Contact Lens & Anterior Eye 33 (2010) 157166

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Review

Kerato

Miguel R , Jaa MGR Doctoreb Menicon Co.,c Ophthalmic R , UK

a r t i c l

Keywords:KeratoconusReviewEpidemiologyClassicationAetiologyManagement

ary estimepened. Dh sperin a

around the cone base. Vogts striaes, which are ne vertical lines produced by Descemets membranecompression, is another characteristic sign. Most patients eventually develop corneal scarring. Munsonssign, a V-shape deformation of the lower eyelid in downward position; Rizzutis sign, a bright reectionfrom the nasal area of the limbus when light is directed to the limbus temporal area; and breakagesin Descemets membrane causing acute stromal oedema, known as hydrops, are observed in advancedstages.

1. Denitio

Keratocoderives fromKeratoconueral [2,3] anby localizedthinned cortemporal alocalizationcauses highquality. It uthe life, noalso been fotypically prstabilizes [

CorresponE-mail add

1367-0484/$ doi:10.1016/j.Classications based on morphology, disease evolution, ocular signs and index-based systems ofkeratoconus have been proposed. Theories into the genetic, biomechanical and biochemical causes ofkeratoconus have been suggested. Management varies depending on disease severity. Incipient cases aremanaged with spectacles, mild to moderate cases with contact lenses and severe cases can be treatedwith keratoplasty. This article provides a review on the denition, epidemiology, clinical features, clas-sication, histopathology, aetiology and pathogenesis, and management and treatment strategies forkeratoconus.

2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

n

nus, which was rst described in detail in 1854 [1],the Greek words Kerato (cornea) and Konos (cone).

s is the most common primary ectasia. It is a bilat-d asymmetric [4,5] corneal degeneration characterizedcorneal thinning which leads to protrusion of the

nea. Corneal thinning normally occurs in the inferior-s well as the central cornea [6], although superiors have also been described [7,8]. Corneal protrusionmyopia and irregular astigmatism, affecting visual

sually becomes apparent during the second decade ofrmally during puberty [3,9], although the disease hasund to develop earlier [10] and latter in life [9], and itogresses until the fourth decade of life, when it usually9]. A recent study has determined that 50% of non-

ding author. Tel.: +34 610 832 234; fax: +34 916 388 774.ress: j.santodomingo@menicon.com (J. Santodomingo-Rubido).

affected eyes of subjects with unilateral keratoconus will developthe disease in 16 years [11].

2. Epidemiology

The incidenceandprevalence in thegeneral populationhasbeenestimated to be between 5 and 23, and 5.4 per 10,000, respectively[3,9,12]. Differences on the rates reported are attributed to differ-ent denitions and diagnostic criteria employed between studies.However, it would not be surprising to expect an increase in theincidence and prevalence rates of this disease over the next fewyearswith the currentwide spread use of corneal topography lead-ing to improved diagnosis.

Keratoconus affects bothgenders, although it is unclearwhethersignicant differences between males and females exist. Somestudies have not found differences in the prevalence between gen-ders [3,13]; others have found a greater prevalence in females[12,14]; while other investigators have found a greater prevalencein males [1518].

Keratoconus is also known to affect all ethnicities [9,1820].In a study conducted in the Midlands area of the United King-

see front matter 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.clae.2010.04.006conus: A review

omero-Jimneza, Jacinto Santodomingo-Rubidob,

s, Madrid, SpainLtd (Madrid Ofce), Iglesia 9, Apartamento 106, 28220 Majadahonda, Madrid, Spainesearch Group, Life and Health Sciences, Aston University, Aston Triangle, Birmingham

e i n f o a b s t r a c t

Keratoconus is themost commonprimboth genders and all ethnicities. The e

Ocular signs and symptoms vary dunless corneal topography is performwhich cannot be compensated for witerate and advance cases, a hemosidec lae

mes S. Wolffsohnc

ctasia. It usually occurs in the second decade of life and affectsated prevalence in the general population is 54 per 100,000.ding on disease severity. Early forms normally go unnoticedisease progression is manifested with a loss of visual acuityctacles. Corneal thinning frequently precedes ectasia. In mod-rc or circle line, known as Fleischers ring, is frequently seen

158 M. Romero-Jimnez et al. / Contact Lens & Anterior Eye 33 (2010) 157166

Fig. 1. Vog

dom, a prevAsians comYorkshire, a7.5 times hhypothesizecially rst-Asian popu

3. Clinical

The oculon disease sical or frustsymptomstionerunlesfor diagnoscant loss ofspectacles.about the pbetter is difmatism [9].expected frpatient. ThretinoscopyThrough recones apexvisual acuitbacklightinatometry reappear irrecornea is nosign preced

