REVIEW

CURRENT
OPINION New classification system for pediatric glaucoma:
implications for clinical care and a
research registry
Avrey Thau a,b, Maureen Lloyd a,b, Sharon Freedman c, Allen Beck d
Alana Grajewski e, and Alex V. Levin a,b

Purpose of review
The Childhood Glaucoma Research Network (CGRN) has created a new classification system for childhood
glaucoma that has become the first International Consensus Classification. The purpose of this review is to
present this classification system and share its use to date.
Recent Findings
Downloaded from http://journals.lww.com/co-ophthalmology by BhDMf5ePHKbH4TTImqenVBhf5K8zlU/3JBfuSrQYdzJhvw8ZAY+JHg5h/obHCS06 on 08/23/2018

The diagnoses of the classification system include glaucoma and glaucoma suspect. The primary
glaucomas include: primary congenital glaucoma and juvenile open-angle glaucoma. The secondary
glaucomas include: glaucoma following cataract surgery, glaucoma associated with nonacquired systemic
disease or syndrome, glaucoma associated with nonacquired ocular anomalies, and glaucoma associated
with acquired conditions. This system reached consensus agreement at the Ninth World Glaucoma
Association Consensus, which has been adopted by the American Board of Ophthalmology, and has been
implemented in outcomes research, incidence studies, and review articles. The new Robison D. Harley, MD
CGRN International Pediatric Glaucoma Registry uses this classification system as a shared language,
allowing international clinicians and researchers to collaborate and make large-scale investigations of this
otherwise rare disease possible.
Summary
The diagnoses in this system are assigned by following a logical and systematically approachable path.
The ability to easily adopt and implement the system lends itself to international research.
Keywords
childhood glaucoma, international, international classification, pediatric glaucoma, research

INTRODUCTION for international research, in particular in the con-

Childhood glaucoma is a varied group of disorders
that each requires careful attention and understand-
ing to prevent a lifetime of vision loss. Standard of
care, collaboration, and dissemination of new
advancements benefit from a unified classification
system that is easy to use, unambiguous, and appli-
cable worldwide. Terms formerly used to describe
childhood glaucoma including ‘developmental’,
‘congenital’, or ‘infantile’ were often unclear. The
result was an array of classification systems with
mixed acceptance across the globe [1–3]. The Child-
hood Glaucoma Research Network (CGRN) pro-
posed a novel classification system that reached
consensus agreement at the Ninth World Glaucoma
&&
Association Consensus [4 ] and was later adopted
by the American Board of Ophthalmology [5]. Here
we present the CGRN classification of childhood
glaucomas, review its use to date, and its application
text of the new Robinson Harley, M.D. CGRN Inter-
national Pediatric Glaucoma Registry. This registry
is a joint effort with contribution by sites across the
world to leverage large amounts of clinical data on
a
Sidney Kimmel Medical College at Thomas Jefferson University,
b
Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital,
Philadelphia, Pennsylvania, cDepartment of Ophthalmology, Duke Uni-
versity Medical Center, Durham, North Carolina, dDepartment of Oph-
thalmology, Emory University School of Medicine, Atlanta, Georgia and
e
Department of Ophthalmology, Bascom Palmer Eye Institute, University
of Miami, Miami, Florida, USA
Correspondence to Alex V. Levin, MD, MHSc Chief, Pediatric Ophthal-
mology and Ocular Genetics Wills Eye Hospital, Suite 1210, 840 Walnut
Street, Philadelphia, PA 19107-5109, USA. Tel: +215 928 3418;
e-mail: ALevin@willseye.org
Curr Opin Ophthalmol 2018, 29:385–394
DOI:10.1097/ICU.0000000000000516

