Histopathologic Analysis of Conjunctival Lymphoproliferative Disease After Topical Brimonidine Use.

Purpose: To describe of histopathological findings of conjunctival lymphoproliferative disease (CLD) after topical brimonidine use. Methods: This is a retrospective medical record review study, including histopathologic description. We reviewed the medical records of 208 patients (415 eyes) who were diagnosed with glaucoma and who were treated with topical brimonidine only for a minimum of 6 months. Of these, the medical records of 19 patients with suspected CLD clinical features were reviewed in detail. When CLD was suspected due to administration of brimonidine, histopathological analysis was performed by biopsy of these lesions. In addition, immunohistochemical staining was performed to analyze lymphocyte markers in some pathological tissues. Results: Nineteen patients had suspected CLD without definite irritative symptoms. Diffuse elevated (11 patients) or follicular lesion (8 patients) of salmon pink appearance was observed in inferior palpebral conjunctiva. Among these patients, 5 patients who agreed to conjunctival biopsy had histopathological findings of CLD such as reactive lymphoid hyperplasia (LH) (2 cases) or atypical LH (2 cases). The mean duration of brimonidine use was 29.00 ± 20.25 months (6-76 months). And follow-up period after discontinuation of brimonidine was 27.93 ± 11.87 months (12-58 months). At the last visit, complete resolution of the lesion was seen in 13 patients, and partial improvement was observed in 6 patients. Conclusions: We found 4 cases of CLD following long-term administration of brimonidine. However, large-scale additional studies should be performed to establish causality, to determine whether these novel side effects were caused by long-term brimonidine treatment.

[1]  I. Riaz,et al.  Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. , 2017, Immunotherapy.

[2]  S. Coupland,et al.  Lymphoid hyperplasia of the orbit and ocular adnexa: A clinical ​pathologic review. , 2016, Survey of ophthalmology.

[3]  H. Shin,et al.  Effect of Brimonidine on the B Cells, T Cells, and Cytokines of the Ocular Surface and Aqueous Humor in Rat Eyes. , 2015, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[4]  Woo Jin Oh,et al.  Nodal involvement of extranodal marginal zone lymphoma with extreme plasmacytic differentiation (Mott cell formation) simulating plasma cell neoplasm and lymphoplasmacytic lymphoma , 2014, Blood research.

[5]  S. Kase,et al.  Conjunctival lymphoma arising from reactive lymphoid hyperplasia , 2012, World Journal of Surgical Oncology.

[6]  Hyun Seung Kim,et al.  Effects of benzalkonium chloride on the ocular surface of the rabbit , 2011, Japanese Journal of Ophthalmology.

[7]  S. Kase,et al.  Conjunctival lymphoproliferative disorder. , 2011, Ophthalmology.

[8]  Arun D. Singh,et al.  Unifocal and multifocal reactive lymphoid hyperplasia vs follicular lymphoma of the ocular adnexa. , 2010, American journal of ophthalmology.

[9]  C. Baudouin Detrimental effect of preservatives in eyedrops: implications for the treatment of glaucoma , 2008, Acta ophthalmologica.

[10]  P. Rojas,et al.  α2‐Adrenoceptor action on cell proliferation and mammary tumour growth in mice , 2008, British journal of pharmacology.

[11]  L. Reiniger,et al.  The cut‐off levels of CD23 expression in the differential diagnosis of MCL and CLL , 2008, Hematological oncology.

[12]  S. Moritani,et al.  High incidence of autoimmune disease in Japanese patients with ocular adnexal reactive lymphoid hyperplasia. , 2007, American journal of ophthalmology.

[13]  T. Zeyen,et al.  Ocular Symptoms and Signs with Preserved and Preservative-Free Glaucoma Medications , 2007, European journal of ophthalmology.

[14]  D. Albert,et al.  Drug-induced cicatrising granulomatous conjunctivitis , 2007, British Journal of Ophthalmology.

[15]  C. Baudouin Allergic reaction to topical eyedrops , 2005 .

[16]  M. Zegans,et al.  Anterior uveitis and concurrent allergic conjunctivitis associated with long-term use of topical 0.2% brimonidine tartrate. , 2004, Archives of ophthalmology.

[17]  R. Noecker,et al.  Corneal and Conjunctival Changes Caused by Commonly Used Glaucoma Medications , 2004, Cornea.

[18]  A. Bron,et al.  Grading Of Corneal and Conjunctival Staining in the Context of Other Dry Eye Tests , 2003, Cornea.

[19]  M. Jeffrey,et al.  Granulomatous anterior uveitis associated with 0.2% topical brimonidine , 2003, Eye.

[20]  C. Baudouin,et al.  Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication , 2002, The British journal of ophthalmology.

[21]  P. Isaacson,et al.  Mucosa‐associated lymphoid tissue (MALT) in the human conjunctiva , 1994, The Journal of pathology.

[22]  J. Chan,et al.  A simple guide to the terminology and application of leucocyte monoclonal antibodies , 1988, Histopathology.

[23]  F. M. Wilson Adverse external ocular effects of topical ophthalmic medications. , 1979, Survey of ophthalmology.

[24]  A. Barak,et al.  Drug modification of angiogenesis in a rat cornea model. , 2008, Investigative ophthalmology & visual science.