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. 2000 Aug;84(8):826–833. doi: 10.1136/bjo.84.8.826

Amniotic membrane transplantation for severe neurotrophic corneal ulcers

H Chen 1, R Pires 1, S Tseng 1
PMCID: PMC1723607  PMID: 10906085

Abstract

AIMS—To evaluate whether amniotic membrane transplantation can be an effective alternative treatment for neurotrophic corneal ulcers.
METHODS—Amniotic membrane transplantation was performed in 16 eyes of 15 patients with neurotrophic corneal ulcers and vision equal to or worse than 20/200. The neurotrophic state was developed following keratoplasty (four eyes), herpes zoster ophthalmicus (four eyes), diabetes mellitus (four eyes), radiation (two eyes), removal of acoustic neuroma with neuroparalysis (one eye), and herpes simplex keratitis (one eye).
RESULTS—During a mean follow up period of 18.8 (SD 13.0) months, one to three layers of amniotic membrane with or without additional membrane as a patch were used for 17 procedures in 16 eyes for persistent neurotrophic corneal ulcers. All but four (76.4%) instances of amniotic membrane transplantation achieved rapid epithelialisation in 16.6 (9.0) days. Of the four eyes showing delayed healing, three eyes healed by tarsorrhaphy, and the remaining one eye with corneal perforation required penetrating keratoplasty and tarsorrhaphy. Two eyes gained vision better than 20/200. The healed corneal surface was accompanied by reduced inflammation.
CONCLUSION—Amniotic membrane transplantation can be considered an effective alternative for treating severe neurotrophic corneal ulcers.



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Figure 1  .

Figure 1  

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Case 3 had previously undergone a penetrating keratoplasty with tarsorrhaphy for a progressive ulcer and descemetocele caused by herpes zoster ophthalmicus on the left eye. He developed a recurrent herpes zoster with epithelial dendrites and ulcers stained with rose bengal (A) and fluorescein (B), and progressed into disciform and necrotising stromal keratitis. This was complicated by bacterial keratitis, and a large inferior one third hypopyon (C). Following appropriate antibiotics and aciclovir, the sterilised ulcer became thin in several locations of the cornea. Amniotic membrane transplantation was performed and resulted in total healing of the ulcer with a quiet ocular surface in 13 days (D and E). After the corneal surface had been stable for 15 months (F), a repeat PKP was performed and covered with an amniotic membrane as a patch, which was dissolved in 2 weeks, and the graft showed a smooth surface and clear stroma 8 months later (G and H).

Figure 2  .

Figure 2  

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Case 4 had AIDS, had discontinued anti-HIV medications for 1 month, and developed acute herpes zoster ophthalmicus on the left eye (A) with diffuse conjunctival redness and corneal involvement (B). The cornea showed a peripheral circumlinear ulcer with infiltrate, diffuse oedema with keratic precipitates and hypopyon (C and D). Ten days after amniotic membrane transplantation the membrane dissolved, the corneal and conjunctival surfaces were no longer inflamed, and the ulcer healed with resolution of oedema, keratic precipitates, and hypopyon (E and F).

Figure 3  .

