tear preservation. Case series explored difficult-to-treat disease, but they cannot isolate a treatment effect as well as a randomized trial.

1. Cyclosporine, punctal plugs, and their combination

   Thirty patients with dry eye were randomized to cyclosporine drops, lower punctal plugs, or both and followed for six months. Plug-containing groups gained tear wetness sooner, while groups receiving cyclosporine showed later improvement in rose bengal staining. The combination reduced artificial tear use more than plugs alone at six months. With only about ten people per arm, the comparison was too small to establish a preferred regimen for all patients.

2. Umbilical cord serum versus a patient's own serum

   A prospective comparison treated 48 patients with severe dry eye using either their own serum or donated umbilical cord serum drops for two months. Both groups improved; symptom and surface-damage scores generally favored cord serum, with a goblet-cell advantage in the Sjögren subgroup. Treatment was assigned by patient rather than randomized, and analyses included both eyes from some participants.

3. Platelet-rich plasma drops in a small series

   Eighteen consecutive patients with symptomatic dry eye used drops made from their own platelet-rich plasma for one month. Most reported improvement, and the investigators observed less staining and better tear-meniscus and conjunctival-cell measures. Without a comparison group, the study cannot tell how much of the change came from the drops or whether benefit would persist.

4. Tamarind seed polysaccharide compared with hyaluronate

   An open-label randomized study assigned 30 patients to one of two tamarind seed polysaccharide concentrations or hyaluronate drops for 90 days. Tolerability and most measured outcomes were similar; the higher tamarind concentration favored a few reported symptoms. The ten-person groups and lack of masking make small differences uncertain, despite the formulation's interesting surface-binding properties.

5. Castor-oil emulsion reduced tear evaporation

   In a randomized, examiner-masked month-long study, 53 people with mild to moderate dry eye used either a castor-oil emulsion or hypromellose drops. Tear evaporation fell in both groups but more with the emulsion; tear production and osmolality did not change significantly. The physiology result suggests a possible role for lipid-containing drops, while the trial did not establish superior long-term symptom control.

6. Three lubricants compared during the hour after dosing

   Fifty patients completed a randomized, double-masked crossover comparison of three commercial lubricants. A hydroxypropyl-guar formulation prolonged tear breakup time more than two carboxymethylcellulose formulations at several points in the following hour; differences in an ocular-protection index were narrower. These were short-term surface measurements, not proof of better sustained comfort or clinical outcomes.

7. A mid-viscosity carboxymethylcellulose tear

   A report combined three human studies, including a 39-person masked crossover experiment and a 103-person masked randomized month-long comparison. The thicker carboxymethylcellulose drop prolonged short-term tear protection and improved staining and symptoms, but users reported more blur than with thinner drops. The separate study designs and outcomes should be read individually rather than as one large trial.

8. Lipid-layer effects of two emulsion drops

   Forty-one people with symptoms and a thin tear-film lipid layer received one emulsion drop in each eye, with different brands assigned to fellow eyes. Both increased measured lipid-layer thickness over 15 minutes, and one produced a larger increase. The experiment measured an immediate physical effect; it did not show that the thicker layer led to better symptoms or longer-lasting protection.

9. Recurrence after a steroid pulse in Sjögren-related dry eye

   Fifty-three patients with Sjögren-related keratoconjunctivitis sicca received a tapering course of preservative-free methylprednisolone drops and were followed for recurrence. Symptoms, staining, and tear measures improved, but about one in five patients recurred after the first course. This uncontrolled series supplies follow-up information for a selected group; it does not establish comparative effectiveness or safety across broader use.

10. How long silicone punctal plugs remained in place

    A prospective cohort tracked 95 silicone plugs placed in 47 dry-eye patients for up to eight years. Retention fell from about 84% at three months to about 56% by a median of two years, and some eyes developed canalicular narrowing after spontaneous plug loss. The study describes device durability and complications rather than comparing symptom relief with another treatment.

11. Scleral lenses for severe graft-versus-host dry eye

    Thirty-three consecutive patients with severe dry eye from chronic graft-versus-host disease received a scleral lens device after conventional care had failed. A later survey found that many reported less pain and light sensitivity and better reading and driving. The survey was retrospective and had no untreated comparison, so the size of the treatment effect remains uncertain.

