REVIEW

CURRENT
OPINION Glaucoma secondary to intraocular tumors:
mechanisms and management
David A. Camp a, Prashant Yadav a, Lauren A. Dalvin a,b, and Carol L. Shields a

Purpose of review
Glaucoma secondary to intraocular tumors is important to consider in eyes with a known tumor and those
with unilateral or refractory glaucoma. The purpose of this review is to discuss the mechanisms and
management of intraocular tumors with related secondary glaucoma.
Recent findings
Several intraocular tumors can lead to glaucoma, including iris melanoma, iris metastasis, iris lymphoma,
trabecular meshwork melanoma, choroidal melanoma, choroidal metastasis, retinoblastoma, and
medulloepithelioma. The mechanisms for glaucoma include solid tumor invasion into the angle, tumor
seeding into the angle, angle closure, and iris neovascularization. Management of the tumor can lead to
resolution of glaucoma. Management of the secondary glaucoma may involve medical therapy, transscleral
cyclophotocoagulation, laser trabeculoplasty, and potentially antivascular endothelial growth factor
therapy. Minimally invasive glaucoma surgery (MIGS) can be considered for eyes with treated, regressed
posterior segment malignancies if there is no iris or ciliary body involvement. Importantly, avoidance of
MIGS, filtering, or shunting surgery in eyes with active malignancies is emphasized.
Summary
Intraocular tumors can produce secondary glaucoma. Treatment of the primary tumor can sometimes
resolve the glaucoma. Topical, oral, or laser therapies can be considered. Avoidance of MIGS, filtering, or
shunting surgery is advised until the malignancy is completely regressed.
Keywords
angle closure, angle infiltration, eye, glaucoma, iris, melanoma, neovascular, pigment dispersion, tumor, uvea

INTRODUCTION The management of tumor-induced secondary

Intraocular tumors can lead to secondary glaucoma
through several mechanisms that vary according to
the tumor type, growth pattern, location, size, and
secondary features related to the tumor. Tumor-
related secondary glaucoma is most often associated
with malignancies such as iris melanoma, iris metas-
tasis, iris lymphoma, and retinoblastoma but can be
found with benign tumors such as iris melanocytoma,
tapioca iris nevus, benign ciliary body medulloepithe-
lioma, and diffuse choroidal hemangioma [1]. Tumors
located in the anterior segment are particularly prone
to inducing glaucoma, often by direct infiltration of
the anterior chamber angle or with related iris neo-
vascularization [1]. In contrast, tumors located in the
posterior segment are more likely to cause glaucoma
by inducing iris neovascularization from large tumor
size or chronic retinal detachment, or by rotation of
the lens iris diaphragm with angle closure from large
tumor size or total retinal detachment [1].
glaucoma depends on several factors related to the
tumor and the glaucoma. In some cases, treatment
of the tumor and resolving the retinal detachment
or iris neovascularization can reverse the glaucoma,
particularly in eyes with retinoblastoma [2]. For
other forms of glaucoma, control with topical or
oral medications, transscleral cyclophotocoagula-
tion, and laser trabeculoplasty are generally first line
of therapy. Minimally invasive glaucoma surgery
a
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson Univer-
sity, Philadelphia, Pennsylvania and bDepartment of Ophthalmology,
Mayo Clinic, Rochester, Minnesota, USA
Correspondence to Carol L. Shields, MD, Ocular Oncology Service, 840
Walnut Street, Suite 1440, Philadelphia, PA 19107, USA.
Tel: +1 215 928 3105; fax: +1 215 928 1140;
e-mail: carolshields@gmail.com
Curr Opin Ophthalmol 2019, 30:71–81
DOI:10.1097/ICU.0000000000000550

