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


Neurotrophic Keratopathy Clinical Presentation

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


A careful medical and surgical history should be obtained. Inquire about the following:

  • Previous surgical or traumatic injury to the trigeminal nerve, ocular surgery, or laser treatment, which may have damaged the ciliary nerves
  • Previous herpetic eye disease or a history of herpes zoster ophthalmicus [7]
  • Diabetes mellitus [8]
  • Use of topical medications, including potential abuse of topical anesthetics or nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Use of contact lenses
  • Exposure to chemical fumes

Physical Examination

Poor lid closure promotes exposure and can hasten progression, while the presence of scars from surgery, chemical burns, or thermal burns can provide clues as to the cause of the hypesthesia. Ectropion, lagophthalmos, or thyroid ophthalmopathy increase the risk of progression.

Cranial nerve examination

A cranial nerve examination can help to localize the cause of corneal hypesthesia. Pupillary abnormality may indicate pathology of the intraconal orbit or cavernous sinus or may reveal an Adie pupil. Dysfunction of cranial nerves III, IV, and VI may indicate an aneurysm or cavernous sinus pathology. Dysfunction of cranial nerves VII and VIII may indicate acoustic neuroma or injury from its resection.

Cranial nerve VII function should be assessed not only because of its value in localizing the cause of hypesthesia but also because of its prognostic value.

Ocular surface examination

The function of the tear film should be carefully examined for its impact on the management of neurotrophic keratopathy.[10, 11] Corneal sensitivity should be assessed as well; to do so, a piece of twisted cotton or the corner of a tissue is used.


A Cochet-Bonnet esthesiometer is a device that can give a quantitative measurement of corneal sensitivity, a determination that is diagnostically and prognostically crucial.

The esthesiometer consists of a nylon filament, which can be extended from the device to different lengths and touched to the cornea until it bends or the patient responds. The small diameter of the instrument allows accurate testing of different areas of the cornea. The shorter the length of filament required, the less sensitive the cornea. In one study, only patients with readings of 2 cm or less developed epithelial sloughing and ulceration.

Slitlamp examination

Slitlamp examination may show indications of the underlying cause of corneal hypesthesia. These include herpetic epithelial disease, stromal scarring from previous infection, lattice or granular stromal dystrophy, and enlarged or beaded corneal nerves from leprosy.

Anterior segment examination

This may reveal iris atrophy from a prior herpetic infection or an anterior chamber inflammatory reaction.

Dilated funduscopy

Optic nerve swelling or pallor may indicate an orbital or retro-orbital lesion. Diabetic retinopathy could indicate the likelihood of diabetic neuropathy. Laser scars from panretinal photocoagulation may indicate ciliary nerve damage.

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.