Advanced search
Publication Cover
Expert Review of Ophthalmology Volume 8, 2013 - Issue 2
Submit an article Journal homepage
115
Views
9
CrossRef citations to date
0
Altmetric
Review

Corneal neovascularization: a review of the molecular biology and current therapies

Michael L Rolfsen Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA
,
Nicholas E Frisard Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA
,
Ethan M Stern Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Tulane University, 6823 St. Charles Avenue, New Orleans, LA 70118, USA; Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Tulane University, 6823 St. Charles Avenue, New Orleans, LA 70118, USA
,
Timothy P Foster Department of Microbiology, LSUHSC, 533 Bolivar Street, New Orleans, LA 70112, USA; Stanley S. Scott Cancer Center, LSUHSC, 533 Bolivar Street, Room 459, New Orleans, LA 70112, USA; Department of Microbiology, LSUHSC, 533 Bolivar Street, New Orleans, LA 70112, USA; Stanley S. Scott Cancer Center, LSUHSC, 533 Bolivar Street, Room 459, New Orleans, LA 70112, USA
,
Partha S Bhattacharjee Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Department of Biology, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA; Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Department of Biology, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA
,
Harris E McFerrin Jr Department of Biology, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA; Department of Biology, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA
,
Christian Clement Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA
,
Paulo C Rodriguez Department of Microbiology, LSUHSC, 533 Bolivar Street, New Orleans, LA 70112, USA; Stanley S. Scott Cancer Center, LSUHSC, 533 Bolivar Street, Room 459, New Orleans, LA 70112, USA; Department of Microbiology, LSUHSC, 533 Bolivar Street, New Orleans, LA 70112, USA; Department of Biology, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA
,
Walter J Lukiw Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Neuroscience Center, LSUHSC, 2020 Gravier Street, 8th Floor, New Orleans, LA 70112, USA; Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Neuroscience Center, LSUHSC, 2020 Gravier Street, 8th Floor, New Orleans, LA 70112, USA
,
Donald R Bergsma Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA
,
Augusto C Ochoa Stanley S. Scott Cancer Center, LSUHSC, 533 Bolivar Street, Room 459, New Orleans, LA 70112, USA; Department of Pediatrics, LSUHSC, 200 Henry Clay Avenue, New Orleans, LA 70118, USA; Department of Pediatrics, LSUHSC, 200 Henry Clay Avenue, New Orleans, LA 70118, USA
&
James M Hill Department of Ophthalmology, Louisiana State University Health Sciences Center (LSUHSC), 533 Bolivar Street, New Orleans, LA 70112, USA; Department of Microbiology, LSUHSC, 533 Bolivar Street, New Orleans, LA 70112, USA; Neuroscience Center, LSUHSC, 2020 Gravier Street, 8th Floor, New Orleans, LA 70112, USA; Department of Pharmacology, LSUHSC, 1901 Perdido Street, New Orleans, LA 70112, USA. [email protected]; Department of Pharmacology, LSUHSC, 1901 Perdido Street, New Orleans, LA 70112, USA. [email protected]
 show all
Pages 167-189 | Published online: 09 Jan 2014

References

  • Lee P, Wang CC, Adamis AP. Ocular neovascularization: an epidemiologic review. Surv. Ophthalmol. 43(3), 245–269 (1998).
  • Maddula S, Davis DK, Maddula S, Burrow MK, Ambati BK. Horizons in therapy for corneal angiogenesis. Ophthalmology 118(3), 591–599 (2011).
  • Cursiefen C, Colin J, Dana R et al. Consensus statement on indications for anti-angiogenic therapy in the management of corneal diseases associated with neovascularisation: outcome of an expert roundtable. Br. J. Ophthalmol. 96(1), 3–9 (2012).
  • Qazi Y, Maddula S, Ambati BK. Mediators of ocular angiogenesis. J. Genet. 88(4), 495–515 (2009).
  • Menzel-Severing J. Emerging techniques to treat corneal neovascularisation. Eye (Lond.) 26(1), 2–12 (2012).
  • Qazi Y, Wong G, Monson B, Stringham J, Ambati BK. Corneal transparency: genesis, maintenance and dysfunction. Brain Res. Bull. 81(2–3), 198–210 (2010).
  • Zhang SX, Ma JX. Ocular neovascularization: implication of endogenous angiogenic inhibitors and potential therapy. Prog. Retin. Eye Res. 26(1), 1–37 (2007).
  • Mohan RR, Tovey JC, Sharma A, Tandon A. Gene therapy in the cornea: 2005–present. Prog. Retin. Eye Res. 31(1), 43–64 (2012).
  • Giménez F, Suryawanshi A, Rouse BT. Pathogenesis of herpes stromal keratitis – a focus on corneal neovascularization. Prog. Retin. Eye Res. 33, 1–9 (2013).
  • Goldman JN, Benedek GB. The relationship between morphology and transparency in the nonswelling corneal stroma of the shark. Invest. Ophthalmol. 6(6), 574–600 (1967).
  • Jester JV, Moller-Pedersen T, Huang J et al. The cellular basis of corneal transparency: evidence for ‘corneal crystallins’. J. Cell. Sci. 112 (Pt 5), 613–622 (1999).
  • Kvanta A. Ocular angiogenesis: the role of growth factors. Acta Ophthalmol. Scand. 84(3), 282–288 (2006).
  • Burger PC, Chandler DB, Klintworth GK. Corneal neovascularization as studied by scanning electron microscopy of vascular casts. Lab. Invest. 48(2), 169–180 (1983).
  • Liesegang TJ. Physiologic changes of the cornea with contact lens wear. CLAO J. 28(1), 12–27 (2002).
  • Chen P, Yin H, Wang Y, Wang Y, Xie L. Inhibition of VEGF expression and corneal neovascularization by shRNA targeting HIF-1a in a mouse model of closed eye contact lens wear. Mol. Vis. 18, 864–873 (2012).