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Glaucoma
KEY POINTS
 Glaucoma secondary to intraocular tumor is an
important diagnosis to consider in eyes with known
tumor and those with unilateral or refractory glaucoma.
 Mechanisms for glaucoma can be multifactorial and
include solid tumor invasion into the angle, tumor
seeding into the angle (pigment dispersion), angle
closure, and iris neovascularization.
 Management of glaucoma secondary to intraocular
tumor can involve medical therapy, transscleral
cyclophotocoagulation, laser trabeculoplasty, and
intravitreal anti-VEGF therapy.
 MIGS can be considered for eyes with treated,
regressed posterior segment malignancy if there is no
iris or ciliary body involvement.
 MIGS, filtering, or shunting surgery in eyes with active
malignant intraocular tumor should be avoided to
prevent tumor spread outside the globe.
(MIGS), filtering, or shunting surgery is acceptable,
if necessary, in eyes with benign tumors or eyes with
treated and stable regressed malignancies. Any fea-
ture suggestive of tumor activity, whether benign or
malignant, should caution the clinician to avoid
MIGS, filtering, or shunting surgery so as to prevent
tumor egress out of the eye. This is especially impor-
tant in eyes with iridociliary malignancies, retino-
blastoma, and medulloepithelioma. Herein, we
review specific tumors and the mechanisms and
management of both the intraocular tumors and
the related secondary glaucoma. A summary can be
found in Table 1.
UVEAL TUMORS
Uveal tumors that can produce secondary glaucoma
include iris melanocytoma, iris tapioca nevus/mela-
noma, iris melanoma (nodular/diffuse or trabecular
meshwork type), iris metastasis, iris lymphoma, cili-
ary body melanoma (ring melanoma), choroidal
melanoma, choroidal metastasis, choroidal lym-
phoma, and choroidal hemangioma (circumscribed
or diffuse).
Iris melanocytoma
Iris melanocytoma is a benign tumor that appears as
a deeply pigmented, dark brown to black, circum-
scribed, dome-shaped mass, representing 3% of all
iris nevi [3]. Secondary glaucoma occurs in 11% of
cases (Fig. 1) [3]. Melanocytoma can undergo spon-
taneous necrosis with pigment dispersion, causing
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secondary glaucoma because of pigment-laden
melanophages seeding into the angle [13].
Management options for melanocytoma
include observation or local resection. When mel-
anocytoma causes glaucoma, first-line therapies
include medical management or transscleral cyclo-
photocoagulation [14]. MIGS, filtering, or shunt-
ing surgery should be a last resort due to concern for
malignant transformation and should only be per-
formed after fine-needle aspiration biopsy with
cytopathologic confirmation of a benign lesion
[15]. In some cases, secondary glaucoma can
resolve after complete surgical resection of the
tumor [16].
Iris tapioca nevus/melanoma
Iris tapioca nevus is an uncommon benign tumor
that appears as a multinodular dispersed tumor on
the iris surface, appearing nearly transparent. Trans-
formation into malignant iris tapioca melanoma
can occur [17]. Secondary glaucoma can occur with
both benign and malignant forms of tapioca tumor
because of angle invasion (Fig. 2).
Management options for tapioca nevus include
observation, whereas tapioca melanoma can be
treated with plaque radiotherapy or enucleation.
Therapies for glaucoma control include medical
management or transscleral cyclophotocoagula-
tion. MIGS, filtering, or shunting surgery should
be avoided to prevent tumor egress outside the eye.
Iris melanoma (nodular or diffuse type)
Iris melanoma is a malignant tumor that appears
as a variably pigmented mass, which can be a
well-circumscribed solid mass in the nodular
type or appear as a flat pigmentary mass on the
iris surface in the diffuse type. Uveal melanoma
has an incidence of 5.1 per million, with iris mela-
&&
noma representing only 4% of all cases [4 ,18,19].
Secondary glaucoma occurs in 33% of cases [4 ].
&&
Mechanisms of secondary glaucoma related to
iris melanoma include angle invasion (28.4%), iris
neovascularization (2.3%), and hyphema (2.3%)
&&
[4 ,5]. It should be realized that patients with
iris melanoma and secondary glaucoma are at sig-
nificantly higher risk for metastases, with a hazard
ratio of 4.51 compared with iris melanoma without
&&
glaucoma [4 ].
Management options for nodular iris melanoma
include resection, whereas plaque radiotherapy or
enucleation can be employed for both nodular
and diffuse type iris melanoma [20]. First-line ther-
apies for glaucoma control are medical manage-
ment, transscleral cyclophotocoagulation, or laser
Volume 30  Number 2  March 2019
 Glaucoma secondary to intraocular tumors Camp et al.

