Ординатура / Офтальмология / Учебные материалы / Color Atlas of Ophthalmology The Quick-Reference Manual for Diagnosis and Treatment

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Miotics

Mechanism

Also called parasym p ath om im et ic or ch olin ergic-st im ulat ing agen t s, th is class en - h an ces ch olin ergic sign al to th e an terior ch am ber by eith er direct acet ylch olin e receptor act ivat ion or in h ibit ion of acet ylch olin esterase act ivit y. Th is in creased ch olin ergic act ivit y cau ses a st ate of m iosis th at low ers IOP by en h an cing aqueous h um or outflow th rough th e t rabecu lar m esh w ork. A p ilocarpin e-in du ced m iosis h as been sh ow n to directly in crease th e w idth of th e an terior ch am ber angle in pat ien t s w ith a n arrow angle.

Indications

Miot ics are in dicated for both POAG an d PAC. Th e side-effect profile m akes m iotics a rarely u sed glau com a agen t . Th is class of topical m edicat ion is also used to con t rol accom m odat ive esot ropia.

Contraindications/Adverse Effects

System ic side effect s can on ly occu r at 5 to 10 t im es th e n orm al dose. Classic parasym path et ic syn drom e occu rs, in clu ding lacrim at ion , salivat ion , perspirat ion , n au - sea, vom it ing, an d diarrh ea, bu t ver y rarely at prescribed dosages. Th e ocular side effects are p roblem at ic ow ing to th e dim in ish ed vision w ith pupillar y con st rict ion an d h eadach e from ciliar y m uscle spasm .

Sympathomimetics (Epinephrine)

Mechanism

Adren ergic st im u lat ion decreases IOP by im proving aqueous ou tflow th rough both th e can al of Sch lem m an d th e uveoscleral path w ay.

Indication

Sym path om im et ics are in frequ en tly u sed in th e t reat m en t of POAG ow ing to th eir poten t ially seriou s system ic side effect s. Th ey are also n ot in dicated for PAC becau se of th e adverse effect of m ydriasis on th e an terior ch am ber angle.

Contraindications/Adverse Effects

Epin eph rin e m ay cau se cardiac arrhyth m ia or an in crease in system ic blood pressu re ow ing to it s system ic adren ergic st im ulat ion . Dipivefrin is an epin eph rin e prodr ug th at causes few er system ic side effects.

Alpha2 Selective Agonists

Mechanism

Th e first drug in th is class, apraclon idin e, w as derived from clon idin e an d w as

in ten ded to select ively block th e α 2 adren ergic receptor. Brim on idin e w as th en released an d sh ow n to be 23 to 32 tim es m ore select ive for α 2 receptors versu s

α 1 receptors th an ap raclon idin e. Act ivat ion of th e α 2 receptor is th ough t to h ave

a du al m ech an ism of decreasing aqueous produ ct ion an d in creasing uveoscleral outflow .

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Indications

Th e differen t con cen t rat ion s available for apraclon idin e h ave specific in dicat ion s. A single-dose applicator of a 1%solut ion is available for sup pression of th e acu te IOP spikes th at occur after laser t reat m en t s. A 0.5%con cen t rat ion is also available in a m u lt idose bot tle for glau com a p at ien ts w h ose IOP is n ot adequ ately respon ding to m axim ally tolerated th erapy. Ch ron ic use of apraclon idin e is lim ited by its adverse effects an d tachyphyla xis. Th e h igh er α 2 receptor select ivit y of brim on idin e allow s th is t ype of pressu re-low ering m edicat ion to be u sed on a ch ron ic basis.

Contraindications/Adverse Effects

Apraclon idin e h as been associated w ith tachyphylaxis or rapid physiological toleran ce in u p to 48% of pat ien t s, ren dering it less u sefu l in th e ch ron ic form s of glaucom a. Th e m ost con cern ing adverse effect s in clu de or th ost at ic hyp oten sion an d vasovagal episodes. Th e topical applicat ion of apraclon idin e is associated w ith m ild pupillar y dilat ion , w h iten ing of th e conjun ct iva, an d elevat ion of th e u pper eyelid . Th e adverse effect profile of brim on idin e h as been m in im al but m ay in clude oral dr yn ess, h eadach e, an d fat igue/drow sin ess. Brim on idin e is con t rain dicated in in fan ts because of th e risk of severe hypoten sion an d apn ea. Both drugs m ay cau se a local sen sit ivit y react ion , w ith apraclon idin e h aving a fairly h igh rate of con t act derm at it is of th e lids an d conju n ct iva.

Diagnostic Agents

Oph th alm ology requ ires th e abilit y to see cer tain path ology an d m an ipulate th e eye in cert ain circu m stan ces. Not all path ology is readily visible u n der direct slit lam p exam in at ion . Th e eye is a ver y sen sit ive organ an d w ill n ot tolerate m an ip u - lat ion w ith out appropriate an esth esia. An esth et ics are u sed to h elp w ith m an ip u - lat ion an d cert ain dyes to visualize path ology (Table 14.13).

Fluorescein

Flu orescein com es in m any form s, in clu ding topical drops (Flu ress), topical st rips, oral form s, or in t raven ou s (IV) solu t ion (Fig. 14.5). It appears as a red -orange p ig- m en t un der n at ural ligh t , bu t w h en seen un der a blue filter, it t urn s a fluorescen t green color. Th e m ost com m on use is th e topical form . It can also be top ically u sed to evalu ate corn eal scarring or oth er dam age to th e corn eal epith elium . W h en th e corn ea is dam aged, th e dye is able to pass across t igh t ju n ct ion s an d stain th e un - derlying layers. Recen t pu blicat ion s also n ote th at it h as a diagn ost ic pu rpose in evalu at ing fun ct ion ing of th e glan ds in th e eyelids. IV an d oral flu orescein is used to evaluate ret in al path ology by direct fu n dus ph otography or con focal m icroscopy. Flu orescein angiography allow s visualizat ion of th e vascu lat u re of th e ret in a at differen t t im e in ter vals.

