# Evaluating and Managing the Microbial Contamination of Eye Drops: A Two-Phase Hospital-Based Study
## 1 Introduction  
Eye health is a state of maximized visual and functional ability that affects society's overall health, well-being, and quality of life [1]. Ocular diseases have clinical, economic, and humanistic impacts on individual and national bases [1]. According to the World Health Organization (WHO), at least 2.2 billion individuals worldwide have vision impairments [2]. Notably, nearly half of the reported cases are due to cataracts, refractive errors, age-related macular degeneration, glaucoma, or diabetic retinopathy [3]. However, it is important to note that many vision impairment types are preventable, including eye infections [2]. The eye is a complex-structured organ with specialized anatomy and physiology [4, 5] and a resilient local immune response [6]. Despite these defenses, ocular infection remains theleading cause of ocular injury and blindness [7]. Such infections can be due to multiple causes, among which the microbial contamination of ophthalmic droppers is significant [8]. These infections are the leading cause of ocular injury and blindness [7]. Specifically, the contamination of eye drops can occur throughout the manufacturing process, along the supply chain, and during use. To address this issue, preservatives are one of the solutions intended to decrease and even eliminate the risk of contamination of the formula [8]. Nevertheless, despite their wide use, these substances do not always have the intended effect [8]. Studies have shown that the microbial contamination rate of in-use therapeutic and diagnostic preserved eye drops varies between 11.7% and 94.46% [9; 10; 11; 12; 13; 14]. Furthermore, preservatives can have a toxic effect on corneal and conjunctival surfaces [15; 16; 17]. It is crucial to recognize that the preservative's effect is limited to the content of the eye drops and cannot prevent the microbial contamination of the dropper tip or cap due to having limited to no contact with these surfaces [8]. Indeed, a thirty-year literature review showed that the microbial contamination rate of preserved and preservative-free eye drops ranges from 2.3% to 73% [8]. Within this range, 7.7% to 100% of cases are due to often-disregarded sources, including the contamination of the dropper tip and cap [8]. Significantly, multiple studies have found an association between contaminated eye drops and eye infections [18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28], including keratitis [23; 24; 28], corneal ulcers [23; 26], and bacterial endophthalmitis [27; 21]. In particular, microbial contamination of the dropper tip and cap was associated with corneal injury [20; 28] and bacterial keratitis [24]. Thus, the contaminated dropper tip is a potential leading cause of serious ocular infections due to direct contact with the eyes during medication administration [29; 30; 31; 32]. Eye drops provide a noninvasive method for ocular drug delivery intended to treat, diagnose, and prevent eye diseases [33]. As defined by the _European Pharmacopoeia_, eye drops are sterile solutions, emulsions, or suspensions, aqueous or oily, containing one or more active ingredients intended for ocular instillation [34]. Notably, these conventional forms represent 90% of the marketed ophthalmic solutions [33]. They are available as ready-to-use products, either with or without preservative agents [34], and formulated in single-use or multi-use containers [8]. The production of eye drops relies on Good Manufacturing Practices (GMP) guidelines for preparing ophthalmic forms [35]. However, marketed pharmaceutical products do not meet all needs in ophthalmology. Consequently, eye drops are also prepared in hospitals to meet specific patient requirements, including for patients with allergies to preservatives [36]. This production process follows the Good Preparation Practices (GPP) guidelines [37], quality controls, and the methods for preparing sterile products outlined in the _Pharmacopoeia_[34].