GLAUCOMA: PROBLEMS AND PLEASURES
From Ophthalmology 2006: New Directions in Ocular Therapies, presented December 1-2, 2005, by the University
of California, San Francisco, Beckman Vision Center, Department of Ophthalmology
| ARE β -BLOCKERS OBSOLETE AS FIRST-LINE THERAPY? —Shan C. Lin, MD, Assistant Professor of Ophthalmology,
University of California, San Francisco, School of Medicine
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| Criteria for choice of first-line glaucoma medication: efficacy in lowering intraocular pressure (IOP); circadian fluctuation
of IOP (linked to progression of glaucoma); safety and side effects; ease of use and compliance; cost; new factors—
central corneal thickness; greater longevity of patients; racial factors; every dose unit counts
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| Efficacy of β-blockers vs prostaglandins (study by Van der Valk): IOP decrease (peak to trough) ≈25% with β-blockers
(≈30% with prostaglandins); timolol vs latanoprost (study by Zhang)—trials involving open-angle glaucoma (OAG)
or ocular hypertension; more favorable response at 6 mo with latanoprost (≈30% IOP reduction; 25% with timolol)
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| Safety: timolol—average heart beats/minute decreased; small risk for hypotension and bradycardia; latanoprost—iris
pigmentation (risk ≈20% over 2 yr); greater risk for hyperemia, compared to timolol; potential side effects of systemic
β-blockers—cardiac and pulmonary side effects; depression; erectile dysfunction; consider medical history; bronchial
reactivity in ocular hypertensives (study)—>50% had significant bronchial reactivity on β-blockers, compared to none
in argon laser therapy (ALT) group; prostaglandin side effects—iris and skin pigmentation; eyelash growth; avoid with
history of cystoid macular edema (CME), uveitis, or herpes; long-term safety of latanoprost (study by Pfeiffer)—
increase in pigmentation (specifically, melanosomes); not cause of neoplasms
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| Circadian fluctuation: study by Orzalesi—overall, latanoprost better in minimizing circadian fluctuation, compared to
timolol or dorzolamide (Trusopt)
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| β-blockers: systemic benefits—increased survival after myocardial infarction (MI); topical β-blockers—no evidence of
systemic protective effect; propranolol as adjunct to systemic therapy—depends on dose of systemic β-blocker; at relatively
low dose, efficacy in lowering IOP about same as placebo; at higher dose, no effect with timolol (IOP from baseline
not much different)
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| Persistence (continuation of use): refill rate 30% with latanoprost at 1 yr (18% with timolol); prostaglandins slightly more
expensive than β-blockers
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| Summary: prostaglandins drug of choice for first-line therapy in majority of cases because of enhanced efficacy, better
side-effect profile, and better compliance over time; however, β-blockers still have role as first-line therapy in eg, patients
who have cosmetic concerns about side effects of prostaglandins (iris and skin color change)
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| RESCUING THE FAILING FILTER —Robert Ritch, MD, Chief, Glaucoma Service, and Surgeon Director, New York
Eye and Ear Infirmary, New York City
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| Introduction: filtration pathway dynamic system; fibroblasts, connective tissue elements, growth factors, cytokines, aqueous,
and vascular supply influence course of bleb; bleb failure can occur from day 1 postoperatively or months to years
later; active and early intervention needed to maximize success of filtration surgery
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| Sites of filtration failure: scarring at conjunctiva-Tenon’s-episcleral interface (most common); Tenon’s cyst; scleral flap;
internal ostium (not common)
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| Bleb features: early—3 dimensions; inflammatory reaction to sutures (nylon draws vessels toward it and creates inflammation);
wound leaks; ropy vessels; microcysts good sign of filtration; late—dimensions; thickness of wall; porcelainization
of bleb wall (sutures not visible); cyst formation; ring of steel
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| Intraoperative factors that assist establishment of bleb: 5-fluorouracil (5-FU) or mitomycin; speaker prefers limbus-
based flaps (fornix-based flaps predisposed to wound leaks, overgrow cornea, and are visible); if conjunctiva thin or
problems in surgery, consider injection day after surgery
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| Surgical technique: use corneal traction suture; 5 to 6 mm-wide incision starting 14 mm from limbus; avoid buttonholes
and tears; preserve conjunctiva; fornix-based flap destroys limbal stem cells (consider surgically incorporating limbal
stem cells into flap); use rectangular flap with 3 sutures (risk for shallow anterior chamber with 2 sutures)
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| Scleral flap suture: with mitomycin, speaker almost never performs tenonectomy (especially in primary procedure); sutures
should be visible through conjunctiva and Tenon’s capsule postoperatively (otherwise, laser suture lysis difficult); if
not visible and much Tenon’s tissue present, perform limited tenonectomy
