G
GA
▶ Atrophy, Geographic
Gardner Syndrome: Retinal Pigment
Epithelium Hypertrophy
Jonathan Schell
STL Vision, Saint Louis, MO, USA
Synonyms
Familial adenomatous polyposis
Definition
Variant of familial adenomatous polyposis char-
acterized by pigmented fundus ocular lesions,
adenomatous polyposis of the small and large
intestines, and other various neoplasms, includ-
ing osteomas, fibromas, and desmoid tumors
(Buettner 2006; Gass 1997; Humayun and
Traboulsi 1999).
Etiology
Autosomal dominantly inherited mutation in the
APC gene (tumor suppressor gene) located on the
# Springer-Verlag GmbH Germany 2018
U. Schmidt-Erfurth, T. Kohnen (eds.), Encyclopedia of Ophthalmology,
https://doi.org/10.1007/978-3-540-69000-9
long arm of chromosome 5 (5q21) (Online
Mendelian Inheritance of Man).
Clinical Presentation
Although over 80% of patients with Gardner
syndrome have pigmented fundus lesions,
the majority of patients are visually
asymptomatic. Their pigmented fundus lesions
are identified most often either during general
routine ophthalmoscopy or during ophthalmic
screening for familial adenomatous polyposis.
Ophthalmoscopically, the pigmented fundus
lesions of Gardner syndrome are flat, ovoid, var-
iably pigmented subretinal lesions with a hypo-
pigmented halo or depigmented tail. They can be
differentiated from typical congenital hypertro-
phy of the retinal pigment epithelium (CHRPE)
in the normal population by their smaller, more
ovoid or pisciform, more variegated, multiple,
and bilateral appearance. Histologically, the
pigmented fundus lesions of Gardner syndrome
are adenomas or hamartomas of retinal pigment
epithelium since they can demonstrate multiple
layers of abnormal hypertrophic retinal pigment
epithelium cells. Occasionally, the abnormal
hypertrophic cells of the pigmented fundus
lesions occupy the full thickness of the retina
(Fig. 1).
Patients with Gardner syndrome typically
develop polyps in their small and large intestinal
during their third decade of life. If left untreated,
802
Gardner Syndrome: Retinal Pigment Epithelium
Hypertrophy, Fig. 1 Color fundus photograph demon-
strating pigmented fundus lesion characteristic for Gardner
syndrome (From: Singh AD, Damato BE, Pe’er J,
Murphree L, Perry JD (eds) (2007) Clinical Ophthalmic
Oncology. Elsevier, Philadelphia. With permission)
the gastrointestinal polyps can progress to adeno-
carcinoma by the fifth decade of life.
Diagnostics
Pigmented fundus lesions of Gardner syndrome
are best detected with a dilated fundus exam and
scleral depression. Any abnormal pigmentation
of the fundus should be documented with
fundus photography. Lesions demonstrating
thickness should be measured using ocular
echography. If four or more lesions characteristic
for the pigmented fundus lesions of Gardner syn-
drome are seen in one or both eyes, the patient
should receive genetic studies looking for
the APC mutation. Diagnosis of Gardner syn-
drome is confirmed by documenting adenoma-
tous polyposis of the small and large intestine
during either esophagogastroduodenoscopy or
colonoscopy.
Gardner Syndrome: Retinal Pigment Epithelium Hypertrophy
Differential Diagnosis
Differential diagnosis of pigmented fundus
lesions of Gardner syndrome includes isolated
congenital hypertrophy of retinal pigment epithe-
lium, choroidal nevus, choroidal melanoma, cho-
roidal melanocytoma, hyperplasia of retinal
pigment epithelium, and dark subretinal blood.
Prophylaxis
Although no prophylaxis against Gardner syn-
drome is currently available, routine fundus
examination can be helpful for detecting Gardner
syndrome in asymptomatic individuals. Routine
dilated fundus examination with scleral depres-
sion is recommended for all patients with a family
history of familial adenomatous polyposis.
Therapy
Management of pigmented fundus lesions in
Gardner syndrome is observation. Treatment of
intestinal polyps and adenocarcinoma is deter-
mined under the care of a gastroenterologist.
Prognosis
Visual prognosis of Gardner syndrome is excellent,
as the pigmented fundus lesions of the retinal pig-
ment epithelium are typically asymptomatic. Sur-
vival prognosis of Gardner syndrome is determined
by the intestinal manifestations of the disease.
Epidemiology
Unclear
Cross-References
▶ Choroidal and/or Ciliary Body and/or Iris
Melanoma
Gasserian Ganglion (Semilunar/Trigeminal Ganglion)
▶ Congenital Hypertrophy of Retinal Pigment
Epithelium
▶ Pigmented Lesions of the Conjunctiva
▶ Retinal Pigment Epithelium
▶ Uveitis, Iridocyclitis
References
Buettner H (2006) Congenital hypertrophy of the retinal
pigment epithelium. In: Ryan SJ (ed) Retina, 4th edn.
Elsevier, Philadelphia, pp 667–672
Gass JD (1997) Stereoscopic atlas of macular diseases
diagnosis and treatment, 4th edn. Mosby, St. Louis,
pp 814–815
Humayun M, Traboulsi EI (1999) Congenital hypertrophy
of the retinal pigment epithelium. In: Guyer DR,
Yanuzzi LA, Chang S, Shields JA, Green WR (eds)
Retina-vitreous-macula, 2nd edn. W.B. Saunders, Phil-
adelphia, pp 1058–1066
Online Mendelian Inheritance of Man (OMIM). www.
nslij-genetics.org/search_omim.html
Gas Tamponade
▶ Intraocular Gases
Gass Disease
▶ Adult-Onset Foveomacular Vitelliform
Dystrophy
Gasserian Ganglion
▶ Gasserian Ganglion (Semilunar/Trigeminal
Ganglion)
▶ Trigeminal Ganglion (Gasserian/Semilunar
Ganglion)
803
Gasserian Ganglion (Semilunar/
Trigeminal Ganglion)
Andrew R. Davis4, Sumayya J. Almarzouqi1,
Michael L. Morgan1,7 and Andrew G. Lee1,2,3,5,6
1
Department of Ophthalmology, Blanton Eye
Institute, Houston Methodist Hospital, Houston,
TX, USA
2
Departments of Ophthalmology, Neurology, and
Neurosurgery, Weill Cornell Medical College,
Houston, TX, USA
3
Department of Ophthalmology, The University
of Texas Medical Branch, Galveston, TX, USA G
4
Department of Ophthalmology, College of
Medicine, Texas A&M University, College
Station, TX, USA
5
Department of Ophthalmology, Baylor College
of Medicine, Houston Methodist Hospital,
Houston, TX, USA
6
Department of Ophthalmology, The University of
Iowa Hospitals and Clinics, Iowa City, IA, USA
7
Department of Ophthalmology and Visual
Sciences, University Hospitals Eye Institute, Case
Western Reserve University School of Medicine,
Cleveland, Ohio, USA
Synonyms
Gasserian ganglion; Semilunar ganglion; Trigem-
inal ganglion
Definition
Afferent sensory fibers of the trigeminal nerve orig-
inate from cell bodies within the trigeminal gan-
glion. A fold of dura, named Meckel cave, houses
the sensory trigeminal ganglion also known as the
gasserian or semilunar ganglion. Two of the three
branches (V1 and V2) of the trigeminal nerve serve
solely as sensory nerves whereas the mandibular
division (V3) of the trigeminal nerve has both
motor and sensory fibers.The sensory root of CN
V exits the pons ventrally and fans out to form the
804 General: Astigmatism

trigeminal ganglion meanwhile the motor fibers of Definition

CN V remain separated. Three separate sensory
divisions then come off the trigeminal ganglion Geometrical optics is a method to describe light
and continue as the ophthalmic nerve (V1), maxil- propagation by definition of light rays which are
lary nerve (V2), and mandibular nerve (V3). perpendicular to wave fronts. A ray is a simpli-
fied model of the path of a wave or photon within
Cross-References an optical system which can be calculated by ray
tracing using the laws of refraction and reflec-
▶ V1 (Ophthalmic Nerve) tion. Ray tracing is sufficient for most calcula-
▶ V2 (Maxillary Nerve) tions in ophthalmology and basic optical
▶ V3 (Mandibular Nerve) aberration calculation. Most intraocular lens cal-
culation formulas are based on geometric optical
considerations.
Further Reading

Agarwal A, Athiya A (2009) Trigeminal nerve. In: Manual

of neuro-ophthalmology. McGraw-Hill, New York, Cross-References
pp 140–144
Wasman, SG (2010) The brainstem and cerebellum. In:
Clinical neuroanatomy, 26th edn. McGraw-Hill Medi-
▶ Law of Reflection: Definition
cal, New York, 2013, pp 79–98 ▶ Law of Refraction (Snell’s Law)
▶ Optical Aberrations
▶ Ray Tracing
General: Astigmatism

▶ Corneal Astigmatism
Gerontoxon
Geographic Atrophy ▶ Corneal Arcus

▶ Atrophy, Geographic

Ghost Cell Glaucoma

Geographic Corneal Dystrophy
Christoph Kniestedt1 and Marc Töteberg-Harms2
▶ Reis-Bücklers Dystrophy 1
TAZZ Talacker Augenzentrum Zurich, Zürich,
Switzerland
2
Department of Ophthalmology, University
Geometrical Optics Hospital Zurich, Zürich, Switzerland

Timo Eppig
Institute of Experimental Ophthalmology, Definition
Saarland University, Homburg, Germany
Degenerated red blood cells (ghost cells) cause
secondary open-angle glaucoma by blocking the
Synonyms outflow through the trabecular meshwork (Camp-
bell et al. 1976). After a vitreous hemorrhage, red
Ray optics blood cells degenerate (Campbell et al. 1976).
Giant Cell Arteritis 805

They lose their intracellular hemoglobin and Therapy

appear as small and tan-colored intraocular bodies
with some denatured clumped hemoglobin called
Heinz bodies (Campbell et al. 1976). The ghost
cells migrate into the anterior chamber through a
disrupted anterior hyaloid face. Ghost cells are
more rigid compared to normal red blood cells,
which is a major reason for obstruction of the
trabecular meshwork (Campbell et al. 1976;
Quigley and Addicks 1980).
Local antiglaucomatous therapy should be initi-
ated. Upon failure, irrigation of the anterior cham-
ber, vitrectomy, or trabeculectomy to control IOP
are treatment options, which can be discussed
with the patient.
Prognosis

Heinz bodies may be washed out over time and

Etiology ghost cell glaucoma may resolve.
G
A disruption in the anterior hyaloid membrane by
previous intraocular surgery (e.g., vitrectomy, cat- Epidemiology
aract surgery) or by trauma causes the pathway to
the anterior chamber. One to three months after a Ghost cell glaucoma is very rare.
vitreous hemorrhage, ghost cells appear in the
anterior chamber (Montenegro and Simmons
1995).
Cross-References

▶ Traumatic Glaucoma
Clinical Presentation

Intraocular pressure is elevated typically 1–3

months after a vitreous bleeding (Montenegro
and Simmons 1995).
Diagnosis
IOP is unilaterally elevated in the eye with previ-
ous vitreous hemorrhage. Circulating ghost cells
are visible in the anterior chamber. Signs
of inflammation like superficial conjunctival
injection or intraocular flare are absent.
Gonioscopically, ghost cells could be found
mainly in the inferior hemicircumference on the
trabecular meshwork. Old red blood cells may be
found in the vitreous.
References
Campbell DG, Simmons RJ, Grant WM (1976) Ghost cells
as a cause of glaucoma. Am J Ophthalmol
81(4):441–450
Montenegro MH, Simmons RJ (1995) Ghost cell glau-
coma. Int Ophthalmol Clin 35(1):111–115
Quigley HA, Addicks EM (1980) Chronic experimental
glaucoma in primates. Invest Ophthalmol Vis Sci
19(2):126–152
Ghost Image
▶ Monocular Diplopia

