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142 Color Atlas of Ophthalm ology

Recurrent infect ion stage: Th e virus t ravels dow n n er ve a xon s to sen sor y n er ve en dings to in fect th e ocular su rface. Corn eal fin dings in clu de th e follow ing:

Pu n ctate epith elial keratopathy

Dendrit ic int raepithelial kerat it is: An u lcer of th e epith eliu m w ith th in , bran ch ing figures an d term in al bu lbs at th e en d of each bran ch w ith sw ollen borders

Im m une strom al kerat it is: Grou n d -glass–like corn eal h aze, scarring, an d po-

Neurot rophic ulcer: A corn eal ulcer result ing from corn eal an esth esia from viral dam age to sen sor y corn eal n er ves. Im p aired corn eal in n er vat ion leads to an u lcer w ith an epith elial defect con tain ing sm ooth , rolled borders.

Endothelit is: Focal or disciform corn eal st rom al edem a w ith en doth elial kerat ic precipitate an d an terior ch am ber cellular react ion

Differential Diagnosis

Differen t ial diagn osis of den drit ic epith elial kerat it is:

Oth er viruses [h erpes zoster vir us, Epstein -Barr viru s, epidem ic keratocon - jun ct ivit is (EKC)]

Healing epith elial defect s

Soft con tact len s w ear

Tyrosin em ia t ype II

Acantham oeba

Rosacea

Superficial hyper t roph ic den driform epith eliopathy (SHDE)

Differen t ial diagn osis of st rom al kerat it is

Herpes zoster

Bacterial kerat it is

Acantham oeba

St aphylococcal m argin al kerat it is (m argin al u lcer cases)

Rosacea

Collagen vascular disease

Mooren ulcer (m argin al ulcer cases)

Management

Diagn osis is u sually clin ical, bu t scrapings can be perform ed w ith Giem sa stain or Papan icolaou sm ear. Polym erase ch ain react ion or an t igen detect ion can be used as a diagn ost ic tool to detect viral par t icles from scrapings or cult u re.

Dendrit ic int raepithelial kerat it is: Debridem en t of den drite m ay or m ay n ot be perform ed . Begin t riflu ridin e 1%, on e drop ever y 2 h ou rs (n in e t im es daily) or

vidarabin e oin t m en t five t im es daily for 10 to 14 days. Th e Herpet ic Eye Disease St udies (HEDS) foun d oral an t ivirals do n ot preven t th e subsequ en t risk of st ro- m al kerat it is. Con sider cyclop legic agen ts an d avoid cort icosteroids.

Im m une st rom al k erat it is: An t ivirals w it h eit h er oral agen t s (acyclovir, valacyclovir, or fam ciclovir) or top ical t r iflu r id in e can be u sed in conju n ct ion w it h top ical cor t icosteroid s in cases w it h severe st rom al scar r ing an d d ecreased visu al acu it y; h ow ever, top ical an t ivirals d o n ot p en et rate in t act ep it h eliu m

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w ell; t h u s for d eep st rom al kerat it is cases, oral agen t s m ay w ork best . Th e HEDS t r ial sh ow ed t h at top ical cor t icosteroid toget h er w it h an t ivirals red u ced p ersisten ce an d p rogression of st rom al in flam m at ion an d sh or ten ed t h e d u ra- t ion of st rom al kerat it is. Oral an t ivirals (valacyclovir 500 m g on ce daily or acyclovir 400 m g t w ice a day) can be u sed for long-ter m su p p ression an d avoid cor n eal toxicit y. Long-ter m su p p ression is esp ecially h elp fu l for p at ien t s w it h m u lt ip le recu r ren ces of st rom al kerat it is. High er d oses sh ou ld be u sed for ac- t ive d isease. Cor t icosteroid s sh ou ld be t ap ered to t h e low est d ose t h at con t rols in flam m at ion .

Neurot rophic kerat it is: Preser vat ive-free lu brican t drop s an d oin t m en ts can be ben eficial w ith or w ith ou t blan d an t ibiot ic oin t m en t use to preven t secon d - ar y bacterial in fect ion (i.e., er yth rom ycin oin t m en t). Persisten t epith elial defects can be t reated w ith t arsorrh aphy or au tologous seru m drops. Th erapeut ic ban dage len s w ear can be used tem porarily w ith close obser vat ion an d con - siderat ion of prophylact ic an t ibiot ic t reat m en t . Em ergen t surgical t reat m en t m ay in clude lam ellar or pen et rat ing keratop last y, cyan oacr ylate glu e patch ing, am n iot ic m em bran e graft ing, or conjun ct ival flaps in sit uat ion s w h ere visual reh abilit at ion is poor.

