GLAUCOMA UPDATE
From the 6th Annual Downeast Ophthalmology Symposium, presented by the Maine Society of Eye Physicians and
Surgeons, Manchester, ME
Louis R. Pasquale, MD, Assistant Professor of Ophthalmology, Harvard Medical School, Co-Director, Glaucoma
Service, Massachusetts Eye and Ear Infirmary, and Research Director, Ocular TeleHealth Center, Boston Veterans
Affairs Hospital, Boston, MA
| GLAUCOMA UPDATE: ASSESSING RISK
|
| Overall goal of glaucoma management: keep patients functional (able to perform activities of daily living)
|
| Natural history of glaucoma: optic neuropathy with extension of cup to superior and inferior poles of optic nerve causes
visual disability; disease plays out over decades; preclinical changes that result in pathologic cupping of optic nerve unknown;
if patient already symptomatic (eg, visual-field changes detectable), disease fairly advanced
|
| Glaucoma facts: 1) based on prevention trials, currently no known way to prevent development of primary open-angle
glaucoma (POAG); 2) no known way to prevent disease progression (in Early Manifest Glaucoma Trial [EMGT], treated
patients progressed, but at slower rate); 3) most patients with glaucoma do not go blind, but glaucoma second leading
cause of blindness worldwide
|
 | 1) Risk of converting from ocular hypertension to POAG: Ocular Hypertension Treatment Study (OHTS)—parameters
for entry included intraocular pressure (IOP) >24 mm Hg in one eye and >21 mm Hg in fellow eye, with same IOPs at
second visit; some patients with ocular hypertension at first visit reverted to normal tension on subsequent visits,
without treatment; pearl—even if patient with ocular hypertension calculated to have risk high enough for preemptive
treatment, consider waiting ≥1 visit to see whether IOP elevation sustained
|
| 2) Risk of converting from suspected glaucoma with normal IOP to POAG: patients have glaucoma-like optic discs and
normal IOPs (largest group of patients)
|
| 3) Risk of converting from asymptomatic but advanced POAG to functional blindness
|
| Glaucoma 5-yr risk estimator (Washington University School of Medicine; Gordon et al): best calculator to assess patient’s
risk of converting from ocular hypertension to POAG; combines data from OHTS and European Glaucoma Prevention
Study (EGPS); downloadable from Web site (ohts.wustl.edu/risk)
|
| Case 1: 48-yr-old black woman with ocular hypertension; family history positive for glaucoma; no diabetes; IOP 24 mm
Hg; central corneal thickness 520 µm; cup-to-disc ratio 0.4 (nerves not pathologically cupped); main drivers of risk
calculation—IOP, cup-to-disc ratio, central corneal thickness, and data from visual fields; family history, race, and sex
not part of equation; for this patient, risk ≈15% (without treatment, risk of developing POAG in 10 yr 30%)
|
| When to treat (study): if risk of converting from ocular hypertension to POAG >2% per year, incremental cost effectiveness
of treating patient ≈$43,000 per quality-of-life–year (in United Kingdom, if cost ≥$60,000, treatment not considered
cost effective, and treatment not offered); however, 2% annual risk worth treating (at 15% risk in 5 yr, treatment worthwhile)
|
| Case 2: young patient presented to emergency department with mild dysphasia, no risk factors for stroke, and patent foramen
ovale; work-up included neuro-ophthalmologic examination; patient had large cups; referred to glaucoma service;
borderline elevated IOPs and thin corneas; no signs of pigment dispersion even though patient high myope and cup-to-
disc ratios 0.5 OD and 0.6 OS; examined via GDx with variable corneal compensator (scan shows defect, but could be
normal bifurcated pattern to superior nerve fiber layer); nerve fiber layer intact; visual fields normal
|
| Dilemma in assessing risk: treat patient? IOP slightly high; corneas thin; nerve fiber layer in right eye may be slightly
thin; however, no pathologic thinning of neuroretinal rim; Humphrey visual field full; based on OHTS, patient has thin
cornea, which puts patient at risk for POAG; patient does not meet criteria for OHTS, therefore risk calculator does not
apply (no treatment indicated)
|
| Bottom line: in general, if patient’s risk unknown, consider observation; routine preemptive treatment not cost effective,
may not help, and exposes patient to possible side effects and expense of medical therapy; racial factors—studies indicate