Differential Diagnosis
Giant Cell Arteritis
• Uveitis anterior
• Status post-hyphema ▶ Arteritic Ischemic Optic Neuropathy
806 Giant Papillary (Contact Lens-Induced) Conjunctivitis Disease
Giant Papillary (Contact Lens-
Induced) Conjunctivitis Disease
Sana Idrees
The George Washington University, Washington,
DC, USA
Synonyms
Contact lens-induced conjunctivitis
Definition
Giant papillary conjunctivitis (GPC) An inflam-
matory response of the superior tarsal conjunctiva
to the prolonged presence of a foreign body on the
ocular surface.
Etiology
The condition was first observed in contact lens
wearers. Ocular prostheses, exposed suture ends,
extruded scleral buckles, filtering blebs, corneal
foreign bodies, limbal dermoids, and tissue adhe-
sives have also been implicated (Ehlers and
Donshik 2008). The condition is most commonly
seen in contact lens wearers, particularly patients
who wear soft contact lenses (Manzouri
et al. 2006). It can occur with hydroxyethyl meth-
acrylate (HEMA) or silicone polymer hydrogel
contact lenses. However, it can also occur with
rigid contact lenses of either polymethyl meta-
crylate (PMMA) or gas-permeable polymers
(Ehlers and Donshik 2008).
The development of giant papillary conjuncti-
vitis is attributed to a combination of mechanical
irritation of the superior limbus and a hypersensi-
tivity reaction to material adherent to the contact
lenses, sutures, or ocular prostheses (Dunn and
Heidemann 2011). A study on Rhesus monkeys
demonstrated that coated contact lenses lead to
cellular infiltration of the conjunctiva with eosin-
ophils and plasma cells. This reaction was not
noted in virgin contact lenses or lenses from
non-GPC contact lens wearers. Additionally, the
tears of patients with active GPC have been found
to have elevated levels of immunoglobulin and
various cytokine levels. These findings suggest
that there may be an antigen on coated contact
lenses contributing to the immune reaction in GP-
C. The presence of neutrophil chemotactic factor
released from injured conjunctival cells supports
the theory that a mechanical cause may also be
involved (Ehlers and Donshik 2008). Minimizing
the build-up of lens deposits appears to reduce the
chance of developing mechanical and immuno-
logic stimuli for the condition. The frequency of
contact lens replacement is a significant variable
in the development of giant papillary conjunctivi-
tis. Individuals on a 1-day to 3-week replacement
cycle were less likely to develop this condition
than individuals on a longer replacement schedule
(Dunn and Heidemann 2011).
In some cases, giant papillary conjunctivitis
appears to be related to thimerosal exposure.
Lens care solutions used in most reported cases
contained thimerosal. However, only a minority
of patients exhibited reactions to thimerosal on
patch testing. The incidence of giant papillary
conjunctivitis is decreasing as most contact lens
solutions no longer contain thimerosal. Hypoxia
of the epithelium beneath the lens may be associ-
ated, which would be expected to be most signif-
icant beneath the superior lid (Arffa 1997).
Clinical Presentation
Giant papillary conjunctivitis may present as early
as 3 weeks to 8 months after the start of soft
contact lens use and 14 months to 8 years after
the start of hard contact lens use (Dunn and
Heidemann 2011). Classic symptoms of GPC
include decreased contact lens tolerance,
increased mucus production, and excessive con-
tact lens displacement, usually superiorly (Ehlers
and Donshik 2008). Early symptoms of giant pap-
illary conjunctivitis include inner canthus mucus
discharge in the morning and itching upon
removal of the contact lenses. During the early
stages of the disease, the conjunctiva may appear
normal. The symptoms become more marked as
Giant Papillary (Contact Lens-Induced) Conjunctivitis Disease
the disease progresses. The patient may begin to
experience a foreign body sensation, conjunctival
injection, photophobia, tearing, and crusting.
Blurry vision may also be a symptom of the dis-
ease secondary to mucus coating of the lens and
increased lens mobility and instability. During this
stage of the disease, the superior tarsal conjunc-
tiva becomes thickened and hyperemic. Small
papillae develop initially, which progress in size
and number over time to become giant papillae
(Manzouri et al. 2006).
The papillae of giant papillary conjunctivitis
are defined as greater than 0.3 mm in diameter.
Giant papillae are defined as being greater than
1.0 mm in diameter (Dunn and Heidemann 2011).
The distribution of the giant papillae varies
depending upon the type of lens worn. Soft con-
tact lens wearers develop papillae along the supe-
rior edge of the tarsal plate initially and progress
to involve the entire central area of the tarsal
conjunctiva. Hard contact lenses tend to be
smaller, and wearers of these lenses develop papil-
lae closer to the margin of the superior lid
(Manzouri et al. 2006). These papillae tend to be
fewer in number with a crater-like or flattened
appearance (Dunn and Heidemann 2011). Ocular
prostheses tend to cause a generalized papillary
reaction. Filtering blebs and exposed sutures
cause a more localized GPC, usually centered
around the bleb or exposed suture (Ehlers and
Donshik 2008). Subepithelial opacities are often
present, and a pannus may be noted beneath the
abnormal epithelium (Arffa 1997). The bulbar
conjunctiva and the inferior fornix usually appear
normal. In the advanced stages of the disease,
patients may become increasingly intolerant of
their contact lenses (Manzouri et al. 2006).
Diagnosis
A history of contact lens use with details of con-
tact lens age, type, and frequency of replacement
should be taken. For diagnosis, slit-lamp exami-
nation of the superior tarsal conjunctiva by ever-
sion of the upper lids reveals hyperemia and
injection of the upper tarsal conjunctiva, making
the vascular arcade difficult to discern.
807
Additionally, large papillae greater than 0.3 mm
can be visualized on the superior tarsal conjunc-
tiva (Ehlers and Donshik 2008). Fluorescein
staining of the superior corneal epithelium of the
papillae may be punctate, extending from the lim-
bus in a V pattern toward the visual axis (Arffa
1997).
Differential Diagnosis
Differential diagnosis includes vernal keratocon-
junctivitis. Contact lens history and patient age
may be helpful in distinguishing these conditions G
as vernal keratoconjunctivitis is uncommon after
the early twenties (Manzouri et al. 2006). Addi-
tionally, patients with vernal keratoconjunctivitis
frequently have a history of allergic rhinitis,
atopic dermatitis, and asthma (Dunn and
Heidemann 2011).
Prophylaxis
The development of giant papillary conjunctivitis
can be reduced by meticulous contact lens
hygiene, and frequent replacement of lenses to
minimize lens surface deposits (Dunn and
Heidemann 2011).
Therapy
The goal of therapy in giant papillary conjuncti-
vitis is resolution of the burning, itching, and
excess mucus production that characterize the
condition. Reduction or cessation of contact lens
use for 2–4 weeks is the primary treatment for
giant papillary conjunctivitis (Ehlers and Donshik
2008). After resolution of the signs and symptoms
of GPC, lens wear can be reinstituted by refitting,
switching to alternate better tolerated lenses, or
avoiding solutions containing thimerosal (Arffa
1997). Studies have shown that changing to a
different contact lens polymer allows over 80%
of GPC patients to continue contact lens wear
(Ehlers and Donshik 2008). For patients who
may be significantly handicapped by the
808
discontinuation of contact lens use, including
individuals with keratoconus or anisometropia,
modification of their contact lens care routine
and wear schedule may help to relieve many of
the symptoms of giant papillary conjunctivitis.
Because of the well-established relationship
between lens deposits and giant papillary con-
junctivitis, the use of daily disposable soft contact
lenses or frequent replacement contact lenses is
the best solution. Individuals for whom this may
be cost-prohibitive or who require specialty lenses
or rigid-gas permeable lenses should adopt a daily
lens care regime, including use of a surfactant
cleaner and “rub” routine. Disinfection of the
lenses with hydrogen peroxide is the least likely
method to further traumatize the conjunctiva
(Dunn and Heidemann 2011).
When discontinuation of contact lens wear and
refitting with frequent replacement contact lenses
is unsuccessful, the conjunctival inflammation
may be managed pharmacologically with the
goal of reducing histamine release and local
inflammation (Ehlers and Donshik 2008). Topical
mast cell stabilizers, such as cromolyn sodium,
have been shown to be effective in resolution of
early giant papillary conjunctivitis when com-
bined with lens hygiene. This class of medications
stabilizes the mast cell membrane and inhibits
type I hypersensitivity reactions. Cromolyn
sodium can be applied with continued contact
lens use. If the condition does not improve, dis-
continuation of contact lens wear may be neces-
sary with gradual reintroduction after resolution
of symptoms. Nonsteroidal anti-inflammatory
drugs (NSAIDs), such as suprofen, have been
shown to reduce papillae and symptoms associ-
ated with the condition. NSAIDs appear to work
by inhibiting mast-cell stimulated prostaglandin
biosynthesis. Treatment with topical corticoste-
roids can be beneficial in the acute phase of
giant papillary conjunctivitis to reduce tarsal
hyperemia and inflammation. The need for corti-
costeroids is an indication of severity of disease,
and contact lens use should be discontinued until
corticosteroids are no longer necessary (Dunn and
Heidemann 2011). If corneal epithelial changes
do not resolve with discontinuation of lens wear,
Giant Papillary (Contact Lens-Induced) Conjunctivitis Disease
surgical treatment options may be necessary. In
some cases, limbal or conjunctival autografts have
successfully restored the corneal surface (Arfa
1997).
Prognosis
If contact lens wear is discontinued, the prognosis
is good, and the disease may resolve within a few
weeks to several months. Early recognition and
treatment of the condition is important for ensur-
ing contact lens comfort and the individuals con-
tinued ability to wear contact lenses (Dunn and
Heidemann 2011). If left untreated, the disease
continues to progress. The epithelium thickens,
becomes grayer, and involves an increasingly
greater area of the conjunctiva. The pannus pro-
gresses centrally and vascularization of the deep
stroma may develop. Superficial stromal scarring
may also be present and recurrent ulceration can
occur (Arffa 1997).
Epidemiology
An estimated 1–5% of soft contact lens wearers
and 1% of hard contact lens wearers have clini-
cally significant signs and symptoms of giant pap-
illary conjunctivitis. The incidence of giant
papillary conjunctivitis is generally considered to
be higher amongst extended wear contact lens
users compared to daily wear soft lens wearers.
The syndrome can occur at any age and is seen
with equal frequency between males and females
(Dunn and Heidemann 2011).
Cross-References
▶ Vernal Conjunctivitis/Keratoconjunctivitis
References
Arffa RC (1997) Noninfectious causes of conjunctival
inflammation. In: Grayson’s diseases of the cornea,
4th edn. Elsevier, New York, pp 182–184
Glands of Krause, Glands of Moll, Glands of Wolfring, Glands of Zeis
Dunn SP, Heidemann DG (2011) Giant papillary
conjunctivitis. In: Cornea fundamentals, diagnosis,
and management, 3rd edn. Elsevier, New York,
pp 583–589
Ehlers WH, Donshik PC (2008) Giant papillary
conjunctivitis. Curr Opin Allergy Clin Immunol
8:445–449
Manzouri B, Flynn T, Ono SJ (2006) Allergic eye disease:
pathophysiology, clinical manifestations and treatment.
In: Cornea and external eye disease. Springer, New
York, p 217
Glands of Krause, Glands of Moll,
Glands of Wolfring, Glands of Zeis
1 2
Katherine G. Gold and Tara Uhler
1
Wills Eye Institute, Thomas Jefferson University,
Philadelphia, PA, USA
2
Department of Ophthalmology, Wills Eye
Institute, Thomas Jefferson University,
Philadelphia, PA, USA
Synonyms
Accessory lacrimal glands; Apocrine or sweat
glands of the eyelid; Sebaceous glands of the
eyelid
Definition
Glands of Krause
Exocrine and aqueous secreting accessory lacri-
mal glands located in the lamina propria of the
conjunctival fornices (superior > inferior).
Glands of Wolfring
Exocrine and aqueous secreting accessory lacri-
mal glands located above the superior border of
the upper lid tarsus.
Glands of Moll
Specialized apocrine sweat glands located at the
base of the lashes anterior to the Meibomian
glands.
809
Glands of Zeis
Modified sebaceous holocrine glands located at
the base of eyelash follicles.
Structure
Glands of Krause and Wolfring possess a histo-
logic structure similar to the lacrimal gland.
Glands of Moll are tubular, large apocrine
gland.
Glands of Zeis are unilobular sebaceous gland
units associated with follicles.
G
Function
The eyelid glands produce the tear film which
nourishes, lubricates, and protects the ocular
surface.
• Glands of Krause and Wolfring are responsible
for aqueous tear secretion.
• Glands of Moll and Zeis secrete part of the
lipid component of the tear film. Moll’s secre-
tions have been found to have bacteriolytic
properties as well and may play a role in local
immune defense.
Clinical Relevance
Abnormal functioning of any of the glands may
lead to dry eye conditions. Cysts and carcinomas
of these glands may occur.
• Glands of Krause and Wolfring are affected in
Sjogren syndrome and graft-versus-host
disease.
• Glands of Moll can develop ductal cysts,
including apocrine hidrocystomas (smooth
cysts arising from the glands of Moll); they
can also develop apocrine carcinoma.
• Glands of Zeis can develop an acute infection
of the sebaceous material within these glands
resulting in an external hordeolum; sebaceous
carcinoma may arise in these glands.
810
Cross-References
▶ Accessory Lacrimal Glands
▶ Dry Eye
▶ Graft-Versus-Host Disease: Overview
▶ Hidrocystoma, Apocrine
▶ Hordeolum
▶ Sebaceous Carcinoma
▶ Sweat Glands of Eyelid
▶ Tear Film (Tears)
Further Reading
Amato MM, Monheit B, Shore JW Chapter 72 eyelid
anatomy. In: Tasman W, Jaeger EA (eds) Duane’s oph-
thalmology on DVD-ROM 2011 edition. Lippincott
Williams & Wilkins
Eagle RC (2011) Eye pathology: an atlas and text, 2nd edn.
Lippincott, Williams & Wilkins, Philadelphia,
p 12, 236–248
Glare Testing
Jens Bühren
Department of Ophthalmology, Goethe-University
Frankfurt am Main, Frankfurt am Main, Germany
Synonyms
Disability glare testing
Definition
Methods of psychophysical quantification of the
effects of ▶ glare on visual function. In clinical
use, “glare testing” is synonymous with measuring
the effects of straylight-induced effects on visual
function. Typically, a ▶ contrast sensitivity test is
repeated after introducing glare by a defined glare
source. The difference between the measurement
without and with glare denotes the glare effect, also
referred to as glare sensitivity or disability glare.
There are multiple chart-based tests or view-in
Glare Testing
devices in use. The C-Quant™ (Oculus
Optikgeräte) is the most basic method for the psy-
chophysical quantification of straylight effects.
Questionnaires for the psychometric quantifi-
cation of glare-induced subjective disturbances
and devices for adaptometry also measure
glare effects but are generally not considered
glare tests.
Cross-References
▶ Glare, General
Glare, General
Jens Bühren
Department of Ophthalmology, Goethe-University
Frankfurt am Main, Frankfurt am Main, Germany
Synonyms
Disability glare
Definition
A subjective disturbance of vision induced by too
high luminances or luminance differences across
the visual field. A reduction of visual functions
due to glare is common (disability glare) but not a
necessary feature of glare.
Basic Characteristics
There are different types of glare: (1) adaptation
glare due to (momentary) mis-adaption to the
actual luminance, e.g., changing from a dark to a
brightly lit room after dark adaptation; (2) absolute
glare, if no adaptation is possible, e.g., glare by
sunlight; and (3) simultaneous glare, if lumi-
nances are distributed inequally within visual
field and straylight causes a contrast reduction
Globe, Displacement of, in Orbital Disorders
(veiling) of the retinal image. The latter form is the
clinically most important form of glare and often
meant if clinicians refer to “glare.” A glare source
of defined luminance and size acts at a certain
glare angle. The glare source can either be the
light source itself (e.g., the sun, headlights) or
objects that reflect the light of a light source
(e.g., a newspaper that reflects bright light).
Cross-References
▶ Glare Testing
Glaucoma Associated with Pigment
Dispersion Syndrome (PDS)
▶ Pigmentary Glaucoma
Glaucomatocyclitic Crisis
▶ Posner-Schlossman Syndrome
Globe, Displacement of, in Orbital
Disorders
Pete Setabutr1 and Joann Kang2
1
Department of Ophthalmology and Visual
Sciences, University of Illinois, Chicago, IL, USA
2
Illinois Eye and Ear Infirmary, University of
Illinois at Chicago, Chicago, IL, USA
Synonyms
Proptosis (for forward displacement of the globe)
Definition
Displacement of the globe from its normal ana-
tomical location due to various orbital processes.
811
Etiology and Occurrence
Globe displacement may result from a wide vari-
ety of neoplastic, inflammatory, infectious, trau-
matic, and vascular conditions. Any mass lesion
of the orbit may cause proptosis or displacement
of the eye including primary tumors such as
lacrimal epithelial tumors (pleomorphic ade-
noma, adenoid cystic carcinoma), mesenchymal
tumors (fibrous histiocytoma, rhabdomyosar-
coma), and neurogenic tumors (sphenoid wing
meningioma, optic nerve glioma, neurofibroma,
schwannoma). In addition, metastatic lesions,
representing 2–3% of all orbital tumors, are usu- G
ally characterized by a rapid onset of orbital
symptoms including globe displacement. The
most common primary sites of metastatic carci-
noma to the orbit are the breast, lung, prostate,
gastrointestinal tract, and kidney.
Lymphoproliferative diseases are uncommon
in the orbit and account for 5% of all orbital
mass lesions. Lymphoid lesions include
lymphoproliferative reactive and atypical diseases
and lymphomas. Malignant orbital lymphomas
are usually located in the anterior orbit and may
mold to the globe and adjacent structures.
Inflammatory diseases are the most common
orbital lesions which can cause globe displace-
ment. Most notably Graves’ disease, which
accounts for 50% of all orbital lesions, causes
exophthalmos or forward displacement of the
globe. Other inflammatory causes include idio-
pathic orbital inflammation (pseudotumor), myo-
sitis, and Wegener’s granulomatosis.
Other causes of globe displacement include
infectious processes (orbital cellulitis), trauma
(orbital fractures), and structural disorders
(dermoid cysts, mucoceles). In addition, vascular
lesions are an important cause of globe displacement
including capillary hemangioma, cavernous heman-
gioma, lymphangioma, and arteriovenous fistula.
Classification
The direction of globe displacement may carry
diagnostic significance and can be classified by
the following locations:
812 Glomangioma

