CATARACT: PERIOPERATIVE CONSIDERATIONS
| UPDATE ON ANTIBIOTIC PROPHYLAXIS IN CATARACT AND REFRACTIVE SURGERY —Francis S. Mah, MD,
Assistant Professor and Co-Medical Director, Charles T. Campbell Ophthalmic Microbiology Laboratory, Department of
Ophthalmology, University of Pittsburgh, Eye & Ear Institute, Pittsburg, PA
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| Antibiotic prophylaxis: no large prospective, randomized clinical studies of antibiotic prophylaxis available in ophthalmology;
due to low infection rates (1 in 1000 cataract surgeries; 1 in 3000 refractive surgeries), estimated that 50,000 to
70,000 cases required for adequate study; also, methods and materials variable
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| Causes of surgical infections: endophthalmitis—primarily gram-positive bacteria and among them, primarily coagulase-
negative staphylococci; laser-assisted in situ keratomileusis (LASIK)—primarily gram-positive bacteria and mycobacteria,
although evidence that rash of mycobacterial infections decreasing
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| Source of organisms for endophthalmitis: patients’ lids, lashes, and lacrimal systems most likely sources; recommend lid
draping and preoperative treatment of ocular surface disorders, eg, meibomitis, blepharitis, discharge
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| Methods of prophylaxis: reduction of endogenous surface organisms; eradication of pathogens that gain entry into ocular
tissues (penetration argument)
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 | Endogenous surface organisms: prospective study—>10,000 patients showed 75% to 80% reduction in endophthalmitis
with povidone-iodine scrub on lids and lashes; povidone-iodine solution also applied inside eye; other studies—
several studies show antibiotics in addition to povidone-iodine can reduce endogenous surface organisms
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| Antibiotics only: eye surgery—1974 retrospective study of 36,000 patients showed change in antibiotic yielded reduction
in rates of endophthalmitis; general surgery—perioperative antibiotics understood to reduce infection rates; recommend
short duration to decrease risk for resistance and use of antibiotics active against majority of organisms known to
cause infections; give antibiotic immediately (15 min better than 1 hr) before surgery and do not continue longer than 12
to 48 hr
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| Antibiotics suitable for surgical prophylaxis: in vitro testing—susceptibility charts based on serum standards and do not
give ocular susceptibility standards; need studies examining ocular concentrations (in anterior chamber, cornea, and
conjunctiva); can get more antibiotics into eye than into serum; speaker’s study—used rabbit model infected with
methicillin-resistant Staphylococcus aureus (MRSA); found gatifloxacin bactericidal (better than levofloxacin; ciprofloxacin
ineffective); this corresponds to concentrations that get into cornea; gatifloxacin as effective as vancomycin;
Serratia infection—in rabbit model, greater concentrations of gatifloxacin in cornea led to higher effectiveness than
ciprofloxacin; tobramycin ineffective because aminoglycosides do not penetrate intact corneal epithelium
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| Effect of concentration: measure maximum concentrations of antibiotics in anterior chamber and cornea and concentrations
over time; these can predict performance of antibiotics; studies of concentration in human conjunctival tissue
show fluoroquinolones do better than most classes of antibiotics; high concentrations achieved in cornea and conjunctiva
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| Desirable properties of antibiotics for prophylaxis: commercial availability, broad spectrum, wide safety margin, excellent
pharmacokinetics, ability to kill rapidly before surgery; eliminate—bacteriostatic agents (eg, sulfonamides,
chloramphenicol, tetracycline, macrolides); oxalodinones (linezolid, daptomycin, quinupristine/dalfopristin [Synercid],
and vancomycin; cover only gram-positive organisms; toxic to eye); remaining agents—bactericidal; all broad spectrum;
β-lactams not stable; lipopeptides (eg, polymyxin B) and aminoglycosides do not penetrate corneal epithelium
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| Fluoroquinolones: suitable for prophylaxis; newer generation of fluoroquinolones, eg, gatifloxacin (Zymar) and moxifloxacin
(Vigamox), cover resistant isolates; studies show endophthalmitis, keratitis, and conjunctivitis isolates covered; rabbit
studies show endophthalmitis prevented, and MRSA, Pseudomonas, and mycobacteria treated using fourth-
generation fluoroquinolones
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| Commercial topical formulations: many studies involve pure powder, not commercial formulations that contain benzalkonium
chloride (BAK) as preservative; however, speaker’s study of commercial formulation of Zymar in rabbit model
shows BAK can enhance tissue absorption of drug
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| Can antibiotic prophylaxis prevent endophthalmitis? rabbit study —used moxifloxacin on reasonable dosing schedule
(4 drops 1 hr before S aureus injected into rabbit’s eye, 4 drops for 24 hr afterward); 100% of rabbits treated with saline developed
endophthalmitis (80% had positive cultures); no rabbits given Vigamox had clinical signs of endophthalmitis; antibiotics
without povidone-iodine can prevent endophthalmitis
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| Recommendations for prophylaxis: treat periocular conditions preoperatively; use meticulous lid draping for cataract
