Medscape is available in 5 Language Editions – Choose your Edition here.


Neurotrophic Keratopathy Treatment & Management

  • Author: Robert H Graham, MD; Chief Editor: Hampton Roy, Sr, MD  more...
Updated: Jun 14, 2016

Approach Considerations

Pharmacologic care for neurotrophic keratopathy varies by stage with regard to the number and types of drugs used for treatment.

Surgical care may be necessary in stage 2 or 3 neurotrophic keratopathy. Such treatment has 3 goals, as follows:

  • Protect the epithelium by lid closure
  • Close a persistent epithelial defect
  • Repair a deep ulceration

Inpatient care

Patients with stage 3 neurotrophic keratopathy should be hospitalized for daily follow-up care until significant improvement is seen.


Consult a neurologist if the cause of corneal hypesthesia is not apparent or if any associated neurologic deficits are present.[12]


Patients with stage 1 neurotrophic keratopathy can be monitored on an outpatient basis every 3-7 days.

Patients with stage 2 disease should be monitored on an outpatient basis every 1-2 days until improvement is seen, then every 3-5 days until resolution.


Medications to avoid in patients with neurotrophic keratopathy are as follows:

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

Pharmacologic Therapy

Treatment for stage 1 neurotrophic keratopathy is as follows:

  • Topical lubrication with preservative-free artificial tears, gels, and ointments
  • Discontinuation of any topical ocular therapies, especially those that can decrease corneal sensitivity (eg, timolol, betaxolol, sulfacetamide, diclofenac, ketorolac) or that contain preservatives[13]
  • Reevaluation of 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 qod) can reduce the amount of mucus produced
  • Weyns et al proposed scleral contact lenses as a valid long-term alternative to standard treatment options in patients with neurotrophic keratopathy.[14]
  • Gaudilla et al note 20% autologous topical serum is an effective treatment for stages 1 and 2 neurotrophic keratopathy.[15]
  • Lee and Kim reported that oral nicergoline helped heal corneal epithelial defects among patients who did not respond to conventional therapy. Additionally, in patients treated with nicergoline, levels of tear nerve growth factors were higher than levels before treatment.[16]

Stage 2 treatment 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
  • Patients with stage 2 disease are more likely to require surgical intervention than are those with stage 1 disorder

Treatment for stage 3 neurotrophic keratopathy is as follows:

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

Surgical Repair of Eyelids, Epithelial Defects, and Ulcerations

Closure of the eyelids

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

Repair options for such lesions include the following[17] :

  • Conjunctival flap - Effective, but poor cosmetic and visual result[18]
  • Amniotic membrane transplantation[19]

Repair of a deep ulceration

The following can be used in ulceration repair:

  • Lamellar keratoplasty
  • Penetrating keratoplasty - For large defects
  • Multilayer amniotic membrane transplantation - Has been used in defects as deep as 90% of the depth of the stroma[20, 21]
  • Cyanoacrylate glue with a soft bandage contact lens - For defects smaller than 2 mm
Contributor Information and Disclosures

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

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

Disclosure: Partner received salary from Medscape/WebMD for employment.


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, American Medical Association

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, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.


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.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director 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; RPS Ownership interest Other; EyeGate Pharma Consulting fee Consulting; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting; Merck Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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

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

  3. Groos EB. Neurotrophic keratitis. 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. 1980 Jun. 89(6):795-802. [Medline].

  5. Okada Y, Reinach PS, Kitano A, Shirai K, Kao WW, Saika S. Neurotrophic keratopathy; its pathophysiology and treatment. Histol Histopathol. 2010 Jun. 25(6):771-80. [Medline].

  6. Hauck MJ, Harold Lee H, Timoney PJ, Shoshani Y, Nunery WR. Neurotrophic Corneal Ulcer After Retrobulbar Injection of Chlorpromazine. Ophthal Plast Reconstr Surg. 2011 Nov 11. [Medline].

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

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

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

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

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

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

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

  14. Weyns M, Koppen C, Tassignon MJ. Scleral contact lenses as an alternative to tarsorrhaphy for the long-term management of combined exposure and neurotrophic keratopathy. Cornea. 2013 Mar. 32(3):359-61. [Medline].

  15. Guadilla AM, Balado P, Baeza A, Merino M. [Effectiveness of topical autologous serum treatment in neurotrophic keratopathy]. Arch Soc Esp Oftalmol. 2013 Aug. 88(8):302-6. [Medline].

  16. Lee YC, Kim SY. Treatment of neurotrophic keratopathy with nicergoline. Cornea. 2015 Mar. 34 (3):303-7. [Medline].

  17. 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. 2007 Nov-Dec. 51(6):442-7. [Medline].

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

  19. 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. 2001 Dec. 85(12):1455-63. [Medline].

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

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

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

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

  24. 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):1174-80. [Medline].

  25. Lambiase A, Sacchetti M, Bonini S. Nerve growth factor therapy for corneal disease. Curr Opin Ophthalmol. 2012 Jul. 23(4):296-302. [Medline].

  26. 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. 1995 Mar. 119(3):288-94. [Medline].

  27. Grey F, Carley F, Biswas S, Tromans C. Scleral contact lens management of bilateral exposure and neurotrophic keratopathy. Cont Lens Anterior Eye. 2012 Aug 14. [Medline].

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

  29. 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. 2006 Feb. 141(2):299-307. [Medline].

  30. 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. 2006 Oct. 244(10):1345-9. [Medline].

  31. 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. 2008 Jul. 92(7):896-900. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.