PRACTICE PEARLS
Educational Objectives
| The goal of this program is to improve the management of various ophthalmic conditions. After hearing and assimilating
this program, the clinician will be better able to:
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 | Recognize the indications for nonsteroidal anti-inflammatory drugs in ophthalmic cases.
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| Choose the appropriate intraocular lens based on its properties.
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| Describe the combinations of lenses used.
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| Identify the risk factors for age-related macular degeneration.
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| Describe the various toric lenses available, as well as appropriate indications.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the following has been disclosed: Dr. Silverstein receives research
support from Alcon Laboratories, Allergan, and Ista Pharmaceuticals. Dr. Fishkind is a consultant for Advanced Medical Optics
and has received royalties from Thieme Medical Publishers. Dr. Moshfeghi is a consultant for Genentech, Eyetech Optics, and
Alcon Laboratories, and is on the Speakers’ Bureau of Genentech. Dr. Henderson receives grant support from and is on the
Speakers’ Bureau of Alcon Laboratories and Ista Pharmaceuticals. The planning committee reported nothing to disclose.
Acknowledgements
Drs. Silverstein and Fishkind were recorded at the Annual Clinical Conference, held January 11-12, 2008, in Overland
Park, KS, and sponsored by the Kansas City Society of Ophthalmology and Otolaryngology. Dr. Moshfeghi was recorded
at the 2007 Vitreoretinal Course Update, held May 4-5, 2007, in Miami, FL, and sponsored by the Bascom
Palmer Eye Institute. Dr. Henderson was recorded at the Cataract and Refractive Surgery Congress, held February 8-9,
2008, in Miami, FL, and sponsored by the Bascom Palmer Institute, University of Miami Miller School of Medicine.
The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
| USE OF NSAID THERAPY TO MAXIMIZE OPHTHALMIC SURGICAL OUTCOMES—Steven Silverstein, MD, Clinical
Professor of Ophthalmology, University of Missouri-Kansas City School of Medicine and the University of Health Sciences,
and Partner, Silverstein Eye Centers, Kansas City, MO
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| Indications for nonsteroidal anti-inflammatory drugs (NSAIDs): prevention and treatment of cystoid macular
edema (CME); control of postoperative pain and inflammation; inhibition of intraoperative miosis; ocular allergy;
keratorefractive surgery (ie, laser-assisted in situ keratomileusis [LASIK], photorefractive keratectomy [PRK], epithelial
[Epi]-LASIK); viral keratoconjunctivitis; nonspecific ocular pain in patients with no other disease evident on examination;
pain management for recalcitrant corneal erosion; steroid responders; uveitis; postoperative need in glaucoma filtration surgery,
strabismus surgery, corneal transplantation, pterygium excision, and vitreoretinal procedures; questionable role in
scleritis and episcleritis, orbital inflammatory disease, optic neuritis, and dry eye
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| Adverse events: most commonly reported include burning, stinging, irritation, punctate keratitis, and delayed wound
healing; in severe corneal cases, eg, thinning, melt with perforation (primarily in Japanese literature); corneal toxicity—
due to risk factors of dry eyes (keratoconjunctivitis sicca), blepharitis, rheumatoid disease, and concomitant steroid use
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| Site of activation: inflammation or surgical trauma causes release of prostaglandins in anterior segment that quickly diffuse
and penetrate into posterior segment; mechanism—takes trigger (eg, hormones, inflammation, trauma) to cause hydrolysis of
cell and release of arachidonic acid into intracellular space; once in intracellular space, metabolized via 1 of 2 pathways (lipooxygenase
pathway results in manufacture of leukotrienes; cyclooxygenase [COX] pathway [COX-1 or COX-2] leads to
formation of eicosanoids [prostaglandins most important]); prostaglandins—responsible for itching, burning, photophobia,
and CME; goal to block metabolism of arachidonic acid; COX—in stomach, blood vessels, and kidneys; most important metabolic
enzyme; necessary to have some prostaglandin circulating in body for normal basic metabolic functions; early generation
of COX-1 inhibitors so effective that they caused serious systemic abnormalities, especially in gastrointestinal (GI)
system; as result, COX-2 inhibitors developed, which block prostaglandins formed in response to inflammation and surgical
trauma; problem that selective COX-2 blockers have increased risk for cardiovascular events (particularly myocardial infarction)
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| Dosing regimen: for any drug, determined by its pharmacokinetics and potency; potency measurement for NSAIDs, inhibitory
concentration (IC)50 (drug concentration required to inhibit enzyme activity by 50%); smaller the number, more
potent the molecule; difficult to measure drug in target tissues; animal study of bromfenac (single drop in cornea; similar
study in humans that corroborates rabbit data) showed IC50 maintained in target tissues for 12 hr
