Monitoring VEGF levels with low-volume sampling in major vision-threatening diseases: age-related macular degeneration and diabetic retinopathy.

The purpose of this article is to demonstrate the capacity of paper-based ELISA (P-ELISA) to monitor VEGF in patients requiring treatment for vision-threatening diseases. The most commonly encountered vision-threatening diseases are age-related macular degeneration (AMD) and diabetic retinopathy (DR), both of which may require short-term or life-long anti-VEGF injection treatment therapy. Accurate measurement of VEGF concentration in aqueous humor can provide significant and timely information to diagnose the disease state. Adequate and precise therapy may consequently be provided. At odds with conventional diagnostic approaches is the fact that a maximum of only 200 microliters of aqueous humor can be safely removed from the eye for testing. Fortunately, new diagnostic platforms, such as P-ELISA, require only minute volumes, i.e., approximately 2 microliters per test "well" and approximately 40 microliters total to quantify VEGF levels, and the testing process takes less than an hour. Thus, point-of-care (POC) diagnostics, such as P-ELISA, should be examined and improved upon as needed in order to develop an efficient tool for outpatient clinics and others to obtain semi-quantitative results that might facilitate accurate dosing of anti-VEGF treatment and delay or prevent the progression of AMD and DR.

[1]  Hiroshi Shimizu,et al.  Paper-based ELISA for the detection of autoimmune antibodies in body fluid-the case of bullous pemphigoid. , 2014, Analytical chemistry.

[2]  Chao-Min Cheng,et al.  Monitoring the VEGF level in aqueous humor of patients with ophthalmologically relevant diseases via ultrahigh sensitive paper-based ELISA. , 2014, Biomaterials.

[3]  Q. Nguyen,et al.  Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. , 2013, Ophthalmology.

[4]  Trevor F Peter,et al.  How point-of-care testing could drive innovation in global health. , 2013, The New England journal of medicine.

[5]  M. Shestakova,et al.  Vascular Endothelial Growth Factor in Anterior Chamber Liquid Patients with Diabetic Retinopathy, Cataract and Neovascular Glaucoma , 2013, Ophthalmology and Therapy.

[6]  K. Falavarjani,et al.  Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature , 2013, Eye.

[7]  Ali Kemal Yetisen,et al.  Paper-based microfluidic point-of-care diagnostic devices. , 2013, Lab on a chip.

[8]  B. Kirchhof,et al.  Vascular endothelial growth factor in patients with exudative age-related macular degeneration treated with ranibizumab. , 2012, Ophthalmology.

[9]  N. Engel,et al.  Point-of-Care Testing for Infectious Diseases: Diversity, Complexity, and Barriers in Low- And Middle-Income Countries , 2012, PLoS medicine.

[10]  Quan Dong Nguyen,et al.  Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. , 2012, Ophthalmology.

[11]  P. Rosenfeld,et al.  PHARMACOKINETIC RATIONALE FOR DOSING EVERY 2 WEEKS VERSUS 4 WEEKS WITH INTRAVITREAL RANIBIZUMAB, BEVACIZUMAB, AND AFLIBERCEPT (VASCULAR ENDOTHELIAL GROWTH FACTOR TRAP-EYE) , 2011, Retina.

[12]  U. Schmidt-Erfurth,et al.  Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. , 2011, Ophthalmology.

[13]  K. M. Selim,et al.  Increased levels of vascular endothelial growth factor in the aqueous humor of patients with diabetic retinopathy , 2010, Indian journal of ophthalmology.

[14]  Emanuel Carrilho,et al.  Paper-based ELISA. , 2010, Angewandte Chemie.

[15]  P. Campochiaro,et al.  Monitoring ocular drug therapy by analysis of aqueous samples. , 2009, Ophthalmology.

[16]  P. Mitchell,et al.  Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials , 2009, British Journal of Ophthalmology.

[17]  N. Eter,et al.  Intraocular pharmacokinetics of bevacizumab after a single intravitreal injection in humans. , 2008, American journal of ophthalmology.

[18]  M. Bartoli,et al.  Vascular endothelial growth factor in eye disease , 2008, Progress in Retinal and Eye Research.

[19]  G. Whitesides,et al.  Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. , 2008, Analytical chemistry.

[20]  Sharon D. Solomon,et al.  Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[21]  C. Piggee Research Profile: Enhancing peptide ion charge states for ETD , 2008 .

[22]  Osamu Sawada,et al.  Vascular endothelial growth factor in aqueous humor before and after intravitreal injection of bevacizumab in eyes with diabetic retinopathy. , 2007, Archives of ophthalmology.

[23]  F. Lee,et al.  Management of anaphylactic shock during intravenous fluorescein angiography at an outpatient clinic. , 2007, Journal of the Chinese Medical Association : JCMA.

[24]  T. Ianchulev,et al.  Role of vascular endothelial growth factor in ocular angiogenesis. , 2006, Ophthalmology clinics of North America.

[25]  Ian Constable,et al.  Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience , 2006, Clinical & experimental ophthalmology.

[26]  P.T.V.M. de Jong,et al.  Mechanisms of disease: Age-related macular degeneration , 2006 .

[27]  J E Keeffe,et al.  Impact of unilateral and bilateral vision loss on quality of life , 2005, British Journal of Ophthalmology.

[28]  M. Engelgau,et al.  The Evolving Diabetes Burden in the United States , 2004, Annals of Internal Medicine.

[29]  H. Yamashita,et al.  Aqueous humor levels of cytokines are related to vitreous levels and progression of diabetic retinopathy in diabetic patients , 2004, Graefe's Archive for Clinical and Experimental Ophthalmology.

[30]  Susheel Kumar,et al.  Standardisation and comparison of serial dilution and single dilution enzyme linked immunosorbent assay (ELISA) using different antigenic preparations of the Babesia (Theileria) equi parasite. , 2003, Veterinary research.

[31]  B. Munoz,et al.  Relation between signs and symptoms of dry eye in the elderly. A population-based perspective. , 1997, Ophthalmology.

[32]  Club Jules Gonin,et al.  Graefe's archive for clinical and experimental ophthalmology , 1982 .