Tear osmolarity is a very reliable index to assess the damage caused by the medical therapy of glaucoma in the ocular surface.
Medical therapy is the first line treatment in open-angle glaucoma (80% of glaucoma). However, we know that its prolonged use causes multiple alterations in the ocular surface (OSD), especially when drugs with preservatives (1) and even more if it’s Benzalconium Chloride (BAK) (2).
Epidemiological studies show the relationship between antiglaucoma treatment and significant changes on the ocular surface (3-8), with the presence of symptoms in 60% of cases (5), percentage which increases in proportion to the number of drugs used and whose maximum is reached when it’s a three-drug treatment (8) and when it expands over time (9).
Cases with changes on the ocular surface ((OSD), are usually recognised by the tear hiperosmolarity (the most frequent and the most relevant sign), independent to the origin. The tear hiperosmolarity induces apoptosis and inflammatory processes of the ocular surface, delivering cytokines and some other inflammatory mediators.
The literature review (15-19) shows that 60% of patients who suffer from glaucoma and are treated medically, had changes consistent with ocular surface disease (Figure 1), 67.5% had alterations in the stability of the tear film (BUT reduced) and 47.5% had a higher tear osmolarity than 308 mOsm / L. normal limit value.
- Figura 1.- Superficial punctata queratitis in a glaucomatous patient with medical therapy. Slit lamp picture (A) and with fluorescein staining (B).
In a recent study (20), statistical analysis shows a high correlation between the values of osmolality and the rate OSDI, which measures the symptomatology of the ocular surface’s damage: r: 0.486; P = 0.002, as well as the BUT, which measures the stability of the tear film: r = −0.49; P = 0.009. A high correlation between osmolarity and the number of drugs used (r = 0.409, P = .009), the number of instillations (r = 0.405, P = 0.01), and the number of instillations of drugs with preservatives (r = 0.629, P, 0.0001) is also shown. No correlation was observed between osmolarity and Schirmer test and with vital dyes as well.
It is evident that the degree of severity and symptoms of involvement of the ocular surface is strongly correlated with tear osmolarity (21-28). The more pain felt, the higher the osmolarity will be. (P = 0.016) (20).
Symptoms of discomfort which goes with the treatment of glaucoma (generally due to dry eye), is one of the main factors which explain the poor adherence to treatment or disengagement (26). That’s why it’s really important to evaluate the ocular surface before starting treatment and during this, too, to highlight any changes which need to be treated.
It is important to know that the tests used in the assessment of dry eye have a different value in these patients. The Schirmer test and vital dyes are hardly correlated with the values of OSDI in glaucomatous patients, as it’s not a real dry eye, is due to the toxic effect of the drugs, and even more when preservatives are used.
Benzalconium Chloride (BAK) is one of the most frequent preservatives used in ophthalmic drugs. BAK causes an elevation of the tear osmolarity as it has a detergent effect (quaternary ammonium). BAK acts on lipid layer reducing the stability of the tear film, increasing the evaporative rate and thus increasing the osmolarity, the consequence is an evaporative type dry syndrome. The increase in osmolarity is a fact reflected in the BUT, with a really high correlation between them: Osmolarity increases and BUT is reduced. As the dryness of the eye is not caused by the deficit of the tear secretion, there’s no correlation with the Schirmer test, which keeps with normal values.
Once shown these dates, we think that a patient who suffers from glaucoma, (whether the person has just been diagnosed and the medical treatment is planed, and also if he or she has already been treated), the evaluation of the ocular surface is really important as complementary treatments will have to be approached to any alterations seen, so that it gets better or even to be operated on as an alternative, just not to damage anymore the ocular surface and ovoid the possible breach of the treatment.
To evaluate the status of the ocular surface, especially in patients who are already being medically treated, the test of tear osmolarity is shown as the most significant factor to make decisions. It consists in a no painful test easy to perform and highly accurate, especially now with the new systems as TearLab, based on detection with a chip that requires only 50 nL (Figure 2). (21-22).
- Figura 2.- Tear osmolarity measurement with Tear Lab system
The analysis of the tear osmolarity is thought to be a very important test to value the medical treatment applied to patients who suffer from glaucoma and their possible harmful effect on the ocular surface, causing or aggravating the syndrome of the evaporative dry eye.
1. Asbell PA, Potapova N. Effects of topical antiglaucoma medications on
the ocular surface. Ocul Surf. 2005;3:27–40.
2. Baudouin C, Labbé A, Liang H, et al. Preservatives in eyedrops: the
good, the bad and the ugly. Prog Retin Eye Res. 2010;29:312–334.
