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as a cut an eou s basoph ilic hypersen sit ivit y to surface protein s. It is con sidered th at th e com bin at ion of th e irritat ive m ech an ics in du ced by surface deposit s as w ell as th e an t igen ic respon se of th e den at u red surface protein s w ith in th e dep osits lead to th e in flam m ator y resp on se an d th e developm en t of th e papillae. Mech an ical irrit at ion of th e conju n ct iva n ot on ly occu rs w ith con t act len ses bu t can also occur in isolated areas associated w ith su t u res. Also, th e in t roduct ion of silicon e hydrogel con t act len s m aterials, an d th e related con t in u ou s w ear, h as given a rebirth to an in creasing in ciden ce of CLPC. Th is is related to a h igh er m odulus of elast icit y (1.1 to 1.2 m egapascals) m aking th e len s st iffer th an hydrogel len ses. Th e rigidit y of th e m aterial en courages m ech an ical irrit at ion by ru bbing again st th e su perior palp ebral conju n ct iva, producing a local respon se.

Papillae are m orph ologically differen t from follicles an d less severe com pared w ith an acu te, hypersen sit ive follicu lar or cobbleston e ap pearan ce of a vern al con - jun ct ivit is. GPC or CLPC is best obser ved using a w h ite, diffuse ligh t on low m ag- n ificat ion . Papillae, w h ich are space-occu pying elevat ion s, w ill ten d to grab th e len s u pon th e blin k an d h old it in a sligh tly su perior, decen tered posit ion w h ile im peding th e dow nw ard t ran slat ion of th e len s. Because of th e con stan t irrit at ion of th e palpebral conju n ct iva, a react ive m u cous disch arge w ill in crease, leading to addit ion al len s su rface deposit ing.

Th e palpebral conju n ct iva can be described as sm ooth or sat in , un iform or n on - un iform . Un der low m agn ificat ion , w ith or w ith ou t NaFl stain ing, a variable level of hyp erem ia w ill appear w ith an in creasing degree of edem a. Th e papillae w ill be of var ying sizes, from 0.5 m m an d greater. With th e in st illat ion of NaFl, dist in ct crevices can be visu alized bet w een each papillae, w h ich w ill assist in th e delin ea- t ion of th e severit y of th e pap illar y react ion .

In th e earliest stages th e pat ien t is gen erally asym ptom at ic yet com plain s of frequ en t deposit ing of len ses an d variable vision . As th e con dit ion progresses, th e pat ien t st ar t s to fin d th at clean ing th e len ses becom es som ew h at fu t ile, an d th ere is a sligh t to m ore puru len t m ucou s disch arge. Th is m ay or m ay n ot be sym m et ric to both eyes an d is often bilateral, asym m et ric in presen tat ion . As th e disch arge an d th e vision depreciate, so does th e pat ien t’s len s-w earing t im e. Th e pat ien t w ill also fin d th at th e len s ten ds to decen ter sign ifican tly an d m ay even com plain of a greater len s aw aren ess. Most often th e pat ien t w ill presen t w ith a self-diagn osis of a “com m on conjun ct ivit is or red eye” an d m ay h ave self-t reated w ith over-th e- cou n ter vasocon st rict ive agen ts or been t reated by th e prim ar y care physician for a “garden variet y” bacterial conjun ct ivit is w ith out respon se to an t ibiot ics. Th ere m ay be som e ten dern ess to t act ile m an ipulat ion of th e lid bu t n o sign ifican t pain , n or do system ic sym ptom s suggest bacterial or viral conju n ct ivit is.

CLPC can be st aged in to four levels of severit y. Stage 1 dem on st rates n o an a- tom ical sign s, an d on ly m in or sym ptom s of m u cous disch arge an d itch ing. Stage 2 exh ibit s p apillar y en largem en t to 0.5 m m but less th an 1 m m , m ucou s st rain s, hyperem ia, an d an in crease in len s deposits. Th e pat ien t w ill describe itch in ess, disch arge, len s aw aren ess, an d blu rred acu it y. Stage 3 sh ow s papillae greater th an 1 m m , in creased m u cu s, len s aw aren ess, hyperem ia, edem a, an d len s decen t rat ion su periorly. Th e pat ien t w ill describe m oderate to severe sym ptom s w ith decreased w ear t im e, frequ en t len s deposit ing, an d in creased len s m ovem en t an d blu r. Stage 4 dem on st rates pap illae larger th an 1 m m , w h ich h ave a m u sh room sh ape accom - pan ied by severe sym ptom s an d sign s (Fig. 16.2).

