Reduced in vivo Ocular Surface Toxicity with Polyquad-Preserved Travoprost versus Benzalkonium-Preserved Travoprost or Latanoprost Ophthalmic Solutions

Abstract

The study used a validated acute in vivo model to compare a new formulation of travoprost 0.004% ophthalmic solution (travoprost PQ), preserved with polyquaternium-1 (PQ), with commercially available formulations of benzalkonium-chloride (BAK)-preserved travoprost 0.004% ophthalmic solution (travoprost BAK) and BAK-preserved latanoprost 0.005% ophthalmic solution (latanoprost BAK). Adult male New Zealand albino rabbits (n = 36) were randomly divided into 6 groups. Phosphate-buffered saline (PBS), 0.001% PQ, 0.015% BAK, travoprost PQ, travoprost BAK or latanoprost BAK were applied onto rabbit eyes as 1 drop, for 15 times at 5-min intervals. The ocular surface reactions were investigated at hour 4 and day 1 using slitlamp examination; in vivo confocal microscopy (IVCM) for cornea, limbus and conjunctiva/conjunctiva-associated lymphoid tissue, conjunctival impression cytology and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. PBS, PQ and travoprost PQ did not induce obvious irritation by clinical observation, changes in microstructures of the whole ocular surface as measured by IVCM analysis, inflammatory infiltration or cell damage as measured by impression cytology, altered levels of goblet cell counts or numerous CD45+ cells in the cornea. In contrast, all BAK-containing products induced diffuse conjunctival hyperemia and chemosis, abnormal changes in the ocular surface microstructure, significant total ocular surface toxicity scores, damaged epithelial cells, inflammatory cell infiltration and decreased goblet cell density. Travoprost PQ did not elicit ocular surface toxicity when administered to rabbit eyes. These results suggest a greater safety advantage for the ocular surface of patients receiving chronic glaucoma treatment with PQ-preserved drugs.

In Vivo Confocal Microscopy of Conjunctiva-Associated Lymphoid Tissue in Healthy Humans

“…27,28 To date, IVCM has been used to study CALT in rabbits, to evaluate the toxicity of antiglaucoma drugs (prostaglandin analogs and their preservative [benzalkonium chloride]), and cell reactions occurring during conjunctival inflammation models. 17,18,29 In humans, Zhivov et al 15 first described the characteristics of CALT in vivo in healthy subjects, reporting features in line with histology. In our study, follicles and interfollicular crypts presented at IVCM the same characteristics described by Zhivov and coworkers.…”

The Impact of Glaucoma Medications on Corneal Wound Healing

“…5,6 Attempts have been made to reduce toxicity by creating preservative-free drugs 7 or drugs-containing alternative preservatives such as Polyquad or SofZia. 8,9 Corneal calcification is a vision-threatening side effect of eye drops based on buffer systems that contain high phosphate concentrations. 10,11 Another buffer, citrate-EDTA, possesses direct cytotoxic properties.…”

The Effects of Polyquad-Preserved Travoprost, Benzalkonium Chloride-Preserved Latanoprost, Purite-Preserved Brimonidine and Preservative-Free Tafluprost on Ocular Surface: A Rabbit Ocular Surface Study

“…PQ uygulanan gözlerde ise oküler yüzey toksisite bulguları saptanmamıştır. 17 Çalışmamızda, günümüzde glokom tedavisinde en sık kullanılan antiglokomatöz damlaların preparat hâliyle (etken madde+prezervan+çözelti) göze uygulanarak oküler yüzeyde oluşturdukları etkilerin incelenmesi amaçlanmıştır. Yirmi sekiz günlük tedavi dozunda uygulamayı takiben elde edilen doku kesitlerinin ışık mikroskobu ile incelenmesinde, BAK-latanoprost uygulanan gözlerde kornea epitelinde dökülme, incelme, yassı hücre katlarında azalma ve epitel üzerinde dikensi yapı-larda artış ve kornea stromasında ödem saptandı.…”