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23 Indian Journal of Ophthalmology Vol. ??? No. ???

IJO_404_11R7

OrbidentRefractive Surgery andMedicalCenter, 1Department ofOphthalmology,Medical andHealthScienceCenter,UniversityofDebrecen,Debrecen,Hungary

Correspondence to:Dr.ZiadHassan,OrbidentRefractiveSurgeryandMedicalCenter,Debrecen,Hungary,Nagyerdeiblvd.98,H-4012Debrecen,Hungary.E-mail:zhassan@dote.hu

Manuscriptreceived:04-08-2011;Revisionaccepted:14.03.12

Collagen cross-linking in the treatment of pellucid marginal degeneration

Ziad Hassan, Gabor Nemeth1, Laszlo Modis1, Eszter Szalai1, Andras Berta1

Pellucidmarginal degeneration (PMD) is an uncommon causeof inferior peripheral corneal thinning disorder, characterizedby irregularastigmatism.Weanalyzeda caseofbilateralPMDpatientand treatedoneeyewithcornealcollagencross-linking(CXL) therapy. Corneal topography was characteristic forPMD. Visual acuity, slitlamp examinations, tonometry, andcorneal thickness were observed. Simulated keratometric andtopographicindexvaluesweredetectedwithcornealtopography.Uncorrected,LogMARvisualacuityhasimprovedfrom+0.8to+0.55 duringthe6monthsand+0.3duringthe8monthsfollow-up after CXL. Pachymetry values and intraocular pressureshowednochanges.Keratometricvaluesandtopograficindexesdisclosednoprogressionof thedisease.CXLmaypostponeoreliminatetheneedofcornealtransplantationincaseswithPMD.

Key words: Collagen cross-linking, pellucid marginaldegeneration,PentacamHR

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Pellucidmarginal degeneration (PMD) of the cornea is aprogressive,rare,anduncommonnoninflammatorycornealdisorder characterized by the thinning in the peripheralportionoftheinferiorcorneawithmarkedsteepeningjustsuperiortothethinnedzone.[1,2]Itoccursinbothmenandwomen and can be differentiated from other peripheralcorneal thinning disorders such as keratoconus andkeratoglobusbyitscharacteristicsthatthisthinningoccurs1–3mmfromthelimbusinthe4–8o’clockposition.[3]ItisdifferentiatedfromperipheralcornealdisordersassociatedwithinflammationsuchasTerrien’smarginaldegenerationandMooren’s ulcer by the absence of vascularisation.Althoughhistopathologically it is considered a variant of

keratoconus,itdiffersinthatthemarkedcornealsteepeningoccursmoreinferiorly.[1]

Cornealcross-linkingwasintroducedbyWollensaket al.in2003forthetreatmentofprogressivekeratoconusandrelateddisordersincreasingthebiomechanicalstrengthofthecorneabyabout300%.[4]

Herewepresentone case showing the featuresofPMDbothclinicallyandtopographicallytreatedbycollagencross-linking (CXL). Itwas clinically typical bilateral PMDwitha characteristicpatternof irregular astigmatismon cornealtopography,withchiefcomplaintsofprogressivedimnessofvisioncausedbyirregularastigmatism.TheCXLtreatmentcanstopPMDprogressionandproducebetterqualityofvision.

Case ReportWeanalyzedacaseofadvancedbilateralPMDpatientandtreated one eyewith cornealCXL.A 55-year-oldmale ispresented, complaining of progressive dimness of visionin both eyeswith decreased vision started 1 year beforeexaminationsatourclinic,butthevisuallosswaslargerintherighteye.Therewasnohistoryofexcessiveeyerubbing,trauma, contact lenswear, or episodic redness of the eye.Therewasnofamiliarhistory.Earlier,hewasdiagnosedwithglaucomasimplex treatedwith timolol0.5%.Hisrighteyewaspseudophakic,andhislefteyehadposteriorsubcapsularcataract.Hehadhighbloodpressure and type IIdiabetesmellituswas treated for around9 years. Thepatient triedrigidgas-permeable contact lenses but couldnever get anacceptablefit.Visual acuity, slitlamp examination, cornealthicknessmapmeasurement (PentacamHR,Oculus), andtonometrywerecarriedout,andsimulatedkeratometric(SK1,SK2)andtopographicindexvaluesweredetectedwithcornealtopograph(TomeyTMS4).Ophthalmic examination revealedhis best-uncorrected

visualacuity,avalueof+0.8 in the righteyeand+0.1 in thelefteyeobservedwithalogarithmicscale(LogMAR).Slitlampexaminationofthecorneashowedinferiorperipheralcorneal-thinningwithoutironlines,vascularization,orlipiddeposition[Fig.1].Thelesionwasnonulcerativeandinflammatory,andimpliedtheprotrusionofthecornea.Betweenthethinnedareaand the limbus, thecorneal thicknesswasnormal.However,thelefteyeshowedaclearbandofperipheralthinningabout1–2mmwide,withanteriorprotrusionofthecorneajustabovethe thinnedarea.A2.0-mmzoneofnormal-thickness corneawasseenbetweenthethinnedareaandthelimbus.Scheimpflugimage(OculusPentacamHR)oftheanteriorsegmentoftherighteyeshowsirregularshapedcentralcornealregion[Fig.2aandb].