Table 1. Summary of glaucoma secondary to intraocular tumors: mechanisms and management

Frequency of
secondary
Mechanism glaucoma
for glaucoma per tumor Management of
Specific tumor [references] [references] tumor Management of glaucoma

Uveal tumors
Iris melanocytoma Seeding into angle 11% [3] Observation Medical management
(pigment dispersion) Local resection Transscleral cyclophotocoagulation
MIGS, filtering, or shunting surgery
(after biopsy confirmation) should be last
choice due to concern for malignant
transformation
Note: The secondary glaucoma can
resolve following surgical resection of
the tumor
Iris tapioca nevus Angle invasion NA Observation Medical management
Iris tapioca Plaque radiotherapy Transscleral cyclophotocoagulation
melanoma Enucleation Avoid MIGS, filtering, or shunting
surgerya
Iris melanoma Angle invasion (28.4%) 33% [4 ] Nodular type Medical management
&&

(nodular or diffuse [4 ,5] Resection Transscleral cyclophotocoagulation

&&

type) Iris neovascularization Plaque radiotherapy Laser trabeculoplasty

(2.3%) [4 ,5] Enucleation If neovascular, consider anti-VEGF
&&

Hyphema (2.3%) Diffuse type Enucleation

[4 ,5] Plaque radiotherapy Avoid MIGS, filtering, or shunting
&&

Enucleation surgerya
Iris melanoma Trabecular meshwork 100% [6] Plaque radiotherapy Medical management
(trabecular infiltration Enucleation Transscleral cyclophotocoagulation
meshwork type) Avoid MIGS, filtering, or shunting
surgerya
Iris metastasis Angle invasion (29%) 37% [7 ] Plaque radiotherapy Medical management
&&

[7 ] EBRT Transscleral cyclophotocoagulation

&&

Iris neovascularization Systemic chemotherapy Laser trabeculoplasty

(8%) [7 ] If neovascular, consider anti-VEGF
&&

Enucleation
Iris lymphoma Angle invasion 29% [8] Plaque radiotherapy Medical management
Angle closure EBRT Transscleral cyclophotocoagulation
Hyphema Systemic chemotherapy Laser trabeculoplasty
Enucleation
Ciliary body Angle invasion 35% [9] Plaque radiotherapy Medical management
melanoma (ring Seeding into angle Enucleation Transscleral cyclophotocoagulation to
melanoma) (pigment dispersion) uninvolved ciliary body
Angle closure Laser trabeculoplasty to uninvolved
Iris neovascularization angle
Enucleation
Choroidal Angle invasion (<1%) [1] 2% [1] Plaque radiotherapy Medical management
melanoma Angle closure (<1%) Local resection Transscleral cyclophotocoagulation
[1] Enucleation Laser trabeculoplasty
Iris neovascularization If no tumor in anterior segment or ciliary
(1%) [1] body, then MIGS, filtering, or shunting
Hyphema (<1%) [1] surgery can be considered after
Suprachoroidal complete tumor control is achieved
hemorrhage (<1%) [1] Enucleation
Choroidal Angle closure 1% [1] Plaque radiotherapy Medical management
metastasis Iris neovascularization Photodynamic therapy Transscleral cyclophotocoagulation
EBRT systemic chemotherapy Laser trabeculoplasty
Enucleation If no tumor in anterior segment or ciliary
body, then MIGS, filtering, or shunting
surgery can be considered after
complete tumor control is achieved
Enucleation

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Glaucoma

Table 1 (Continued)

Frequency of
secondary
Mechanism glaucoma
for glaucoma per tumor Management of
Specific tumor [references] [references] tumor Management of glaucoma

Choroidal Angle invasion Rare Plaque radiotherapy Medical management

lymphoma Angle closure EBRT Transscleral cyclophotocoagulation
Systemic chemotherapy Laser trabeculoplasty
Enucleation Enucleation
Note: The secondary glaucoma can
resolve following radiotherapy of the
tumor
Choroidal Angle closure (<1%) [9] 1% [10] Photodynamic therapy Medical management
hemangioma Iris neovascularization Plaque radiotherapy Transscleral cyclophotocoagulation
(circumscribed) (<1%) [9] Laser trabeculoplasty
MIGS
Filtering or shunting surgery
Choroidal Angle closure Rare Plaque radiotherapy Medical management
hemangioma Iris neovascularization Photodynamic therapy Transscleral cyclophotocoagulation
(diffuse) EBRT Laser trabeculoplasty
MIGS
Filtering or shunting surgery
Retinal tumors
Retinoblastoma Angle closure (5%) [1] 17% [1] Chemotherapy Medical management
Tumor seeding (<1%) Plaque radiotherapy Transscleral cyclophotocoagulation
[1] Enucleation Laser trabeculoplasty
Iris neovascularization If neovascular, consider anti-VEGF
(12%) [1] Enucleation
Avoid MIGS, filtering, or shunting
surgerya
Retinal astrocytic Iris neovascularization Rare Observation Medical management
hamartoma/ Photodynamic therapy Transscleral cyclophotocoagulation
astrocytoma Plaque radiotherapy Laser trabeculoplasty
Sirolimus, Everolimus If neovascular, consider anti-VEGF
EBRT MIGS
Enucleation Filtering or shunting surgery
Enucleation
Nonpigmented ciliary epithelial tumors
Medulloepithelioma Angle invasion 44–46% Plaque radiotherapy Medical management
Angle closure [11,12] Enucleation Transscleral cyclophotocoagulation
Iris neovascularization Laser trabeculoplasty
If neovascular, consider anti-VEGF
Enucleation
Avoid MIGS, filtering, or shunting
surgerya

Anti-VEGF, antivascular endothelial growth factor; EBRT, external beam radiotherapy; MIGS, minimally invasive glaucoma surgery; NA, not available.
a
Avoid MIGS, filtering, or shunting surgery as this can lead to egress of tumor outside the eye, at risk for further spread.

trabeculoplasty [21]. Antivascular endothelial
growth factor (anti-VEGF) injections can be consid-
ered for neovascular glaucoma [22]. Enucleation
may be necessary in the setting of refractory glau-
coma resulting in blind, painful eye [23]. MIGS,
filtering, or shunting surgery should be avoided to
prevent tumor egress outside the eye. Unfortu-
nately, diffuse iris melanoma is often misdiagnosed
[24], which can lead to inappropriate initial surgical
treatment that necessitates subsequent enucleation
&&
for tumor control [25 ]. Diffuse iris melanoma
should be considered in the differential diagnosis
of unilateral, refractory glaucoma and ruled out
prior to MIGS, filtering, or shunting surgery.
Iris melanoma (trabecular meshwork type)
Iris melanoma of the trabecular meshwork is a
rare malignant tumor predominantly confined to
the trabecular meshwork and with minimal iris

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 Glaucoma secondary to intraocular tumors Camp et al.

