VITREORETINAL ISSUES
| RECOGNITION, TREATMENT, AND PREVENTION OF ENDOPHTHALMITIS —Harry W. Flynn, Jr, MD, Professor
of Ophthalmology, Bascom Palmer Eye Institute (BPEI), University of Miami Miller School of Medicine, Miami,
FL
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| Endophthalmitis after vitrectomy: rare; current practice nonstitch surgery with 23-gauge needle
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| Prevention: reduce rate by swabbing 10% povidone-iodine on conjunctiva, lid margins, and skin; apply additional
5% solution directly on cul de sac; lid speculum with plastic drape covers lashes; meticulous sterile technique; antibiotic
use controversial
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| Incidence of acute onset: after 20-gauge vitrectomy—0.1% from 1980s to early 1990s; decreased to 0.04%
(based on Eifrig data) from 1995 to 2001; American Journal of Ophthalmology summarized BPEI data; 15,000 vitrectomies;
6 cases of endophthalmitis; involved Proteus, Staphylococcus aureus, Streptococcus; poor outcomes;
data from 2006 (combined meetings of American Society of Retina Specialists and European Vitreoretinal Society)
—rate 1 in 100 after 25-gauge transconjunctival vitrectomy surgery; risk factors included leaking sclerotomies
causing early postoperative hypotony; patient-induced wound distortion (eg, rubbing eye); vitreous wicks; inoculum
into vitreous in diabetic or immunocompromised patient; failure to use subconjunctival antibiotics; increasing
use of adjuvants (eg, intravitreal triamcinolone [eg, Kenalog])
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| Speaker’s data from American Society of Retina Specialists (ASRS): 11 patients, median age 68 yr; follow-up,
median of 8 mo; predominantly straight incisions; adjuvants in 3 patients; subconjunctival antibiotic (cefazolin)
in 9 of 11 cases; presenting visual acuity (VA) hand motion; median intraocular pressure (IOP), 13 mm Hg;
treatments included vitreous tap, injection of intravitreal antibiotics, and vitrectomy; surgical indications—
epiretinal membranes; pseudophakic and phakic eyes; VA—outcome good with coagulase-negative Staphylococcus
, poor with Enterococcus; final VA—20/400 in most cases; causes of decreased vision—cystoid macular
edema (CME), worsening of cataract, persistent epiretinal membrane, corneal edema, vitreous hemorrhage, and effects
of endopthalmitis; macular disease most common cause of poor vision; improving outcomes—in patients with
leaking sclerotomies, use one suture; advise not to rub eyes for ≤2 wk; in patients showing vitreous wick, consider
removing wick and placing suture
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| Intravitreal injections: increasingly used; prevent infections by protecting lashes and eyelids with povidone-iodine;
additional 5% solution in cul de sac; sterile speculum directs lashes away from field; avoid contact with lid
margin and lashes; vitreous wicks can occur after injection; suggested guidelines—povidone-iodine for surface,
eyelids, and eyelashes; use lid speculum; avoid needle contamination from margin or lashes; avoid excessive massage
of eyelids pre- or postinjection; avoid injection in patients with active eyelid disease; dilate pupil to view posterior
segment after procedure; avoid prophylactic or postinjection anterior chamber paracentesis; no consensus
on—use of povidone-iodine flush, sterile drape, and sterile gloves; pre- and postinjection topical antibiotics; patient
follow-up; 2 cases of suspected endophthalmitis after treatment with ranibizumab injection (Lucentis); triamcinolone
for intravitreal use (off-label) can cause endophthalmitis
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Endophthalmitis after Cataract Surgery
| Procedure: clear corneal sutureless surgery
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| Risk factors: systemic immunosuppression; lidocaine (eg, Xylocaine jelly) before preoperative povidone-iodine
wash; intraoperative complications (eg, vitreous loss); perioperative issues (eg, iris prolapse); wound construction
(eg, wound leak, inferior wound placement); chronic blepharitis
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| Rates: steadily decreasing since introduction of cataract surgery; 0.1% in 1970; rates increased in early 1990s, possibly
due to clear corneal cataract surgery; currently, rate at BPEI fairly steady at 1 per 2000 procedures after standard
surgery; unclear whether use of fourth-generation fluoroquinolone helping to reduce endophthalmitis
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| SYSTEMIC VS LOCAL TREATMENT IN UVEITIS —Thomas A. Albini, MD, Assistant Professor of Clinical
Ophthalmology; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine
