Corneal epithelial permeability to fluorescein in humans by a multi-drop method

Area of Science:

• Ophthalmology
• Biomedical Engineering
• Pharmacokinetics

Background:

• Corneal epithelial permeability (Pdc) to fluorescein is a key indicator of ocular surface health.
• Current methods for measuring Pdc can lack sensitivity, particularly with advanced fluorometers.
• Accurate Pdc measurement is crucial for diagnosing and managing various eye conditions.

Purpose of the Study:

• To introduce and validate a novel multi-drop method for measuring corneal epithelial permeability (Pdc) to fluorescein.
• To enhance the sensitivity and reliability of Pdc measurements compared to existing techniques.
• To establish a more robust method for assessing ocular surface health in a clinical setting.

Main Methods:

• A multi-drop protocol involving a probe drop and two loading drops of fluorescein was administered to 29 healthy participants.
• Tear clearance and stromal fluorescence were measured using a spot fluorometer.
• Corneal permeability (Pdc) was calculated using a validated formula, incorporating stromal thickness and area under the fluorescence curve.

Main Results:

• The multi-drop method achieved a high signal-to-noise ratio (SNR > 40) for stromal fluorescence measurements.
• The calculated Pdc values were approximately 11-fold higher than previously reported, aligning better with values for drugs of similar lipophilicity.
• Monte Carlo simulations confirmed the robustness and reliability of the Pdc estimations.

Conclusions:

• The novel multi-drop method offers a more sensitive and accurate alternative to single-drop approaches for measuring corneal epithelial permeability.
• This technique overcomes limitations in fluorometer sensitivity, providing clinically relevant Pdc values.
• The enhanced accuracy of Pdc measurement aids in better assessment of ocular surface health and disease management.