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Clinicopathologic Reports, Case Reports, and Small Case Series |

Topical Cyclosporin in the Treatment of Chronic Sarcoidosis of the Conjunctiva FREE

Esen Karamursel Akpek, MD; Ozge Ilhan-Sarac, MD; W. Richard Green, MD
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Section Editor: W. Richard Green, MD

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Arch Ophthalmol. 2003;121(9):1333-1335. doi:10.1001/archopht.121.9.1333.
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Sarcoidosis is a multisystem, T-lymphocyte–mediated granulomatous inflammatory process of unknown cause. The clinical spectrum varies in severity from single-organ involvement and self-limiting disease to multisystem inflammation with potential mortality. The characteristic noncaseating granulomatous infiltrations can affect almost any tissue, including conjunctivae.1 The granulomatous inflammation of the conjunctivae in the form of conjunctival nodules resembling follicular conjunctivitis is a common initial finding.2 We describe a patient with chronic conjunctivitis who was subsequently diagnosed as having sarcoidosis and successfully treated with topical cyclosporin.

A 58-year-old white woman was referred for further management of ocular rosacea and keratoconjunctivitis sicca, which had been refractory to treatment with multiple medications, including oral and topical doxycycline, 1% topical prednisolone acetate, 0.5% ketorolac tromethamine, 0.1% olopatadine hydrochloride, and preservative-free artificial tears for 7 months. Her ocular history was remarkable for primary open-angle glaucoma, for which she underwent a bilateral laser trabeculoplasty 1 year prior to our initial examination. She was also a steroid-responder, with intraocular pressures rising up to the high 30s(mmHg) while taking topical 1% prednisolone acetate. Her medical history was negative for any known diseases, and review of systems was remarkable only for mild exertional dyspnea.

On initial examination, the intraocular pressures were within normal limits while she was receiving treatment with topical 1% brinzolamide and 0.2% brimonidine. Visual acuity was 20/20 OU. External examination disclosed eyelid margin telangiectases and irregularity, along with mild meibomian gland dysfunction in both eyes. Slitlamp examination demonstrated moderate bilateral bulbar conjunctival hyperemia with subtle lower forniceal follicules and conjunctival subepithelial fibrosis (Figure 1). The corneas were clear with no punctate epitheliopathy. The rest of the anterior segment findings were unremarkable. Ophthalmoscopic examination showed a cup-disc ratio of 9/10 OU. A Schirmer test performed on the right eye with topical anesthesia revealed a wetting of 7 mm at 5 minutes.

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Figure 1

Slitlamp appearance of the right lower forniceal conjunctiva demonstrates subtle follicular reaction along with subepithelial fibrosis.

Graphic Jump Location

A conjunctival biopsy specimen was harvested from the inferior fornix of the left eye for diagnosis. Histopathologic examination of the specimen showed foci of noncaseating granulomas intermingled and surrounded by moderately intense infiltration of normal-appearing lymphocytes (Figure 2). No evidence of acid-fast bacilli, fungi, and foreign bodies was found. The patient underwent a systemic evaluation for presumed sarcoidosis, including complete physical examination, computed tomography of the chest, pulmonary function tests, and serum angiotensin-converting enzyme analysis. The angiotensin-converting enzyme level was within normal limits. Computed tomography showed bilateral hilar lymphadenopathy with no parenchymal involvement. Results of pulmonary function tests were normal.

Place holder to copy figure label and caption
Figure 2.

The conjunctival specimen shows foci of noncaseating granuloma intermingled and surrounded by a moderately intense infiltration of normal-appearing lymphocytes (hematoxylin-eosin, original magnification ×12). Inset: higher magnification demonstrates a multinucleated giant cell in the center (original magnification ×24).

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A pulmonologist elected to defer the oral corticosteroid treatment and serial follow-up, as the patient was asymptomatic with stage I disease. A trial of topical 0.5% cyclosporin A drops (prepared in artificial tears), 4 times daily, resulted in dramatic improvement of conjunctival hyperemia and complete resolution of the lower forniceal nodules within 2 weeks (Figure 3). The patient is currently receiving maintenance therapy with cyclosporin drops, once per day, in each eye.

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Figure 3.

Slitlamp appearance of the right lower fornix after a 2-week treatment with topical cyclosporin demonstrates complete resolution of follicles.