  • Wuest T, Zheng M, Efstathiou S, Halford WP, Carr DJ. The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization. PLoS Pathog. 7(10), e1002278 (2011).
  • Cantin E, Chen J, Willey DE, Taylor JL, O’Brien WJ. Persistence of herpes simplex virus DNA in rabbit corneal cells. Invest. Ophthalmol. Vis. Sci. 33(8), 2470–2475 (1992).
  • Dhaliwal DK, Romanowski EG, Yates KA, Hu D, Goldstein M, Gordon YJ. Experimental laser-assisted in situ keratomileusis induces the reactivation of latent herpes simplex virus. Am. J. Ophthalmol. 131(4), 506–507 (2001).
  • Kaye S, Choudhary A. Herpes simplex keratitis. Prog. Retin. Eye Res. 25(4), 355–380 (2006).
  • Suryawanshi A, Mulik S, Sharma S, Reddy PB, Sehrawat S, Rouse BT. Ocular neovascularization caused by herpes simplex virus type 1 infection results from breakdown of binding between vascular endothelial growth factor A and its soluble receptor. J. Immunol. 186(6), 3653–3665 (2011).
  • Hayashi K, Hooper LC, Detrick B, Hooks JJ. HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic factor VEGF and MMP-9. Arch. Virol. 154(2), 219–226 (2009).
  • Abu El-Asrar AM, Al-Kharashi SA, Missotten L, Geboes K. Expression of growth factors in the conjunctiva from patients with active trachoma. Eye (Lond.) 20, 362–369 (2006).
  • Bachmann B, Taylor RS, Cursiefen C. Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty: an evidence-based meta-analysis. Ophthalmology 117(7), 1300.e7–1305.e7 (2010).
  • Cursiefen C, Cao J, Chen L et al. Inhibition of hemangiogenesis and lymphangiogenesis after normal-risk corneal transplantation by neutralizing VEGF promotes graft survival. Invest. Ophthalmol. Vis. Sci. 45(8), 2666–2673 (2004).
  • Altenburger AE, Bachmann B, Seitz B, Cursiefen C. Morphometric analysis of postoperative corneal neovascularization after high-risk keratoplasty: herpetic versus non-herpetic disease. Graefes Arch. Clin. Exp. Ophthalmol. 250(11), 1663–1671 (2012).
  • Lam VM, Nguyen NX, Martus P, Seitz B, Kruse FE, Cursiefen C. Surgery-related factors influencing corneal neovascularization after low-risk keratoplasty. Am. J. Ophthalmol. 141(2), 260–266 (2006).
  • Cursiefen C, Wenkel H, Martus P et al. Impact of short-term versus long-term topical steroids on corneal neovascularization after non-high-risk keratoplasty. Graefes Arch. Clin. Exp. Ophthalmol. 239(7), 514–521 (2001).
  • Bachmann BO, Luetjen-Drecoll E, Bock F et al. Transient postoperative vascular endothelial growth factor (VEGF)-neutralisation improves graft survival in corneas with partly regressed inflammatory neovascularisation. Br. J. Ophthalmol. 93(8), 1075–1080 (2009).
  • Dua HS, Azuara-Blanco A. Limbal stem cells of the corneal epithelium. Surv. Ophthalmol. 44(5), 415–425 (2000).
  • Staton CA, Reed MW, Brown NJ. A critical analysis of current in vitro and in vivo angiogenesis assays. Int. J. Exp. Pathol. 90(3), 195–221 (2009).
  • Dursun A, Arici MK, Dursun F et al. Comparison of the effects of bevacizumab and ranibizumab injection on corneal angiogenesis in an alkali burn induced model. Int. J. Ophthalmol. 5(4), 448–451 (2012).
  • Singh N, Jani PD, Suthar T, Amin S, Ambati BK. Flt-1 intraceptor induces the unfolded protein response, apoptotic factors, and regression of murine injury-induced corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 47(11), 4787–4793 (2006).
  • Stuart PM, Pan F, Plambeck S, Ferguson TA. FasL-Fas interactions regulate neovascularization in the cornea. Invest. Ophthalmol. Vis. Sci. 44(1), 93–98 (2003).
  • Ebrahem Q, Minamoto A, Hoppe G, Anand-Apte B, Sears JE. Triamcinolone acetonide inhibits IL-6- and VEGF-induced angiogenesis downstream of the IL-6 and VEGF receptors. Invest. Ophthalmol. Vis. Sci. 47(11), 4935–4941 (2006).
  • Jain RK, Munn LL, Fukumura D. Corneal pocket assay in rabbits. Cold Spring Harb. Protoc. 2012(9), 1017–1018 (2012).
  • Goodwin AM. In vitro assays of angiogenesis for assessment of angiogenic and anti-angiogenic agents. Microvasc. Res. 74(2-3), 172–183 (2007).
  • Rogers MS, Birsner AE, D’Amato RJ. The mouse cornea micropocket angiogenesis assay. Nat. Protoc. 2(10), 2545–2550 (2007).
  • Itoh N, Ornitz DM. Evolution of the Fgf and Fgfr gene families. Trends Genet. 20(11), 563–569 (2004).
  • Onguchi T, Han KY, Chang JH, Azar DT. Membrane type-1 matrix metalloproteinase potentiates basic fibroblast growth factor-induced corneal neovascularization. Am. J. Pathol. 174(4), 1564–1571 (2009).
  • Chang JH, Han KY, Azar DT. Wound healing fibroblasts modulate corneal angiogenic privilege: interplay of basic fibroblast growth factor and matrix metalloproteinases in corneal angiogenesis. Jpn. J. Ophthalmol. 54(3), 199–205 (2010).