• Inferior displacement: fibrous dysplasia, fron-

tal mucocele, lymphoma, neuroblastoma, neu- Glucocorticoids
rofibroma, schwannoma, subperiosteal
hematoma, thyroid orbitopathy ▶ Corticosteroids, Use in Ophthalmology
• Superior displacement: lacrimal sac tumors,
lymphoma, maxillary sinus tumors, metastatic
tumors
• Lateral displacement: ethmoid mucocele, lac- Glue
rimal sac tumors, metastatic tumors, nasopha-
ryngeal tumors, rhabdomyosarcoma ▶ Tissue Adhesives, Cyanoacrylate, for Anterior
• Medial displacement: lacrimal fossa tumors, Segment
sphenoid wing meningioma

Diagnostics
GM2 Gangliosidoses
A complete medical and ophthalmic history includ-
▶ Tay-Sachs Disease (GM2 Gangliosidosis Type I)
ing time course of the disease, past trauma, and
systemic illnesses should be elicited. A careful and
complete ophthalmic exam including external and
periorbital inspection for lid findings (edema, pto-
sis, retraction) and assessment for a palpable mass Goblet Cells, Mucin Tear Secretion by
should be completed. Hertel exophthalmometry
should be done to measure the degree of anterior Daniel Montenegro and Nadeem Fatteh
displacement, and motility should be assessed. Department of Ophthalmology, Kresge Eye
Imaging by computed tomography or magnetic Institute, Wayne State University, Detroit, MI,
resonance imaging is almost always indicated. USA

Cross-References Synonyms
▶ Accessory Lacrimal Glands Mucus-secreting cells
▶ Orbit, Inflammation of
▶ Proptosis
▶ Trauma, Lacrimal Sac and Nasolacrimal Duct Definition

