OXERVATE® is a recombinant human nerve growth factor indicated for the treatment of neurotrophic keratitis (NK).

Prescribing Information

NK may be caused by corneal nerve damage1

Neurotrophic keratitis (NK) is a rare degenerative corneal disease, which may be caused by trigeminal nerve impairment, resulting in a cascade of effects that may include a breakdown of the corneal epithelium.2

Damage to corneal innervation may lead to a decrease in or total loss of corneal sensitivity—a hallmark of NK.2

This nerve damage impacts ocular surface homeostasis by disrupting the interplay between corneal nerves and corneal epithelial cells, which may lead to epithelial breakdown, including ulceration and, in severe cases, melting and perforation.1,3

OXERVATE has not demonstrated clinically significant change in corneal sensitivity in clinical studies.4

This image is for illustrative purposes only.

Etiologies

Injury or systemic conditions affecting corneal sensory innervation may lead to NK2,5-7

Ocular

  • Post-herpetic infection
  • Ocular surgery (eg, refractive surgery, cataract surgery, corneal transplant, vitrectomy)
  • Chronic ocular surface inflammation or injury (eg, dry eye disease)
  • Contact lens wear
  • Topical ophthalmic drug toxicity
  • Chemical and physical burns

Systemic

  • Diabetes
  • Multiple sclerosis
  • Vitamin A deficiency
  • Leprosy
  • Amyloidosis

CNS

  • Post-neurosurgical procedures
  • Stroke
  • Neoplasm
  • Aneurysms
  • Degenerative CNS disorders (eg, Parkinson’s)

Genetic/Congenital

  • Riley-Day syndrome
  • Goldenhar-Gorlin syndrome
  • Moebius syndrome
  • Familial corneal hypoesthesia

 

These images are for illustrative purposes only. These are not an exact representation of a patient. This list is not exhaustive.
PATIENT PRESENTATION

Patients with NK may not complain of symptoms due to decreased corneal sensitivity8

In the presence of more significant corneal involvement, patients with NK may experience blurry vision, while symptoms of ocular surface discomfort are uncommon.*8

*OXERVATE is not indicated for the treatment of the symptoms of NK.

CLINICAL PRESENTATION

NK presentation varies based on level of corneal damage2,9

NK manifests as corneal epithelial changes ranging from superficial punctate keratopathy (SPK) to persistent epithelial defects (PEDs) and ulcers, which may progress to stromal melting and corneal perforation9

The Mackie classification system is a commonly used grading system for NK, separating the disease into distinct stages based on severity2,9

Stage 1

Superficial punctate keratopathy (SPK)9

Stage 2

Persistent epithelial
defect (PED)9

Stage 3

Corneal ulcer9

In some cases, NK may be a progressive disease2,6,9

The image is for illustrative purposes only. This is not an exact representation of a patient, or a structure and function.

Fluorescein staining may be useful in assessing corneal epithelial damage in NK2:

Based on the Mackie classification2:

Stage 1 is characterized by2:

  • Punctate corneal epithelial fluorescein staining
  • Decreased tear breakup time
  • Staining of the inferior palpebral conjunctiva
Stage 2 is characterized by2:

  • Epithelial defect—usually oval and in the central/superior cornea
  • Defect surrounded by a rim of loose epithelium
  • Edges may become smooth and rolled
  • Stromal swelling with folds in the Descemet’s membrane
Stage 3 is characterized by2:

  • Stromal lysis/melting
  • May result in perforation
Diagnosis

Diagnosis of NK includes history, clinical examination, and diagnostic tests2,9

An assessment of etiologies is part of the identification process of NK1

Select NK etiologies include2,5-7:
  • Post herpetic infection (HZV/HSV)
  • Chronic ocular surface inflammation or injury (eg, dry eye disease)
  • Contact lens wear
  • Ocular surgery
  • Topical ophthalmic drug toxicity
  • Diabetes
  • Stroke
  • Multiple sclerosis

A complete slit lamp examination allows for evaluation of corneal and conjunctival changes2,9

Assessment of corneal sensation is a fundamental part of the diagnosis of NK2

Clinically, corneal sensation may be assessed by using a “wisp” of cotton2
When the cotton thread touches the cornea, normal subjects show a blink reaction and can describe the sensation of touch, while patients with loss of corneal sensitivity do not react, or display reduced blinking/sensation to the stimulus.2,9
Or (semi-)quantitatively, measured by the Cochet-Bonnet esthesiometer2
The nylon filament of the Cochet-Bonnet esthesiometer can be set to different lengths, touching the cornea to elicit a blink or a patient response.9

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For US healthcare professionals only.

Important Safety Information

WARNINGS AND PRECAUTIONS

Contact lenses, either therapeutic or corrective, should be removed before applying OXERVATE. Contact lenses may be reinserted 15 minutes after OXERVATE administration.

Eye Discomfort, such as eye pain, that can be mild to moderate can occur with OXERVATE. Patients should contact their health care provider if a more serious eye reaction occurs.

ADVERSE REACTIONS

The most common adverse reaction with OXERVATE (~16%) was eye pain. Other adverse reactions with OXERVATE (1% to 10%) included corneal deposits, foreign body sensation, ocular hyperemia, ocular inflammation, photophobia, tearing, and headache.

Please read the full Prescribing Information for OXERVATE.

References: 1. Mastropasqua L, Massaro-Giordano G, Nubile M, Sacchetti M. Understanding the pathogenesis of neurotrophic keratitis: the role of corneal nerves. J Cell Physiol. 2017;232:717-724. 2. Dua HS, Said DG, Messmer EM, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107-131. 3. Ruiz-Lozano RE, Hernandez-Camarena JC, Loya-Garcia D, Merayo-Lloves J, Rodriguez-Garcia A. The molecular basis of neurotrophic keratopathy: Diagnostic and therapeutic implications. A review. Ocul Surf. 2021;19:224-240. 4. OXERVATE® (cenegermin-bkbj) ophthalmic solution 0.002% (20 mcg/mL) [US package insert]. San Mateo, CA: Dompé U.S. Inc.; 2024. 5. Choi CJ, Liu L, Qian Y, Herrinton LJ. Neurotrophic keratopathy: clinical presentation and outcomes in 354 eyes in a community-based population. Eur J Ophthalmol. 2024;34(4):1085-1094. 6. Saad S, Abdelmassih Y, Saad R, et al. Neurotrophic keratitis: frequency, etiologies, clinical management and outcomes. Ocul Surf. 2020;18:231-236. 7. Roth M, Dierse S, Alder J, Holtmann C, Geerling G. Incidence, prevalence, and outcome of moderate to severe neurotrophic keratopathy in a German tertiary referral center from 2013 to 2017. Graefes Arch Clin Exp Ophthalmol. 2022;260:1961-1973. 8. Vera-Duarte GR, Jimenez-Collado D, Kahuam-López N, et al. Neurotrophic keratopathy: general features and new therapies. Surv Ophthalmol. 2024;69(5):789-804. 9. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571-579.