Figure 3  

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Case 15 had received multiple surgeries for recurrent retinal detachment in the left eye resulting in a persistent neurotrophic corneal ulcer with band keratopathy (A and B). Eight days after amniotic membrane transplantation (AMT), part of the membrane used as a patch started to dissolve (arrow) (C), while epithelial healing had taken place as shown by fluorescein staining (D). One month after AMT the membrane covered surface was totally healed and smooth with a small part of the membrane dissolved (indicated by asterisks) (E and F). The corneal surface continued to be stable and remained uninflamed (F).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Azuara-Blanco A., Pillai C. T., Dua H. S. Amniotic membrane transplantation for ocular surface reconstruction. Br J Ophthalmol. 1999 Apr;83(4):399–402. doi: 10.1136/bjo.83.4.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beuerman R. W., Schimmelpfennig B. Sensory denervation of the rabbit cornea affects epithelial properties. Exp Neurol. 1980 Jul;69(1):196–201. doi: 10.1016/0014-4886(80)90154-5. [DOI] [PubMed] [Google Scholar]
  3. Brown S. M., Lamberts D. W., Reid T. W., Nishida T., Murphy C. J. Neurotrophic and anhidrotic keratopathy treated with substance P and insulinlike growth factor 1. Arch Ophthalmol. 1997 Jul;115(7):926–927. doi: 10.1001/archopht.1997.01100160096021. [DOI] [PubMed] [Google Scholar]
  4. Donzis P. B., Mondino B. J. Management of noninfectious corneal ulcers. Surv Ophthalmol. 1987 Sep-Oct;32(2):94–110. doi: 10.1016/0039-6257(87)90102-0. [DOI] [PubMed] [Google Scholar]
  5. Dua H. S. The conjunctiva in corneal epithelial wound healing. Br J Ophthalmol. 1998 Dec;82(12):1407–1411. doi: 10.1136/bjo.82.12.1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Duchesne B., Mans B., Lavalleye B., Gerard C., Marechal-Courtois C., Betz P., Tseng S. C. Utilisation de la membrane amniotique humaine cryo-préservée pour la reconstruction de la surface oculaire. Bull Soc Belge Ophtalmol. 1998;268:73–77. [PubMed] [Google Scholar]
  7. Fujishima H., Shimazaki J., Shinozaki N., Tsubota K. Trabeculectomy with the use of amniotic membrane for uncontrollable glaucoma. Ophthalmic Surg Lasers. 1998 May;29(5):428–431. [PubMed] [Google Scholar]
  8. Fujishima H., Shimazaki J., Tsubota K. Temporary corneal stem cell dysfunction after radiation therapy. Br J Ophthalmol. 1996 Oct;80(10):911–914. doi: 10.1136/bjo.80.10.911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Golubović S., Parunović A. Cyanoacrylate glue in the treatment of corneal ulcerations. Fortschr Ophthalmol. 1990;87(4):378–381. [PubMed] [Google Scholar]
  10. Gould H. L. Treatment of neurotrophic keratitis with scleral contact lenses. Eye Ear Nose Throat Mon. 1967 Nov;46(11):1406–1414. [PubMed] [Google Scholar]
  11. Holland E. J., Schwartz G. S. The evolution of epithelial transplantation for severe ocular surface disease and a proposed classification system. Cornea. 1996 Nov;15(6):549–556. [PubMed] [Google Scholar]
  12. Hyndiuk R. A., Kazarian E. L., Schultz R. O., Seideman S. Neurotrophic corneal ulcers in diabetes mellitus. Arch Ophthalmol. 1977 Dec;95(12):2193–2196. doi: 10.1001/archopht.1977.04450120099012. [DOI] [PubMed] [Google Scholar]
  13. Kim J. C., Tseng S. C. Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea. 1995 Sep;14(5):473–484. [PubMed] [Google Scholar]
  14. Kruse F. E., Rohrschneider K., Völcker H. E. Multilayer amniotic membrane transplantation for reconstruction of deep corneal ulcers. Ophthalmology. 1999 Aug;106(8):1504–1511. doi: 10.1016/S0161-6420(99)90444-X. [DOI] [PubMed] [Google Scholar]
  15. Lambiase A., Rama P., Bonini S., Caprioglio G., Aloe L. Topical treatment with nerve growth factor for corneal neurotrophic ulcers. N Engl J Med. 1998 Apr 23;338(17):1174–1180. doi: 10.1056/NEJM199804233381702. [DOI] [PubMed] [Google Scholar]
  16. Lee S. H., Tseng S. C. Amniotic membrane transplantation for persistent epithelial defects with ulceration. Am J Ophthalmol. 1997 Mar;123(3):303–312. doi: 10.1016/s0002-9394(14)70125-4. [DOI] [PubMed] [Google Scholar]
  17. Liesegang T. J. Corneal complications from herpes zoster ophthalmicus. Ophthalmology. 1985 Mar;92(3):316–324. doi: 10.1016/s0161-6420(85)34034-4. [DOI] [PubMed] [Google Scholar]
  18. Lugo M., Arentsen J. J. Treatment of neurotrophic ulcers with conjunctival flaps. Am J Ophthalmol. 1987 May 15;103(5):711–712. doi: 10.1016/s0002-9394(14)74337-5. [DOI] [PubMed] [Google Scholar]