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A B

C

D

E

Fig. 16.2 (A) Papillary formation right eye (ocular dextrose, OD). (B) Nonpapillary satin left eye (ocular sinistras, OS). (C) Grade 1 contact lens–induced papillary conjunctivitis (CLPC) marginal papillary formation with hyperemia Pre -Tx OD. (D) Grade 3 CLPC with isolated giant papillary formation with hyperemia Pre -Tx OS. (E) Grade 1 CLPC with hyperem ia post-Tx OD 2 weeks: significant decrease in hyperemia and early papillary formation.

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F

G

Fig . 16.2 (Continued) (F) Grade 3 CLPC with hyperemia post-Tx OS 2 weeks: significant decrease in hyperem ia and early papillary form ation. (G) Zonal diagram of the superior everted lid.

Differential Diagnosis

Involves iden t ifying th e un derlying cu lprit of m ech an ics, protein den at urat ion , an t igen ic-related respon se, or environ m en t al in flu en ces giving rise to sim ilar fin d - ings an d sym ptom s exacerbated by th e use of con t act len ses, yet th ey are n ot th e cau se. By h istor y alon e, th e et iology an d differen t ial can be m ade. If th ere is hydrogel con tact len s w ear, exten ded m ore th an daily; if th ere is a h istor y of cat aract or corn eal procedures w ith su t u res; or if th e pat ien t h as a sign ifican t h istor y of season al or vern al allergy, th e h istor y is th e t ru e stor y. Treat m en t w ill th us follow th e scen ario of th e h istor y.

CLPC m ay also presen t w ith sim ilar sym ptom s t ypical of a variet y of conjun ct i- vit is, in cluding bacterial, viral, vern al, atopic, or m ech an ically in du ced by su t u res postoperat ively. Th e h allm ark differen t ial of CLPC is a m ore rapid on set w ith in - creased m u cous disch arge an d th e in abilit y to properly m ain tain th e con t act len s on th e eye, u su ally exh ibited by excessive len s m ovem en t du e to th e m ech an ical in fluen ce of th e en larged pappilae. Follicles of variable size are seen in a hyperem ic conjun ct iva, in ferior m ore so th an sup erior (un like CLPC seen in th e su perior palp ebral conju n ct iva) w ith t ran slu cen t , avascular fluid–lym p h oid accu m ulat ion an d are accom pan ied by system ic fin dings as in ph ar yngoconjun ct ival fever (PCF) or epidem ic keratoconjun ct ivit is (EKC), as w ell as ru ling out ch lam ydial disease. Th e Academ y of Op h th alm ology h as presen ted an excellen t differen t ial form at for conju n ct ivit is as seen in Table 16.3.

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Table 16.3 Typical Clinical Signs of Conjunctivitis

Typical Clinical Signs of Conjunctivitis

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Note: Typical clinical signs m ay n ot be presen t in all cases. Dist inct ive signs are m ost useful in m aking a clinical diagn osis, but m ay occur un com m on ly. In all en t it ies, lateralit y m ay var y and m ay be asym m et rical.

Source: Matoba AY. Preferred Pract ice Pat tern s, Conjun ct ivit is. San Fran cisco: Am erican Academ y of Op h th alm ology; 2003. Available at: h t t p ://w w w .aao.org/aao/edu cat ion /librar y/p pp /u p load/ Conjun ct ivit is_.pdf. (Accessed 12–08–2008). Reprinted w ith perm ission .

