Secondary glaucomas represent only a small percentage of all
glaucomas but these conditions are important to understand as there
are critical differences in their diagnosis and management. This section
will discuss several of the most common secondary glaucomas.
NEOVASCULAR GLAUCOMA (NVG)
NVG is a condition caused by new blood vessel growth on the iris
and in the anterior chamber angle usually resulting from retinal ischemia
and hypoxia. NVG is an unusual condition that is more common
in older populations. Retinal ischemia and hypoxia associated
with conditions such as central retinal vein occlusion and proliferative
diabetic retinopathy are implicated in the development of neovascularization
of the anterior segment. In the presence of retinal
ischemia, angiogenic factors such as vascular endothelial growth factor
(VEGF) stimulate the proliferation of new vessels. These angiogenic
factors diffuse into the anterior chamber and promote new
vessel growth, especially in tissues with prolonged exposure to the
aqueous. Obstruction of the angle occurs as a result of the formation
of fibrovascular membranes, which serve as scaffolding for the new
blood vessels. Subsequent contracture of this membrane can lead to
progressive peripheral anterior synechia and subsequent angle closure.
Due to its prolonged contact time with the aqueous, neovascularization
usually appears first on the surface of the iris adjacent to
the pupillary border. These vessels are fine in caliber and may have
aneurism-like out-pouchings. Gonioscopic evaluation may reveal
vessels in the anterior chamber angle, even in the absence of iris
vessels. One emerging treatment for the management of neovascular
glaucoma is the use of bevacizumab (Avastin). Avastin is a monoclonal
antibody that works by attaching to and inhibiting the
action of vascular endothelial growth factor (VEGF). When VEGF is
bound to Avastin, it cannot stimulate the formation and growth of
new blood vessels. Injected into the vitreous, this compound has
been shown to produce a rapid improvement of retinal and iris neovascularization
after a single injection. In addition to this emerging
therapy, treatment of the underlying retinal ischemia with panretinal
photocoagulation can also prevent anterior chamber neovascularization.
Neovascular glaucoma can lead to a blind, painful eye. Management
includes the use of topical atropine 1% to decrease ocular
congestion and topical steroids to decrease inflammation along
with concurrent use of antiglaucoma medications. Still, surgery remains
the main form of therapy. Surgical procedures include cyclocryotherapy,
trabeculectomy and tube implant. In general,
outcomes are less successful compared to primary open angle glaucoma,
although used with Avastin, results may be improved.
GLAUCOMA ASSOCIATED WITH INFLAMMATION
Inflammation associated with different sectors of the eye (scleritis,
uveitis, keratitis, trabeculitis) may lead to an increase in IOP
substantial enough to cause glaucomatous optic atrophy. In addition,
the use of corticosteroid for the treatment of these conditions
may also be responsible for increased IOP (steroid responder). In
both the pediatric and adult populations, the prevalence of glaucoma
associated with uveitis ranges from 5% to 14%, although the
etiology of the uveitis varies between these populations. In the
general glaucoma population, inflammatory etiologies account for
only a small percentage (< 2%) of all glaucomas. Uveitis associated
with glaucoma can result from different conditions, such as anterior
uveitis (e.g. idiopathic, the spondylarthropathies, juvenile rheumatoid arthritis associated uveitis), Fuch’s Heterochromic
uveitis, Posner-Schlossman, Herpetic uveitis, traumatic uveitis, and
lens-induced uveitis. In most cases of glaucoma associated with inflammation,
the anterior chamber angle is open and the increase
in IOP results from direct involvement of the trabecular meshwork
as a consequence of local inflammation (e.g. secondary trabeculitis),
spill-over from more generalized inflammation (e.g. panuveitis),
or as a consequence of accumulation of inflammatory
debris. Less commonly, local inflammation causes an increase in
IOP as result of a secondary angle closure (see section on angle closure
The pathogenesis of steroid induced glaucoma is not fully understood.
Theories include the accumulation of glycosaminoglycans in
the anterior chamber angle and increased production of the
TIGR/Myoc protein. The result produces increased resistance to
In addition to the treatment of the underlying cause of the
uveitis, in most cases, the treatment of the ocular component of
these conditions will involve both anti-inflammatory (topical corticosteroids)
and anti-glaucoma medications (aqueous suppressants).
Cycloplegics are used to prevent or manage posterior
synechia, secondary neovascular glaucoma and choroidal effusion.
Miotics are avoided because their use may exacerbate ciliary spasm,
inflammation and increase the likelihood of synechia.
Prostaglandins are also avoided, as this group of medications may
exacerbate the inflammatory component. If the patient is found to
be a steroid responder (IOP elevates over time), the initial consideration
is to discontinue or change the steroid medication. If this
is not feasible, given the nature of the patient’s condition, then
more aggressive management of the intraocular pressure may be
warranted until the steroid can be discontinued. In general, surgical
(trabeculectomy and tube shunts) have less successful outcomes
compared to primary open angle glaucoma.
