A Case of Neurotrophic Keratitis:

Is Afatinib The Culprit?

Fathin AR1, Farah NF1, Juliana MT1, Mokhlisoh A1,
1
Department of Opthalmology, Hospital Selayang, Selangor Darul Ehsan.

PURPOSE
Neurotrophic Keratitis (NK) is a corneal
degenerative disease typically presenting with
reduced or absent corneal sensitivity that may lead
to epithelial defect, stromal ulceration, and
eventually corneal perforation. Afatinib is a tyrosine
kinase inhibitor used as treatment in various solid
tumors. However, in year 2018 there was a first
reported case of cornea adverse event in a patient
consuming Afatinib. [1]

Figure 1 : Anterior segment photo of Figure 2 : Anterior segment photo of

METHODS patient’s left eye with upper lid papilloma, patient’s left eye focusing on anterior
This is a case report of neurotrophic keratitis conjunctival redness, corneal thinning,
vascularization and multiple feeder
chamber hypopyon

following Afatinib usage in our center. vessels.

Theories of Afatinib-associated keratitis circles

RESULTS
around changes in corneal epithelium due to
A 67-year-old lady presented with left eye (LE)
the alterations in EGFR signaling. EGFR is
corneal opacity and blurring of vision for 1 year
expressed in basal cells of limbal and
which progressively worsened within 3 months. She
conjunctival epithelia. The Epidermal Growth
was initially diagnosed with brain cancer in 2016
Factor (EGF) ligand promotes migration and
which unfortunately then metastasized to the lungs.
proliferation of epithelial cells which aids
She underwent primary brain surgery in 2016 and
corneal wound healing. Endogenous EGF
completed multiple cycles of chemotherapy and
produced by lacrimal glands is imperative in
radiotherapy. She was then started on oral Afatinib
ocular surface homeostasis as evidenced by
40mg daily, and is on a regular review with the
its increased production following any corneal
respiratory clinic.
epithelial injury. The lower nerve fiber density
[2]

Upon presentation, her LE visual acuity was caused by EGFRi can lead to persistent
counting finger, with normal intraocular pressure epithelial damage, reduction in corneal
and marked absence of cornea sensation. Other thickness and progression to corneal
findings showed congested conjunctiva, paracentral perforation.[2] Studies in rats treated with
cornea epithelial defect measuring 2.6mm vertically EGFRi demonstrated reduced epithelial
by 3.6mm horizontally with infiltrates, associated thickness, dose-dependent reductions in
with central thinning and vascularization. Anterior epithelial wound healing and decreased
chamber showed cell activity of 4+, streak of epithelial cell division. [3]

hypopyon and no view of the posterior segment. LE

B-scan showed clear vitreous. Blood parameters, CONCLUSION
cornea swab culture and sensitivity (C&S) were A thorough history taking is detrimental in
unremarkable diagnosing NK. Ophthalmologists need to be
equipped with the knowledge of side effects of
She was then referred to co-manage with Cornea various drugs on the cornea when handling
Team. Gutt cefuroxime and gutt gentamicin was cases of neurotrophic keratitis especially in
commenced, with prophylactic gluing and bandage absence of known risk factors.[2] A prompt
contact lens (BCL) application. Cyclosporin treatment should be initiated in order to
eyedrops were subsequently added and her corneal prevent further complications. It is
ulcer has healed to a corneal scar with latest vision quintessential for ophthalmologists,
of hand movement. oncologists, and general practitioners to be
aware of association between Afatinib and
DISCUSSION ulcerative keratitis and monitor patients
The main molecular target of Afatinib is Epidermal appropriately.
growth Factor Receptors (EGFR). These EGFR- REFERENCES
inhibitors (EGFRi) target tyrosine kinase domains, 1. McKelvie, J., McLintock, C. and Elalfy, M. (2018) “Bilateral ulcerative keratitis associated with
afatinib treatment for non–small-cell lung carcinoma,” Cornea, 38(3), pp. 384–385.

hampering the constant activation of their 2. Gozzi, F. et al. (2021) “Bilateral severe corneal ulcer in a patient with lung adenocarcinoma
treated with gefitinib,” Case Reports in Ophthalmology, 12(1), pp. 288–292.

downstream signaling pathways and the
consequent uncontrolled cell proliferation occuring
in malignancy.[1,2]
3. Nakamura, Y., Sotozono, C. and Kinoshita, S. (2001) “The epidermal growth factor receptor
(EGFR): Role in corneal wound healing and homeostasis,” Experimental Eye Research, 72(5), pp.
511–517..