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| Oral corticosteroids: treatment duration often too long; aim for 1 to 2 mo at >10 mg daily; switch to other forms
of immunosuppression; eg, patient on 60 mg daily tapered to 20 mg for 6 mo has 20% chance of developing ischemic
necrosis of bone; azathioprine, methotrexate, cyclosporine, and cyclophosphamide (eg, Cytoxan) most
commonly used; efficacy data depend on type of trial (randomized vs uncontrolled case series); efficacy usually
50% to 80%; drug substitutions improve treatment success; serious side effects include increased risk for hematologic
cancer and sterility
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| Biologic agents: tumor necrosis factor alpha (TNF-á) inhibitors—infliximab (Remicade); etanercept (Enbrel); adalimumab
(Humira); daclizumab (Zenaprax)—anti–interleukin (IL)-2 antibody; used in small prospective multicenter
trial in uveitis patients; some benefit in treating ocular disease, Behçet’s syndrome, juvenile rheumatoid
arthritis (JRA), and human leukocyte antigen (HLA) B27-associated conditions; no comparative data; infrequently
used as first-line approach, unless patient has systemic condition warranting use; daclizumab being studied at National
Eye Institute’s uveitis service; side effects of biologic agents include reactiviation of latent tuberculosis, unmasking
of demyelinating disease, and congestive heart failure; future research may focus on tailoring anti-
inflammatory regimen, based on matching cytokine profile
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| Local therapy: avoids most systemic complications; use of sub-Tenon triamcinolone injection in certain patients; intravitreal
triamcinolone to treat uveitic cystoid macular edema (CME); can cause recurrent infection if patient has toxoplasmosis;
do not use in patients with syphilis; may cause higher IOP; pseudohypopyon problematic; injection effective for
3 mo; bevacizumab (Avastin) for uveitic CME; limited data; monthly injections for recalcitrant CME; intravitreal triamcinolone
for uveitis without CME reviewed in case reports; chronic diseases chosen; Vogt-Koyanagi-Harada (VKH)
syndrome successfully treated with bilateral injections; no systemic treatment; other injections—methotrexate to treat
intraocular lymphoma; short-term benefit in one case study of patients with recalcitrant uveitis; cyclosporine, tacrolimus
(FK506), and other biologic agents nontoxic when injected into vitreous; efficacy data not available
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| Local therapy cautions: draining lymph node “driving force” behind uveitis; are there negative consequences to not
treating lymph node? is disease being prolonged? is systemic disease being missed that might otherwise manifest? fluocinolone
intravitreal implant (Retisert); only device approved by Food and Drug Administration (FDA) for uveitis;
$18,000; effective for 2.5 yr; studies show decreased need for systemic medications; decreased recurrences; serious local
side effects; cataract surgery; 40% require filtering procedure for treatment of glaucoma; constant delivery of medication
works “wonderfully”; avoids side effects of systemic medication
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| New trials: Posurdex (dexamethasone) in phase 2 clinical trial evaluating safety and efficacy in treating diabetic
macular edema (DME); also enrolling patients for trial in posterior uveitis; biodegradable dexamethasone implant
applied in office setting; injected through 22-gauge applicator system; 6-mo half-life vs 3-mo half-life for triamcinolone;
no dispersion; similar half-life whether used in vitrectomized or nonvitrectomized eyes
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| Other steroid implants: Medidur—free-floating implant injected with 25-gauge needle; delivers fluocinolone; in trials
for macular edema; 2-yr duration; I-vation helical coil—some of same technology as used in heparin-release stent;
conjunctival cutdown; screwed into sclera; easy removal and replacement; triamcinolone-coated implant
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| Conclusion: uveitis difficult to treat; outcomes poor; requires aggressive immunosuppression while trying to avoid side
effects; vast areas of comparative data lacking; new therapeutic strategies challenge old paradigms; possible tailor-made
immunosuppression with advent of biologic therapies
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| INTRAVITREAL PHARMACOTHERAPIES FOR DIABETIC RETINOPATHY —Andrew A. Moshfeghi, MD,
Assistant Professor of Clinical Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of
Medicine