FIGURE 1. Iris melanocytoma with secondary glaucoma from angle seeding Iris melanocytoma (a) treated with partial
lamellar iridocyclectomy (b) with a small focus of melanoma found histopathologically. Subsequent tumor infiltration of the
angle (c) resulted in elevated intraocular pressure, treated with medical glaucoma management and plaque radiotherapy,
resulting in (d) pigment resolution and decreased intraocular pressure. IOP, intraocular pressure.

involvement. The tumor grows along the anterior
chamber angle and can assume a ring configuration
with 360 degrees of angle involvement. In a series of
14 cases from our department, secondary glaucoma
was found in all cases (100%) [6]. The mechanism of
secondary glaucoma was tumor infiltration of the
trabecular meshwork (Fig. 3).
Management options for trabecular meshwork
iris melanoma include plaque radiotherapy or enu-
cleation. Therapy for secondary glaucoma is medical
management or transscleral cyclophotocoagulation.
MIGS, filtering, or shunting surgery should be
avoided to prevent tumor egress outside the eye.
Trabecular meshwork melanoma is often misdiag-
nosed [6], which can lead to inappropriate surgical
treatment that necessitates enucleation for tumor
control. Trabecular meshwork melanoma should be
ruled out prior to MIGS, filtering, or shunting sur-
gery, especially in refractory unilateral glaucoma.
dependent hyphema or pseudohypopyon. Metastasis
can also present as ill-defined iris thickening or iri-
docyclitis. Intraocular metastasis occurs in 4% of
patients with known metastatic cancer at time of
autopsy, with iris metastasis representing 9% of intra-
ocular metastasis [26,27]. In a recent large cohort
analysis of 1111 patients with uveal metastasis, iris
metastasis represented 8% of all cases [28]. Secondary
&&
glaucoma occurs in 37% of iris metastasis [7 ]. Mech-
anisms of secondary glaucoma include angle inva-
&&
sion (29%) and iris neovascularization (8%) [7 ].
Management options for iris metastasis include
plaque radiotherapy, external beam radiotherapy
&&
(EBRT), or systemic chemotherapy [7 ]. First-line
therapies for glaucoma control are medical manage-
ment, transscleral cyclophotocoagulation, or laser
trabeculoplasty. Anti-VEGF injections can be con-
& & &
sidered for neovascular glaucoma [29 ,30 ,31 ].
Refractory cases might require enucleation.

Iris metastasis Iris lymphoma

Iris metastasis appears as single or multiple yellow, Iris lymphoma is a localized or diffuse infiltration of
white, or pink nodules in the iris stroma, often with the uveal tract by neoplastic lymphoma cells, which

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Glaucoma

FIGURE 2. Iris tapioca melanoma with secondary glaucoma Enlarging tapioca iris melanoma (a) with elevated intraocular
pressure (IOP) secondary to angle infiltration of the tumor (b) with tumor adherence to corneal endothelium on anterior
segment optical coherence tomography (c). Following plaque radiotherapy, the tumor regressed and IOP decreased on topical
medications (d). IOP, intraocular pressure.

can simulate diffuse iris melanoma, metastasis, or
uveitis. Intraocular lymphoma can also present as
uveitis–glaucoma–hyphema syndrome or neovas-
&
cular glaucoma complicated by hyphema [32 ,33].
Histopathologically proven ocular involvement has
been found in 7% of patients with systemic lym-
phoma at time of death [26]. Secondary glaucoma
occurs in 29% of cases [8]. Mechanisms of secondary
glaucoma include angle invasion, angle closure, and
&
hyphema [23,32 ].
Management options for iris lymphoma include
plaque radiotherapy, EBRT, or systemic chemother-
apy. First-line therapies for glaucoma control are
medical management, transscleral cyclophotocoa-
gulation, or laser trabeculoplasty. Refractory cases
may require enucleation.
Ciliary body melanoma (ring melanoma)
Ring melanoma of the ciliary body is a rare variant of
uveal melanoma that extends circumferentially,
involving the entire ciliary body and occasionally
the iris, often hidden from ophthalmoscopic exami-
nation. Prominent episcleral sentinel vessels, multi-
lobular mass, shadow on transillumination, and
ultrasonographic hollowness with intrinsic vascular
pulsations can be diagnostic clues [9]. Secondary
glaucoma occurs in 35% of cases [9]. The mechanisms
of secondary glaucoma include angle invasion, seed-
ing into the angle (pigment dispersion), angle clo-
&&
sure, and iris neovascularization [9,25 ,34–37].
Management options for the tumor include pla-
&&
que radiotherapy or enucleation [9,25 ]. First-line
therapies for glaucoma control are medical manage-
ment, transscleral cyclophotocoagulation to un-
involved ciliary body, or laser trabeculoplasty to
uninvolved angle. Refractory cases can require enu-
cleation. Ring melanoma is occasionally misdiag-
nosed as uveal effusion [9], which can lead to
inappropriate filtering or shunting surgery, necessi-
tating subsequent enucleation for tumor control
&&
[25 ]. Ring melanoma should be considered in
the differential diagnosis of unilateral or refractory
glaucoma and ruled out prior to MIGS, filtering, or
shunting surgery.
Choroidal melanoma
Choroidal melanoma is a malignant tumor that
appears as a sessile, dome-shaped, or mushroom-
shaped pigmented mass located deep to the sensory
retina, often with associated subretinal fluid, orange