12. One-eye punctal occlusion in severe Sjögren dryness

    In 20 people with severe Sjögren-related dry eye, investigators randomly chose one eye for upper and lower punctal plugs and left the other eye untreated while usual drops continued. Among 13 who completed at least six weeks, discomfort and rose bengal staining improved in the plugged eye, but Schirmer wetting did not. The seven dropouts and small final sample limit confidence.

Daily impact, surgery, and environment

These studies connected dry eye with everyday tasks and examined changes after refractive surgery and environmental or hormonal exposure.

13. Dry eye and difficulty with daily visual tasks

    A questionnaire substudy in the Women's Health Study and Physicians' Health Study compared participants with and without diagnosed or severe-symptom dry eye. After adjustment for several health factors, dry eye was associated with more difficulty reading, using a computer, working, watching television, and driving. The cross-sectional, self-reported outcomes establish a meaningful burden but cannot prove that dry eye alone caused every difficulty.

14. Dry eye six months after LASIK

    A retrospective series assessed 190 LASIK eyes whose patients had reported no preoperative dry-eye symptoms. At six months, about 20% of eyes met the study's definition of persistent dry eye; female sex and greater attempted refractive correction were associated with risk. Eye-level analysis and a single surgical setting limit how directly that percentage applies to today's procedures.

15. Persistent symptoms after high-myopia LASIK

    Twenty patients examined two to five years after high-myopia LASIK were compared with ten controls. More than half of the surgery group reported dry-eye symptoms, yet tear secretion, breakup time, and measured corneal sensitivity did not clearly differ. The small cross-sectional sample cannot establish the cause of symptoms, but it reinforces that discomfort may persist without matching routine signs.

16. Femtosecond LASIK hinge position did not change dry-eye outcomes

    A randomized fellow-eye study compared superior and temporal flap hinges in 33 people undergoing bilateral femtosecond LASIK. Corneal sensation declined after surgery in both eyes and remained reduced at measured visits through one year, but hinge position did not produce a detectable difference in sensation or dry-eye measures. This addresses hinge orientation for the technique used, not every approach to refractive surgery.

17. Ocular surface measures across the menstrual cycle

    Fourteen women with dry-eye symptoms and 15 without were tested during three menstrual phases over two cycles. Symptoms and several tear and surface measures varied with hormonal phase, with larger changes in the symptomatic group. The small observational design supports timing as a possible source of measurement variation, but it does not show that a particular hormone level causes dry eye.

18. Airplane-like low humidity increased tear evaporation

    An environmental-chamber experiment measured tear evaporation in 18 dry-eye patients and 11 healthy volunteers at two humidity ranges. Evaporation was nearly twice as high in the lower, airplane-like humidity condition across the combined sample. This demonstrates an immediate physical effect of dry air; it does not estimate the risk of persistent disease after travel.

19. A dry chamber exposed changes in minimally symptomatic eyes

    Ten contact lens wearers with minimal symptoms underwent two-hour exposures to a dry chamber and, a month later, a more typical indoor environment. Without lenses, the dry condition worsened several tear and surface measures; with lenses, some measures changed under both conditions. The effects were reversible, but the small sample and fixed exposure order make generalization cautious.

20. Preserved glaucoma drops were associated with more ocular discomfort

    A four-country practice survey examined 9,658 patients using glaucoma beta-blocker drops with or without preservatives. Dry-eye sensation was reported by 35% of users of preserved drops versus 16% of users of preservative-free drops; symptoms and surface signs also decreased among many patients who later reduced preserved-drop exposure. Treatment was not randomized and patients were enrolled nonconsecutively, so the comparison cannot isolate the preservative effect.

Questionnaires and tear measurements

Patient-reported scales and imaging methods were developed alongside older tests. Their validation samples and reference standards differed, so no single result defines dry eye on its own.

21. OSDI scores and tear tests in a clinic sample

    Sixty-eight clinic patients completed the Ocular Surface Disease Index before Schirmer and tear breakup testing. Higher symptom scores were associated with shorter tear breakup time but not clearly with Schirmer wetting. The study supports the OSDI as a structured symptom measure, while its small convenience sample and lack of an independent diagnostic reference limit claims about diagnostic accuracy.

