• Therapeutic Cataract & Refractive
  • Lens Technology
  • Glasses
  • Ptosis
  • Comprehensive Eye Exams
  • AMD
  • COVID-19
  • DME
  • Ocular Surface Disease
  • Optic Relief
  • Geographic Atrophy
  • Cornea
  • Conjunctivitis
  • Myopia
  • Presbyopia
  • Allergy
  • Nutrition
  • Pediatrics
  • Retina
  • Cataract
  • Contact Lenses
  • Lid and Lash
  • Dry Eye
  • Glaucoma
  • Refractive Surgery
  • Comanagement
  • Blepharitis
  • OCT
  • Patient Care
  • Diabetic Eye Disease
  • Technology

Toxicity, therapeutics studied


Results of an in vitro study of the potentially adverse effects of different topical glaucoma medications and preservatives showed that the preservatives polyquad and sofZia had much less toxicity when used in place of benzalkonium chloride in prostaglandin analog formulations.

The study, published in the November issue of Advances in Therapy, compared the in vitro effects on both cultured human corneal and conjunctival epithelial cells of five prostaglandin analog formulations.

Test solutions

Dr. Kahook and colleagues found that exposure to an increasing percentage of BAK caused a dose-dependent increase in both conjunctival and corneal epithelial cell death compared with BSS control.

"The higher the concentration of BAK, the more likely you are to see changes in cell metabolism in vitro," he said. "We noticed that there was a definite advantage to having the alternative preservatives in place compared with the standard BAK-preserved travoprost."

Possible cytoprotective effect

The study also found that the toxicity of the prostaglandin analogs preserved with BAK was close to that of their respective BAK concentrations alone. Confirming previously reported findings, the study additionally determined that travoprost with 0.015% BAK performed better than 0.015% BAK alone, indicating a possible cytoprotective effect of the prostaglandin analog.

In the study, confluent cultures of human corneal and conjunctival cells were assayed with 100 µL of the different glaucoma medications for 25 minutes at 37 degrees C and 5% CO2. SofZia and a range of concentrations of BAK (0.001% to 0.050%) also were tested.

According to Dr. Kahook, a tremendous amount of information about the tolerability of different formulations of glaucoma drugs has been reported, but the lack of appropriate metrics has limited the clinical relevance of the obtained data.

"We don't have any great, reproducible metrics for ocular surface disease that can be done in a multi-site study. Because of the lack of metrics, there has been difficulty in correlating in vitro and in vivo findings," he explained.

Data from in vivo studies are available on specific patient populations, such as those who have had previous problems with formulations containing BAK or patients who have severe ocular surface disease. These studies have shown that changing from a drop preserved with BAK to one that is not results in improvement in metrics such as tear break-up time or lissamine green staining.1, 2

However, it would be difficult to expand these findings to all patient populations because current metrics are insufficient to identify the subtle changes that can occur in the ocular surface when switching medications, Dr. Kahook said. He added that many laboratories are investigating better ways to understand how in vitro findings compare with in vivo responses and developing better clinical diagnostic methodologies for making direct comparisons, if any exist.


1. Horsley MB, Kahook MY. Effects of prostaglandin analog therapy on the ocular surface of glaucoma patients. Clin Ophthalmol. 2009;3:291-295.

2. Uusitalo H, Chen E, Pfeiffer N, et al. Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication. Acta Ophthalmol. 2010;88:329-336.


Malik Y. Kahook, MDPhone: 720/848-2500
E-mail: malik.kahook@ucdenver.edu

Dr. Kahook has received research support from Actelion, Alcon, Allergan, American Glaucoma Society, Genentech, Merck, and the State of Colorado.

Related Videos
Raman Bhakhri, OD, FAAO, overviews his talk on medications' potential side effects on the retina with Optometry Times
Jacobi Cleaver, OD, FAAO
Jade Coats, OD, overviews a lecture on ocular pain and patient care
Jade Coats, OD, outlines two poster presentations she gave on a novel lipid-containing eye drop at the AOA Optometry's Meeting
Adam Alexander, OD, chats with Optometry Times about his AOA e-poster presentation on Miebo
Lorraine Provencher, MD, presenting slides
Megan Cavet, PhD
Nazlee Zebardast, MD, MSc, overviews her ARVO 2024 presentations on glaucoma and polygenic risk scores
© 2024 MJH Life Sciences

All rights reserved.