  • Risau W. Mechanisms of angiogenesis. Nature 386(6626), 671–674 (1997).
  • Behzadian MA, Wang XL, Al-Shabrawey M, Shabrawey M, Caldwell RB. Effects of hypoxia on glial cell expression of angiogenesis-regulating factors VEGF and TGF-β. Glia 24(2), 216–225 (1998).
  • Ferrara N, Carver-Moore K, Chen H et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573), 439–442 (1996).
  • Papapetropoulos A, García-Cardeña G, Dengler TJ, Maisonpierre PC, Yancopoulos GD, Sessa WC. Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors. Lab. Invest. 79(2), 213–223 (1999).
  • Maisonpierre PC, Suri C, Jones PF et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277(5322), 55–60 (1997).
  • Asahara T, Chen D, Takahashi T et al. Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization. Circ. Res. 83(3), 233–240 (1998).
  • Singh N, Macnamara E, Rashid S et al. Systemic soluble Tie2 expression inhibits and regresses corneal neovascularization. Biochem. Biophys. Res. Commun. 332(1), 194–199 (2005).
  • Suryawanshi A, Veiga-Parga T, Reddy PB, Rajasagi NK, Rouse BT. IL-17A differentially regulates corneal vascular endothelial growth factor (VEGF)-A and soluble VEGF receptor 1 expression and promotes corneal angiogenesis after herpes simplex virus infection. J. Immunol. 188(7), 3434–3446 (2012).
  • Kato T, Kure T, Chang JH et al. Diminished corneal angiogenesis in gelatinase A-deficient mice. FEBS Lett. 508(2), 187–190 (2001).
  • Kure T, Chang JH, Kato T et al. Corneal neovascularization after excimer keratectomy wounds in matrilysin-deficient mice. Invest. Ophthalmol. Vis. Sci. 44(1), 137–144 (2003).
  • Chang JH, Javier JA, Chang GY, Oliveira HB, Azar DT. Functional characterization of neostatins, the MMP-derived, enzymatic cleavage products of type XVIII collagen. FEBS Lett. 579(17), 3601–3606 (2005).
  • Fini ME, Parks WC, Rinehart WB et al. Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury. Am. J. Pathol. 149(4), 1287–1302 (1996).
  • Zhang H, Li C, Baciu PC. Expression of integrins and MMPs during alkaline-burn-induced corneal angiogenesis. Invest. Ophthalmol. Vis. Sci. 43(4), 955–962 (2002).
  • Azar DT, Casanova FH, Mimura T, Jain S, Chang JH. Effect of MT1-MMP deficiency and overexpression in corneal keratocytes on vascular endothelial cell migration and proliferation. Curr. Eye Res. 33(11), 954–962 (2008).
  • Bernhagen J, Calandra T, Mitchell RA et al. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 365(6448), 756–759 (1993).
  • Usui T, Yamagami S, Kishimoto S, Seiich Y, Nakayama T, Amano S. Role of macrophage migration inhibitory factor in corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 48(8), 3545–3550 (2007).
  • Pérez-Santonja JJ, Campos-Mollo E, Lledó-Riquelme M, Javaloy J, Alió JL. Inhibition of corneal neovascularization by topical bevacizumab (anti-VEGF) and sunitinib (anti-VEGF and anti-PDGF) in an animal model. Am. J. Ophthalmol. 150(4), 519–528 (2010).
  • Makino Y, Cao R, Svensson K et al. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 414(6863), 550–554 (2001).
  • Ambati BK, Joussen AM, Kuziel WA, Adamis AP, Ambati J. Inhibition of corneal neovascularization by genetic ablation of CCR2. Cornea 22(5), 465–467 (2003).
  • Ambati BK, Anand A, Joussen AM, Kuziel WA, Adamis AP, Ambati J. Sustained inhibition of corneal neovascularization by genetic ablation of CCR5. Invest. Ophthalmol. Vis. Sci. 44(2), 590–593 (2003).
  • Ambati BK, Patterson E, Jani P et al. Soluble vascular endothelial growth factor receptor-1 contributes to the corneal antiangiogenic barrier. Br. J. Ophthalmol. 91(4), 505–508 (2007).
  • Ambati BK, Nozaki M, Singh N et al. Corneal avascularity is due to soluble VEGF receptor-1. Nature 443(7114), 993–997 (2006).
  • Kommineni VK, Nagineni CN, William A, Detrick B, Hooks JJ. IFN-γ acts as anti-angiogenic cytokine in the human cornea by regulating the expression of VEGF-A and sVEGF-R1. Biochem. Biophys. Res. Commun. 374(3), 479–484 (2008).
  • Hisatomi T, Nakao S, Murakami Y et al. The regulatory roles of apoptosis-inducing factor in the formation and regression processes of ocular neovascularization. Am. J. Pathol. 181(1), 53–61 (2012).
  • Hahn N, Dietz CT, Kühl S, Vossmerbaeumer U, Kroll J. KLEIP deficiency in mice causes progressive corneal neovascular dystrophy. Invest. Ophthalmol. Vis. Sci. 53(6), 3260–3268 (2012).
  • O’Reilly MS, Boehm T, Shing Y et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88(2), 277–285 (1997).
  • Lai LJ, Xiao X, Wu JH. Inhibition of corneal neovascularization with endostatin delivered by adeno-associated viral (AAV) vector in a mouse corneal injury model. J. Biomed. Sci. 14(3), 313–322 (2007).
  • Mwaikambo BR, Sennlaub F, Ong H, Chemtob S, Hardy P. Activation of CD36 inhibits and induces regression of inflammatory corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 47(10), 4356–4364 (2006).
  • Mwaikambo BR, Yang C, Ong H, Chemtob S, Hardy P. Emerging roles for the CD36 scavenger receptor as a potential therapeutic target for corneal neovascularization. Endocr. Metab. Immune Disord. Drug Targets 8(4), 255–272 (2008).
