title: The importance of eyelid closure and nasolacrimal occlusion following the ocular instillation of topical glaucoma medications, and the need for the universal inclusion of one of these techniques in all patient treatments and clinical studies.
abstract: OBJECTIVE
  To review the effects of nasolacrimal occlusion (NLO) and eyelid closure (ELC) on the ocular and systemic absorption of topically applied glaucoma medications and emphasize the need for the universal application of these techniques during patient treatment and in clinical studies of topically applied glaucoma medications.
  
  
  METHODS
  Following a review of data suggesting great clinical benefit from NLO and ELC, the absence of inclusion of these simple techniques in published studies of topical glaucoma medications is identified. The effect of this oversight on these studies is noted with reference to each of the 5 major groups of glaucoma medications.
  
  
  RESULTS
  A review of the literature suggests that NLO and ELC improve intraocular penetration of topically applied glaucoma medications and discourage systemic absorption. The US Food and Drug Administration and the National Institutes of Health discourage the inclusion of these techniques in studies of the efficacy and toxicity of topically applied glaucoma medications. Consequently, all glaucoma studies reported in the literature lack the inclusion of these techniques for 5 minutes. This omission has major implications for patient informed consent, study protocol consistency, and the value of clinical studies, and directly affects the therapeutic index of glaucoma medications in unpredictable and undesirable ways. The undesirable influence on the therapeutic index of each drug influences the safety and efficacy and has implications for the cost of medical treatments, the reproducibility of clinical study results, and dosing regimens, including those of combination therapy, as reflected in the peer-reviewed literature.
  
  
  CONCLUSIONS
  Patients should use NLO or ELC for 5 minutes following eye drop treatment with topically applied glaucoma medications. Furthermore, it is essential that these techniques be included in all clinical studies of topically applied glaucoma medications to ensure the most favorable therapeutic index and its accurate determination. This will also help provide the most consistent, reliable, and reproducible study results.
authors.affiliation: Department of Ophthalmology, University of California, San Francisco Medical Center, San Francisco, California, USA.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Flach
mesh_terms: D000042:Absorption; D000287:Administration, Topical; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D005143:Eyelids / Q000502:physiology*; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D009301:Nasolacrimal Duct / Q000502:physiology*; D009885:Ophthalmology / Q000379:methods*; D012683:Sensory Deprivation; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents