Polymethylmethacrylate (PMMA) segments are normally used in additive surgery to treat both corneal ectasia post laser-assisted in situ keratomileusis and keratoconus. The aim of this work was to develop an experimental animal model to induce wound healing in the deep stroma in corneas of hens.
Methods
PMMA segments were implanted in the right eyes of 40 adult hens without suture in the wound incision. Animals were randomized for 5 time points to histopathology study (1, 3, 15, 30, and 90 days) being clinically evaluated during the experiment.
Results
Thirty-four eyes (85%) had a successful clinical outcome and intraoperative mistakes occurred in 6 eyes (15%), including anterior chamber perforation resulting in abscess (1), excess of lamellar dissection with segment migration (3), and peripheral incisions evolving with neovascularization (2). At 24 hours, all the epithelial injuries were completed in integrity, but a persistent stromal incision, with a fish mouth form, was observed until day 15. Corneal edema disappeared at the fifth day. Haze, keratocyte cell death, keratocyte proliferation, myofibroblast differentiation, and new matrix production were observed in length around the segment.
Conclusions
Wound healing was induced in the deep corneal stroma by means of PMMA segment implantation in a new animal model developed in hens.
ErtanA., ColinJ.Intracorneal rings for keratoconus and keratectasia. J Cataract Refract Surg2007; 33: 1303–14.
4.
McMonniesC.W.The biomechanics of keratoconus and rigid contact lenses. Eye Contact Lens2005; 31: 80–92.
5.
WollensakG., SpoerlE., SeilerT.Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol2003; 135: 620–7.
6.
FunnellC.L., BallJ., NobleB.A.Comparative cohort study of the outcomes of deep lamellar keratoplasty and penetrating keratoplasty for keratoconus. Eye2006; 20: 527–32.
ClinchT.E., LempM.A., FoulksG.N., SchanzlinD.J.Removal of INTACS for myopia. Ophthalmology2002; 109: 1441–6.
9.
RuckhoferJ., StoiberJ., TwaM.D., GrabnerG.Correction of astigmatism with short arc-length intrastromal corneal ring segments: preliminary results. Ophthalmology2003; 110: 516–24.
10.
GuellJ.L., VelascoF., SanchezS.I., GrisO., Garcia-RojasM.Intracorneal ring segments after laser in situ keratomileusis. J Refract Surg2004; 20: 349–55.
11.
SiganosC.S., KymionisG.D., AstyrakakisN., PallikarisI.G.Management of corneal ectasia after laser in situ keratomileusis with INTACS. J Refract Surg2002; 18: 43–6.
12.
Uceda-MontanesA., TomasJ.D., AlioJ.L.Correction of severe ectasia after LASIK with intracorneal ring segments. J Refract Surg2008; 24: 408–11.
SiganosD., FerraraP., ChatzinikolasK., BessisN., PapastergiouG.Ferrara intrastromal corneal rings for the correction of keratoconus. J Cataract Refract Surg2002; 28: 1947–51.
15.
RuckhoferJ., StoiberJ., AlznerE., GrabnerG.One year results of European Multicenter Study of intrastromal corneal ring segments. Part 2: complications, visual symptoms, and patient satisfaction. J Cataract Refract Surg2001; 27: 287–96.
16.
TwaM.D., RuckhoferJ., KashR.L., CostelloM., SchanzlinD.J.Histologic evaluation of corneal stroma in rabbits after intrastromal corneal ring implantation. Cornea2003; 22: 146–52.
17.
KolozsvariL., NogradiA., HoppB., BorZ.UV absorbance of the human cornea in the 240- to 400-nm range. Invest Ophthalmol Vis Sci2002; 43: 2165–8.
18.
NagyZ.Z., HiscottP., SeitzB., Schlotzer-SchrehardtU., SuvegesI., NaumannG.O.Clinical and morphological response to UV-B irradiation after excimer laser photorefractive keratectomy. Surv Ophthalmol1997; 42 Suppl 1: S64–76.
FowlerW.C., ChangD.H., RobertsB.C., ZarovnayaE.L., PraiaA.D.A new paradigm for corneal wound healing research: the white leghorn chicken (Gallus gallus domesticus). Curr Eye Res2004; 28: 241–50.