In modearc or circleseen arounbe an accumcornea as athediseaseprocess [24striae (Fig. 1of Descemepressure iscontact len(Fig. 2) and(Fig. 3) are

Fig. 2. Increased visibility of corneal nerves in a keratoconus.

verity stages of the disease [13]. The majority of contacttients eventually develop corneal scarring. Munsons sign, ae deformation of the lower eyelid when the eye is in down-ositilimbns frets

g acud sig

ssic

eral cvoluted in

orph

ssica

Thted ifero-mallts Striae sign. Vertical lines in Descemets membrane are noted.

alence of 4:1, and an incidence of 4.4:1 was found inpared to Caucasians [17]. In other study undertaken inlso in the United Kingdom, the incidence found was

igher in Asians compared to Caucasians. The latter wasd to be attributed to consanguineous relations, espe-

cousin marriages, which commonly take place in thelation of the area assessed [21].

features

ar symptoms and signs of keratoconus vary dependingeverity. At incipient stages, also referred to as subclin-re forms, keratoconus does not normally produce anyand thus can go unnoticed by the patient and practi-s specic tests (i.e., corneal topography) areundertakenis [22]. Disease progression is manifested by a signi-visual acuity which cannot be compensated for with

Therefore, eye care practitioners should be suspiciousresence of keratoconus when a visual acuity of 6/6 orcult to achieve with increasing against-the-rule astig-Near visual acuity is generally found to be better thanom the refraction, distance visual acuity and age of thee appearance of scissor shadows while performingsuggests the development of irregular astigmatism.

tinoscopy it is possible to estimate the location of theand its diameter, and the adjustable spectacle correctedy achievable. The Charleux oil drop that is observed byg themydriatric pupil also poses awarning sign [9]. Ker-

ent selens paV-shapward pof theare sigDescemcausinloss an

4. Cla

Sevease epropos

4.1. M

Cla

Nippleis locathe inis noradings are commonlywithin the normal range, butmaygular. Corneal thinning, where the thinnest part of thermally located outside the visual axis, is also a commoning ectasia.rate and advance cases of keratoconus, a hemosiderinline, commonly known as Fleischers ring, is frequently

d the cone base [23]. This line has been suggested toulation of iron deposits from the tear lm onto the

result of severe corneal curvature changes induced byand/or due tomodication of thenormal epithelial slide]. Another characteristic sign is the presence of Vogts),which are ne vertical lines producedby compressionts membrane, which tend to disappear when physicalexerted on the cornea digitally [13] or by gas permeables wear [25]. The increased visibility of corneal nervesobservation of supercial and deep corneal opacitiesalso common signs, which can be present at differ- Fig. 3on, and Rizzutis sign, a bright reection of the nasal areaus when light is directed to the temporal limbal area,equently observed in advanced stages [13]. Breaks inmembrane have been described in severe keratoconus,te stromal oedema, known as Hydrops, sudden visionnicant pain [26].

ation

lassications of keratoconus basedonmorphology, dis-ion, ocular signs and index-based systems have beenthe literature:

ology

lly, keratoconus has been classied into [9,2729]:

e cone has a diameter5mm, round morphology andn the central or paracentral cornea, more commonly innasal corneal quadrant. Correction with contact lensesy relatively easy.. Signicant corneal scarring induced by contact lens wear.

M. Romero-Jimnez et al. / Contact Lens & Anterior Eye 33 (2010) 157166 159

Table 1Keratoconus classication based on disease evolution. VA, visual acuity; D, dioptres.

Stage Description

1 Frustre or subclinical form; diagnosed by cornealtopography; 6/6VA achievable with spectacle correction.

2 Early form; mild corneal thinning; corneal scarring absent.3 Moderate form; corneal scarring and opacities absent;

Vogts striae; Fleischers ring; 55.00D; cornealscarring, 5mmand a paracentral to periph-eral location, more commonly in the infero-temporal cornealquadrant. Contact lens correction is more difcult.KeratoglobusThe cone is located throughout 75% of the cornea.Contact lens correction is a difcult challenge, except in very lim-ited cases.

The wide spread use of corneal topography has allowed thedetection of new keratoconus patterns affecting the superior, nasaland central cornea [30]. More recently, a new D-shape keratoconuspattern,whichaffects subjectswhohaveundergoneLasik refractivesurgery pro

4.2. Disease

The rstwas proposdifferent se[28] (Table

4.3. Index-b

Diseaseingly imporecstasia forwidely docconus whoFor this reascorneal tophave been

coherence tomography and corneal aberrometer instruments havedemonstrated their utility in keratoconus detection based on theassessment of corneal thickness [44] and the difference in cornealaberrations from normal subjects [45], respectively.

