GLAUCOMA: SELECTED TOPICS
| GLAUCOMA AND NEOVASCULARIZATION OF THE ANTERIOR SEGMENT —James C. Tsai, MD, Associate
Professor of Ophthalmology and Director, Glaucoma Division, Edward S. Harkness Eye Institute, Columbia University
Medical Center, New York, NY
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| Clinical hallmarks: neovascularization of iris (NVI); neovascularization of angle may appear before NVI; end-
stage disease—progressive angle closure leading to intractable glaucoma and irreversible loss of vision; hallmark
presentation—prominent rubeotic vessels; edematous cornea; cataract often present
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| Predisposing conditions: retinal ischemic diseases, eg, diabetes, central retinal vein occlusion, ocular ischemic
syndrome, sickle cell retinopathy; inflammatory disease (3%-5% of cases), eg, Vogt-Koyanagi-Harada syndrome
(VKH); radiation; ocular tumors; surgically induced neovascular glaucoma reported
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| Molecular mechanisms: hypothesized that cascade occurs involving proliferation and migration of endothelial
cells, characterized by formation of new leaky, fragile vessels; research focused on homeostatic equilibrium between
vascular endothelial growth factor (VEGF; proangiogenic factor) and antiangiogenic factors (eg, pigment
epithelial-derived factor [PEDF])
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| Stages of glaucoma: initial preglaucoma—rubeosis iridis first seen; intermediate open-angle glaucoma—growth of
fibrovascular tissue; aqueous becomes congested, and hyphema can occur; gonioscopy essential for any patient
suspected of developing neovascular glaucoma; rubeotic vessels often seen around pupillary margin; progressive
angle-closure glaucoma—360° peripheral anterior synechiae (PAS); increased intraocular pressure (IOP) often recalcitrant
to medical, laser, or surgical therapy
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| Clinical diagnosis: in predisposed patient, need high index of suspicion; comprehensive ocular evaluation with
nondilated slit-lamp examination and gonioscopy; detailed pupil examination to check for relative afferent pupillary
defect
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| Differential diagnosis: open-angle stage—inflammatory glaucoma; intermittent angle closure; Fuchs’ heterochromatic
iridocyclitis; closed-angle stage—iridocorneal endothelial (ICE) syndrome; chronic inflammation; old ocular
trauma
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| Clinical management: early detection of anterior segment neovascularization important; if associated with retinal
ischemia, adequate panretinal photocoagulation (PRP) indicated; initial control of IOP and inflammation crucial;
surgery indicated when medical therapy fails; central retinal vein occlusion study—suggested PRP should be performed
if 2 clock hours of NVI or when NVA present; panretinal cryotherapy or diathermy indicated if unable to
perform PRP; in cases of vitreous hemorrhage, consider pars plana vitrectomy with endolaser
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| Treatment of elevated IOP: medical management; topical steroids and cycloplegics; literature suggests goniophotocoagulation
has poor long-term efficacy and may accelerate angle closure
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| Glaucoma surgery: poor long-term outcomes, emphasizing importance of early detection of neovascularization
and institution of retinal ablation
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| Treatment algorithm: patient with no useful vision—if no pain, monitor patient; if pain present, consider medical
therapy; if medical therapy unsuccessful, consider cyclodestruction, retrobulbar alcohol, and enucleation; if IOP
normal, steroids and cycloplegia may be sufficient; patient with useful vision—if associated with inflammation,
anti-inflammatory therapy indicated; if high IOP associated with retinal ischemia, PRP indicated (diode retinopexy,
retinal cryoablation, and vitrectomy with endolaser may be necessary to ensure adequate retinal ablation); if patient
has neovascularization of anterior segment that is not florid, surgical interventions include trabeculectomy with antimetabolites;
if NVI florid, aqueous shunt indicated (diode laser cyclophotocoagulation may be useful in reducing
IOP to allow ablation to take hold)
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| Future therapeutic options: VEGF inhibitors; α-interferon; platelet-aggregation inhibitor (troxerutin); speaker
focusing on balance between VEGF and PEDF; 100% O2 under hyperbaric conditions
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| FRUITS AND VEGETABLES: SHOULD GLAUCOMA PATIENTS BE EATING MORE OF THEM? —Anne L.