Management

As w ith any poten t ial an t igen ic–allergic respon se, on e m u st first rem ove th e in i- t iat ing st im u lus. Th e sim p le rem oval an d discon t in u an ce of th e len s are th e easiest t reat m en t , bu t for som e pat ien ts th e m ost t rau m at ic. Th erefore a com bin at ion th erapy is suggested based on th e level of disease. It is im port an t to n ote th at th e use of vasocon st rict ive agen ts, an t ibiot ics, an d/or an t ivirals th at h ave been star ted prior to presen tat ion can be safely discon t in u ed . How ever, if th ere is con cern abou t bacterial coin fect ion , m ain t ain th e appropriate level of an t ibiot ics such as four th - gen erat ion fluoroquin olon e w h en involving con tact len s.

The m ost expedient treatm ent is the sim ple discontinuation of w earing contact lenses and converting to eyeglass w ear until the condition im proves. How ever, in m any cases, the patient m ay not have eyeglasses or m ay not be tolerant of the alternative. Therefore, the use of soft daily disposable lenses w ith a high m oisture content in conjunction w ith a steroidal antiinflam m atory serves as the best overall therapy.

Stage 1 CLPC requires m inim al intervention, such as refitting the patient w ith a frequent replacem ent or disposable lens. In this situation, the simple conversion to a “daily disposable–single use lens” is the m ost appropriate. Another option would be to continue conventional, disposable, or frequent replacem ent lenses but change the care product to a peroxide-based system and possibly add an enzym atic cleaning solution.

In an unpu blish ed st u dy by K. Dan iels, daily disposable len ses dem on st rated a m ore rapid resolu t ion of p at ien t sym ptom s w ith grade 2 to 4 CLPC w ith ou t th e u se of m edicin als follow ed by 1-w eek an d 2-w eek disposable len ses, respect ively. Th is suggest s th at th e sim ple u se of daily disposable–single use len ses m igh t be th e m ost appropriate single or adjuvan t t reat m en t for CLPC.

St age 2 CLPC requ ires len s replacem en t , frequen t irrigat ion w ith lu bricat ing drops to rid m ucus, lid hygien e to avoid lid w ipers epith eliopathy, an d possibly

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a prescript ion for a m ast cell st abilizer such as such as lodoxam ide (Alom ide, Allergan , Ir vin e, CA), crom olyn (Crolom , Bausch & Lom b, Roch ester, NY) (Opt icrom , Allergan , Ir vin e, CA), n edocrom il (Alocril, Allergan ), pem irolast (Alam ast , Vist akon Ph arm aceu t icals, Jacksonville, FL), or olopatadin e (Pataday or Patan ol, Alcon Laboratories, For t Wor th , TX) for sh ort-term to ch ron ic th erapy.

Stage 3 CLPC requires a discontinuation of lenses for a short tim e w hile prescribing a m ast cell stabilizer or low -concentration steroid such as prednisolone 1%. Lenses can be refit to daily disposable or short-term frequent replacem ent lenses w ith peroxide care products until resolution of the papillae to a w hitened cap called hypertrophy.

St age 4 CLPC requires com plete discon t in u at ion of len ses an d m ore aggressive steroid in ter ven t ion u n t il resolu t ion . Up on resolut ion , frequ en t replacem en t or disposable len ses sh ould be fit ted u sing a peroxide-based product system .

In gen eral, w h en u t ilizing steroids for t reat m en t , it is h igh ly suggested to adju - vantly treat the patient w ith single-use daily disposable lenses, w hich w ill satisfy the patient’s needs w hile allow ing for a bandage lens–drug delivery efficiency. The steroid (prednisolone 1%) should be aggressively dosed for the first 1 to 2 w eeks at four tim es a day and then taper slow ly over the next 2 to 3 w eeks. As one tapers the prednisolone dow n to t w ice a day, start the addition of a soft steroid such as loteprednol either 1%or 0.2%for 1 to 2 weeks or until resolution of clinical findings. Long-term m aintenance is m ost appropriate w ith shorter-term , frequently replaced hydrogel lenses of 2 to 4 w eeks of nonionic, high -w ater-content m aterials and peroxide cleaning or a conversion to gas perm eable high Dk–plasm a-treated designs.

