CLINICAL SCIENCES

Clinical Classification of Childhood Glaucomas

Helen H. Yeung, MD; David S. Walton, MD

Objective: An updated classification of the primary and
secondary childhood glaucomas is offered for clinical use,
and associated systemic diseases are included to enable their
early recognition in children with known glaucoma.
Methods: Approximately 650 clinical records of pa-
tients with pediatric glaucoma were reviewed for type of
glaucoma and associated systemic disease. A literature
search was done for additional reported causes of child-
hood glaucoma. Previous classifications of pediatric glau-
comas were also reviewed. Pertinent references to sup-
port inclusion of each clinical entity in the updated
classification are included.
Results: A comprehensive and referenced classifica-
tion of the pediatric glaucomas was enabled by this
review.
Conclusion: A comprehensive, etiologically based
classification of the pediatric glaucomas is now
available to assist with the recognition of the many
causes of primary and secondary glaucoma in child-
hood and to support the selection of specific treatment
choices.
Arch Ophthalmol. 2010;128(6):680-684

Author Affiliations:
Department of Pediatrics,
Massachusetts General Hospital
(Dr Yeung), and Department of
Ophthalmology, Massachusetts
Eye and Ear Infirmary
(Dr Walton), Harvard Medical
School, Boston, Massachusetts.
T
HE CHILDHOOD GLAUCO -
mas have been classified by
the age of onset, inherit-
ance, associated systemic
findings, and anatomy, ac-
cording to the associated and responsible
anterior segment anomalies.1,2 In this ar-
ticle, we offer a comprehensive classifica-
tion of the childhood glaucomas to assist
in the recognition and differential diag-
nosis of the reported clinically recogniz-
able causes of primary and secondary pe-
diatric glaucomas (Table).
TERMINOLOGY
Historically, the childhood glaucomas have
been labeled developmental glaucomas
based on the associated presence of de-
velopmental defects of the eye.1 Primary
childhood glaucomas will be classified as
those caused by anomalies of the filtra-
tion angle. These glaucomas are often of
genetic origin and may be associated with
systemic diseases and other ocular de-
fects. We have identified the systemic dis-
eases that have been described in associa-
tion with childhood glaucoma.
Congenital glaucoma denotes a glau-
coma that occurs early in life related to a
congenital anomaly. Newborn primary con-
genital glaucoma defines a glaucoma en-
tity that is recognized immediately at birth
with the presence of profound defects of the
anterior segment. Infantile primary congen-
ital glaucoma includes patients with evi-
dence of glaucoma most often recognized
in the first year of life. Late recognized pri-
mary congenital glaucoma indicates an en-
tity diagnosed significantly after an age
when ophthalmologic examination of the
patient would have recognized the presence
of abnormalities related to glaucoma.
Juvenile glaucoma has been used to de-
scribe glaucoma in childhood. We have
continued its use specifically with juve-
nile open-angle glaucoma that characteris-
tically develops during childhood.
The secondary childhood glaucomas are
those that occur as the result of indepen-
dent disease mechanisms that second-
arily impair the function of the filtration
angle.
COMMENT
All classifications of the childhood glau-
comas have revealed the impressive num-
ber of clinical entities that may feature or
be complicated by childhood glaucoma.
Previously these diseases have been vari-
ably identified and classified.2 The term as-
sociation in reference to glaucoma with sys-
temic diseases does not require that the
glaucoma is an essential aspect of the dis-
ease. In our classification, we list these

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 Table. Childhood Glaucomas Table. Childhood Glaucomas (continued)