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| Introduction: DME most common cause of vision loss in diabetic patients; prevalence of DME after 15 yr, 20% in
type 1 patients, 25% in insulin-dependent type 2 patients, and 35% in all type 2 patients; according to Ferris and
Potts, 53% of patients with DME lost >2 lines of vision at 2 yr; according to Early Treatment Diabetic Retinopathy
Study (ETDRS), 33% lost ≥3 lines of vision at 3 yr (definition of doubling of vision angle or moderate visual loss)
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| Treatment: focal laser photocoagulation gold standard; reduces risk for moderate visual loss by 50% in patients
with clinically significant macular edema; seen as absolute reduction from 24% to 12% at 3-yr end point; 12% of
treated eyes developed moderate visual loss despite treatment; focal laser photocoagulation not perfect; 40% of
treated patients with baseline foveal edema (FE) had FE at 1 yr; 25% of patients with baseline FE still had FE at 3
yr
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Off-label Treatments
| Medications: triamcinolone (Kenalog); pegaptanib (Macugen); bevacizumab (Avastin); ranibizumab (Lucentis);
expensive; insurance reimbursement on a case-by-case basis
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| Retisert: 3-yr data from phase 3 trials—28% of patients with DME obtained 3-line gains vs 15% in usual care group
(focal laser photocoagulation or observational management); significant side effects; 95% of patients develop cataracts,
compared to 19% in usual care group; significant IOP elevations in 35% of those in Retisert group vs 5% in
usual care group; of 35% with IOP elevations in Retisert group, 30% required trabeculectomy and 5% required device
explantation to control IOP; intraocular triamcinolone—currently, no large prospective controlled randomized
clinical trials; data soon available from Diabetic Retinopathy Clinical Research (DRCR) Network; different formulations
prevent good data comparison; drug appears to work at least short-term; side effects include cataracts and glaucoma
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| Macugen: phase 2 data—best corrected VA at 36 wk (6 wk after last injection) showed modest improvement compared
to sham; larger proportion receiving lowest dose of 0.3 mg gained 2 lines, 34% with Macugen vs 10% with
usual care; 18% gained 3 lines with Macugen vs 7% with usual care; optical coherence tomography (OCT) central
retinal thickness—0.3-mg group had greatest reduction of central subfield thickness, compared to other doses and
sham; Macugen reduced neovascularization of disc; on-off effect related to administration and withdrawal of drug
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| Avastin: for vein occlusions and DME; good high-level data lacking; small case series suggest modest benefit; requires
multiple injections; useful as pre- and postsurgical adjunct
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| Lucentis: 2 major phase 3 studies; manufacturer-sponsored multicenter trial; DRCR trial—4 groups being studied; Kenalog
group, Lucentis-only group, focal laser photocoagulation group, focal laser followed by Lucentis group; very expensive;
reimbursement not currently available
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| Newer agents: Medidur—injectable implant of sustained-release fluocinolone; for use in DME; in phase 3 trial (Fluocinolone
Acetonide for Macular Edema; FAME); clinic-based implant using 25-gauge transconjunctival injection
into vitreous cavity for treatment of recurrent or persistent DME after focal laser photocoagulation; Posurdex—
sustained-release dexamethasone device; office-based injectable bioerodable polymer; small and long; data from
phase 2 trial based on persistent macular edema from diabetes and other nondiabetes causes; photocoagulation allowed
with DME patients; 1:1:1 randomization of 350 mg vs 700 mg vs observation; main outcome proportion of patients
with ≥2 lines of visual improvement, compared to baseline; I-vation—helical triamcinolone implant; small
surgically implanted “steroid screw”; helical design maximizes surface area for drug exposure; triamcinolone layered
on top of metallic nonferrous core; surgically implanted in operating room (25-gauge needle perforates sclera; device
screwed into position; conjunctiva closed over screw cap, keeping metallic cap flush with sclera); 2 formulations
(both 925 µg total), slow release (1 µg/day for 2 yr) and fast release (3 µg/day for 9 mo); phase 1 results; indicated if
refractory to laser, or investigator felt laser not helpful; slight elevation in IOP at 6-mo follow-up; cataract progression
noted; at baseline, 20% of patients had 20/40 vision or better; 6 mo later, 43% maintained vision; 30% had vision <20/