Also con sider th e long-term u se of an t ih ist am in e–m ast cell st abilizer for longterm m ain ten an ce. Addit ion ally, if on e w as to be con ser vat ive w ith long-term m e- dicin als, con sider t w ice-a-day to th ree-t im es-a-day u se of physiologically based w et t ing drops such as vit am in A drops (ViVa, Corn eal Scien ces, Gaith ersbu rg, MD) or elect rolyte-balan ced form ulas such as Th era–Tears (Advan ced Vision Research , Boston , MA) or Sooth e (Bau sch & Lom b, Roch ester, NY; Alm ira Scien ces, Atlan t a, GA). Th ere is also suggest ion th at cyclosporin e drops (Rest asis, Allergan , Ir vin e, CA) m ay also be h elpful in a t w ice-a-day dosage for long-term con t rol of ocular in flam - m ator y respon se as w ell as being a veh icle carrier h elpfu l in m ain tain ing a h ealthy ocu lar m ucin surface to avoid m ech an ical irritat ion from th e len s m aterial.

Vascularization

Vascularizat ion is con sidered to be th e gen eral form at ion an d exten sion of capillaries th at h ad n ot previously existed w ith in th e avascu lar corn ea. Neovasculariza- t ion is th e form at ion of n ew vessels as an exten sion or sh u n ts to preexist ing vascularized areas of th e avascular corn ea. To differen t iate fur th er is to classify form s of redn ess an d vascu larizat ion by locat ion . Lim bal engorgem en t or hyperem ia is th e disten sion of lim bal blood vessels in th e absen ce of n ew vessel grow th . Vessel ingrow th or pen et rat ion is n ot n eovascularizat ion , bu t sim ply an exten sion of a vessel inw ard tow ard th e cen t ral corn ea. Pan n u s, w h ich is h igh ly vascularized, is exten sion of conju n ct ival t issue overlapping th e clear avascular corn ea seen as an an atom ical varian ce or in duced by t rau m a to th e eye.

Ch ron ic hypoxia is th e u n derlying con dit ion th at in it iates th e vascu larizat ion respon se. Hypoxia cau ses lactate acidosis, w h ich decreases th e in tegrit y of th e epith elium an d st rom al soften ing. Th is yields an oppor t un it y for vessel ingrow th . Du e to hyp oxia, an early ph ase of vascu larizat ion occu rs in ducing a release of in flam - m ator y m ediators. Th is st im ulates addit ion al vessel grow th called an angiogenic response. Tigh t len ses, lim bal com pression , an d/or t rau m a m ay also st im ulate a

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Presentation

Vascular respon ses to ch ron ic hyp oxia can var y from m in or to severe based on th e associat ion w ith possible m icrobial in filt rat ion . Som e form of corn eal vascularizat ion occurs in ~34% of cases associated w ith hydrogel len s u se versu s 2% w ith n on len s w earers, w ith 98%of th e vascularizat ion occu rring w ith in th e superficial st rom a. Th e pat ien t is oth er w ise asym ptom at ic oth er th an n ot ing an apparen t hyperem ia or lim bal engorgem en t , w h ich app ears to th e pat ien t as a “ch ron ic red eye” w h en w earing con tact len ses. Th is is sim ply an engorgem en t of th e m argin al arcade capillaries. Th ese vessels h ave a st raigh t prot uberan ce w ith a defin ed loop at th e en d . Hyperem ic episcleral lim bal vessels are differen t iated from n eovessels th at exten d for w ard w ith leaflike fron ds th at in terdigitate.