Primary (Developmental) Glaucomas Secondary (Acquired) Glaucomas

Primary congenital glaucoma3,4 Traumatic glaucoma
Newborn primary congenital glaucoma Acute glaucoma
Infantile primary congenital glaucoma Hyphema89,90
Late-recognized primary congenital glaucoma Ghost cell glaucoma91-93
Juvenile open-angle glaucoma5 Glaucoma related to angle recession94-96
Primary angle-closure glaucoma6,7 Arteriovenous fistula97,98
Primary glaucomas associated with systemic diseases Glaucoma with intraocular neoplasms
Sturge-Weber syndrome8 Retinoblastoma99,100
Neurofibromatosis (NF-1)9-11 Juvenile xanthogranuloma101,102
Stickler syndrome12 Leukemia103,104
Oculocerebrorenal syndrome (Lowe a)13 Melanoma of ciliary body105,106
Rieger syndrome14,15 Melanocytoma107
SHORT syndrome16 Iris rhabdomyosarcoma108
Hepatocerebrorenal syndrome (Zellweger a)17-19 Aggressive iris nevi109
Marfan syndrome20 Medulloepithelioma99,110,111
Rubinstein-Taybi syndrome21-23 Mucogenic glaucoma with iris stromal cyst112
Infantile glaucoma with retardation and paralysis24 Glaucoma related to chronic uveitis
Oculodentodigital dysplasia25,26 Open-angle glaucoma113-115
Glaucoma with microcornea and absent sinuses27
Angle-blockage mechanisms
Mucopolysaccharidosis28,29
Synechial angle closure116
Trisomy 1330
Iris bombe with pupillary block117
Caudal regression syndrome31
Trisomy 21 (Down syndrome)32,33 Trabecular Meshwork Endothelialization118
Cutis marmorata telangiectatica congenita34,35 Lens-related glaucoma
Walker-Warburg syndrome36,37 Subluxation-dislocation with pupillary block
Kniest syndrome (skeletal dysplasia)38-40 Marfan syndrome20,119,120
Michels syndrome41 Homocystinuria121-123
Nonprogressive hemiatrophy42 Weill-Marchesani syndrome124,125
PHACE syndrome43,44 Axial-subluxation high myopia syndrome126
Soto syndrome45 Ectopia lentis et pupillae127
Linear scleroderma46
Spherophakia128,129
GAPO syndrome47,48
Phacolytic glaucoma130
Roberts pseudothalidomide syndrome49
Glaucoma following lensectomy for congenital cataracts
Wolf-Hirschhorn syndrome50
Pupillary-block glaucoma131
Robinow syndrome51, b
Infantile aphakic open-angle glaucoma132,133
Nail-Patella syndrome52,53
Glaucoma related to corticosteroids134,135
Proteus syndrome54
Glaucoma secondary to rubeosis
Fetal hydantoin syndrome55
Retinoblastoma136,137
Cranio-cerebello-cardiac syndrome56,57
Brachmann-deLange syndrome58 Coats disease138
Rothmund-Thomson syndrome59,60 Medulloepithelioma139,140
9p Deletion syndrome61,62 Familial exudative vitreoretinopathy141
Phakomatosis pigmentovascularis63,64 Subacute/chronic retinal detachment142
Nevoid basal cell carcinoma syndrome (Gorlin syndrome)65, c Retinopathy of prematurity143
Epidermal Nevus syndrome (Solomon syndrome)66 Angle-closure glaucoma
Androgen insensitivity, pyloric stenosis67 Retinopathy of prematurity144-146
Diabetes mellitus, polycystic kidneys, hepatic fibrosis, Microphthalmos b
hypothyroidism68 Nanophthalmos147-149
Diamond-Blackfan syndrome69 Retinoblastoma100,150
Primary glaucomas with profound ocular anomalies Persistent hyperplastic primary vitreous151
Aniridia70,71 Congenital pupillary iris-lens membrane152,153
Congenital aniridic glaucoma Topiramate therapy154,155
Acquired aniridic glaucoma Central retinal vein occlusion156
Congenital ocular melanosis72,73 Ciliary body cysts157,158
Sclerocornea74 Malignant glaucoma159
Congenital iris ectropion syndrome75,76 Glaucoma associated with increased venous pressure
Peters syndrome77 Sturge-Weber syndrome160-162
Iridotrabecular dysgenesis (iris hypoplasia)78,79 Intraocular infection related glaucoma
Posterior polymorphous dystrophy80,81 Acute recurrent toxoplasmosis163,164
Idiopathic or familial elevated venous pressure82 Acute herpetic iritis165
Congenital anterior (corneal) staphyloma83,84 Maternal rubella infection166,167
Congenital microcoria85,86 Endogenous endophthalmitis168
Congenital hereditary endothelial dystrophy87,88 Glaucoma secondary to unknown etiology
Axenfeld-Rieger anomaly14,15 Iridocorneal endothelial syndrome169,170

