GLAUCOMA TOPICS
| EFFECTIVENESS OF ALTERNATIVE MEDICATIONS FOR GLAUCOMA —John Hetherington Jr, MD, Clinical
Professor of Ophthalmology, University of California, San Francisco, School of Medicine
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| Definition: use of nonstandard, unconventional therapy; includes vitamins, herbs, acupuncture, meditation, and
even holy water; use has increased 10% to 15% within past 10 yr; in United States, highest use in women, whites,
and well-educated individuals; 72 million Americans spend an estimated $27 billion on alternative medications
each year, including 50% of people with glaucoma; in China, 70% to 80% of patients use alternative therapies
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| Vitamins: vitamin A—antioxidant; studies show no effect on intraocular pressure (IOP) or visual field; vitamin B1
(thiamine)—no effect on IOP or visual field; low levels associated with alcoholism; vitamin B12 —shown to improve
visual field in one study (but study criticized as inadequate and poorly controlled); vitamin C—high levels
of ascorbic acid concentrate in anterior chamber; massive doses reduce IOP but also cause diarrhea and dehydration,
making such doses inadvisable for this purpose; topical application produces only minor decrease in IOP (not
worthwhile); free radicals may mediate death of retinal ganglion cells; vitamin C may protect trabecular meshwork
and alter outflow (studies under way); vitamin E—another antioxidant; does not change IOP; one uncontrolled
study reported vague “expansion of visual field”; inhibits cell proliferation; sometimes used to reduce scar
formation in patients undergoing filtering surgery
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 | Nurse and Health Profession Study: lengthy follow-up of 474 patients with chronic open-angle glaucoma (OAG); examined
effects of antioxidant supplementation in patients with field defects and vision loss; authors concluded vitamins
had no proven value in treating glaucoma
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| Marijuana: contains 400 chemicals; cannabinoids of most interest, but so far no effect on glaucoma seen with moderately
long-term follow-up, despite 25% decrease in IOP; effect short-lived, so must be taken many times daily;
side effects — loss of concentration and coordination; emphysema; lung cancer; topical application ineffective; certain
derivatives show promise, including dexanabinol (HU2; animal studies suggest neuroprotective as well as
IOP-lowering effect); WIN-55 (binds CB1 and CB2 receptors in ciliary body and trabecular meshwork; in animal
studies, reduces IOP by 2-4 mm Hg)
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| Ginkgo biloba: antioxidant; produces modest improvement in cognitive ability; in poorly controlled study,
seemed to improve visual field in some patients with chronic OAG; increases ocular blood flow; may have neuroprotective
effect
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| Bilberry: Vaccinium Myrtillus; no evidence that it promotes optic nerve health
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| Water: in Collaborative Glaucoma Study, IOP increased after patients drank 1 L water
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| Alcohol: 30 to 60 min after ingesting 4 oz 40% alcohol, IOP 13 to 19 mm Hg; regardless of baseline pressure; effect
short-lived, but might be good emergency remedy if medicolegal questions can be resolved
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| Meditation: over long term, produces insignificant reduction in IOP
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| Acupuncture: not associated with any change in IOP; only one report of minor change in visual field
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| Exercise: “the best deal going”; after brief rise, IOP falls by 14% within 1 hr; over time, moderate exercise associated
with reduction in IOP lasting several months
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| Lutein: in recent analysis at National Institutes of Health, one commercial preparation contained <0.02 mg lutein (according
to label, 20 mg/capsule); lutein might have been oxidized
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| Conclusions: patients may not be getting what they think they are getting; side effects possible; pharmaceutical
companies reluctant to conduct more research (not required by Food and Drug Administration)
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| LASER AND SURGICAL THERAPY: WHAT’S NEW ?—Peter A. Netland, MD, PhD, Siegal Professor of Ophthalmology,
Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis
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| Peripheral iridotomy: most commonly performed procedure for angle-closure glaucoma in United States