Recently, two relatively new optical instruments for assessingdifferent characteristics of the anterior eye have included built-insoftware for the detection and monitoring of keratoconus dis-ease: the Pentacam (Oculus,Wetzlar, Germany) [46] and theOcularResponse Analyzer (Reichert Inc., Depew, NY, USA) [47].

The Pentacam instrument, which is based on the Scheimplugworking principle, takes 1250 images of the cornea at differ-ent angles using a rotating camera (Fig. 4). This method evaluatesdisease severity and progression based on changes in corneal vol-ume and anterior chamber angle, depth and volume. The Pentacamhas been found useful in discriminating keratoconic from normalcorneas, although a relatively low sensitivity in detecting subclin-ical forms of keratoconus has been reported. The images providedby the instrument should be interpretedwith caution because theydo not provide enough data on changes in the posterior cornealsurface to make a clinical diagnosis of abnormality. Additionally,interpretation of the posterior corneal surfaces aberrations shouldbe also carried out with caution as reported outcomes show theposterior corneal surface to be more aberrated than the anteriorsurface in keratoconic eyes, which is in contradiction with the the-oretical optical properties of the corneal surface [48]. As a result,placidodisc-based topographersmightbebetter suited todetecting

nt caOcucatiostudyin ke

topa

topate kerreakbasakeratrateby on eprison

Table 2Index-based sy ts the

Author

Rabinowitz/

Maeda/Klyce

Smolek/Klyc

Schwiegerlin

Rabinowitz/

Mc Mahon e

Mahmoud ecedures, has been described in the literature [31].

evolution

keratoconus classication based on disease evolutioned by Amsler [32,33], who classied the disease in fourverity stages, similar to that reported byHomand Bruce1).

ased systems

detection, even at early stages, has become increas-tant particularly in an attempt to prevent iatrogenicmation the lost of corneal shape which has beenumented in patients with subclinical forms of kerato-have undergone refractive surgery procedures [3436].on, several index-based classicationmethods build onography systems for grading the severity of keratoconusdeveloped [26,3743] (Table 2). Furthermore, optical

incipieThe

classiviouslower[47].

5. His

Hisacterizlayer bliums

Indegenenotedbetweecompa

stems for keratoconus detection. A higher value than the point of cut value sugges

Index Point of cut

Mc Donnel [37] K Value 47.2

I-S Value 1.4

[38] KPI 0.23

KCI% 0%

e [39,40] KSI 0.25g/Greivenkamp [41] Z3 0.00233

Rasheed [42] KISA% 100%

t al. [43] KSS 0.5

t al. [44] CLMI >0.45ses of keratoconus [49].lar ResponseAnalyzer allowskeratoconusdiagnosis andn by assessing corneal hysteresis and resistance. A pre-has found the latter two values to be signicantly

ratoconus compared to normal and post-lasik subjects

thology

hologically, there are three signs which typically char-atoconus: (1) stromal corneal thinning; (2) Bowmansage; and (3) iron deposits within the corneal epithe-l layer [9,12].oconus disease, the corneal epitheliums basal cellsand grow towards Bowmans layer and this can bebserving accumulation of ferritin particles into andithelial cells [50]. Basal cell density is also decreased into normal corneas [51]. Bowmans layer often shows

presence of keratoconus.

Description

Diagnosis is performed based on the central keratometry andthe inferiorsuperior asymmetry in keratometric power

KPI is derived from eight quantitative videokeratographyindexes. KCI% is derived from KPI and other four indexes.

Keratoconus detection and the level of severity is assessedusing an articial intelligent system.

Diagnosis is performed based in videokeratoscopic height datadecomposed into orthogonal Zernike polynomials.

Diagnosis is derived from K value, I-S value, AST and SRAX.

Diagnosis is performed based on slit-lamp ndings, cornealtopography, corneal power and higher order rst cornealsurface wavefront root mean square error.

Diagnosis based in detecting the presence or absence ofkeratoconic patterns and determining the location andmagnitude of the curvature of the cone.

160 M. Romero-Jimnez et al. / Contact Lens & Anterior Eye 33 (2010) 157166

l thinn

breakages,positive nodruptions dudecrease inbroblastsand unevenintra-lamelobserved [5demonstratconus compthe more adally unaffecthe endothalthough pling towarddemonstratbundles, renormal sub

6. Aetiolog

Despiteinto the aeand possibunderstoodinto the geassociationgated.