and refractive surgery; preoperative antiseptic (povidone-iodine) placed in eye for cataract surgery but not for refractive
surgery; to be effective, must be used at least 3 min before irrigation
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| Topical antibiotics: preoperative—use fourth-generation fluoroquinolones on day of surgery; for high-risk cataract patients,
may use systemic fluoroquinolone or subconjunctival antibiotic; postoperative—recommend high doses first day
after cataract surgery; drops every 1 to 2 hr for first 24 hr, then qid until epithelium healed in refractive and cataract surgery
(usually ≈1 wk); do not taper (promotes resistance); stop antibiotics after 1 wk
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| Conclusion: need better understanding of factors that affect clinical efficacy of topical and systemic antibiotics in ophthalmic
surgery; in vitro minimal inhibitory concentrations (MICs) and susceptibilities small initial part of determining clinical efficacy
in ophthalmology; no other commercial topical antibiotics now offer spectrum of pharmacokinetic and pharmacodynamic
properties with history of safety like fluoroquinolones
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| Questions and answers: continued occurrence of endophthalmitis despite pre- and postoperative fluoroquinolone—
endophthalmitis multifactorial process; cannot prevent all cases; until something better comes along, fluoroquinolones
best antibiotics we have; warning about gatifloxacin (Tequin)—causes hypoglycemia; not recommended for diabetics;
vancomycin—not proven to prevent endophthalmitis; type of anesthetic—speaker uses lidocaine gel; can prevent clearance
of surface organisms and penetration of topical antibiotic; use lidocaine gel after antibiotic and antiseptic as last step
before prepping and draping; clear corneal incision—may increase susceptibility to endophthalmitis
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| VIRAL EXTERNAL OCULAR DISEASES IN CATARACT AND REFRACTIVE SURGERY —Dr. Mah
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| Adenoviral infections: no way to diagnose; empiric treatment expensive, involving multiple physician visits, loss of work
and income, and morbidity
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| Treatment options: no specific antiviral agent; academic guidelines recommend symptomatic relief, eg, antihistamines,
vasoconstrictors, artificial tears, compresses, avoidance of topical antibiotics and steroids, good hygiene, isolation
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| Clinical pearls from literature: shaking hands—not advised with patients with epidemic keratoconjunctivitis (EKC) unless
physician wearing gloves; in study of 26 patients with adenovirus, 42% had positive hand culture; adenovirus survival on office
surfaces (study)—8 days to 7 wk, depending on surface; 8 days on paper, 10 days on cloth, 7 wk on metal surfaces (eg,
doorknobs); waiting room excellent site for transmission; when patients with adenovirus arrive, direct them away from waiting
room
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| Rapid diagnosis of EKC in office: immunochromatography— like pregnancy test; uses small tear sample and takes 15
to 30 min; sensitivity low (identification 30%-50% of time); however, positive result definitive for adenovirus; real-time
polymerase chain reaction (PCR)—90 min; extremely sensitive and specific; not office-based; in ≈5 yr, will be able to
determine whether patient with red eye has bacteria, fungus, or parasite and whether it is resistant to antibiotic or antiviral
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| Topical antibiotics in EKC: not indicated if sure of viral diagnosis (bacterial superinfection rare); most physicians prescribing
anyway; 1977 survey of academicians and general ophthalmologists in community found that one third of time,
both groups prescribing antibiotics for viral infections
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| Topical steroids in EKC: rarely indicated but prescribed one third of time; can prolong shedding of virus (up to 9 days)
and produce office or community epidemic
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| Antiviral agents: cidofovir (Vistide)—was in phase 3 trial, then discontinued because of truncal stenosis side effect; topical
ganciclovir—used for cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV); topical
N-chlorotaurine—found in all polymorphonucleocytes; kills bacteria, fungi, parasites, and viruses; in phase 2 trials;
doxivir and NMSO3—investigational
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| How long to keep EKC patient out of school or work: 3 to 7 days, depending on clinical signs; in study, patients culture-
negative after 7 days 88% of time
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| Herpes simplex virus: typically clinical diagnosis; dendrite or geographic ulcers seen; sometimes associated with contact
lenses or abrasions; no rapid sensitive office-based test; do culture (takes ≈1 wk) or Enzyme Linked Virus Inducible System
(ELVIS; 24-hr culture test for HSV); real-time PCR (diagnosis within 1 hr) in future
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| Treatment of herpes epithelial keratitis: topical and/or oral; speaker does not recommend use of topical agents, uses oral
agents due to greater tolerance; for children, 12 to 15 mg/kg per day of oral acyclovir (Zovirax) in divided doses shown effective
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| Immunologic herpes: stromal keratitis, iridocyclitis; study recommends topical steroid for inflammation and antiviral