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 Glaucoma secondary to intraocular tumors Camp et al.

FIGURE 3. Trabecular meshwork melanoma with secondary glaucoma Unilateral glaucoma secondary to trabecular meshwork
melanoma with sub-Tenon’s extrascleral extension (a) and massive angle infiltration (b). Plaque radiotherapy led to tumor
regression and decreased intraocular pressure with medical management (c). Gonioscopy confirmed regressed trabecular
meshwork melanoma (d). IOP, intraocular pressure.

pigment, and exudative retinal detachment. Uveal
melanoma has an incidence of 5.1 cases per million,
with choroidal melanoma representing 90% of all
cases [18,19]. Secondary glaucoma occurs in 2%
of cases [1]. Mechanisms of secondary glaucoma
include angle invasion (<1%), angle closure
(<1%), iris neovascularization (1%), hyphema
(<1%), and suprachoroidal hemorrhage (<1%) [1].
Management options for choroidal melanoma
include plaque radiotherapy, local resection, or enu-
cleation. First-line therapies for glaucoma control
are medical management, transscleral cyclophoto-
coagulation, or laser trabeculoplasty. If there is no
tumor in the anterior segment or ciliary body, MIGS,
filtering, or shunting surgery can be considered after
complete tumor control is achieved. Refractory
cases may require enucleation.
Choroidal metastasis
Choroidal metastasis appears as one or more cream-
colored or yellow lesions in one or both eyes.
Exceptions include metastatic melanoma, which
appears brown or gray, and metastatic carcinoid,
thyroid cancer, and renal cell carcinoma, which
appear orange in color. Choroidal metastasis is often
associated with serous retinal detachment. Intraoc-
ular metastasis occurs in 4% of patients with known
metastatic cancer at time of autopsy, with choroidal
metastasis representing 88% of intraocular metasta-
sis [26,27]. In a comprehensive analysis on 1111
patient with uveal metastasis, choroidal metastasis
represented 90%. The leading malignancies to
spread to the eye include breast (37%), lung
(27%), kidney (4%), gastrointestinal tract (4%),
cutaneous melanoma (2%), lung carcinoid (2%),
prostate (2%), thyroid (1%), and pancreas (1%)
[28]. Secondary glaucoma occurs in 1% of cases
[1]. Mechanisms of secondary glaucoma include
angle closure and iris neovascularization [1,23].
Management options for choroidal metastasis
include plaque radiotherapy, photodynamic ther-
apy, EBRT, systemic chemotherapy, or enucleation.
First-line therapies for glaucoma control are medical

