• COVID-19
  • Biosimilars
  • Cataract Therapeutics
  • DME
  • Gene Therapy
  • Workplace
  • Ptosis
  • Optic Relief
  • Imaging
  • Geographic Atrophy
  • AMD
  • Presbyopia
  • Ocular Surface Disease
  • Practice Management
  • Pediatrics
  • Surgery
  • Therapeutics
  • Optometry
  • Retina
  • Cataract
  • Pharmacy
  • IOL
  • Dry Eye
  • Understanding Antibiotic Resistance
  • Refractive
  • Cornea
  • Glaucoma
  • OCT
  • Ocular Allergy
  • Clinical Diagnosis
  • Technology

Neurotrophic keratopathy: Finding different treatments


Slit-lamp examination

Impairment or total absence of corneal sensation are the hallmarks of neurotrophic keratopathy, an uncommon degenerative disease. Depending on the severity of the disease, the clinical manifestations can range from punctate epitheliopathy, persistent epithelial defects, to corneal perforation.

A specific therapeutic approach is required to address the disease presentation, which is described by Mackie’s classification of three stages of severity. The clinical presentation is always the same regardless of the etiology, according to Francisco C. Figueiredo, MD, PhD, FRCOphth.

Related: Compound eye as treatment for neurotrophic keratitis 

Stage I is characterized by epithelial hyperplasia and irregularity, haze, punctate keratopathy, superficial vascularization, and stromal scarring; stage II by a superior epithelial defect usually in the superior quadrant, with smooth and rolled edges of the defect, and stromal edema; and stage III corneal ulceration, stromal melting, and even perforation.

The causes of the disease are highly variable and range from genetic, ocular, neurological, and systemic, with herpes virus, post-surgical trigeminal nerve damage, chemical burns, and diabetes causing the preponderance of the cases, according to Dr. Figueiredo, professor of ophthalmology, Department of Ophthalmology, Newcastle University, Newcastle-upon-Tyne, United Kingdom.

Related: Facing challenge of corneal infection management in operated eyes

Diagnosis and management
Patients present with nonspecific complaints such as dryness, discomfort, photophobia, decreased vision, and worse symptoms upon awakening that are aggravated by environmental factors such as air conditioning and personal computers.

Slit-lamp examinations show findings similar to dry eye disease, i.e., decreased tear film breakup time, superficial punctate keratitis, and decreased blinking. Dr. Figueiredo noted that the clinical picture may progress to slow healing of the epithelial defect with smooth and rolled edges with or without stromal involvement. 

A diagnosis can be established by testing the corneal sensation using corneal esthesiometry in the central and peripheral parts of the cornea. Touching the cornea with a cotton swab is a qualitative test of sensation. 

The most widely used test is the Cochet-Bonnet direct contact test. This noninvasive test measures corneal sensitivity. In vivo confocal microscopy can provide quantitative and qualitative assessment of the corneal nerves and can show mild to total damage of the corneal nerves. A neurologic examination can provide a full assessment of the cranial nerves. 

Related: Doing justice to corneal irregularities 

Managing disease
Management requires grading of the disease stage and an array of medical and surgical interventions. 

Dr. Figueiredo noted that with stage I disease,  it is imperative to review the use of all the topical treatments, and discontinue most of them, particularly the ones with preservatives because of potential toxicities that can worsen the corneal surface. 

This may be combined with “unpreserved lubricants, i.e., artificial tears and ointments, and punctal plugs,” he said.

In stage II disease, he recommends the same approach as in stage I with the addition of prophylactic topical antibiotics; eyelid closure that includes tarsorrhaphy, taping, pads, or botulinum toxin; bandage contact lens; serum eye drops, including autologous/allogeneic; and amniotic membrane transplantation in some cases.

Stage III requires all the factors in stages I and II plus topical matrix metalloproteinase inhibitors to prevent collagen layer breakdown, tissue adhesives plus amniotic membrane plus bandage contact lens for small perforations, and surgery such as corneal gluing, tectonic lamellar or penetrating keratoplasty for larger perforations.

Related: Color-LED topography measures corneas consistently in analysis 

Newest treatments
The newest treatments include the use of ReGeneraTing Agent, which facilitates reconstruction of the extracellular matrix that will help tissue repair and regeneration. Cacicol (Thea Labs), a new matrix therapy to promote corneal healing, is currently in a clinical trial. However, the results are as of yet unpublished. 

Recombinant human nerve growth factor (rhNGF), a topical therapy applied six times daily for eight weeks, also is being used rather successfully in moderate to severe neurotrophic keratopathy that has been refractory to surgical treatment; the product was approved recently in the United States, and is available under the name Oxervate (cenegermin, Dompe). 

Direct corneal neurotization involves transplanting contralateral supraorbital and supratrochlear branches of the ophthalmic division of the trigeminal nerve. 

Related: Treating dry eye with recombinant human nerve growth factor  

Indirect neurotization involves using sural nerve transplantation that connects the contralateral branches of the ophthalmic division of the trigeminal nerve, Dr. Figueiredo explained.

Dr. Figueiredo described the case of a 24-year-old man who sustained severe ocular chemical burns bilaterally and underwent a series of repeated treatments that provided partial healing in the left eye and not in the right eye. 

According to Dr. Figueiredo, he began instilling Oxervate in the right eye of the patient and after only eight weeks was completely healed. 

Related: Neuropathic corneal pain: The new 'umbrella'

According to Dr. Figueiredo, rhNGF is promising and has shown extremely good results. 

“Neurotrophic keratopathy is a chronic, serious potentially blinding and refractory corneal degenerative disease that often poses significant treatment challenges, especially when complicated by other concurrent ocular comorbidities, such as exposure keratopathy, dry eyes, and limbal stem cell deficiency,” he concluded. “New treatments, such as rhNGF, neurotization, and matrix therapy are helpful and has completely changed our current treatment protocol.”

Read more by Lynda Charters 

Related Videos
Moving beyond the drop: CEO provides updates on Oyster Point's pipeline
© 2024 MJH Life Sciences

All rights reserved.