Preservative‐free versus preserved glaucoma eye drops and occurrence of glaucoma surgery. A retrospective study based on the French national health insurance information system, 2008‐2016

Abstract

Purpose: Preservatives contained in glaucoma eye drops have been shown to have a deleterious impact on the ocular surface. We aimed to assess the association between preservative exposure and the occurrence of further glaucoma surgery among patients with glaucoma or ocular hypertension in France. Methods: The study concerned all patients who first received glaucoma eye drop treatments in a French medical-administrative database (EGB) between 2008 and 2015. Three groups were created according to the level of preservative exposure during the whole follow-up: '0% preservatives', 'mixed' and '100% preservatives'. The occurrence of glaucoma surgery was estimated according to preservative exposure indicators in Cox multivariate models adjusted on age, sex, number of glaucoma eye drops simultaneously used, systemic antihypertensive treatment and duration of treatment. Results: The sample consisted of 12 454 patients. The median (interquartile range) follow-up was 4.1 (1.7-6.1) years. A total of 231 (1.9%) patients underwent glaucoma surgery during follow-up. On multivariable analysis, the risk of glaucoma surgery was increased for the 'mixed' group (hazard ratio [HR] = 3.94 [95% CI, 1.54-10.05]) and for the '100% preservative' group (HR = 7.97 [95% CI, 3.07-20.67]) when compared with the 0% preservative group. Conclusion: We found an association between exposure to glaucoma eye drop preservatives and the prevalence of further glaucoma surgery. While these data might be used to support the consideration of routine use of preservative-free drops, in the absence of a randomized clinical trial, they cannot prove a direct cause-and-effect relationship between preservative-free glaucoma eye drops and further glaucoma surgery.

Preparing the ocular surface for glaucoma filtration surgery: an unmet clinical need

“…The modulation of medical therapy represents the first important step for mitigating GTOSD before surgery. Some of the recommended measures include switching from preserved to unpreserved formulations and limiting the number of pre-operative medications for an adequate period before surgery (Boimer & Birt 2013;Tailor et al 2016;Chamard et al 2020). The rationale for this approach is to contain inflammation by reducing the cumulative daily dose of preservatives and active compounds.…”

Cataract extraction and intraocular pressure-lowering agents delivery: A nationwide French study between 2005 and 2017

“…Details on the EGB database have been described elsewhere 9,10,12 and the database was previously used in other IOP-lowering agents studies. 13 The study was approved by the Montpellier University Hospital Institutional Review Board (2018_IRB_MTP_12-05).…”

Ocular benzalkonium chloride exposure: problems and solutions

“…Clinical manifestations of BAK-induced ocular surface toxicity in glaucoma patients using BAK-preserved medications (Table 3 ) include pain and discomfort (including stinging, burning, foreign body sensation, itching, and ocular dryness) [ 45 , 46 ], tearing [ 46 ], increased staining of conjunctival and corneal epithelial surfaces [ 27 , 46 – 48 ], increased tear break-up time [ 25 , 27 , 30 , 46 , 47 , 49 – 51 ], lower Schirmer scores [ 46 , 47 ], higher prevalence of punctate keratitis [ 25 , 26 , 30 ], and overall worse scores on the Ocular Surface Disease Index (OSDI), a validated instrument for assessing the presence and severity of ocular surface symptoms [ 27 , 30 , 48 , 49 , 52 , 53 ]. Other manifestations of chronic BAK exposure in eyes with glaucoma include conjunctival subepithelial inflammation and fibrosis [ 9 , 54 – 56 ], which can reduce the success of subsequent filtering surgery [ 9 , 57 – 59 ], as well as a higher rate of cataract surgery in eyes on long-term glaucoma therapy compared to those without such exposure [ 60 , 61 ], potentially related to the known actions of BAK in increasing expression of inflammatory and apoptotic mediators in lens epithelial cells [ 62 ]. OSD as a comorbidity to glaucoma adversely affects the quality of life [ 63 , 64 ], and the use of BAK-preserved medications has also been associated with worse quality of life than BAK-free medications [ 47 , 52 ].…”