Vascu larizat ion appears sim ilar to a m esh like plexal grow th in th e m idepith e- lium project ing tow ard th e corn ea like sm all, lin ear spikes an d bran ch es called fronds (sim ilar to th e vein s w ith in a leaf). Th ere is gen erally n o sym ptom atology associated w ith th e fin dings. Th ese are differen t iated from n orm al lim bal vessels th at “loop” back tow ard th e lim bu s. Low -grade (grade 1) vessels w ill ten d to m i- grate inw ard to approxim ately 0.4 to 0.6 m m (daily w ear) to 1.4 m m (exten ded w ear). Grade 2 w ill be grade 1 vessels th at w ill ten d to m igrate tow ard th e pupil w ith ou t p assing in to th e pupillar y zon e. Th e m ost severe, grade 3, w ill pen et rate th e pu pillar y region . It is im por tan t to ph otodocum en t th e vessels an d determ in e th e locat ion on th e lim bus, depth (su perficial or deep), degree of p en et rat ion , an d severit y defin ed as th e depth of pen et rat ion (an d th e advan cem en t of grow th to- w ard th e papillar y region ).

Differential Diagnosis

Vascularizat ion an d n eovascu larizat ion are differen t iated from lim bal vessels th at m ay be dilatated by t rau m a, in fect ion , in flam m at ion , t um or, conjun ct ival in - grow th or pter ygiu m , or postoperat ive com plicat ion . Differen t iat ion m ust also be m ade from vascu larized pan n us, w h ich is th e ingrow th of vessels an d con n ect ive w ith in th e epith eliu m . Th e differen t iat ion of vessel depth is im port an t . Su perficial vessels or vascularizat ion in it iates from th e lim bal capillar y arcade, an d th e vessels are m ore tor t u ou s an d of sm aller caliber th an deep st rom al vessels, w h ich em erge from w ith in th e lim bal m idst rom al region an d are larger in caliber, h ave abr upt en d bulbs, an d m ay disru pt th e regu larit y of th e lim bal corn ea. Oth er factors th at m ay be associated w ith con t act len s–related vascularizat ion are dr y eyes (keratoconjun ct ivit is sicca) or ocular su rface disease an d oth er diseases, su ch as bleph arit is, acn e rosacea, Sjögren syn drom e, an d im m u n e dysfun ct ion , as w ell as in terst it ial kerat it is, h erpes kerat it is, t u bercu losis, m easles, syph ilis, an d th e possibilit y of am in o acid deficien cies.

Because of th e p oten t ial of n on – con t act len s–related con cern s associated w ith corn eal vascularizat ion , biom icroscop ic exam sh ould in clude direct illu m in at ion an d ret roillu m in at ion , part icu larly of th e lim bal periph eral vessel arcades. In gen - eral, superficial vessels w ill em erge in to th e an terior st rom a an d appear as single or m ult ip le (pan n u s) tor t uous vessels un der low m agn ificat ion , yet deeper st rom al vessels course th rough th e corn ea as m ore lin ear vessels th at arborize. Lip id deposit ion appears as yellow -w h ite opacit ies at th e leading edge or surrou n ding th e st rom al vessels. Obser vat ion of lipid exu dates su rrou n ding an act ively engorged vessel(s) sh ould raise th e con cern of a possible iris-angle carcin om a requiring diligen t gon ioscopic exam in at ion . If th ere is a conju n ct ival grow th closely ju xt aposed to th e lim bu s adjacen t to th e corn eal vascularizat ion , conju n ct ival carcin om a m ay be suspected .

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Management

Th e pat ien t w ith lim bal hyp erem ia or vessel engorgem en t ten ds to self-t reat w ith over-th e-cou n ter vasocon st rict ive agen t s. Th ese pat ien ts w ill fin ally presen t st ating th at even w ith th ese agen t s th eir len ses feel dr y an d th eir eyes are red . In th is sit u at ion , sim ply an d forcefu lly tell th e pat ien t to discon t in u e drops th at “get th e red ou t .” Th ese drop s ten d to yield reboun d congest ion as w ell as a m ild m ydriasis an d slow ing of accom m odat ion du e to th e sym path om im et ic effects. In th is sit u - at ion , it is best to discon t in u e th e len ses for a sh or t period —2 to 3 days—an d prescribe a soft steroid to rid any low -level in flam m ator y com pon en t s.

