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Conjunctival histopathological changes associated with netarsudil 0.02%

Abstract

Objective

To investigate histopathological conjunctival changes associated with topical netarsudil 0.02%.

Methods

Observational comparative case series. Histopathological analysis of conjunctival specimens taken from adult patients undergoing glaucoma surgery. Inflammation score was graded by three independent pathologists.

Results

29 samples were included for analysis. Mean age was 72.4 years and 44.8% were female. Most patients underwent trabeculectomy with mitomycin C (22/29, 76%) while the remainder underwent tube shunt surgery, and one patient underwent insertion of an experimental NT-501 intravitreal implant. All patients were taking ≥2 topical IOP lowering medications, and 12 patients (41.3%) were using topical netarsudil, with mean duration 26.8 months. Compared to those on other glaucoma medications, patients taking netarsudil had significantly thicker conjunctival epithelium (mean 90.1 µm vs 43.2 µm, p = 0.03) and a trend toward higher epithelial cell thickness count (mean 7.7 cells thick vs. 4.9 cells thick, p = 0.07), both of which remained significant and trending respectively when adjusted for confounders (p = 0.02 and p = 0.06). All netarsudil treated samples demonstrated inflammation (graded score ≥0.5) compared to 64.7% of those not on netarsudil (p = 0.03). There were no significant differences in any histopathological parameters in patients who had ceased netarsudil prior to analysis (n = 7) compared to those who had never taken netarsudil (p > 0.05 for all).

Conclusion

Conjunctiva treated with netarsudil may be more likely to demonstrate inflammation compared to those treated with other combinations of glaucoma medications. These findings may have surgical implications and additional studies correlating clinical outcomes are required.

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Fig. 1: Histopathological differences between netarsudil-treated and non-netarsudil treated conjunctiva.
Fig. 2: Clinical intraoperative differences between netarsudil-treated and non-netarsudil treated conjunctiva.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

KS is a consultant for: Alcon, Allergan, Glaukos, Ivantis, Santen and Sight Sciences. The sponsor or funding organisations had no role in the design or conduct of this research.

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Contributions

MTS was responsible for the study design, recruitment, data analysis and drafting of the manuscript. CC, JL and DSM were responsible for the histopathological protocol and review, and approval of the final manuscript. KS was responsible for the study conception, design, oversight and approval of the final manuscript.

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Correspondence to Michelle T. Sun.

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Sun, M.T., Charoenkijkajorn, C., Lin, J.H. et al. Conjunctival histopathological changes associated with netarsudil 0.02%. Eye (2025). https://doi.org/10.1038/s41433-025-04063-y

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