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Year : 2013  |  Volume : 6  |  Issue : 3  |  Page : 211  

Corneal neovascularization: An enigma

1 Department of Ophthalmology, Post raduate nstitute of edical ducation and esearch, Dr. RML Hospital, New Delhi, India
2 NIRVANA Eye Care and Aesthetics, New Delhi, India

Date of Web Publication30-Nov-2013

Correspondence Address:
Pulkit Gupta
Department of Ophthalmology, JSS Medical College and Hospital, Mysore, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0974-620X.122283

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How to cite this article:
Gupta P, Malik PK, Gupta HL. Corneal neovascularization: An enigma. Oman J Ophthalmol 2013;6:211

How to cite this URL:
Gupta P, Malik PK, Gupta HL. Corneal neovascularization: An enigma. Oman J Ophthalmol [serial online] 2013 [cited 2023 Mar 31];6:211. Available from: https://www.ojoonline.org/text.asp?2013/6/3/211/122283


Every ophthalmologist is confronted by this dreadful antagonist called corneal neovascularization in her/his practice. We take this opportunity to share our experiences with this enigma.

Etiology of corneal neovascularization is multifactorial, for example, inflammatory, traumatic, infective, degenerative, dystrophic, and so on. It results whenever the armamentarium of keratic physical and physiological factors is disrupted. A multitude of cytokines, extracellular matrix proteins, and growth factors as well as regulatory mechanisms involving interleukin-1 and matrix metalloproteinase-9 and their complex interactions block angiogenesis. The activated macrophages express proangiogenic factors, for example, cyclooxygenase-2, platelet-derived growth factor, transforming growth factor beta, interleukin-1 alpha, and vascular endothelial growth factor (VEGF) in messenger ribonucleic acid (RNA). Stem cell deficiency also leads to invasion of the cornea by vascularized epithelium leading to functional blindness. [1],[2]

This complex framework renders it exceedingly tortuous to devise an effective treatment to retard, arrest, and regress the process. The various modalities practiced are as follows.

Targeting VEGF has proved to be an excellent approach. Administration of anti-VEGF agents, for example, bevacizumab and trastuzumab achieve significant reduction in neovascularization. Other than these conventional agents, advanced research programs are investigating an array of novel angiostatic agents, a few of which have been exemplified. Studies have shown cyclosporine to block corneal neovascularization induced by interleukin-2, cytokine interleukin-1 receptor antagonist to produce a transient reduction in angiogenesis, and somatostatin, endostatin (neuropeptides), and combretastatin A-4 (a tubulin-binding agent) to cause regression of established new vessels. Steroids AL-3789 and AL-4940 (proteolytic enzyme inhibitors) and anecortave acetate (angiostatic cortisone) are currently under research for their angiostatic properties. [3,4]

Innovative delivery methods for these agents include collagen shields, iontophoresis, and so on. Nanotechnology emerges as a boon in this arena. Nanoparticles, that is, colloidal carrier systems improve the efficacy of drug, reduce dosage, and enable efficient tissue targeting and sustained delivery. Albumin-derived nanoparticles that deliver plasmids contain genes for the Flt receptor, which binds free VEGF, penetrates keratocyte cytoplasm, and provides sustained inhibition of injury-induced corneal neovascularization. [5]

Surgical procedures to combat neovascularization involve peritomy or restoration of stem cells by limbal stem cell transplantation (limbal autograft transplantation, allograft transplantation, bioengineered ocular surface equivalents, and serum-free conjunctival tissue equivalents, which represent the latest advancements). Amniotic membrane grafting may act by reducing proinflammatory cytokines with a reduced tendency for neovascularization and also fibrosis. Increase in blood supply may be achieved by a conjunctival (Gundersen) flap. [4]

Deoxyribonucleic acid (DNA) delivery into the eye represents the future. It involves forcing various forms of DNA through preparations of human sclera electrophoretically, passive diffusion of oligonucleotides across the same preparation, electrophoresis of dyes into an isolated intact globe, and electrophoresis of a plasmid. Naked DNA injected into the corneal stroma is an effective method to deliver, transfect, and express a gene in therapeutic doses. Alternatively, regenerative nanomedicine uses nanoparticles containing gene transcription factors and other modulating molecules that allow reprogramming of cells in vivo. [5]

Despite exponential leaps in technology, we have touched just the tip of the iceberg. Further dedicated research and studies will help us strengthen our quest to achieve our goals.

   References Top

1.Li ZR, Li YP, Lin ML, Su WR, Zhang WX, Zhang Y, et al. Activated macrophages induce neovascularization through upregulation of MMP-9 and VEGF in rat corneas. Cornea 2012;31: 1028-35.  Back to cited text no. 1
2.Ang LP, Tan DT. Ocular surface stem cells and disease: Current concepts and clinical applications. Ann Acad Med Singapore. 2004;33:576-80.  Back to cited text no. 2
3.Güler M, Yilmaz T, Ozercan I, Elkiran T. The inhibitory effects of trastuzumab on corneal neovascularization. Am J Ophthalmol 2009;147:703-8.  Back to cited text no. 3
4.Saltzman WM, Langer R. Transport rates of proteins in porous materials with known microgeometry. Biophys J 1989;55:163-71.  Back to cited text no. 4
5.Zarbin MA, Montemagno C, Leary JF, Ritch R. Nanotechnology in ophthalmology. Can J Ophthalmol 2010;45:457-76.  Back to cited text no. 5


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