6.1. Genetic

Family,attempt to

I. Family sStudie

becamewith ke[56]. Hoshownleast onstudy estimes hi

e relde oted [in stuo daus hns wels oentironns fatheratocoatocobeenty ofsistewinsel of]. TheticzygobryoeticFig. 4. Scheimpug image in severe keratoconus. Signicant cornea

which are lled with collagen from the stroma andules of Schiffs periodic acid. They formZ-shaped inter-e to collagen bundles separation [52]. In the stroma, athe number of lamellae and keratocytes, degradation of[52], changes in the gross organization of the lamellae,distribution of collagen brillar mass and inter- and

lae, particularly around the apex of the cone have been3]. Studies carried out using confocal microscopy haveed a reduction in the number of keratocytes in kerato-ared to normal subjects; the reduction being greatervanced the disease [54]. Descemets membrane is usu-ted, except in cases of breakages of this tissue, andelium is also generally unaffected by the disease [51],eomorphism and elongation of endothelial cells point-s the cone have been reported [52]. It has also beened that corneal nerves inkeratoconicshave thickerbreduced density, and subepithelial plexus compared tojects [55].

y and pathogenesis

the intensive research activity over the last few decadestiology and pathogenesis of keratoconus, the cause(s)le mechanisms for its development remain poorly

havmoges

II. TwT

contwilevponenvtwi

Okerkernotbilitheof tlev[64gentheem

III. Gen

. Albeit, there have been several hypotheses proposednetic and biochemical mechanisms. Furthermore, theof other diseases to keratoconus has also been investi-

s

twins and genetic studies have been conducted in anfurther understand the genetic nature of keratoconus:

tudies:s carried out before corneal topography techniquescommercially available reported that 68% of subjectsratoconus had close relatives affected by the diseasewever, studies assisted by corneal topography havethat up to 50% of subjects with keratoconus have ate close relative affected by the disease [57]. A recenttimated that relatives of keratoconics have a risk 1567gher of developing keratoconus than those who do not

Linkagtoconusgeneticbeen as(Table 3

HonR166W,

Table 3Identied Loci

Author

Fullerton J eTyynismaa HHughes et aBrancati F etHutchings HTang YG et aLi X et al. [72Bisceglia L eing is appreciated in the central cornea.

atives with keratoconus [58]. An autosomal dominantf inheritance with variable expression has been sug-57,59].dies:

te, 19 pairs of monozygotic twins affected with kerato-ave been described in the literature. In most cases, bothere affected, although with different [59,60] or similarf severity [61], which suggests a strong genetic com-of disease development, perhaps also combined withmental factors. However, another study on two pairs ofiled to detect keratoconus in both twins [62].studies have assessed the mode of transmission innus disease. A study in an 18-year-old monozygoticnus twin, their 8-year-old sister and parents, who havediagnosed with keratoconus [63], suggests the possi-

a recessive mode of inheritance, although it is possibler could develop the disease over time. The rst casewith keratoconus in opposite eyes but with a similar

severity and clinical features has been recently reportedis may have resulted as a consequence of the rise inand/or environmental factors during the acquisition ofte symmetry, before it divides into two monozygotic

s.analyses:

e studies carried out in families affected with kera-to identify the genetic regions (Loci) have reported

susceptibility to the disease [6572]. Several loci, havesociated to keratoconus disease in different studies).et al. identied four mutations of the VSX1 gene (i.e.,L159M, D144E and H244R) in different keratoconic

in keratoconus disease.

Locus

t al. [66] 20q-12et al. [67] 16q22.3-q23.1

l. [68] 15q22.33-24.2al. [69] 3p14-q13et al. [70] 2p24l. [71] 5q14.3-q21.1] 9q

t al. [73] 5q21.2

M. Romero-Jimnez et al. / Contact Lens & Anterior Eye 33 (2010) 157166 161

patients [73]. Bisceglia et al. also found four mutations of theVSX1 gene (i.e., D144R, G160D, P247R and L17P) in 7 out of 80keratoconus subjects assessed [74]. Recently, Eran et al. iden-tied the D144E mutation linkage in a Jewish family affectedby kerat2 out of[76]. MoD144E iand Tanand H24

6.2. Biochem

Several bbeen propooccurs as a

Mtt eXVIII [80] bsuggestionwound heacorneas.