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Glaucoma
management, transscleral cyclophotocoagulation,
or laser trabeculoplasty. If there is no tumor in
the anterior segment or ciliary body, MIGS, filtering,
or shunting surgery can be considered after com-
plete tumor control is achieved. Refractory cases
may require enucleation.
Choroidal lymphoma
Choroidal lymphoma can appear as multifocal
creamy yellow patches, a solitary amelanotic mass,
or diffuse choroidal thickening [38]. Choroidal lym-
phoma can occur in isolation (69%) or can be asso-
ciated with systemic lymphoma (31%) [38].
Secondary glaucoma is rare. Mechanisms of second-
ary glaucoma include angle invasion and angle clo-
sure [23].
Management options for choroidal lymphoma
include plaque radiotherapy, EBRT, systemic che-
motherapy, or enucleation [38]. First-line therapies
for glaucoma control are medical management,
transscleral cyclophotocoagulation, or laser trabe-
culoplasty. Refractory cases can require enucleation.
In some cases, secondary glaucoma can resolve after
radiotherapy of the tumor.
Choroidal hemangioma (circumscribed)
Circumscribed choroidal hemangioma is a rare
benign vascular tumor that appears as a discrete,
round, orange-red lesion, often surrounded by a
lightly pigmented rim. Secondary glaucoma occurs
in 1% of cases [10]. Mechanisms of secondary glau-
coma include angle closure (<1%) and iris neovascu-
larization (<1%) from total retinal detachment [10].
Management options for circumscribed choroidal
hemangioma include photodynamic therapy or plaque
radiotherapy. Therapies for glaucoma control include
medical management, transscleral cyclophotocoagula-
tion, laser trabeculoplasty, MIGS, filtering, or shunting
surgery. In some cases, radiotherapy for the primary
tumor can completely resolve iris neovascularization
before neovascular glaucoma occurs [39].
Choroidal hemangioma (diffuse)
Diffuse choroidal hemangioma is a rare benign vas-
cular tumor that appears as diffuse choroidal thick-
ening and gives the impression of a ‘tomato-catsup’
fundus. This variant of choroidal hemangioma is
associated with Sturge–Weber syndrome, occurring
in approximately 55% of cases [40]. The mechanism
of glaucoma in Sturge–Weber syndrome is usually
unrelated to choroidal hemangioma and includes
developmental anomaly of the anterior chamber or
elevated episcleral venous pressure. Rarely, secondary
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glaucoma is related to diffuse choroidal hemangioma
with total retinal detachment as a result of iris neo-
vascularization [41].
Management options for diffuse choroidal
hemangioma include plaque radiotherapy, photo-
dynamic therapy, or EBRT [42]. Therapies for glau-
coma control are medical management, transscleral
cyclophotocoagulation, laser trabeculoplasty, MIGS,
filtering, or shunting surgery.
RETINAL TUMORS
Retinal tumors that can produce secondary glaucoma
include retinoblastoma and retinal astrocytic hamar-
toma.
Retinoblastoma
Retinoblastoma is a malignant tumor that appears
as a white, elevated lesion in the sensory retina with
prominent afferent and efferent blood vessels and
intratumoral calcification. Retinoblastoma is the
most common malignant intraocular tumor of
childhood with an estimated incidence of 1 in
16 000– 18 000 live births [43]. Secondary glau-
coma occurs in 17% of cases [1]. Mechanisms of
secondary glaucoma include angle seeding (<1%),
angle closure (5%), and iris neovascularization
(12%) [1].
Management options for retinoblastoma
include chemotherapy, plaque radiotherapy, or
enucleation. First-line therapies for glaucoma con-
trol are medical management, transscleral cyclo-
photocoagulation, or laser trabeculoplasty. Anti-
VEGF injections can be considered for neovascular
glaucoma after tumor control is achieved. Refrac-
tory cases can require enucleation. MIGS, filtering,
or shunting surgery should be avoided to prevent
tumor egress outside the eye. In some cases, second-
ary glaucoma is prevented or resolves after chemo-
therapy [2,44].
Retinal astrocytic hamartoma/astrocytoma
Retinal astrocytic hamartoma (astrocytoma) is a
benign tumor that appears as a sessile or slightly
elevated transparent or white lesion in the nerve
fiber layer of the retina, which can become calcified
over time. Larger lesions have a gray color and can
cause retinal traction. Retinal astrocytic hamartoma
is associated with tuberous sclerosis complex, occur-
ring in approximately 44% of cases [45]. In rare
cases, aggressive growth of an astrocytic hamartoma
can cause secondary retinal detachment [46]. Sec-
ondary glaucoma can occur as a result of iris neo-
vascularization, though this is rare.
Volume 30  Number 2  March 2019
 Glaucoma secondary to intraocular tumors Camp et al.