(continued) Abbreviations: GAPO, growth retardation, alopecia, pseudoanodontia, and

entities together; however, the strength of the glaucoma
relationship might be different. Glaucoma may be coin-
cidental or strongly genetically related to the systemic
disease. In the future, additional clinical experience and
genetic testing may establish the relative importance of
these relationships.
optic atrophy; PHACE, posterior fossa abnormalities and
other structural brain abnormalities, hemangioma(s) of the cervical facial
region, arterial cerebrovascular anomalies, cardiac defects,
aortic coarctation and other aortic abnormalities, and eye anomalies; SHORT,
short stature, hyperextensibility of joints and/or inguinal
hernia, ocular depression, Rieger anomaly, and teething delay.
a Indicates physician who first identified the disease.
b Walton DS, written communication, January 1, 2009.
c Kane SA, written communication, February 5, 2008.

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 The use of this classification as a clinical aid can fa-
cilitate early recognition of glaucoma and identification
of the specific glaucoma diagnosis as well as meaning-
fully influence the choice of treatment. Without recog-
nition of specific types of childhood glaucoma, it is more
difficult for the clinician to appropriately select treat-
ment that has been found to be most beneficial. The sec-
ondary glaucomas are an important and large group of
childhood glaucomas. When confronted with a child with
glaucoma and atypical clinical findings, the clinician may
be assisted in making an accurate etiologic diagnosis by
reviewing the tabulated causes of both the primary and
secondary glaucomas. Finally, this childhood glaucoma
classification can enable improved communication be-
tween those who care for these particular patients.
Submitted for Publication: August 21, 2009; final revi-
sion received August 21, 2009; accepted November 12,
2009.
Correspondence: David S. Walton, MD, 2 Longfellow
Place, Ste 201, Boston, MA 02114 (walton.blackeye
@gmail.com).
Author Contributions: The authors had full access to all
of the data in the study and take responsibility for the
integrity of the data and the accuracy of the analysis and
presentation.
Financial Disclosure: None reported.
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 tified in this clinical situation. Justification for a random-
ized clinical trial usually includes the following8: (1) evidence
of a significant public health problem, (2) a scientifically
plausible intervention, (3) preliminary information that war-
rants the trial, and (4) the ability to enroll a significant num-
ber of patients, with an outcome obtained within a reason-
able time frame. Regarding the criteria above, we believe a
randomized clinical trial is not justifiable because (1) while
intravitreal injections are common, endophthalmitis fol-
lowing injections may not be, (2) the intervention has not
previously been proven to be scientifically plausible, (3) there
is not sufficient preliminary information from endophthal-
mitis rates following this intervention or even other inter-
ventions such as those that occur during cataract surgery
(and risks of endophthalmitis following cataract surgery
would not be expected to be the same as risks following an
intravitreal injection of a drug using a 30 gauge needle),
and (4) enrollment for between 1.5 million and 15 million
injections, depending on outcome assumptions, could take
so many years that the antibiotic and intravitreal proce-
dure being tested may no longer be relevant.
We agree that it is important to determine the risk of en-
dophthalmitis after an intravitreal drug injection when topi-
cal antibiotics are not required either before, during, or af-
ter the injection because there is little scientific rationale to
support topical antibiotic use in this situation. As Drs Zi-
emssen and Bartz-Schmidt state, omitting its use would avoid
the cost, potential toxicity, and burden to patients follow-
ing millions of intravitreal injections each year. To address
this situation in the absence of randomized clinical trials,
which may not be justified, we hope to continue to provide
information that is of potential value related to the millions
of intravitreal injections currently provided around the world
for common retinal conditions.
Abdhish R. Bhavsar, MD
Cynthia R. Stockdale, MSPH
Neil M. Bressler, MD
for the Diabetic Retinopathy Clinical Research Network