The excobserved inactivity thaand other cainhibitors [8

It has alstimes greatmal subjecmodulatorit has beenmight occumal mass lto an increatowards thelens wear aICAM-1 andanti-inamtimes in keto normalwear might6 cytokinesupports thpathogenes

6.3. Biomec

The diffelae in keratoproposed asultimately loxidative dconus progaldehyde denzymes [9reactive oxgen accumuand peroxy[92]. The multraviolet roccur as a r

Conictiregards tokeratoconutheir eyesmstudy found

reported differences in progression between keratoconus patientswith and without atopy [100]. Interestingly, the latter study foundthat keratoconic patients with atopy tend to have faster kerato-conus progression and more frequent refractive and immunologic

icatios wehowdevetectivt kelter-stervatived c

lated

atocogh its andts wissoci[12ult oapp

lso buros

05]. Aen dyes wenetilso bus ame sypermmeconureporrola

nage

atocoy. Trmildan bs inclrocekerats or

ectac

ctacldiseavisuation [

ntac

rstwasresely tontac

eyes)oconus [75]. In contrast, Aldave et al. reported that just100 keratoconus subjects showed any gene mutationre recently, Liskova et al. have shown that mutation ofs not the direct cause of keratoconus development [77]g et al. have identied that mutations L159M, R166W4R are not related to keratoconus [78].

ical factors

iochemical theories for keratoconusdevelopmenthavesed to support the hypothesis that corneal thinningresult of the loss of corneal structural components.t al. founddifferences in collagen types XIII [79], XV andetween normal and keratoconic corneas, leading to thethat these differences might play an active role in theling process observed between normal and keratoconic

essive degradation of the corneal stroma commonlykeratoconus might be the result of proteolitic enzymet can be initiated by an increased level of proteasestabolic enzymes [81], or decreased levels of proteinase2] such as2-macroglobulin and1-antiprotease [83].o been found that keratocytes in keratoconus have fourer numbers of Interleukin-1 receptors compared to nor-ts [84]. As Interleukin-1 has been postulated to be aof keratocytes proliferation, differentiation and death,suggested that the loss of anterior stromal keratocytesr due to an excess of apoptotic cell death and stro-oss [85]. Furthermore, if epithelial microtrauma leadssed release of Interleukin-1, the latter provides supportassociation of keratoconus with eye rubbing, contact

nd atopy [86]. Proinammatory markers Interleukin-6,VCAM-1 are over expressed by 240 times, whereas

matory marker Interleukin-10 is under expressed by 8ratoconic patients who wear contact lenses comparedmyopic subjects [87]. This suggests that contact lensbe a precursor for ectasia development. Interleukin-

is over expressed in early forms of keratoconus, whiche development of chronic inammatory events in theis cascade of the disease [88].

hanical factors

rent distribution and lower number of stromal lamel-conic compared with normal corneas [52,53] has beena precursor for corneal rigidity reduction and thinning,eading to keratoconus development [89]. Furthermore,amage has been described as a co-factor in kerato-ression. Keratoconic corneas have decreased levels ofehydrogenase Class 3 [90] and superoxide dismutase1]. Both of these enzymes play important roles in theygen processes of different species. The reactive oxy-lation causes cytotoxic deposition of malondialdehydenitrites, which could potentially damage corneal tissuesain factors related to increased oxidative damage areadiation, atopy andmechanical trauma; the latter couldesult of chronic eye rubbing and contact lens wear [92].ng results have been reported in the literature withwhether [93,94] or not [95] atopy is associated withs development, as keratoconus subjects appear to rubuchmore frequently thannormal subjects [9698].Onetopographic differences [99], whereas another study

compltact len[101];conus

Proprevenvioletof nonpreserimprov

6.4. Re

Keralthoudromesubjecto an aulationas a resseen inIt has atal ama[104,1has betheir ener), ghave aatoconsyndrojoint hally, sokeratostudyvalve p

7. Ma

Kerseverittacles,cases coptionlaser ppeuticimplan

7.1. Sp

SpeAs thequatecorrec

7.2. Co

Theconushas repfor earated co(1004ns leading to theearlierneedofkeratoplasty [100]. Con-ar has also been associated to keratoconus progressionever, whether contact lens wear could trigger kerato-lopment remains unclear [9].e steps to reduce oxidative damage and potentially

ratoconic development include: (1) the use of ultra-s; (2) improvement of ocular comfort with the useoidal anti-inammatory medications; (3) the use ofe-free articial tears and allergy medications and; (4)ontact lens t to minimize corneal microtrauma [93].

