CASE STUDY

Sight-Threatening Dry Eye

BY JEFFREY P. GILBARD, M.D.

A 25-year-old Caucasian woman was referred to the office with "severe dry eyes" and decreased vision in the left eye. The ocular history consisted of sandy-gritty eye irritation in both eyes associated with a decrease in vision in the left during the past year.

Five months ago, the inferior and superior puncta were occluded in both eyes, which only provided brief and limited relief of symptoms. The patient was previously treated with a series of different over-the-counter ocular surface lubricants that failed to improve her condition. The patient’s medical history was significant for endometriosis (which was treated with gonadotropin-releasing hormone [GnRH] analogue) and salivary gland hypofunction based on exam and flow testing.

The patient was using Refresh PM ointment (Allergan, Irvine, Calif.), pressure patching of the left eye and moist chamber spectacles. The patient reported that in the absence of the patch, corneal defects, at varying locations, continually reappeared in the left eye.

The exam findings showed BCVA of 20/25 OD and 20/60 OS. On slit-lamp examination, tear film volume was decreased in both eyes yet had a "watery" quality. There was greater mucous debris in the tear film of the left eye than the right eye.

All four puncta were occluded. The lid margins appeared clean and sharp. The lashes were clean. There were no visible meibomian gland orifices. Eversion of the lower lids in both eyes found that the meibomian glands were virtually absent (Figure 1). The conjunctiva was quiet with the exception of a mild papillary reaction of the superior tarsal conjunctiva in the left eye. Both the nasal and temporal bulbar conjunctiva stained with fluorescein and rose bengal in the exposure zones of both eyes.

Both corneas were transparent and compact. The right cornea stained inferiorly, and the left eye showed dense and diffuse staining with a frank corneal epithelial defect off-center at 2 o’clock (Figure 2). Cochet-Bonnet esthesiometer (Luneau Ophthalmologie, Chartres, France) testing revealed that corneal sensation was intact in both eyes.

Figure 1. No visible meibomian gland orifices: Eversion of the lower lids in both eyes showed atresic meibomian glands.

The patient had been seen by multiple ophthalmologists for her condition and had a folder of laboratory results. Review revealed normal serum levels for testosterone, progesterone, estriol and estrone. Erythrocyte sedimentation rate was 16. The antinuclear antibody was less than 1:40. The patient was also negative for anti-SSA (Ro), anti-SSB (La) and rheumatoid factor antibodies. The rapid plasma reagent was non-reactive. The patient was also negative for hepatitis B. The complete blood count, electrolytes and liver function tests were all within normal limits. The only remarkable lab test result was slightly elevated total serum cholesterol at 232 mg/dL.

Diagnosis and Treatment

This patient was diagnosed with congenital atresia of the meibomian glands in both eyes in the context of a forme fruste version of ectodermal dysplasia syndrome. One German study involving 36 patients with ectodermal dysplasia found that more than 94% of these patients suffered from dry eye symptoms. In addition, more than 95% had absence of meibomian glands confirmed by meibomoscopy.

Figure 2. Corneal defect: Left eye showed dense and diffuse staining with a frank comeal epithelial defect off-center at 2 o’clock.

There is an additional report from Japan of a patient with ectodermal dysplasia in which transillumination of the lids show the atresia of meibomian glandular structures, and interferometry reveals a deficient tear film lipid layer, shortened tear break-up time and increased tear evaporation.

For the patient in this case, the slit-lamp exam found absent meibomian gland orifices and virtual absence of the meibomian glands. The meibomian gland atresia was later confirmed by meibomoscopy (Figure 3). A tear film that appears watery is a sign of lipid layer loss.

This patient did not have typical meibomian gland dysfunction resulting from meibomitis. Note that this patient’s lids were thin, smooth and free of the signs of chronic inflammation. A patient with meibomian gland orifice closure from chronic meibomitis would have thickening of the lid, with relatively large telangectatic blood vessels crossing the lid margin. Beneath the tarsal conjunctiva there would be obliteration of the meibomian gland pattern rather than absence of the glands.

Figure 3. Meilbomoscopy results: Meibomoscopy confirms atresia of the meibomian glands.

The non-healing corneal defects seen in severe dry eye result from a depletion of corneal glycogen levels. Normal corneal anatomy depends upon the mitosis of stem cells at the limbus and the movement of these cells centripitally, powered by corneal glycogen, toward the center of the cornea. Central corneal cells normally undergo apoptosis, programmed cell death, and are replaced by these new cells. Increased tear film osmolarity depletes corneal glycogen in dry eye disorders, and in severe dry eye glycogen levels become seriously depleted, leading to non-healing corneal defects.

The goal of treatment was to reduce elevated tear film osmolarity by reducing evaporation and topically "osmo-correcting" the tear film. Corneal healing in the left eye was achieved by decreasing evaporation with a Boston gas-permeable scleral contact lens (The Boston Foundation for Sight, Needham, Mass.) used with preservative-free TheraTears (Advanced Vision Research). Hypotonic TheraTears was used under the lens to promote healing by lowering elevated tear film osmolarity, while providing the electrolytes needed for ocular surface growth, maintenance and repair. The tearmatched electrolyte balance of TheraTears also avoided the medicamentosa and glycogen depletion associated with electrolyte-imbalance toxicity.

After the left cornea had remained intact for several months, the scleral lens was discontinued, and the patient was placed on TheraTears lubricant eye drops, six times per day in the right eye and every hour inn the left eye. TheraTears was gradually tapered to q.i.d. and then to b.i.d. daily in both eyes with maintenance of clear and intact corneas. TheraTears has been shown to restore corneal glycogen levels in experimental models of dry eye and, based on this case, appears to do the same in dry eye patients. OM

Suggested Reading

Albietz J. Dry eye: An update on clinical diagnosis, management and promising new treatments. Clin Exp Optom 2001;84:4-18.

Gilbard JP, Rossi SR. An electrolyte-based solution that increases corneal glycogen and conjunctival goblet-cell density in a rabbit model for keratoconjunctivitis sicca. Ophthalmology 1992;99:600-604.

Gilbard JP, Rossi SR, Heyda KG. Ophthalmic solutions, the ocular surface, and a unique therapeutic artificial tear formulation. Am J Ophthalmol 1989;107:348-355.

Kaercher T. Ocular symptoms and signs in patients with ectodermal dysplasia syndromes. Graefes Arch Clin Exp Ophthalmol 2004;242:495-500.

Kuwabara T, Perkins DG, Cogan DG. Sliding of the epithelium in experimental corneal wounds. Invest Ophthalmol 1976;15:4-14.

Matsumoto Y, Dogru M, Goto E, Endo K, Tsubota K. Increased tear evaporation in a patient with ectrodactyly-ectodermal dysplasia-clefting syndrome. Jpn J Ophthalmol 2004;48:372-375.

Jeffrey P. Gilbard, M.D., is clinical assistant professor of ophthalmology at Harvard Medical School, director of the Dry Eye and Ocular Surface Disease Clinic at the New England Eye Center and founder, chief executive officer and chief scientific officer for Advanced Vision Research. Dr. Gilbard can be reached at 660 Main St., Woburn, Mass. 01801; jgilbard@theratears.com.