Author Affiliations: Retina Center of Minnesota, Min-
neapolis (Dr Bhavasar); Jaeb Center for Health Re-
search, Tampa, Florida (Ms Stockdale); and Wilmer Eye
Institute, Johns Hopkins University School of Medi-
cine, Baltimore, Maryland (Dr Bressler).
Correspondence: Ms Stockdale, Jaeb Center for Health
Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647
(drcrstat3@jaeb.org).
Group Information: A published list of the Diabetic Reti-
nopathy Clinical Research (DRCR) Network investiga-
tors and staff who participated in this protocol can be
found in Ophthalmology. 2008;115(9):1447-1449, with
a current list available at www.drcr.net.
Financial Disclosure: A complete list of all DRCR Net-
work investigator financial disclosures can be found at
www.drcr.net.
Funding/Support: This study was supported by a coop-
erative agreement from the National Eye Institute and the
National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health, and grants
EY14231, EY14229, and EY018817 from the US Depart-
ment of Health and Human Services. Allergan Inc pro-
(REPRINTED) ARCH OPHTHALMOL / VOL 128 (NO. 9), SEP 2010
1224
©2010 American Medical Association. All rights reserved.
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vided the triamcinolone, and Genentech Inc provided the
ranibizumab. Both companies provided funds for part of
the clinical care costs of the DRCR Network laser-
ranibizumab-triamcinolone protocols. Allergan, Inc also
has provided unrestricted funds to DRCR Network for
its discretionary use. As per the DRCR Network Indus-
try Collaboration Guidelines (www.drcr.net), the DRCR
Network had complete control over the design of the pro-
tocol, ownership of the data, and all editorial content of
presentations and publications related to the protocol.
Role of the Sponsors: The funding organization partici-
pated in oversight of the conduct of the study and re-
view of the manuscript but not directly in the design of
the study, the conduct of the study, data collection, data
management, data analysis, interpretation of the data, or
preparation of the manuscript.
Trial Registration: clinicaltrials.gov Identifier:
NCT00444600 and NCT00445003
1. Bhavsar AR, Googe JM Jr, Stockdale CR, et al; Diabetic Retinopathy Clinical
Research Network. Risk of endophthalmitis after intravitreal drug injection
when topical antibiotics are not required: the diabetic retinopathy clinical re-
search network laser-ranibizumab-triamcinolone clinical trials. Arch Ophthalmol.
2009;127(12):1581-1583.
2. Hariprasad SM, Blinder KJ, Shah GK, et al. Penetration pharmacokinetics of
topically administered 0.5% moxifloxacin ophthalmic solution in human aque-
ous and vitreous. Arch Ophthalmol. 2005;123(1):39-44.
3. Puustjärvi T, Teräsvirta M, Nurmenniemi P, Lokkila J, Uusitalo H. Penetra-
tion of topically applied levofloxacin 0.5% and ofloxacin 0.3% into the vit-
reous of the non-inflamed human eye. Graefes Arch Clin Exp Ophthalmol. 2006;
244(12):1633-1637.
4. Sakamoto H, Sakamoto M, Hata Y, Kubota T, Ishibashi T. Aqueous and vit-
reous penetration of levofloxacin after topical and/or oral administration. Eur
J Ophthalmol. 2007;17(3):372-376.
5. Bhavsar AR, Ip MS, Glassman AR; DRCRnet and the SCORE Study Groups.
The risk of endophthalmitis following intravitreal triamcinolone injection in the
DRCRnet and SCORE clinical trials. Am J Ophthalmol. 2007;144(3):454-456.
6. Fintak DR, Shah GK, Blinder KJ, et al. Incidence of endophthalmitis related
to intravitreal injection of bevacizumab and ranibizumab. Retina. 2008;28
(10):1395-1399.
7. Mason JO III, White MF, Feist RM, et al. Incidence of acute onset endoph-
thalmitis following intravitreal bevacizumab (Avastin) injection. Retina. 2008;
28(4):564-567.
8. Bressler NM. Submacular surgery: are randomized trials necessary? Arch
Ophthalmol. 1995;113(12):1557-1560.
Corneal Thickness Changes
in Very-High-Altitude Mountaineers
B osch and colleagues1 performed a very nice study
of corneal thickness at high altitude. However,
some statements may benefit from clarification.
Specifically, “Besides AMS [acute mountain sickness], cor-
neal changes during high-altitude climbs may also be a
dangerous hazard owing to a potential significant de-
crease in visual acuity. The often-quoted experience of
Dr Beck Weathers, a Mount Everest climber who had un-
dergone radial keratotomy prior to ascent and incurred
severe vision loss during the climb, is such an ex-
ample.” The authors correctly imply that corneal thick-