Angle recession glaucoma is the most common form of glaucoma
associated with trauma. Other forms include: glaucoma associated
with hyphema (acute) or later onset (ghost cell glaucoma), trabeculitis,
phacolytic glaucoma, and glaucoma associated with lens
dislocation. In the acute phase, the presence of blood in the anterior
chamber (hyphema) or inflammation as a result of injury (e.g.
traumatic iridocyclitis) may cause an increase in intraocular pressure
that mandates treatment. The long term effects of ocular trauma
associated with the pathogenesis of glaucoma often occur as a
result of the initial damage (angle recession) and subsequent healing
of the anterior chamber angle (Figure 1). Since most patients
with traumatic angle recession will not develop glaucoma (5% to
20% develops glaucoma), and elevated IOP occurs long after the antecedent
trauma, it is conceivable that many cases are overlooked.
Angle recession glaucoma is relatively uncommon when the recession
is less than 180 degrees. Angle recession glaucoma often presents
as a unilateral, or asymmetric, glaucoma without symptoms
unless in an advanced stage. The patient may not recall a history
of blunt ocular trauma. Diagnosis requires a 360 degree gonioscopic
assessment of each eye.
Since acute increases
in intraocular pressure in
the setting of blunt trauma
may be of short duration,
careful follow-up may be
all that is required (assuming
the presence of a
healthy optic nerve prior
to injury). If treatment is
indicated, aqueous suppressants
blockers, alpha agonists) are the mainstay of treatment. Angle recession
glaucoma should be treated in a similar fashion as primary open
angle glaucoma (POAG). If customary glaucoma management does not
produce an adequate IOP reduction, a course of cycloplegia may produce
positive results. Surgical washout of the anterior chamber may
be indicated in the presence of hyphema, especially if the corneal endothelium
shows signs of compromise (e.g. corneal blood staining), if
the hyphema does not resolve over time, or if a subsequent new hypema
For angle recession glaucoma, in general, the results of laser and
surgical procedures have less successful outcomes compared to primary
open angle glaucoma.
Patients with sickle cell disease are more sensitive to increases
in IOP, even of short duration (2 to 4 days). These conditions are
capable of occluding the central retinal artery (due, in part, to
stagnation of blood in small vessels, excessive deoxygenation of
erythrocytes, erythrostasis, sickling and increased blood viscosity).
It is, therefore, prudent to order a sickle prep (Sickledex) or hemoglobin
electrophoresis on all patients suspected of having sickle
cell disease or trait (more common among African Americans and
people of Mediterranean descent) in the presence of increased IOP
associated with hyphema.
PSEUDOEXFOLIATIVE GLAUCOMA (PXG)
PXG occurs throughout the world. In the United States, the
prevalence ranges from 5% to 15% of all glaucoma cases. It is
more common in patients > 60 y/o and uncommon in patients
<40. Pseudoexfoliation syndrome is a systemic disease associated
with abnormalities of the basement membrane in epithelial cells,
which are found throughout the body. The accumulation of pseudoexfoliative
material in the trabecular meshwork and the juxtacanicular
tissue next to the Schlemm’s canal leads to obstruction
syndrome typically presents
may become bilateral
and can be an aggressive
form of glaucoma
that can progress rapidly.
The initial signs are
usually noted with slit
lamp exam by observing the deposition of white, flaky material on the anterior lens capsule
(Figure 3) and iris border.
Treatment of PXG is similar to that of POAG. In general, patients
respond well to argon laser trabeculoplasty (ALT). Unfortunately,
within five years, approximately half are back to baseline
IOPs and some will have a rapid sustained increase in IOP within
tend to occur at a relatively
early age (20 to
45 years) with most individuals
(80%), Caucasian and
male. Pigment is released
from the iris due
to lens-iris contact,
leaving radially oriented transillumination defects. The pigment
circulates in the convection currents of the aqueous before adhering
to the corneal endothelium forming Krukenburg’s spindle and
depositing in the anterior chamber angle. PDS is generally bilateral
and asymptomatic. Common signs include a Krukenburg spindle,
radially oriented iris transillumination defects, and heavy
pigment in the anterior chamber). In some instances, a concave
iris may be present (Figure 3).
PDS can resemble postoperative conditions such as IOL-iris chafing
and pseudoexfoliation; however, these are often unilateral and
present with less and unevenly dispersed pigment.
Treatment should take into account the needs of the patient
and the extent of glaucomatous optic neuropathy and/or visual
field loss. Like pseudoexfoliative glaucoma, patients typically respond
well to ALT at least initially. Laser iridotomy may alter the
pressure gradient associated with a concave iris, allowing it to flatten
in the anterior chamber thereby decreasing the likelihood of
contact. When medical and laser intervention fail, surgical intervention
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