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Pediatrics and strabismus

difficult to apply in clinical practice as glaucoma-

KEY POINTS
 The CGRN classification system for childhood
glaucoma was designed to unify nomenclature in
pediatric glaucoma.
 The diagnoses of the classification system are
glaucoma suspect, primary glaucoma including juvenile
open-angle glaucoma and primary congenital
glaucoma, and secondary glaucoma including
glaucoma following cataract surgery, glaucoma
associated with nonacquired systemic disease or
syndrome, glaucoma associated with nonacquired
ocular anomalies, and glaucoma associated with
acquired conditions.
 The ability to assign diagnoses systematically allows
new users to easily adopt the CGRN classification
system, which has found its place in international
research through the new Robison D. Harley, MD
CGRN International Pediatric Glaucoma Registry.
this otherwise rare group of disorders in order to
serve as a collaborative platform for research.
tous changes are varied and can be caused by mul-
tiple mechanisms, the recognition of which directly
influences management and treatment. The CGRN
classification system also recognizes that in some
children, the diagnosis of glaucoma may be sus-
pected but not proven. Factors which are used to
make the diagnosis include elevated IOP, visual
field defects, changes in the size of the eye, corneal
changes, and optic nerve changes (Table 1). In order
to facilitate the use of this classification system, a
flowchart has been developed to systematically
&&
arrive at the correct classification [4 ]. This flow-
chart is shown in Fig. 1. Users begin at the upper
left-hand corner of this chart and answer a series of
conditions and questions (yes/no) to arrive at a
classification. The classification refers to each
eye individually. For example, if each eye has a
cataract as part of a nonacquired ocular anomaly,
but the glaucoma occurs after cataract surgery in
one eye and before cataract surgery in the other eye,
then the categorization would be different for
each eye.

GLAUCOMA FOLLOWING CATARACT

THE CHILDHOOD GLAUCOMA RESEARCH
NETWORK CLASSIFICATION SYSTEM
Essential to the understanding and management of
childhood glaucoma is its definition. In its most
simple form, childhood glaucoma describes ocular
damage related to elevated intraocular pressure
(IOP). Although this definition has much in com-
mon across all types of pediatric glaucoma, it is
SURGERY (TABLE 2)
Glaucoma that develops after a cataract (or clear
lens extraction) surgery is classified as glaucoma
following cataract surgery. All cataract types are
included. Glaucoma that exists prior to cataract
removal is given a different classification. The glau-
coma may be subcategorized by gonioscopy find-
ings into open angle (50% open) or angle closure

Table 1. CGRN Definitions

Childhood: based on national criteria, <18 years old (USA); 16 years old (UK, Europe, UNICEF)
Childhood glaucoma: two or more of the following are required
 Intraocular pressure: >21 mmHg (investigator discretion on method of measurement and if EUA data alone is sufficient).
 Visual fields: reproducible visual field defect that is consistent with glaucomatous optic neuropathy with no other observable reason for the
visual field defect.
 Axial length: progressive myopia or myopic shift with increased ocular dimensions that outpace normal growth.
 Cornea: findings including Haab striae, corneal diameter >11 mm in newborns, >12 mm in children younger than 1 year old, and
>13 mm in children older than 1 year old.
 Optic nerve: progressive increase in cup-disc ratio, cup-disc asymmetry of 0.2 when optic discs are of similar size, and focal rim
thinning.
Childhood glaucoma suspect: at least one of the following is required
 Intraocular pressure: >21 mmHg on two separate occasions
 Visual fields: suspicious visual field defect for glaucoma
 Axial length: increased axial length in the setting of normal IOP
 Cornea: increased corneal diameter in the setting of normal IOP
 Optic nerve: suspicious optic disc appearance for glaucoma

CGRN, Childhood Glaucoma Research Network; EUA, Examination Under Anesthesia.

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 Classification of childho od glaucoma Thau et al.

FIGURE 1. The Childhood Glaucoma Research Network Classification System Flowchart. AL, axial length; c/d, cup to disk
ratio; VF, visual field.

glaucoma (<50% open or acute angle closure). Cat-
aracts may occur along with other anomalies, such
as aniridia, which have an independent risk for
glaucoma even if there was not a cataract present.
If the glaucoma develops after cataract surgery,
having not been present before the surgery, then
the classification of glaucoma following cataract
surgery supersedes an attribution to the ocular
anomalies. In young children, buphthalmos and
Haab stria, as well as other features usually associ-
ated with primary congenital glaucoma, may be
seen. The classification remains as glaucoma follow-
ing cataract surgery.