that black patients more likely to progress; summary—no calculators predict which patients with glaucoma will become
blind
|
| Risk for blindness: Collaborative Initial Glaucoma Treatment Study (CIGTS)—high percentage of patients with glaucoma
worried about going blind from disease when initially diagnosed, and concerns persisted even after patients educated
about natural history of disease; patients with juvenile rheumatoid arthritis and secondary glaucoma (Kanski)—
35% of patients legally blind in glaucomatous eye at 10 yr; uveitis relentless; patients develop cataract, then glaucoma;
difficult to manage; speaker worries most about patients with secondary uveitic glaucoma
|
| Case 3: 56-yr-old man (psychiatrist) with high myopia and advanced glaucoma; patient on maximal medical therapy and
has had laser trabeculoplasty in both eyes; vision good; IOPs in low-normal range; patient worried that disease progression
may render him unable to practice medicine; advanced disc cupping in both eyes; Humphrey visual fields show advanced
damage; according to Goldmann visual fields, patient not legally blind, but significantly disabled; glaucomatous
optic neuropathy in patients with cup-to-disc ratios ≥ 0.9 for ≥10 yr (study by speaker)—68 patients who had large
cup/disc ratios, Snellen acuity at least 20/40, and not legally blind for 10 yr; after 10 yr, 20% of those patients met state
criteria for legal blindness (in majority, IOPs 12-16 mm Hg); conversation with patient—sobering; blindness from glaucoma
can and does occur; at 56 yr of age, not many retinal ganglion cells left
|
| Conclusion: as stated by Parrish, “we cannot simply put numbers in a calculator and know whether patient will be safe or
will develop progressive glaucomatous damage; the risk calculators are really a call to continuously involve patients in
the long-term management of their disease as we continue to follow them”
|
| In future: expect more accurate calculators as more discovered about spectrum of factors associated with development and
progression of glaucoma; speaker conducting research on how genes and environment interact to produce POAG; many
risk factors (ocular, systemic, lifestyle, and genetic) will enter into calculus of assessing whether patients will develop
glaucoma and, if so, whether they will progress to later stages of disease
|
| DISC HEMORRHAGES: WHAT TO KNOW, WHAT TO DO
|
| Historical background: disc hemorrhages popularized by Drance (1970) as sign of glaucomatous optic neuropathy;
Chumbley and Brubaker, 1976—disc hemorrhage marker for progressive visual field loss
|
| Case: woman referred to ophthalmologist after optometrist noticed disc hemorrhage; ocular history of low myopia; patient’s
father (also speaker’s patient) had had symptoms suggestive of cataract, but actually had advanced open-angle
glaucoma (OAG); history of thyroiditis; no surgical history; patient young and healthy (not vasculopathic; occasionally
runs marathons); slit lamp examination normal; disc hemorrhage in left eye and associated wedge-shaped defect in nerve
fiber layer; visual field normal in right eye, but left eye has dense paracentral scotoma that crosses fixation; pattern deviation
plot (nerve fiber layer dead; no light perception in that area); speaker’s approach—neuroimaging not worthwhile;
patient has paracentral scotoma that corresponds to papillomacular bundle below horizontal meridian, producing superior
paracentral defect (rules out brain tumor); magnetic resonance imaging (MRI) or computed tomography (CT) usually of
little use (may show some small bright lesions in brain consistent with small vessel disease)
|
| Differential diagnosis of disc hemorrhages: glaucoma number one probability; occasionally, posterior vitreous detachment
might cause disc hemorrhage (not field defect); diabetic retinopathy possible etiology, but usually additional sites in
retina affected (not just disc); occlusive venous disease may cause venous engorgement and splinter hemorrhages on
disc; rarely, occult peripapillary neovascular membrane, suggesting that other optic neuropathies can produce disc hemorrhages
(eg, anterior ischemic optic neuropathy), but distinguishable from OAG
|
| Retinal vascular autoregulation: hypothesis—disc hemorrhages reflect abnormal vascular autoregulation within optic
nerve head; faulty retinal vascular autoregulation contributing to glaucomatous optic neuropathy; definition—
