Every year about this time the finest ophthalmic researchers assemble for the annual Association for Research in Vision and Ophthalmology (ARVO) meeting. Much of the research is summarized in the ARVO Abstracts, published annually in the journal Investigative Ophthalmology and Visual Science. An online search of the ARVO abstracts reveals some interesting information and answers some of the current questions in visual science, especially in the area of dry eye.

Space does not permit, nor does time allow me to discuss the literally hundreds of abstracts devoted to research in dry eye. While there is a tremendous amount of work being done in the laboratory on dry eye, I tried to limit my review to human studies and clinical findings, hopefully on items that can perhaps translate to our daily in-the-trenches clinical practice.

DED Progression
For instance, we all recognize dry eye to be a chronic disease, but is it progressive? Little information is available regarding the long-term natural history of dry eye disease (DED). In one study, 398 men and 386 women with DED of over ten years duration were questioned to evaluate the degree to which various aspects of their DED had changed in the time since their initial diagnosis. The authors concluded that most people with DED did not experience worsening over time. They found that when worsening did occur (in about 20% to 30% of cases), it was more likely to be seen among women, people who take systemic beta-blockers, and among those who experience severe symptoms earlier in the course of their disease.¹

Another interesting study compared reading speed between normal patients and those suffering from dry eye.² As one might expect, reading speed was found to be reduced in patient with DED versus that in normal subjects, and as the severity of dry eye increased, the reading rate decreased. A Wilmer Eye Institute study also found that patients with symptomatic dry eye read significantly slower than subjects without dry eye symptoms and the researchers also noted greater reading speed decreases with more severe dry eye symptoms.³

Diagnostics
Several studies were presented that attempt to correlate commonly used clinical tests with dry eye signs and symptoms. We all know there is little correlation between our patient's symptoms and clinically observable signs, and this is very frustrating clinically. One study of 598 eyes across 11 clinical sites tested tear osmolarity, tear break up time (TBUT), Schirmer test, corneal and conjunctival staining and meibomian gland dysfunction grading and compared the clinical signs with the patient symptoms using the OSDI questionnaire. The investigators found no correlation between any of the signs or symptoms except for corneal and conjunctival staining.⁴ This did not surprise the authors, who concluded that "the clinical presentation of dry eye disease is multifactorial, with each test contributing different information, thus correlation between different tests should not be expected." Very weak correlations were also found between tear osmolarity, Schirmer test, TBUT, fluorescein corneal staining and ocular symptoms in another multi-center study of 168 subjects,⁵ while yet another study of 33 subjects found some correlation between tear osmolarity and symptoms.⁶

Tear osmolarity is a topic of much research interest. A study out of Australia found that tear hyperosmolarity had no adverse effect on the biophysical properties and stability of the tear film.⁷ A German study found tear osmolarity to be significantly increased in patients with meibomian gland disease⁸ and this osmolarity increase correlated to tear film break up time, Schirmer testing and vital dye staining. In a Pennsylvania study of patients with Graves' disease, the investigators did not find any significant difference in tear osmolarity between patients with Graves' disease and normal controls.⁹

Vital Dye Studies
I personally find vital dye studies to be of interest. There are a number of investigational studies of vital dye use in the eye, most of which deal with staining internal ocular structures such as the lens capsule¹⁰ and retina.¹¹ A study out of Brazil found the staining patterns in dry eye patients to be similar between rose bengal and trypan blue.¹² As with comparative studies between rose bengal and lissamine green, rose bengal was found to cause greater patient discomfort. One particularly interesting study out of Italy attempted to ascertain if lissamine green staining of the conjunctiva correlates with inflammation in dry eye patients. This small pilot study of thirty patients looked for inflammatory markers (in particular, creatine kinase and lymphocytes) in areas of conjunctival lissamine green staining. Their findings indicate that lissamine green staining of the conjunctiva could be correlated to immune cell infiltration of the conjunctival epithelium.¹³

Treatment
Finally, allow me to mention a few studies concerning dry eye treatment. There are more studies of novel and investigational medications than I can discuss here. Several abstracts dealt with the use of autologous serum in the treatment of DED. In a Spanish study, 203 DED patients¹⁴ as well as 97 DED patients in a French study¹⁵ were treated with autologous serum. Both studies noted improvement in patient symptoms and clinical signs. A study of preservative-free 0.1% cyclosporine emulsion (Cyclokat) showed great benefit in patients with severe keratitis in Sjogren and non-Sjogren's patients.¹⁶ And finally, a study out of the University of California, San Francisco, found a 1 gram dose of oral azithromycin dosed once weekly improved meibomitis in 64% of test subjects. The authors concluded that azithromycin's "well-documented anti-inflammatory and anti-microbial properties…and azithromycin's ocular pharmacokinetics allow for a much simpler and shorter dosing regimen than other frequently used medications."¹⁷

REFERENCES
1. Tarko LM, Li JZ, Dartt DA, Schaumberg DA. The natural history of dry eye disease from the patient's perspective. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 5442.
2. Ridder III WH, Zhang Y, Huang J-F. Reading speed and contrast sensitivity in a prospective, non-interventional study of normal and dry eye subjects. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 534.
3. Akpek EK, van Landingham S, Rubin G, et al. Difficulty with sustained silent reading in dry eye. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 535.
4. Sullivan BD, Crews LA, Messmer EM, et al. Correlation between commonly used clinical tests in the management of dry eye disease. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 550.
5. Yang Y, Abrams M, Garner W, et al. An exploration of the relationships between tear osmolarity and other measures of dry eye signs and symptoms. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 548.
6. Feng JJ, Starr C. Correlation between tear osmolarity, tear meniscus height and subjective symptoms of dry eye disease. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 559.
7. Mudgil P. Hyperosmolarity and tear film stability: Are they related? Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 555.
8. Messmer EM, Drillisch J, Kampik A. Osmolarity in patients with meibomian gland dysfunction (MGD). Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 556.
9. Medina ED, Massaro-Giordano M, Tamhankar MA, et al. Tear osmolarity in patients with Graves' disease. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 561.
10. Laubichler P, Karnt M, Varja A, et al. Evaluation of the biocompatibility of a new cyanine dye for lens capsule staining. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 1052.
11. Maia M, Barroso L, Filho MM, et al. Use of leutein and zeaxanthin alone or combined with brilliant or trypan blue to identify intraocular structures intraoperatively in cadaveric eyes. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 3790.
12. Castro RS, Freire LM, Ambrosio R. Staining patterns in dry eye syndrome: Rose Bengal versus tripan blue. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 545.
13. Barabino S, Valente C, Montaldo E, et al. Does lissamine green staining of the ocular surface correlate with inflammation in dry eye patients? Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 546.
14. Martinez-Osoria H, Yaya MM, De la Paz M, et al. Effectiveness of chronic treatment with autologous serum eyedrops in severe ocular surface disorders. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 2352.
15. Basli E, Laroche L, Laurent M, et al. The effects of autologous serum eyedrops in the treatment of dry eye disease and epithelial defects: A retrospective study. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 3570.
16. Buggage RR, Amrane M, Ismail D, et al. The effect of Cyclokat (preservative-free cyclosporine 0.1% cationic emulsion) on dry eye signs and symptoms in Sjogren and non-Sjogren patients with moderate to severe DED in a phase III randomized clinical trial. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 576.
17. Greene JB, Margolis TP, Fentelmann R, et al. Oral azithromycin for the treatment of meibomitis. Invest Ophthalmol Vis Sci 2012; 53: E-Abstract 606.