GLAUCOMA ASSOCIATED WITH

Table 2. Glaucoma following cataract surgery
 The CGRN definition of childhood glaucoma is met only after
cataract surgery is performed.
 Supersedes conflicting classifications.
 Includes all cataract etiologies:
1. Congenital idiopathic cataract
2. Congenital cataract associated with systemic syndrome or
ocular anomalies
3. Acquired cataract
 Categorized by gonioscopy findings:
1. Open-angle glaucoma ( 50% open)
2. Angle-closure glaucoma (<50% open or acute angle closure)
CGRN, Childhood Glaucoma Research Network.
NONACQUIRED SYSTEMIC DISEASE OR
SYNDROME (TABLE 3)
If the patient has not had cataract surgery, even if
the patients does have a cataract, glaucoma is then
classified by the presence of any relevant systemic or
ocular nonacquired condition (present at birth). If
the disorder is predominantly systemic with or with-
out ocular manifestations, the glaucoma is classified
as glaucoma associated with nonacquired systemic
disease or syndrome. Examples are presented in
Table 3. Note that this classification is used regard-
less of the mechanism of the glaucoma (e.g.,
increased episcleral venous pressure in Sturge–
Weber syndrome, deposition in trabecular mesh-
work in mucopolysaccharidoses, progressive angle

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Pediatrics and strabismus

Table 3. Glaucoma associated with nonacquired systemic GLAUCOMA ASSOCIATED WITH

disease or syndrome NONACQUIRED OCULAR ANOMALIES
 The CGRN definition of childhood glaucoma is met. When glaucoma develops without antecedent cata-
 Condition of predominately systemic disease/syndrome present at ract surgery, in the setting of a nonacquired condi-
birth. tion that is predominately ocular, it is classified as
 Ocular signs may or may not be present. glaucoma associated with nonacquired ocular
Examples of glaucoma associated with nonacquired systemic anomalies. Examples are presented in Table 4. This
disease or syndrome includes conditions that may or may not have sys-
 Chromosomal disorders temic findings, such as Axenfeld–Rieger spectrum or
* Trisomy 21 Peters anomaly. There is no further subcategoriza-
 Connective tissue disorders
tion with regards to glaucoma pathophysiology.
Should the nonacquired ocular anomaly also
* Marfan syndrome
involve cataract, this classification is used provided
* Weill–Marchesani syndrome
that the onset of glaucoma occurs before cataract
* Stickler syndrome
surgery.
 Metabolic disorders
* Homocystinuria
* Lowe syndrome GLAUCOMA ASSOCIATED WITH
* Mucopolysaccharidoses ACQUIRED CONDITIONS
 Phacomatoses Glaucoma that develops due to a condition that is
* Neurofibromatosis not present at birth is classified as glaucoma associ-
* Sturge–Weber syndrome ated with acquired conditions. It is further catego-
 Rubinstein–Taybi
rized by gonioscopy findings as open-angle (50%
open) or angle-closure (<50% open or acute angle
 Congenital rubella
closure) glaucoma. Although this classification
CGRN, Childhood Glaucoma Research Network; Adapted from the World includes glaucoma due to iatrogenic causes, such
Glaucoma Association Consensus Series-9: Childhood Glaucoma4. as steroids and surgery, glaucoma following cataract
surgery is given a separate classification to empha-
size its uniqueness and prevalence. Nonacquired
closure in Weill–Marchesani syndrome). Although conditions that may result in glaucoma through
congenital rubella is an infection acquired by the an acquired mechanism, but due to a congenital
mother, associated abnormalities are present at anomaly, such as closed angle glaucoma due to
birth and thus it is included in this category. unoperated persistent fetal vasculature or micro-
spherophakia, maintain their classification as asso-
ciated with a nonacquired condition. Examples of
Table 4. Glaucoma associated with nonacquired ocular common acquired conditions associated with glau-
anomalies coma are listed in Table 5.
 The CGRN definition of childhood glaucoma is met.
 Condition of predominately ocular anomaly present at birth. PRIMARY CONGENITAL GLAUCOMA
 Systemic signs may or may not be present. Glaucoma that develops in the absence of any
Examples of glaucoma associated with nonacquired ocular acquired or nonacquired conditions, with buphthal-
anomalies mos, is defined as primary congenital glaucoma
 Aniridia (PCG). PCG is further classified as neonatal onset
 Axenfeld–Rieger spectrum (0–1 month), infantile onset (>1–24 months), and
 Congenital ectropion uveae late onset (>24 months). This is outlined in Table 6.
 Iris hypoplasia This disorder is a primary goniodysgenesis and often
 Microphthalmia has distinctive angle anomalies with patches of high
 Oculodermal melanocystosis iris insertion. These mild anomalies would not allow
 Peters anomaly for classification as glaucoma associated with non-
 Persistent fetal vasculature (before cataract surgery)
acquired ocular anomalies, which covers more rep-
resentative anterior segment disorders. Although
 Posterior polymophous dystrophy
the flow sheet requires buphthalmos for this classi-
 Ectopia lentis
fication, it is conceivable that young children with
CGRN, Childhood Glaucoma Research Network; Adapted from the World characteristic angle anomalies and glaucoma, could
Glaucoma Association Consensus Series-9: Childhood Glaucoma4. be placed in this category without buphthalmos