Further Reading Cells recognized as a source of mucus for the tear-

Dutton J (2004) Orbital diseases. In: Yanoff M, Duker JS
(eds) Ophthalmology, 2nd edn. Mosby, Philadelphia,
pp 729–743
Karcioglu Z (2005) Diagnosis of orbital tumors. In:
Karcioglu Z (ed) Orbital tumors: diagnosis and treat-
ment. Springer, New York, pp 49–60
Glomangioma
▶ Vascular Tumors Disease of the Conjunctiva
film complex.
Structure
Conjunctival goblet cells appear in histological
sections as oval-shaped cells containing rich
amounts of intracytoplasmic mucus (Doughty
2012). Cytoplasmic staining is characteristically
periodic acid-Schiff (PAS) positive, reflecting the
high density of glycosylated glycoproteins within
these cells (Doughty 2012). Goblet cell location
Goldenhar Syndrome
varies depending on their degree of maturation
with more mature cells residing near the apical
surface of the conjunctival epithelium; the distri-
bution of goblet cells is related to differences in
exposure, with cell numbers being higher in
the superior and inferior bulbar conjunctiva
compared to the interpalpebral conjunctiva
(Doughty 2012).
Function
Goblet cells comprise the main source of mucus
secreted into the tear-film complex (Inatomi
et al. 1996; Doughty 2012; Gipson 2004). Mucus
secretion is influenced by environmental and auto-
nomic factors (Plugfelder 2011). A gel-forming
mucin, MUC5AC, secreted by conjunctival goblet
cells assists in the maintenance of a moist and
lubricated ocular surface (Inatomi et al. 1996).
Secreted mucins are negatively charged and move
freely over similarly negatively charged
membrane-associated mucins of the conjunctival
and corneal epithelium also known as glycocalyx
(Gipson 2004). It is believed that repellent forces
between these two mucin layers promote debris
removal from the surface epithelium, hence their
recognition as an integral component of the lacri-
mal function unit (Plugfelder 2011).
Clinical Relevance
Ocular surface diseases are associated with dry-
ing, increased deposition of keratin in the con-
junctival epithelium, reduced goblet cell density,
and reduced secretion of gel-forming mucins
(Plugfelder 2011; Doughty 2012). A broad
group of entities are associated with impaired
goblet cell function. These include tear-film dys-
function, Stevens-Johnson syndrome, and ocular
cicatricial pemphigoid (Sangwan and Tseng
2001).
Cross-References
▶ Tear Film (Tears)
813
References
Doughty MJ (2012) Goblet cells of the normal human
bulbar conjunctiva and their assessment by impression
cytology sampling. Ocul Surf 10:149–169
Gipson IK (2004) Distribution of mucins at the ocular
surface. Exp Eye Res 78:379–388
Inatomi T et al (1996) Expression of secretory mucin genes
by human conjunctival epithelia. Invest Ophthalmol
Vis Sci 37:1684–1692
Plugfelder SC (2011) Tear dysfunction and the cornea:
LXVII Edward Jackson memorial lecture. Am
J Ophthalmol 152:900–909
Sangwan VS, Tseng SCG (2001) New perspectives in
ocular surface disorders. An integrated approach for
diagnosis and management. Indian J Ophthalmol
49:153–168 G
Goldenhar Syndrome
Suzanne K. Jadico and Tara Uhler
Department of Ophthalmology, Wills Eye
Institute, Thomas Jefferson University,
Philadelphia, PA, USA
Synonyms
Facio-auriculo-vertebral spectrum; First and sec-
ond branchial arch syndrome; Oculo-auriculo-
vertebral spectrum
Definition
Congenital syndrome of the first and second bra-
chial arches that includes malformations of the
eyes, ears, mandible, and cervical spine.
Etiology
Because there has been no agreement on the min-
imal diagnostic criteria, Goldenhar syndrome may
be more appropriately termed oculo-auriculo-
vertebral spectrum (OAVS). This nomenclature
emphasizes the continuum of ocular, auricular,
and vertebral anomalies also referred to as
hemifacial microsomia, facio-auriculo-vertebral
814
syndrome, otomandibular dysostosis, Goldenhar
syndrome, or first and second branchial arch
anomalies.
In most cases, OAVS appears to occur sporad-
ically; however, family histories suggest an auto-
somal dominant or recessive inheritance in several
documented cases. Possible loci have been
suggested at 14q22 and 5p15.33-pter. Mutations
in the SALL1 gene at 16q12.1 can result in an
OAVS phenotype (Tasse et al. 2007). In addition,
some researchers suggest that this condition may
result from a somatic mutation or disruption dur-
ing embryogenesis which interferes with the
development of the first two brachial arches.
Also, there has been speculation of its association
with maternal diabetes and with thalidomide or
retinoic acid intake during pregnancy. The terato-
gen thalidomide appears to result in OAVS anom-
alies particularly when the drug is ingested during
weeks 6–8 of gestation (Gorlin et al. 1990).
Clinical Presentation
Patients with the OAV spectrum have unilateral or
bilateral hemifacial microsomia, including
decreased jaw and cheek growth, microtia, pre-
tragal skin tags or blind fistulas, hearing loss, and
facial weakness. Patients may also have vertebral,
neurologic, cardiovascular, and genitourinary
abnormalities, in addition to characteristic oph-
thalmic abnormalities (Alecksic et al. 1975).
Ocular manifestations include epibulbar
dermoid (78%), lipodermoid (47%), upper eyelid
coloboma (24%), Duane syndrome, and, less
commonly, corneal hypoesthesia, microcornea,
microphthalmia, anophthalmia, ocular coloboma,
iris atrophy, and anterior polar cataract. An absent,
abnormal, or ectopic caruncle may predict nasal
involvement and help to make a diagnosis
of OAVS (Spierer and Wygnanski-Jaffe 2011).
Epibulbar dermoids (Fig. 1) usually occur in
the inferotemporal quadrant, straddling the lim-
bus, and are covered by conjunctiva. They are
mixed tissue choristomas and can have hair shafts
protruding from the surface. They occur bilater-
ally in 25% of patients. These dermoids can cause
amblyopia either by direct obstruction of the
Goldenhar Syndrome
Goldenhar Syndrome, Fig. 1 Photograph of an
inferotemporal, limbal epibulbar dermoid (Courtesy of
Dr. Alex V. Levin, Wills Eye Institute)
visual axis or, more commonly, by anisometropic
amblyopia resulting from induced astigmatism
(Baum and Feingold 1973).
Lipodermoids are reported less frequently,
occurring either alone or in association with an
epibulbar dermoid. They are most commonly
located over the lateral rectus muscle or in the
superotemporal quadrant, do not invade the cor-
nea, and are often bilateral. They may infiltrate
extraocular muscles and restrict eye movement
(Baum and Feingold 1973).
Diagnostics
The minimum criteria for the clinical diagnosis of
OAVS are the presence of at least two of the
following: otic hypoplasia, hemifacial micro-
somia, lateral facial cleft, epibulbar dermoid
and/or upper eyelid coloboma, and vertebral
anomalies.
Differential Diagnosis
Treacher Collins-Franceschetti syndrome
Pierre Robin syndrome
Hemifacial microsomia
Cervico-oculo-acoustic syndrome
Townes-Brocks syndrome
Microtia-anotia syndrome
Aplasia cutis with epidermal dermoids
Gonococcal Conjunctivitis 815

Oculo-auriculo-frontonasal syndrome dysplasia-hemifacial microsomia (Goldenhar-Gorlin

Goltz syndrome syndrome). J Neurol Neurosurg Psychiatry 38:
1033–1035
Baum JL, Feingold MD (1973) Ocular aspects of
Goldenhar’s syndrome. Am J Ophthalmol 75(2):
Prophylaxis 250–256
Gorlin RJ, Cohen MM, Levin LS (1990) Syndromes of the
Prenatal ultrasound may identify facial and ocular head and neck. Oxford University Press, New York,
anomalies. pp 641–649, 707–708
Spierer A, Wygnanski-Jaffe (2011) The eye in skeletal
disorders. In: Tasman W, Jaeger EA (eds) Duane’s
ophthalmology on DVD-ROM, 2011 edn. Lippincott
Therapy Williams & Wilkins, Baltimore Maryland
Tasse A, Majewski F, Bohringer S et al (2007) A family
with autosomal dominant oculo-auriculo-vertebral
Amblyopia should be treated appropriately. Sur-
spectrum. Clin Dysmorphol 16:1–7
gical excision, usually via superficial keratec-
G
tomy, is indicated for epibulbar dermoid tumors
that exhibit continued growth, ocular irritation,
amblyopia unresponsive to glasses and occlusion,
or unacceptable cosmesis. Oculoplastic repair of
Gonococcal Conjunctivitis
upper eyelid colobomas are usually performed
after the first year of life. Although lipodermoid
Vishwanath Srinagesh
may represent a cosmetic concern, surgery is often
Sinai Hospital, Krieger Eye Institute, Baltimore,
difficult, and it is best to restrict excision to the
MD, USA
surface of the mass.

Definition
Prognosis
Inflammation of the conjunctiva caused by
Individuals typically have a normal life span and
Neisseria gonorrhoeae infection.
normal intelligence.

Etiology
Epidemiology
Gonococcal conjunctivitis may be acquired
Incidence estimated to be 1 in 5,600 births.
through direct genital-eye transmission, genital-
hand-eye contact, or maternal-neonate transmis-
sion during vaginal delivery.
Cross-References

