Preclinical studies evaluating the effect of semifluorinated alkanes on ocular surface and tear fluid dynamics

Agarwal, Priyanka; Khun, Darina; Krösser, Sonja; Eickhoff, Kirsten; Wells, Frederick S.; Willmott, Geoff R.; Craig, Jennifer P.; Rupenthal, Ilva D.

doi:10.1016/j.jtos.2019.02.010

Cited by 31 publications

(36 citation statements)

References 39 publications

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“…Surfactants and penetration enhancers, such as tetracaine, polysorbate 80 and benzalkonium chloride (BAK), can also reduce the drop size to some extent by reducing the surface tension of the formulation [33]; however, due to the toxicity typically associated with these excipients, their inclusion is rarely justified for the purpose of reducing drop size alone. Certain non-aqueous liquids, such as semifluorinated alkanes (SFAs), which inherently have lower surface tension and viscosity than aqueous eyedrops, may help in achieving a smaller drop size and minimise overflow [38].…”

Section: Dose Volumementioning

confidence: 99%

Formulation Considerations for the Management of Dry Eye Disease

2021

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Dry eye disease (DED) is one of the most common ocular surface disorders characterised by a deficiency in quality and/or quantity of the tear fluid. Due to its multifactorial nature involving several inter-related underlying pathologies, it can rapidly accelerate to become a chronic refractory condition. Therefore, several therapeutic interventions are often simultaneously recommended to manage DED efficiently. Typically, artificial tear supplements are the first line of treatment, followed by topical application of medicated eyedrops. However, the bioavailability of topical eyedrops is generally low as the well-developed protective mechanisms of the eye ensure their rapid clearance from the precorneal space, thus limiting ocular penetration of the incorporated drug. Moreover, excipients commonly used in eyedrops can potentially exhibit ocular toxicity and further exacerbate the signs and symptoms of DED. Therefore, formulation development of topical eyedrops is rather challenging. This review highlights the challenges typically faced in eyedrop development, in particular, those intended for the management of DED. Firstly, various artificial tear supplements currently on the market, their mechanisms of action, as well as their application, are discussed. Furthermore, formulation strategies generally used to enhance ocular drug delivery, their advantages and limitations, as well as their application in commercially available DED eyedrops are described.

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Section: Dose Volumementioning

confidence: 99%

Formulation Considerations for the Management of Dry Eye Disease

2021

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“…35,36 Numerous studies have evaluated and reported the beneficial effects of EvoTears in patients with dry eye disease. 6,11,13,14 In a prospective observational study, Steven et al 14 administered EvoTears four times a day for 6 weeks in patients with evaporative dry eye disease and observed significant improvements of the tear film stability, TBUT, and Schirmer I, and a significant reduction of overall corneal staining. In another study, Steven et al 13 assessed the effect of perfluorohexyloctane in patients with meibomian gland dysfunction and reported that 6 to 8 weeks of topical application not only led to increased meibum quality, quantity, and expressibility, but also improved TBUT and corneal staining.…”

Section: Adverse Eventsmentioning

confidence: 99%

“…Second, perfluorohexyloctane is amphiphilic and able to dissolve lipids, which may contribute to dissolution of thickened meibum that could be blocking the meibomian glands, 38,39 resulting in lipid layer stabilization of the tear film. Finally, thanks to its water-free nature, it discourages microbial growth and does not require any preservatives, 6,13 allowing patients to administer drops more frequently without having to worry about the potential toxic effects of preservatives. 11,12 This study is limited to the extent that it is a prospective open-label study without a control group, which makes it difficult to assess the potential placebo effects.…”

Section: Adverse Eventsmentioning

confidence: 99%

“…1,4,5 The lipid coat of the tear film, primarily produced by the meibomian glands, covers the aqueous-mucous layers and plays a crucial role in ensuring tear stability and hindering evaporation by serving as a protective hydrophobic barrier. [6][7][8] An absent or insufficient lipid layer, as is the case in meibomian gland dysfunction, can precipitate up to a four-fold increase in tear evaporation. 8 Therefore, restoration of the lipid film and prevention of tear evaporation is the aim of effective therapy in evaporative dry eye disease.…”

mentioning

confidence: 99%

“…11 Due to its complete aqueous-free nature, it does not promote microbial growth or necessitate preservatives, demonstrates good spreading properties, and restores the lipid layer of the tear film, preventing excessive evaporation of the aqueous-mucous layers. 6,13,14 Clinical studies have shown significant beneficial effects of EvoTears in patients with evaporative dry eye disease 14 and meibomian gland dysfunction 13 when topically administered for 6 to 8 weeks.…”

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confidence: 99%

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Semi-fluorinated Alkane Eye Drops Reduce Signs and Symptoms of Evaporative Dry Eye Disease After Cataract Surgery