21.
Martinez-GarciaM.C., Merayo-LlovesJ., Blanco-MezquitaT., Mar-SardanaS.Wound healing following refractive surgery in hens. Exp Eye Res2006; 83: 728–35.
22.
GomezS., HerrerasJ.M., MerayoJ., GarciaM., ArguesoP., CuevasJ.Effect of hyaluronic acid on corneal haze in a photorefractive keratectomy experimental model. J Refract Surg2001; 17: 549–54.
23.
Merayo-LlovesJ., YanezB., MayoA., MartinR., PastorJ.C.Experimental model of corneal haze in chickens. J Refract Surg2001; 17: 696–9.
24.
TorresR.M., Merayo-LlovesJ., Blanco-MezquitaJ.T.. Experimental model of laser in situ keratomileusis in hens. J Refract Surg2005; 21: 392–8.
25.
LeeJ.B., JavierJ.A., ChangJ.H., ChenC.O., KatoT., AzarD.T.Confocal and electron microscopic studies of laser subepithelial keratomileusis (LASEK) in the white leghorn chick eye. Arch Ophthalmol2002; 120: 1700–6.
26.
NozalM.J., BernalJ.L., MartinM.T., BernalJ., TorresR.M., MerayoJ.LC-ESI-MSD fast determination of residual mitomycin C in hen aqueous humour after corneal refractive surgery. J Pharm Biomed Anal2006; 40: 100–4.
27.
TorresR.M., Merayo-LlovesJ., DayaS.M.. Presence of mitomycin-C in the anterior chamber after photorefractive keratectomy. J Cataract Refract Surg2006; 32: 67–71.
28.
FantesF.E., HannaK.D., WaringG.O.3rd, PouliquenY., ThompsonK.P., SavoldelliM.Wound healing after excimer laser keratomileusis (photorefractive keratectomy) in monkeys. Arch Ophthalmol1990; 108: 665–75.
29.
SeilerT., KahleG., WollensakJ.[Scar formation in the cornea after photorefractive keratectomy.]Ophthalmologe1995; 92: 492–5.
30.
LinsenmayerT.F., FitchJ.M., GordonM.K.. Development and roles of collagenous matrices in the embryonic avian cornea. Prog Retin Eye Res1998; 17: 231–65.
31.
PatelS., ReinsteinD.Z., SilvermanR.H., ColemanD.J.The shape of Bowman's layer in the human cornea. J Refract Surg1998; 14: 636–40.
32.
SundarrajN., FiteD., BelakR.. Proteoglycan distribution during healing of corneal stromal wounds in chick. Exp Eye Res1998; 67: 433–42.
33.
MarchantJ.K., ZhangG., BirkD.E.Association of type XII collagen with regions of increased stability and keratocyte density in the cornea. Exp Eye Res2002; 75: 683–94.
34.
MullerL.J., PelsE., VrensenG.F.The specific architecture of the anterior stroma accounts for maintenance of corneal curvature. Br J Ophthalmol2001; 85: 437–43.
35.
AmmM., WetzelW., WinterM., UthoffD., DunckerG.I.Histopathological comparison of photorefractive keratectomy and laser in situ keratomileusis in rabbits. J Refract Surg1996; 12: 758–66.
36.
HolzerM.P., VargasL.G., SandovalH.P.. Corneal flap complications in refractive surgery: Part 1: development of an experimental animal model. J Cataract Refract Surg2003; 29: 795–802.
37.
MohanR.R., HutcheonA.E., ChoiR.. Apoptosis, necrosis, proliferation, and myofibroblast generation in the stroma following LASIK and PRKExp Eye Res2003; 76: 71–87.
38.
CochenerB., Savary-LeFlochG., ColinJ.Effect of intrastromal corneal ring segment shift on clinical outcome: one year results for low myopia. J Cataract Refract Surg2000; 26: 978–86.
39.
StultingR.D., LahnersW.J., CarrJ.D.Advances in refractive surgery: 1975 to the present. Cornea2000; 19: 741–53.
40.