ening plays a major role in radial keratotomy visual
changes at high altitude. However, the mechanism of these
changes is a bit more complicated and warrants a more
precise explanation.
It is well known that any cornea thickens with expo-
sure to hypoxia.2,3 However, when the normal corneal
architecture is weakened by radial incisions, the hy-
WWW.ARCHOPHTHALMOL.COM
 poxic cornea remains clear but the incisions may allow
swelling to occur in an anterior direction. This anterior
elevation in the midperiphery causes central corneal flat-
tening and a resultant hyperopic shift.2,3 Thus, alter-
ations in corneal structure caused by radial keratotomy
incisions, combined with increased corneal thickness, ac-
count for the induced refractive changes. Although plus
lenses were required for clear vision, a climber with bi-
lateral radial keratotomy successfully ascended Mount
Everest (8 850 m).4 Similarly, owing to structural change
from flap creation, corneas that receive Lasik and are ex-
posed to hypoxia are thought to have a preferential cen-
tral expansion, causing a slight myopic shift.5 This con-
trasts with normal and photorefractive keratectomy
corneas that do not undergo refractive change with hy-
poxia because they thicken uniformly, thus preserving
the shape of the anterior corneal surface.
Thomas H. Mader, MD
Lawrence J. White, MD
Author Affiliations: Alaska Native Medical Center, An-
chorage, Alaska (Dr Mader); and Cascade Eye and Skin
Centers, Puyallup, Washington (Dr White).
Correspondence: Dr Mader, Department of Ophthal-
mology, Alaska Native Medical Center, Anchorage, AK
99508 (thmader@anthc.org).
Financial Disclosure: None reported.
1. Bosch MM, Barthelmes D, Merz TM, et al. New insights into changes in cor-
neal thickness in healthy mountaineers during a very-high-altitude climb to
Mount Muztagh Ata. Arch Ophthalmol. 2010;128(2):184-189.
2. Mader TH, Blanton CL, Gilbert BN, et al. Refractive changes during 72-hour
exposure to high altitude after refractive surgery. Ophthalmology. 1996;103
(8):1188-1195.
3. Winkle RK, Mader TH, Parmley VC, White LJ, Polse KA. The etiology of re-
fractive changes at high altitude after radial keratotomy: hypoxia versus
hypobaria. Ophthalmology. 1998;105(2):282-286.
4. Mader TH, White LJ, Johnson DS, Barth FC. The ascent of Mount Everest fol-
lowing radial keratotomy. Wilderness Environ Med. 2002;13(1):53-54.
5. Nelson ML, Brady S, Mader TH, White LJ, Parmley VC, Winkle RK. Refrac-
tive changes caused by hypoxia after laser in situ keratomileusis surgery.
Ophthalmology. 2001;108(3):542-544.
In reply
We welcome the comments regarding our article1 from Drs
Mader and White, who have published several articles on
refractive changes induced by hypoxia in subjects after re-
fractive surgery. We value their additional account of the
mechanism of the corneal changes in Dr Beck Weathers’
eyes during his climb on Mount Everest that led to severe
vision loss. This is an interesting amendment to our manu-
script, which focuses primarily on mountaineers with
healthy corneas.
Martina M. Bosch, MD
Daniel Barthelmes, MD
Pascal Knecht, MD
Konrad E. Bloch, MD
Urs Hefti, MD
Klara Landau, MD
Author Affiliations: Department of Ophthalmology, Uni-
versity Hospital Zurich, Zurich (Drs Bosch, Barthelmes,
and Landau); and the Department of Surgery, Cantonal
Hospital, Liestal (Dr Hefti), Switzerland.
Correspondence: Dr Bosch, Department of Ophthalmol-
ogy, University Hospital Zurich, Frauenklinikstrasse 24,
CH-8091 Zurich, Switzerland (martina.boesch@usz.ch).
Financial Disclosure: None reported.
1. Bosch MM, Barthelmes D, Merz TM, et al. New insights into changes in cor-
neal thickness in healthy mountaineers during a very-high-altitude climb to
Mount Muztagh Ata. Arch Ophthalmol. 2010;128(2):184-189.

Correction

Error in Table. In the Clinical Sciences article titled

“Clinical Classification of Childhood Glaucomas” by
Yeung and Walton, published in the June issue of the
Archives (2010;128[6]:680-684), the Table was format-
ted incorrectly. In the right column, the subheading
“Trabecular Meshwork Endothelialization” should not
have been a subheading. It should be aligned below
“Iris bombe with pupillary block” under “Angle-block-
age mechanisms,” and there should have been no line
above it. The only two column subheadings should
have been “Primary (Developmental) Glaucomas” and
“Secondary (Acquired) Glaucomas.”

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