Herpes Zoster Virus

Herpes zoster viru s (HZV) is a DNA virus also kn ow n as varicella virus. It h as a prim ar y in fect ion m an ifested as a self-lim ited in fect ion of ch ildh ood (ch icken pox) follow ed by a p eriod of laten cy in w h ich th e viru s is dorm an t in th e n eural ganglia. React ivat ion cau ses h erpes zoster (sh ingles) in ~20%of in dividuals. Herp es zoster cases in clu de 15%th at affect th e oph th alm ic n er ve dist ribut ion of th e t rigem in al n er ve (cran ial n er ve V1 division ). In fect ion alw ays involves a single derm atom e, m aking it un ilateral.

Presentation

Prim ary infect ion stage: Ch icken pox. Occurs as a self-lim ited in fect ion in ch il-

dren . Sym ptom s in clude a m aculopapu lar rash , along w ith p rodrom al sym p - tom s of fever, m alaise, an d upp er respirator y in fect ion sym ptom s. A vaccin e is n ow available for ch ildren t ypically at 12 m on th s of age to p reven t ch icken pox. A vaccin e is also available for im m un ocom p eten t in dividuals over th e age of 65. Can be life th reaten ing if a prim ar y in fect ion develops in adu lth ood or in im - m u n osu ppressed pat ien t s.

Latent stage: Viru s is dorm an t in th e n eural ganglia.

Recurrent or react ivat ion stage: Viru s t ravels dow n a single derm atom e w ith

pain , paresth esias, an d dysesth esia, follow ed by a u n ilateral m aculopapular rash along th e involved derm atom e. Ocular involvem en t occu rs in m ore th an 70% of pat ien ts w ith cran ial n er ve V1 involvem en t . Corn eal fin dings in clu de a pu n ctate or den drit ic epith elial kerat it is, n u m m u lar su bepith elial in filt rates, st rom al kerat it is, disciform kerat it is, an d gran u lom atou s kerat ic precipit ate from uveit is. Neu rot roph ic keratopathy, corn eal scarring, corn eal n eovascu larizat ion , in terst it ial kerat it is, lipid keratopathy, an d keratolysis can also occu r (Fig. 5.2A,B,C).

Differential Diagnosis

HSV, bacterial, or fungal in fect ion ; collagen vascular disease or im m u n e-related corn eal u lcers; exposure-related corn eal ulcers

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A

B

Management

Oral an t ivirals (acyclovir, valacyclovir, or fam ciclovir) reduce viral sh edding from lesion s an d decrease th e in ciden ce an d severit y of th e m ost com m on ocular com - plicat ion s for h erpes zoster oph th alm icu s. Oral th erapy, if begu n w ith in 72 h ou rs of sym ptom on set , m ay redu ce th e in ciden ce an d durat ion of posth erpet ic n eu ralgia. Treat m en t is t ypically used for 7 to 10 days (valacyclovir, 1 g th ree t im es a day; acyclovir, 800 m g five t im es daily; or fam ciclovir, 500 m g th ree t im es a day. Topical an t ivirals are n ot effect ive in h erpes zoster. In t raven ous an t ivirals are in dicated for p at ien ts at risk for system ic dissem in at ion due to severe im m u n osu ppression .

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Bacterial Corneal Ulcer

An in fect iou s in filt rate of th e corn ea, bacterial corn eal ulcer is also kn ow n as a bacterial corn eal u lcer. Risk factors in clude con tact len s w ear (m ost com m on cause), corn eal t rau m a, an d an altered corn eal surface such as a corn eal abrasion or pun ct ate keratopathy. Any disorder com prom ising th e corn eal epith elial in tegrit y can lead to a bacterial in fect ion . Com m on gram -posit ive bacterial cau ses in clude Staphylococcus species, St reptococcu s species, an d Bacillus species (com m on after t rau m a). More com m on gram -n egat ive bacterial causes in clude Pseudom onas aeruginosa, Proteus, Enterobacter, an d Serrat ia.

Presentation

Often acu te pain , redn ess, ph otoph obia, tearing, an d disch arge. A w h ite spot m ay be visible to th e pat ien t th at m ay represen t eith er th e in filt rate w ith in th e corn ea or a layered hypopyon if in th e low er port ion of th e corn ea. Bacterial kerat it is m ay presen t w ith con curren t corn eal edem a, corn eal st rom al th in n ing, n ecrosis, pu ru - len t debris w ith in th e u lcer, an d w h ite blood cell in filt rat ion w ith in th e corn ea or th e an terior ch am ber (Fig. 5.4).