Flu orescein is u su ally adm in istered in com bin at ion w ith an esth et ic or by m oisten ed st rips. Slit-lam p exam in at ion provides bet ter diagn ost ic view ing w h en st rips are u sed becau se th e con cen t rat ion of flu orescein delivered in m ost drops is too h igh for discrim in at ing evalu at ion . IV fluorescein is usually injected at a dose of 500 m g. More recen t research n otes th at doses as low as 166 m g are effect ive for evalu at ion w h en u sing con focal scan n ing laser im aging. Oral flu orescein m ay be a possible diagn ost ic agen t as con focal im aging progresses, bu t curren t angiography st ill requ ires th e u se of IV flu orescein .

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Fig . 14.5 Combined fundus fluorescein angiography and indocyanine green (ICG) angiography. It reveals a pigment epithelial detachment with pooling of dye with a notch, and the ICG is suggestive of a focal hot spot in the area of the notch. (Courtesy of Dr. Manish

Nagpal)

Adverse effects are m in im al for th e topical form s of th e drug. More effect s are p ossible w h en IV flu orescein is u sed . Nausea, vom it ing, dizzin ess, an d a bit ter taste m ay resu lt during IV adm in ist rat ion . Many pat ien ts develop cough or dr y th roat , an d som e can develop u r t icaria, or localized in flam m at ion of th e inject ion site from allergies. An aphylactoid react ion s, sickle cell crises, h em olyt ic an em ia, seizure, m yocardial in farct ion , an d death s are all docu m en ted in th e literat ure, but th eir occu rren ce is rare.

Indocyanine Green

An oth er poten t ial agen t used to evalu ate posterior com par t m en t path ology is ICG. Mu ch like its closely related su bst an ce, flu orescein , th is dye is injected in t rave- n ou sly to evaluate th e ret in a an d ch oroid . It h as a dist in ct advan tage over flu orescein in th at it can bet ter diagn ose ch oroidal n eovascu larizat ion . Th is is due par tly to th e fact th at ICG is h igh ly plasm a protein bou n d . Flu orescein , w h ich usu ally leaks out of th e capillaries, can n ot defin e vasculat ure as w ell as ICG, w h ich stays w ith in th e vessels. Oth er advan tages in clu de th e fact th at th e flu orescen t w avelength of ICG places it in th e n ear in frared spect ru m . Th is factor allow s pen et rat ion of t issu es th at n orm ally absorb th e sh or ter w avelength fluorescen ce of flu orescein .

ICG is usu ally adm in istered in doses of 25 m g for proper im aging. Because of advan ces in con focal oph th alm oscopy, adequ ate diagn ost ics can be obtain ed by as lit tle as 5 m g of ICG. Adverse react ion s are rare bu t can in clude n au sea, vom iting, an d gen eral discom for t . An aphylaxis h as been repor ted in cer tain cases. ICG sh ould n ot be u sed in in dividuals w ith kn ow n allergy to th e su bst an ce or allergies to iodide becau se m any preparat ion s of ICG con tain iodide. In in dividu als w ith allergies to flu orescein , use of ICG m ay avoid serious react ion s.

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Agents Used in the Diagnosis and Management of

Neuro-ophthalmological Conditions

Most pupillar y disorders of th e sym path et ic or parasym path et ic n er vou s system are p h arm acologically diagn osed by u sing specific oph th alm ic drops (Table 14.14).

Medications and Therapeutics for Dry Eye

An est im ated 7.1 m illion people in th e Un ited St ates over th e age of 40 are afflicted w ith keratoconju n ct ivit is sicca (KCS, also kn ow n as dr y eye) (Fig. 14.6). Dr y eye is par t icularly prevalen t in w om en aged 50 years an d older, bu t in pat ien t s aged 75 an d older, th is prevalen ce is dim in ish ed . Table 14.15 provides a list ing of th e t ypes of targeted an d palliat ive t reat m en t s available.

Fig . 14.6 Severe dry-eye syndrome with corneal neovascularization.

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Table 14.15 Therapeutic Options fo r Dry Eye Syndrom e*

1Alcon Laboratories, In c., For t Worth , TX USA: 2Allergan , In c., Ir vin e, CA USA; 3Advan ced Vision Research , In c., Woburn, MA USA; 4Abbot t Medical Opt ics, Abbot t Park, IL USA; 5Cyn acon/OcuSoft , In c., Richm ond, TX USA; 6Novar t is Ph arm aceut icals, St . Louis, MO USA; 7Bausch an d Lom b, In c., Roch ester, NY zer Labs, In c., New York, NY USA; 9Aton Ph arm aceu ticals, In c., Law ren ceville, NJ USA; 10Mead -Joh n son Laboratories, Evan sville, ID USA; an d 11MGI PHARMA, In c., Bloom - ington , MN USA.

Acknowledgments

Th is w ork w as m ade possible, in par t , by NEI-EY-006311 (JMH), Research to Preven t Blin dn ess Sen ior Scien t ific Invest igator Aw ard (JMH), EY02672 (HEK) an d LSU Eye Cen ter Core Gran t EY02377. Th e Depart m en t of Oph th alm ology h as an un rest ricted gran t from Research to Preven t Blin dn ess, New York, NY an d fu n ds from th e Lou isian a Eye Foun dat ion , New Orlean s.