MaD.H., ChenJ.K., ZhangF., LinK.Y., YaoJ.Y., YuJ.S.Regulation of corneal angiogenesis in limbal stem cell deficiency. Prog Retin Eye Res2006; 25: 563–90.
41.
Al-TorbakA., Al-AmriA., WagonerM.D.Deep corneal neovascularization after implantation with intrastromal corneal ring segments. Am J Ophthalmol2005; 140: 926–7.
42.
CoskunsevenE., KymionisG.D., TsiklisN.S.. One-year results of intrastromal corneal ring segment implantation (KeraRing) using femtosecond laser in patients with keratoconus. Am J Ophthalmol2008; 145: 775–9.
43.
JesterJ.V., PetrollW.M., CavanaghH.D.Corneal stromal wound healing in refractive surgery: the role of myofibroblasts. Prog Retin Eye Res1999; 18: 311–56.
44.
Moller-PedersenT., CavanaghH.D., PetrollW.M., JesterJ.V.Corneal haze development after PRK is regulated by volume of stromal tissue removal. Cornea1998; 17: 627–39.
45.
RajanM.S., O'BrartD., JaycockP., MarshallJ.Effects of ablation diameter on long-term refractive stability and corneal transparency after photorefractive keratectomy. Ophthalmology2006; 113: 1798–806.
46.
SpadeaL., SabettiL., D'AlessandriL., BalestrazziE.Photorefractive keratectomy and LASIK for the correction of hyperopia: 2-year follow-up. J Refract Surg2006; 22: 131–6.
47.
JesterJ.V., Ho-ChangJ.Modulation of cultured corneal keratocyte phenotype by growth factors/cytokines control in vitro contractility and extracellular matrix contraction. Exp Eye Res2003; 77: 581–92.
48.
IvarsenA., LaurbergT., Moller-PedersenT.Role of keratocyte loss on corneal wound repair after LASIK. Invest Ophthalmol Vis Sci2004; 45: 3499–506.
49.
WilsonS.E.Analysis of the keratocyte apoptosis, keratocyte proliferation, and myofibroblast transformation responses after photorefractive keratectomy and laser in situ keratomileusis. Trans Am Ophthalmol Soc2002; 100: 411–33.
50.
WilsonS.E., ChaurasiaS.S., MedeirosF.W.Apoptosis in the initiation, modulation and termination of the corneal wound healing response. Exp Eye Res2007; 85: 305–11.
51.
HelenaM.C., BaerveldtF., KimW.J., WilsonS.E.Keratocyte apoptosis after corneal surgery. Invest Ophthalmol Vis Sci1998; 39: 276–83.
52.
WilsonS.E., HeY.G., WengJ.. Epithelial injury induces keratocyte apoptosis: hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization and wound healing. Exp Eye Res1996; 62: 325–7.
53.
WilsonS.E., MohanR.R., MohanR.R., AmbrosioR.Jr., HongJ., LeeJ.The corneal wound healing response: cytokine-mediated interaction of the epithelium, stroma, and inflammatory cells. Prog Retin Eye Res2001; 20: 625–37.
54.
GörgesH.W., HohH., RehfeldtK.[Intracorneal ring segments for correction of myopia. Results of microsurgery technique.] Ophthalmologe2001; 98: 617–22.
55.
LingE., RobinsonD.S.Transforming growth factor-beta1: its anti-inflammatory and pro-fibrotic effects. Clin Exp Allergy2002; 32: 175–8.
56.
HyytiainenM., PenttinenC., Keski-OjaJ.Latent TGF-beta binding proteins: extracellular matrix association and roles in TGF-beta activation. Cht Rev Clin Lab Sci2004; 41: 233–64.
57.
YuQ., StamenkovicI.Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev2000; 14: 163–76.
58.
Murphy-UllrichJ.E., PoczatekM.Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev2000; 11: 59–69.
59.
AzarD.T., HahnT.W., JainS., YehY.C., Stetler-StevensenW.G.Matrix metalloproteinases are expressed during wound healing after excimer laser keratectomy. Cornea1996; 15: 18–24.
60.
OhJ.Y., KimM.K., ShinM.S.. The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury. Stem Cells2008; 26: 1047–55.