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Table 5. Glaucoma associated with acquired conditions
 The CGRN definition of childhood glaucoma is met.
 Acquired conditions are those that are not present at birth but
later develop (unless they develop over time due to a condition
present at birth).
 Categorized by gonioscopy findings:
1. Open-angle glaucoma ( 50% open)
2. Angle-closure glaucoma (<50% open or acute angle closure)
Examples of glaucoma associated with acquired conditions
 Postsurgical (not including cataract surgery)
 Retinopathy of prematurity
 Steroid induced
 Trauma
 Tumors
 Uveitis
CGRN, Childhood Glaucoma Research Network; Adapted from the World
Glaucoma Association Consensus Series-9: Childhood Glaucoma4.
through early detection. Common signs of PCG,
such as buphthalmos and Haab striae, may be seen
with a normal appearing optic disc, no corneal
edema and normal IOP. These cases are classified
as spontaneously arrested PCG.
Some disorders, such as Sturge–Weber, can have
early infantile onset glaucoma that is otherwise
identical to PCG of infantile onset with buphthal-
mos. The context of the glaucoma (i.e., the presence
of a nonacquired systemic syndrome) defines the
classification. This case would be defined as glau-
coma associated with nonacquired systemic disease
or syndrome.
Table 6. Primary congenital glaucoma and juvenile open-
angle glaucoma
Juvenile open-angle glaucoma
 The CGRN definition of childhood glaucoma is met.
 No ocular enlargement
 Normal appearing angle (open angle)
Primary congenital glaucoma
 The CGRN definition of childhood glaucoma is met.
 Ocular enlargement is usually seen (buphthalmos)
 Isolated angle anomalies (with or without mild congenital iris
anomalies)
 Subcategories based on age of onset
1. Neonatal onset (0–1 month)
2. Infantile onset (>1–24 months)
3. Late onset (>24 months)
 Signs present with normal IOP and no progressive optic nerve
changes: spontaneously arrested PCG
CGRN, Childhood Glaucoma Research Network.
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Classification of childho od glaucoma Thau et al.
JUVENILE OPEN-ANGLE GLAUCOMA
Glaucoma that develops in isolation from any
acquired or nonacquired conditions, without ocular
enlargement, and with a normal appearing angle is
classified as juvenile open-angle glaucoma (JOAG).
In general, the earliest age of onset is considered as
4 years and may extend to 30 or 40 years, after which
the glaucoma would be classified as adult onset
primary open angle glaucoma. JOAG is typically
an autosomal dominant disorder characterized by
variable penetrance and expressivity.
THE CGRN CLASSIFICATION SYSTEM IN
USE
Since consensus agreement was reached at Ninth
World Glaucoma Association Consensus in 2013
&&
[4 ], the CGRN classification system has seen use
in clinical and research realms. The ability to reli-
ably implement this classification system in a wide
variety of patients was demonstrated by Hoguet
et al. in 2016 [6]. They reviewed the clinic charts
of children who had met the CGRN definition of
glaucoma or glaucoma suspect and reassigned
them a diagnosis according to the CGRN classifica-
tion system. This process distilled 26 different
diagnoses into the seven CGRN classifications.
The authors felt the system was easy to apply,
assignments were clear-cut with no overlap in cate-
gories, and that new assignments became more
descriptive of glaucoma cause. Other studies have
applied the CGRN classification for outcomes
research [7–9], incidence studies [10], and review
articles [11].
THE ROBISON D. HARLEY, MD CGRN
INTERNATIONAL PEDIATRIC GLAUCOMA
REGISTRY
The Robison D. Harley, MD CGRN International
Pediatric Glaucoma Registry aims to surmount a
challenge common to the study of rare disorders:
small study sizes. This registry acts as a centralized
database that houses clinical data populated by sites
across the globe for the purposes of making large-
scale investigations possible. The international
scope is achieved through a shared dialect, the
CGRN classification system. This project is the first
of its kind and has the potential for significant
advancement in the care and research of childhood
glaucoma. It is funded through the generosity of the
Robison D. Harley, M.D. Fund of the Wills Eye
Alumni Society. While Wills Eye Hospital acts as
the host, an Advisory Board with diverse represen-
tation provides governance. Invitae (San Francisco,
www.co-ophthalmology.com 389
Pediatrics and strabismus

FIGURE 2. Sample of Registry demographic data fields.