  • Volpert OV, Tolsma SS, Pellerin S et al. Inhibition of angiogenesis by thrombospondin-2. Biochem. Biophys. Res. Commun. 217(1), 326–332 (1995).
  • Zhou Z, Wang J, Cao R et al. Impaired angiogenesis, delayed wound healing and retarded tumor growth in perlecan heparan sulfate-deficient mice. Cancer Res. 64(14), 4699–4702 (2004).
  • Matsui T, Nishino Y, Maeda S, Yamagishi S. PEDF-derived peptide inhibits corneal angiogenesis by suppressing VEGF expression. Microvasc. Res. 84(1), 105–108 (2012).
  • Dawson DW, Volpert OV, Gillis P et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science 285(5425), 245–248 (1999).
  • Chan CK, Pham LN, Zhou J, Spee C, Ryan SJ, Hinton DR. Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization. Lab. Invest. 85(6), 721–733 (2005).
  • Ambati BK, Joussen AM, Ambati J et al. Angiostatin inhibits and regresses corneal neovascularization. Arch. Ophthalmol. 120(8), 1063–1068 (2002).
  • Johnson MD, Kim HR, Chesler L, Tsao-Wu G, Bouck N, Polverini PJ. Inhibition of angiogenesis by tissue inhibitor of metalloproteinase. J. Cell. Physiol. 160(1), 194–202 (1994).
  • Anand-Apte B, Pepper MS, Voest E et al. Inhibition of angiogenesis by tissue inhibitor of metalloproteinase-3. Invest. Ophthalmol. Vis. Sci. 38(5), 817–823 (1997).
  • Ozerdem U, Stallcup WB. Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan. Angiogenesis 7(3), 269–276 (2004).
  • Motiejunaite R, Kazlauskas A. Pericytes and ocular diseases. Exp. Eye Res. 86(2), 171–177 (2008).
  • Yoeruek E, Ziemssen F, Henke-Fahle S et al.; Tübingen Bevacizumab Study Group. Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn. Acta Ophthalmol. 86(3), 322–328 (2008).
  • You IC, Kang IS, Lee SH, Yoon KC. Therapeutic effect of subconjunctival injection of bevacizumab in the treatment of corneal neovascularization. Acta Ophthalmol. 87(6), 653–658 (2009).
  • Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350(23), 2335–2342 (2004).
  • Koenig Y, Bock F, Horn F, Kruse F, Straub K, Cursiefen C. Short- and long-term safety profile and efficacy of topical bevacizumab (Avastin) eye drops against corneal neovascularization. Graefes Arch. Clin. Exp. Ophthalmol. 247(10), 1375–1382 (2009).
  • Bock F, König Y, Kruse F, Baier M, Cursiefen C. Bevacizumab (Avastin) eye drops inhibit corneal neovascularization. Graefes Arch. Clin. Exp. Ophthalmol. 246(2), 281–284 (2008).
  • DeStafeno JJ, Kim T. Topical bevacizumab therapy for corneal neovascularization. Arch. Ophthalmol. 125(6), 834–836 (2007).
  • Bahar I, Kaiserman I, McAllum P, Rootman D, Slomovic A. Subconjunctival bevacizumab injection for corneal neovascularization. Cornea 27(2), 142–147 (2008).
  • Jarrín E, Ruiz-Casas D, Mendivil A. Efficacy of bevacizumab against interface neovascularization after deep anterior lamellar keratoplasty. Cornea 31(2), 188–190 (2012).
  • Kim SW, Ha BJ, Kim EK, Tchah H, Kim TI. The effect of topical bevacizumab on corneal neovascularization. Ophthalmology 115(6), e33–e38 (2008).
  • Rosenfeld PJ, Brown DM, Heier JS et al.; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 355(14), 1419–1431 (2006).
  • Hosseini H, Nejabat M. A potential therapeutic strategy for inhibition of corneal neovascularization with new anti-VEGF agents. Med. Hypotheses 68(4), 799–801 (2007).
  • Van Bergen T, Vandewalle E, Van de Veire S et al. The role of different VEGF isoforms in scar formation after glaucoma filtration surgery. Exp. Eye Res. 93(5), 689–699 (2011).
  • Rinaldi M, Chiosi F, Dell’omo R et al. Intravitreal pegaptanib sodium (Macugen®) for treatment of myopic choroidal neovascularization: a morphologic and functional study. Retina (Philadelphia, Pa.) 33(2), 397–402 (2013).
  • Sener E, Yuksel N, Yildiz DK et al. The impact of subconjunctivally injected EGF and VEGF inhibitors on experimental corneal neovascularization in rat model. Curr. Eye Res. 36(11), 1005–1013 (2011).
  • Stewart MW. Clinical and differential utility of VEGF inhibitors in wet age-related macular degeneration: focus on aflibercept. Clin. Ophthalmol. 6, 1175–1186 (2012).
  • Oliveira HB, Sakimoto T, Javier JA et al. VEGF Trap(R1R2) suppresses experimental corneal angiogenesis. Eur. J. Ophthalmol. 20(1), 48–54 (2010).
  • Bhattacharjee PS, Huq TS, Mandal TK et al. A novel peptide derived from human apolipoprotein E is an inhibitor of tumor growth and ocular angiogenesis. PLoS ONE 6(1), e15905 (2011).
  • Kim IT, Park HY, Choi JS, Joo CK. Anti-angiogenic effect of KR-31831 on corneal and choroidal neovascularization in rat models. Invest. Ophthalmol. Vis. Sci. 53(6), 3111–3119 (2012).
  • Andrieu-Soler C, Berdugo M, Doat M, Courtois Y, BenEzra D, Behar-Cohen F. Downregulation of IRS-1 expression causes inhibition of corneal angiogenesis. Invest. Ophthalmol. Vis. Sci. 46(11), 4072–4078 (2005).