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| Laser trabeculoplasty: most common procedure for treating OAG; number peaked in 1992, then started falling
due to reduced reimbursement, introduction of new medications, and changes in health care delivery; recent resurgence
in interest, and concomitant increase in number of procedures, due partly to use of prostaglandins and
partly to use of selective laser trabeculoplasty (SLT)
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| Procedure: requires use of Q-switched, frequency-doubled yttrium aluminum garnet (YAG) laser; pulse rate 3 nanoseconds;
delivers 0.4 to 1.0 mJ; typical treatment 25 laser spots on 90° of trabecular meshwork, or 50 laser spots on
180° of trabecular meshwork; key is selective treatment of pigmented cells in trabecular meshwork; associated with
fewer structural changes than argon laser trabeculoplasty (ALT); efficacy identical to that of laser trabeculoplasty
(LTP) for initial treatment and first retreatment of glaucoma; for most patients, complications similar to those of
LTP; repeatability theoretically possible, but not confirmed; procedure expensive (special machine required), but
many clinicians now substituting SLT for ALT
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| Surgery: modified trabeculectomy still gold standard; safety and efficacy improved by 2 adjunctive techniques (use
of mitomycin C or 5-fluorouracil, and laser suture lysis or releasable sutures); however, results still less predictable
and less immediately gratifying than cataract surgery
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| Ex-PRESS: miniature glaucoma implant under scleral flap; 50-µm or 200-µm opening on internal diameter; placed
under scleral flap in technique identical to trabeculectomy; device tip goes into anterior chamber to permit aqueous
drainage through device, under scleral flap, and through conjunctiva to form bleb; technique associated with
reduced tissue trauma and inflammation (no peripheral iridectomy; less tissue dissection required due to omission
of sclerostomy); results more predictable, with fewer complications than standard trabeculectomy;
disadvantages—cost; issues of implant biocompatibility; in first 100 eyes treated with this procedure, compared
to standard trabeculectomy, implant associated with slightly less postoperative hypotony; long-term success rates
for IOP nearly identical, with less inflammation; result—more predictable procedure; all other steps identical to
those involved in trabeculectomy, including use of mitomycin C and suture lysis
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| Nonpenetrating glaucoma surgery: deep sclerectomy with or without collagen implant, and viscocanalostomy—advantages
include little to no bleb formation and no peripheral iridectomy; initially described 30 yr ago, but interest
now rekindling, due to recent studies showing fewer complications (after learning curve), compared to trabeculectomy;
however, IOP levels achieved with nonpenetrating surgery slightly higher than those associated with
trabeculectomy; nonpenetrating procedures also more difficult technically; niche not yet found
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| New procedures: cyclophotocoagulation (CYC) performed endoscopically; goniocurettage; transciliary filtration;
excimer laser trabeculostomy; Trabectome (NeoMedix, Inc); iTrack Microcatheter (iScience Interventional); EyePass
Glaucoma Implant (GMP Vision Solutions); SOLX Gold Shunt (OccuLogix, Inc); iStent (Glaukos Corp);
MiDi Shunt (InnFocus, Inc); pneumatic trabeculoplasty; companies hope procedures will replace medical therapy
as well as trabeculectomy; in various stages of development and evaluation (none yet ready for market)
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| Secondary surgical procedures: drainage implants (useful in refractory glaucoma); CYC; some procedures under
development for primary use; speaker prefers drainage implants whenever possible; choice between open-
tube implants and flow-resistive valves; decision depends on surgeon’s preference and experience; speaker prefers
Ahmed Glaucoma Valve (New World Medical, Inc) due to low rate of early postoperative hypotony and associated
complications
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| Anti-fibrosis drugs: prospective randomized clinical trial conducted by speaker and colleagues showed little to no
effect on success or mean IOP after placement of drainage implant
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| Implant plate size: double plate associated with lower mean IOP and greater reduction in need for medications than
single plate; however, increasing plate size does not improve results
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| Implant materials: in Ahmed Glaucoma Valve, silicone associated with slightly higher success rate than polypropylene