▶ Choristomas Clinical Presentation

▶ Limbal Dermoid
▶ Nutritional Amblyopia Gonococcal conjunctivitis is characterized by
▶ Treacher Collins-Franceschetti Syndrome hyperacute onset of purulent exudates, conjuncti-
(Mandibulofacial Dysostosis) val chemosis and hyperemia, and eyelid swelling.
It may also be associated with the formation of
membranes and preauricular lymphadenopathy.
References
Keratitis is the most frequent cause of sight-
Alecksic S, Budzilovich G, Reuben R et al (1975) Con- threatening complication and occurs in 15–40%
genital trigeminal neuropathy in oculoauriculovertebral of cases.
816
Notable signs of corneal involvement include
marginal infiltrates, epithelial haze, epithelial
defects, and peripheral infectious keratitis. If left
untreated, keratitis may progress to ulceration and
eventually perforation.
In neonates, symptoms are typically bilateral
and begin within 2–5 days after parturition.
Diagnosis
In cases of neonatal gonococcal conjunctivitis, a
prenatal history is vital and cervical specimens
should be taken from the mother for culture.
A full ocular and general physical exam should
be performed to diagnose and assess the extent of
disease.
Conjunctival scrapings submitted for Gram
and Giemsa staining should reveal intracellular
gram-negative diplococci present inside
neutrophils.
Conjunctival swabs should also be planted on
chocolate agar in a CO2-enriched atmosphere or
Thayer-Martin media.
Differential Diagnosis
Differential diagnosis includes chemical conjunc-
tivitis, chlamydial and other nongonococcal bac-
terial conjunctivitis, and herpetic conjunctivitis.
Prophylaxis
Prophylactic recommendations include tetracy-
cline (1%) drops and erythromycin (0.5%) oint-
ment. Silver nitrate drops are used less commonly
as they may cause chemical conjunctivitis and do
not provide prophylaxis against chlamydia.
Therapy
The mainstay of treatment of gonococcal disease
is systemic antibiotics. Due to increasing preva-
lence of penicillin-resistant N. gonorrhoeae,
Gonococcal Conjunctivitis
ceftriaxone is prescribed as first-line treatment.
Gonococcal conjunctivitis without ulceration
may be treated with a one-time, intramuscular
dose of ceftriaxone (1 g). Patients with corneal
ulceration should be admitted to the hospital and
treated with intravenous ceftriaxone (1 g IV every
12 h) for 3 days. Patients with a penicillin allergy
may be treated with spectinomycin (2 g IM) or
ciprofloxacin (500 mg bid for 5 days).
Non-disseminated neonatal conjunctivitis is
treated with a single intravenous or intramus-
cular ceftriaxone (25–50 mg/kg or up to
125 mg). Alternatively, cefotaxime may be pre-
scribed as an intramuscular or intravenous
injection (100 mg/kg). In disseminated infec-
tions, hourly saline irrigation of the conjunctiva
may be initiated to clear discharge. If clinical
signs of corneal involvement are present, topi-
cal erythromycin or gentamicin ointment or a
topical flouroquinolone should be considered.
Patients should also be treated for chlamydia
with systemic erythromycin (12.5 mg/kg oral or
IV qid for 14 days) as coinfection can occur
and systemic involvement, such as pneumonitis
and otitis media, can lead to significant
morbidity.
Prognosis
Prognosis is excellent if treatment is started while
infection is localized. Visual prognosis may be
limited in patients with significant corneal
involvement with subsequent scarring and/or
perforation.
Disseminated gonococcal infection with men-
ingitis, pneumonia, and sepsis resulting in death is
a rare complication in neonates.
Epidemiology
The incidence of neonatal gonococcal conjuncti-
vitis is estimated at approximately 100 per
100,000 in the United States.
Non-neonatal infections are most common in
adolescents and young adults.
Gorlin Syndrome
Cross-References
▶ Conjunctivitis
Further Reading
Albert et al (1994) Albert & Jakobiec principles and prac-
tice of ophthalmology. (4) 2827–2829
American Academy of Pediatrics (2009) Gonococcal
infections. In: Pickering LK, Baker CJ, Kimberlin
DW, Long SS (eds) Red book: report of the Committee
on Infectious Diseases, 28th edn. American Academy
of Pediatrics, Elk Grove Village, pp 305–313
Centers for Disease Control and Prevention, Workowski
KA, Berman SM (2006) Sexually transmitted diseases
treatment guidelines 2006. MMWR Recomm Rep
55(RR- 11):1–94
Laga M, Plummer F, Piot P et al (1988) Prophylaxis of
gonococcal and chlamydial ophthalmia neonatorum.
N Engl J Med 318:653–657
Good Acuity Plus Photophobia
▶ Transient Light-Sensitivity Syndrome
Gorlin Syndrome
Jeremiah Tao and Steven J. Yoon
Division of Oculofacial Plastic and Orbital
Surgery, Gavin Herbert Eye Institute, University
of California, Irvine, CA, USA
Synonyms
Basal cell nevus syndrome; Nevoid basal cell
carcinoma syndrome
Definition
A rare autosomal dominant disorder characterized
by multiple nevoid basal cell carcinomas early in
life. It is a multisystemic disease involving multiple
817
organ systems (American Academy of Ophthal-
mology 2006–2007; Albert and Jakobiec 2008).
Etiology
Tumors are indistinguishable from noninherited
forms of basal cell carcinoma, arising from the
basal cell layer of the epithelium. The gene though
to be responsible for Gorlin syndrome is the
patched gene (PTCH), found on 9q22.3-q31. It
is thought to be a tumor suppressor with one
germline defect in affected families. Complete
penetrance with variable expressivity is observed G
(Gorlin 1995; Bale 1997; Shields and Shields
1999; American Academy of Ophthalmology
2006–2007; Albert and Jakobiec 2008).
Clinical Presentation
Gorlin syndrome may present with multiple basal
cell carcinomas at a young age. Eyelid basal cell
carcinomas occur in 25% of cases and are indis-
tinguishable from noninherited forms of basal cell
carcinoma.
Other ophthalmic findings in Gorlin syndrome
include congenital cataracts, orbital cysts, hyper-
telorism, colobomas, and medullated nerve fiber
layer of the retina. Other features include man-
dibular cysts, macrocephaly, frontal bossing,
polydactyly, palmar or plantar pits, and medullo-
blastoma (Gorlin 1995; Bale 1997; Shields and
Shields 1999; American Academy of Ophthal-
mology 2006–2007; Albert and Jakobiec 2008).
Diagnostics
Excisional biopsies of suspect lesions are histo-
logically indistinguishable from basal cell carci-
noma. Imaging is necessary when clinically
correlated, including MRI of the brain, dental
radiography, and a skeletal survey (Gorlin 1995;
Bale 1997; Shields and Shields 1999; American
Academy of Ophthalmology 2006–2007; Albert
and Jakobiec 2008).
818
Differential Diagnosis
Xeroderma Pigmentosa
Prophylaxis
Patients with Gorlin syndrome may be extremely
susceptible to ionizing radiation and sun exposure.
Patient should be counseled to avoid sun exposure
(Gorlin 1995; Bale 1997; Shields and Shields
1999; American Academy of Ophthalmology
2006–2007; Albert and Jakobiec 2008).
Therapy
Surgical excision is recommended for a patient
with a limited number of lesions. Topical 5-
fluorouracil with or without topical tretinoin may
be useful for patients with extensive lesions. Oral
isotretinoin may be an option for patients who are
at high risk for developing many additional lesions.
Prognosis
Patients may have multiorgan involvement and
will need care by appropriate specialists, includ-
ing dermatologists, dentists, oncologists, cardiol-
ogists, and orthopedic surgeons.
Epidemiology
Incidence is rare and occurring in about 1 per
50,000–150,000 people and in 0.7% of patients
with basal cell carcinoma. Fair skinned patients
with substantial sun exposure may be more sus-
ceptible (Shields and Shields 1999; American
Academy of Ophthalmology 2006–2007; Albert
and Jakobiec 2008).
Cross-References
▶ Basal Cell Carcinoma of Eyelid
▶ Basal Cell Nevus Syndrome (Gorlin Syndrome)
Gradenigo Syndrome
References
Albert D, Jakobiec F (2008) Principles and practice of
ophthalmology, 3rd edn. Saunders, Philadelphia,
pp 3279–3292
American Academy of Ophthalmology (2006–2007) Basic
and clinical science course. Orbit, eyelids, and lacrimal
system. 7. p 174
Bale AE (1997) The nevoid basal cell carcinoma syn-
drome: genetics and mechanism of carcinogenesis.
Cancer Invest 15(2):180–186
Gorlin RJ (1995) Nevoid basal cell carcinoma syndrome.
Dermatol Clin 13(1):113–125
Shields JA, Shields CL (1999) Eyelid, conjunctival, and
orbital tumors: an atlas and textbook. LWW, Philadel-
phia, pp 22–31
Gradenigo Syndrome
Sneha Konda1,2, Sumayya J. Almarzouqi3,
Michael L. Morgan3,8 and Andrew G. Lee3,4,5,6,7
1
Department of Ophthalmology, The Methodist
Hospital, Houston, TX, USA
2
Department of Ophthalmology, College of
Medicine, Texas A&M University, Temple,
TX, USA
3
Department of Ophthalmology, Blanton Eye
Institute, Houston Methodist Hospital, Houston,
TX, USA
4
Departments of Ophthalmology, Neurology, and
Neurosurgery, Weill Cornell Medical College,
Houston, TX, USA
5
Department of Ophthalmology, The University
of Texas Medical Branch, Galveston, TX, USA
6
Department of Ophthalmology, Baylor College
of Medicine, Houston Methodist Hospital,
Houston, TX, USA
7
Department of Ophthalmology, The University of
Iowa Hospitals and Clinics, Iowa City, IA, USA
8
Department of Ophthalmology and Visual
Sciences, University Hospitals Eye Institute, Case
Western Reserve University School of Medicine,
Cleveland, Ohio, USA
Synonyms
Gradenigo-Lannois syndrome; Petrous apicitis
Gradenigo Syndrome
Definition
Gradenigo syndrome is a rare but sometimes seri-
ous infectious/inflammatory syndrome, associ-
ated with localized inflammation at the apex of
the petrous temporal bone, a location in which the
trigeminal (CN V) nerve is closely related to
abducens nerve (CN VI) and facial (CN VII) and
vestibulocochlear (CN VIII) nerves.
Etiology
Causes include inflammation (e.g., petrositis sec-
ondary to otitis and mastoiditis), infection typi-
cally due to aerobic microorganisms, extradural
abscess, tumors (e.g., cholesteatoma, chordoma,
meningioma, nasopharyngeal carcinoma, meta-
static disease), and skull base fracture.
Clinical Presentation
Gradenigo syndrome is characterized by a clinical
triad: retro-orbital pain in the distribution of the
ophthalmic division of trigeminal nerve (CN V),
diplopia due to abducens nerve (CN VI) palsy, and
otorrhea due to suppurative otitis media. Facial
(CN VII) palsy and deafness, due to compromise
of vestibulocochlear nerve (CN VIII), also may
manifest as components of the syndrome.
History
It was first described by Giuseppe Gradenigo in
1904, as a serious complication of otitis media. In
the postantibiotic era, infection is a much less
common cause of the syndrome.
Diagnosis
The diagnosis of Gradenigo syndrome is a clinical
diagnosis supported by either computed tomogra-
phy (CT) or magnetic resonance imaging (MRI)
findings.
819
Differential Diagnosis
The differential diagnosis of Gradenigo syndrome
includes Ramsay Hunt syndrome (geniculate
Herpes Zoster), neoplastic disorders involving
petrous bone, and closed head trauma.
Therapy
High-dose antibiotic treatments, both systemic
and topical, are recommended for infectious eti-
ologies. Treatment, in severe cases failing maxi-
mum medical therapy, may also require more G
aggressive and radical surgical intervention (e.g.,
apical petrosectomy) to debulk the infection.
Prognosis
Earlier diagnosis and treatment may limit disease
progression and more severe and potentially life-
threatening complications.
Epidemiology
The incidence of infectious Gradenigo syndrome
in the United States has been reduced by earlier
diagnosis and treatment with broad-spectrum anti-
biotics but may still be as high as 2 per 100,000
individuals with acute otitis media. Gradenigo
syndrome however remains a problem in lesser-
developed countries.
Cross-References
▶ Facial Nerve Palsy
▶ Sixth Nerve Palsy
Further Reading
Acton QA (2011) “University of California, San Diego:
Gradenigo’s Syndrome.” Headache and migraine: new
insights for the healthcare professional. Edition. Print
Barker RA (2005) The A-Z of neurological practice: a
guide to clinical neurology. Cambridge UP, Cambridge,
p 308. Print
820
Friedman NJ, Kaiser PK (2007) Essentials of ophthalmol-
ogy. Saunders Elsevier, Philadelphia, pp 68–70. Print
Millichap GJ (2013) Neurological syndromes a clinical
guide to symptoms and diagnosis. Springer, Dordrecht,
p 85. Print
Pendlebury ST, Anslow P, Rothwell PM (2007) Neurolog-
ical case histories: case histories in acute neurology and
the neurology of general medicine. Oxford UP, Oxford,
pp 126–127. Print
Gradenigo-Lannois Syndrome
▶ Gradenigo Syndrome
Graft-Versus-Host Disease: Overview
Jiawei Zhao
Department of Ophthalmology, Johns Hopkins
School of Medicine, Baltimore, MD, USA
Definition
Graft-versus-host disease (GVHD) is a major
complication from allogeneic hematological
stem cell transplantation. It is a systemic inflam-
matory condition due to attack of host tissue by
immunocompetent cells from the donor (Albert
et al. 2008).
Etiology
GVHD is the recognition of allogeneic differences
and destruction of host peptides by immune cells
of the donor. Activation of donor immune cells
leads to secretion of IL-2, resulting in clonal
expansion and proliferation of T lymphocytes
(Albert et al. 2008).
Acute GVHD is due to conditioning regimen
(radiation and/or chemotherapy) that damages
host tissue (Albert et al. 2008). This leads to
production of pro-inflammatory cytokines such
as IL-1 and TNF-a that increase expression of
human leukocyte antigen (HLA) alloantigens
Gradenigo-Lannois Syndrome
and adhesion molecules on the surface of host
cells, activating donor type 1 helper T cell (Albert
et al. 2008).
Chronic GVHD is predominantly a type
2 helper T cell response with lymphoproliferation,
increased IgE synthesis, and production of IL-4
and IL-10 (Albert et al. 2008). In contrast to
acute GVHD, donor antigen-presenting cells are
also involved in the pathogenesis (Albert et al.
2008).
Clinical Presentation
Acute GVHD develops within 100 days of trans-
plantation and chronic GVHD develops after day
100 (Albert et al. 2008). Ocular GVHD can affect
all layers of the eye including the lid, meibomian
gland, vitreous, and choroid, but it mainly affects
ocular surface and lacrimal gland (Hasanain et al.
2013). Acute ocular GVHD often presents with
conjunctival hyperemia, chemosis, and pseudo-
membrane formation (Hasanain et al. 2013).
Chronic GVHD often presents with keratocon-
junctivitis sicca along with chronic blepharitis
and meibomian gland dysfunction (Hasanain et
al. 2013). Sterile conjunctivitis, cicatricial
lagophthalmos, and retinal microvascular occlu-
sive disease are also commonly observed (Hessen
and Akpek 2012).
Diagnosis
Acute ocular GVHD is diagnosed by clinical pre-
sentation. Diagnosis of chronic ocular GVHD
needs to be confirmed by (1) biopsy or Schirmer
test and (2) involvement of at least one other organ
(Hasanain et al. 2013).
Differential Diagnosis
Infection, total body irradiation, ocular toxicity of
chemotherapy, immunosuppressive therapy,
meibomian gland dysfunction, and keratocon-
junctivitis sicca are due to other causes.
Gram-Negative Bacteria
Prophylaxis
One major prophylaxis method is optimal
HLA-matching between donor and recipient.
Donor T cell depletion through alemtuzumab
(anti-CD52) and anti-thymocyte globulin can
also prevent GVHD, but this increases the rate of
graft failure, relapse of malignancy, infections,
and Epstein-Barr virus-associated lymphoproli-
ferative disorder (Hasanain et al. 2013). Pharma-
cologic agents that can be used are the combined
use of calcineurin inhibitors with low doses of
methotrexate (Hasanain et al. 2013). Reduced
intensity conditioning regimens reduce tissue
damage and thus lower intensity of cytokine
storm (Hasanain et al. 2013).
Therapy
Treatment options for ocular GVHD include
lubrication with artificial non-preserved
phosphate-free tears (Hessen and Akpek 2012);
tear preservation with punctal occlusion (silicone
plugs or thermal cauterization) (Hessen and
Akpek 2012); reduction of inflammation with
short-term, low-frequency application of topical
steroids and long-term control with topical cyclo-
sporine eye drops (Hessen and Akpek 2012);
prevention of tear evaporation with warm
compresses and ointments such as erythromycin
(Hessen and Akpek 2012); epithelial support with
autologous serum eye drops, contact lenses
(bandage soft contact lenses, scleral lenses, or
prosthetic replacement of ocular surface ecosys-
tem), or sutureless amniotic membrane; and sur-
gery for severe cases of ocular surface disruption
(Hessen and Akpek 2012).
Prognosis
Mortality due directly or indirectly to acute
GVHD may reach 50% (Albert et al. 2008).
Acute GVHD leading directly to chronic GVHD
has the worse prognosis compared to chronic
GVHD with a remission period after acute
GVHD and de novo chronic GVHD (Hasanain
821
et al. 2013). Presence of pseudomembranous
conjunctivitis is associated with poor prognosis
(Hasanain et al. 2013).
Epidemiology
Acute and chronic GVHD develops in approxi-
mately 40% and 30–70%, respectively, in
HLA-matched patients (Hessen and Akpek
2012). Ocular manifestations occur in 60–90%
of patients with chronic GVHD but are uncom-
mon in acute GVHD (Hessen and Akpek 2012).
G
Cross-References
▶ Blepharitis
▶ Conjunctivitis
▶ Keratoconjunctivitis: Overview
▶ Lagophthalmos
▶ Meibomian Gland Dysfunction
▶ Thermal Cautery
References
Albert DM, Miller JW et al (2008) Albert & Jakobiec’s
principles & practice of ophthalmology, 3rd edn.
Saunders, Philadelphia, pp 4821–4830
Hasanain S, Antin JH, Dana R (2013) Ocular graft-versus-
host disease: a review. Surv Ophthalmol 58(3):233–251
Hessen M, Akpek EK (2012) Ocular graft-versus-host
disease. Curr Opin Allergy Clin Immunol 12(5):
540–547
Gram-Negative Bacteria
Khaled Tuwairqi
Wilmer Eye Institute, Baltimore, MD, USA
Department of Ophthalmology, University of
Utah, Salt Lake City, UT, USA
Definition
A group of microorganisms that will not retain a
crystal violet stain on gram staining method.
822
Structure
As opposed to gram-positive bacteria, gram-
negative bacteria maintain the cell wall shape by
a thin layer of peptidoglycan that is surrounded by
an outer membrane. The outer membrane pro-
vides an important role in the protection from
host environment, and it is linked to the peptido-
glycan through lipoproteins. Lipid A is a compo-
nent of the outer membrane which acts as a strong
activator of the innate immune system. Few kinds
of proteins that are found on the outer membrane
play a role in the virulence of these organisms.
Periplasmic space is an area that is found between
the inner and outer membranes that many enzy-
matic processes will take place at. Other structures
which could also be found in the gram-positive
bacteria include capsule which is useful in the
protection from phagocytosis, pili that are used
by bacteria for adherence or sexual reproduction
and flagellum for movement.
Function
Certain types of bacteria are found in the normal
flora of human bodies. In the ocular flora, gram-
negative bacteria that could be isolated include
Haemophilus species, Neisseria species, and
Pseudomonas species. Recent studies suggested
that normal flora could help minimize the inflam-
mations, act as a barrier against harmful patho-
gens, maintain the immune system, inhibit the
apoptosis, and accelerate the wound repair.
Clinical Relevance
Many ocular infections have been related to gram-
negative bacteria. These infections could involve
any part of the eye and vary in their course and
treatment. Keratitis, dacryocystitis, cellulitis, con-
junctivitis, corneal ulcer infections, and endo-
phthalmitis are examples of ocular diseases that
could be a result of gram-negative bacterial
pathology.
Gram-Positive Bacteria
Cross-References
▶ Gram-Positive Bacteria
Further Reading
Deibel JP, Cowling K (2013) Ocular inflammation and
infection. Emerg Med Clin North Am 31:387–397
Miller D, Iovieno A (2009) The role of microbial flora on
the ocular surface. Curr Opin Allergy Clin Immunol
9:466–470
Murray PR, Rosenthal KS, Pfaller MA (2013) Medical
microbiology, 7th edn. Saunders, Philadelphia,
pp 109–121
Gram-Positive Bacteria
Khaled Tuwairqi
Wilmer Eye Institute, Baltimore, MD, USA
Department of Ophthalmology, University of
Utah, Salt Lake City, UT, USA
Definition
A group of microorganisms that will stain crystal
violet on gram staining method.
Structure
The main theme for the gram-positive bacteria is a
thick layer of peptidoglycan that will provide
protection and maintain the cell wall shape and
structure. Additionally, few bacteria have
lipoteichoic acid and teichoic acid in their walls.
The main functions of teichoic acid are to further
strengthen the cell wall, help in the sequestration
of calcium ion, and act as an activator of innate
immune system. Other structures which could be
found regardless of the bacteria gram stain include
capsule which is useful in the protection from
phagocytosis, pili that are used by bacteria for
adherence or sexual reproduction and flagellum
for movement.
Granulation Tissue-Type Hemangioma 823

