GLAUCOMA CARE
From the Midwest Glaucoma Symposium, presented September 15-16, 2006, jointly sponsored by the University of
Pittsburgh School of Medicine, the Center for Continuing Education in the Health Sciences, the UPMC Eye Center, and the
Midwest Glaucoma Symposium
| WHY I USE PROSTAGLANDINS AS FIRST-LINE TREATMENT —John S. Cohen, MD, Volunteer Clinical Professor,
University of Cincinnati College of Medicine, and Director, Glaucoma Service, Cincinnati Eye Institute, Cincinnati, OH
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| Challenges of glaucoma therapy: chronic disease; patients asymptomatic; lifelong therapy needed; multiple medications
possibly necessary; medications expensive; administration of medications potentially difficult; success of glaucoma
care—study looking at percentage of patients with occurrence of blindness showed that after 20 yr, 27% of patients in
group comprising all types of glaucoma (n=295) had blindness in at least one eye; of patients with classic glaucoma, incidence
of blindness 54% in at least one eye
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| Goals of glaucoma therapy: establish a “regimen of maximal effectiveness with the least medication to achieve the desired
therapeutic response” (American Academy of Ophthalmology [AAO] Preferred Practice Pattern for open-angle glaucoma
[OAG]); desired therapeutic response—prevent damage from occurring or worsening by lowering intraocular pressure
(IOP), reducing diurnal fluctuation, and promoting compliance with therapy; lower IOP—population studies indicate incidence,
severity, and progression of glaucoma correlate with elevated IOP; aggressive IOP reduction can minimize progression
of visual field defects; target pressure (AAO Preferred Practice Pattern) described as upper limit of IOP to retard progression
of glaucoma, at least 20% reduction from pretreatment IOP, and >20% reduction, depending on severity and speed of progression;
reduced diurnal fluctuation—study of patients performing home tonometry showed incidence of progression 57% in
patients in lower quartile of home diurnal IOP fluctuation and 88% in patients in upper quartile; data comparing highest quartile
vs lowest quartile of office IOP measurement for visual field preservation show similar curves; sense of diurnal fluctuation
important (not just office measurement); compliance—adequate treatment requires good compliance; physicians poor at
judging patient compliance; compliance poor in at least one third of patients; compliance measured as adherence to regimen
of care (prevalence of use) and persistence with care over time (duration of continuous care); study showed ≈50% of patients
discontinued therapy within 6 mo (persistence) and only 37% of patients obtained refills within 2 to 3 mo of due dates over 3-
yr period (adherence)
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| Successful glaucoma therapy: factors affecting success—IOP reduction (amount of reduction; duration of effect of agent;
reduction of diurnal fluctuation; ease of use of medication (frequency of dosing; ease of administration); side effects (ocular;
systemic); cost
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| Prostaglandins: lowest frequency of administration; greatest reduction in IOP; fewest systemic side effects; moderate number
of ocular side effects; greatest cost; prostaglandins on market—latanoprost (Xalatan); bimatoprost (Lumigan; also may act
on prostamide receptor); travoprost (Travatan); relatively new class of glaucoma medication; mechanism of action—
increase aqueous outflow (uveoscleral); increase trabecular outflow (some agents); IOP reduction—25% to 35%; duration
of effect—24 hr; peak effect—10 to 14 hr after administration; dosing—once daily; most effective single agent for lowering
IOP
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| Mechanism of action: potentially important factor in determining which medication to use; increasing outflow—α-agonists
and prostaglandins; conventional or unconventional; decreasing inflow— β-blockers; carbonic anhydrase inhibitors (CAIs),
and α-agonists; theoretical basis favoring increased outflow—maintains nutrition of trabecular meshwork; increasing coefficient
of outflow beneficial in decreasing diurnal fluctuation of IOP
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| Side effects of prostaglandins: darkening of iris and skin; conjunctival hyperemia; hypertrichosis, trichiasis, and distichiasis;
possible risk for uveitis, cystoid macular edema (CME), and herpes simplex keratitis
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| WHEN GLAUCOMA IS BAD —Frederick M. Kapetansky, MD, Clinical Professor, Department of Ophthalmology, Ohio
State University College of Medicine, Columbus
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| Medical approach: compliance—study showed many patients do not use medication as much as they claim; study on
compliance showed 59% of patients had not used their eye drops precisely as prescribed due to, eg, forgetfulness, being
away from home; study of refill compliance (checking pharmacy records) showed patients not refilling prescriptions as
prescribed; study of persistency rates of patients on glaucoma monotherapy (latanoprost, β-blockers, CAIs, or brimonidine)
showed latanoprost group stuck with medication ≈60% of time (better than other medications); study of persistence