diseases

nus commonly develops as an isolated condition,has also been described in association with many syn-diseases [9,13]. Studies have reported that 0.515% of

th Downs syndrome suffer from keratoconus, leadingation 10300 times higher than that of the normal pop-,102,103]. This association has been suggested to occurf eye rubbing owing to the increased rate of blepharitisroximately 46% of Downs syndrome individuals [103].een found that 3041%of subjectswith Lebers congeni-is, a rare genetic disorder, also suffer from keratoconuslthough keratoconus in Lebers congenital amaurosis

ocumented as an oculo-digital sign (i.e., patients rubith the ngers in a strongly and compulsively man-

c rather than eye rubbing mechanisms for keratoconuseen identied [104]. Other associations between ker-nd connective tissue disorders, such as Ehlers-DanlosubtypeVI [106,107], Osteogenesis Imperfecta [108] andobility [108] have previously been reported. Addition-

studies have found an association between advanceds andmitral valveprolapse [109,110].However, anotherted a lack of association between keratoconus, mitralpse and joint hypermobility [111].

ment and treatment

nus management varies depending on the diseaseaditionally, incipient cases are managed with spec-to moderate cases with contact lenses, and severe

e treated with keratoplasty. Other surgical treatmentude intra-corneal rings segments, corneal cross-linking,dures (i.e., photorefractive keratectomy, photothera-toctomy, lasik in situ keratomileusis) intra-ocular lensa combination of these.

les

es are normally used in early cases of keratoconus only.se progresses, irregular astigmatism develops and ade-l acuity cannot be achieved with this type of visual9].

t lenses

to describe the use of contact lenses to manage kerato-Adolf Fick in 1888 [112]. Since then, contact lens wearnted themost commonand successful treatment optionmoderate cases of keratoconus. A study which evalu-t lens prescribing trends in 518 keratoconus patientsover a 30-year period showed that contact lens wear

162 M. Romero-Jimnez et al. / Contact Lens & Anterior Eye 33 (2010) 157166

Table 4Contact lens types for keratoconus. Bc, Base curve; Dia, diameter. Power expressed in diopters. *Synergeyes Clear Kone provides vault in microns instead of back surfacecurve in millimetres.

Lens type Proprietary name Manufacturer Bc (mm) Dia (mm) Power (D)

Soft Kerasoft Ultravision 8.009.00 14.0015.00 30.00Soft K Soex 7.008.20 14.20 +10.00 to 20.00

Gas permeable Rose K2 Menicon Co., Ltd. 4.308.60 7.9010.40 30.00IKone Valley Contax 4.807.70 8.8010.40 30.00Soper David Thomas 5.207.50 7.509.50 30.00McGuire David Thomas 5.607.35 8.609.60 30.00Dyna Intralimbal Lens Dymanics 5.929.28 10.412.00 25.00

Mini-scleral SoClear Dakota Science 5.827.82 13.3015.50 +20.00 to 15.00Digi Form Truform Any 13.5016.00 AnyMaxim Aculens Any 15.4016.40 Any

Scleral Innovative Innovative Sclerals Any 18.0024.00 AnyGelFlex Ezekiel Optom. Any 18.0024.00 AnyTru-Scleral Truform 7.259.00 16.0020.00 Any

Hybrid Clear-Cone Synergeyes 100600* 14.50 +5.00 to 15.00SoftPerm CibaVision 6.508.10 14.30 +6.00 to 16.00

represented a satisfactory treatment method and delayed the needfor surgery in approximately 99% of all ttings [113]. Althoughcontact lensilicone hydsoft skirt) mcommonlyular astigmlens types (

Frustrecases, succesoft contac(Table 4) [1and modulusuited for ktact lenses.soft contactmance of m

Three ting apical cltraditionalllens supporcentral cornhowever, thassociated[119]. The aviding primcentral opti

tral cornea (Fig. 5). This technique provides good visual acuity andkeratoconus progression control; however, an increase in corneal

g haschniqr at sex anchniratodiffeand agh coe-poarrie

bepites coms wiccesenic

s hav[123atocs [12rida, Uly, Syen u

Fig. 5. Fluoreson the centralses for keratoconus are manufactured with hydrogel,rogel, gas permeable and hybrid (i.e., rigid centre andaterials, gas permeable contact lenses remain the mostused contact lens type [114,115], as high levels of irreg-atism cannot normally be corrected with other contactTable 4).and early forms of keratoconus can be, in somessfully corrected with hydrogel contact lenses. Severalt lens designs for keratoconus are currently available16]. Features such as the higher oxygen permeabilitys of rigidity of silicone hydrogels makes them better