Differential Diagnosis

Viral cau se (part icu larly HSV or HZV), fu ngal cause, Acantham oeba, sh ield ulcer from vern al keratoconjun ct ivit is, im m un e-m ediated corn eal u lcer, sterile m argin al ulcer, staphylococcal m argin al kerat it is

Management

Obtain a h istor y of con t act len s w ear, t raum a, or foreign body.

Obtain an ocular history of system ic disease or previous eye conditions that m ay pre-

dispose to breakdow n or instability of the corneal epithelium (exposure keratopathy, recurrent erosion, dry-eye disease, corneal abrasions, eyelid abnorm alities).

Obt ain a corn eal scraping for various cu lt ure m edia an d a Gram st ain or pot assium hydroxide prep on glass slides. Con sider cu lt u ring con t act len ses, cases, an d solut ion w h en available.

Fig . 5.4 Central bacterial corneal ulcer, epithelial/mucous debris, and hypopyon from Pseudom onas aeruginosa.

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Large cen t ral u lcers sh ould be placed on broad -spect rum for t ified topical an - t ibiot ics u sing eith er cefazolin (50 m g/m L) or van com ycin (25 or 50 m g/m L), on e drop ever y 30 m in u tes for gram -p osit ive coverage along w ith a topical am in oglycoside for gram -n egat ive coverage. A com m on agen t is tobram ycin (14 m g/m L), on e drop ever y 30 m in utes. Sm all periph eral u lcers can be t reated w ith m on oth erapy w ith a fluoroquin olon e u sed on e drop ever y 30 m in utes. Treat m en t can be adju sted w ith close follow -up exam in at ion s an d by ut ilizat ion of bacterial cu lt u re resu lt s, in cluding iden t ificat ion an d m edicat ion sen sit ivi- t ies/su scept ibilit ies. Som e physician s m ay also u se a loading dose of an t ibiot ics ever y 15 m in u tes for th e first 2 h ou rs.

Cycloplegia (h om at ropin e or scopolam in e, on e drop t w ice a day) is h elpfu l for pain relief from ciliar y spasm an d preven t ion of posterior syn ech iae.

Con tact len s w ear sh ould be discon t in u ed w h en app licable.

Hospit alizat ion sh ould be con sidered if com p lian ce is an issue w ith m edicat ion use.

Aca ntha moeba

Acan th am oeba kerat it is is a corn eal in fect ion or u lcerat ion caused by a u biqu itou s protozoan foun d in fresh w ater an d soil. It exist s as a dorm an t cyst or an act ive m obile form kn ow n as a t roph ozoite. Most cases occu r in associat ion w ith p oor con tact len s hygien e, con t act len s w ear in fresh w ater sources, or clean ing con tact len ses in fresh w ater, w ell w ater, or h om em ade salin e solut ion s.

Presentation

Pat ien ts experien ce acu te, severe pain , often ou t of proport ion to corn eal fin d - ings. Associated redn ess, ph otoph obia, tearing, an d blurred vision p rogress over th e cou rse of several w eeks. Seek a con t act len s h istor y or fresh w ater exp osure in associat ion w ith con t act len s w ear or clean ing. Fin dings begin w ith a pu n ctate epith elial kerat it is follow ed by su bepith elial h aze an d in filt rat ion . A radial peri- n eurit is m ay be seen along w ith pseudoden drit ic kerat it is. A late an d om in ous fin ding is st rom al ulcerat ion , n ecrosis, an d su bsequen t ring u lcerat ion w ith keratolysis (Fig. 5.5A,B,C).

Differential Diagnosis

HSV, HZA, bacterial kerat it is, fu ngal kerat it is, im m un e-related u lcer

Management

Obtain a corn eal scraping or corn eal biopsy. Ut ilize calcofluor w h ite, Giem sa,

H&E, or Gram st ain to iden t ify cyst s of t roph ozoites. Corn eal cult u re on n on - n ut rien t agar w ith Escherichia coli overlay can detect in fect ion . Con sider cult u r- ing th e con t act len s or case.

Con focal m icroscopy w h en available can be ben eficial for iden t ificat ion of th ese st ru ct u res in th e absen ce of severe st rom al u lcerat ion .