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| ENDOSCOPIC CYCLOPHOTOCOAGULATION —Brian A. Francis, MD, Associate Professor of Ophthalmology,
Doheny Eye Institute, The Keck School of Medicine of the University of Southern California, Los Angeles
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| Background: cyclodestructive procedures lower IOP by lowering production of aqueous; modes include transscleral
(contact and noncontact using YAG and semiconductor diode lasers), transvitreal (performed during intravitreal
surgery), or endoscopic cyclophotocoagulation (ECP) using diode laser
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| Equipment: 19.5-gauge probe; consists of fiberoptic light source, endoscopic camera, aiming beam, and treatment
laser; attached to console with foot pedal, which is attached to monitor
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| ECP vs YAG: normal ciliary process consists of stroma, blood vessels, and pigmented and nonpigmented ciliary
epithelium; unlike photocoagulation with YAG laser, ECP leaves stroma and vessels intact, and preserves architecture
of ciliary process
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| Phaco-ECP vs phacoemulsification alone: unpublished study by Burke and colleagues; mean follow-up 3 yr; reduction
in IOP greater with phaco-ECP than with phacoemulsification alone; medications also reduced accordingly;
IOP reductions with phacoemulsification alone sustained ≤1 yr (final IOP higher than baseline); considerable
savings in medication costs associated with ECP
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| ECP vs Ahmed Glaucoma Valve: alternating allocation design; 68 patients with uncontrolled IOP; similarly effective
for lowering IOP and reducing need for medications
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| ECP vs trabeculectomy: randomized prospective trial of 58 patients with IOP >30 mm Hg or progressive cupping
or visual field loss; IOP decreased by 8.5 mm Hg in both groups (≈30% reduction); need for medication lower
among patients undergoing trabeculectomy, but overall success and failure rates similar in both groups
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| ECP for refractory glaucoma: retrospective case series of 68 patients for whom medical therapy and various surgical
treatments failed; ECP reduced average IOP by 34%; effect persisted ≥1 yr; overall success rate at 1 yr, 94%,
and at 2 yr, 82%; concomitant reduction in medications; complications included fibrin formation, hyphema, cystoid
macular edema, and choroidal effusion (rare)
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| ECP for patients who failed tube-shunt surgery: study conducted by speaker and colleagues; on average, IOP reduced
from beginning measure of 24 mm Hg to 16 mm Hg at 1 yr (overall average reduction 7.5 mm Hg from
baseline [30% reduction]); medications per patient reduced from preoperative average of 3.2 medications to 1.5
medications at 1 yr; overall success rate ≈85%; conclusion—good intermediate-term success in this subset of patients;
procedure highly versatile (effective in wide variety of patients); overall, greater reductions in postsurgical
hypotony, pain, and inflammation than with transscleral CYC; also less risky than trabeculectomy or tube shunts;
useful for those who are poor candidates for (or have already failed) filtering surgery, and for those who have
sustained ocular burns
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| Risks: cataract formation; cystoid macular edema; pressure spikes; inflammation; possible iris or lens trauma; failure
usually due to undertreatment (treatment should cover as close to 360° as possible)
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| GLAUCOMA: WHEN TO REFER —Robert J. Noecker, MD, Vice Chair of Ophthalmology, Director of Glaucoma
Service, and Associate Professor of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA
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| Disease-specific: more aggressive the case, greater the need for referral; eg, neovascular or uveitic glaucoma, steroid
response, pediatric glaucoma
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| Practice-specific: depends on local availability of specialists; availability of imaging devices, pachymeters, and
other types of devices can vary from practice to practice (may “tip the balance” for or against referral); presence of
adequate resources and support staff also factor; handicap access is consideration
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| Practitioner-specific: little experience, especially with difficult cases; relationship (“dialogue”) with patient (or
lack thereof) possible reason to refer; other considerations include inability to move forward with treatment algorithm
without more specialized care