eratoconus correction than conventional hydrogel con-Recently, several new custom-made aberration-controllenses have been developed to improve visual perfor-ild to moderate keratoconus [117,118].ting strategies of gas permeable contact lenses, includ-earance, apical touch and three-point touch, have beeny used for keratoconus tting. Apical clearance providest and bearing directed off the apex and onto the para-ea, with clearance (vaulting) of the apex of the cornea;is strategy is no longer in current use as it has been

with poor visual acuity and cone progression controlpical touch tting technique is characterized by pro-ary lens support on the apex of the cornea, in which thec zone of the lens actually touches or bears on the cen-

scarrinting teto beathe apThis teand kefoundtouchalthouto threbeen cperform

Desdesigndesignand sulens (Mdesignconusfor kersucces

HybGeorgirecentalso becein patterns of two different gas permeable contact lens ttings in keratoconus. The gcornea. The gure on the right shows a three-point-touch tting with slight central toucalso beendocumented [119]. The three-point toucht-ue, perhaps the most popular, allows the contact lenseveral points on the cornea, including a light touch ond a heavier touch on the paracentral cornea (Fig. 5).

que has also been associated with good visual acuityconus progression control. Previous studies have notrences in contact lens wearing comfort between apicalpical clearance ttings techniques [120]. Furthermore,rneal scarring might occur with apical touch comparedint touch ttings [121], no randomized clinical trial hasd out to assess which of these two tting philosophiesst.the different keratoconus gas permeable contact lensmercially available, including multicurve and aspheric

th unique or variable asphericity, the most popularsful design currently available is probably the Rose Kon Co., Ltd., Nagoya, Japan) [122]; however, other lense also been reported to be successful in treating kerato-]. More recently, reverse geometry contact lens designsonus management have also been used with relative4].contact lenses, such as SoftPerm (Ciba Vision, Duluth,SA) [125], Solotica (Solotica, Brazil) [126] and morenergeyes (SynergEyes, Carlsbard, CA, USA) [127] havesed with relative success in keratoconus management.ure on the left shows a at tting with a signicant touch of the lensh and peripheral bearing on the cornea.

M. Romero-Jimnez et al. / Contact Lens & Anterior Eye 33 (2010) 157166 163

However, thrent designdo not normcomfort in c

Piggy baon top of amanagemenfort and prolenses to siused for prof high oxypermeablemanagemen[129].

7.3. Surgica

Althoughthickness ocorneal tissfor advancemanaged wtively low nof 1065 kerrequired PKwere followrequired PKkeratoconureported toto undergoity worse thkeratometrage of kera[130,132,13

Deep Lalayers are rintact) andin keratocoeyes undergthan thoseof endothelthe use of P

Radial kperipheral c

of keratoconus with very limited success. Thus, the technique is nolonger conventionally performed for the treatment of keratoconus[137,138].

Photorefractive keratectomy (PRK), a technique which perma-chaimert ofenthav

ectsacuithniqf eccoms witreprer coratocplastmileuing Pvelsriskl teca coped fd forthents inmptevenonlyl cor

athasst coorneneall rigs re

l zonl radrad

s thal strod re5]. IteasFig. 6. Piggy-Back tting in keratoconus.

ese lenses have not been widely accepted as the cur-s, generally more expensive than gas permeable lenses,ally provide improved visual correction and wearingomparison with gas permeable contact lenses.ck systems, consisting on the tting a gas permeablesoft contact lens, have also been used for keratoconust. The soft contact lens isused to improvewearingcom-vide a more regular area for the gas permeable contactt, whereas the gas permeable contact lens is primarilyoviding adequate visual acuity [128] (Fig. 6). The usegen permeability soft (i.e., silicone hydrogel) and gascontact lenses is highly recommended for keratoconust as these corneas are well known to be compromised

l procedures

penetrating keratoplasty (PKP), in which the entiref the cornea is removed and replaced by transparentue, is perhaps the most commonly used surgical optiond cases of keratoconus which cannot be successfullyith contact lenses [9,130], its use is limited to a rela-umber of cases. A recent study has shown that just 12%atoconus subjects who were followed-up for 8 yearsP [131]. Another study in which keratoconus subjectsed-up for 48 years reported that less than 20% of them

nentlyan excamountreatmstudiesin subjvisualthe tecment olongercorneaalways

Othate kekeratokeratofollowhigh lehighersurgica

Intrdeveloadaptesist insegmean atteand prcommnorma450moptionand beorder c

CorcorneainvolvecentracorneaA lightspeciecornealens anold [15in cornP intervention [3]. In a 7 years follow-up study of 2363s subjects, 21.6% required PKP [132]. The risk factorsincrease the likelihood of keratoconic patients havingPKP are the presence of corneal scarring, visual acu-an 6/12 (20/40) with contact lens correction, corneal

