Pr Eric E. GabisonOphthalmology · Cornea & refractive · Paris
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Home › Pro area › Chronic corneal ulcer › Algorithm & references
Course contents ▾
  1. Introduction & definitions
  2. Epithelial & stromal healing
  3. Stromal melt, nerves & tears
  4. Diagnostic approach
  5. Etiologies & staging
  6. Setting, lubrication, proteolysis
  7. Trophic factors & regeneration
  8. Amniotic, scleral lenses
  9. Grafts, neurotization, cells
  10. Algorithm
  11. What changed since 2010
  12. References
Chapitre 10

Treatment algorithm

Management is a stepwise escalation, reassessed at each stage.

Treatment algorithm

1. Exclude infection — scraping/cultures + PCR at the slightest doubt, before any corticosteroid therapy or membrane placement.

2. Correct the setting — stop iatrogenic agents (drug holiday); treat any associated disease: rosacea → doxycycline + ciclosporin; Sjögren → ciclosporin + plugs; immunological → immunosuppressants; mechanical/exposure correction.

3. PED at D5–D7 without thinning — preservative-free substitutes ± doxycycline ± debridement of hyperplastic edges; add autologous serum/PRP, RGTA, and according to context cenegermin (neurotrophic form) or topical insulin.

4. Failure or stromal ulcer — AMT (inlay ± overlay) and/or scleral lens; cover exposure with tarsorrhaphy / botulinum toxin.

5. Threatened or actual perforation — cyanoacrylate glue, multilayer AMT, tectonic graft, conjunctival flap.

6. Refractory neurotrophic form / limbal deficiency — consider corneal neurotization and/or limbal cell therapy (CLET/SLET) before visual rehabilitation.

Chapitre 11

What has changed since 2010

Over a decade, the therapeutic armamentarium for chronic ulcers has been profoundly renewed.

Summary of advances
  • Recombinant NGF (cenegermin / Oxervate®): moved from "experimental" to a treatment with marketing authorization in neurotrophic keratitis.
  • Matrix regenerating agents (RGTA / Cacicol®): a new class aimed at rebuilding the extracellular matrix.
  • Topical insulin: an emerging, inexpensive option for refractory PEDs.
  • Broadened blood derivatives: cord serum, PRP/PRGF beyond autologous serum alone.
  • Scleral lenses: a protective and trophic reservoir, now well codified.
  • Corneal neurotization: re-innervation surgery for severe neurotrophic forms.
  • Limbal cell therapies: CLET (Holoclar®, MA 2015) and SLET for limbal deficiency.
  • Imaging: anterior-segment OCT (follow-up of thinning) and confocal microscopy (sub-basal innervation).
Chapitre 12

References

  1. Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. WB Saunders.
  2. Bonini S, Lambiase A, Rama P, et al. Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology. 2000;107(7):1347-51.
  3. Gabison EE, Huet E, Baudouin C, Menashi S. Direct epithelial-stromal interaction in corneal wound healing: role of EMMPRIN/CD147 in MMPs induction and beyond. Prog Retin Eye Res. 2009;28(1):19-33.
  4. Gabison EE, Mourah S, Steinfels E, et al. Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas. Am J Pathol. 2005;166(1):209-19.
  5. Gabison EE, Chastang P, Menashi S, et al. Late corneal perforation after photorefractive keratectomy associated with topical diclofenac. Ophthalmology. 2003;110(8):1626-31.
  6. Gabison EE, Doan S, et al. Modified deep anterior lamellar keratoplasty in the management of descemetocele. Cornea. 2011.
  7. Bonini S, Lambiase A, Rama P, et al. Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis (REPARO). Ophthalmology. 2018;125(9):1332-1343.
  8. Pflugfelder SC, Massaro-Giordano M, Perez VL, et al. Topical recombinant human nerve growth factor (cenegermin) for neurotrophic keratopathy: a multicenter randomized vehicle-controlled pivotal trial. Ophthalmology. 2020;127(1):14-26.
  9. Aggarwal S, Kheirkhah A, Cavalcanti BM, et al. Autologous serum tears for treatment of neurotrophic keratopathy and corneal nerve regeneration. Ocul Surf.
  10. Aifa A, Gueudry J, Portmann A, et al. Topical treatment with a new matrix regenerating agent (RGTA) in patients with corneal neurotrophic ulcers. Invest Ophthalmol Vis Sci.
  11. Wang AL, et al. Topical insulin for persistent epithelial defects and neurotrophic keratopathy: a systematic review. 2024–2025.
  12. Terzis JK, et al. Corneal neurotization: techniques and outcomes (reviews 2021–2025).
  13. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis (Mackie classification). Clin Ophthalmol.
  14. Rama P, Ferrari G, Pellegrini G. Cultivated limbal epithelial transplantation (Holoclar®) and SLET for limbal stem cell deficiency.
Disclaimer

The precise bibliographic details (volume/pages) of some references are to be verified before publication. This is an educational document for healthcare professionals: dosages and marketing-authorization statuses are indicative and must be checked against the current SmPCs and guidelines. Several of the uses cited are off-label (topical insulin, certain indications of blood derivatives). This course updates the original article published in Réflexions Ophtalmologiques (no. 137, vol. 15, September 2010).