More than just dry eyes

Editor’s Note: Ophthalmology Times is pleased to announce Evan Warner, MD, of the University of Wisconsin, as the third-place winner of the publication’s 2014 Resident Writer’s Award Program, sponsored by Allergan. Dr. Warner’s submission is featured here.

The Ophthalmology Times Resident Writer’s Award Program is a unique recognition opportunity designed to promote excellence in Ocular Surface Disease education. It was created to acknowledge outstanding case identification and written presentation skills in ophthalmology residents.

Bradley Shoss, MD, of Washington University in St. Louis, is the first-place winner of the publication’s 2014 Resident Writer’s Award Program. Dr. Shoss’ winning submission-“Sniffing Up The Wrong Tree”-is featured at http://bit.ly/1xenlzd.

Seanna Grob, MD, MAS, of the Massachusetts Eye and Ear Infirmary at Harvard University, is the second-place winner. Dr. Grob’s submission-“A Pharmacological Approach to Dry Eye Syndrome in a Case of Graft-Versus-Host Disease (GVHD)”-is featured at http://bit.ly/1uKh1Pr.

To read all of the case study submissions in this year’s Ophthalmology Times Resident Writer’s Award Program, visit http://bit.ly/1tAgVVy.

Dr. WarnerBy Evan Warner, MD

A 16-year-old female was referred to The University of Wisconsin ophthalmology department for evaluation of dry eyes. She described both eyes as dry, scratchy, and painful; with itching and mucoid discharge. She reported that her vision was intermittently blurry in both eyes. These symptoms had been present for about 24 months, with minimal fluctuation in severity. At the time of presentation, she was using preservative-free artificial tears every 2 hours and a polyethylene glycol-based gel lubricant at night, each in both eyes.

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Her medical history was significant for longstanding eczema, for which she used a triamcinolone acetonide 0.1% topical cream. She denied frequent rhinorrhea, sneezing, asthma, or other systemic allergy symptoms. She had no other history of ocular problems and no family history of eye disease.

Over the past 2 years, she had followed regularly with a local optometrist, who diagnosed her with keratoconjunctivitis sicca and started her on multiple topical lubrication regimens. Silicone punctal plugs had been placed in both lower lids without improvement in symptoms, and the patient had them removed after three months due to epiphora. She felt her current regimen of lubrication was helpful, but did not resolve her symptoms.

Four months before presentation, she had been placed on a 3-week course of loteprednol 0.5% ophthalmic solution, which improved her symptoms during treatment, but control was quickly lost after discontinuing the drops.

Examination

At the time of her referral, ocular examination showed a best-corrected visual acuity of 20/20 in the right eye and 20/25 in the left eye. Pupils, motility, and IOP were unremarkable. Anterior segment examination revealed bilateral madarosis of the upper and lower lids, mild erythema of all four lid margins, and 3+ meibomian gland dysfunction (MGD). There was 2+ bulbar conjunctival injection and 2+ papillae on the tarsal conjunctiva of both eyes.

Fluorescein exam demonstrated 3-4+ confluent punctate epithelial erosions across the entire corneal surface bilaterally, and a tear break-up time of six seconds in each eye. The right eye had five small, cellular aggregates (Horner-Trantas dots) at the superior limbus. Dilated fundoscopic examination was unremarkable bilaterally.

Discussion and diagnosis

Although this patient’s primary symptomatic complaints, prominent MGD with tear film instability, and diffuse superficial punctate keratitis can call be seen in typical dry eye patients, her age, history of eczema, and prominent pruritus with mucoid discharge all point to an allergic etiology.

The spectrum of chronic allergic eye disease encompasses seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC), as well as the corneal-involving conditions vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). While there is crossover between all these entities, this patient’s severe corneal involvement, year-round symptoms, and history of atopy was deemed most consistent with AKC.

AKC was first described by Hogan in 1952.¹ It is best-defined as a chronic, non-seasonal, bilateral allergic ocular disease that involves the cornea, and occurs in association with other atopic disease including atopic dermatitis, asthma, or allergic rhinitis. Common symptoms include pruritis, tearing, mucoid discharge, pain, and blurry vision.

Eyelids may exhibit periorbital eczema, lid edema, lichenification, blepharitis/MGD, madarosis, and cicitricial changes. Conjunctiva may become injected or chemotic, and typically develops a tarsal micropapillary reaction with mucoid discharge. Horner-Trantas dots, aggregates of eosinophils and degenerated epithelial cells, may be seen near the limbus.

The corneal findings range from superficial keratopathy to pannus, scarring, shield ulcers, and thinning or perforation. There is a high rate of subcapsular cataract, particularly anteriorly.

Onset of AKC is typically between the teens and fifth decade of life, with chronic symptoms over many years, and often spontaneous resolution late in life. It has a prevalence of 1-8% in the adult population. ² The frequency in atopic dermatitis patients, which is roughly 11% of the U.S. population, ³ is reported most often between 20% to 40%², but as high as 77%.⁴

Pathogenesis of AKC is poorly understood and is thought to involve type I and type IV hypersensitivity reactions. Histologically, there are increased mast cells, eosinophils, and a high CD4/CD8 T-cell ratio in conjunctiva of AKC patients. ⁵ Their tears have elevated IgE, IFN-γ, and TNF-α; and low levels of secretory IgA compared with normal controls. ^6-8

Importantly, atopic diseases share an impairment of innate, cell-mediated immunity, which leads to increased susceptibility to skin and eye infection with Staphylococcus and the herpes simplex virus.⁹

Management of AKC can be complicated by secondary bacterial infections, HSV keratitis, and treatment-related complications such as steroid-induced glaucoma and cataract. For mild cases, lubrication, oral antihistamines, and topical mast cell stabilizer/antihistamine combinations can provide relief, along with standard treatment for associated MGD.

