Neurotrophic Keratopathy Treatment & Management

  • Author: Robert H Graham, MD; Chief Editor: Hampton Roy Sr, MD   more...
 
Updated: Feb 3, 2009
 

Medical Care

Stage 1 is as follows:

  • Topical lubrication with preservative-free artificial tears, gels, and ointments
  • Discontinue any topical ocular therapies, especially those that can decrease corneal sensitivity (eg, timolol, betaxolol, sulfacetamide, diclofenac, ketorolac) or contain preservatives.[10]
  • Reevaluate the need for systemic drugs, such as neuroleptics, antipsychotics, and antihistamines.
  • Punctal occlusion may need to be considered.
  • Oral tetracycline (250 mg PO bid) or doxycycline (100 mg PO every other day) can reduce the amount of mucus produced.

Stage 2 is as follows:

  • All of stage 1 treatments
  • Topical tetracycline reportedly increases the healing of epithelial defects (not available in an ophthalmic drop preparation)
  • Topical cycloplegia with atropine 1% or scopolamine 0.25% once daily in the presence of anterior chamber inflammation
  • More likely to require surgical intervention than stage 1

Stage 3 is as follows:

  • All of stage 1 and stage 2 treatments
  • Surgical intervention

Medications to avoid are as follows:

  • Topical corticosteroids may increase collagenase activity and stromal melting.
  • Topical NSAIDs have not shown any benefit in wound healing, and diclofenac and ketorolac use can decrease corneal sensitivity.

Future treatments[11] are as follows:

  • Nerve growth factor has been shown to induce healing of stage 3 keratopathy in one open, uncontrolled study.[12, 13]
  • Aldose reductase inhibitor, CT-112, has been shown to reverse abnormal morphology of corneal epithelial cells and to increase corneal sensitivity.[14]
  • Topical pindolol has been reported to speed the healing of epithelial defects in rabbits.
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Surgical Care

Surgical care for neurotrophic keratopathy has 3 goals, as follows: (1) to protect the epithelium by lid closure, (2) to close a persistent epithelial defect, and (3) to repair a deep ulceration. Note the following:

  • Closure of the lids - In the presence of severe or total loss of corneal sensation, keratitis sicca, or exposure keratopathy, a lateral tarsorrhaphy, palpebral spring, or botulinum A toxin injection in the levator muscle may prevent progression to stage 2.
  • Closure of a persistent epithelial defect[15] - Conjunctival flap (effective but poor cosmetic and visual result[16] ); amniotic membrane transplantation[17]
  • Repair of a deep ulceration - Lamellar keratoplasty; penetrating keratoplasty (for large defects); multilayer amniotic membrane transplantation (has been used in defects as deep as 90% of the stroma[18, 19] ); cyanoacrylate glue with a soft bandage contact lens (for defects smaller than 2.0 mm)
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Consultations

Consult a neurologist if the cause of corneal hypesthesia is not apparent or if any associated neurologic deficits are present.[20]

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Contributor Information and Disclosures
Author

Robert H Graham, MD  Senior Associate Consultant, Department of Ophthalmology, Mayo Clinic, Scottsdale, Arizona

Robert H Graham, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, and Arizona Ophthalmological Society

Disclosure: WebMD/eMedicine Salary Employment

Coauthor(s)

Mark A Hendrix, MD  Consulting Staff, Department of Ophthalmology, Suburban Hospital, Shady Grove Hospital

Mark A Hendrix, MD is a member of the following medical societies: American Academy of Ophthalmology and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Stephen D Plager, MD, FACS  Chief, Department of Ophthalmology, Dominican Hospital; Assistant Clinical Professor, Department of Ophthalmology, Stanford University Hospital

Stephen D Plager, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and California Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Christopher J Rapuano, MD  Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Institute

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery, and Pan-American Association of Ophthalmology

Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; Inspire Honoraria Speaking and teaching; RPS Ownership interest Other; Vistakon Honoraria Speaking and teaching; EyeGate Pharma Consulting; Inspire Consulting fee Consulting; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting fee Consulting

Lance L Brown, OD, MD  Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD  Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

References

  1. Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye. Nov 2003;17(8):989-95. [Medline].

  2. Cohen EJ, Rapuano CJ. Neurotrophic keratopathy. In: Friedberg MA, Rapuano CJ, eds. Wills Eye Hospital office and emergency room diagnosis and treatment of eye. 54-55.

  3. Groos EB. Neurotrophic keratitis. In: Krachmer JH, ed. Cornea: Fundamentals of Corneal and External Disease. Mosby: St. Louis; 1997:1339-62.

  4. Fogle JA, Kenyon KR, Foster CS. Tissue adhesive arrests stromal melting in the human cornea. Am J Ophthalmol. Jun 1980;89(6):795-802. [Medline].