Both anterior chamberswere 4.11mmdeep. Cornealthicknessmeasuredbyultrasonicpachymeteroftherighteyewere502μmcentrally and520μmperipherally; in the lefteye, thereadingswere540μmcentrally,and520μmat theperiphery.Theintraocularpressuremeasuredbynoncontacttonometrywasinnormalrangeinbotheyes.

CornealtopographywascharacteristicforPMD.Theverticalaxisimagesshowedsignificantcentralirregularagainst-the-ruleastigmatism,markedperipheralthinningwithin2.0mmofthelimbus,andmorenormalcornealthicknessinferiortothebandof thinning.Topograph sagittal curvaturemaponthe right eye showedverticalflattingand irregular inferior

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24 Indian Journal of Ophthalmology Vol. ??? No. ???

corneal astigmatism.Thehorizontal axishadmorenormalcorneal contour and thickness.Keratometric readingswere53.98D/36.04Dintherighteye.Inbotheyes,therewasabow-tie-shapedcornealastigmatismwithavalueof17.96Dintherighteye[Fig.3].ThisclinicalpicturewasconsistentwithadiagnosisofPMDofbotheyes.

CXLwasperformedontherighteyeusingInProCCL-Lixdevice (Norderstadt,Germany).During treatment, 8mmof the central corneal epitheliumwas removed and 0.1%riboflavinsolution(with20%dextrane)wasinstilledonthesurfaceofthecorneawitheccentricmethodofSpadea[5]andwasrepeatedevery2minutesthereafter.Inthemeantime,UV-Airradiationwasperformedwithanemissionat370nm,withradiantenergyof3mW/cm2,focusingdistanceof60mm,andlastedfor30minutes.Thepostoperativetreatmentwasantiobiotic eyedrops for 5days (tobramycin) and steroideyedrops(fluorometholone)andartificial teardropsforatleast1month.Wedidnotusecontactlenspostoperatively.There was no corneal edema or endothelial damagepostoperatively.

The follow-up periodwas 8months. Visual acuity,simulatedkeratometricindexes,andcornealthicknessvaluesweredetectedduringthepostoperativeperiod.Uncorrectedvisualacuityhasincreasedfrom+0.8to+0.55;best-correctedvisualacuitywas+0.25withacorrectionofsphericalequivalentof-4.0D8monthsafterCXLtreatment.AfterCXLtreatment,SK1decreasedto50.48DandSK2to33.97D[Fig.4].Pre-andpostoperative corneal back surface Scheimpflug pictures(PentacamHR)donotshowdifference[Fig.5].

Pachymetrymapshowedminimal increase inperipheralcorneal thickness (from520μmpreoperatively to 528μmpostoperatively) 8months after treatment.No change inintraocular pressurewasmeasured, during the follow-upperiod.IOPvariedbetween14and19mmHg.OurdataaresummarizedinTables1and2.

DiscussionPMDhasbeenpostulatedtotheabnormalityoftheconnectivetissue,buttheexactpathogenesisisstillunknown.Oncornealtopography,marked steepening of the inferior cornealperipherycanbeseen,whichalsoextendsintomid-peripheralinferior cornealmeridians. Themid-peripheral cornea isgraduallydecreasedinkeratometricpowerabovetheinferiorobliquemeridians.[3,6]Ourpatienthadallthesefeaturesinbotheyes,andtherewasnostromalthicknesslessthan400μm,butthelefteyeshowedlessdeviationthantherighteye.TheusualtreatmentsforPMDareintrastromalringinsertion,lamellarkeratoplasty, crescentic lamellar keratoplasty, penetratingkeratoplasty,cyanoacrylateadhesive,andabandagecontactlens.Conservativetreatmentisalsopossible.[7]Corneal transplantation for keratectasia is a difficult

procedurewitha longanduncertainvisual recovery.Ertanet al.[8] inserted intacs ring using a femtosecond laser tocorrect pellucidmarginal corneal degenerationwith safeandefficientresults.InthereportofStojanovicet al.,12eyeswere treatedwith topography-guided customablationandCXL,which afteruncorrectedvisual acuity increased andastigmatismandkeratometricasymmetrydecreased.[9]Spadeadescribed eccentric irradiationCXL technique followedbyusincaseofPMD.[5]Kymioniset al.[10]treatedawomanwithsimultaneousphotorefractivekeratectomyandcornealCXLwithriboflavin-ultraviolet-Airradiationforthetreatmentofprogressivepellucidmarginal cornealdegeneration inbotheyeswithgoodresults.Histologicallyandclinically,CXL isawell-circumscribedandwell-publishedtherapicpossibilityofcornealectasias.[11,12]TherearesomepossiblecomplicationsafterCXL:earlypseudo-haze,bacterialinfection,[13]scarring,melting,orperforation.The safetyparameterof aminimalstromalthicknessof400μmtosparetheendothelium.[14]

In this case, progression had been stopped by CXLtreatment, and the best-corrected visual acuity increasedduring the observationperiod.No intraoperative or earlypostoperativecomplicationsoccurred.TheCXLirradiationwassafeandefficientinthetreatmentofcertainstagesofPMDs withthehelpofwhichprogressioncanbereversedoratleaststopped,andvisualacuitycanbeimproved.ThismethodmaypostponeoreliminatetheneedofcornealtransplantationincaseswithPMD.

