Home › Review — modulators of corneal healing › Mechanical adjuncts and modulation of corneal fibrosis
Mechanical adjuncts and modulation of corneal fibrosis
Two distinct problems are grouped here because they arise at the two ends of the same story. At the beginning: a surface that cannot heal because it is exposed. At the end: a cornea that has healed, but turned opaque.
The first problem is mechanical and is solved mechanically. No molecule compensates for defective lid closure: in facial palsy or proptosis, tarsorrhaphy or botulinum ptosis achieve more than all the eye drops in this review. It is the procedure most often postponed, out of cosmetic reluctance, although it is reversible.
The second problem is cellular: the transformation of keratocytes into myofibroblasts under TGF-β, producing haze and scarring. Mitomycin C prevents it bluntly, by killing keratocytes; topical losartan proposes to temper it by blocking the TGF-β pathway upstream.
Overview
| Agent | Mechanism | Level of evidence |
|---|---|---|
| Tarsorrhaphy · punctal occlusion · botulinum-induced ptosis | Mechanical/physiological: tarsorrhaphy & botulinum-induced ptosis reduce exposure/evaporation and blink-related micr… | Oxford II–IV Moderate Present · established |
| Mitomycin C (MMC) | DNA cross-linking → inhibition of proliferation and apoptosis of activated keratocytes/myofibroblasts in the anterior st… | Oxford I–II Strong (anti-haze) Present · refractive |
| Topical losartan | Blocks downstream TGF-β signaling (TGF-β→Smad pathway, via inhibition of angiotensin signaling and transactivation) → pr… | Oxford IV Weak–Moderate · emerging Present-emerging · off-label |
| Hyperbaric oxygen therapy (HBOT) | ↑Tissue O₂ pressure → supports epithelial mitochondrial/ATP metabolism (migration/proliferation), limbal neovascularizat… | Oxford IV–V (clin.) · II (exp.) Weak / Investigational Present · niche |
Tarsorrhaphy · punctal occlusion · botulinum-induced ptosis
Eyelid closure (suture/glue), punctal plugs or cauterization, chemodenervation of the levator muscle (botulinum toxin A)
Mechanical/physiological: tarsorrhaphy & botulinum-induced ptosis reduce exposure/evaporation and blink-related micro-trauma, cover the ocular surface and increase tear film contact time (protection of the neurotrophic epithelium). Botulinum toxin acts as a reversible “temporary tarsorrhaphy.” Punctal occlusion: ↑tear film volume/residence time, ↓MMP/inflammatory load.
IndicationsPersistent epithelial defect (PED), neurotrophic keratopathy, exposure keratopathy (facial palsy, lagophthalmos), severe aqueous-deficient dry eye, complex post-graft cases.
Route & dosingLateral/central tarsorrhaphy (temporary with glue/suture, or permanent); collagen punctal plugs (temporary) or silicone plugs/cauterization; botulinum toxin ~2.5–7.5 U into the levator muscle (ptosis develops within days, lasting ~4–12 weeks, repeatable).
Level of evidenceOxford III–IV (case series, long-standing practice; a few controlled series for botulinum toxin); punctal occlusion in dry eye: Oxford II · Scale: Moderate.
Detailed sheet →Mitomycin C (MMC) — anti-fibrotic modulator
Antineoplastic alkylating agent, intraoperative application 0.02% (0.2 mg/mL)
DNA cross-linking → inhibition of proliferation and apoptosis of activated keratocytes/myofibroblasts in the anterior stroma → prevention of sub-epithelial fibrosis (haze) and fibrovascular regrowth of pterygium. Does not accelerate epithelial healing (may transiently delay it); endothelial toxicity if exposure is excessive.
IndicationsProphylaxis of haze after surface photoablation (PRK/PTK), especially high myopia/retreatments; adjunct to pterygium excision (↓recurrence); glaucoma filtering surgery.
Route & dosingSingle intraoperative application to the stromal bed via sponge — 0.02% for 12 s–2 min (titrated to depth), followed by copious irrigation (BSS). No chronic topical use.
Level of evidenceOxford I–II (RCTs, dose-response) · Scale: Strong (haze prevention, pterygium recurrence).
Detailed sheet →Topical losartan — anti-TGF-β anti-fibrotic agent
Angiotensin II AT1 receptor antagonist, repurposed as an eye drop · work by S. Wilson (Cleveland Clinic)
Blocks downstream TGF-β signaling (TGF-β→Smad pathway, via inhibition of angiotensin signaling and transactivation) → prevents differentiation of keratocytes into myofibroblasts (α-SMA) responsible for corneal fibrosis/opacity (haze). A stromal anti-scarring agent (does not accelerate epithelialization — conversely, epithelial toxicity is possible at high concentrations).
IndicationsPrevention/treatment of corneal fibrosis and opacity (haze) — best results in post-HSV/VZV scars, post-LASIK/PRK, post-infectious keratitis (Pseudomonas), post-keratectomy. A “pharmacological” alternative to mitomycin C, applicable post hoc (on an established scar) and not only intraoperatively.
Route & dosingCompounded eye drop 0.8 mg/mL, 6×/day, ≥6 months. In the presence of an epithelial defect: start at 0.2 mg/mL 6×/day until healing, then switch to 0.8 mg/mL. Toxic at high concentrations: 40 mg/mL highly toxic; 8 mg/mL → persistent epithelial defects on a compromised surface.
Level of evidenceOxford IV (case series and reports; robust preclinical basis in rabbits) · Scale: Weak–Moderate (emerging). E.g.: HSV/VZV series — VA 20/400 → 20/25 and 20/200 → 20/20; post-LASIK 20/200 → 20/30 (4 months); keratectomy: opacity 0.7 → 0.4 mm (9 months).
Detailed sheet →Hyperbaric oxygen therapy (HBOT)
100% O₂ at 2–2.5 ATA · niche adjunct
↑Tissue O₂ pressure → supports epithelial mitochondrial/ATP metabolism (migration/proliferation), limbal neovascularization in cases of ischemia, anti-edema/antimicrobial effect. Animal data: accelerated healing (acetylcholine pathway).
IndicationsRefractory/ischemic ulcers, chemical burns with limbal ischemia, anterior segment ischemia, post-embolic keratitis (adjunct, not routine).
Route & dosingHBOT sessions ~90 min at 2–2.5 ATA, daily, multiple sessions; or localized O₂ (experimental).
Level of evidenceOxford IV–V clinical · Scale: Weak / Investigational (cornea).
Detailed sheet →Key points
Remember the hierarchy first: faced with an ulcer that will not close, check lid closure and corneal sensitivity before prescribing anything. Botulinum ptosis gives three months of closure without scarring, and often settles the question: if the ulcer closes, exposure was the cause.
Mitomycin C is effective and dangerous — the keratocyte aplasia it causes is lasting, and neither concentration nor application time can be improvised. Topical losartan is one of the most interesting current leads: an old molecule, safe systemically, with converging preclinical results on corneal scarring — but no sizeable clinical trial.
Hyperbaric oxygen remains marginal, reserved for anterior segment ischaemia.
The other families in this review
Updated 26 August 2026