Clinical Evaluation of Biotrue Hydration Plus Multipurpose Solution in Daily Use with Planned Replacement Soft Contact Lenses

An estimated 45 million people wear contact lenses (CLs) in the USA [1], with 150 million wearers worldwide [2]. Planned replacement soft CLs (PRSCLs) remain popular, despite the trend towards increased fitting of daily disposable soft CLs [3, 4]; PRSCLs account for 40% of all global CL fits [3], and 84% of 742 habitual soft CL wearers surveyed in the USA wore PRSCLs in 2023. [4]

Two primary CL disinfection regimens are available for PRSCLs—a multipurpose solution (MPS) or a hydrogen peroxide solution (HPS) [5, 6]—and globally, 91% of PRSCL wearers were prescribed an MPS in 2023 [3]. MPSs are formulated with a variety of components intended to improve the wear experience [7]. Functional components include antimicrobial agents for disinfection, surfactants for lens cleaning and conditioning to improve lens wetting, buffering agents, chelating agents to improve cleaning, nonsurfactant wetting agents to help maintain a stable lens tear film, and demulcents and lubricants for hydration and comfort [7‐10]. Despite high reported satisfaction with contemporary lens care options, dryness remains the most common problem for soft CL wearers, reportedly experienced by nearly half (47%) in the their previous year of use. [11]

PRSCL wearers are typically motivated to continue with their preferred CL wear modality, and the choice of CL care solution for disinfecting their lenses can play an important role in CL comfort and maintaining successful CL wear. A real-world evaluation including more than 3000 PRSCL wearers demonstrated that Biotrue MPS (Bausch & Lomb Incorporated, Rochester, NY) [12] improved PRSCL comfort, with high eye care practitioner satisfaction [13, 14]. Additionally, 90% of PRSCL wearers on the verge of CL discontinuation owing to discomfort and dryness who switched from their habitual MPS to Biotrue MPS reported increased likelihood of continuing CL wear; 6 months later, 93% of responding subjects were still wearing CLs at least once per week [15].

The Tear Film & Ocular Surface Society (TFOS) International Workshop on Contact Lens Discomfort highlighted research into wetting agents that could be included in CL solutions to sustain CL surface wettability [16]. Subsequently, the TFOS International Dry Eye Workshop II (TFOS DEWS II) identified various agents used to alleviate the symptoms of dry eye disease [17]. These include hyaluronan (HA), which acts as a lubricant [18, 19], erythritol, a four-carbon polyol which acts as an osmoprotectant [20], and potassium, a tear-native electrolyte that plays an important role in ocular homeostasis. [17, 21]

Applied learning from TFOS DEWS II and Biotrue MPS clinical performance informed the development of Biotrue Hydration Plus (BHP) MPS, which was formulated to maintain ocular surface homeostasis and improve comfort during CL wear [17, 22, 23]. The solution contains 25% more HA than Biotrue MPS to increase moisture, as well as poloxamine 1107 and poloxamer 181 surfactants [12, 22]. In addition, it includes potassium and erythritol to help maintain ocular surface homeostasis [22, 24] and a triple disinfection system of polyaminopropyl biguanide, polyquaternium-1, and alexidine dihydrochloride at concentrations to ensure good ocular compatibility and provide broad disinfection efficacy [22, 25]. The BHP MPS pH of 7.5 is in the middle of the range of healthy tears, which supports comfort during lens insertion [22, 26].

A multicenter two-arm study was conducted to assess the clinical performance and biocompatibility of BHP MPS with hydrogel and silicone hydrogel PRSCLs over 3 months of CL wear. Here, we present a subanalysis of the BHP MPS arm from this study.

A total of 17 investigative sites in the USA participated in this multicenter 3-month, two-arm, randomized, masked, bilateral study (NCT03897751) for which results have already been posted to clinicaltrials.gov [27]. This study was approved by Western Institutional Review Board (Puyallup, WA) and was in accordance with the Helsinki Declaration of 1964 and its later amendments. All subjects were recruited as part of routine practice, and informed consent was provided to participate in the study. The study also complied with the Health Insurance Portability and Accountability Act.

