April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Safety and Efficacy of Topical 1% docosahexaenoic acid (DHA) and 1% alpha-linoleic acid (ALA) in a Canine Model
Author Affiliations & Notes
  • Mausam R. Damani
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Simone Iwabe
    Department of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • Gustavo D Aguirre
    Department of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • Karla Carlisle
    Department of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • Maxwell Pistilli
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Vatinee Y Bunya
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships Mausam Damani, None; Simone Iwabe, None; Gustavo Aguirre, None; Karla Carlisle, None; Maxwell Pistilli, None; Vatinee Bunya, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3688. doi:
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      Mausam R. Damani, Simone Iwabe, Gustavo D Aguirre, Karla Carlisle, Maxwell Pistilli, Vatinee Y Bunya; Safety and Efficacy of Topical 1% docosahexaenoic acid (DHA) and 1% alpha-linoleic acid (ALA) in a Canine Model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3688.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To evaluate the safety and effect on tear film cytokine levels of a topical fatty acid formulation consisting of 1% docosahexaenoic acid (DHA) and 1% alpha-linoleic acid (ALA).

 
Methods
 

The right eye of 10 dogs was treated with the study drug (1% DHA and 1% ALA) three times a day for 4 weeks, while the left eye was treated at the same frequency with a control vehicle. Ocular surface examinations, including portable slit lamp examination and ocular surface staining with fluorescein, were performed at baseline and weekly thereafter for a total of 6 weeks. Schirmer strips were analyzed for cytokine levels of the following cytokines: IFNg, TNFa, IL-1a, IL-1b, IL-2, IL-6, IL-8 and IL-10. Conjunctival biopsies were performed at 4 weeks and mRNA levels of the same cytokines were assessed. Systemic toxicity was monitored with blood samples to evaluate the complete blood count (CBC), basic metabolic panel (BMP), and liver function tests (LFTs).

 
Results
 

The study drug was well tolerated by all dogs, with no signs of local erythema, irritation or inflammation. In addition, no evidence of systemic toxicity was noted on serum testing of CBC, BMP and LFTs. At 4 weeks, there was no difference in the tear film concentration of any of the studied cytokines between the treatment and control eye in any of the dogs (Table 1). Intra-eye comparisons were also done to look for changes in absolute cytokine levels throughout the course of the study. Most notable was the trend in IL-8 in the treated eye, which dropped dramatically from baseline and then slowly began to rise again after treatment was complete (P<0.01, Table 2).

 
Conclusions
 

We found that the combination of 1% docosahexaenoic acid (DHA) and 1% alpha-linoleic acid (ALA) was a well tolerated topical fatty acid formulation. Secondary analysis of the effects of this formulation revealed no significant difference between the treated and control eye on the absolute levels of most cytokines in the tears. However, treatment had a significant impact on decreasing IL-8 levels, a key component in the inflammatory pathway. Although safety was established, our study was not powered to detect subtle differences in cytokine levels. Larger studies to evaluate the impact of topical fatty acids on cytokine levels are needed in order to further explore the role of these substances in treating inflammation-mediated diseases such as dry eye syndrome.

     
Keywords: 486 cornea: tears/tear film/dry eye • 503 drug toxicity/drug effects • 490 cytokines/chemokines  
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