  • Kain H, Goldblum D, Geudelin B, Thorin E, Beglinger C. Tolerability and safety of GS-101 eye drops, an antisense oligonucleotide to insulin receptor substrate-1: a ‘first in man’ Phase I investigation. Br. J. Clin. Pharmacol. 68(2), 169–173 (2009).
  • Cursiefen C, Bock F, Horn FK et al. GS-101 antisense oligonucleotide eye drops inhibit corneal neovascularization: interim results of a randomized Phase II trial. Ophthalmology 116(9), 1630–1637 (2009).
  • Lu P, Li L, Liu G, Zhang X, Mukaida N. Enhanced experimental corneal neovascularization along with aberrant angiogenic factor expression in the absence of IL-1 receptor antagonist. Invest. Ophthalmol. Vis. Sci. 50(10), 4761–4768 (2009).
  • Jin UH, Chung TW, Kang SK et al. Caffeic acid phenyl ester in propolis is a strong inhibitor of matrix metalloproteinase-9 and invasion inhibitor: isolation and identification. Clin. Chim. Acta 362(1–2), 57–64 (2005).
  • Liao HF, Chen YY, Liu JJ et al. Inhibitory effect of caffeic acid phenethyl ester on angiogenesis, tumor invasion, and metastasis. J. Agric. Food Chem. 51(27), 7907–7912 (2003).
  • Totan Y, Aydin E, Cekiç O et al. Effect of caffeic acid phenethyl ester on corneal neovascularization in rats. Curr. Eye Res. 23(4), 291–297 (2001).
  • Aydin E, Kivilcim M, Peyman GA, Esfahani MR, Kazi AA, Sanders DR. Inhibition of experimental angiogenesis of cornea by various doses of doxycycline and combination of triamcinolone acetonide with low-molecular-weight heparin and doxycycline. Cornea 27(4), 446–453 (2008).
  • Su W, Li Z, Li Y et al. Doxycycline enhances the inhibitory effects of bevacizumab on corneal neovascularization and prevents its side effects. Invest. Ophthalmol. Vis. Sci. 52(12), 9108–9115 (2011).
  • Xiao O, Xie ZL, Lin BW, Yin XF, Pi RB, Zhou SY. Minocycline inhibits alkali burn-induced corneal neovascularization in mice. PLoS ONE 7(7), e41858 (2012).
  • Regenfuss B, Bock F, Parthasarathy A, Cursiefen C. Corneal (lymph)angiogenesis – from bedside to bench and back: a tribute to Judah Folkman. Lymphat. Res. Biol. 6(3–4), 191–201 (2008).
  • Crum R, Szabo S, Folkman J. A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 230(4732), 1375–1378 (1985).
  • Boneham GC, Collin HB. Steroid inhibition of limbal blood and lymphatic vascular cell growth. Curr. Eye Res. 14(1), 1–10 (1995).
  • Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids – new mechanisms for old drugs. N. Engl. J. Med. 353(16), 1711–1723 (2005).
  • Jones IS, Meyer K. Inhibition of vascularization of the rabbit cornea by local application of cortisone. Proc. Soc. Exp. Biol. Med. 74(1), 102–104 (1950).
  • McNatt LG, Weimer L, Yanni J, Clark AF. Angiostatic activity of steroids in the chick embryo CAM and rabbit cornea models of neovascularization. J. Ocul. Pharmacol. Ther. 15(5), 413–423 (1999).
  • Li WW, Casey R, Gonzalez EM, Folkman J. Angiostatic steroids potentiated by sulfated cyclodextrins inhibit corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 32(11), 2898–2905 (1991).
  • Hos D, Saban DR, Bock F et al. Suppression of inflammatory corneal lymphangiogenesis by application of topical corticosteroids. Arch. Ophthalmol. 129(4), 445–452 (2011).
  • Murata M, Shimizu S, Horiuchi S, Taira M. Inhibitory effect of triamcinolone acetonide on corneal neovascularization. Graefes Arch. Clin. Exp. Ophthalmol. 244(2), 205–209 (2006).
  • Nakao S, Hata Y, Miura M et al. Dexamethasone inhibits interleukin-1β-induced corneal neovascularization: role of nuclear factor-κB-activated stromal cells in inflammatory angiogenesis. Am. J. Pathol. 171(3), 1058–1065 (2007).
  • Tokida Y, Aratani Y, Morita A, Kitagawa Y. Production of two variant laminin forms by endothelial cells and shift of their relative levels by angiostatic steroids. J. Biol. Chem. 265(30), 18123–18129 (1990).
  • Ingber DE, Madri JA, Folkman J. A possible mechanism for inhibition of angiogenesis by angiostatic steroids: induction of capillary basement membrane dissolution. Endocrinology 119(4), 1768–1775 (1986).
  • Stokes CL, Weisz PB, Williams SK, Lauffenburger DA. Inhibition of microvascular endothelial cell migration by β-cyclodextrin tetradecasulfate and hydrocortisone. Microvasc. Res. 40(2), 279–284 (1990).
  • Folkman J, Ingber DE. Angiostatic steroids. Method of discovery and mechanism of action. Ann. Surg. 206(3), 374–383 (1987).
  • Saud EE, Moraes HV Jr, Marculino LG, Gomes JA, Allodi S, Miguel NC. Clinical and histopathological outcomes of subconjunctival triamcinolone injection for the treatment of acute ocular alkali burn in rabbits. Cornea 31(2), 181–187 (2012).
  • Becker B. The side effects of corticosteroids. Invest. Ophthalmol. 3, 492–497 (1964).
  • Utine CA, Stern M, Akpek EK. Clinical review: topical ophthalmic use of cyclosporin A. Ocul. Immunol. Inflamm. 18(5), 352–361 (2010).