Informed consent was obtained from all potential participants at the screening/dispensing visit. To participate in the study, subjects 18 years of age or older were required to be adapted habitual wearers of either one of four silicone hydrogel, single-vision CLs, these being lotrafilcon B (Air Optix Aqua, Alcon, Fort Worth, TX), balafilcon A (PureVision2, Bausch + Lomb Incorporated), samfilcon A (Bausch + Lomb ULTRA, Bausch & Lomb Incorporated), and senofilcon C (Acuvue Vita, Johnson & Johnson Vision, Jacksonville, FL), or the hydrogel, single-vision CL etafilcon A (Acuvue2, Johnson & Johnson Vision). Additionally, they had to habitually use lens care systems for cleaning, disinfecting, and storage of their lenses. Subjects also agreed to wear their respective habitual lenses on a daily wear basis for approximately 3 months and to use only BHP MPS for cleaning, disinfecting, and storing their lenses. Potential subjects who were aphakic, amblyopic, or who habitually wore daily disposable, monovision, multifocal, or toric CLs, as well as those with ≥ Grade 2 finding during the eligibility slit lamp examination were excluded from the study.

Enrolled subjects were 18–67 years old; each received BHP MPS and three new pairs of PRSCLs for daily wear (one pair was dispensed at study start, with replacement pairs at the 1-month and 2-month follow-up visits). Subjects were instructed not to use any other cleaning and disinfecting solution during the study. Subjects returned to the clinic for follow-up visits after 2 weeks, 1 month, 2 months, and 3 months of lens wear, during which they rated 13 lens performance attributes (burning/stinging on insertion, comfort on insertion, overall comfort, comfort at end of day, dryness, vision on insertion, overall vision, vision in low light, vision at end of day, ease of handling/insertion, ease of handling/removal, lens cleanliness on removal, and overall impression) using a 0–100 scale, with higher scores being more favorable (e.g., 100 = excellent, 80 = very good, etc.). For each subject, the scores from both eyes were averaged to calculate a subject score for each attribute. At each visit, a “comfort” group score was calculated as the average score of the five comfort-related attributes (burning/stinging on insertion, comfort on insertion, overall comfort, comfort at end of day, and dryness), a “vision” group score as the average score of the four vision-related attributes (vision on insertion, overall vision, vision in low light, and vision at end of day), and a “handling” group score as the average score of the two handling-related attributes (ease of handling/insertion, ease of handling/removal). Subjects were also asked to rate the degree to which their lenses needed cleaning using a 0–4 scale, where 0 indicates none, 1 indicates slight (felt occasionally), 2 indicates mild (noticeable but not irritating), 3 indicates moderate (moderately irritating and annoying), and 4 indicates severe (noticeable and irritating). A clinically acceptable need for lens cleaning was considered to be none to mild.

Subjects also underwent a thorough slit lamp examination performed by the investigators at the screening/dispensing visit, as well as each follow-up visit. Slit lamp signs of corneal infiltrates, bulbar injection, limbal injection, corneal staining, upper lid tarsal conjunctival abnormalities, corneal neovascularization, epithelial edema, and epithelial microcysts were graded using an ordinal, text-based scale, from which numeric grades in integer steps were assigned, 0 (no finding), 1 (trace), 2 (mild), 3 (moderate), and 4 (severe). Fluorescein corneal staining grades were computed as the maximum grade taken within each of five different corneal locations (central, inferior, nasal, superior, and temporal), and the worst case was used as the single corneal staining grade. Only those subjects who presented with 0 (no finding) or 1 (trace finding) at the screening/dispensing visit were enrolled in the study. Subjects presenting with persistent grade 3 or 4 slit lamp findings at any visit were subject to removal from the study at the discretion of the investigator. Slit lamp signs of external adnexa abnormalities, conjunctivitis, corneal striae, and new corneal scar were not graded but recorded as absent or present. All investigators and their site staffs were trained to ensure consistent standard procedures were used for grading the findings.

At each follow-up visit, the degree of lens deposits was assessed for each eye as none, light, medium, or heavy. Lenses were examined on the eye with a slit lamp using 7× to 15× magnification for this determination. Maximum deposits over all follow-up visits (none or light, medium or heavy) were summarized as a measure of cleaning performance. Optimal cleaning effectiveness was the proportion of lenses with clinically acceptable deposits (none or light). The wettability of the lens surface was assessed at each follow-up visit on a 0–4 scale, where 0 indicated that the anterior lens surface was 100% wettable; 1 indicated that small (< 0.1 mm), individual discrete nonwetting areas were present; 2 indicated that a single area of nonwetting between 0.1 mm and 0.5 mm in size was present; 3 indicated that several areas of nonwetting between 0.1 mm and 0.5 mm in size were present; and 4 indicated that one or more nonwetting areas greater than 0.5 mm in size were present. Clinically acceptable wettability was considered to be no dewetting or a single area of nonwetting ≤ 0.5 mm.

