Tear Film Dynamics

The cul-de-sac compartment is the space into which topical eye medications are instilled. The human cul-de-sac has a volume of about 7mL, which can expand momentarily and variably to 30 mL. That fraction of an instilled drop that is in excess of the cul-de-sac volume drains into the nasolacrimal duct within 15 seconds after instillation or is lost by overflow onto the cheek with forceful blinking. A normal blink eliminates about 2mL of fluid from the cul-de-sac.4

The volume of eye drops delivered from commercial product containers is typically in the 25- to 35-mL range but can be as high as 75 mL. Currently, the practical lower limit of drop volume deliverable from commercial containers is 20-25 mL without further modification of the container's tip. For optimal ocular bioavailability, the drop size should be 20 mL or less.25,26

Instillation of multiple drops at one time, in the belief that it will increase ocular bioavailability, achieves little more than increasing the possibility for delivering a large systemic dose of the drug, which could result in a higher incidence of side effects or toxicity. If a drop of one medication is followed closely by a drop of another medication or of saline solution, a substantial washout occurs, with a concomitant lessening of the effect.27 A 30-second interval between drops results in a 45% washout loss of drug effect, whereas a 2-minute interval results in only 17% loss of effect. After a 5-minute interval, a second drop will cause almost no washout effect on the first drop.

In the normal, nonirritated eye, the tear turnover rate averages 16% per minute. Instillation of the average drop stimulates lacrimation to increase the turnover rate to 30% per minute. The washout effect of this spontaneous tear flow results in almost complete disappearance of an instilled drug from the cul-de-sac within 5 minutes. At least 80% of eye-drop-applied drug leaves by lacrimal drainage and not by entering the eye. In general, drugs are readily absorbed across the highly vascularized nasopharyngeal mucosa into the systemic circulation.

Nasolacrimal occlusion may decrease the systemic absorption, increase the ocular penetration of topically applied ophthalmic drugs, and improve the therapeutic index.27-29 Nasolacrimal occlusion may allow a reduction in the dosage and frequency of administration of various glaucoma drugs. The benefit of nasolacrimal occlusion should be determined individually for each patient. The patient must be trained to perform punctal occlusion properly, or its benefit may not be realized. Simple eyelid closure, so that the lacrimal pump system is not activated, may also reduce nasolacrimal drainage of topical medication.

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