  19. McCulley J. P., Horowitz B., Husseini Z. M., Horowitz M. Topical fibronectin therapy of persistent corneal epithelial defects. Fibronectin Study Group. Trans Am Ophthalmol Soc. 1993;91:367–390. [PMC free article] [PubMed] [Google Scholar]
  20. Meller D., Tseng S. C. Conjunctival epithelial cell differentiation on amniotic membrane. Invest Ophthalmol Vis Sci. 1999 Apr;40(5):878–886. [PubMed] [Google Scholar]
  21. Phan T. M., Foster C. S., Boruchoff S. A., Zagachin L. M., Colvin R. B. Topical fibronectin in the treatment of persistent corneal epithelial defects and trophic ulcers. Am J Ophthalmol. 1987 Nov 15;104(5):494–501. doi: 10.1016/s0002-9394(14)74107-8. [DOI] [PubMed] [Google Scholar]
  22. Pires R. T., Tseng S. C., Prabhasawat P., Puangsricharern V., Maskin S. L., Kim J. C., Tan D. T. Amniotic membrane transplantation for symptomatic bullous keratopathy. Arch Ophthalmol. 1999 Oct;117(10):1291–1297. doi: 10.1001/archopht.117.10.1291. [DOI] [PubMed] [Google Scholar]
  23. Prabhasawat P., Barton K., Burkett G., Tseng S. C. Comparison of conjunctival autografts, amniotic membrane grafts, and primary closure for pterygium excision. Ophthalmology. 1997 Jun;104(6):974–985. doi: 10.1016/s0161-6420(97)30197-3. [DOI] [PubMed] [Google Scholar]
  24. Puangsricharern V., Tseng S. C. Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology. 1995 Oct;102(10):1476–1485. doi: 10.1016/s0161-6420(95)30842-1. [DOI] [PubMed] [Google Scholar]
  25. Reed J. W., Joyner S. J., Knauer W. J., 3rd Penetrating keratoplasty for herpes zoster keratopathy. Am J Ophthalmol. 1989 Mar 15;107(3):257–261. doi: 10.1016/0002-9394(89)90309-7. [DOI] [PubMed] [Google Scholar]
  26. Schwartz G. S., Holland E. J. Iatrogenic limbal stem cell deficiency. Cornea. 1998 Jan;17(1):31–37. doi: 10.1097/00003226-199801000-00006. [DOI] [PubMed] [Google Scholar]
  27. Shimazaki J., Shinozaki N., Tsubota K. Transplantation of amniotic membrane and limbal autograft for patients with recurrent pterygium associated with symblepharon. Br J Ophthalmol. 1998 Mar;82(3):235–240. doi: 10.1136/bjo.82.3.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shimazaki J., Yang H. Y., Tsubota K. Amniotic membrane transplantation for ocular surface reconstruction in patients with chemical and thermal burns. Ophthalmology. 1997 Dec;104(12):2068–2076. doi: 10.1016/s0161-6420(97)30057-8. [DOI] [PubMed] [Google Scholar]
  29. Sorsby A., Haythorne J., Reed H. FURTHER EXPERIENCE WITH AMNIOTIC MEMBRANE GRAFTS IN CAUSTIC BURNS OF THE EYE. Br J Ophthalmol. 1947 Jul;31(7):409–418. doi: 10.1136/bjo.31.7.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sorsby A., Symons H. M. AMNIOTIC MEMBRANE GRAFTS IN CAUSTIC BURNS OF THE EYE: (Burns of the second degree). Br J Ophthalmol. 1946 Jun;30(6):337–345. [PMC free article] [PubMed] [Google Scholar]
  31. Tseng S. C., Li D. Q., Ma X. Suppression of transforming growth factor-beta isoforms, TGF-beta receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. J Cell Physiol. 1999 Jun;179(3):325–335. doi: 10.1002/(SICI)1097-4652(199906)179:3<325::AID-JCP10>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  32. Tseng S. C., Prabhasawat P., Barton K., Gray T., Meller D. Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol. 1998 Apr;116(4):431–441. doi: 10.1001/archopht.116.4.431. [DOI] [PubMed] [Google Scholar]
  33. Tseng S. C., Prabhasawat P., Lee S. H. Amniotic membrane transplantation for conjunctival surface reconstruction. Am J Ophthalmol. 1997 Dec;124(6):765–774. doi: 10.1016/s0002-9394(14)71693-9. [DOI] [PubMed] [Google Scholar]
  34. Tseng S. C., Tsubota K. Important concepts for treating ocular surface and tear disorders. Am J Ophthalmol. 1997 Dec;124(6):825–835. doi: 10.1016/s0002-9394(14)71700-3. [DOI] [PubMed] [Google Scholar]
  35. Tsubota K., Satake Y., Kaido M., Shinozaki N., Shimmura S., Bissen-Miyajima H., Shimazaki J. Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation. N Engl J Med. 1999 Jun 3;340(22):1697–1703. doi: 10.1056/NEJM199906033402201. [DOI] [PubMed] [Google Scholar]
  36. Tsubota K., Satake Y., Ohyama M., Toda I., Takano Y., Ono M., Shinozaki N., Shimazaki J. Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol. 1996 Jul;122(1):38–52. doi: 10.1016/s0002-9394(14)71962-2. [DOI] [PubMed] [Google Scholar]

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