Jayanti Chaudhary, B. Optom, F. Optom

Optometrist, Dr Shroff’s Charity Eye Hospital, Delhi, India

Glaucoma is an irreversible optic neuropathy which is characterized from an acquired loss of retinal ganglion cells, and corresponding atrophy of the optic nerve head. The objective of glaucoma management is to control IOP, limit optic nerve and retinal ganglion cell damage and preserve vision, ensuring good quality of life.⁽¹⁾

We are passing through an exciting phase in glaucoma therapy. Pilocarpine, beta-blockers, and oral CAI’s (Carbonic anhydrase inhibitors) have remained core of glaucoma therapy for a long time. In the last decade newer drugs like prostaglandins, alpha- adrenergic agonists and topically instilled CAI’s have been proved to be potential weapons for medical management of glaucoma.⁽²⁾

Dry eye is a complex syndrome caused and or aggravated by multiple factors such as old age, hormonal changes in women, nutrition ,various diseases of the eyelids and conjunctiva, prolonged contact lenses wearing , Sjogren’s syndrome, dermatological disease, refractive surgery, cataract surgery, androgen deficiency, radiotherapy.

Another cause of dry eye development is the long-term use of anti-glaucoma (IOP lowering) eye drops.⁽³⁾  Several researchers consider that ocular hypotensive medications play the main role in the development of dry eye symptoms in glaucoma patients.⁽⁴⁾ It has been found that the severity of dry eye symptoms are positively correlated with the number of IOP lowering medications been used and this seems to be more common with aging. Studies suggest that 40-50% of glaucoma patients have dry eye and women are more likely to develop the condition than men.^(5,6)

Preservatives present in the composition of eye drops can inhibit the process of mitosis and can have cytotoxic effects which might even cause cellular apoptosis.^(7,8) Long term use of eye drops with preservatives can result in squamous metaplasia of epithelial cells.⁽⁹⁾

The most used preservatives in hypotensive eye drops is benzalkonium chloride with a concentration of 0.005% to 0.02%. The toxic effect of benzalkonium chloride causes disturbance of the barrier function of epithelial cells due to intracellular pathological changes.⁽¹⁰⁾

A concentration of 0.1%-0.05% of these preservatives immediately causes cell lysis , a concentration of 0.01% – cell necrosis within 24 hours and benzalkonium chloride 0.005-0.0001% inhibits the process of growth and differentiation of cells leading to their apoptosis within 24-72 hours. Benzalkonium chloride also disrupts the lipid layer in the tear film composition and consequently increases evaporation of tears.^(11,12) Thus, disturbance in the tear film causes chain reaction which leads to inflammation, which consecutively causes the alteration in the quality of tears.

Another factor that would trigger dry eye in glaucoma patients is the use of drops containing beta-blockers. One of the properties of beta-adrenergic blocking agents is to affect basal and reflective tear secretion which might amounting up to 28-30% reduction from the baseline. Prolong use of beta-blockers stimulate these alterations in the central epithelial cells. Additionally, several studies show that regular use of timolol maleate 0.25%, for as minimum as 1 week can cause punctate keratitis as well as alteration of tear film, which was reported in every third person.⁽¹²⁾

Conclusion

Dry eye syndrome is a current challenge among glaucoma patients.⁽¹²⁾ Important objectives for glaucoma patients with dry eye symptoms include the reduction of local toxicity of eye drops, the development of glaucoma medications combined with artificial tears in addition with the adjustment of specified treatments for ocular surface alternations.^(12-14)

References:

1. Quaranta L, Riva I, Gerardi C, Oddone F, Floriani I, KonstasAG.Quality of Life in Glaucoma: A Review of the Literature. Adv Ther. 2016 Jun;33(6):959-81.
2. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review.JAMA. 2014 May 14;311(18):1901-11.
3. 3.Zhang, X., Vadoothker, S., Munir, W. M., &Saeedi, O. (2018). Ocular Surface Disease and Glaucoma Medications. Eye & Contact Lens: Science & Clinical Practice, 1.
4. Fogagnolo P, Torregrossa G, Tranchina L, Ferreras A, et al.Tear Film Osmolarity, Ocular Surface Disease and Glaucoma: A Review. Curr Med Chem. 2019;26(22):4241-4252.
5. 5. Nijm, Lisa M. MD, JD; De Benito-Llopis et al. Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review. Asia-Pacific Journal of Ophthalmology: November-December 2020 – Volume 9 – Issue 6 – p 481-490
6. DEWS II. The epidemiology of dry eye disease: report of the International Dry Eye Workshop (DEWS II). Ocul Surf2017; 15:334–365.
7. Baudouin C, Labbé A, Liang H, Pauly A, Brignole-Baudouin F. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010 Jul;29(4):312-34.
8. Jaenen, N., Baudouin, C., Pouliquen, P., Manni, G., Figueiredo, A., &Zeyen, T. (2007). Ocular Symptoms and Signs with Preserved and Preservative-Free Glaucoma Medications. European Journal of Ophthalmology, 17(3), 341–349.
9. Erichev VP, Petrov SY, Volzhanin AV, Ghazaryan SA .Continuous anti-glaucoma drug therapy as a risk factor of dry eye. VestnOftalmol. 2019;135(6):117-123.
10. Benzalkonium chloride in glaucoma medications. Noecker R, Miller KV.Ocul Surf. 2011 Jul;9(3):159-62.
11. Ammar, D. A., Noecker, R. J., &Kahook, M. Y. (2011). Effects of benzalkonium chloride- and polyquad-preserved combination glaucoma medications on cultured human ocular surface cells. Advances in Therapy, 28(6), 501–510.
12. Nina Bulat , ValeriuValeriuCuşnir , VitalieProcopciuc , VitalieCușnir et al.Diagnosing the Dry Eye Syndrome in modern society and among patients with glaucoma: a prospective study. Rom J Ophthalmol. Jan-Mar 2020;64(1):35-42
13. Voicu, Laura aSalim, Sarwat. New strategies for the management of ocular surface disease in glaucoma patients. Current Opinion in Ophthalmology.March 2021, Volume 32 (2), p 134–140
14. Muzychuk, Adam MD ^*Racine, Louis MD et al. Management of Ocular Surface Disease in Glaucoma: A Survey of Canadian Glaucoma Specialists. Journal of Glaucoma.December 2020, Volume 29 (12), p 1162–1172