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| Early postoperative phase: critical for bleb formation; bleb should be ischemic, elevated, and diffuse; boggy flat blebs
pose problems; if bleb flat and injected postoperative day 1, apply light massage to cornea or press posterior to scleral
flap to push down sclera and elevate bleb; if massage too forceful, risk indented cornea; if massage ineffective, speaker
may inject Balanced Salt Solution (BSS; intraocular irrigating solution) with 30-gauge needle under conjunctiva and
Tenon’s capsule to elevate bleb
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| Early postoperative intervention: digital massage or point pressure; laser suture lysis; injection elevation (wait 2 wk if
possible); steroids every hour; consider prednisolone (Pred Forte or Econopred; red blebs at 2 wk associated with generic
formulation); if bleb has problems after mitomycin, give 5-FU injections; check IOP 3 or 4 hr postoperatively (especially
if viscoelastic in anterior chamber [AC]); if viscoelastic in AC after trabeculectomy, IOPs as high as 40 mm Hg at 3 or 4
hr postoperatively; start topical medication 3 hr after surgery; (much inflammation by, eg, 24 hr); massage or point pressure
if IOP elevated; massage if IOP ≥14 mm Hg (unless bleb large and diffuse)
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| Laser suture lysis: timing depends on number and tightness of sutures, appearance of bleb, and IOP; if wall beginning to
porcelainize (becoming thicker and more opaque), intervene earlier (otherwise, suture not visible through bleb); concern
about hypotony in early postoperative period (if possible, wait 2 wk; never perform 2 suture procedures same day); use
0.05 sec (raise power if Tenon’s capsule thick); if conjunctiva thin or lightly pigmented, speaker uses 100-µm spot size;
if blood present, consider krypton laser
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| Ropy vessels: blood vessels that do not resolve with steroids; when bleb covered with ropy vessels, needling ineffective
(bleb sticks back down); to eliminate ropy vessels, close with laser; use 200-µm spot size and 0.3 sec (240 mW); 2 sessions
at 150 spots/session; works well one third of time (“okay” one third; in one third, ropy vessels recur)
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| Needling encapsulated blebs: in routine primary trabeculectomy, start with 30-gauge needle; if not effective, go to 25-
gauge needle (next step needle knife); afterward, give steroids and 5-FU; if reneedling indicated, speaker may inject mitomycin
half hour before procedure; often get bleeding into bleb or hyphema (may require paracentesis); advise patient
that blurry vision will resolve; needle knife procedure (indications)—ring of steel; scarred bleb; third needling on patient
who has had previous surgery (eg, penetrating keratoplasty [PK] and cataract extraction); thick, porcelainized bleb
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| Late bleb failure: polycystic flower-red bleb with ring of steel (cannot needle); bleb functional, but IOP high and patient
on medications due to scarring at base of scleral flap; goal to reconnect AC with inside of bleb; can run 25-gauge needle
across AC into ostium under gonioscopic control
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| Automated trephination: zero success with flat-scarred blebs; good success with mature blebs; use 600-µm trephine tip;
make microvitreoretinal (MVR)-20 blade incision; use acetylcholine (Miochol); fill AC with viscoelastic; run trephine
across AC and into bleb; 2 or 3 passes (2 or 3 openings into bleb); pull back immediately to avoid vortexing conjunctiva
into trephine; increased incidence of late blebitis and endophthalmitis, but blebs highly amenable to trephination
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| PIGMENT DISPERSION SYNDROME AND PIGMENTARY GLAUCOMA —Dr. Ritch
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| Theoretic mechanism of pigment dispersion syndrome (PDS): reverse pupillary block—contact between iris and lens
greater than normal; when aqueous moves from posterior chamber (PC) to AC, it does not equilibrate; although IOP or
volume in AC increased, iris pushed against zonules; iridozonular friction of pupillary movement and dilation and constriction
of iris allows iris to rub against zonules; rubbing and iridozonular friction disrupts iris pigment epithelium,
which disperses pigment throughout AC (more easily seen with infrared pupillography than on transillumination at slit
lamp); pigment deposition on cornea forms Krukenberg spindle; usually inferior and just nasal of center; cell count in patients
with primary open-angle glaucoma (POAG) lower than age-matched normals; Alvarado hypothesized that people
who develop juvenile glaucoma or POAG born with decreased complement of cells in trabecular meshwork
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| Epidemiology of PDS: common; autosomal-dominant disease with incomplete penetrance; 80% myopes (20% ametropes;
of 900 patients with pigment dispersion, 7 or 8 hyperopes); pigmentary glaucoma affects whites almost exclusively; age
of onset—20 to 30 yr of age; PDS affects men and women equally, but men develop pigmentary glaucoma 3 times more
often; genetic component—affects 2.45% of white population; 3 or 4 million people in United States carry gene; screen
family members; according to some papers, glaucoma develops in about one third to one half of patients with PDS; degree
