Diagnosis and Management of

Lens-induced Glaucoma
DAVID L. EPSTEIN, MD

Abstract: Lens-induced glaucoma may occur as either secondary

angle-closure or open-angle glaucoma. Dislocation or swelling of the
lens can cause pupillary block and subsequent angle-closure
glau90ma. Leakage of soluble lens proteins from a relatively intact
cataractous lens can result in a severe secondary open-angle glaucoma
(phacolytic glaucoma). Heavy molecular weight protein, believed to be
of lens origin, has now been identified in 12 of 12 anterior chamber speci-
mens from such patients. This liberated lens protein can directly obstruct
the trabecular outflow pathways. After extracapsular cataract surgery or
after lens trauma, liberated fragments of lens material may mechanically
impair the drainage of aqueous humor through the outflow channels (lens
particle glaucoma). The diagnosis and management of these different
lens-induced glaucomas are reviewed. With proper recognition, these
glaucomas are promptly cured by the surgical removal of the lens (ma-
terial). [Key words: cataract, heavy molecular weight lens protein, lens-
induced glaucoma, phacolytic glaucoma, pupillary block, secondary
glaucoma.] Ophthalmology 89:227 -230, 1982

Abnormalities in the crystalline lens can cause sec-
ondarily either angle-closure or open-angle glaucoma.
The former is invariably a result of pupillary block,l
whereas the latter has been ascribed to the leakage of
lens proteins and particles from the lens or to the cel-
lular reaction to this. 2.3
LENS~INDUCEDANGLE-CLOSURE
GLAUCOMA; LENS DISLOCATION
Dislocation of the crystalline lens may cause pupil-
lary block by the filling of the pupil with the lens,
vitreous, or both} This form of glaucoma can be cured
by peripheral iridotomy or iridectomy. Laser
iridotomy is the treatment of first choice sirice it avoids
From the Glaucoma Clinical Research Center and Howe Laboratory
of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard
Medical School, Boston, Massachusetts.
Supported in part by grants P50 EY 02518, R01 EY 01894, and R01
EY 00002 from the National Eye Institute, Bethesda, Maryland.
Reprint requests to David L. Epstein, MD,243 Charles Street Bos-
ton, MA 02114.
surgical entry of the anterior chamber and the atten-
dant problems of vitreous loss, etc. Although laser
iridotomies are not always successful, they may close
after several weeks (and require retreatment),4 and,
rarely, they may be blocked by movement ofthe dislo-
cated lens or vitreous, the procedure can be remark-
ably effective for the mechanism of the glaucoma is
usually simple pupillary block. (Anterior movement of
the dislocated lens behind the iris may mechanically
force the iris directly into the angle iri a portion of the
circumference, but the opposite half of the angle re-
mains open unless vitreous occludes the pupil). If a
visual need exists, the dislocated lens (and invariably
vitreous) may be removed by a variety of techniques
employing microvitrectomy instrumentation. Before
such techniques, the visual prognosis was poor due to
complications of the invariable vitreous loss.5 Even
with such instrumentation, iridotomy should be con-
sidered first because of its simplicity and safety.
LENS SWELLING
Swelling of a cataractous lens may occur and cause
secondary angle-closure glaucoma because of pupil-