Function
Granular Corneal Dystrophy
Certain types of bacteria are found in the normal Type 2 (Granular-Lattice) (GCD2),
flora of human bodies. In the ocular flora, gram- Combined Granular-Lattice Corneal
positive bacteria that could be isolated include Dystrophy or Avellino Corneal
Staphylococci, Corynebacterium, Streptococcus Dystrophy
species, and Propionibacterium species. Recent
studies showed that this flora could help mini- ▶ Stromal Dystrophies
mize the inflammations, act as a barrier against
harmful pathogens, maintain the immune sys-
tem, inhibit the apoptosis, and accelerate the
wound repair.
Granular Corneal Dystrophy
Type I G
Clinical Relevance
▶ Groenouw Dystrophy Type 1 Disease
Many ocular infections have been related to gram-
positive bacteria. These infections could involve
any part of the eye and vary in their course and
treatment. Hordeolum, blepharitis, keratitis,
dacryocystitis, cellulitis, conjunctivitis, corneal Granular Corneal Dystrophy,
ulcer infections, and endophthalmitis are exam- Type III
ples of ocular diseases that could be a result of
gram-positive bacterial pathology. ▶ Reis-Bücklers Dystrophy

Cross-References

▶ Gram-Negative Bacteria Granular Dystrophy

▶ Corneal Dystrophies
Further Reading

Deibel JP, Cowling K (2013) Ocular inflammation and

infection. Emerg Med Clin North Am 31:387–397
Miller D, Iovieno A (2009) The role of microbial flora on
the ocular surface. Curr Opin Allergy Clin Immunol Granular Keratinocytes
9:466–470
Murray PR, Rosenthal KS, Pfaller MA (2013) Medical
microbiology, 7th edn. Saunders, pp 109–121 ▶ Keratinocytes: Overview