Coleman, MD, Professor of Ophthalmology and Director, Center for Eye Epidemiology and Mobile Eye Clinic, Jules
Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles
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| Oxidative stress and glaucoma: in vivo and in vitro studies have shown oxidative stress damages retinal ganglion
cells and trabecular meshwork cells
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| Pasquale et al (2003): epidemiologic study examining association between antioxidants and glaucoma in participants
of Nurses’ Health Study and Health Professionals Follow-up Study, in which food frequency questionnaires
performed every 2 yr; 474 cases of glaucoma identified (112 334 controls); researchers looked specifically at relationship
between vitamins A, C, and E and diagnosis of primary open-angle glaucoma (POAG); results—authors
concluded no strong association between antioxidant consumption and POAG; however, risk for POAG at 4 yr reduced
32% (statistically significant) for patients with highest lutein and zeaxanthin intake, compared to patients
with lowest intake; risk for POAG reduced 33% (statistically significant) for patients with highest vitamin E intake
from food items, compared to patients with lowest intake; study limitations—not all controls examined (50% of patients
with glaucoma unaware they have disease [up to 75% in Latino population]); patients with glaucoma at study
entry not eliminated
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| Effects of fruit and vegetable consumption on glaucoma risk: study—eye examinations performed on 4820
white women (mean age 80 yr) and 662 black women (mean age 75 yr) originally enrolled in Study of Osteoporotic
Fractures; random sample of 1274 patients graded by masked graders and evaluated by glaucoma specialists; food
consumption assessed using Block Food Frequency Questionnaire; results analyzed using logistical regression after
adjusting for potential confounding variables; results—106 patients (mean age 75 yr) diagnosed with glaucoma; 12
of 151 black women and 94 of 1123 white women had glaucoma; consumption of 2 fresh oranges per week associated
with small decrease in risk for POAG (not statistically significant); patients consuming 1 serving of orange
juice per day had statistically significant increase in risk for POAG (potentially because patients take medications
with orange juice); consumption of >2 servings of carrots per week associated with statistically significant reduction
in risk for POAG; collard greens and kale demonstrated protective effect; carrots, spinach, collard greens, and
kale had greater protective benefits in black women than white women; summary—high intake of carrots, spinach,
collard greens, and kale associated with lower rate of glaucoma; drinking 1 serving of orange juice per day may increase
risk for glaucoma; study limitations—limited generalizability; temporal ambiguity; survivors’ cohort
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| GLAUCOMA SURGERY AND THE CORNEA —JoAnn A. Giaconi, MD, Assistant Clinical Professor of Ophthalmology,
Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles
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| Corneal endothelial cells: concentration—highest at birth (up to 6000 cells/mm2 ); declines rapidly by age 5; at
18 yr of age, loss stabilizes at 0.6% per year; adults have 1500 to 2000 cells/mm2 ; corneal decompensation occurs
at 500 cells/mm2 ; other age-related changes—cells can increase in size (increase in coefficient of variation) and
lose healthy hexagonal shape; permeability to fluorescein can decrease because barrier function of whole endothelial
layer increases; pump function can decrease
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| Glaucoma and endothelial cells: postulated that aqueous of eye with glaucoma thickened and does not provide
adequate nutrition for endothelium; also suggested that sickness of corneal endothelium may be congenital problem;
Canadian study—endothelial cell counts lower in glaucoma eyes than control eyes, lower in primary angle-
closure glaucoma than POAG, and lower in patients taking 3 to 4 glaucoma medications than patients taking 1 to 2;
use of laser did not affect endothelial cell count
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| Intraocular pressure: acute elevation—can lead to acute and substantial loss (up to 66%) of endothelial cells and
corneal decompensation (loss related to duration of elevation); chronic elevation—in Canadian study, endothelial
density correlated with IOP level, not duration of glaucoma diagnosis
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| Treatment toxicity: in small clinical series, 1 yr of timolol treatment associated with decrease of 6% in endothelial
cell density; however, not borne out in larger studies; carbonic anhydrase inhibitors—acceptable to use in healthy
corneas, but avoid in poorly functioning corneas; laser treatment—argon laser not associated with loss of endothelial
cells; yttrium aluminum garnet (YAG) laser associated with loss of endothelial cells locally (central corneal