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| Patient-specific: desire for second opinion; concern over medicolegal consequences; failure of initial intervention;
rapid progression of disease
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| Environment-specific: availability of resources and expert help (mostly consideration in rural areas); community standard
of care (local presence of specialists and tertiary care centers vs mostly primary care providers); medicolegal issues
(clustering of lawsuits in particular areas); local demographics (may be unrealistic to ask patient on low or fixed income
to drive long distances and take time from work to see specialist)
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| Indications for referral: practitioner doubts about diagnosis and/or treatment; patient doubts about prognosis or
adequacy of treatment; clinician’s reluctance or inability to treat more aggressively (eg, treating with medication vs
incisional surgery)
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Suggested Reading
Al-Aswad LA et al: Clinical experience with the double-plate Ahmed glaucoma valve. Am J Ophthalmol 141:390,
2006; Bloom PA, Dharmaraj S: Endoscopic and transscleral cyclophotocoagulation. Br J Ophthalmol 90:666,
2006; Damji KF et al: Selective laser trabeculoplasty verus argon laser trabeculoplasty: results from a 1-year randomised
clinical trial. Br J Ophthalmol 90:1490, 2006; Gunasekera V et al: Systematic internet-based review of
complementary and alternative medicine for glaucoma. Ophthalmology Sept 25, 2007 [Epub ahead of print]; Holz HA,
Lim MC: Glaucoma lasers: a review of the newer techniques. Curr Opin Ophthalmol 16:89, 2005; Jones LD et al:
General practitioner with special interest improves the efficiency of glaucoma referrals. Eye 20:942, 2005; Lin SC et
al: Vascular effects on ciliary tissue from endoscopic versus trans-scleral cyclophotocoagulation. Br J Ophthalmol
90:496, 2006; Maris PJ Jr et al: Comparison of trabeculectomy with Ex-PRESS miniature glaucoma device implanted
under scleral flap. J Glaucoma 16:14, 2007; McIlraith I et al: Selective laser trabeculoplasty as initial and adjunctive
treatment for open-angle glaucoma. J Glaucoma 15:124, 2006; Papadaki TG et al: Long-term results of
Ahmed glaucoma valve implantation for uveitic glaucoma. Am J Ophthalmol 144:62, 2007; Ritch R: Complementary
therapy for the treatment of glaucoma: a perspective. Ophthalmol Clin North Am 18:597, 2007; Song J et al: High failure
rate associated with 180 degrees selective laser trabeculoplasty. J Glaucoma 14:400, 2005; Werner M et al: Selective
laser trabeculoplasty in phakic and pseudophakic eyes. Ophthalmic Surg Lasers Imaging 38:182, 2007.
Educational Objectives
| The goal of this program is improve management of glaucoma. After hearing and assimilating this program, the clinician
will be better able to:
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| 1. Name the single best form of alternative treatment for glaucoma.
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| 2. Explain why laser trabeculoplasty is enjoying a resurgence in popularity after several years of decline.
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| 3. Describe the adjunctive techniques that have helped make modified trabeculectomy the gold standard for glaucoma
surgery.
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| 4. Compare the clinical results achieved with endoscopic cyclophotocoagulation to results achieved with therapies
such as phacoemulsification and trabeculectomy.
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| 5. Determine circumstances in which referral to a glaucoma specialist might be appropriate.
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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. The following
has been disclosed: Dr. Netland has received research funding from Alcon, Allergan, and Merck; Dr. Noecker has received
research funding from Allergan, Zeiss, and Lumenis, is a consultant for Allergan, and is on the Speakers’ Bureaus
of Allergan, Alcon, Lumenis, and Endo-Optics.
Acknowledgements
Dr. Hetherington spoke at Glaucoma Update 2007, held February 10, 2007, in San Francisco, CA, and sponsored by
the Glaucoma Research and Education Group; Dr. Netland was recorded at What’s New in Anterior Segment Disorders,
held October 21, 2006, in Cambridge, MA, and sponsored by the Massachusetts Eye and Ear Research and Surgery
Institute; Dr. Francis appeared at the 2007 Ophthalmology Symposium, held June 2, 2007, in Anaheim, CA, and sponsored
by Kaiser Permanente; and Dr. Noecker was recorded at the 29th Annual Midwest Glaucoma Symposium, held
September 15-16, 2006, in Pittsburgh, PA, and sponsored by the University of Pittsburgh Medical Center. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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