Long-term topical application of preservative-free prostaglandin analogues evokes macrophage infiltration in the ocular adnexa.
Success of the long-term glaucoma therapy and preservation of the visual function strongly depend on patients' compliance which may be affected by the inconvenience of treatment and its side effects. Recently, introduction of preservative-free anti-glaucoma agents has become an important step towards improved glaucoma care by eliminating the negative effects of preservatives on the eye surface. Although, newly developed eye drop formulations do not contain standard preservatives, they still can be harmful to ocular surface due to other excipients. In this study, we compared tolerability of commercial preservative-free (pf) prostaglandin analogues (pf tafluprost, pf latanoprost and pf bimatoprost) in long-term topical application in rabbits in vivo. We found that after eight weeks treatment, pf latanoprost was the worst tolerated among the tested drops. It expressed increased conjunctival redness and blinking frequency. Furthermore, it caused increased LDH release in the aqueous humour, infiltration of macrophages in the eyelids and visible defects in conjunctival goblet cells. However, we did not detect increased levels of inflammatory markers in the tear fluid or in the aqueous humour. Based on our study, we suspect that these negative effects are related to excipients included in pf latanoprost formulation.
Department of Ophthalmology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Anna
A
Trzeciecka
Department of Ophthalmology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Department of Ophthalmology, Kuopio University Hospital, P.O. Box 1777, 70211 Kuopio, Finland.
J Jussi
JJ
Paterno
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Elisa
E
Toropainen
Department of Ophthalmology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Ali
A
Koskela
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Lucia
L
Podracka
Department of Ophthalmology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Eveliina
E
Korhonen
Department of Ophthalmology, Kuopio University Hospital, P.O. Box 1777, 70211 Kuopio, Finland; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Anu
A
Kauppinen
Department of Ophthalmology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Department of Ophthalmology, Kuopio University Hospital, P.O. Box 1777, 70211 Kuopio, Finland. Electronic address: kai.kaarniranta@kuh.fi.
Kai
K
Kaarniranta
Department of Ophthalmology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland; Department of Ophthalmology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Panewnicka 65, 40-760 Katowice, Poland; Chair and Department of Physiology, School of Medicine in Katowice, Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland. Electronic address: adrian.smedowski@gmail.com.
Adrian
A
Smedowski
D000287:Administration, Topical; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001767:Blinking / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D003228:Conjunctiva / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D005123:Eye / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005143:Eyelids / Q000166:cytology / Q000187:drug effects; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D011310:Preservatives, Pharmaceutical; D011465:Prostaglandins, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects* / Q000737:chemistry; D011817:Rabbits; D013997:Time Factors
D015415:Biomarkers; D004268:DNA-Binding Proteins; D011310:Preservatives, Pharmaceutical; D011465:Prostaglandins, Synthetic; D007770:L-Lactate Dehydrogenase
Macrophages; Preservative-free prostaglandin analogues; Tolerability; Topical application