Topical steroids are successful at quieting exacerbations, but symptoms tend to recur quickly after taper. Especially in this young patient, long-term use of topical steroids carries significant risks, making them a poor choice for chronic management.

The most common and successful steroid-sparing agents for chronic control of AKC are the calcineurin inhibitors cyclosporine and tacrolimus, which block expression of IL-2 and inhibit the T-cell response. Topical cyclosporine 2% has been shown effective compared with steroid treatment,¹⁰ while lower concentrations have given mixed or poor results.^11-13 Topical tacrolimus as 0.03% ointment to the lid margins and 0.02% ophthalmic solution have repeatedly demonstrated substantial improvement in previously steroid-requiring AKC patients,^14-18 with no effect on IOP.¹⁹ This patient was placed on tacrolimus 0.02% ophthalmic suspension BID.

By 2 months out, her symptoms had resolved and she was using artificial tears an average of only twice daily. Exam revealed white and quiet conjunctiva, and only trace inferior punctate staining of the cornea.

Conclusion

This case demonstrates the importance of proper evaluation, diagnosis, and management of patients with suspected atopic keratoconjunctivitis. While AKC can present with a wide spectrum of symptoms, it is a common condition that is important to consider early, as proper treatment can achieve sustained symptomatic control, prevent vision-threatening corneal complications, and minimize treatment side effects.

References

       1. Hogan MJ. Atopic keratoconjunctivitis. Trans Am Ophthalmol Soc. 1952;50:265–281.

       2. Bielory B, Bielory L. Atopic dermatitis and keratoconjunctivitis. Immunol Allergy Clin North Am. 2010;30:323.

       3. Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the United States: data from the 2003 National Survey of Children's Health. J Invest Dermatol. 2011;131:67.

       4. Moscovici BK, Cesar AS, Nishiwaki-Dantas MC, et al. [Atopic keratoconjunctivitis in patients of the pediatric dermatology ambulatory in a reference center]. Arq Bras Ophtalmol. 2009;72:805.

       5. Montan PG, van Hage-Hamsten M. Eosinophil cationic protein in tears in allergic conjunctivitis. Br J Ophthalmol. 1996;80:556–560.

       6. Leonardi A, Curnow SJ, Zhan H, Calder VL. Multiple cytokines in human tear specimens in seasonal and chronic allergic eye disease and in conjuncttival fibroblast cultures. Clin Exp Allergy. 2006;36:777.

       7. Metz DP, Hingorani M, Calder VL, et al. T-cell cytokines in chronic allergic eye disease. J Allergy Clin Immunol. 1997;100:817.

       8. Leonardi A, De Dominicis C, Motterle L. Immunopathogenesis of ocular allergy: a schematic approach to different clinical entities. Curr Opin Allergy Clin Immunol. 2007;7:429.

       9. Tuft SJ, Kemeny DM, Dart JK, Buckley RJ. Clinical features of atopic keratoconjunctivitis. Ophthalmology. 1991;98:150.

       10. Hingorani M, Moodaley L, Calder VL, et al. A randomized, placebo-controlled trial of topical cyclosporin A in steroid-dependent atopic keratoconjunctivitis. Ophthalmology. 1998;105:1715.

       11. Akpek EK, Dart JK, Watson S, et al. A randomized trial of topical cyclosporin 0.05% in topical steroid-resistant atopic keratoconjunctivitis. Ophthalmology. 2004;111:476.

       12. Daniell M, Constantinou M, Vu HT, Taylor HR. Randomised controlled trial of topical ciclosporin A in steroid dependent allergic conjunctivitis. Br J Ophthalmol. 2006;90:461.

       13. Ebihara N, Ohashi Y, Uchio E, et al. A large prospective observational study of novel cyclosporine 0.1% aqueous ophthalmic solution in the treatment of severe allergic conjunctivitis. J Ocul Pharmacol Ther. 2009;25:365.

       14. Rikkers S, Hollard G, Drayton G, et al. Topical tacrolimus treatment of atopic eyelid disease. Am J Ophthalmol. 2003;135:297–302.

       15. Nivenius E, van der Ploeg I, Jung K, et al. Tacrolimus ointment vs steroid ointment for eyelid dermatitis in patients with atopic keratoconjunctivitis. Eye (Lond). 2007;21:968.

       16. Zribi H, Descamps V, Hoang-Xuan T, et al. Dramatic improvement of atopic keratoconjunctivitis after topical treatment with tacrolimus ointment restricted to the eyelids. J Eur Acad Dermatol Venereol. 2009;23:489.

       17. Miyazaki D, Tominaga T, Kakimaru-Hasegawa A, et al. Therapeutic effects of tacrolimus ointment for refractory ocular surface inflammatory diseases. Ophthalmology. 2008;115:988.

       18. Remitz A, Reitamo S. Long-term safety of tacrolimus ointment in atopic dermatitis. Expert Opin Drug Saf. 2009; 8:501–506.

       19. Remitz A, Virtanen HM, Reitamo S, Kari O. Tacrolimus ointment in atopic blepharoconjunctivitis does not seem to elevate intraocular pressure. ActaOphthalmol. 2010.

Evan Warner, MD

E: evanwarner@gmail.com

Dr. Warner is pursuing his ophthalmology residency at the University of Wisconsin School of Medicine, Madison, WI. He did not indicate any proprietary interests in the subject matter.