cover, eg, trifluridine (Viroptic), or oral agent and steroid; speaker bypasses topical agent, uses acyclovir (inexpensive,
generic)
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| Long-term antiviral therapy: indicated only for recurrent epithelial or stromal disease; not cost-effective to treat all HSV-1
cases; take into account significant visual loss and frequency of occurrences; recommend oral agent (acyclovir) for first episode
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| Preoperative patients with history of recurrent ocular HSV: short- or long-term steroids biggest issue; for cataract,
glaucoma, or refractive surgery, prophylactic regimen (acyclovir 400 mg bid or tid) used 2 days preoperatively and 7
days postoperatively; for penetrating keratoplasties, use acyclovir long-term with immunosuppressant (eg, mycophenylate
[CellCept]; reduces graft rejection as well as HSV recurrence)
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| Varicella zoster: important to start all patients on oral antivirals as soon as possible; shown that 1 day makes significant
difference in neurotropic keratitis and adverse outcomes, eg, decreased vision
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| Hutchinson’s sign: has important prognostic value for neurotropic keratitis; if positive, look for corneal denervation as
well as ocular inflammation after shingles
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| Office pearls for VZV: younger patients—rule out HIV and AIDS (VZV 20 times more likely); immediate therapy—
use oral antivirals; sometimes tricyclic antidepressants reduce pain and prevent postherpetic neuralgia; oral steroids—
controversial; often started by primary care physician (PCP); speaker says no benefit for ocular VZV; immunosuppressed
patients—may need acyclovir indefinitely
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| CATARACT SURGERY IN PATIENTS WITH PREEXISTING RETINAL DISEASE —Carmen A. Puliafito, MD, Professor
and Chair, Kathleen and Stanley J. Glaser Chair in Ophthalmology, Department of Ophthalmology, Bascom Palmer
Eye Institute, and University of Miller School of Medicine, Miami, FL
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| Macular disease: in anterior segment patients, very common to have preexisting retinal disease; clinical examination can
be misleading (no longer ultimate standard of care)
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| Optical coherence tomography (OCT): 6000 performed in 2003 at Bascom Palmer Eye Institute, last year 25,000; not all
ordered by retina specialists, ie, physicians using OCT as quick, noninvasive way to examine patient’s macula; first test retina
specialists do, but diagnosis using OCT difficult, eg, patient with serous pigment epithelial detachment (PED); get OCT
if preexisting retinal disease or macular pathology suspected; cataract specialists can learn to use as skillfully as macula specialists
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| Cataract surgery patient with macular degeneration: study did not appear to show progress of age-related macular degeneration
(ARMD) more rapid in patients who have cataract surgery; however, since neovascular ARMD characterized
by changes in biologic factors in eye, eg, epidermal growth factor (EGF), plausible that opening eye for surgery might
upset balance and promote upregulation of EGF
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| Deciding whether to operate: make sure risk-benefit assessment positive if patient has ARMD; if patient has intermediate
ARMD (relatively large, numerous drusen), speaker tends toward conservative treatment, especially if other eye shows
neovascularization; good treatments available for wet macular degeneration; discuss with patient; case—patient with retained
cortical material after cataract surgery sent to speaker; material removed, and vision 20/25 at 1 mo; returned 1 mo
later with reduced vision due to macular edema; whenever patient has complicated cataract surgery, OCT indicated to
look for cystoid macular edema (CME)
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| Treatment: new agents nepafenac (Nevanac) and bromfenac allegedly better than ketorolac (Acular) and diclofenac
(Voltaren); increasing number of physicians routinely using nonsteroidal agents on cataract surgery patients; use topical
treatment; never use systemic steroids for macular edema in this setting; speaker also does not favor sub-Tenon’s injection;
if patient has no anatomic complication, intravitreal triamicinolone (Kenalog) works well
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| Vitreal macular traction (VMT) syndrome: not uncommon; difficult to diagnose by clinical examination, even by retinal
specialist; frequently bilateral
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| Problems with injections: increased intraocular pressure most common problem, so routine intravitreal Kenalog not recommended;
most patients with CME need only one injection; most glaucoma occurs after ≥2 injections, but some patients
have persistent increased pressure after 1 injection (speaker urges caution); case—patient with trabeculectomy,
cataract surgery, CME, and poor vision given intravitreal Kenalog and developed pseudohypopyon; Kenalog got into anterior
segment; patient observed and improved over time
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Educational Objectives
| The goal of this program is to educate the listener on preoperative issues in cataract surgery, including preexisting retinal
disease. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Identify current uses for antibiotics as prophylaxis for cataract and refractive surgery.