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 OPHTHALMOLOGY • MARCH 1982 • VOLUME 89 • NUMBER 3
lary block. Cataract surgery is definitive in restoring
vision and curing the glaucoma, unless permanent
peripheral anterior synechiae have formed. In eyes
with no visual potential, iridotomy or iridectomy may
be employed. Such swollen lenses, however, should
be followed for subsequent signs of leakage of lens
proteins and secondary open-angle glaucoma.
LENS-INDUCED
OPEN-ANGLE GLAUCOMA; PHACOL YTIC
Secondary open-angle glaucoma is perhaps the most
interesting form of lens-induced glaucoma. The classic
type is that of phacolytic glaucoma, in which a mature
or hypermature (rarely immature) cataract begins to
leak its soluble contents into the anterior chamber,
resulting in a severe, acute open-angle glaucoma that
must be differentiated from acute angle-closure
glaucoma or neovascular glaucoma. 2,3,6,7 Patients
present with acutely injected eyes and corneal edema,
but open angles on gonioscopy (after clearing the
cornea with topical glycerin). The anterior chamber
contains a heavy flare, but a variable cell content that
is often small. Many of these anterior chamber cells
are macrophages that are larger and clearer than white
blood cells. Small chunks of white particles, presum-
ably derived from the lens, are often also seen cir-
culating in the aqueous. The cataractous lens typically
contains white capsular patches. In eyes with a dense
white cataract, light projection is often faulty.
In phacolytic glaucoma cataract surgery is cura-
tive. 6- 8 Patients should be hospitalized as emergency
admissions since the intraocular pressure may con-
tinue to rise precipitously despite antiglaucomatous
therapy. Urgent cataract surgery may be required.
Before operation osmotics, carbonic anhydrase inhib-
itors, and timolol are effective in temporarily lowering
the intraocular pressure. 8 Miotics seem without effect,
and, although steroids may quiet the eye and occa-
sionally seem to temporarily lower the pressure, this is
most often without sustained effect. 2,3 Sector iridec-
tomy and use of alpha chymotrypsin are preferred be-
cause of the dire consequences, including possible
phacoanaphylaxis, that follow breakage of the capsule
and spilling of the "bag of lens proteins" back into the
eye. 2,3 Curiously, alpha-chymotrypsin-associated
postoperative glaucoma is rare, and visual results, if
the condition has been promptly treated, are good de-
spite the usually poor preoperative vision.
Originally, the pathogenesis of phacolytic glaucoma
was believed to involve obstruction of the outflow
channels for aqueous humor by a combination of lens
debris and swollen macrophages. 6,7 In ensuing years
somehow only the latter has been emphasized. Recent
work in our laboratory has indicated that direct block-
age of the trabecular meshwork by the leaking lens pro-
teins may, in fact, be the most important mecha-
nism. 9,10 Initially we identified heavy molecular weight
(HMW) protein, believed to be of lens origin, in the
228
aqueous humor of six patients with clinical phacolytic
glaucoma, but not in aqueous humor from patients
with nonphacolytic cataracts or those with other forms
of glaucoma. 10 Experimental anterior chamber perfu-
sion studies with like amounts of HMW lens protein
caused a severe secondary open-angle glaucoma. 9 We
have now identified such HMW protein in 12 of 12
phacolytic aqueous humor specimens.
In several of these 12 cases, no macrophages were
identified upon morphologic examination of the
anterior chamber fluid. Yet all patients responded to
cataract surgery with complete alleviation of their
glaucoma. Ordinarily if the diagnosis is suspected but
uncertain, paracentesis and examination of the
anterior chamber fluid by either phase contrast mi-
croscopy or Millipore filter technique 7 for the presence
of macrophages is performed. We are aware of cases in
which no macrophages were seen, and, therefore,
cataract surgery was inappropriately delayed because
the glaucoma was mistakingly felt not to be of lens
origin. These findings indicate that the presence of
HMW protein in the aqueous humor specimen may be
more specific than the identification of macro phages
(which perhaps may be suppressed by the use of
preoperative topical steroids).2,3
Thus, examination of anterior chamber fluid for the
presence of HMW protein is an important diagnostic
aid in suspected cases of phacolytic glaucoma. How-
ever, until this assay method is more widely available,
the clinician should also rely on the clinical signs of
phacolysis if the characteristic bloated macrophages 6,7
are not seen on microscopic examination. The most
characteristic of these signs is the presence of white
patches on the anterior lens capsule (which are mac-
rophages attempting to seal capsular leaks) and the
peculiar small white chunks of presumed lens origin
that are seen circulating in the anterior chamber on
slit-lamp examination. Often there is a very heavy
flare, but small cellular reaction in the anterior
chamber and the large size of these macrophagic cells
are helpful in suspecting phacolysis. When in doubt, if
the glaucoma is not too severe, a diagnostic trial of
topical steroids with careful follow-up may be indi-
cated to differentiate uveitis from phacolysis. In
phacolysis the glaucoma invariably returns to uncon-
trollable levels.
Analysis of anterior chamber fluid for the presence
