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INTERLEUKIN 8 PROMOTER POLYMORPHISM PREDICTS THE INITIAL RESPONSE TO BEVACIZUMAB TREATMENT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION

Hautamäki, Asta MD*; Kivioja, Jarno MSc; Vavuli, Satu MD‡,§; Kakko, Sakari MD§; Savolainen, Eeva-Riitta MD; Savolainen, Markku J. MD§; Liinamaa, M. Johanna MD‡,§; Seitsonen, Sanna MD*; Onkamo, Päivi PhD**; Järvelä, Irma MD; Immonen, Ilkka MD*

doi: 10.1097/IAE.0b013e318285cf92
Original Study

Purpose: To study the association of single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes with the response to bevacizumab treatment in exudative age-related macular degeneration.

Methods: Clinical records, smoking history, optical coherence tomography, and angiographies of 96 bevacizumab-treated exudative age-related macular degeneration patients were analyzed retrospectively. Blood DNA was collected. Based on the disappearance of intra- or subretinal fluid in optical coherence tomography, patients were graded as responders, partial responders, or nonresponders after 3 initial treatment visits and a median time of 3.5 months.

Results: Interleukin 8 promoter polymorphism −251A/T was significantly associated with persisting fluid in optical coherence tomography. The A allele was more frequent in nonresponders than in responders (P = 0.033). In multivariate modeling, the AA genotype of −251A/T (P = 0.043) and occult (P = 0.042) or predominantly classic (P = 0.040) lesions predicted poorer outcome. Visual acuity change was better in responders than in nonresponders (P = 0.006). Baseline lesion size (P = 0.006) and retinal cysts after the treatment (P < 0.001) correlated with less visual acuity gain.

Conclusion: The A allele and the homozygous AA genotype of interleukin 8 −251A/T were associated with anatomical nonresponse to bevacizumab treatment.

Supplemental Digital Content is Available in the Text.The genotype AA of interleukin 8 promoter polymorphism −251A/T was associated with persisting intra- or subretinal fluid in exudative age-related macular degeneration patients after the initial treatment with intravitreal bevacizumab. Interleukin 8 seems to modulate the response to anti–vascular endothelial growth factor therapy at least during the first months of the .treatment

*Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland

Department of Medical Genetics, University of Helsinki, Helsinki, Finland

Departments of Ophthalmology, Institute of Clinical Medicine, and

§Internal Medicine, Clinical Research Center and Biocenter Oulu, University of Oulu, Oulu, Finland

Department of Clinical Chemistry, Oulu University Hospital, Oulu, Finland

**Department of Biosciences, University of Helsinki, Helsinki, Finland.

Reprint requests: Asta Hautamäki, MD, Department of Ophthalmology, Helsinki University Central Hospital, PO Box 220, 00029 HUS, Helsinki, Finland; e-mail: asta.hautamaki@hus.fi

Supported by grants from The Eye Foundation, Helsinki, Finland; The Eye and Tissue Bank Foundation, Helsinki, Finland; The Evald and Hilda Nissi Foundation, Helsinki, Finland; and Mary and Georg C. Ehrnrooth Foundation, Helsinki, Finland.

The authors have no conflict of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.retinajournal.com).

© 2013 by Ophthalmic Communications Society, Inc.