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| 2. List the ideal properties of an antibiotic for ocular prophylaxis.
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| 3. Identify common external ocular viral infections.
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| 4. Understand issues for cataract surgery in patients with macular disease.
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| 5. Explain the role of optical coherence tomography in preparation for cataract surgery.
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Discussed on this Program
Acyclovir (acycloguanosine) [Zovirax]
Bromfenac 0.09% ophthalmic solution [Xibrom]
Cidofovir [Forvade (investigational), Vistide]
Chloramphenicol [Chloramphenicol Sodium Succinate, Chloromycetin, Chloromycetin Sodium Succinate]
Diclofenac [Cataflam, Voltaren, Voltaren-XR]
Doxivir (investigational)
Ganciclovir intravitreal implant [Vitrasert Implant]
Gatifloxacin [Tequin, Zymar]
Ketorolac tromethamine [Acular, Acular LS, Acular PF, Toradol]
Lidocaine (several trade names)
Moxifloxacin [Avelox, Avelox I.V., Vigamox]
Mycophenylate mofetil (MMF) [CellCept]
N-chlorotaurine (investigational)
Nepafenac (Nevanac)
Povidine-Iodine (several trade names)
Triamcinolone acetonide (several trade names)
Trifluridine (trifluorothymidine) [Viroptic]
Vancomycin [Vancocin, Vancoled]
Varicella virus vaccine [Varivax]
Suggested Reading
Broecker EH et al: Optical coherence tomography: its clinical use for the diagnosis, pathogenesis, and management of
macular conditions. Cornea Jan 24:1 2005; Chan A et al: Stage 0 macular holes: observations by optical coherence tomography.
Ophthalmology 111:11 2004; Chamberlain MD et al: Heritability of macular thickness determined by optical coherence
tomography. Invest Ophthalmol Vis Sci 47:1 2006; Custis PH et al: An unusual case of cryptococcal
endophthalmitis. Retina. 15:4 1995; Das T: Is continuous research necessary in management of post cataract surgery endophthalmitis?
Indian J Ophthalmol 49:1 2001; Goguen E et al: Perioperative pharmacology in cataract surgery. Insight
30:2 2005; Herrygers LA: Comparison of corneal surface effects of gatifloxacin and moxifloxacin using intensive and prolonged
dosing protocols. Kehdi EE et al: Spectrum of clear corneal incision cataract wound infection. J Cataract Refract
Surg 31:9 2005; Ko TH et al: Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging
macular pathology. Ophthalmology 2005 Nov;112(11):1922. Epub 2005 Sep 23. Lai WW et al: Prevention of endophthalmitis.
J Cataract Refract Surg 31:9 2005; McCulley JP et al: Fourth-Generation Fluoroquinolone Penetration into the
Aqueous Humor in Humans. Ophthalmology 2006 [Epub ahead of print] 2006; Mendivil Soto A et al: The effect of topical
povidone-iodine, intraocular vancomycin, or both, on aqueous humor cultures at the time of cataract surgery. Am J
Ophthalmol 131:3 2001; Ta CN et al: Minimizing the risk of endophthalmitis following intravitreous injections. Retina
24:5 2004; Taban M et al: Acute endophthalmitis following cataract surgery: a systematic review of the literature. Arch
Ophthalmol 123:5 2005; Troll GF: Regional ophthalmic anesthesia: safe techniques and avoidance of complications. J
Clin Anesth. 7:2 1995 Wu PC et al: Risk of endophthalmitis after cataract surgery using different protocols for povidone-
iodine preoperative disinfection. J Ocul Pharmacol Ther 22:1 2006; Optometry 76:2, 2005; Yamada N et al: Tomographic
features and surgical outcomes of vitreomacular traction syndrome. Am J Ophthalmol 139:1 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, Dr. Mah reported
a relationship with Alcon Labs, Inc. and Allergan, Inc.
Drs. Mah and Puliafito gave their scientific presentations at the Cataract and Refractive Surgery Congress, held February
24-25, 2006, in Miami, FL, sponsored by the Bascom Palmer Eye Institute. The Audio-Digest Foundation thanks the speakers
and the sponsor for their cooperation in the production of this program.
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