maintaining steady-state blood flow in face of changing perfusion pressures; normally, retinal blood flow remains constant
despite postural changes (sitting, standing, lying down)
|
| Retinal blood flow response to postural changes in glaucoma patients, compared to healthy individuals (Feke and
Pasquale, in press)
|
| Doppler blood flow meter: allows direct calculation of blood flow; blood flow measured in inferotemporal branch of retinal
artery of left eye of every patient (manifest glaucoma more prevalent in left eye); note—patient in case presented
with superior paracentral scotoma (in patients with glaucoma, inferior neuroretinal rim tends to erode before superior
neuroretinal rim); inferior neuroretinal rim examined in every patient, regardless of disease location; left eye of every
patient studied, regardless of location of visual field defect; protocol takes ≈45 min to measure blood flow in retinal
vessel while patient sitting, lying down, and sitting up again (mimics, eg, getting up in morning)
|
| Findings: experimental data compared to that of age-matched controls; normal controls maintained fairly stable flow
rates despite postural change; alternatively, in patient from case, for instance, blood flow increased ≈60% while lying
down and remained elevated when patient sat up again (counterintuitive finding in patients with OAG; would expect
blood flow rates to drop); 18 glaucoma patients and 8 controls; 6 additional OAG patients responded similarly to patient
described in case (hyperperfusion in ≈7 patients, but ≈7 behaved normally); 5 of 7 participants who behaved normally
were on brimonidine (Alphagan; surprising to speaker); findings suggest that brimonidine might improve retinal
vascular autoregulation in patients with focal ischemic OAG (more study needed); brimonidine frequently discontinued
due to allergic response; some patients with low ocular perfusion pressure at baseline had vacillating responses
(blood flow increased, but quickly went back down; expected in all patients with disc hemorrhages, but only seen in 4
of 18); some controls not “normal,” but majority had nearly 0% change in flow over time; much broader range of responses
in OAG patients
|
| Conclusion: data supported fact of abnormal retinal vascular autoregulation in patients with this type of OAG, normal
IOP, and tendency toward disc hemorrhage
|
| Possible explanation: at optic nerve head, vessels make acute right- and left-hand changes at surface of optic disc; when
vessels make this bend, shear forces at work; perhaps in patients with hyperperfusion, small vessel in lamina cribrosa
capillaries breaks open and bleeds (could explain why disc hemorrhages occur in OAG); explaining why disc hemorrhage
produced damage when IOP 18 mm Hg did not—if disc hemorrhage large enough to straddle neuroretinal rim
and scleral ring (Elschnig ring), blood pins nerve fiber layer against lamina cribrosa and scleral ring; when blood resorbed,
notch results
|
| More facts about disc hemorrhage derived from randomized clinical trials
|
| OHTS: patients without elevated IOPs get disc hemorrhages too; patient who converted from normal IOPs to POAG—
width of disc hemorrhage and nerve fiber layer defect same (suggests that abnormal retinal vascular autoregulation
leads to sheer forces at disc head that cause small blood vessels to bleed, causing focal compressive optic neuropathy
[regardless of IOP] and nerve fiber layer dropout); in OHTS, disc hemorrhages stronger risk factor than central corneal
thickness for conversion from ocular hypertension to POAG
|
| EMGT and Collaborative Normal-Tension Glaucoma Study (CNTGS): disc hemorrhage independent risk factor for disease
progression
|
| Is disc hemorrhage inevitable with OAG? probably not; Bengtsson—patients followed 5 to 10 yr; 35 of 44 patients developed
disc hemorrhage; Yang, 2003—no disc hemorrhages found among Asians with chronic angle closure glaucoma
|
| Managing the patient who presents with disc hemorrhage and IOP 16 mm Hg: if old photographs available, reevaluate
them (may have missed disc hemorrhage); if disc hemorrhages discovered, go back and look at visual fields over time; if
no progression in 10 yr, level of concern lower because indicates disc hemorrhages small and would not cause mechanical
changes necessary to affect nerve fiber layer; if signs of visual field progression present, change target IOP (in this
