Glaucoma and Dry Eye Disease: Opportunity to Assess and Treat

Figures & data

Table 1 Studies Examining the Ocular Surface Effects of Preservatives in Glaucoma Medications

Study	Patient Population	Methodology	Key Findings on Preservatives
Leung et al, 2008^Citation17	N=101 (202 eyes; 78% of patients with OAG; 22% of patients with ocular hypertension)	Cross-sectional, multivariate evaluation of OSD in glaucoma patients	Each additional BAK-containing eyedrop is associated with 2.03 increase in odds of abnormal lissamine green staining (OR: 2.03; 95% CI: 1.06–3.89; p=0.034)
Labbé et al, 2012^Citation44	N=40 patients treated for glaucoma or ocular hypertension with IOP-lowering drugs	Univariate and multivariate analysis of tear film osmolarity in patients treated with IOP-lowering drugs	Increased tear film osmolarity was significantly correlated with the number of instillations of preservative-containing eyedrops (r = 0.629, p<0.0001) Patients treated with more than one instillation of preservative-containing drops exhibited significantly increased osmolarity compared with patients treated without preservatives (p=0.002) and patients receiving only one instillation of preservative-containing drops (p=0.004) Number of instillations of preservative-containing drops was significantly correlated with TBUT (r = −0.479, p=0.002) and OSDI (r = 0.372, p=0.019)
Rossi et al, 2013^Citation45	N=233 patients with topically treated glaucoma	Observational, cross-sectional study of OSD risk factors in glaucoma patients	Multivariate analysis revealed that prolonged use of preservative-containing drops (OR: 5.25; p=0.005) and total BAK exposure (OR: 104.92; p<0.001) are significantly related to OSD
Lee et al, 2013^Citation48	N=187 glaucoma patients using topical IOP-lowering drugs in 300 eyes	Cross-sectional analysis of the effect of antiglaucoma drugs on corneal punctate epithelial erosion and TBUT	Cumulative BAK exposure was significantly and positively correlated with corneal punctate epithelial erosion (r = 0.208, p=0.001) and significantly negatively correlated with TBUT (r = −0.131, p=0.042) Corneal punctate epithelial erosion was significantly more severe in patients using β-blockers when adjusted for cumulative BAK exposure compared with those not using β-blockers (p=0.016)
Chen et al, 2015^Citation9	N=2065 glaucoma patients with newly diagnosed DED	Univariate and multivariate analysis of claims data to estimate effects of glaucoma treatments on DED risk	Increased risk of DED was observed in all medications (prostaglandin analogues, β-blockers, carbonic anhydrase inhibitors, pilocarpine, and combinations) except for α-agonists, presumably due to the use of Purite^® preservative as opposed to BAK
Villani et al, 2016^Citation39	N=100 patients with medically controlled POAG	Evaluation of the effect of glaucoma medication on ocular surface findings	Patients treated with preservative-containing drugs (n=80) had reduced TBUT (p<0.05) compared with patients treated with preservative-free drugs (n=20) Patients treated with BAK-containing drugs (n=72) had lower Schirmer test values than patients treated with Polyquad-containing drugs (n=8) and preservative-free drugs (p<0.001)
Pérez-Bartolomé et al, 2017^Citation19	N=211 glaucoma patients using IOP-lowering drugs and N=51 untreated healthy controls	Univariate and multivariate analysis of OSD in glaucoma patients	Patients using preservative-free medications showed lower prevalence of corneal staining than those using BAK-containing drops, which, in turn, showed lower prevalence than BAK + polyquaternium–containing drops (p=0.000) Presence of epitheliopathy correlated with higher daily preservative concentration and cumulative preservative concentration (p<0.005) Abnormal fluorescein corneal staining was associated with BAK-containing drops (OR: 1.567) and drops containing BAK + polyquaternium (OR: 5.09)
Rolle et al, 2017^Citation49	N=51 patients with POAG (27 treated with tafluprost; 24 treated with timolol) and N=20 age-matched healthy controls	Cross-sectional evaluation of long-term safety and tolerability of tafluprost and timolol	TBUT was significantly lower in patients treated with preservative-free timolol than in controls (p<0.05) Patients treated with either preservative-free timolol or preservative-free tafluprost had significantly higher OSDI scores than controls (p<0.0001 for both comparisons)
Zaleska-Żmijewska et al, 2019^Citation46	N=60 patients with POAG; N=30 individuals with suspected POAG who were untreated	Extracellular MMP-9 assessment of ocular surface inflammation in glaucoma patients	46.7% of subjects treated with BAK-containing drops exhibited clinically significant levels of MMP-9 compared with 16.7% of untreated individuals or those using preservative-free medication (p=0.0125) 50% of individuals using BAK-containing drugs and 10% of individuals using preservative-free or no treatment had TBUTs <5 s (p<0.05)

Abbreviations: BAK, benzalkonium chloride; CI, confidence interval; DED, dry eye disease; IOP, intraocular pressure; MMP-9, matrix metalloproteinase-9; OAG, open-angle glaucoma; OR, odds ratio; OSD, ocular surface disease; OSDI, Ocular Surface Disease Index; POAG, primary open-angle glaucoma; TBUT, tear breakup time.