Figure 1: Slit-lamp photograph of the right eye shows inferior steepening with a clear zone between limbus and the steep band

Table 1: Patient data before and after collage cross-linking treatment

Central corneal thickness (µm)

Peripheral corneal thickness (µm)

UCVA BCVA Intraocular pressure (mmHg)

Preoperative 505 520 +0.8 +0.7 14

Postoperative 1 month 589 530 +0.6 +0.4 19

Postoperative 3 months 506 527 +0.55 +0.3 14

Postoperative 6 months 501 518 +0.55 +0.3 16 Postoperative 8 months 499 528 +0.3 +0.25 14

UCVA: Uncorrected LogMAR visual acuity, BCVA: Best-corrected visual acuity

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Figure 3: Preoperative corneal topographic picture of the right eye shows the characteristic bow-tie appearance of corneal steepening (red zones) and midperipheral inferior corneal flattening

Figure 4: Corneal topograph shows flattening of the inferior cornea 8 months after CXL treatment

Figure 5: Pre- and postoperative corneal back surface Scheimpflug pictures (Pentacam HR) do not show difference

4. WollensakG,SpoerlE,SeilerT.Riboflavin/ultraviolet-A-inducedcollagencrosslinkingforthetreatmentofkeratoconus.JCataractRefractSurg2003;135:620-7.

5. SpadeaL.Corneal collagen cross-linkingwith riboflavin andUVAirradiationinpellucidmarginaldegeneration.JRefractSurg2010;26:375-7.

6. KlyceSD.Computer-assistedcornealtopography:highresolutiongraphic presentation and analysis of keratoscopy. InvestOphthalmolVisSci1984;25:1426-35.

7. Forooghian F,AssaadD,DixonWS. Successful conservativetreatment of hydropswith perforation in pellucidmarginaldegeneration.CanJOphthalmol2006;41:74-7.

8. ErtanA, BahaditM. Intrastromal ring segment insertionusinga femtosecond laser to correctpellucidmarginal corneal

References1. KrachmerJH.Pellucidmarginaldegeneration.ArchOphthalmol

1978;96:1217-21.

2. WalkerRN,KhachikianSS,BelinMW.Scheimpflugphotographicdiagnosisofpellucidmarginaldegeneration.Cornea2008;27:963-6.

3. Krachmer JH, FederRS, BelinMW.Keratoconus and relatednoninflammatory corneal thinningdisorders. SurvOphthalmol1984;28:293-322.

Table 2: Patient data before and after surgery

K1 K2 SAI SRI

Preoperative 53.98 D 36.02 D 5.37 2.40

Postoperative 1 month 54.45 D 37.44 D 7.01 2.43

Postoperative 3 months 45.34 D 41.93 D 2.91 2.13

Postoperative 6 months 43.44 D 38.57 D 2.21 2.01Postoperative 8 months 50.48 D 33.97 D 1.52 2.22

K1, K2: Keratometric data, SAI: Surface asymmetry index, SRI: surface regularity index

Figure 2: (a and b) Scheimpflug image (Oculus Pentacam HR) of the anterior segment shows irregular shaped central corneal region

ba

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degeneration.JCataractRefractSurg2006;32:1710-6.9. StojanovicA,Zhang J,ChenX,Nitter TA,Chen S,WangQ.

Topography-guidedtransepithelialsurfaceablationfollowedbycorneal collagen cross-linkingperformed in a single combinedprocedureforthetreatmentofkeratoconusandpellucidmarginaldegeneration.JRefractSurg2010;26:145-52.

10. Kymionis GD, KaravitakiAE, Kounis GA, Portaliou DM,YooSH,PallikarisIG.Managementofpellucidmarginalcornealdegenerationwith simultaneous customized photorefractivekeratectomyand collagen crosslinking. JCataractRefract Surg2009;35:1298-301.

11. WollensakG.Crosslinkingtreatmentofprogressivekeratoconus:Newhope.CurrOpinOphthalmol2006;17:356-60.

12. WollensakG.Cornealcollagencross-linking:Newhorizons.ExpertRevOphthalmol2010;5:201-15.

13. SharmaN,MaharanaP,SinghG,TitiyalJS.Pseudomonaskeratitisaftercollagencrosslinkingforkeratoconus:Casereportandreviewofliterature.JCataractRefractSurg2010;36:517-20.

14. WollensakG,SpoerlE,WilschM,SeilerT.Endothelialcelldamageafter riboflavin-ultraviolet-A treatment in the rabbit. JCataractRefractSurg2003;29:1786-90.

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Source of Support: Nil. Conflict of Interest: None declared.