In conju n ct ion , im plem en t physiologically based w et t ing drops su ch as vit am in A (ViVA, Corn eal Scien ces, Gaith ersbu rg, MD), Th era-Tears (Advan ced Vision Research , Boston , MA), Bion Tears (Alcon Laboratories, For t Wor th , TX), or Sooth e (Bau sch & Lom b, Roch ester, NY, Alm ira Scien ces, Atlan ta, GA). In addit ion to topical su pplem en t at ion , con sider th e u se of om ega 3-6 com bin at ion s for th eir in h eren t an t iin flam m ator y an d m u cin com plem en tar y abilit ies. Also, on e sh ou ld con sider agen ts su ch as Syst an e (Alcon Laboratories, Fort Wor th , TX) or En dura (Allergan , Ir vin e, TX) for topical su rface t reat m en t .

After th e discon t in uan ce of th e con tact len s u se an d after vessel regression , th ere w ill be gh ost vessels or ch an n els th at develop . Th ese m u st be w ell docu - m en ted to differen t iate th en from gh ost vessels th at m ay be associated w ith an in terst it ial kerat it is.

On ce th e lim bal hyperem ia is ten ded to, a refit to con tact len ses sh ou ld be com - pleted w ith th e ph ilosophy of h igh w etabilit y, m oderate m odu lu s, an d h igh oxygen perm eabilit y. Th e pat ien t can be refit to n on ion ic, h igh -w ater-con ten t hydrogel, silicon e hydrogel of a low er m odu lu s. If th e m odu lus is h igh , th ere ten ds to be st iff- n ess to th e len s th at can in du ce conju n ct ival irritat ion an d repeat of conju n ct ival hyperem ia. In addit ion , on e sh ou ld con sider a h igh diffu sion coefficien t of a rigid gas p erm eable len s w ith su fficien t axial edge clearan ce to en h an ce th e flu id–tear ch an n el an d avoid corn eal an d lim bal edge in flu en ces. Th ese len ses sh ould also in - corporate an app ropriate plasm a t reat m en t for w et abilit y. Care produ cts an d len s sch edu les sh ould be revisited, an d pat ien t educat ion n eeds to be com preh en sive.

In th e even t of m ore pron ou n ced an d progressive vascu larizat ion , such as n eovascu larizat ion , on e m u st be con cern ed abou t th e fragilit y of th ese vessels.

It is n ot un com m on to obser ve an in t racorn eal h em orrh age as a direct sequ ela of n eovascu larizat ion . If a h em orrh age occu rs, it w ill app ear as a “red spot on th e corn ea” sim ilar to a “petech ial conjun ct ival h em orrh age” located at th e proxim al en d of a vascular fron d . Th ese h em orrh ages sh ould be ph otograph ed an d m on i- tored for spread . Th e pat ien t sh ou ld refrain from any agen t th at h as an an t icoagu - lan t effect su ch as aspirin , Plavix, w arfarin , as w ell as n eut raceu t icals th at h ave an an t ith rom bot ic ch aracter. Addit ion ally, th ese n eed to be w ell docum en ted as w ell as th e n eovascu larizat ion in th e even t th e pat ien t decides to pursu e in t racorn eal refract ive surgical procedu res in w h ich in t raoperat ive corn eal h em orrh age could be sign ifican t .

Essen t ially, th e t reat m en t for any vascular respon se w ith in th e corn ea from con - tact len ses is th e sam e, an d th e varian ce is th e un derlying cau se an d in ter ven t ion . On ce th e pat ien t h as been properly refit , edu cat ion an d m on itoring are th e keys to avoidan ce of recu rren ce. Addit ion ally, as part of th e t reat m en t gu idelin e, on e m ust clin ically m on itor for issu es th at m ay in duce ocu lar irrit at ion an d vascu larizat ion oth er th an con t act len ses, such as acn e rosacea, system ic m edicat ion s, an d con - dit ion s th at in clu de con n ect ive t issu e disorders, autoim m u n e an d in flam m ator y disease, im m u n ocom prom ised disorders, vascular st im u lator y disease su ch as kid - n ey problem s an d diabetes, keratoconjun ct ivit is sicca, an d associated h orm on ally related disorders of th e eye, as w ell as environ m en tal irritan t s, use of diu ret ics (m edicin al or as beverage–alcoh ol an d caffein e), an d sm oking.