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| New demands on cataract surgery: higher surgical standards and demands by patient, due to new instrumentation
and optical coherence tomography (OCT); any vessel leakage constitutes CME; more demanding patients require that
prophylaxis be routine (easier to prevent than to treat CME)
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| Intraoperative benefits in lens surgery: maintenance of better surgical mydriasis and inhibition of intraoperative
miosis
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| Cystoid macular edema: most frequent cause of visual decline after uncomplicated or routine cataract surgery; typically
presents 4 to 6 wk postoperatively; risk factors—preexisting ocular inflammation; epiretinal or vitreoretinal interface
membrane problems; diabetic retinopathy; patients suffering from oculovascular or cardiovascular disease; history
of retinitis pigmentosa; prophylaxis started earlier for high-risk patients; study—compared use of NSAID with steroid vs
steroid alone in uncomplicated cataract patients; showed significant reduction of postoperative CME and macular thickening
in combined group; also showed correlation between macular thickening and decrease in contrast sensitivity
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| Use in refractive cataract surgery: patients receiving multifocal or pseudoaccommodation lenses more critical of vision
and more demanding about early return of vision; Donnenfeld, et al—found that group receiving ketorolac (Acular LS)
had better outcomes than group not using NSAID
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| When to initiate treatment: Donnenfeld study looked at 100 participants using ketorolac; found that dosing 1 to 3
days with NSAID significantly improved all parameters, compared to group that did not receive medication; length of
treatment—for patients not at risk and who have expected uncomplicated course, 1 day to 1 wk before surgery and typically
for 1 mo after surgery; for patients with risk factors, 1 wk before surgery and 1 to 3 mo postoperatively
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| MANAGEMENT OF THE CATARACT PATIENT—William J. Fishkind, MD, Clinical Professor of Ophthalmology,
University of Utah, Clinical Instructor of Ophthalmology, University of Arizona, and Co-Director, Fishkind and Bakewell
Eye Care and Surgery Center, Tucson, AZ
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| Introduction: new focus to optimize patient satisfaction based on needs (ie, optimize, rather than just improve, vision); necessary
to target emmetropia (spherical equivalent of <0.25 diopter [D]); reduce astigmatism to ≤0.5 D; maintain axis of preexisting
astigmatism; be ready to deal with demanding patients and perform enhancements for minor residual refractive
errors
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| Refractive intraocular lens (IOL) exchange: effective for presbyopic middle-aged patients and hyperopic patients;
good alternative to lasers and phakic lenses; provides accommodative or multifocal outcomes; requires accurate A-scan
(speaker prefers Zeiss IOL Master); Accutome immersion performed on all patients (shows shorter axial length, due to
pressure on cornea); IOL Master speaker’s choice for making calculations; keratometry critical; choose appropriate formula;
consistency important; 0.5 D goal for presbyopic patients; speaker performs limbal-relaxing incisions (LRIs) on every
patient with >0.5 D of cylinder to get as close to plano as possible; speaker uses Nichamin nomogram; LRIs not as
precise
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| Surgical techniques: speaker’s technique for LRIs—performed before phacoemulsification; all patients marked;
capsulorrhexis—should be centered (less risk for decentration) and smaller than optic (permits exchange); unwise to
perform yttrium aluminum garnet (YAG) laser capsulotomy (more difficult to remove lenses); smaller rhexis allows
placement of lens in sulcus for sulcus fixation and optic capture in case of tear of posterior capsule; must break connections
between nucleus and bag (otherwise, when nucleus rotates, bag stressed); cortical cleaving hydrodissection important
part of procedure
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| Mix and match: patient’s lifestyle should determine choice of lens; speaker’s opinion that reading most important consideration
for patients; all patients counseled on technology of implants and warned that glasses needed for fine print
and computer (patient can expect to be spectacle-independent ≈90% of time); every patient told that time (3-6 mo not
unusual) needed for adaptation; 1 in 2000 patients unable to adapt and requires lens exchange; speaker documents patient’s
expectations; every patient informed of multifocal implant; some surgeons start with ReZoom in distance-
dominant eye, and others start with ReSTOR in near eye; speaker always operates on worst eye first and places appropriate
lens in worst eye (if dominant eye, usually ReZoom used [Tecnis in future] and ReSTOR in nondominant eye)
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| Crystalens: not used by speaker for mix and match; 5-mm optic Crystalens better than 4.5-mm lens because of bigger optic,