  • Gupta D, Illingworth C. Treatments for corneal neovascularization: a review. Cornea 30(8), 927–938 (2011).
  • Heiligenhaus A, Steuhl KP. Treatment of HSV-1 stromal keratitis with topical cyclosporin A: a pilot study. Graefes Arch. Clin. Exp. Ophthalmol. 237(5), 435–438 (1999).
  • Lepri A, Benelli U, Bernardini N et al. Effect of low molecular weight heparan sulphate on angiogenesis in the rat cornea after chemical cauterization. J. Ocul. Pharmacol. 10(1), 273–280 (1994).
  • Chang CT, Chen YL, Lee SH, Lue CM, Lin MT. The inhibition of prostaglandin E1-induced corneal neovascularization by steroid eye drops. Taiwan Yi Xue Hui Za Zhi. 88(7), 707–711 (1989).
  • BenEzra D. Neovasculogenic ability of prostaglandins, growth factors, and synthetic chemoattractants. Am. J. Ophthalmol. 86(4), 455–461 (1978).
  • Castro MR, Lutz D, Edelman JL. Effect of COX inhibitors on VEGF-induced retinal vascular leakage and experimental corneal and choroidal neovascularization. Exp. Eye Res. 79(2), 275–285 (2004).
  • Frucht J, Zauberman H. Topical indomethacin effect on neovascularisation of the cornea and on prostaglandin E2 levels. Br. J. Ophthalmol. 68(9), 656–659 (1984).
  • Yamada M, Kawai M, Kawai Y, Mashima Y. The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesis in the rat. Curr. Eye Res. 19(4), 300–304 (1999).
  • Robin JB, Regis-Pacheco LF, Kash RL, Schanzlin DJ. The histopathology of corneal neovascularization. Inhibitor effects. Arch. Ophthalmol. 103(2), 284–287 (1985).
  • Mahoney JM, Waterbury LD. Drug effects on the neovascularization response to silver nitrate cauterization of the rat cornea. Curr. Eye Res. 4(5), 531–535 (1985).
  • Dana MR, Streilein JW. Loss and restoration of immune privilege in eyes with corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 37(12), 2485–2494 (1996).
  • Takahashi K, Saishin Y, Saishin Y et al. Topical nepafenac inhibits ocular neovascularization. Invest. Ophthalmol. Vis. Sci. 44(1), 409–415 (2003).
  • Guidera AC, Luchs JI, Udell IJ. Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs. Ophthalmology 108(5), 936–944 (2001).
  • Joussen AM, Kruse FE, Völcker HE, Kirchhof B. Topical application of methotrexate for inhibition of corneal angiogenesis. Graefes Arch. Clin. Exp. Ophthalmol. 237(11), 920–927 (1999).
  • Kenyon BM, Browne F, D’Amato RJ. Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp. Eye Res. 64(6), 971–978 (1997).
  • D’Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc. Natl Acad. Sci. USA 91(9), 4082–4085 (1994).
  • Hosseini H, Nowroozzadeh MH, Salouti R, Nejabat M. Anti-VEGF therapy with bevacizumab for anterior segment eye disease. Cornea 31(3), 322–334 (2012).
  • Nomoto H, Shiraga F, Kuno N et al. Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits. Invest. Ophthalmol. Vis. Sci. 50(10), 4807–4813 (2009).
  • Chen WL, Lin CT, Lin NT et al. Subconjunctival injection of bevacizumab (Avastin) on corneal neovascularization in different rabbit models of corneal angiogenesis. Invest. Ophthalmol. Vis. Sci. 50(4), 1659–1665 (2009).
  • Hashemian MN, Zare MA, Rahimi F, Mohammadpour M. Deep intrastromal bevacizumab injection for management of corneal stromal vascularization after deep anterior lamellar keratoplasty, a novel technique. Cornea 30(2), 215–218 (2011).
  • Bock F, Onderka J, Dietrich T et al. Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 48(6), 2545–2552 (2007).
  • Turgut B, Guler M, Akpolat N, Demir T, Celiker U. The impact of tacrolimus on vascular endothelial growth factor in experimental corneal neovascularization. Curr. Eye Res. 36(1), 34–40 (2011).
  • Güler M, Yilmaz T, Ozercan I, Elkiran T. The inhibitory effects of trastuzumab on corneal neovascularization. Am. J. Ophthalmol. 147(4), 703–708 (2009).
  • Kwon YS, Hong HS, Kim JC, Shin JS, Son Y. Inhibitory effect of rapamycin on corneal neovascularization in vitro and in vivo. Invest. Ophthalmol. Vis. Sci. 46(2), 454–460 (2005).
  • Keskin U, Totan Y, Karadag R, Erdurmus M, Aydin B. Inhibitory effects of SU5416, a selective vascular endothelial growth factor receptor tyrosine kinase inhibitor, on experimental corneal neovascularization. Ophthalmic Res. 47(1), 13–18 (2012).
  • Mackenzie SE, Tucker WR, Poole TR. Bevacizumab (Avastin) for corneal neovascularization – corneal light shield soaked application. Cornea 28(2), 246–247 (2009).
  • Lim M, Jacobs DS, Rosenthal P, Carrasquillo KG. The Boston Ocular Surface Prosthesis as a novel drug delivery system for bevacizumab. Semin. Ophthalmol. 24(3), 149–155 (2009).
  • Sharma A, Ghosh A, Hansen ET, Newman JM, Mohan RR. Transduction efficiency of AAV 2/6, 2/8 and 2/9 vectors for delivering genes in human corneal fibroblasts. Brain Res. Bull. 81(2–3), 273–278 (2010).
  • Cheng HC, Yeh SI, Tsao YP, Kuo PC. Subconjunctival injection of recombinant AAV-angiostatin ameliorates alkali burn induced corneal angiogenesis. Mol. Vis. 13, 2344–2352 (2007).