y steeper than 55D, corneal astigmatism>10D, earlytoconus development and poor contact lens tolerance3].mellar Keratoplasty (DLK), in which supercial cornealemoved (descements layer and endothelium remainreplaced with healthy donor tissue has been employednus management in recent years [134136]. However,oing PKP are more likely to achieve 6/6 (20/20) vision

undergoing DLK [134]. On the other hand, a higher riskial cells loss and graft rejection has been reported withKP in comparison with DLK [134,136].eratotomy, in which longitudinal incisions along theornea are performed, has been used for the treatment

take placeon subjectsan improvekeratometrsion [156,1in combinarings segmhas been asimmediatelpost-operatment, accom[159].

The impof keratocotypes of coror keratoplaaffect cornebination ofnges the shape of the anterior central cornea usinglaser to ablate (i.e., remove by vaporization) a smalltissue from the corneal stroma has been used in theof keratoconus with modest success. Although somee reported a signicant reduction in cone progressionwith early keratoconus [139] as well as an increase iny and a decrease in high-order aberrations [140,141],ue has been frequently associated with the develop-tasias post-treatment and thus, this procedure is notmonly used. However, it has been reported that someh inferior steepening on corneal topography should notesent a contraindication for PRK treatment [142].rneal surgical procedures for the treatment of moder-onus include excimer laser-assisted anterior lamellary [143], epikeratoplasty [144] and laser-assisted in situsis [144]. Although laser refractive surgery proceduresKP and DLK have been commonly used to correctof surgery-induced astigmatism [134136,145148], aof ectasia has been reported following the use of thesehniques [35,36].rneal rings segments, a surgical technique originallyor the treatment of lowmyopia [149], has been recentlythe treatment of keratoconus [150]. The technique con-implantation of one or two polymethyl methacrylatethe corneal stroma to reshape its abnormal shape in

to improve visual acuity, contact lens tolerance [151]t or, at least, delay the need for corneal graft [152]. It isused to treat mild to moderate cases of keratoconus, asneal transparency and a minimum corneal thickness ofthe site of the incision are required [153]. This surgicalbeen associated with an improvement in uncorrectedrrected visual acuity [152,153], and a decrease in high-al aberrations, especially coma [154].cross-linking is a technique which aims to increaseidity and biomechanical stability. The proceduremoving the corneal epithelium in a 67mm diametere followed by rivoavin 0.1% solution application andiation with ultraviolet-A light at 370nm. Ultraviolet-iation activates riboavin generating reactive oxygent induce covalent bonds between collagen brils in thema. The irradiation level at the corneal endothelium,tina is signicantly smaller than the damage thresh-has been recommended not to perform this techniquethinner than 400m [155] as toxic reactions couldin the corneal endothelium. Several long-term studieswho underwent corneal cross-linking have reportedment in best corrected visual acuity, a attening ofic readings and a signicant reduction in cone progres-57]. Also, this technique has been successfully usedtion with other surgery techniques, such as cornealents [158]. The use of corneal cross-linking, however,sociated with a decrease in the number of keratocytesy after treatment, followed by a progressive recoveryively reaching baseline levels six months after treat-panied by an increase in the density of stromal bres

lantation of an intraocular lens for the managementnus is normally undertaken in combination with otherneal refractive surgery techniques, such as corneal ringssty, as intraocular lens implantation does not normallyal shape and cone progression. Furthermore, the com-these techniques, which allows the correction of high

164 M. Romero-Jimnez et al. / Contact Lens & Anterior Eye 33 (2010) 157166

levels of astigmatism by placing an intraocular lens in the ante-rior or posterior chamber, has been used with relative successin a limited number of subjects, normally intolerant contact lenswearers, who has shown signicant improvement in visual acuity[160162].

Thermaltion of heat[163]; howpredictabiliscars and oconsisting ocorneal strotreatment [them to sharound a 5subsequentuse of therhave been sby improvin

8. Conclus

Keratocoappears inand all ethnbeen estimsymptomsseverity. Dedecades intblemechanhave been,environmenanisms. Kesubstantiallthe most suof keratococross-linkinate to severbeing condease.

Conict of

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HX34

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Keratoconus: A reviewDefinitionEpidemiologyClinical featuresClassificationMorphologyDisease evolutionIndex-based systems

HistopathologyAetiology and pathogenesisGeneticsBiochemical factorsBiomechanical factorsRelated diseases

Management and treatmentSpectaclesContact lensesSurgical procedures

ConclusionConflict of interestReferences