Discon t in ue con t act len s w ear.

Com bin at ion th erapy is m ost effect ive, bu t early diagn osis is th e m ost crit ical factor for su ccessful t reat m en t:

Diam idin es (propam idin e, h exam idin e)

Biguan ides (ch lorh exidin e diglu con ate, polyh exam ethylen e bigu an ide, alexidin e)

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A

B

C

Fig. 5.5 (A) Acantham oeba keratitis with severe punctate keratopathy and early central corneal haze. (B) Central corneal ulcer and radial perineuritis from Acantham oeba. (C) Ring ulcer and stromal necrosis from late Acantham oeba keratitis.

Am in oglycosides (parom om ycin , n eom ycin )

Im idazoles/t riazoles (clot rim azole, it racon azole, ketocon azole, m icon azole, m et ron idazole)

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Management

All corn eal ulcers sh ou ld be t reated as w ith bacterial kerat it is in it ially an d star ted on broad -sp ect ru m topical an t ibacterial m edicat ion s un t il cu lt ure-proven fu ngal in fect ion is iden t ified from corn eal scrapings or cu lt ure m edia. Scrapings w ith Giem sa, periodic acid –Sch iff, or Grocot t- Gom ori m eth en am in e-silver n it rate st ain s can iden t ify fu ngal elem en ts. Cult ure m edia sh ou ld in clu de eith er Sabou raud agar or brain –h ear t in fu sion broth . Nat am ycin 5%is th e t reat m en t of ch oice for filam en - tous Fusariu m in fect ion s, w h ereas topical m icon azole 1%is th e t reat m en t of ch oice for Paecilom yces. Am ph otericin B 0.15% or topical voricon azole is th e t reat m en t of ch oice for yeast kerat it is an d Aspergillu s in fect ion . Drops are t ypically star ted ever y 1 to 2 h ou rs an d often supp lem en ted w ith oral an t ifu ngal im idazoles or voricon azole. Corn eal debridem en t m ay be n eeded in su bsequ en t visit s to im prove topical m edicat ion pen et rat ion . Surgical keratoplast y tech n iqu es m ay be n eeded in severe cases w ith keratolysis or sign ifican t n on respon sive posterior corn eal plaqu es. Treat m en t is often n eeded for several m on th s, an d cor t icosteroids sh ould be avoided du ring th is t im e. Cycloplegia m ay be ben eficial in cases w ith sign ifican t uveit is or hypopyon to preven t p osterior syn ech iae form at ion .

Corneal Inflammation and Surface Disorders

Interstitial Keratitis

Th is is a n on suppu rat ive in flam m at ion of th e corn eal st rom a th at t ypically in - volves corn eal n eovascularizat ion an d even t ual lipid deposit ion an d scarring. Most cases resu lt from a hypersen sit ivit y react ion to in fect ious m icrobes or associated an t igen w ith in th e corn ea. Several viral, bacterial, an d h elm in th in fect ion s are associated w ith th is con dit ion .

Presentation

In it ial sym ptom s in clu de pain , tearing, p h otoph obia, an d perilim bal inject ion . Kerat ic precipit ate an d an terior uveit is m ay develop . With progression , deep st rom al n eovascularizat ion develops w ith cen t ral spread . Corn eal scarring an d edem a m ay en sue. A salm on -pin k patch m ay appear w ith in th e corn ea from severe st rom al n eovascularizat ion cases. Gh ost vessels even t u ally develop w ith lipid an d scar for- m at ion . St rom al scarring an d opacificat ion can becom e severe. (Fig. 5.7A,B).

Differential Diagnosis

Congenital syphilis (usually bilateral and develops late in the first decade of life)

Acqu ired syph ilis (rare an d usu ally u n ilateral w ith occu rren ce in adu lth ood)

Viral corn eal in fect ion s (HSV, HZV, EBV, m u m ps, rubeola)

Tu bercu losis (con firm w ith Tb skin test)

Leprosy

Chlam ydia t rachom at is (h istor y of sexu al con t act)

Helm in th in fect ion s [Onchocerca volvulus (on ch ocerciasis) from foreign t ravel in

en dem ic region ]

Lym e disease (h istor y of t ick exposu re; ch eck Lym e t iters)

Sarcoidosis (ch est x-ray, ser um calcium , lysosym e, an d angioten sin -conver t ing

en zym e level)

Cogan syn drom e (autoim m u n e disorder w ith in terst it ial kerat it is, ver t igo, an d h earing loss)