100 at baseline; diminished from 50% to 14% at 6 mo
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Suggested Reading
Avery RL et al: Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology
113:1695, 2006; Awwad ST et al: A comparison of higher order aberrations in eyes implanted with
AcrySof IQ SN60WF and AcrySof SN60AT intraocular lenses. Eur J Ophthalmol 17:320, 2007; Bakri SJ, Kitzmann
AS: Retinal pigment epithelial tear after intravitreal ranibizumab. Am J Ophthalmol 143:505, 2007; Doft BH
et al: Diabetes and postoperative endophthalmitis in the endophthalmitis vitrectomy study. Arch Ophthalmol
119:650, 2001; Eifrig CW et al: Endophthalmitis after pars plana vitrectomy: Incidence, causative organisms, and
visual acuity outcomes. Am J Ophthalmol 138:799, 2004; ESCRS Endophthalmitis Study Group: Prophylaxis
of postoperative endophthalmitis following cataract surgery: Results of the ESCRS multicenter study and identification
of risk factors. J Cataract Refract Surg 33:978, 2007; Frenkel RE et al: Intraocular pressure effects of pegaptanib
(macugen) injections in patients with and without glaucoma. Am J Ophthalmol 143:1034, 2007; Fung AE et
al: An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for
neovascular age-related macular degeneration. Am J Ophthalmol 143:566, 2007; Hogan AC et al: Long-term efficacy
and tolerance of tacrolimus for the treatment of uveitis. Ophthalmology 114:1000, 2007; Ke Y et al: Suppression
of Established Experimental Autoimmune Uveitis by Anti-LFA-1{alpha} Ab. Invest Ophthalmol Vis Sci
48:2667, 2007; Kuppermann BD et al: Randomized controlled study of an intravitreous dexamethasone drug delivery
system in patients with persistent macular edema. Arch Ophthalmol 125:309, 2007; Mantovani A et al:
Work-up, diagnosis and management of acute Vogt-Koyanagi-Harada disease: A case of acute myopization with
granulomatous uveitis. Int Ophthalmol 27:105, 2007; Mohammad DA et al: Retisert: is the new advance in treatment
of uveitis a good one? Ann Pharmacother 41:449, 2007; Morlet N: How might we halve the risk of endophthalmitis?
Clin Experiment Ophthalmol 35:303, 2007; Morrison VL et al: Intravitreal triamcinolone acetonide for
the treatment of immune recovery uveitis macular edema. Ophthalmology 114:334, 2007; Olson RJ: Reducing the
risk of postoperative endophthalmitis. Surv Ophthalmol 49:S55-61, 2004; Sharma NS et al: Corneal perforation
and intraocular lens prolapse in Serratia marcescens endophthalmitis. Clin Experiment Ophthalmol 35:381, 2007;
Thoms SS et al: Postoperative endophthalmitis associated with sutured versus unsutured clear corneal cataract incisions.
Br J Ophthalmol 91:728, 2007; Thorne JE et al: Optic neuropathy complicating multifocal choroiditis and
panuveitis. Am J Ophthalmol 143:721, 2007; Wisniewski SR et al: Characteristics after cataract extraction or secondary
lens implantation among patients screened for the Endophthalmitis Vitrectomy Study. Ophthalmology
107:1274, 2000; Writing Committee for the Diabetic Retinopathy Clinical Research Network et al:
Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation
strategies for diabetic macular edema. Arch Ophthalmol 125:469, 2007.
Educational Objectives
| The goal of this program is to improve treatment and overall management of vitreoretinal disorders. After hearing
and assimilating this program, the clinician will be better able to:
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 | 1. Summarize the causes and explain the management of endophthalmitis.
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| 2. Describe the use of systemic and local modalities in the treatment of uveitis.
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| 3. Assess the new implant trials being undertaken to treat uveitis.
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| 4. Discuss the causes and explain standard treatment of diabetic macular edema.
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| 5. Evaluate off-label treatment options for diabetic macular edema.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members 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. Flynn is a consultant
to Alcon, Allergan, Eyetech, Genentech, Eli Lilly, Novartis, and Pfizer. Dr. Moshfeghi receives grant funding from
Genentech and Eyetech, is a consultant to Genentech, Alcon, and Eyetech, and is on the Speakers’ Bureau at Genentech.
Dr. Albini has reported nothing to disclose.
Acknowledgements
Drs. Flynn, Albini, and Moshfeghi addressed the 2007 Vitreoretinal Course Update, held May 4-5, 2007, in Miami,
FL, and sponsored by the Bascom Palmer Eye 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.
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