Molecular Diagnosis & Therapy

, Volume 15, Issue 4, pp 195–210 | Cite as

Genetic Predictors of Response to Photodynamic Therapy

  • Francesco Parmeggiani
  • Donato Gemmati
  • Ciro Costagliola
  • Francesco Semeraro
  • Paolo Perri
  • Sergio D’Angelo
  • Mario R. Romano
  • Katia De Nadai
  • Adolfo Sebastiani
  • Carlo Incorvaia
Review Article

Abstract

In Western countries, therapeutic management of patients affected by choroidal neovascularization (CNV) secondary to different typologies of macular degeneration represents a major health care problem. Age-related macular degeneration is the disease most frequently associated with CNV development. Schematically, CNVs can be distinguished into classic and occult subtypes, which are characterized by variable natural history and different responsiveness to some therapeutic procedures. At present, the dramatic vision loss due to CNV can be mainly treated by two interventional strategies, which are utilizable in either single or combined modalities: photodynamic therapy with verteporfin (PDT-V), and intravitreal administration of drugs acting against vascular endothelial growth factor. The combined use of PDT-V and anti-angiogenic drugs represents one of the most promising strategies against neovascular macular degeneration, but it unavoidably results in an expensive increase in health resource utilization. However, the positive data from several studies serve as a basis for reconsidering the role of PDT-V, which has undergone a renaissance prompted by the need for a more rational therapeutic approach toward CNV. New pharmacogenetic knowledge of PDT-V points to exploratory prospects to optimize the clinical application of this intriguing photothrombotic procedure. In fact, a Medline search provides data regarding the role of several single nucleotide polymorphisms (SNPs) as genetic predictors of CNV responsiveness to PDT-V. Specifically, correlations between SNPs and different levels of PDT-V efficacy have been detected by examining the gene variants influencing (i) thrombo-coagulative pathways, i.e. methylenetetrahydrofolate reductase (MTHFR) 677C>T (rs 1801133), factor V (F5) 1691 G>A (rs6025), prothrombin (F2) 20210G>A (rs1799963), and factor XIII-A (F13A1) 185G>T (rs5985); (ii) complement activation and/or inflammatory processes, i.e. complement factor H (CFH) 1277T>C (rs1061170), high-temperature requirement factor A1 (HTRA1) promoter -512G>A (rs11200638), and two variants of the C-reactive protein (CRP) gene (rs2808635 and rs876538); and (iii) production and bioavailability of vascular endothelial growth factor (VEGFA-2578C>A [rs699947] and rs2146323). This article critically evaluates both the clinical plausibility and the opportunity to utilize the most important SNP-response interactions of PDT-V for an effective upgrade of the current anti-CNV therapeutic scenario. In addition, the pharmacogenetics of a very severe post-PDT-V adverse event, i.e. a decrease in acute vision, is briefly discussed. A comprehensive appraisal of the findings reviewed in this article should be carefully considered to design future trials aimed at verifying (after proper genotypic stratification of the enrolled patients) whether these innovative pharmacogenetic approaches will be able to improve the multifaceted interventional management of neovascular macular degeneration.

Notes

Acknowledgments

The authors wish to thank Ms Graziella Ferraresi and Mr Giuseppe Gilli for their assistance in reviewing and discussing this work.

No sources of funding were used to prepare this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Francesco Parmeggiani
    • 1
  • Donato Gemmati
    • 2
  • Ciro Costagliola
    • 3
  • Francesco Semeraro
    • 4
  • Paolo Perri
    • 1
  • Sergio D’Angelo
    • 1
  • Mario R. Romano
    • 3
  • Katia De Nadai
    • 5
  • Adolfo Sebastiani
    • 1
  • Carlo Incorvaia
    • 1
  1. 1.Department of OphthalmologyUniversity of FerraraFerraraItaly
  2. 2.Department of Hematology, Center of Hemostasis and ThrombosisUniversity of FerraraFerraraItaly
  3. 3.Department of Health SciencesUniversity of MoliseCampobassoItaly
  4. 4.Department of OphthalmologyUniversity of BresciaBresciaItaly
  5. 5.Center for Retinitis Pigmentosa of Veneto RegionUnita Locale Socio Sanitaria 15 Alta Padovana, Camposampiero HospitalCamposampieroItaly

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