of myopia correlates inversely with age of onset (the higher the myopia, the younger the age of onset of glaucoma)
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| Why some patients with PDS develop glaucoma while others do not: speaker’s hypothesis—1 gene causes pigment
dispersion; not everyone with pigment dispersion develops external blockage (another gene confers susceptibility of
meshwork to elevated IOP); not everyone with elevated IOP develops disc damage (third gene confers susceptibility to
disc damage); other correlates—retinal detachment occurs in 6% to 7% of patients with PDS or pigmentary glaucoma;
prevalence of lattice degeneration in patients with PDS twice that in age- and-refraction-matched general population
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| Exercise-induced pigment liberation: minority of patients; jogging exercises (basketball, dance, tennis); IOP can increase
to 40 or 50 mm Hg with blurred vision and resulting glaucomatous damage
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| Natural history of PDS: begins in third decade of life; strongly associated with myopia; begins to regress in mid-40s (cessation
of pigment release); Campbell hypothesized cause relative pupillary block; speaker’s view—spontaneous regression
more loss of accommodation and onset of presbyopia; pigment reversal sign—pigment in inferior angle goes away
first; soft sign (no blood or genetic test); pathognomonic for PDS (exception pseudophakics and patients on pilocarpine
long term)
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| More about mechanism of pupillary block: lid blinking may transiently deform cornea, increase IOP, and push iris posteriorly
against lens (reverse pupillary block); prevention of blinking leads to loss of iris concavity; increased iridolenticular
contact decreases to point where iris no longer touching lens; speaker’s view—mechanism simple mechanical pump;
aqueous builds up in PC; patient blinks, aqueous moves into AC, and iris returns to original position; study by Chew—
looked at nictitating membrane in chicks during blink with ultrasound biomicroscopy (UBM); membrane indents cornea
and indentation transmitted to iris; pilocarpine—causes convexity (takes iris away from zonules)
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| Miotics: effective treatment for pigment dispersion; problem—induced accommodation, blurred vision, induced myopia;
in past, pilocarpine (Ocuserts) treatment of choice (product no longer available; alternative needed)
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| Effect of accommodation on iris configuration: concave iris configuration induced by accommodation indistinguishable
from that in PDS (accommodation pushes iris against zonules); with onset of presbyopia, iridozonular contact ceases and
pigment dispersion goes away; same concavity in myopes—6 to 8 diopters (D) myopia; increased with accommodation; if
iris rubbing against zonules, why does pigment dispersion occur in some and not others? theory that congenital weakness of
iris pigment epithelium also involved; on electrooculography, decreased retinal pigment epithelium (RPE) function (indirect
evidence of iris pigment epithelial weakness)
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| More about genetic component: in eighth month of gestation, zonules forming and tertiary and secondary vitreous eroding;
hypothesis—ciliary processes move backward and iris stretched forward; adhesions in secondary vitreous put tension on peripheral
retina being formed; tension on ciliary processes may help iris move backward and cause traction on retina that accounts
for lattice degeneration later; other possible mechanisms
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| Medical therapy: latanoprost more effective than timolol at reducing IOP; combination of Ocuserts and latanoprost decreased
IOP to 10 or 12 mm Hg (laser iridotomy not neces-sary); aqueous suppressants worsen course by decreasing PC
volume and decreasing aqueous flow through trabecular meshwork; in paper by Haines, pilocarpine completely inhibited
pigment liberation during exercise
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| Laser iridotomy: significantly inhibits pigment dispersion into AC with dilation or exercise; criteria for surgery—iris concavity
(not every patient with pigment dispersion has iris concavity); patient in pigment-liberation stage (otherwise, iridotomy
not helpful); iridotomy “blasts” pigment throughout AC, putting more pigment into meshwork; speaker uses ALT
(yttrium-aluminum-garnet [YAG] laser associated with greater IOP increase and more pigment in AC); patient should have
elevated IOP with no damage or early damage; best prognosis—patients <30 yr of age who have large concavity and liberate
pigment easily on dilation; IOPs decreased from high 20s; speaker does not treat patients with normal IOPs (not all develop
elevated IOP)
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| Conclusion: early and accurate diagnosis key to effective therapy; screen family members; need directed therapy; do not
apply aqueous suppression; consider interventions to eliminate pigment release and improve outflow
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Educational Objectives
| The goal of this program is to educate the listener about recent developments in glaucoma care. After hearing and assimilating
this program, the clinician will be better able to:
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 | 1. Choose appropriate first-line medication for managing glaucoma.