22. The short SANDE symptom scale

    Investigators prospectively tested the Symptom Assessment iN Dry Eye, a short visual-analog scale, in 52 patients, repeating it over days and months. Scores repeated reasonably well over a few days but showed more drift over a two-month interval. The tool offered a compact way to track symptoms, though the authors called for refinement and testing in larger groups.

23. An interval-scale Ocular Comfort Index

    A 12-question Ocular Comfort Index was developed and tested in 452 participants using methods designed to make score differences more interpretable. Repeatability was favorable, scores tracked another dry-eye questionnaire and tear breakup time, and the index detected symptom change after lubricants. It was a promising measurement tool, with clinical usefulness still dependent on testing in varied populations.

24. Noninvasive tear-meniscus imaging in Sjögren syndrome

    A tear-interference imaging method measured lower tear-meniscus height in 27 Sjögren patients and 17 healthy volunteers. Menisci were lower in the patient group; in a small subset, height rose after punctal occlusion. This proof of concept shows that tear volume can be tracked without touching the eye, but its diagnostic performance needs larger validation.

25. Tear evaporation in Sjögren and other aqueous-deficient dry eye

    A case-control study used a ventilated chamber to compare evaporation in 21 patients with Sjögren-related aqueous deficiency and 12 with non-Sjögren aqueous deficiency. Evaporation was higher in the Sjögren group, which also had worse lipid-layer and meibomian findings. The groups were small and differed clinically, so the result identifies a pattern rather than a stand-alone diagnostic cutoff.

26. Tear osmolality in symptomatic postmenopausal women

    Among 37 postmenopausal women not using hormone therapy, those reporting dry-eye symptoms had higher tear osmolality and different tear-ferning patterns than those without symptoms. Osmolality and ferning did not strongly correlate with each other. The small, symptom-defined comparison suggests these tests capture related but distinct tear properties, without establishing a universal threshold.

27. Staining patterns, tear deficiency, and meibomian dropout

    Twenty-two dry-eye patients and 11 controls had lissamine staining, Schirmer testing, and meibomian gland assessment. Greater staining aligned with lower tear production, and gland dropout was more common in the patient group. The small cross-sectional study helps interpret staining patterns but cannot determine whether gland changes preceded the surface damage.

28. Tear-meniscus height from standard photographs

    Researchers measured the tear meniscus in fluorescein photographs from 19 healthy volunteers and 14 dry-eye patients. Upper and lower menisci were smaller in the dry-eye group, and height correlated with Schirmer results. The approach could make tear-volume assessment more accessible, but its modest sample did not establish how accurately it distinguishes dry eye in routine practice.

Corneal and inflammatory biology

Small human tissue and imaging studies looked beyond tear volume to inflammation, corneal nerves, and conjunctival cells.

29. Inflammatory proteins in dry-eye tears

    Tear samples from 18 dry-eye patients and 14 controls were tested for interleukin-6 and tumor necrosis factor-alpha. Both were higher in the patient group; interleukin-6 also tracked several tear and surface measures and was higher in Sjögren than non-Sjögren dry eye. This small observational study supports an inflammatory component, but the proteins were not validated as clinical tests.

30. Corneal cells and nerves in Sjögren syndrome

    In vivo confocal microscopy compared 35 people with Sjögren syndrome and 20 matched controls. The Sjögren group had a thinner cornea, fewer superficial epithelial cells and subbasal nerves, and more tortuous nerves; some imaging results related to clinical findings. Cross-sectional images reveal structural differences but cannot establish when or why they developed.

31. Corneal nerve density tracked sensitivity in dry eye

    Confocal imaging and noncontact sensory testing compared 21 people with Sjögren or non-Sjögren dry eye with 20 healthy volunteers. Dry-eye eyes had fewer subbasal corneal nerves and lower mechanical, chemical, and thermal sensitivity; nerve density correlated with measured sensation. This small case-control study cannot show whether nerve changes preceded dry eye or whether the pattern applies to every clinical subtype.

32. Goblet-cell loss shortly after LASIK

    Investigators sampled conjunctival cells in 11 patients before LASIK and at one week and one month afterward. Goblet-cell density was lower at both follow-ups, suggesting that the surgery or suction-ring step affected the ocular surface. The tiny sample and absence of a nonsurgical control do not show how much this change contributed to patients' dry-eye symptoms.