case, 16 mm Hg too high; patient not doing well); therapy to lower IOP only tool at physician’s disposal; patient whose
IOP 12 mm Hg—no good answers; consider tracking diurnal curve to detect elevated IOPs at other times of day; if IOP
10 to 12 mm Hg, and disc hemorrhage detected at 12 mm Hg, treatment may be worse than disease
|
| Genetic determinants of abnormal retinal vascular autoregulation: endothelin causes constriction, but not involved in
POAG; nitric oxide causes vasodilation; 3 genes responsible for producing nitric oxide; in case example, patient producing
slightly less nitric oxide than age-matched control; study of large population required to claim that particular gene locus
involved in OAG; studies by Wiggs and speaker—OAG population stratified into paracentral endophenotype with
loss of near fixation (initial manifestation of disease) vs patients with peripheral defects; patients with paracentral scotomas
have higher percentage of CC genotype associated with reduced nitric oxide production (20% of controls also have
CC genotype); speaker suspects gene-gene interactions or gene-environment interactions triggered disc hemorrhage in
patient from case (not CC genotype alone)
|
| Conclusion: for patients with OAG, disc hemorrhages, and IOPs in mid-to-high teens, try to reduce IOP to low teens (if
IOPs already in low teens, examine diurnal curve; speaker not more aggressive in those patients); brimonidine may be
useful first-line treatment for endophenotype of young women with focal ischemic OAG; disc hemorrhages important in
pathogenesis of OAG (may reflect abnormal retinal vascular autoregulation); more research needed to determine molecular
factors involved
|
Suggested Reading
Boland MV, Quigley HA: Risk factors and open-angle glaucoma: classification and application. J Glaucoma 16:406,
2007; Budenz DL et al: Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension
Treatment Study. Ophthalmology 113:2137, 2006; Gazzard G et al: Optic disc hemorrhage in Asian glaucoma patients. J
Glaucoma 12:226, 2003; Healy PR et al: Optic disc hemorrhages in a population with and without signs of glaucoma.
Ophthalmology 105:216, 1998; Leske MC et al: Factors for glaucoma progression and the effect of treatment: the early
manifest glaucoma trial. Arch Ophthalmol 121:48, 2003; Leske MC et al: Nine-year incidence of open-angle glaucoma in
the Barbados Eye Studies. Ophthalmology 114:1058, 2007; Medeiros FA et al: Validation of a predictive model to estimate
the risk of conversion from ocular hypertension to glaucoma. Arch Ophthalmol 123:1351, 2005; Ocular Hypertension
Treatment Study Group; European Glaucoma Prevention Study Group, Gordon MO et al: Validated prediction
model for the development of primary open-angle glaucoma in individuals with ocular hypertension. Ophthalmology
114:10, 2007; Oliver JE et al: Blindness and glaucoma: a comparison of patients progressing to blindness from glaucoma
with patients maintaining vision. Am J Ophthalmol 133:764, 2002; Wiggs JL: Genetic etiologies of glaucoma. Arch Ophthalmol
125:30; 2007; Yang CH et al: Characteristics of optic disc changes in Taiwanese patients with primary angle closure
glaucoma. J Formos Med Assoc 102:183, 2003.
Educational Objectives
| The goal of this program is to improve risk assessment and management of disc hemorrhage in patients with glaucoma.
After hearing and assimilating this program, the clinician will be better able to:
|
| 1. Assess the risk for development of primary open-angle glaucoma (POAG) in a patient with ocular hypertension.
|
| 2. Recognize limitations of current risk assessment tools for patients with POAG.
|
| 3. Explain differential diagnosis of optic disc hemorrhage.
|
| 4. Describe the role of disc hemorrhage in the natural history of open-angle glaucoma.
|
| 5. Choose appropriate therapy for patients who present with disc hemorrhage.
|
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. Pasquale has been a research consultant for
Allergan and Pfizer, and a speaker for Alcon.
Acknowledgments
Dr. Pasquale was recorded at the 6th Annual Downeast Ophthalmology Symposium, presented September 28-30, 2007, in
Bar Harbor, ME, by the Maine Society of Eye Physicians and Surgeons. The Audio-Digest Foundation thanks Dr. Pasquale
and the sponsor for their cooperation in the production of this program.
|