Granular Corneal Dystrophy Type 1

(GCD1), Groenouw Corneal Granulation Tissue-Type
Dystrophy Type I Hemangioma

▶ Stromal Dystrophies ▶ Pyogenic Granuloma

824 Graves Ophthalmopathy

than 50, rapid onset of symptoms under 3 months,

Graves Ophthalmopathy cigarette smoking, diabetes, hyperthyroidism,
hyperlipidemia, and peripheral vascular disease.
Maxwell Su4, Sumayya J. Almarzouqi1,
Michael L. Morgan1,7 and Andrew G. Lee1,2,3,5,6
1
Department of Ophthalmology, Blanton Eye
History
Institute, Houston Methodist Hospital, Houston,
TX, USA
2 Robert James Graves first described the disorder
Departments of Ophthalmology, Neurology, and
in 1835. The disease was associated with thyroid
Neurosurgery, Weill Cornell Medical College,
goiter and exophthalmos of the eye.
Houston, TX, USA
3
Department of Ophthalmology, The University
of Texas Medical Branch, Galveston, TX, USA
4
Department of Ophthalmology, College of Clinical Features
Medicine, Texas A&M University, College
Station, TX, USA TED is characterized by unilateral or bilateral
5
Department of Ophthalmology, Baylor College upper eyelid retraction, lid lag in downward bilat-
of Medicine, Houston Methodist Hospital, eral or unilateral proptosis, ophthalmoplegia, and
Houston, TX, USA sometimes compressive optic neuropathy.
6
Department of Ophthalmology, The University of
Iowa Hospitals and Clinics, Iowa City, IA, USA
7
Department of Ophthalmology and Visual
Tests
Sciences, University Hospitals Eye Institute, Case
Western Reserve University School of Medicine,
After a complete ocular history and physical exam-
Cleveland, Ohio, USA
ination, if TED is suspected, then thyroid function
studies (e.g., TSH, T3, T4) should be performed.
Thyroid antibodies (e.g., TPO and TSIG
Synonyms
antibodies) might also be helpful especially for
confirming autoimmune hypothyroidism or in
Dysthyroidal/thyroid-associated orbitopathy;
euthyroid patients. Orbital imaging including ultra-
Graves’ orbitopathy; Thyroid eye disease
sound, computed tomography (CT) scan, or mag-
netic resonance imaging (MRI) of the orbit can be
Definition done if there is diagnostic uncertainty. The distinc-
tive radiographic sign of TED is enlargement of the
Graves disease (GD) is an autoimmune condition extraocular muscles typically with sparing of the
associated with hyperthyroidism. Thyroid eye dis- tendon. The most common order of involvement
ease (TED) is a disease of the orbit that typically for the extraocular muscles in TED is inferior rec-
presents with upper eyelid retraction, lid lag, tus, then medial rectus, then superior rectus, and
swelling, erythema, conjunctivitis, and proptosis lastly the lateral rectus muscles.
and can be associated with GD but is not unique to
GD-related hyperthyroidism.
Differential Diagnosis
Epidemiology
Previous eyelid surgeries
GD occurs four times more often in females than Third, fourth, or sixth cranial nerve palsy
in males. However, the prognosis for males is Myasthenia gravis
typically worse. Risk factors include age greater Parinaud syndrome
Graves’ Disease
Etiology
GD is a systemic autoimmune disorder in which
antibodies are produced against the receptor for
thyroid stimulating hormone (TSH). The abnor-
mally high production of T3 and T4 may lead to
an enlargement of the thyroid gland, seen as a
goiter. It is postulated that the TSH receptor anti-
bodies share a similar antigen that is present on the
extraocular muscles. Therefore, TSH receptor and
other thyroid-related antibodies bind to extra-
ocular muscles and cause TED.
Diagnosis
GD is a clinical syndrome supported by laboratory
and radiographic testing.
Treatment
The patient should consult with a medical internist
or endocrinologist for management of the autoim-
mune thyroid disease. Conservative treatment for
exposure keratopathy includes artificial tears and
lubricating ointment. Elevation of the head of the
bed might be useful for lid and orbital edema.
Prednisone can be used to treat inflammatory
TED and might reduce proptosis, corneal ulcera-
tion, acute disturbing double vision, and visual
loss from optic neuropathy. Patients with com-
pressive optic neuropathy due to TED however
may require surgical decompression. In general,
the surgical treatment of TED should follow a
stepwise approach with orbital decompression
first as this might change the pattern of strabismus,
then strabismus surgery second as this might alter
the lid position, and then eyelid surgery last.
Further Reading
Braverman LE, Utiger RD. Thyrotropin receptor structure
and functions. In: Braverman LE, Utiger RD (eds)
Werner & Ingbar’s the thyroid: a fundamental & clini-
cal text, 9th edn. pp 356–369
Kunimoto DY, Kanitkar KD, Makar MS, Friedberg MA,
Rapuano CJ. Thyroid-related orbitopathy (graves dis-
ease). In: Kunimoto DY, Kanitkar KD, Makar MS,
Friedberg MA, Rapuano CJ (eds) Wills eye manual:
825
office and emergency room diagnosis & treatment of
eye disease. 4th edn. pp 128–129, 130
Miller NR, Newman NJ. Endocrine myopathies graves’
disease. In: Miller NR, Newman NJ (eds) Walsh &
hoyt’s clinical neuro-ophthalmology, 6th edn.
pp 1117–1119
Graves’ Disease
Pete Setabutr1 and Joann Kang2
1
Department of Ophthalmology and Visual
Sciences, University of Illinois, Chicago,
IL, USA
2
Illinois Eye and Ear Infirmary, University of
G
Illinois at Chicago, Chicago, IL, USA
Synonyms
Dysthyroid ophthalmopathy; Thyroid eye dis-
ease; Thyroid-associated orbitopathy
Definition
Graves’ disease is an autoimmune inflammatory
disorder that affects orbital and periorbital tissue.
It is associated with hyperthyroidism at some
point in most patients, although in less than 10%
of cases, patients are hypothyroid or euthyroid.
Clinical Presentation
Graves’ disease is always a bilateral process,
although it is often asymmetrical. Many of the
clinical signs and symptoms arise from soft tissue
enlargement in the orbit including both extra-
ocular muscles and adipose tissue. Patients under
40 years of age typically have a predominance of
fat expansion, while patients over 60 years of age
often have more extraocular muscle swelling.
Although multiple muscles may be involved, the
inferior rectus is the most common, followed by
the medial rectus.
The most common symptoms include orbital
pain or discomfort, diplopia, lacrimation, photo-
phobia, and dry eye symptoms. The clinical
826
characteristic signs include lid retraction with
temporal flare, lid lag, exophthalmos, restrictive
extraocular myopathy, erythema of the periorbital
tissues, or conjunctiva and corneal exposure.
Three to five percent of cases are sight threatening
due to optic nerve compression or corneal
decompensation.
In patients with hyperthyroidism, pretibial
myxedema and acropachy, which manifests as
clubbing of the fingers or toes, may occur. The
course of ophthalmopathy does not necessarily
parallel the state of thyroid dysfunction.
Diagnosis
Diagnosis of thyroid abnormalities can be made
with thyroid studies. Measurement of circulating
thyrotropin-receptor antibodies may have diag-
nostic value due to their high specificity and sen-
sitivity for Graves’ disease. Orbital imaging with
computed tomography (CT) or magnetic reso-
nance imaging (MRI) may show fusiform extra-
ocular muscle enlargement with sparing of the
tendons and/or an increase in orbital fibroadipose
tissue. Neuroimaging is particularly useful to
evaluate optic nerve compression by enlarged
muscles, especially at the orbital apex, known as
apical crowding.
Differential Diagnosis
Orbital inflammatory syndrome, preseptal or
orbital cellulitis, sarcoidosis, orbital metastases,
dorsal midbrain syndrome, carotid-cavernous
fistula.
Prophylaxis
Primary prevention of the disease is not feasible.
However, the strongest modifiable risk factor is
cigarette smoking, with a 7.7 odds ratio of devel-
oping the disease in smokers versus nonsmokers.
Early and accurate control of thyroid dysfunction
may also be important.
Graves’ Disease
Therapy
Thyroid dysfunction should be treated if present
with antithyroid medications or radioactive
iodine. However, radioiodine therapy can cause
progression of ophthalmopathy in about 15% of
patients, especially in smokers and patients with
severe hyperthyroidism, which may be pre-
vented with concomitant treatment with oral
prednisone.
Specific treatment depends on the severity of
the disease. Patients with mild disease only
require supportive therapy including ocular lubri-
cation for dry eye or temporary prisms for
diplopia.
For more severe disease, therapy is directed
toward decreasing inflammation or acute orbital
congestion with systemic corticosteroids or
orbital radiotherapy, particularly for impaired
motility.
Approximately 20% of patients require surgi-
cal intervention. Surgery is generally considered
only after stabilization of the disease. Orbital
decompression surgery is often done to restore
normal globe position by expanding the orbital
bony volume. Strabismus surgery and eyelid sur-
gery to correct eyelid retraction may be indicated
to correct diplopia and for cosmesis. If multiple
surgeries are indicated, orbital decompression is
done first, followed by strabismus surgery and
then eyelid surgery.
Urgent intervention without waiting for stabi-
lization may be needed to treat or prevent optic
neuropathy or corneal decompensation by high-
dose systemic corticosteroids, orbital radiother-
apy, or orbital decompression.
Prognosis
Generally there is an initial active phase lasting
1–2 years, followed by stabilization. Only 5–10%
of patients have reactivation of inflammation over
their lifetime.
Smokers have a poorer prognosis, a longer
duration of disease, and are less likely to respond
to immunosuppressive therapy. Other poor prog-
nostic features include male gender, older age,
Groenouw Dystrophy Type 1 Disease 827

rapidly progressive disease, and presence of

dermopathy. Groenouw Dystrophy Type 1 Disease

Allen O. Eghrari
Epidemiology Johns Hopkins University School of Medicine,
Baltimore, MD, USA
Graves’ disease has an annual incidence of Cornea and Anterior Segment, Wilmer Eye
16 women and 3 men per 100,000 population. Institute at Johns Hopkins, Baltimore, MD, USA
Two age peaks of incidence are observed in the
fifth and seventh decade of life, varying slightly
between men and women. Synonyms

Granular corneal dystrophy type I

Cross-References G

▶ Proptosis Definition
▶ Retractors, Lower Eyelid
First described by German ophthalmologist Arthur
Groenouw in 1890; Groenouw Dystrophy Type
Further Reading 1 is a bilateral, progressive, noninflammatory cor-
Bahn RS (2010) Graves’ ophthalmopathy. N Engl J Med
neal condition marked by the development of focal
362(8):726–738 anterior stromal opacities in a granular pattern.
Bartalena L, Tanda ML (2009) Clinical practice. Graves’
ophthalmopathy. N Engl J Med 360(10):994–1001
Wiersinga WM, Bartalena L (2002) Epidemiology and Etiology
prevention of Graves’ ophthalmopathy. Thyroid
12(10):855–860
A mutation in the TGFBI gene from Arg to Trp at
position 555 in Chromosome 5q31 codes for
keratoepithelin and is causative for Groenouw
Dystrophy. It is inherited through autosomal dom-
inant inheritance.
Graves’ Eye Disease

▶ Thyroid Eye Disease Clinical Presentation

Groenouw Dystrophy Type 1 often presents in

childhood, affecting males and females equally.
Patients are initially comfortable but may develop
Graves’ Ophthalmopathy photophobia from light scattering and/or discom-
fort from recurrent corneal erosions. Visual acuity
▶ Thyroid Eye Disease may be maintained for decades, until the disease
has progressed to an advanced state.
On physical examination, central, fine, granu-
lar “bread crumb-,” snowflake-, or ring-like
lesions with empty intervening spaces present in
Graves’ Orbitopathy the anterior stroma (Fig. 1). The peripheral cornea
is often spared. With slit-lamp examination,
▶ Diplopia in Graves’ Ophthalmopathy lesions are opaque with direct illumination but
▶ Graves Ophthalmopathy translucent with retroillumination. Superficial
828
Groenouw Dystrophy Type 1 Disease, Fig. 1 Corneal
photograph of a 37-year-old male with Groenouw Dystro-
phy Type 1, confirmed with genetic testing for the common
TGFBI mutation
lesions may be associated with negative fluores-
cein staining.
Diagnosis
Diagnosis is primarily conducted by slit-lamp
biomicroscopy. While focal lesions are generally
round, lines may radiate from the individual
lesions and should not be confused for lattice
lines. Genetic testing for TGFBI mutations is
commercially available and can help to differen-
tiate Groenouw Dystrophy Type 1 from Avellino
corneal dystrophy but is not necessary for
diagnosis.
Histological evaluation of the cornea,
conducted if corneal transplant is required, reveals
strong, bright red staining of hyaline deposits with
Masson Trichrome and weak staining with period
acid-Schiff. These deposits may be eosinophilic,
rod-like or trapezoidal in shape, and are appreci-
ated anteriorly but can be deposited throughout
the stroma.
Differential Diagnosis
Groenouw Dystrophy I differs clinically from
Avellino corneal dystrophy (or granular-lattice
corneal dystrophy) in that it is without lattice
lines, although ray-like features in granular
deposits may be deceiving in appearance. Both
Groenouw Dystrophy Type 1 Disease
conditions originate from mutations in TGFBI.
While both conditions demonstrate staining with
Masson trichrome, amyloid deposits in Avellino
corneal dystrophy stain positively with Congo
Red. Laboratory genetic testing is beneficial in
cases of a diagnostic dilemma.
Prophylaxis
None. Groenouw Dystrophy Type 1 is inherited;
no known genetic therapy exists at this time.
Therapy
Many patients have few symptoms, requiring no
treatment. Lubrication is helpful in the setting of
recurrent corneal erosions.
In cases of advanced disease, surgical interven-
tion is based on lesion depth, which can be mea-
sured with anterior segment optical coherence
tomography. Superficial keratectomy or epithelial
scraping can be utilized to address subepithelial
deposits. Argon-fluoride excimer laser ablation
may reduce or eliminate deposits in the anterior
stroma, although vision may be limited by poste-
rior lesions. Deep anterior lamellar keratoplasty or
penetrating keratoplasty may be utilized in the
setting of deep lesions.
Prognosis
Visual acuity is generally well maintained until
middle age, but patients may present with severe
disease at an earlier age, particularly those homo-
zygotic for the mutation in TGFBI. Stromal haze
may develop between hyaline granules in
advanced disease, affecting visual acuity.
Phototherapeutic keratectomy in early-to-
middle age maintains corneal transplantation as a
future surgical option. Recurrence of Groenouw
corneal dystrophy following corneal transplanta-
tion is common and independent of the size or
type of graft. Lesions often re-appear superficially
but may differ from primary presentation,
appearing peripherally.
Guerin (Maxillary) Fracture 829

Epidemiology Definition

Rare. In 1901, Rene Le Fort categorized fracture pat-

Cross-References
▶ Congenital Hereditary Stromal Dystrophy
▶ Crystalline Dystrophy
▶ Lattice Corneal Dystrophy
Further Reading
DeSousa LB, Mannis MJ (2011) The Stromal Dystrophies.
In: Krachmer JH, Mannis MJ, Holland EJ (eds) Cornea,
3rd edn. Mosby Elsevier, Maryland Heights,
pp 823–844
Lyons CJ, McCartney AC, Kirkness CM, Ficker LA,
Steele AD, Rice NS (1994) Granular corneal dystro-
phy: visual results and pattern of recurrence after lamel-
lar or penetrating keratoplasty. Ophthalmology
101:1812–1817
Møller HU (1990) Granular corneal dystrophy Groenouw
type I. 115 Danish patients. An epidemiological and
genetic population study. Acta Ophthalmol 68:297–303
Groenouw Dystrophy Type I
▶ Corneal Dystrophies
terns of the Maxilla resulting from a single blow to
cadevaric skulls. The fracture lines, or “linea
minoros resistentiae,” described by Le Fort in
1901 are the basis for the modern Le Fort classi-
fication. The midface is attached to the cranium by
three vertical buttresses that help distribute masti-
catory forces and stabilize the midface: the medial
buttress (frontomaxillary buttress) and lateral but-
tress (zygomatico-maxillary buttress) anteriorly
and the pterygomaxillary buttress posteriorly.
The fractures described by Le Fort disrupt these G
buttresses. A Guerin fracture is equivalent to a Le
Fort I fracture (also known as a horizontal frac-
ture) and is a single horizontal fracture through the
maxilla that passes through the septum medially,
extending laterally through the pyriform rims,
passing below the zygomatico-maxillary suture
line, and transecting the pterygomaxillary junc-
tion to interrupt the pterygoid plates (Cummings
2005). Guerin fractures result in a mobile hard
palate. It is important to realize that pure Guerin
fractures are uncommon in clinical practice, and
most midfacial fractures are an amalgam of
various types of midfacial fractures (Figs. 1, 2,
3, and 4).