density unaffected); filtering surgery—on average, loss of endothelial cells no higher than, eg, phaco surgery; mitomycin-C
trabeculectomy—no change to loss of 14% in endothelial cell count
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| Corneal decompensation after tube implant surgery: more likely to occur in eyes having undergone previous
surgery; complications such as flat anterior chamber (AC) and hypotony increase risk; postulated that jet of
aqueous fluid passes into AC and hits endothelium during diastole, which over time damages cells; malpositioned
tube can damage cornea; intermittent touch between cornea and tube can occur when blinking or rubbing eye, leading
to wounded endothelium and chronic loss of cells; tube touching iris or uvea can incite low-grade inflammation
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| Study: retrospective analysis of 55 POAG patients who had not undergone previous corneal transplant; in patients
undergoing multiple intraocular surgeries, with last surgery being Molteno tube implant, corneal decompensation
rate 50%; in matched group of patients undergoing multiple intraocular surgeries, with last surgery being trabeculectomy,
corneal decompensation rate 6.7%; in eyes undergoing trabeculectomy only, no decompensation reported
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| SURGICAL ASPECTS OF PEDIATRIC GLAUCOMA —Maya Eibschitz-Tsimhoni, MD, Assistant Professor of Ophthalmology,
University of Michigan Kellogg Eye Center, Ann Arbor
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| Presentation of pediatric glaucoma: symptoms—excessive tearing; photophobia; signs—large cornea; corneal
edema; optic nerve cupping; myopia; conjunctival injection; buphthalmos; glaucoma-associated conditions—
Sturge-Weber syndrome; Axenfeld-Rieger syndrome; aphakia or pseudophakia; aniridia; enlarged cornea—
breaks in Descemet’s membrane create scars (Haab's striae); immature corneal endothelium and ruptures in Descemet’s
membrane lead to corneal edema and corneal scarring, and optic nerve cupping occurs rapidly; note—be
wary of patient with asymmetry of signs or symptoms
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| Evaluation: assess visual acuity and ability to fix and follow; check for nystagmus and amblyopia; under anesthesia,
inspect anterior segment with portable slit lamp, inspect angle, perform cycloplegic refraction, inspect optic
nerve and fundus, and measure axial lengths and IOP
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| Interventions: once glaucoma diagnosed, act promptly to prevent vision loss (vision loss occurs secondary to optic
nerve damage, corneal edema, corneal scarring, and amblyopia); amblyopia—important cause of vision loss in
children with glaucoma because of anisometropia from anisomyopia and anisoastigmatism; address aggressively
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| Treatment: unlike in adults, in children, surgery usually first-line treatment; infants do not respond well to medications,
and medications have higher complication rate because of immature metabolizing system
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| Goniotomy and trabeculotomy: should be considered as initial procedure; success rate 75% to 95%; associated
with fewer complications than other surgical options; have no effect in 10% to 15% of pediatric glaucoma cases; if
procedure fails first time, try again
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| Trabeculectomy with mitomycin-C: indicated if goniotomy and trabeculotomy fail; for trabeculectomy alone,
success rate at 1 yr 35% to 50%; intraoperative mitomycin becoming more popular, and studies have shown it to increase
success rate, although likely not appropriate for children <1 yr of age or with aphakia; mitomycin-C
associated with many complications (eg, endophthalmitis reported to occur in up to 17% of patients at 2 yr)
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| Glaucoma drainage devices: can be considered as primary procedure, especially in children with thin sclera in
buphthalmic eye, conjunctival scarring, or Sturge-Weber syndrome; in children, success rate at 1 yr 80% to 90%
and at 4 yr 50%; complications—migration of tube because of growth of eye or collapse of thin sclera in buphthalmic
eye (to prevent migration, place tube far posterior, ie, close to iris); exposure of tube or plate (reported in
up to 13% of children, leading to endophthalmitis in up to 5%)
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| Cyclodestructive procedures: as in adults, difficult to titrate amount of treatment; increase risk for retinal detachment
and phthisis bulbi; success and complication rates for endoscopic approaches similar to external approaches
(15% at 1 yr)
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Educational Objectives
| The goal of this activity is to educate the listener about selected topics in glaucoma. After hearing and assimilating
this program, the clinician will be better able to:
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 | 1. Diagnose patients with glaucoma.