Son¹,

Yildirim²,

Khoramnia³

et al. 2020

J Refract Surg

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PURPOSE: To clinically evaluate the efficacy and tolerability of semi-fluorinated alkane eye drops (EvoTears; URSAPHARM GmbH) as ocular surface treatment after cataract surgery in patients with evaporative dry eye disease. METHODS: This prospective, monocentric, open-label clinical trial included 40 patients undergoing cataract surgery and showing symptoms of evaporative dry eye disease as measured by the Symptom Assessment in Dry Eye (Visual Analogue Scale [VAS]) questionnaire, Ocular Surface Disease Index (OSDI), and tear break-up time (TBUT) of less than 10 seconds. EvoTears was prescribed four times a day for 5 weeks and administered 15 minutes after the standard postoperative topical anti-inflammatory regimen. The primary endpoint was the change in TBUT. Secondary endpoints included assessment of the subjective symptoms (VAS), corrected distance visual acuity (CDVA), slitlamp examination, intraocular pressure, and Schirmer's test, which were evaluated at 1 day, 1 week, and 5 weeks postoperatively. At 5 weeks postoperatively, the tolerability and efficacy of EvoTears were evaluated by physicians and patients. RESULTS: At 5 weeks postoperatively, the median TBUT increased from 6.8 (preoperative) to 14 seconds (P < .001) and the average total corneal staining score decreased from 3.53 (preoperative) to 2.36 (P < .001). The mean CDVA improved from 0.41 (preoperative) to 0.14 logMAR (P < .001) and there was a statistically significant decrease in all scores from the VAS questionnaire at 5 weeks postoperatively. There was no statistically significant change in Schirmer's test (P = .150). CONCLUSIONS: EvoTears improved tear film, ocular surface, and subjective impressions of patients with dry eye disease 5 weeks after cataract surgery. Patients' and physicians' assessment indicated good efficacy and high tolerability of EvoTears, suggesting its suitability in postoperative management of the ocular surface in patients with dry eye disease.

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Perfluorohexyloctane Eye Drops for Dry Eye Disease Associated With Meibomian Gland Dysfunction in Chinese Patients

et al. 2023

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ImportanceMeibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye disease (DED). Medical and surgical management for DED is limited; therefore, new treatment options are sought.ObjectiveTo evaluate the efficacy and safety of SHR8058 (perfluorohexyloctane) eye drops in Chinese patients with DED associated with MGD through 57 days.Design, Setting, and ParticipantsThis was a randomized, multicenter, double-masked, saline-controlled, phase 3 clinical trial conducted from February 4, 2021, to September 7, 2022. Patients were recruited from the departments of ophthalmology in 15 hospitals in China. Patients with DED associated with MGD were enrolled between February 4 and July 1, 2021. The diagnosis was based on patient complaint of DED symptoms, an ocular surface disease index of 25 or higher, tear film break-up time of 5 seconds or less, Schirmer I test without anesthesia results of 5 mm or more at 5 minutes, total corneal fluorescein staining (tCFS) score of 4 to 11, and an MGD score of 3 or higher.InterventionsEligible participants were randomly assigned 1:1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]) 4 times per day.Main Outcomes and MeasuresThe primary end points were the changes from baseline in tCFS and eye dryness scores at day 57.ResultsA total of 312 participants were included in the analysis: 156 (mean [SD] age, 45.4 [15.2] years; 118 female [75.6%]) in the perfluorohexyloctane group and 156 (mean [SD] age, 43.7 [15.1] years; 127 female [81.4%]) in the NaCl group. Both primary end points were achieved, ie, changes from baseline at day 57 of tCFS score (mean [SD], −3.8 [2.7] vs −2.7 [2.8]) and eye dryness score (mean [SD], −38.6 [21.9] vs −28.3 [20.8]) in the perfluorohexyloctane group were superior to the control group, with estimated mean differences of −1.14 (95% CI, −1.70 to −0.57; P &lt; .001) and −12.74 (95% CI, −17.20 to −8.28, P &lt; .001), respectively. Improvements on both end points appeared to be noted on day 29 and day 15, respectively, and maintained through day 57. Compared with the control, perfluorohexyloctane eye drops also alleviated symptoms including pain (mean [SD] tCFS score, 26.7 [23.7] vs −18.7 [22.5]; P = .003), awareness of DED symptoms (mean [SD] tCFS score, −38.1 [25.1] vs −23.7 [27.6]; P &lt; .001), and frequency of dryness (mean [SD] tCFS score, −43.3 [23.8] vs −29.1 [24.8]; P &lt; .001). Treatment-emergent adverse events occurred in 34 participants (21.8%) and 40 participants (25.6%) in the perfluorohexyloctane and control groups, respectively.Conclusions and RelevanceResults of this randomized clinical trial demonstrate that perfluorohexyloctane eye drops significantly ameliorated the signs and symptoms of DED associated with MGD with a rapid efficacy as well as satisfactory tolerability and safety through 57 days. Findings support the use of these eye drops if results can be confirmed independently and over longer time periods.Trial RegistrationClinicalTrials.gov Identifier: NCT05515471

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Preclinical studies evaluating the effect of semifluorinated alkanes on ocular surface and tear fluid dynamics

Cited by 31 publications

References 39 publications

Formulation Considerations for the Management of Dry Eye Disease

Formulation Considerations for the Management of Dry Eye Disease

Semi-fluorinated Alkane Eye Drops Reduce Signs and Symptoms of Evaporative Dry Eye Disease After Cataract Surgery

Perfluorohexyloctane Eye Drops for Dry Eye Disease Associated With Meibomian Gland Dysfunction in Chinese Patients

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