and adherence showed persistence and adherence better with prostaglandins than with other drug classes, and adherence
better with patients who actually had glaucoma vs glaucoma suspects; toxicity—study showed significant ocular surface
alteration with timolol (decrease in normal Schirmer’s and break-up time tests; decrease in goblet cell density, mucus
granules, and reticular sheets; increase in pathologic crystallization patterns); study looking at inflammatory changes in
conjunctiva and trabecular meshwork showed infiltration by inflammatory cells and/or fibroblastic markers in these areas
with topical antiglaucoma drugs; study of latanoprost vs timolol in rabbits showed increased subepithelial collagen density
in timolol-treated eyes but not in latanoprost-treated eyes; impression cytology of conjunctival epithelium after treatment
with latanoprost showed density of nongoblet epithelial cells did not change during treatment, but their size did
(goblet cells decreased after long period of treatment); study showed increase in goblet cells with all prostaglandin analogues
and more inflammatory infiltrates and subepithelial collagen with timolol; cost—direct annual cost $623 (glaucoma
suspect) and $2511 (end-stage glaucoma)
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| Medicine vs surgery: study of patients treated with laser, medicine, or surgery showed trabeculectomy provided lowest
mean IOP and preservation of visual fields; another study of 24-hr IOP control after surgery vs medical treatment showed
surgery produced superior results in mean IOP, lower average maximum IOP, and lower 24-hr range of IOP; study of
newly diagnosed patients with OAG showed more advanced visual field loss; surgical group had significantly lower
mean and maximum IOP than medically treated group
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| Speaker’s surgical approach: delivery of mitomycin (MMC)—Weck Cel sponges (3; in wedges) with MMC across top of
eye to make broad filtering area; trabeculectomy-treated eyes respond to digital ocular pressure (for 1, 5, or 10 sec); prevention
of ocular hypotony—delay suture lysis; if IOP decreases ≥20% after digital ocular compression, should postpone laser
suture lysis; early laser suture lysis defined as all sutures cut within 2 mo after operation; late laser suture lysis defined as sutures
cut after 2 mo postoperatively; IOP 10±2 mm Hg (total success), 15±2 mm Hg or 6±2 mm Hg (partial success), >18
mm Hg (failure); <5 mm Hg (hypotony); speaker’s data show no patients with hypotony in late suture lysis group (2 in early
suture lysis)
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| TREATING CHILDREN WITH GLAUCOMA —Peter A. Netland, MD, PhD, Siegal Professor of Ophthalmology, Hamilton
Eye Institute, University of Tennessee Health Science Center, Memphis
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| Natural history: blindness; rare to find patient with no type of treatment; medical therapy often fails; primary surgery with
goniotomy or trabeculotomy controls IOP in majority of patients (failure rate 20%)
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| Medical therapy: potentially used before surgery to temporarily reduce IOP and improve corneal clarity; potentially used
as adjunctive therapy after surgery; classes of medical therapy— β-blockers (0.25% concentration) still useful; CAIs (acetazolamide
elixir; topical); prostaglandin analogues helpful, but high nonresponder rate in children; avoid miotics and
adrenergic agonists (side effects)
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| Surgery: factors influencing clinical decisions about type of surgery—anatomy of angle (primary importance; most have
open angle); age (better prognosis with goniotomy or trabeculotomy in children 1-3 yr of age); corneal clarity (trabeculotomy
useful with poor corneal clarity); corneal diameter (higher risk for complications with enlarged cornea); systemic
syndromes (bilateral Sturge-Weber); severity of glaucoma; previous failed surgery; ethnicity; types of surgery—primary
treatment goniotomy or trabeculotomy; other procedures considered if poor prognosis for success with goniotomy or trabeculotomy;
goniotomy—complications rare; hyphema not considered complication, but expected result; ≥120° incision
in tissue that overlies Schlemm’s canal; trabeculotomy—useful in corneal edema; trabeculotome inserted into Schlemm’s
canal and rotated into anterior chamber to open flow of aqueous to Schlemm’s canal; data show 30-yr success rate >80%;
technique familiar to most clinicians; goniotomy advantage—faster (few minutes); less dissection; both procedures have
high success rate in long term; suture trabeculotomy—variant; provides long-term success in IOP control in most patients;
since suture does not always pass 360°, cutdowns potentially required to retrieve suture and to complete trabeculotomy;
combination trabeculotomy and trabeculectomy as primary surgery—some patients not responsive to goniotomy or
trabeculotomy alone as primary surgery (Arab and Indian populations); cutdown done in standard way to perform trabeculotomy;
trabeculotome used to enter anterior chamber in both directions; sclerostomy (sterile punch or excise block of
tissue); iridectomy; flap in conjunctiva closed
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| Aphakia and pseudophakia: glaucoma associated with aphakia and pseudophakia; occurs more in older children than with