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Cyclosporin is an immunomodulator with a selective inhibitory effect on CD4+ T-lymphocyte proliferation via inhibition of interleukin 2 receptor expression.3 Although the pathogenesis of sarcoidosis is not fully understood, T-lymphocyte–mediated hypersensitivity appears to play a central role, and corticosteroids remain the mainstay of therapy.4 Although no controlled trial data exist, uncontrolled case reports or small case series demonstrate favorable outcomes of oral cyclosporin therapy in refractory pulmonary sarcoidosis, neurosarcoidosis, and vision-threatening sarcoid-associated uveitis.5

Topical administration of cyclosporin has been highly effective in the treatment of various cell-mediated anterior segment inflammatory conditions.68 In our patient, topical cyclosporin therapy was preferred, owing to the patient's history of increased intraocular pressures with topical steroid use. Dramatic improvement of symptoms and signs occurring within a short time suggests that sarcoid conjunctivitis may represent another indication for cyclosporin eyedrops.

Corresponding author and reprints: Esen Karamursel Akpek, MD, Wilmer Eye Institute, 600 N Wolfe St, Maumenee Bldg 321, Baltimore, MD 21287-9238(e-mail: esakpek@jhmi.edu).

Kimani  APAguayo  SM Sarcoidosis: an overview for the primary care physician. Compr Ther. 1998;2420- 25
PubMed
Obenauf  CDShaw  HESydnor  CFKlinthworth  GK Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol. 1978;86648- 655
PubMed
Nussenblatt  RBPalestine  AG Cs A: immunology, pharmacology and therapeutic uses. Surv Ophthalmol. 1986;31159- 169
PubMed
Costabel  U Sarcoidosis: clinical update. Eur Respir J Suppl. 2001;32 ((suppl)) S56- S68
Baughman  RPLower  EE Steroid-sparing alternative treatments for sarcoidosis. Clin Chest Med. 1997;18853- 864
PubMed
Holland  EJOlsen  TWKetcham  JM  et al.  Topical cyclosporin A in the treatment of anterior segment inflammatory disease. Cornea. 1993;12413- 419
PubMed
Gottsch  JDAkpek  EK Topical cyclosporin stimulates neovascularization in resolving sterile rheumatoid central corneal ulcers. Trans Am Ophthalmol Soc. 2000;9881- 7discussion 87-90.
PubMed
Akpek  EKDart  JKWatson  S  et al.  A randomized trial of topical cyclosporin 0.05% in steroid-resistant atopic keratoconjunctivitis. Ophthalmology. In press.

Figures

Place holder to copy figure label and caption
Figure 1

Slitlamp appearance of the right lower forniceal conjunctiva demonstrates subtle follicular reaction along with subepithelial fibrosis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

The conjunctival specimen shows foci of noncaseating granuloma intermingled and surrounded by a moderately intense infiltration of normal-appearing lymphocytes (hematoxylin-eosin, original magnification ×12). Inset: higher magnification demonstrates a multinucleated giant cell in the center (original magnification ×24).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Slitlamp appearance of the right lower fornix after a 2-week treatment with topical cyclosporin demonstrates complete resolution of follicles.

Graphic Jump Location

Tables

References

Kimani  APAguayo  SM Sarcoidosis: an overview for the primary care physician. Compr Ther. 1998;2420- 25
PubMed
Obenauf  CDShaw  HESydnor  CFKlinthworth  GK Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol. 1978;86648- 655
PubMed
Nussenblatt  RBPalestine  AG Cs A: immunology, pharmacology and therapeutic uses. Surv Ophthalmol. 1986;31159- 169
PubMed
Costabel  U Sarcoidosis: clinical update. Eur Respir J Suppl. 2001;32 ((suppl)) S56- S68
Baughman  RPLower  EE Steroid-sparing alternative treatments for sarcoidosis. Clin Chest Med. 1997;18853- 864
PubMed
Holland  EJOlsen  TWKetcham  JM  et al.  Topical cyclosporin A in the treatment of anterior segment inflammatory disease. Cornea. 1993;12413- 419
PubMed
Gottsch  JDAkpek  EK Topical cyclosporin stimulates neovascularization in resolving sterile rheumatoid central corneal ulcers. Trans Am Ophthalmol Soc. 2000;9881- 7discussion 87-90.
PubMed
Akpek  EKDart  JKWatson  S  et al.  A randomized trial of topical cyclosporin 0.05% in steroid-resistant atopic keratoconjunctivitis. Ophthalmology. In press.

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