Management options for retinal astrocytic Medulloepithelioma

hamartoma include observation, photodynamic
therapy, plaque radiotherapy, sirolimus [47], ever-
olimus [48], EBRT, or enucleation. First-line thera-
pies for glaucoma control are medical management,
transscleral cyclophotocoagulation, or laser trabe-
culoplasty. Anti-VEGF injections can be considered
for neovascular glaucoma. In refractory cases, MIGS,
filtering, or shunting surgery can be used, with rare
cases requiring enucleation [46].
NONPIGMENTED CILIARY EPITHELIAL
TUMORS
Nonpigmented ciliary epithelial tumors that can
produce secondary glaucoma include medulloepi-
thelioma.
Medulloepithelioma appears as a pink-to-tan ciliary
body mass, often with intralesional cysts, that can
extend into the anterior chamber. The tumor can be
benign or malignant and classified as nonteratoid or
teratoid. Secondary glaucoma is common with
this tumor and occurs in 44–46% of cases [11,12].
Mechanisms of secondary glaucoma include angle
invasion, angle closure, and, most often, iris neo-
vascularization (Fig. 4) [11].
Management options for medulloepithelioma
include plaque radiotherapy, enucleation, and
rarely resection. First-line therapies for glaucoma
control are medical management, transscleral cyclo-
photocoagulation, or laser trabeculoplasty. Anti-
VEGF injections can be considered for neovascular
glaucoma. Refractory cases can require enucleation

FIGURE 4. Medulloepithelioma with secondary glaucoma Medulloepithelioma (a) with anterior subcapsular cataract, diffuse iris
neovascularization confirmed on fluorescein angiography (b), and ciliary body mass on ultrasonography (c). Intraocular pressure
decreased following plaque radiotherapy, leading to enucleation. Histopathology confirmed partially regressed
medulloepithelioma (M) with iris neovascular membrane, angle occluded by peripheral anterior synechiae (arrow), and a
prominent mass of vascular connective tissue surrounding the lens () [stain, hematoxylin-eosin; original magnification 10] (d).

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Glaucoma
[11,12,23]. MIGS, filtering, or shunting surgery
should be avoided to prevent tumor egress outside
the eye. Medulloepithelioma is occasionally mis-
diagnosed, which can lead to inappropriate surgical
treatment that necessitates subsequent enucleation
&&
for tumor control [25 ,49,50]. Medulloepithelioma
should be considered in the differential diagnosis
of unilateral or refractory glaucoma, especially in
children, and ruled out prior to MIGS, filtering, or
shunting surgery.
CONCLUSION
Intraocular tumors can cause secondary glaucoma.
Common mechanisms include solid tumor invasion
into the angle, tumor seeding into the angle (pig-
ment dispersion), angle closure, and iris neovascu-
larization. Depending on tumor type and location,
secondary glaucoma can be treated with medical
management, transscleral cyclophotocoagulation,
laser trabeculoplasty, anti-VEGF injections, MIGS,
filtering, or shunting surgery, or enucleation. MIGS,
filtering, or shunting surgery should be avoided
in eyes with active malignant tumors to prevent
extraocular tumor extension. Intraocular tumors
should be considered in the differential diagnosis
of secondary glaucoma, especially in unilateral or
refractory cases.
Acknowledgements
None.
Financial support and sponsorship
C.L.S. was supported by Eye Tumor Research Founda-
tion, Philadelphia, PA, USA. The funders had no role in
the design and conduct of the study, in the collection,
analysis, and interpretation of the data, and in the
preparation, review, or approval of the article. C.L.S.
has had full access to all the data in the study and takes
full responsibility for the integrity of the data and the
accuracy of the data analysis.
Conflicts of interest
There are no conflicts of interest.
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