primary congenital glaucoma; children develop open-angle glaucoma; patients usually asymptomatic (different from primary
congenital glaucoma); usually no corneal enlargement; delay in diagnosis typical; ≈2 yr after removal of cataract, patients
may develop glaucoma; over long term, majority of patients develop elevated IOP (lifelong monitoring necessary);
medical therapy, without surgical treatment can control IOP in these patients; risk factors for earlier elevated IOP—
patients treated at earlier age with cataract surgery; preexisting ocular and systemic abnormalities; type of cataract; microcornea;
postoperative inflammation and time after surgery; management—rely more on trabeculectomy with MMC (success
rate 50%-85%); drainage implants (success rate 33%-60%); cyclodestructive procedures (usually reserved for
refractory cases)
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| When primary treatment fails: 20% of total group; options—repeat goniotomy or trabeculotomy; trabeculectomy with
antifibrosis drugs; drainage implants; cyclodestructive procedures; trabeculectomy with MMC—success rate 70% to
80%; complications include hypotony maculopathy, chronic bleb leaks, and severe vision-threatening infections due to
phlebitis and endophthalmitis; drainage implants—success rate 56% to 95%; complication rates and types vary with type
of implant used; 2-stage implants considered to minimize complications due to hypotony in early postoperative period
(especially with severe buphthalmos or corneal enlargement); few studies comparing trabeculectomy with drainage implants;
laser cyclophotocoagulation—average success rate 50%; most clinicians use after primary and secondary treatments
as adjunctive treatment (sparingly for IOP control)
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| Long-term care: additional patient care most important for achieving long-term success; problem with untreated refractive
errors and amblyopia (vision-threatening); multidisciplinary team effort (physicians, teachers, mobility instructors, low
vision specialists, and parents)
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| ANTIMETABOLITES IN GLAUCOMA SURGERY —Garry P. Condon, MD, Associate Professor of Ophthalmology,
Drexel University College of Medicine, Clinical Assistant Professor of Ophthalmology, University of Pittsburgh, and Director,
Glaucoma Division, Department of Ophthalmology, Allegheny General Hospital, Pittsburgh, PA
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| General: trabeculectomy with antiproliferative agent considered undisputed champion of IOP lowering; lesson—not everyone
needs antimetabolite
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| Fluorouracil: landmark case of 5-FU filtering surgery (1980s) showed significant improvement in 5-yr success; risk for
early and late bleb leak identified (late bleb infection noted); biggest difference in failure rate between 5-FU and placebo
noted at 6 mo; 3-yr failure rate curves similar; other studies with shorter follow-up may not show same success if followed
longer; initial drawbacks—discomfort; corneal toxicity; inconvenience; early leaks; intraoperative 5-FU (1990s)—
studies demonstrate effectiveness; despite early fibroblast inhibition, success wanes similar to nonס-FU rate at ≈3 yr (uninhibited
late fibrosis); higher risk for blebitis remains; current target IOP in midteens places limitations on 5-FU process;
lesson—not everyone does well with IOP of 12 mm Hg; glaucoma thought of as pressure too high for health of optic
nerve; hypotony thought of as pressure too low for health of optic nerve
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| Mitomycin: issue with glaucoma surgery—continued wound remodeling over time (uncontrollable variable); MMC—
strong antibiotic; powerful antiproliferative effect enhanced in hypoxic tissue; potentially toxic directly to ciliary body; study
(1995) looking at effect of MMC on fibroblasts (modeling trabeculectomy) showed widening of wound and paucity of cellularity
with MMC (wound never closed) vs wound healing and closure in control by day 3; apoptotic death of fibroblasts seen
by day 3 with MMC; fibroblast growth factor had no effect on course; co-culture of exposed cells inhibited unexposed cells;
same procedure with 5-FU showed no impact on wound closure; lesson—MMC can cause hypotony (new cases several
years after surgery); methods available to treat events caused by MMC (conjunctivoplasty; scleral reinforcement; conjunctival-free
grafts)
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| Trabeculectomy: remains gold standard; tube shunt or drainage device current competition; speaker recommendations—
topical and subconjunctival anesthesia better and safer (subconjunctival anesthesia can dilute effect of MMC); fornix-
based conjunctival flaps preferred (vs limbus-based); make sense with antimetabolites; posterior exposure; excellent conjunctival
closure; posterior sponge application for more diffuse bleb
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Educational Objectives
| The goal of this program is to provide the listener with information on prostaglandins in the treatment of glaucoma, medical
vs surgical treatment of glaucoma, treatment of children with glaucoma, and antimetabolites in glaucoma surgery. After
hearing and assimilating this program, the clinician will be better able to:
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 | 1. Discuss the challenges and goals in treating glaucoma.
