Safety and efficacy of amniotic cytokine extract in the treatment of dry eye disease

Elizabeth Yeu, Damien F Goldberg, Francis S Mah, Kenneth A Beckman, Jodi I Luchs, Jonathan D Solomon, Darrell E White, Preeya K Gupta, Elizabeth Yeu, Damien F Goldberg, Francis S Mah, Kenneth A Beckman, Jodi I Luchs, Jonathan D Solomon, Darrell E White, Preeya K Gupta

Abstract

Purpose: Evaluate the safety and efficacy of cryopreserved amniotic cytokine extract (ACE) in the treatment of subjects with dry eye disease (DED). Patients and methods: This was a retrospective, multicenter, chart review of adult patients with DED that instilled cryopreserved ACE drops twice-daily for 4 or 12 weeks. Patients had corneal fluorescein staining (0-20 range) and/or a lissamine green conjunctival staining score (0-18 range) of ≥3 and ≤9 in at least 1 eye and a score ≥40 (0-100 range) of eye dryness/irritation on a visual analog scale (VAS). Following completion of a treatment course, medical records were reviewed from the initiation of therapy (baseline), and at post-treatment visits (4 weeks, 8 weeks, and 12 weeks). Patient records for visual acuity, adverse events, corneal fluorescein staining, conjunctival lissamine green staining, and symptom scores of ocular dryness/irritation were reviewed for each visit, as available. Safety and tolerability were assessed through the evaluation of patient-reported adverse events recorded in the medical records. Results: A total of 54 eligible patients were identified at 7 clinical sites; 16 patients administered ACE drops for 4-weeks, and 38 patients instilled ACE drops for 12 weeks. Significant improvements in the mean changes from baseline were observed for corneal fluorescein staining, lissamine green staining, visual acuity (LogMar) and VAS ocular symptom scores at the 4-week post-treatment visit (p<0.01). Additional improvements continued out to the 12-week follow-up assessment visits. Two patients discontinued therapy due to reports of ocular burning or foreign body sensation. Conclusion: The cryopreserved ACE formulation was well-tolerated and effective in reducing the clinical signs and symptoms of DED. Conduct of a vehicle-controlled prospective study is warranted.

Keywords: amnion extract; amniotic membrane; cytokine; dry eye; inflammation.

Conflict of interest statement

E Yeu, KA Beckman, JI Luchs, JD Solomon, DE White, and PK Gupta are consultants to Ocular Science. DF Goldberg, FS Mah and DE White have ownership interests in Ocular Science. E Yeu is consultant for: Alcon; Allergan; Aurea Medical; Avedro; Baush & Lomb; BioTissue; Bruder; EyePoint Pharm.; iOptics; Guidepoint; J&J Vision; LENSAR; Kala Pharm.; Merck; Mynosys; Novartis; Ocular Science; Ocular Therapeutix; Ocusoft; Omeros; Oyster Point Pharm.; Science Based Health; Shire; Sight Sciences; SightLife Surgical; Sun; TopCon; TearLab Corporation; TearScience & Zeiss. DF Goldberg reports equity from Ocular Science, during the conduct of the study and outside the submitted work. FS Mah reports equity from Ocular Science, during the conduct of the study; received grants from Allergan, reports personal fees from Shire/Takeda, outside the submitted work. KA Beckman was a consultant for Ocular Science, during the conduct of the study. JI Luchs reports personal fees including consultancy for allergan, received personal fees from Bausch and Lomb, Shire, Tear Lab, Aerie, Alcon, Ocular Sciences, Insightful Solutions, Kala, Eyevance Pharma, Calhoun Vision, Trefoil Therapeutics, RPS, Sun, and Omega Ophthalmics, outside the submitted work. PK Gupta reports personal fees from Ocular science, during the conduct of the study. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
The mean changes from baseline in the subject-reported symptoms of ocular dryness/irritation assessed by visual analog scale (VAS) on a 0–100 scale (0= no ocular dryness/irritation, 100= severe ocular dryness/irritation) are presented by visit. The mean changes from baseline were considered statistically significant at week 4 and week 8 (p<0.01), and week 12 (p<0.001). A paired t-test was used to analyze within-group changes from baseline. Abbreviations: SD, standard deviation; VAS, visual analog scale.
Figure 2
Figure 2
The mean changes from baseline in the corneal fluorescein staining on a 0–20 scale (0–4 scale per region for each of the 5 regions of the cornea) are presented by visit. Analysis of the mean changes from baseline in corneal fluorescein staining indicated that the improvements were statistically significant at week 4 (p<0.01), week 8 (p<0.01), and week 12 (p<0.001). A paired t-test was used to analyze within-group changes from baseline. Abbreviation: SD, standard deviation.
Figure 3
Figure 3
The mean changes from baseline in the conjunctival lissamine green staining on a 0–18 scale (0–3 scale per region for each of the 6 regions of the conjunctiva) are presented by visit. Changes from baseline were determined to be statistically significant at week 4 (p<0.01), week 8 (p<0.01), and week 12 (p<0.001). A paired t-test was used to analyze within-group changes from baseline. Abbreviation: SD, standard deviation.
Figure 4
Figure 4
The mean changes from baseline in visual acuity (LogMAR) are presented by visit. SD = standard deviation. The improvement from baseline at follow-up visits was statistically significant at week 4 (p<0.01), week 8 (p<0.01), and week 12 (p<0.001). A paired t-test was used to analyze within-group changes from baseline. Abbreviation: SD, standard deviation.

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