and haptics straight instead of angulated (gives more contact to posterior capsule and adds to lens stability); 80% to
90% successful (10%-20% of patients have unexpected residual refractive errors)
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| Tecnis multifocal IOL: aspheric surface makes difference; European data show Tecnis lens excellent for distance and
near vision (fair for intermediate vision), and fewer halos, with exceptional quality, sharpness, and clarity of vision;
strengths—good distance, low contrast loss, and excellent vision, with good spectacle independence (spectacles still
needed for intermediate and close fine vision)
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| ReZoom IOL: limitations—excellent for distance vision, fair at intermediate vision, and poor at near vision; good degree
of pupil resiliency; creates night halos; spectacles required for near vision
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| ReSTOR and ReSTOR aspheric IOL: apodized; strengths—excellent near vision, fair intermediate vision, and improvement
in distance vision; issue of large pupils interfering with vision
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| Tecnis and ReSTOR combined: Tecnis provides reduced spherical aberration, is pupil-independent, provides better contrast,
and works well with ReSTOR (complementary); study found incidence of spectacle independence 84%, and incidence of
LASIX touch-ups 33%; expect to perform enhancements
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| ReZoom and ReSTOR combined: ReSTOR not aspheric; study showed spectacle independence increased from 65% to 94%;
only 4% of participants not satisfied; expect to deal with refractive surprises; if >4 D, exchanges or “piggybacks” necessary
(speaker prefers over LASIK or laser epithelial keratomileusis [LASEK]); if refraction between +4 and -4 D, laser or low-
power piggybacks effective; if between +50 and +1, conductive keratoplasty and laser highly effective; if patient myopic
with cylinder, treat cylinder with repeat LRI
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| RISK FACTORS FOR PROGRESSION OF AMD—Andrew A. Moshfeghi, MD, Assistant Professor of Ophthalmology,
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL
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| Etiology: multifactorial; risk factors—advanced age; light ocular pigmentation; positive family history; hypertension; environmental
factors, eg, smoking; dietary factors; signs include drusen, hyperpigmented changes in macula, and areas of chorioretinal
atrophy; late onset; caused by multiple genes; genes identified to date responsible for <2% of association with AMD;
research by Hageman showed that drusen formation product of localized inflammatory responses after initial retinal pigment
epithelim (RPE) injury; complement cascade implicated in drusen formation; drusen contains inflammatory modulators (eg,
complement, membrane attack complex); role of infectious inflammatory mediators—patients with AMD had statistically
significantly higher titers of cytomegalovirus (CMV), IgG, and Chlamydia than controls; membranoproliferative glomerulonephritis
type II (MPGN2)—has similar ocular phenotype as AMD
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| Complement factor H (CFH): inhibits complement cascade in which complement factor C3b labels host and foreign
cells; CFH involved by binding and inactivating complement factor C3b on host cells; allows for destruction of foreign cells,
while preserving host cells; complement pathway—complex cascade that involves classic antigen-antibody complex pathway
and alternative microbial pathway (and similarly, lectin pathway); end of cascade lysis and cytotoxicity to surrounding
tissue or foreign cells; CFH inhibits process, reducing lysis and cytotoxicity; works directly on alternative and classic pathways
and indirectly on lectin pathway; regulates complement activation region; newer technology allows evaluation of many
single nucleotide polymorphisms (SNPs); nonsynonymous SNPs related to disease development; Y402H nonsynonymous
SNP in CFH gene; 7.4 times higher likelihood of developing AMD if individual carries polymorphism; if risk 100%, Y402H
responsible for 50% of that risk; located near 1q32 region; region on 1q that contains 20 short consensus repeats (SCRs)
joined by 2 disulfide bridges; on SCRs, find binding sites for C3b, heparin, sialic acid, and C-reactive protein; affinity of particles
for SCR leads to variable expression in CFH gene product; CFH does not explain everything (“what about the other
50% attributable risk?”); other genes and loci responsible for AMD; one resides on chromosome 10q and results in protein
product called transporter associated with antigen processing (TAP) 1; TAP1 modifies local lymphocyte activation; unlike
CFH gene polymorphisms with odds ratio of 7, TAP1 has slightly lower risk for AMD (odds ratio of 5); responsible for 57%
of attributable risk; normal CFH has 4 haplotypes thought to be protective (H2, H3, H4, and H5); individual with homozygous
presentation of H2/H2 has lowest risk for AMD (odds ratio <1); other protective factors include complement factor B and
complement component 2 (C2) located on chromosome 6p; results in similarly reduced risk for AMD
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| UPDATE ON TORIC IOLS—Bonnie An Henderson, MD, Assistant Clinical Professor of Ophthalmology, Harvard Medical