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| 2. Describe why prostaglandins are used as first-line medical treatment for glaucoma.
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| 3. Explain the issues with medical vs surgical management of glaucoma.
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| 4. Discuss primary treatment, alternative treatment, and treatment options for children with refractory glaucoma.
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| 5. Describe the role of antimetabolites and trabeculectomy in the treatment of glaucoma.
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Discussed on This Program
Acetazolamide [Dazamide, Diamox, Diamox Sequels]
Benzalkonium chloride (BAC) [several trade names]
Bevacizumab [Avastin]
Bimatoprost [Lumigan]
Brimonidine tartrate [Alphagan, Alphagan P]
Cyclosporine, ophthalmic [Restasis]
Fluorouracil (5-fluorouracil, 5-FU) [Adrucil, Carac, Efudex, Fluoroplex]
Latanoprost [Xalatan]
Mitomycin (mitomycin-C; MTC) [Mutamycin]
Pilocarpine HCl [several trade names]
Timolol maleate [several trade names]
Travoprost [Travatan]
Suggested Reading
Al-Hazmi A, et al: Correlation between surgical success rate and severity of congential glaucoma. Br J Ophthalmol
89:449, 2005; Anand N, et al: Mitomycin C augmented glaucoma surgery: evolution of filtering bleb avascularity, transconjunctival
oozing, and leaks. Br J Ophthalmol 90:175, 2006; Covert D, Robin AL: Adjunctive glaucoma therapy use associated
with travoprost, bimatoprost, and latanoprost. Curr Med Res Opin 22:971, 2006; Fontana H, et al: Trabeculectomy
with mitomycin C: outcomes and risk factors for failure in phakic open-angle glaucoma. Ophthalmology 113:930, 2006;
Friedman DS, et al: Variations in treatment among adult-onset open-angle glaucoma patients. Ophthalmology 112:1494,
2005; Fukuchi T, et al: The outcome of mitomycin C trabeculectomy and laser suture lysis depends on postoperative management.
Jpn J Ophthamal 50:455, 2006; Ishida K, et al: Glaucoma drainage implants in pediatric patients. Ophthalmol
Clin North Am 18:431, 2005; Kymes S: Cost-effectiveness of monotherapy treatment of glaucoma and ocular hypertension
with the lipid class medications. Am J Ophthalmol 142:354, 2006; Lawrence MG, et al: Glaucoma following cataract surgery
in children: surgically modifiable risk factors. Trans Am Ophthalmol Soc 103:46, 2005; Ozkiris A, Tamcelik N:
Long-term results of trabeculectomy with different concentrations of mitomycin C I refractory developmental glaucoma. J
Pediatr Ophthalmol Strabismus 42:97, 2005; Polikoff LA, et al: Is intraocular pressure in the early postoperative period
predictive of antimetabolite-augmented filtration surgery success? J Glaucoma 14:497, 2005; Resch H, Garhofer G: Topical
Drug Therapy in Glaucoma. Wien Med Wochenschr 156:501, 2006; Rossetti L, et al: An evaluation of the rate of nonresponders
to latanoprost therapy. J Glaucoma 15:238, 2006; Sit AJ, et al: Sustained effect of travoprost on diurnal and
nocturnal intraocular pressure. Am J Ophthalmol 141:1131, 2006; Soto J: Cost considerations in the medical management
of glaucoma in the US: estimated yearly costs and cost effectiveness of bimatoprost compared with other medications.
Pharmacoeconomics 24:519, 2006; Strom CM, et al: Prenatal diagnosis for primary congenital glaucoma (bupthalmous).
Prenat Diagn 26:877, 2006; Walton DS, Katsavounidou G: Newborn primary congenital glaucoma: 2005 update. J Pediatr
Ophthalmol Strabismus 42:333, 2005; Wilkins M, et al: Intra-operative mitomycin C for glaucoma surgery. Cochrane
Database Syst Rev CD002897, 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. Cohen reports
being a consultant, researcher, and on the Speakers’ Bureau for Allergan Pharmaceuticals, and researcher and on the
Speakers’ Bureau for Alcon Pharmaceuticals. Dr. Condon reports being on the Speakers’ Bureau for Alcon Pharmaceuticals,
Merck, and Pfizer.
Drs. Cohen, Kapetansky, Netland, and Condon were recorded at the 29th Annual Midwest Glaucoma Symposium, presented
September 15-16, 2006, in Pittsburgh, PA, and sponsored by the University of Pittsburgh School of Medicine, the Center
for Continuing Education in the Health Sciences, the UPMC Eye Center, and the Midwest Glaucoma Symposium. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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