Pr Eric E. GabisonCornea and ocular surface · Paris
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3 · Anticollagenolytics & anti-melt agents

N-acetylcysteine (NAC)

Review — modulators of corneal healing3 · Anticollagenolytics & anti-melt agents › N-acetylcysteine (NAC)

N-acetylcysteine (NAC)

Eye drops 5–20% (diluted from the systemic form, compounded)

Oxford IV–V (human) Weak / Investigational Present · niche
Mechanism of actionAnticollagenolytic: an N-acetylated derivative of cysteine, NAC behaves as a pseudopeptide bearing a thiol group — this free thiol chelates the zinc/calcium of the MMP catalytic site, on the same principle (active-site zinc chelation) as the synthetic pseudopeptide inhibitors (hydroxamates of the ilomastat/batimastat class, see the "MMP inhibitors" panel), but via a thiol rather than a hydroxamate moiety; it also directly reduces the disulfide bridges of pro-MMP-9, limiting its activation, and down-regulates MMP transcription through inhibition of NF-κB [Kim et al., Eye 2012]; in addition it is mucolytic (cleaving disulfide bonds in mucus/filaments) and antioxidant (a glutathione precursor).
IndicationsStromal melting / keratomalacia / descemetocele (alkali burns, collagenolytic ulcers) to halt thinning; filamentary keratitis (mucolytic). Widely used in veterinary corneal disease.
Route & dosageTopical, ~10% (5–20%), 1 drop every 1–4 hours during active melting, then tapered. Refrigerated, short shelf life, irritant.
Level of evidenceOxford IV–V in humans (solid in-vitro/veterinary data) · Scale: Weak / Investigational.
FDANo approved NAC eye drop — ocular use is off-label / compounded.
EU MANo dedicated eye drop in most markets (compounded/hospital preparation). Historically Ilube 5% (UK).
FranceHospital/compounded preparation.
USACompounded / off-label.
AsiaCompounded; variable availability.
Key studies: Berman/Slansky et al. (collagenase inhibitors, foundational); comparative in-vitro model of serum/EDTA/tetracyclines/NAC, Am J Vet Res 2018 — PMID 29688786; Kim WJ et al., effects of NAC on MMP-9 secretion and migration of human corneal epithelial cells, Eye 2012 — PMID 22766540.

Prof. Eric E. Gabison — cornea and ocular surface, Paris