Introduction

The cornea derives its sensations through the Trigeminal nerve. Loss of its function causes a sequence of corneal epithelium changes, ultimately leading to ulceration, and is termed Neurotrophic keratitis (NK). The term ‘trophus’ signifies nutrition that is contributed by the Trigeminal nerve.[1] According to Mackie’s classification,[2] the initial stages of NK are characterized by corneal epithelial irregularities and Gaule spots, which later form persistent epithelial defects and finally ulceration and perforation. Common etiologies include Herpetic eye disease, diabetes, Leprosy, intracranial pathologies, and surgical procedures.[3] Characterized by corneal anesthesia and thus, painless ulceration, Neurotrophic ulcers tend to be circular with a clean base and smooth rolled-out edges.

Nasopharyngeal carcinoma (NPC) is a rare locally aggressive malignancy arising from the nasopharynx with a propensity to involve and invade neighboring structures. With a probable underlying viral etiology,[4] NPC commonly presents with nasal and otological symptoms. Due to its proximity, the orbit is frequently involved in NPC [5] through the pterygopalatine fossa and orbital apex. In this report, we present orbital apex involvement that causes corneal anesthesia, leading to NK in a patient with locally advanced NPC.

Case Report

A 65-year-old man presented to us with two months of redness and watering in his left eye with no history of pain. A local ophthalmologist had prescribed topical Moxifloxacin, Homatropine, Natamycin, and Tobramycin for this condition. He had been receiving chemotherapy for a year for left-sided nasopharyngeal carcinoma, and five months prior, he had experienced drooping of the left upper lid. Examining the right eye, the findings for the anterior and posterior segments, extraocular motility, and visual acuity all seemed normal. Visual acuity in the left eye was only a perception of hand movements.

In the left eye, axial proptosis (4mm), complete ptosis with frontalis overaction (Fig 1A), and total external ophthalmoplegia were noted. The conjunctiva was congested and the cornea showed a central 6.5mm circular corneal ulcer with clear margins. There was a 2mm hypopyon and the pupil was 6mm in size. (Fig 1B and 1C) The lens was clear, but the fundus could not be visualized. Corneal sensations were absent. Based on these clinical findings, we made a diagnosis of superior orbital fissure syndrome with stage III NK according to Mackie classification.[2]

After careful corneal scraping, we placed a bandage contact lens to facilitate further healing. We started on preservative-free sodium hyaluronate 0.1% eyedrops every 2 hours along with fortified Vancomycin eyedrops and stopped the topical antifungals. The corneal scrapings did not yield any microbiological results. Also, we ordered a computed tomography (CT) scan of the head and the orbit to identify tumor recurrence. CT scan confirmed a soft tissue mass in the left superior orbital region and the apex, abutting the cavernous sinus. (Fig 2) We referred the patient to a medical oncologist who staged the tumor as T4N2M0 (TNM staging of Nasopharyngeal carcinoma) and advised him of palliative radiotherapy of 20 Gy units in five sittings. After two months, the patient revisited us and showed marked improvement in ptosis, decrease in proptosis, improvement of extraocular motility,(Fig 3), and return of corneal sensations. The ulcer had healed well with the formation of a macular opacity.

Fig 1A: Left eye showing axial proptosis (4mm), complete ptosis with frontalis overaction, and total external ophthalmoplegia. Fig 1B and 1C: Conjunctival congestion, central 6.5mm circular corneal ulcer with clear margins, a 2mm hypopyon, pupil 6mm in size

Fig 2: CT scan showing a soft tissue mass in the left superior orbital region and the apex, abutting the cavernous sinus.

Fig 3: Decrease in proptosis, improvement of extraocular motility at two months follow-up

Discussion

The orbital apex is the conduit for the passage of an important neurovascular bundle that supplies the structures of the eye. It has the (a) optic canal which transmits the optic nerve and central retinal vessels and (b) the superior orbital fissure which transmits the oculomotor, trochlear, trigeminal, and abducens nerve. The superior orbital fissure syndrome includes total ophthalmoplegia, loss of corneal sensations, pupillary dilatation, and ptosis. In orbital apex syndrome, there is an additional component of loss of vision owing to the involvement of the optic nerve. Common causes of orbital apex syndrome include infectious, inflammatory, vascular, and carcinomatous disorders.[6]

Neurotrophic keratitis (NK) is a degenerative condition that results from a decrease or loss of corneal sensations accompanied by a loss of trophic factors, decreased healing, and impaired metabolism of the corneal epithelial cells.[7] In our patient, the cause for the loss of trigeminal function was the recurrent nasopharyngeal carcinomatous lesion compressing the structures at the orbital apex. Thus, despite having a florid corneal ulcer, the patient remained pain-free. It is advisable to test corneal sensations in all patients with painless epithelial defects and those showing no improvement despite 14 days of treatment.[8] Removal of the offending factor may not be possible in all cases of NK due to permanent damage to the corneal nerves.

Nasopharyngeal carcinoma causing ophthalmic repercussions is not an uncommon finding and NK unresponsive to treatment has been reported in such cases, due to an advanced form of the disease.[9] However, on the other end of the spectrum, the resolution of ophthalmoplegia and return of corneal sensations has also been reported.[10] Timely intervention in the form of radiotherapy helped in causing tumor remission and healing of the NK.

Conclusion

Nasopharyngeal carcinoma is a locally aggressive tumor with frequent orbital invasion. Spread of the tumor superiorly can cause superior orbital fissure syndrome characterized by total ophthalmoplegia with loss of corneal sensation, leading to Neurotrophic keratitis. With timely treatment of the tumor in the form of chemotherapy and radiation, there is a possibility to reverse the ophthalmic consequences.

References

1. Müller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76:521–542.
2. Mackie I. Neuroparalytic keratitis. In: Fraunfelder F, Roy F, Meyer S, editors. Current Ocular Therapy. 1995. p. 452–4.
3. Dua HS, Said DG, Messmer EM et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018 Sep;66:107-131. doi: 10.1016/j.preteyeres.2018.04.003.
4. Young LS, Dawson CW. Epstein-Barr virus and nasopharyngeal carcinoma. Chin J Cancer. 2014 Dec;33(12):581-90. doi: 10.5732/cjc.014.10197.
5. Lee KY, Seah LL, Tow S, Cullen JF, Fong KS. Nasopharyngeal carcinoma with orbital involvement. Ophthalmic Plast Reconstr Surg. 2008 May-Jun;24(3):185-9. doi: 10.1097/IOP.0b013e318171a629.
6. Badakere A, Patil-Chhablani P. Orbital Apex Syndrome: A Review. Eye Brain. 2019 Dec 12;11:63-72. doi: 10.2147/EB.S180190.
7. Semeraro F, Forbice E, Romano V et al. Neurotrophic keratitis. Ophthalmologica. 2014;231[4):191-7
8. Vaidyanathan U, Hopping GC, Liu HY, et al. Persistent corneal epithelial defects: a review article. Med Hypothesis Discov Innov Ophthalmol. 2019;8:14
9. Sato T, Sugioka K, Kodama-Takahashi A, Fukuda M, Mishima H, Shimomura Y. A Case of Neurotrophic Keratopathy Associated with Nasopharyngeal Carcinoma. Case Rep Ophthalmol. 2018 Feb 16;9(1):114-118.
10. Kamath GM, Nayak MK, Gupta M, D′Souza S, Kamath MM. Resolution of total ophthalmoplegia following treatment in a case of nasopharyngeal carcinoma: A case report. Journal of Clinical Ophthalmology and Research. 2015. 3(3):148-150.