Preserved vs Preservative-Free Artificial Tears: A 6-Month Trial Found No Clear Change in Corneal Nerves

Benzalkonium chloride, or BAK, is a common preservative in multi-dose eye drops. Laboratory studies have suggested it can harm corneal nerves, depending on the concentration and how long it is used. A substudy of a randomized trial, published in 2026 in the Romanian Journal of Ophthalmology, asked whether six months of BAK at the concentration used in artificial tears is linked to detectable changes in the cornea’s subbasal nerve plexus in people with dry eye.

What was compared

This was a secondary, imaging analysis from a six-month, randomized, single-masked trial. The two drops had the same active ingredient, 0.15% sodium hyaluronate. One was preserved with 0.005% BAK; the other was preservative-free. Both were used as needed. Of 43 people who completed the trial, 32 had in vivo confocal microscopy of the central cornea at the start and at six months: 19 on the preservative-free drop and 13 on the BAK-preserved drop. Seven nerve measurements were analyzed with mixed-effects models that included both eyes.

What they found

• Baseline characteristics and all baseline nerve measurements were comparable between groups.
• Over six months, no nerve parameter showed a statistically significant difference in change between the two drops.
• For corneal nerve fiber density, the change in the BAK group was 3.52 fibers/mm² higher than in the preservative-free group, but the 95% confidence interval ran from -2.32 to 9.37 and was not statistically significant.

The authors noted that this design avoids a common problem in glaucoma research, where the active glaucoma drug can confound the effect of the preservative. They also said the estimates are imprecise and that the study cannot prove the two drops are equivalent. In short, this small imaging substudy did not detect a between-group difference in corneal nerves after six months, and it should not be read as a green light or a ban on preserved tears. If you use artificial tears many times a day, or you already have a vulnerable ocular surface, it is still reasonable to discuss preservative-free options with your eye doctor.

Source: BAK-preserved hyaluronate and corneal nerves (Romanian Journal of Ophthalmology (PubMed), 2026). This article is an educational summary written by Khanna Vision Institute and is not a substitute for medical advice.