of HMW protein probably is most useful in atypical
cases of phacolytic glaucoma. Phacolytic glaucoma
may uncommonly occur with an immature cataract,
and we have recently observed cases in which a
hypermature cataract seemed to leak lens proteins into
the aqueous humor only intermittently.
These studies have led us to suspect that there may
be other unusual "protein-obstructive" glaucomas as
well as phacolytic glaucoma. Serum proteins that leak
into the aqueous humor in various forms of uveitis can
cause moderate obstruction of aqueous outflow, 11,12
and this may be a mechanism for open-angle glaucoma
in some patients with uveitis. Ordinarily, classic
 EPSTEIN • LENS-INDUCED GLAUCOMA
phacolytic glaucoma does not occur in children or
young adults, 13 and it is noteworthy that HMW protein
is not present in the lenses of patients in this age
group.14-18 On the other hand, it is possible that leak-
age of lower molecular weight proteins from lower age
cataracts, similar to leakage of serum proteins in
uveitis, could be responsible for certain milder forms
of secondary open-angle glaucoma. There is evidence
that immature cataracts may commonly be leaking
very small amounts of lens proteins into the aqueous
humor .19 The most important aspect of our study may,
in fact, be the recognition of this mechanism of protein
obstruction of outflow.
Although our studies suggest to us that HMW pro-
tein obstruction may be the most important factor in
phacolytic glaucoma, we do not rule out entirely that
the cellular reaction to this protein leakage may also
contribute to the glaucoma, although there is some
evidence against this.2,3 When phacolysis occurs with a
lens dislocated into the vitreous, in which case the glau-
coma and other clinical signs are more subtle and sub-
acute, cellular reaction may be an important factor since
HMW protein must diffuse through the vitreous and
may enter the anterior chamber in only small amounts.
LENS-PARTICLE GLAUCOMA
In contrast to phacolytic glaucoma in which soluble
lens proteins leak from the lens through a relatively
intact lens capsule, there is another form of lens-
induced secondary open-angle glaucoma that is as-
sociated with a grossly disrupted lens capsule and the
presence of obvious fragments of lens material cir-
culating in the aqueous humor. 2,3 This condition may
occur after extracapsular cataract surgery or trauma to
the lens, or an advanced cataract may rarely rupture
spontaneously. These fragments of the lens leave the
eye via the trabecular outflow pathways, and experi-
mental studies have indicated that such lens particles
can directly cause a severe obstruction of aqueous
humor outflow. 9 The cellular reaction to these lens
particles possibly may also contribute to the glaucoma,
but it seems clear that these lens particles, themselves,
can mechanically impair trabecular drainage of fluid.
This is most important to the clinician because lens
particle glaucoma responds very well to simple surgi-
cal irrigation and removal of the lens material from
the eye. 8
If there is only a moderate glaucoma and a small
amount of liberated lens material present, a trial of
medical anti-glaucomatous therapy such as timolol and
carbonic anhydrase inhibitors may be attempted to
allow the normal cellular processes in the trabecular
meshwork to "clear" the offending lens material.
Miotics should be avoided. Since some inflammation
invariably accompanies the lens injury or surgery, mild
to moderate topical steroid therapy should be initiated
to prevent synechiae, pupillary membranes, etc, but
intensive steroid therapy probably should be avoided
since this might, in fact, delay "absorption" of free
lens material. If the glaucoma is severe and/or there is
a large amount of lens material in the anterior chamber
that will continue to flow into the trabecular
meshwork, surgical removal of this lens material
should be undertaken. 8
If one keeps in mind that the glaucoma is commonly
related to the "dose" of free lens material that flows
into the trabecular meshwork, the diagnosis usually
can be made on slit-lamp examination. Diagnostic
paracentesis will merely confirm the presence of lens
material seen on slit-lamp examination. Since the
glaucoma is due to particulate lens material rather than
leakage of soluble lens proteins, HMW protein need
not be present in the anterior chamber specimen.
An unusual form of lens-particle glaucoma can occur
many years after extracapsular surgery when lens
material somehow is spontaneously freed into the
anterior chamber. Occasionally there may be a spon-
taneous dislocation of a Soemmering's ring into the
anterior chamber. 3
When the liberated lens particles have been "ab-
sorbed" via cellular processes in the trabecular
meshwork, intraocular pressure returns to normal un-
less complications such as peripheral anterior
synechiae have formed. However, we have wondered
whether "absorption" of excessive quantities of lens
material by the trabecular meshwork could result in
premature "wearing out" of this tissue and subsequent
open-angle glaucoma many years later, as has been
described after congenital cataract surgery. 20
ACKNOWLEDGMENT
The author wishes to express his long-standing gratitude to
W. Morton Grant, MD, and Paul Chandler, MD, for their
advice and encouragement in these studies and to Judith
Jedziniak-MacGregor, PhD, and Levon Karageuzian for
their biochemical analyses.
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