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| 2. Manage patients with glaucoma.
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| 3. Make recommendations about the consumption of fruits and vegetables for patients with glaucoma.
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| 4. Describe how glaucoma and glaucoma surgery can affect the cornea.
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| 5. Treat pediatric patients with glaucoma.
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Discussed on This Program
Mitomycin (mitomycin-C; MTC) [Mutamycin]
Timolol maleate [Betimol, Blocadren, Isatol, Timoptic, Timoptic-XE]
Suggested Reading
Blanc JP et al: Life expectancy of patients with neovascular glaucoma drained by Molteno implants. Clin Experiment
Ophthalmol 32:360, 2004; Bohringer D et al: Influencing factors on chronic endothelial cell loss characterised
in a homogeneous group of patients. Br J Ophthalmol 86:35, 2002; Hu DN et al: Vascular endothelial growth
factor is increased in aqueous humor of glaucomatous eyes. J Glaucoma 11:406, 2002; Every SG et al: Long-term
results of Molteno implant insertion in cases of neovascular glaucoma. Arch Ophthalmol 124:355, 2006; Fukuchi T
et al: Corneal endothelial damage after trabeculectomy with mitomycin C in two patients with glaucoma with cornea
guttata. Cornea 21:300, 2002; Garweg JG et al: Effects of daunorubicin, mitomycin C, azathioprine and cyclosporin
A on human retinal pigmented epithelial, corneal endothelial and conjunctival cell lines. Graefes Arch Clin
Exp Ophthalmol 244:382, 2006; Ishikawa A: Risk factors for reduced corneal endothelial cell density before cataract
surgery. J Cataract Refract Surg 28:1982, 2002; Kang JH et al: Dietary fat consumption and primary open-angle
glaucoma. Am J Clin Nutr 79:755, 2004; Kang JH et al: Antioxidant intake and primary open-angle glaucoma:
a prospective study. Am J Epidemiol 158:337, 2003; Maher P, Hanneken A: Flavonoids protect retinal ganglion
cells from oxidative stress-induced death. Invest Ophthalmol Vis Sci 46:4796, 2005; Moreno MC et al: Retinal oxidative
stress induced by high intraocular pressure. Free Radic Biol Med 37:803, 2004; Ollivier FJ et al: Corneal
thickness and endothelial cell density measured by non-contact specular microscopy and pachymetry in Rhesus
macaques (Macaca mulatta) with laser-induced ocular hypertension. Exp Eye Res 76:671, 2003; Parodi MB, Iacono
P: Photodynamic therapy with verteporfin for anterior segment neovascularizations in neovascular glaucoma.
Am J Ophthalmol 138:157, 2004; Reinhard T et al: Accelerated chronic endothelial cell loss after penetrating
keratoplasty in glaucoma eyes. J Glaucoma 10:446, 2001; Ren H et al: Primary open-angle glaucoma patients have
reduced levels of blood docosahexaenoic and eicosapentaenoic acids. Prostaglandins Leukot Essent Fatty Acids
74:157, 2006; Sihota R et al: Corneal endothelial status in the subtypes of primary angle closure glaucoma. Clin Experiment
Ophthalmol 31:492, 2003; Tsai JH et al: Incidence and prevalence of glaucoma in severe ocular surface
disease. Cornea 25:530, 2006.
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 following has been reported: Dr. Tsai has received research funding from Alcon, Allergan, and Pfizer, and is a
consultant or on the Speaker’s Bureau for Alcon, Allergan, Merck, and Pfizer.
Dr. Tsai was recorded at the 4th Annual Downeast Ophthalmology Symposium: Practical Solutions in Ophthalmology,
presented September 23-25, 2005, in Bar Harbor, ME, by the Maine Society of Eye Physicians and Surgeons; Drs.
Coleman and Giaconi were recorded at the Jules Stein Clinical and Research Seminar 2005, presented May 20-21,
2005, in Los Angeles, CA, by the Jules Stein Eye Institute, David Geffen School of Medicine at the University of
California, Los Angeles; Dr. Eibschitz-Tsimhoni was recorded at the 8th Annual Ophthalmology Spring Conference:
Glaucoma—Consensus and Controversy, presented June 2-3, 2006, in Ann Arbor, MI, by the University of Michigan
Medical School. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production
of this program.
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