3. Fechtner RD, Godfrey DG, Budenz D, et al. Prevalence of ocular surface
complaints in patients with glaucoma using topical intraocular pressurelowering
medications. Cornea. 2010;29:618–621.
4. Jaenen N, Baudouin C, Pouliquen P, et al. Ocular symptoms and signs
with preserved and preservative-free glaucoma medications. Eur J Ophthalmol.
5. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface
disease in glaucoma patients. J Glaucoma. 2008;17:350–355.
6. Levrat F, Pisella PJ, Baudouin C. Clinical tolerance of antiglaucoma
eyedrops with and without a preservative. Results of an unpublished
survey in Europe [in French]. J Fr Ophtalmol. 1999;22:186–191.
7. Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular symptoms and
signs with preserved and preservative free glaucoma medication. Br J
8. Erb C, Gast U, Schremmer D. German register for glaucoma patients
with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin
Exp Ophthalmol. 2008;246:1593–1601.
9. Broadway DC, Grierson I, O’Brien C, et al. Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile. Arch Ophthalmol. 1994;112:1437–1445
10. The definition and classification of dry eye disease: report of the Definition
and Classification Subcommittee of the International Dry Eye Work-Shop (2007). Ocul Surf. 2007;5:75–92.
11. Tomlinson A, Khanal S, Ramaesh K, et al. Tear film osmolarity:
determination of a referent for dry eye diagnosis. Invest Ophthalmol
Vis Sci. 2006;47:4309–4315.
12. Yeh S, Song XJ, Farley W, et al. Apoptosis of ocular surface cells in
experimentally induced dry eye. Invest Ophthalmol Vis Sci. 2003;44:
13. Luo L, Li DQ, Doshi A, et al. Experimental dry eye stimulates production
of inflammatory cytokines and MMP-9 and activates MAPK signaling
pathways on the ocular surface. Invest Ophthalmol Vis Sci. 2004;45:
14. Murube J. Tear osmolarity. Ocul Surf. 2006;4:62–73.
15. Kuppens EV, Stolwijk TR, de Keizer RJ, et al. Basal tear turnover and
topical timolol in glaucoma patients and healthy controls by fluorophotometry.
Invest Ophthalmol Vis Sci. 1992;33:3442–3448.
16. Shimazaki J, Hanada K, Yagi Y, et al. Changes in ocular surface caused
by antiglaucomatous eyedrops: prospective, randomised study for the
comparison of 0.5% timolol v 0. 12% unoprostone. Br J Ophthalmol.
17. Bonomi L, Zavarise G, Noya E, et al. Effects of timolol maleate on tear
flow in human eyes. Albrecht Von Graefes Arch Klin Exp Ophthalmol.
18. Chong RS, Jiang YZ, Boey PY, et al. Tear cytokine profile in
medicated glaucoma patients: effect of monocyte chemoattractant protein
1 on early posttrabeculectomy outcome. Ophthalmology. 2010;117:
19. Malvitte L, Montange T, Vejux A, et al. Measurement of inflammatory
cytokines by multicytokine assay in tears of patients with glaucoma topically
treated with chronic drugs. Br J Ophthalmol. 2007;91:29–32.
20. Labbé A, Terry O, Brasnu E, et al. Tear Film Osmolarity in Patients Treated for Glaucoma or Ocular Hypertension. Cornea 2012;31:994–999.
21. Suzuki M, Massingale ML, Ye F, et al. Tear osmolarity as a biomarker for
dry eye disease severity. Invest Ophthalmol Vis Sci. 2010;51:4557–4561.
22. Sullivan BD, Whitmer D, Nichols KK, et al. An objective approach
to dry eye disease severity. Invest Ophthalmol Vis Sci. 2010;51: 6125–6130.
23. Schiffman RM, Christianson MD, Jacobsen G, et al. Reliability and
validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;
24. Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival
staining in the context of other dry eye tests. Cornea. 2003;22:640–650.
25. Rossi GC, Tinelli C, Pasinetti GM, et al. Dry eye syndrome-related
quality of life in glaucoma patients. Eur J Ophthalmol. 2009;19:572–579.
26. Nordmann JP, Auzanneau N, Ricard S, et al. Vision related quality of life
and topical glaucoma treatment side effects. Health Qual Life Outcomes.
27. Versura P, Profazio V, Campos EC. Performance of tear osmolarity
compared to previous diagnostic tests for dry eye diseases. Curr Eye
28. Johnson ME. The association between symptoms of discomfort and signs
in dry eye. Ocul Surf. 2009;7:199–211.