Table 2 Considerations for the Assessment and Management of DED in Patients with Glaucoma

Assessment of DED in patients with glaucoma^Citation6

DEQ-5 Tear breakup time Osmolarity testing Ocular surface staining Tear volume Meibography Meibomian gland expressibility MMP-9 levels

Management of DED in patients with glaucoma

Modifications to glaucoma therapy Switch to preservative-free antiglaucoma medications Consider laser, MIGS, or incisional procedures Modify glaucoma drug delivery Treatment of DED Preservative-free ocular lubricants Topical anti-inflammatory therapy MGD-targeted therapy Antibiotics Meibomian gland expression Thermal pulsation Intraductal probing Intense pulsed light Tear conservation with punctal plugs Nasal spray tear stimulation

Abbreviations: DED, dry eye disease; DEQ-5, Dry Eye Questionnaire – 5 item; MGD, meibomian gland dysfunction; MIGS, minimally invasive glaucoma surgery; MMP-9, matrix metalloproteinase-9.

Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17(5):350–355. doi:10.1097/IJG.0b013e31815c5f4f

 PubMed Web of Science ®Google Scholar

Labbé A, Terry O, Brasnu E, Van Went C, Baudouin C. Tear film osmolarity in patients treated for glaucoma or ocular hypertension. Cornea. 2012;31(9):994–999. doi:10.1097/ICO.0b013e31823f8cb6

 PubMed Web of Science ®Google Scholar

Rossi GCM, Pasinetti GM, Scudeller L, Raimondi M, Lanteri S, Bianchi PE. Risk factors to develop ocular surface disease in treated glaucoma or ocular hypertension patients. Eur J Ophthalmol. 2013;23(3):296–302. doi:10.5301/ejo.5000220

 PubMed Web of Science ®Google Scholar

Lee S, Kim MK, Choi HJ, Wee WR, Kim DM. Comparative cross-sectional analysis of the effects of topical antiglaucoma drugs on the ocular surface. Adv Ther. 2013;30(4):420–429. doi:10.1007/s12325-013-0021-8

 PubMed Web of Science ®Google Scholar

Chen HY, Lin CL, Tsai YY, Kao CH. Association between glaucoma medication usage and dry eye in Taiwan. Optom Vis Sci. 2015;92(9):e227–232. doi:10.1097/OPX.0000000000000667

 PubMed Web of Science ®Google Scholar

Villani E, Sacchi M, Magnani F, et al. The ocular surface in medically controlled glaucoma: an in vivo confocal study. Invest Ophthalmol Vis Sci. 2016;57(3):1003–1010. doi:10.1167/iovs.15-17455

 PubMed Web of Science ®Google Scholar

Pérez-Bartolomé F, Martínez-de-la-Casa JM, Arriola-Villalobos P, Fernández-Pérez C, Polo V, García-Feijoó J. Ocular surface disease in patients under topical treatment for glaucoma. Eur J Ophthalmol. 2017;27(6):694–704. doi:10.5301/ejo.5000977

 PubMed Web of Science ®Google Scholar

Rolle T, Spinetta R, Nuzzi R. Long term safety and tolerability of Tafluprost 0.0015% vs Timolol 0.1% preservative-free in ocular hypertensive and in primary open-angle glaucoma patients: a cross sectional study. BMC Ophthalmol. 2017;17(1):136. doi:10.1186/s12886-017-0534-z

 PubMedGoogle Scholar

Zaleska-Żmijewska A, Strzemecka E, Wawrzyniak ZM, Szaflik JP. Extracellular MMP-9-based assessment of ocular surface inflammation in patients with primary open-angle glaucoma. J Ophthalmol. 2019;2019:1240537. doi:10.1155/2019/1240537

 PubMed Web of Science ®Google Scholar

Wolffsohn JS, Arita R, Chalmers R, et al. TFOS DEWS II diagnostic methodology report. Ocul Surf. 2017;15(3):539–574. doi:10.1016/j.jtos.2017.05.001

 PubMed Web of Science ®Google Scholar