  • He Z, Pipparelli A, Manissolle C et al. Ex vivo gene electrotransfer to the endothelium of organ cultured human corneas. Ophthalmic Res. 43(1), 43–55 (2010).
  • Sonoda S, Tachibana K, Uchino E et al. Gene transfer to corneal epithelium and keratocytes mediated by ultrasound with microbubbles. Invest. Ophthalmol. Vis. Sci. 47(2), 558–564 (2006).
  • Lai CM, Brankov M, Zaknich T et al. Inhibition of angiogenesis by adenovirus-mediated sFlt-1 expression in a rat model of corneal neovascularization. Hum. Gene Ther. 12(10), 1299–1310 (2001).
  • Yu H, Wu J, Li H et al. Inhibition of corneal neovascularization by recombinant adenovirus-mediated sFlk-1 expression. Biochem. Biophys. Res. Commun. 361(4), 946–952 (2007).
  • Singh N, Amin S, Richter E et al. Flt-1 intraceptors inhibit hypoxia-induced VEGF expression in vitro and corneal neovascularization in vivo. Invest. Ophthalmol. Vis. Sci. 46(5), 1647–1652 (2005).
  • Zhou SY, Xie ZL, Xiao O, Yang XR, Heng BC, Sato Y. Inhibition of mouse alkali burn induced-corneal neovascularization by recombinant adenovirus encoding human vasohibin-1. Mol. Vis. 16, 1389–1398 (2010).
  • Mohan RR, Tovey JC, Sharma A, Schultz GS, Cowden JW, Tandon A. Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo. PLoS ONE 6(10), e26432 (2011).
  • Reed JW, Fromer C, Klintworth GK. Induced corneal vascularization remission with argon laser therapy. Arch. Ophthalmol. 93(10), 1017–1019 (1975).
  • Gerten G. Bevacizumab (Avastin) and argon laser to treat neovascularization in corneal transplant surgery. Cornea 27(10), 1195–1199 (2008).
  • Nirankari VS, Baer JC. Corneal argon laser photocoagulation for neovascularization in penetrating keratoplasty. Ophthalmology 93(10), 1304–1309 (1986).
  • Peter J, Fraenkel G, Goggin M, Drew A. Fluorescein angiographic monitoring of corneal vascularization in lipid keratopathy. Clin. Experiment. Ophthalmol. 32(1), 78–80 (2004).
  • Cherry PM, Garner A. Corneal neovascularization treated with argon laser. Br. J. Ophthalmol. 60(6), 464–472 (1976).
  • Fossarello M, Peiretti E, Zucca I, Serra A. Photodynamic therapy of corneal neovascularization with verteporfin. Cornea 22(5), 485–488 (2003).
  • Qian CX, Bahar I, Levinger E, Rootman D. Combined use of superficial keratectomy and subconjunctival bevacizumab injection for corneal neovascularization. Cornea 27(9), 1090–1092 (2008).
  • Pillai CT, Dua HS, Hossain P. Fine needle diathermy occlusion of corneal vessels. Invest. Ophthalmol. Vis. Sci. 41(8), 2148–2153 (2000).
  • Wertheim MS, Cook SD, Knox-Cartwright NE, Van DL, Tole DM. Electrolysis-needle cauterization of corneal vessels in patients with lipid keratopathy. Cornea 26(2), 230–231 (2007).
  • Stahl A, Stumpp MT, Schlegel A et al. Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications. Angiogenesis 16(1), 101–111 (2013).
  • Lee MY, Chung SK. Treatment of corneal neovascularization by topical application of ascorbic acid in the rabbit model. Cornea 31(10), 1165–1169 (2012).
  • Peyman GA, Kivilcim M, Morales AM, DellaCroce JT, Conway MD. Inhibition of corneal angiogenesis by ascorbic acid in the rat model. Graefes Arch. Clin. Exp. Ophthalmol. 245(10), 1461–1467 (2007).
  • Ribeiro JC, Vagnaldo Fechine F, Ribeiro MZ et al. Potential inhibitory effect of LASSBio-596, a new thalidomide hybrid, on inflammatory corneal angiogenesis in rabbits. Ophthalmic Res. 48(4), 177–185 (2012).
  • Rocher N, Behar-Cohen F, Pournaras JA et al. Effects of rat anti-VEGF antibody in a rat model of corneal graft rejection by topical and subconjunctival routes. Mol. Vis. 17, 104–112 (2011).
  • Hashemian MN, Z-Mehrjardi H, Moghimi S, Tahvildari M, Mojazi-Amiri H. Prevention of corneal neovascularization: comparison of different doses of subconjunctival bevacizumab with its topical form in experimental rats. Ophthalmic Res. 46(1), 50–54 (2011).
  • Habot-Wilner Z, Barequet IS, Ivanir Y, Moisseiev J, Rosner M. The inhibitory effect of different concentrations of topical bevacizumab on corneal neovascularization. Acta Ophthalmol. 88(8), 862–867 (2010).
  • Ahmed A, Berati H, Nalan A, Aylin S. Effect of bevacizumab on corneal neovascularization in experimental rabbit model. Clin. Experiment. Ophthalmol. 37(7), 730–736 (2009).
  • Manzano RP, Peyman GA, Khan P et al. Inhibition of experimental corneal neovascularisation by bevacizumab (Avastin). Br. J. Ophthalmol. 91(6), 804–807 (2007).
  • Yang LL, Zhou QJ, Wang Y, Gao Y, Wang YQ. Comparison of the therapeutic effects of extracts from Spirulina platensis and amnion membrane on inflammation-associated corneal neovascularization. Int. J. Ophthalmol. 5(1), 32–37 (2012).