Etiology

Guerin (Maxillary) Fracture Guerin fractures are generally the result of blunt-
force trauma to the midface. More specifically,
Gary Joseph Lelli1, Dara Liotta2 and Guerin fractures are most likely to occur after a
Ashutosh Kacker2 blow to the inferior aspect of the maxilla, the
1
Department of Ophthalmology, Weill Cornell maxillary alveolar ridge, directed downward.
Medical College, Cornell University, New York, Common causes include motor vehicle accidents,
NY, USA interpersonal altercations, assaults, falls, and
2
Department of Otorhinolaryngology, Weill sports-related injuries.
College of Medicine of Cornell University,
New York, NY, USA
Clinical Presentation

Synonyms In the case of isolated Guerin fracture, overt

clinical signs can be minimal (Papel 2002).
Horizontal fracture; Le Fort I fracture; Maxillary Intraoral ecchymosis, lacerations, or palpable
fracture step-offs may be appreciated. The mobile bone
830 Guerin (Maxillary) Fracture

Guerin (Maxillary)
Fracture,
Fig. 1 Anteroposterior
view of the vertical
buttresses of the facial
skeleton

Guerin (Maxillary)
Fracture, Fig. 2 Lateral
view of the vertical
buttresses of the facial
skeleton

fragment resulting from a Guerin fracture tends
to be driven posteroinferiorly along the slope of
the skull base, resulting in malocclusion and an
anterior open bite with posterior molars
contacting before incisors. There may be crepitus
at the gingival buccal sulcus from subcutaneous
emphysema. Mobility of the hard palate at the
pyriform rims can generally be appreciated. Pal-
atal fractures and fractures of the dentoalveolar
ridge may also occur. Significant facial edema is
Guerin (Maxillary) Fracture
Guerin (Maxillary) Fracture, Fig. 3 Anteroposterior
view of a Guerin fracture (Le Fort I fracture or horizontal
fracture). The shaded area represents the resultant mobile
bone fragment
Guerin (Maxillary) Fracture, Fig. 4 Lateral view of a
Guerin fracture. The shaded area represents the resultant
mobile bone fragment
common with midfacial fractures, and it is
important to keep in mind that presence of a
Guerin fracture does not rule out presence of
additional maxillofacial injuries.
831
Diagnostics
Maxillary fractures often occur as the result of
significant trauma, and evaluation should begin
with airway control and hemodynamic stabiliza-
tion. Serious intracranial injury may be seen in up
to 38% of patients with midfacial fractures; seri-
ous ophthalmologic injury may be seen in up to
28% of patients. Spinal cord injury should be
ruled out, and any overt globe injury should be
evaluated. A thorough history and physical,
including a complete head and neck exam, may
then be performed. With any midfacial fracture,
suspicion for CSF rhinorrhea and/or otorrhea G
should be high. Examination of dental occlusion
is important. Maxillofacial CT scan is considered
the modality of choice for diagnosis of Guerin
fractures.
Differential Diagnosis
Le Fort II fracture, Le Fort III fracture, naso-
orbital-ethmoid fracture, zygomatico-maxillary
complex fracture, palatal fracture.
Prophylaxis
The use of restraints, seat belts, and protective
headgear can help prevent maxillary fractures.
Therapy
Treatment of ocular and CNS injuries should pre-
cede treatment of Le Fort fracture in the presence
of a stable airway. Proper repair of complex mid-
facial fractures may require a surgical airway.
When palatal fractures are present, the repair gen-
erally requires a custom-made reducing splint
adapted to the palatal fragments and wired to the
maxillary teeth. Palatal fractures should be
reduced before plating of other maxillary fractures
to ensure that proper dental occlusion is ultimately
restored. Proper plating of Guerin fractures first
requires mobilization of the resultant bone frag-
ment and application of intermaxillary fixation
832 Guerin Fracture (Le Fort I)

(Stewart 2005). Reconstruction and plating of

disrupted facial buttresses is an important part of Gul Schematic Eye
restoring normal occlusion and vertical height of
the midface and stabilizing the midfacial skeleton Rahul Yadav
against masticatory forces. Perioperative antibi- Department of Ophthalmology, Center for Visual
otics should be considered in patients with facial Sciences, University of Rochester, Rochester,
fractures. NY, USA

Schematic eyes are used in theoretically model-

Prognosis
ing the real human eye as an optical instrument.
The most popular schematic eye currently used
Long-term prognosis after repair of Guerin
is the Gullstrand model eye, which was pro-
fractures is excellent. Postoperative infection
posed by Allvar Gullstrand and for which he
rates are low and generally resolve with oral
received Nobel Prize in 1911. This model
antibiotics.
assumes all the ocular surfaces to be spherical
and mentions their radius of curvatures. The
model also mentions the thickness and refractive
Epidemiology indices of different media inside the eye (the
refractive indices are defined for 587 nm
Maxillary (Guerin) fractures are most common in wavelength).
men aged 21–40. It was well known even at the time of Gull-
strand that the representation of the eye as an
optical system made up of spherical surfaces
and homogeneous refractive index medium is a
Cross-References
simplification. The profiles of all the ocular sur-
faces in reality are aspheric, and the refractive
▶ Le Fort Fractures
indices can have a spatial variation (gradient
▶ Naso-Orbital-Ethmoid Fractures
refractive index). The Gullstrand’s model how-
▶ Orbit, Inflammation of
ever has been popular in the vision science
▶ Zygomatic Bone
area over the last century as it serves well for
▶ Zygomatic-Maxillary Complex Fractures
paraxial calculations. There are four different
Gullstrand model eyes that are currently being
used.
References

Cummings C (2005) Otolaryngology, head & neck surgery, 1. Gullstrand exact eye or Gullstrand eye #1
4th edn. Mosby, Philadelphia, pp 602–636 2. Simplified Gullstrand eye or Gullstrand eye #2
Papel ID (2002) Facial plastic and reconstructive surgery, 3. Gullstrand-Emsley eye
2nd edn. Thieme, New York, pp 759–767 4. Gullstrand-Legrand eye
Stewart M (2005) Head, face and neck trauma, compre-
hensive management. Thieme, New York,
pp 39-5177–85
Gullstrand Exact Eye

Gullstrand exact eye is a detailed representation

of the eye; it assumes the eye’s optical system
Guerin Fracture (Le Fort I) to be having six surfaces. The cornea in this
model is described to be a two-surface element
▶ Le Fort Fractures with finite thickness. The lens is described to
Gul Schematic Eye 833

Gul Schematic Eye, Table 1 Structural parameters of Gullstrand exact eye

Relaxed eye Accommodated eye
Radius Thickness Refractive Radius Thickness Refractive
Surface (mm) (mm) index (mm) (mm) index
Anterior cornea 7.7 0.5 1.376 7.7 0.5 1.376
Posterior cornea 6.8 3.1 1.336 6.8 2.7 1.336
Anterior lens 10 0.55 1.386 5.33 0.67 1.386
surface
Anterior lens 7.91 2.42 1.406 2.65 2.65 1.406
nucleus
Posterior lens 5.76 0.63 1.386 2.65 0.67 1.386
surface
Anterior lens 6 17.18 1.336 5.33 16.8 1.336
nucleus
Image 17.2 17.2 G

Gul Schematic Eye,

Fig. 1 Gullstrand exact
eye schematic

have an inner nucleus and outer shell thus mak-
ing it a four-surface element. The model
describes the eye in both relaxed and accom-
modated states. Table 1 gives the details on the
dimensions and refractive indices for the
relaxed and accommodated Gullstrand exact
eye. Figure 1 shows the schematic of the Gull-
strand exact eye.
Simplified Gullstrand Eye
This model is a simplified version of the Gull-
strand exact eye, which assumes the eye’s optical
system to have four surfaces. The cornea in this
model is the same as in the exact eye, while the
crystalline lens is simplified to a two-surface ele-
ment. Table 2 shows the structural parameters of
834 Gul Schematic Eye

Gul Schematic Eye, Table 2 Structural parameters of simplified Gullstrand eye

Relaxed eye Accommodated eye
Radius Thickness Refractive Radius Thickness Refractive
Surface (mm) (mm) index (mm) (mm) index
Anterior cornea 7.70 0.50 1.376 7.70 0.50 1.376
Posterior cornea 6.80 3.10 1.336 6.80 2.70 1.336
Anterior lens 10.00 3.60 1.408 5.33 4.00 1.426
surface
Posterior lens 6.00 17.18 1.336 5.33 13.82 1.336
surface
Image 17.20 17.20

Gul Schematic Eye,

Fig. 2 Relaxed simplified
Gullstrand eye schematic

this model. Figure 2 shows the schematic of the Table 3 shows the structural parameters of the
simplified Gullstrand eye. model, while Fig. 3 shows the schematic of the
Gullstrand-Emsley model eye.

Gullstrand-Emsley Eye
This model further simplifies the Gullstrand
model by providing a three-surface representation
of the eye where the cornea is assumed to be a
single surface and the lens is assumed to be a
two-surface optical element. Accommodated
state of the eye is not described in the model.
Gullstrand-Legrand Eye
Gullstrand-Legrand eye is perhaps the most
widely used Gullstrand model and is inspired
from the simplified Gullstrand eye. As in sim-
plified Gullstrand eye, this model also assumes
the eye’s optical system to have four surfaces,
Gul Schematic Eye 835

Gul Schematic Eye, Table 3 Structural parameters of Gullstrand-Emsley eye

Surface Radius (mm) Thickness (mm) Refractive index
Cornea 7.8 3.6 1.336
Anterior lens surface 10 7.2 1.413
Posterior lens surface 6 17 1.336
Image –

Gul Schematic Eye,

Fig. 3 Schematic of the
Gullstrand-Emsley eye

Gul Schematic Eye, Table 4 Structural parameters of Gullstrand-Legrand eye

Relaxed eye Accommodated eye
Radius Thickness Refractive Radius Thickness Refractive
Surface (mm) (mm) index (mm) (mm) index
Anterior cornea 7.8 0.55 1.377 7.7 0.55 1.377
Posterior cornea 6.5 3.05 1.337 6.5 2.65 1.337
Anterior lens 10.2 4 1.42 6 4.5 1.42
surface
Posterior lens 6 16.6 1.336 5.5 14.23 1.336
surface
Image 17.2 17.2

two for the cornea and two for the crystalline accommodated states. Table 4 shows the struc-
lens. The curvature, thickness, and refractive tural parameters of the model. Figure 4
index values however are different. This shows the schematic of the Gullstrand-Legrand
model also describes both relaxed and model eye.
836 Gunn Pupillary Test

Gul Schematic Eye,

Fig. 4 Schematic of the
Gullstrand-Legrand
model eye

Cross-References
Gyrate Atrophy of the Choroid and
▶ Accommodation, Cataract Retina
▶ Cornea
▶ Crystalline Lens ▶ Atrophy, Gyrate

Further Reading

Gross H (2008) Handbook of optical systems, vol 4. Wiley-

VCH, Weinheim. Ch. 36
Gyrate Atrophy of the Retina and
Choroid

▶ Choroid, Gyrate Atrophy of

Gunn Pupillary Test

▶ Swinging-Light Test, for RAPD Identification