A total of 127 adapted PRSCL wearers were enrolled in this arm of the study; of these, 117 completed all follow-up visits. Of those who did not complete all follow-up visits, five did not attend the 3-month visit, three attended the 3-month visit outside of the required ± 7 day visit window, one violated inclusion/exclusion criteria, and one was excluded for “other” reason. No participants discontinued owing to an adverse event (AE). Enrolled subject demographics are shown in Table 1.

CL wear satisfaction is driven by lens comfort and eye health; these can be affected by the CL material, design, and care system [28]. This subanalysis provides insight from the first large-scale evaluation of the clinical performance of BHP MPS among habitual wearers of both hydrogel and silicone hydrogel lenses. BHP MPS performed admirably on the basis of both objective and subjective assessments.

BHP MPS achieved consistently high subjective ratings for performance parameters of lens comfort, vision, handling, cleanliness, and overall impression. Performance parameter ratings remained consistent for this study arm over the 3 months of the study, with no decrease in rating noted for any parameter over all follow-up visits. Notably, lens comfort group scores remained between “very good” and “excellent” at all follow-up visits, suggesting that ocular homeostasis was maintained in this arm over the course of the study. This finding is of utmost clinical importance, as eye care practitioners and the CL industry have come to better appreciate the importance of ocular surface homeostasis during CL wear, which involves several key processes, including the maintenance of a stable tear film in addition to the maintenance of lens cleanliness [28, 29].

Investigator slit lamp evaluations for solution biocompatibility found no subject presenting with > Grade 2 slit lamp findings at any visit. Absence of any serious, clinically significant AE or adverse device effect in either eye at any of the 496 follow-up visits after nearly 23,000 exposures to the MPS, as well as no subject discontinuation from the study arm due to an AE, reflect maintenance of ocular surface homeostasis in the study arm population. In addition, the absence of ungraded slit lamp findings of conjunctivitis, corneal striae, or new corneal scar and the infrequency of external adnexa abnormalities and other anterior segment abnormalities at any visit reflect good biocompatibility of BHP MPS.

Preventing buildup of lens deposits by using an MPS contributes to maintenance of ocular surface homeostasis. In this study arm, optimal cleaning effectiveness was demonstrated with 100% of lenses having clinically acceptable deposit at the 3-month follow-up visit. BHP MPS effectively maintained lens cleanliness, with 97.6% of lenses acceptably clean at the 3-month follow-up visit. Excessive surface deposits can lead to decreased lens wettability and disrupted homeostasis. BHP MPS effectively maintained lens wettability, with 99.6% of lenses acceptably wettable at the 3-month follow-up visit.

In vitro studies of the performance of BHP MPS described in the literature support the findings of the current study subanalysis [30‐32]. CLs soaked overnight in BHP MPS were found to retain and release HA over 20 h of simulated wear, and more HA was released in the first 12 h of simulated wear from BHP MPS-soaked CLs than from Biotrue MPS-soaked CLs, which is meaningful as 12h can represent a full day of CL wear for most users [31, 32]. Previously, CLs soaked overnight in Biotrue MPS were also reported to retain HA and release it over 20 h of simulated wear [32], and at least 2 h of clinical wear [33]. With respect to antimicrobial efficacy, BHP MPS was found to be as effective as HPS and more effective than four competitive MPSs at disinfecting compendial organisms in the presence of organic soil [25], when evaluated using the International Organization for Standardization (ISO, Geneva, Switzerland) ISO 14729 stand-alone test protocol [34].

The findings presented here should be considered in the context of the limitations intrinsic to the single-arm subanalysis and study design, including the subjective nature of wearers self-reporting BHP MPS performance. While the findings demonstrate the effectiveness of BHP MPS, the current study did not specifically assess its performance in wearers with severe dryness or other ocular conditions, which may limit its generalizability and would be of interest for further study.