  • Di Tommaso C, Bourges JL, Valamanesh F et al. Novel micelle carriers for cyclosporin A topical ocular delivery: in vivo cornea penetration, ocular distribution and efficacy studies. Eur. J. Pharm. Biopharm. 81(2), 257–264 (2012).
  • Han Y, Shao Y, Lin Z et al. Netrin-1 simultaneously suppresses corneal inflammation and neovascularization. Invest. Ophthalmol. Vis. Sci. 53(3), 1285–1295 (2012).
  • Hagigit T, Abdulrazik M, Valamanesh F, Behar-Cohen F, Benita S. Ocular antisense oligonucleotide delivery by cationic nanoemulsion for improved treatment of ocular neovascularization: an in-vivo study in rats and mice. J. Control. Release 160(2), 225–231 (2012).
  • Li T, Hu A, Li S et al. KH906, a recombinant human VEGF receptor fusion protein, is a new effective topical treatment for corneal neovascularization. Mol. Vis. 17, 797–803 (2011).
  • BenEzra D, Griffin BW, Maftzir G, Sharif NA, Clark AF. Topical formulations of novel angiostatic steroids inhibit rabbit corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 38(10), 1954–1962 (1997).
  • Byun YS, Chung SK. The effect of methotrexate on corneal neovascularization in rabbits. Cornea 30(4), 442–446 (2011).
  • Zhong YY, Zhang HF, Zhong JX, Bai L, Lu XH. Topical dihydroartemisinin inhibits suture-induced neovascularization in rat corneas through ERK1/2 and p38 pathways. Int. J. Ophthalmol. 4(2), 150–155 (2011).
  • Kim JS, Choi JS, Chung SK. The effect of curcumin on corneal neovascularization in rabbit eyes. Curr. Eye Res. 35(4), 274–280 (2010).
  • Erdurmus M, Yagci R, Yilmaz B et al. Inhibitory effects of topical thymoquinone on corneal neovascularization. Cornea 26(6), 715–719 (2007).
  • Cole N, Hume EB, Jalbert I, Vijay AK, Krishnan R, Willcox MD. Effects of topical administration of 12-methyl tetradecanoic acid (12-MTA) on the development of corneal angiogenesis. Angiogenesis 10(1), 47–54 (2007).
  • Riazi-Esfahani M, Peyman GA, Aydin E, Kazi AA, Kivilcim M, Sanders DR. Prevention of corneal neovascularization: evaluation of various commercially available compounds in an experimental rat model. Cornea 25(7), 801–805 (2006).
  • Peyman GA, Kazi AA, Riazi-Esfahani M, Aydin E, Kivilcim M, Sanders DR. The effect of combinations of flurbiprofen, low molecular weight heparin, and doxycycline on the inhibition of corneal neovascularization. Cornea 25(5), 582–585 (2006).
  • Zhang Z, Ma JX, Gao G et al. Plasminogen kringle 5 inhibits alkali-burn-induced corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 46(11), 4062–4071 (2005).
  • Wu PC, Yang LC, Kuo HK et al. Inhibition of corneal angiogenesis by local application of vasostatin. Mol. Vis. 11, 28–35 (2005).
  • Gohto Y, Obana A, Kanai M, Nagata S, Miki T, Nakajima S. Photodynamic therapy for corneal neovascularization using topically administered ATX-S10 (Na). Ophthalmic Surg. Lasers 31(1), 55–60 (2000).
  • Stevenson W, Cheng SF, Dastjerdi MH, Ferrari G, Dana R. Corneal neovascularization and the utility of topical VEGF inhibition: ranibizumab (Lucentis) vs bevacizumab (Avastin). Ocul. Surf. 10(2), 67–83 (2012).
  • Cheng SF, Dastjerdi MH, Ferrari G et al. Short-term topical bevacizumab in the treatment of stable corneal neovascularization. Am. J. Ophthalmol. 154(6), 940–948 (2012).
  • Dastjerdi MH, Al-Arfaj KM, Nallasamy N et al. Topical bevacizumab in the treatment of corneal neovascularization: results of a prospective, open-label, noncomparative study. Arch. Ophthalmol. 127(4), 381–389 (2009).
  • Michels R, Michels S, Kaminski S. Effect of combined topical heparin and steroid on corneal neovascularization in children. Ophthalmic Surg. Lasers Imaging 43(6), 452–458 (2012).
  • Chen P, Yin H, Wang Y et al. Multi-gene targeted antiangiogenic therapies for experimental corneal neovascularization. Mol. Vis. 16, 310–319 (2010).
  • Kuo CN, Yang LC, Yang CT et al. Inhibition of corneal neovascularization with plasmid pigment epithelium-derived factor (p-PEDF) delivered by synthetic amphiphile INTeraction-18 (SAINT-18) vector in an experimental model of rat corneal angiogenesis. Exp. Eye Res. 89(5), 678–685 (2009).
  • Jani PD, Singh N, Jenkins C et al. Nanoparticles sustain expression of Flt intraceptors in the cornea and inhibit injury-induced corneal angiogenesis. Invest. Ophthalmol. Vis. Sci. 48(5), 2030–2036 (2007).
  • Kim B, Lee S, Suvas S, Rouse BT. Application of plasmid DNA encoding IL-18 diminishes development of herpetic stromal keratitis by antiangiogenic effects. J. Immunol. 175(1), 509–516 (2005).
  • Murthy RC, McFarland TJ, Yoken J et al. Corneal transduction to inhibit angiogenesis and graft failure. Invest. Ophthalmol. Vis. Sci. 44(5), 1837–1842 (2003).

Website

  • ClinicalTrials.gov. Massachusetts Eye and Ear Infirmary. Topical IL-1-Ra for treatment of corneal neovascularization (NCT00915590). www.clinicaltrials.gov (Accessed 19 April 2012)

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.