California) maintains the registry. Invitae is a glaucoma specialist, an Invitae representative, a

genetic information company that maintains a genetic counselor, and a bioethicist.
number of registries in its Patient Insights Net- The registry is currently active with representa-
workTM program. The Advisory Board is comprised tion from six continents across the globe. Any oph-
of international CGRN members, a lay member, a thalmic practice, clinic, hospital, institution, or

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 Classification of childho od glaucoma Thau et al.

FIGURE 3. Sample of Registry cataract history data fields.

individual involved in the care of children with
glaucoma may participate. The registry is securely
hosted with an online portal, allowing user access
from anywhere in the world. To protect the data in
this open platform, interested users must first have
approval from their local Ethics Board, Ethics Com-
mittee, Institutional Review Board, or equivalent
before access is granted. Compliant with the require-
ments of the United States Health Insurance Porta-
bility and Privacy Act, the data is maintained as

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Pediatrics and strabismus

FIGURE 4. Sample of Registry gonioscopy data fields.

de-identified. As participating members rely on the The areas contained in the registry address all
registry data for research purposes, any clinical aspects of childhood glaucoma including demo-
data entered becomes a permanent part of the graphics (Fig. 2), cause (Fig. 3), diagnosis (Fig. 4),
registry. and management (Fig. 5). There are two arms to the

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 Classification of childho od glaucoma Thau et al.

FIGURE 5. Sample of Registry medication follow-up data fields.

data entry, retrospective and prospective. This will
allow for longitudinal studies in the areas of epide-
miology, natural history, and treatment outcomes.
To expedite the process of entering data, the online
portal guides users by prompting data entry fields
that are only relevant to the assigned glaucoma
classification. For example, if a subject is given a
diagnosis of JOAG they will not be prompted to
enter any information related to a nonacquired
condition.

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Pediatrics and strabismus
Any participating member may use the registry
data to develop their own research. To use the
registry data for this purpose a participant must have
entered a minimum of ten patients and submit an
Ethics Board (or equivalent) approved research pro-
tocol to the Advisory Board.
The registry is linked to the Wills Eye-Thomas
Jefferson University Ocular Genetic Disease DNA
Bank. Users may deposit glaucoma-related DNA
(as whole blood or extracted DNA) that may then
be accessed by any registrant participant. DNA is
linked to the registry information by de-identified
coding. Once a registrant has contributed ten DNA
specimens, they have access to the entire Bank. This
DNA bank has a separate Advisory Board.
An interested individual may join the Robison
D. Harley, MD CGRN International Pediatric Glau-
coma Registry by contacting a representative from
Wills Eye Hospital (alevin@willseye.org).
CONCLUSION
The CGRN classification system for childhood
glaucoma has been developed to unify the nomen-
clature through a logical and systematically-
approachable path. This system reached consensus
agreement at the Ninth World Glaucoma Associa-
tion Consensus, and has been adopted by the Amer-
ican Board of Ophthalmology, and implemented in
outcomes research, incidence studies, and review
articles. The ability to easily adopt and implement
the system lends itself to research. The new Robison
D. Harley, MD CGRN International Pediatric Glau-
coma Registry uses this classification system as a
shared language that allows international clinicians
and researchers to collaborate and make large-
scale investigations of this otherwise rare disease
possible.
Acknowledgements
The authors acknowledge the contributions of Drs. Maria
Papadopoulos, Ta Chen Peter Chang, and Elizabeth
Hodapp who also served on the CGRN Classification
Committee.
394 www.co-ophthalmology.com
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Financial support and sponsorship
Funded in part by the Foerderer Fund (A.V.L.), the
Robison D. Harley, MD Endowed Chair in Pediatric
Ophthalmology and Ocular Genetics (A.V.L.), and the
Joseph F. Bradway Endowed Research Fellow (A.T.). The
Robison D. Harley, MD Fund of the Wills Eye Alumni
Society, along with Brandon’s Eye Research Fund and the
Albert Meadow Eye Foundation have supported the Rob-
inson Harley, MD CGRN International Pediatric Glau-
coma Registry.
Conflicts of interest
S.F., A.B., A.G, and AVL are members of the CGRN. No
financial support for this project was provided by the
CGRN.
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READING
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& of special interest
&& of outstanding interest
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