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| 2. Recognize common complications of filtration surgery.
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| 3. Describe strategies for prevention and treatment of failed filtration surgery.
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| 4. Explain the pathophysiology of pigment dispersion syndrome.
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| 5. Describe therapeutic interventions for managing pigmentary glaucoma.
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Discussed on This Program
Acetylcholine chloride, intraocular [Miochol-E]
Dorzolamide [Trusopt]
Dorzolamide HCl and timolol maleate [Cosopt]
Fluorouracil (5-fluorouracil, 5-FU) [Adrucil, Carac, Efudex, Fluoroplex]
Latanoprost [Xalatan]
Mitomycin (mitomycin-C; MTC) [Mutamycin]
Pilocarpine HCl (several formulations and trade names)
Pilocarpine Ocular Therapeutic System (discontinued)
Prednisolone (several formulations and trade names)
Prednisolone acetate ophthalmic (several formulations and trade names)
Propranolol HCl [Inderal, Inderal LA, InnoPran XL]
Sodium chloride, potassium chloride, magnesium chloride, sodium acetate [BSS, others]
Timolol maleate [Betimol, Blocadren, Istalol, Timoptic, Timoptic-XE]
Suggested Reading
Borras T et al: Gene therapy for glaucoma: treating a multifaceted, chronic disease. Invest Ophthalmol Vis Sci 43:2513,
2002; Gandolfi SA et al: Bronchial reactivity in healthy individuals undergoing long-term topical treatment with beta-
blockers. Arch Ophthalmol 123:35, 2005; Liebmann JM, Ritch R: Laser surgery for angle closure glaucoma. Semin
Ophthalmol 17:84, 2002; Liu JH et al: Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular
pressure. Am J Ophthalmol 138:389, 2004; Moroi SE et al: Long anterior zonules and pigment dispersion. Am J
Ophthalmol 136:1176, 2003; Orzalesi N et al: Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma
or ocular hypertension. Invest Ophthalmol Vis Sci 41:2566, 2000; Pfeiffer N et al: Fine structural evaluation of the
iris after unilateral treatment with latanoprost in patients undergoing bilateral trabeculectomy (the Mainz II study). Arch
Ophthalmol 121:23, 2003; Reistad C et al: The influence of peripheral iridotomy on the intraocular pressure course in patients
with pigmentary glaucoma. J Glaucoma 14:255, 2005; Ritch R et al: A conjunctival retractor for glaucoma filtering
surgery. Ophthalmic Surg Lasers Imaging 35:261, 2004; Ritch R et al: Long-term success of argon laser peripheral iridoplasty
in the management of plateau iris syndrome. Ophthalmology 111:104, 2004; Ritch R: Assessing the treatment of
angle closure. Ophthalmology 110:1867, 2003; Schwartz GF et al: Persistency with latanoprost or timolol im primary
open-angle glaucoma suspects. Am J Ophthalmol 137:S13, 2004; Van der Valk R et al: Intraocular pressure-lowering effects
of all commonly used glaucoma drugs: a meta-analysis of randomized clinical trials. Ophthalmology 112:1177, 2005;
Zafar S et al: Retinal nerve fiber layer loss in pigment dispersion syndrome. Eur J Ophthalmol 14:449, 2004; Zhang WY
et al: Meta-anaylsis of randomized controlled trials comparing latanoprost with timolol in the treatment of patients with
open angle glaucoma or ocular hypertension. Br J Ophthalmol 85:983, 2001.
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, the faculty reported
nothing to disclose.
Drs. Lin and Ritch were recorded at Ophthalmology 2006: New Directions in Ocular Therapies, presented December
1-2, 2005, in San Francisco, by the University of California, San Francisco, Beckman Vision Center, Department of
Ophthalmology. The Audio-Digest Foundation thanks Drs. Lin and Ritch and the sponsors for their cooperation in
the production of this program.
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