Clinical studies suggest that in symptomatic populations, modification to lens material, design, and care system, as well as wear modality can potentially improve comfort [6]. Of note, a portion of CL wearers may even be unaware that they experience signs or symptoms, with half of apparently “asymptomatic” PRSCL wearers being found to have an undiagnosed condition in a study of CL wearers undergoing routine eye examination [35]. Meanwhile, CL-related dryness persists as a common symptom reported by wearers of all types of lenses and remains one of the main reasons for discontinuation of CL wear [36]. Strategies reported to address CL dryness include fitting with daily disposable lenses, use of wetting agents (both topical and internal to the CL), ophthalmic inserts, punctal plugs, omega fatty acids, antibiotics, reducing CL wear time, or dropping out of lens wear altogether [37]. In the case of PRSCLs, manufacturers have included components in MPSs that sorb onto the CL during storage, then either remain localized at the lens surface or passively elute from the lens during wear or both [6, 38, 39]. Among these are surfactants such as poloxamers, poloxamines, and polyoxyethylene-polybutylene (EOBO) copolymer intended to improve wetting while also acting as moisturizers [6, 38]. For example, poloxamine 1107 sorbed on etafilcon A lenses was shown to increase lens wettability over at least the first 4 h of wear and was retained by the lens over at least 8 h of wear, manifesting as improved subjective comfort [40].

In addition to surfactants, manufacturers sometimes include other humectants and wetting agents in an MPS to address dryness, such as polysaccharides (e.g., HA) and other polyols (e.g., sorbitol and propylene glycol) [8, 16]. In a study of test subjects who wore senofilcon A lenses that had been soaked 14 h in Biotrue MPS prior to wear, HA concentrations in the subjects’ tear films remained elevated relative to baseline after 2 h of lens wear [33]. The addition of ingredients to BHP MPS and other CL solutions, informed by evidence-based insights from TFOS DEWS II, suggests that modification of MPS formulations can lead to high PRSCL user satisfaction [16, 17, 22].

In one study, PRSCL wearers intending to drop out of CL wear altogether within 6 months owing to CL discomfort and dryness switched from using their habitual MPS to using BHP MPS; 90% of study subjects reported improved comfort after using the BHP MPS for 7 days, and 86.6% were more likely to continue CL wear [22]. The specific lens properties and solution components that most contributed to BHP MPS user satisfaction and homeostasis remain to be confirmed, but similar high satisfaction among users of Biotrue MPS suggest that HA plays a key role [13‐15]. Further, high satisfaction among CL wearers with habitual lens-related dryness who wore a daily disposable silicone hydrogel CL with a blister package solution containing several of the same ingredients as found in BHP MPS suggests that poloxamine 1107, poloxamer 181, erythritol, and potassium may also count as contributing factors to a more satisfying wear experience for lens wearers experiencing CL discomfort [41].

Several MPS components can serve multiple functions. Surfactants, while recognized as lens-wetting agents through interaction with lens polymer, also interact with proteins deposited on the lens [38]. The dual-surfactant system comprising highly hydrophilic poloxamine 1107 in combination with hydrophobic poloxamer 181 in BHP MPS contributes to the maintenance of tear proteins in their natural state by interaction with both hydrophilic and hydrophobic regions of protein molecules [38, 42, 43]. This was demonstrated previously in a study of daily disposable soft CL packaging solutions, in which the tear protein lysozyme, when challenged with the protein denaturant sodium lauryl sulfate, retained over 90% of its enzymatic activity in the presence of the solution containing the dual surfactants, compared with less than 5% in the presence of eight other packaging solutions or saline [39]. In a similar study of BHP MPS, the protein retained over 87% of its enzymatic activity in the presence of the MPS, compared with 88% in the presence of Biotrue MPS and less than 4% in the presence of four other MPSs, two HPSs, or saline [30]. Erythritol, while recognized as an osmoprotectant, further acts as an antioxidant [44], which may protect HA from free radical degradation [45]. HA, while recognized as a humectant, lubricant, and wetting agent, is also reported to have antioxidant properties itself [46]. Which of these functions are critical to ocular surface homeostasis remains to be elucidated.

BHP MPS, a unique formulation that includes ingredients informed by TFOS DEWS II, performed well in habitual hydrogel and silicone hydrogel PRSCL wearers with respect to comfort, vision, and handling. High ratings for these parameters were consistent and persisted over the 3-month time course of the study. Slit lamp examinations demonstrated the solution to be biologically compatible with the eyes. Lenses remained clean and wettable, with minimal deposit accumulation throughout the study. BHP MPS provides PRSCL wearers with a favorable lens wearing experience and represents a promising option for eye care practitioners to recommend before switching symptomatic PRSCL wearers to a different CL wear modality.