School, and Ophthalmologist, Ophthalmic Consultants of Boston, MA
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| Astigmatism: 20% of patients have >1.5 D of preexisting astigmatism; methods of correcting—operating on steep axis;
LRIs; astigmatic keratotomy (AK); toric lenses; postoperatively, laser refractive surgery and AK; disadvantages of non-
IOL options—as with any incisional surgery, unpredictable, imprecise, and may regress over time; if done postoperatively,
additional costs, additional surgery, and not ideal for typical cataract patient; disadvantages of toric IOLs—
available only in few corrective powers; IOL may rotate; currently available only in one-piece model (cannot be placed
in sulcus); additional cost; available toric IOLs include Staar Surgical and Alcon AcrySof; toric phakic lens (eg, Artisan,
Visian)
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| Staar toric lens: approved in 1998; made of silicone; powers available, 2.0 and 3.5 D
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| AcrySof toric lens: approved in 2005; has blue-light filtering platform; powers available, 1.25, 2.25, and 3.0 D at IOL
plane; has square truncated edge; study by Lane found lens rotation of 4°, and 97% of patients spectacle-free for distance vision;
another study found even less rotation (0.7°) and no lens rotated >1.8°; study comparing toric IOL to spherical IOL
with LRI found significantly better correction with toric IOL
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| Indications for use: patients with >1.0 to 1.5 D of corneal astigmatism; those not good candidates for LRI or AK because
of previous corneal surgery; patients who had lenticular and corneal astigmatism in opposing meridians; preoperative counseling
important; how to use—be meticulous with preoperative measurements; contact applanation A-scan not accurate
enough for premium IOLs; speaker always performs manual and automated keratometry and corneal topography; software
program available for Staar toric lenses; refer to Web site for Alcon Acrysof (www.acrysoftoriccalculator.com); data to be
entered by physician—spherical lens power being put into eye; know normally induced astigmatism (default 0.50 D;
speaker recommends physician refer to his or her own cases); techniques—make aligned marks on cornea when patient sitting
up to avoid cyclorotation; mark axis of steepening; place lens in capsular bag 1 to 2 clock-hours counterclockwise so
able to rotate into position (speaker puts in even more counterclockwise [ie, 3 clock-hours]; much easier to then rotate clockwise
if necessary); wait for IOL to unfold before removing viscoelastic (to prevent rotation); remove viscoelastic completely;
align marks on IOL along with corneal marks for steep meridian; more viscoelastic required if further rotation
needed; do not overinflate anterior chamber, and ensure that not too soft (increases chance that IOL will rotate); keep at normal
pressure
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Suggested Reading
Ah-Chan JJ et al: Anti-inflammatory fibrosis suppression in threatened trabeculectomy bleb failure. Arch Ophthalmol
124:603, 2006; Bucci FA Jr et al: Prostaglandin E2 inhibition and aqueous concentration of ketorolac 0.4% (acular LS)
and nepafenac 0.1% (nevanac) in patients undergoing phacoemulsification. Am J Ophthalmol 144:146, 2007; Despriet DD
et al: Predictive value of multiple genetic testing for age-related macular degeneration. Arch Ophthalmol 125:1270, 2007;
Fraser-Bell S et al: Cardiovascular risk factors and age-related macular degeneration: the Los Angeles Latino Eye Study.
Am J Ophthalmol 145:308, 2008; Güell JL et al: Artisan toric phakic intraocular lens for the correction of high astigmatism.
Am J Ophthalmol 136:442, 2003; Klein R et al: The epidemiology of retinal reticular drusen. Am J Ophthalmol
145:317, 2008; Neumayer T et al: Effect of topical prednisolone and diclofenac on the short-term change in morphology
of posterior capsular opacification. Am J Ophthalmol 142:550, 2006; Nixon DR et al: Evaluation of lens epithelial cell migration
in vivo at the haptic-optic junction of a one-piece hydrophobic acrylic intraocular lens. Am J Ophthalmol 142:557,
2006; Pulido JS et al: Relationship between age-related macular degeneration-associated variants of complement factor H
and LOC387715 with coronary artery disease. Mayo Clin Proc 82:301, 2007; Sacu S et al: Effect of optic material and haptic
design on anterior capsule opacification and capsulorrhexis contraction. Am J Ophthalmol 141:488, 2006; Shuler RK Jr
et al: Neovascular age-related macular degeneration and its association with LOC387715 and complement factor H polymorphism.
Arch Ophthalmol 125:63, 2007; Shuler RK Jr et al: Phenotype analysis of patients with the risk variant
LOC387715 (A69S) in age-related macular degeneration. Am J Ophthalmol 145:303, 2008; Souza CE et al: Visual performance
of AcrySof ReSTOR apodized diffractive IOL: a prospective comparative trial. Am J Ophthalmol 141:827, 2006; Epub
2006 Mar 20. Tejedor J et al: Choosing the location of corneal incision based on preexisting astigmatism in phacoemulsification.
Am J Ophthalmol 139:767, 2005; Woodcock M et al: Recent advances in customising cataract surgery. BMJ
328:92, 2004.
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