CASE STUDY

Asymmetric Dry Eye

Neurological injury is the culprit.

BY WILLIAM G. CRANE, JR, M.D., AND MAHDI M. BASHA, D.O.

Patient KD presented in March 2008 after suffering for years with dry eye, especially in her right eye. The 48-year-old white female had been seen by several ophthalmologists with no relief and had even ended up quitting her job as a bartender in 1996 because her eyes kept swelling shut. In addition to the discomfort of dry eye, her complaints included decreased near vision ("difficulty reading") in the right eye.

KD has a history of other medical problems including osteoarthritis, Crohn's disease, neurodermatitis, hypertension and depression. In 1982, she experienced a fracture of cervical vertebrae C3-C4. She has been on a variety of medications which can cause dry eye, including paroxetine, alprazolam, hydroxyzine and hydrochlorothiazide. Sjögren's disease was suspected in 2002 but ruled out by negative laboratory test results.

On initial presentation KD was using artificial tears OD every few minutes. Her right eye exhibited upper lid ptosis and severe dry eye. A review of her family and social history and review of systems indicated that none of these were contributory. Visual acuity without correction was OD 20/50 PH with pinhole 20/25, and OS 20/20. Near vision without correction was OD < Jaeger card J6 and OS J6. Her pupillary function, extraocular movement and confrontation visual fields were normal.

Slit lamp examination revealed 2+ erythema in the right upper lid and moderate injection (2+) with a tear breakup time of less than 1 second OD, and epithelial punctuate keratitis (3+ EPK OD, 2+ EPK OS). Iris, anterior chamber, lens, IOP and fundae appeared normal.

Our initial diagnosis was severe dry eye in OD and moderate dry eye OS. The initial treatment plan was to stop artificial tear use due to possible toxicity and to prescribe erythromycin ointment and cyclosporine A (Restasis, Allergan). We also recommended OTC reading glasses.

At 10-day follow-up visit, KD reported the glasses were helpful but still complained of photophobia, burning and itching in the right eye. Visual acuity was 20/25 OD. Epithelial punctuate keratitis and conjunctival injection were still present, and the inflammation was worse (1+ cell/2+ flare). We suspected Thygeson's superficial punctuate keratitis and prescribed prednisolone acetate OD and Restasis OU b.i.d.

At four weeks, KD complained of pain and filamentary keratitis ("stringy mucous") OD and had resorted to patching the eye. We prescribed dexamethasone-tobramycin ointment OD and continuation of Restasis OU.

Five weeks later, the anterior chamber reaction was gone but the right eye was still severely dry ("my eye hurts and feels like sand is in it"). Visual acuity was no better (20/30 OD) and filaments (2+) were still present. The left dry eye, which was attributable to her age/gender and medications taken, had responded to Restasis. We performed inferior punctal cautery OD.

When KD returned at 2.5 months, there was no change in her condition and visual acuity was 20/25 OD. At this point, suspecting lacrimal gland dennervation because of her cervical spine fracture, I performed a more thorough examination of the cranial nerves. Light touch was intact to the corneas bilaterally, indicating intact trigeminal nerves. The lids had palpebral fissures measuring 7mm and 11mm respectively. Administration of phenylephrine 2.5% resulted in raising the right lid to the level of the left upper lid, indicating sympathetic denervation of Mueller's muscle on the right. Levator function was intact OU, and the margin reflex distance was 0.5mm and 3mm respectively. Inferior scleral show was -2mm OU.

Finding the Source

To understand the relationship of the central nervous system and dry eye in this patient, it is helpful to review the neuroanatomy of tear production (Figure 1). The accessory lacrimal glands of Krause and Wolfring are located in the conjunctival stroma and are thought to be responsible for baseline tear production. The main lacrimal gland is located in the anterolateral portion of the roof of the orbit. This gland is responsible mainly for reflex tearing, but was found recently to contribute to basal tear secretion also. Autonomic nerves responsible for both baseline and reflex lacrimation and originate at spinal level T1 near the patient's former site of injury.

Figure 1. Neuroanatomy of tear production.

The parasympathetic nerve supply originates from the lacrimal nucleus of the facial nerve in the pons. This nerve gives off the greater petrosal nerve just distal to the geniculate ganglion and carries the parasympathetic secretomotor fibers through the pterygoid canal to the pterygopalatine ganglion. Here they synapse, and postganglionic fibers join the fibers of the maxillary nerve, which travels through the inferior orbital fissure. After traversing this opening, the parasympathetic secretomotor fibers branch off with the zygomatic nerve and then branch off again, joining with the lacrimal branch of the ophthalmic division of the fifth cranial nerve, which innervates the lacrimal gland

The sympathetic nerves originate in the spinal cord T1 region then synapse in the superior cervical ganglion. The postganglionic fibres travel as a periarteriolar plexus with the middle meningeal artery, before they merge and form the deep petrosal nerve, which joins the greater petrosal nerve in the pterygoid canal. Together, greater petrosal and deep petrosal nerves form the nerve of the pterygoid canal (vidian nerve) and reach the pterygopalatine ganglion in the pterygopalatine fossa. In contrast to their parasympathetic counterparts, sympathetic fibers do not synapse in the pterygopalatine ganglion, having done so already in the sympathetic trunk. However, they continue to course with the parasympathetic fibers innervating the lacrimal gland.

We concluded that KD's ptosis OD was due to denervation of Muller's muscle, which helped explain the reduced tear production leading to her asymmetric dry eyes. The tear glands and Mueller's muscle share a common sympathetic efferent innervation. Rather than being an inflammatory problem, which Restasis would have treated, this was a problem with innervation of the tear glands. The solution required providing extra tears or preserving the tear film.

An Ideal Solution

We believed that the hydroxypropyl cellulose ophthalmic insert Lacrisert (Aton Pharma, Lawrenceville, NJ) might be a successful treatment for this patient's right eye. The sustained-release insert is administered into the inferior cul-de-sac, where it dissolves to provide lubrication and protection to the surface of the eye over the course of the day, a simpler regimen that frequent instillations of artifical tears. We prescribed a Lacrisert q.d./b.i.d. for the right eye.

At her 3-month follow-up, KD reported experiencing some relief and less pain. Examination revealed some trace filaments and EPK(2+) in the right eye. I instructed the patient to discontinue Restasis in the right eye.

At 4 months, the patient reported substantial improvement and was enthusiastic, referring to the Lacrisert therapy as "a Godsend" and commenting that it allowed her to resume wearing makeup again. There was much less erythema and edema of the right upper lid. The filaments were gone and the EPK had improved (OD 1+ EPK, OS trace). Schirmer tests confirmed severe lack of tear production in the right eye (Schirmer I OD 0.5 mm, OS 12 mm, Schirmer II OD 0 mm, OS 8 mm). The patient was continued on Lacrisert therapy.

Lacrisert has been FDA-approved for use in patients with moderate to severe dry eye and available by prescription for more than two decades. Recently increased distribution and marketing efforts by Aton Pharma have resulted in increased profile and availability of the product. OM