July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Ocular surface kinetics of fluorescein in human eyes: Effect of viscosity enhancing agents and drop size
Author Affiliations & Notes
  • Subashree Murugan
    Cornea and Refractive surgery, Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • Prema Padmanabhan
    Cornea and Refractive surgery, Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • Rachapalle Reddi Sudhir
    Cornea and Refractive surgery, Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • ARUSHI GOYAL
    Cornea and Refractive surgery, Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • Dr. Deepti Talele
    Cornea and Refractive surgery, Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • Sangly P Srinivas
    School of Optometry, Indiana University, Bloomington , Indiana, United States
  • Footnotes
    Commercial Relationships   Subashree Murugan, None; Prema Padmanabhan, None; Rachapalle Sudhir, None; ARUSHI GOYAL, None; Dr. Deepti Talele, None; Sangly Srinivas, None
  • Footnotes
    Support  Obama-Singh Initiative (SPS and PP)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5709. doi:
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      Subashree Murugan, Prema Padmanabhan, Rachapalle Reddi Sudhir, ARUSHI GOYAL, Dr. Deepti Talele, Sangly P Srinivas; Ocular surface kinetics of fluorescein in human eyes: Effect of viscosity enhancing agents and drop size. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5709.

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

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Abstract

Purpose : Most ophthalmic drugs are administered topically on the ocular surface. This study has examined the potential impact of mucoadhesive and/or viscosity enhancing agents frequently included in the topical formulations and of drop size on the parameters governing the ocular surface pharmacokinetics.

Methods : We tested clearance of fluorescein (0.35%) in saline, HD (Hydroxymethyl cellulose- 0.3% + Dextran70- 1%) and HA (Hyaluronate- 0.18%) following 6 and 30 mL of topical drops.The clearance was assessed as the decline in tear fluorescence, which was measured using a custom-made ocular fluorometer. The dynamics of tear fluorescence was fitted to mono exponential decay model to compare elimination rate constant (expressed as half-life in min and denoted by t1/2) and dilution of fluorescein by the tears (i.e., fluorescence at zero time, expressed in mV and denoted by Fdp0) amongst the different preparations. To assess the corneal epithelial permeability, a key determinant of intraocular bioavailability of drugs, three drops of HA (6 mL each) were instilled 15 min apart, and fluorescence of the stroma was measured 15 min after the third drop in addition to t1/2 and Fdp0 after the first drop.

Results : For HA, the exponential decline in tear fluorescence following 6 and 30 mL showed t1/2 of 6.0 ± 2.3mins (n = 12) and 8.5 ± 2.0 mins (n = 10), respectively. The corresponding values for HD and saline were significantly smaller and much more variable (Saline: 2.3 ± 2.1 mins (n = 26) for 6 mL, respectively; HD: 2.4 ± 1.3 mins (n = 9) and 2.1 ± 1.4 mins (n = 10), for 6 and 30 mL, respectively). In contrast, Fdp0 increased with increase in drop size for both HA and HD drops (HA :7.5 ± 1.8 and 12.3 ± 2.4 at 6 and 30 mL, respectively; HMC: 6.2 ± 1.6 and 16.0 ± 8.8 at 6 and 30 mL, respectively).The epithelial permeability, which could be computed based on the increase in stromal fluorescence 15 min after the third HA drop was found to be 1.5 x 10-8 ± 0.37 x 10-8 cm/sec (n = 3).

Conclusions : The tear half-life is not significantly altered by the drop size, with viscosity enhancing and/or mucoadhesive agents. In contrast, the tear fluorescence at zero time increases with increase in drop size in the presence of mucoadhesive agents. Since HA enbles consistent clearance of fluorescein from tears, sequential multi-drops of HA can be used to determine the corneal epithelial permeability.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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