  5. Pavan-Langston D, Dohlman CH. Boston keratoprosthesis treatment of herpes zoster neurotrophic keratopathy. Ophthalmology. Feb 2008;115(2 Suppl):S21-3. [Medline].

  6. Lockwood A, Hope-Ross M, Chell P. Neurotrophic keratopathy and diabetes mellitus. Eye. Jul 2006;20(7):837-9. [Medline].

  7. Allen VD, Malinovsky V. Management of neurotrophic keratopathy. Cont Lens Anterior Eye. Sep 2003;26(3):161-5. [Medline].

  8. Lambiase A, Rama P, Aloe L, Bonini S. Management of neurotrophic keratopathy. Curr Opin Ophthalmol. Aug 1999;10(4):270-6. [Medline].

  9. Latvala T, Linna T, Tervo T. Corneal nerve recovery after photorefractive keratectomy and laser in situ keratomileusis. Int Ophthalmol Clin. Fall 1996;36(4):21-7. [Medline].

  10. Mackie IA. Neuroparalytic keratitis. In: Fraunfelder F, Roy FH, eds. Current Ocular Therapy. 5th ed. Philadelphia: WB Saunders; 2000:369-371.

  11. Goins KM. New insights into the diagnosis and treatment of neurotrophic keratopathy. Ocul Surf. Apr 2005;3(2):96-110. [Medline].

  12. Bonini S, Lambiase A, Rama P, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology. Jul 2000;107(7):1347-51; discussion 1351-2. [Medline].

  13. Lambiase A, Rama P, Bonini S, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for corneal neurotrophic ulcers. N Engl J Med. Apr 23 1998;338(17):1174-80. [Medline].

  14. Hosotani H, Ohashi Y, Yamada M, Tsubota K. Reversal of abnormal corneal epithelial cell morphologic characteristics and reduced corneal sensitivity in diabetic patients by aldose reductase inhibitor, CT-112. Am J Ophthalmol. Mar 1995;119(3):288-94. [Medline].

  15. Nishida T, Chikama T, Morishige N, Yanai R, Yamada N, Saito J. Persistent epithelial defects due to neurotrophic keratopathy treated with a substance p-derived peptide and insulin-like growth factor 1. Jpn J Ophthalmol. Nov-Dec 2007;51(6):442-7. [Medline].

  16. Lugo M, Arentsen JJ. Treatment of neurotrophic ulcers with conjunctival flaps. Am J Ophthalmol. May 15 1987;103(5):711-2. [Medline].

  17. Prabhasawat P, Tesavibul N, Komolsuradej W. Single and multilayer amniotic membrane transplantation for persistent corneal epithelial defect with and without stromal thinning and perforation. Br J Ophthalmol. Dec 2001;85(12):1455-63. [Medline].

  18. Kruse FE, Rohrschneider K, Volcker HE. Multilayer amniotic membrane transplantation for reconstruction of deep corneal ulcers. Ophthalmology. Aug 1999;106(8):1504-10; discussion 1511. [Medline].

  19. Solomon A, Meller D, Prabhasawat P, et al. Amniotic membrane grafts for nontraumatic corneal perforations, descemetoceles, and deep ulcers. Ophthalmology. Apr 2002;109(4):694-703. [Medline].

  20. Reynolds SA, Kabat AG. Therapeutic options for the management of early neurotrophic keratopathy: a case report and review. Optometry. Oct 2006;77(10):503-7. [Medline].

  21. Cavanagh HD, Colley AM. The molecular basis of neurotrophic keratitis. Acta Ophthalmol Suppl. 1989;192:115-34. [Medline].

  22. Matsumoto Y, Dogru M, Goto E, et al. Autologous serum application in the treatment of neurotrophic keratopathy. Ophthalmology. Jun 2004;111(6):1115-20. [Medline].

  23. Parmar DN, Alizadeh H, Awwad ST, et al. Ocular surface restoration using non-surgical transplantation of tissue-cultured human amniotic epithelial cells. Am J Ophthalmol. Feb 2006;141(2):299-307. [Medline].

  24. Schrader S, Wedel T, Moll R, Geerling G. Combination of serum eye drops with hydrogel bandage contact lenses in the treatment of persistent epithelial defects. Graefes Arch Clin Exp Ophthalmol. Oct 2006;244(10):1345-9. [Medline].

  25. Yamada N, Matsuda R, Morishige N, et al. Open clinical study of eye-drops containing tetrapeptides derived from substance P and insulin-like growth factor-1 for treatment of persistent corneal epithelial defects associated with neurotrophic keratopathy. Br J Ophthalmol. Jul 2008;92(7):896-900. [Medline].

 
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