Transcript A pinguecula is a whiteyellow nodule (thick, blue arrows) at the medial and/or temporal limbus (corneoscleral junction, curved black arrows), occurring as a result of.

A pinguecula is a whiteyellow nodule (thick, blue
arrows) at the medial and/or
temporal limbus
(corneoscleral junction,
curved black arrows),
occurring as a result of sun
exposure. It is therefore more
common in persons with
prolonged outdoor activities
such as farmers or fishermen.
A pterygium (arrows) is
histologically identical to a
pinguecula, but clinically is
a triangular (“wingshaped”) fibrovascular
growth onto the corneal
surface, which requires
excision if it encroaches
into the pupillary axis. It
also is due to sun damage
and typically occurs at the
medial limbus of the eye.
Both pinguecula and pterygium
occur as a result of solar damage to
subepithelial collagen,
characterized histologically by loss
of eosinophilia, and fragmentation
and clumping of these fibers.
Although originally thought to be
damage of elastic fibers, due to the
positive reaction of fibers with a
histochemical stain for elastin,
pretreatment of the tissue with
elastase fails to quench the
positivity. Therefore, it is also
called elastotic degeneration
("elastic-like") of stromal collagen.
The overlying epithelium may be
either atrophic, normal, or
dysplastic.
Herpes simplex keratitis
causes a characteristic
dendritic (branching, arrows)
ulcer of the corneal epithelium
(here stained with rose bengal).
Herpes simplex, once
established, remains latent in
the trigeminal ganglion and
when triggered by stimuli such
as cold or stress reactivates to
cause recurrent bouts of
ulceration. The cornea is
hypesthetic (decreased
sensation) due to the nerve
involvement, and prone to
superinfection by other
organisms.
Recurrent bouts of herpes
simplex keratitis may
cause inflammation to
extend into the corneal
stroma (stromal keratitis),
with subsequent
vascularization and
scarring. This is a
histologic section of a
corneal transplant from a
patient with stromal
keratitis. Note the
vascularization (arrows) at
all levels of the corneal
stroma, with associated
chronic inflammation.
Corneal dystrophies are inherited,
bilateral, progressive, alterations of
corneal structure that may involve
any of the corneal layers. This is
an example of Fuchs’ dystrophy of
the corneal endothelium. Although
there is no recognized familial
inheritance pattern, it typically
manifests as corneal edema and
bullous keratopathy in elderly
individuals, women more
commonly than men. The clinical
hallmark of Fuchs’ dystrophy is
the development of central corneal
guttata (“drops”), seen best on
specular reflection of the
endothelial surface, using the slit
lamp (blue arrows).
Histologic section of a
cornea with Fuchs’
dystrophy shows guttata to
be flat-topped excrescences
of Descemet’s membrane
(PAS stain) with
discontinuity of the
endothelial mosaic
allowing fluid into the
corneal stroma.
Glaucoma is damage to the retinal
nerve fibers associated with an
increase in intraocular pressure. It
can be divided into 2 major
categories: angle-closure (or closed
angle glaucoma) and open angle
glaucoma. Aqueous humor, the
principal determinant of intraocular
pressure, is formed by the ciliary
processes, flows from behind the iris
through the pupil into the anterior
chamber and then out through the
trabecular meshwork or the
suprachoroidal space. If the
trabecular meshwork is physically
blocked by the peripheral iris, the
angle is considered closed. If it is
not, then it is considered open.
Angle-closure glaucoma is
an acute rise in pressure due
to physical blockage of the
anterior chamber angle
structures, leading to
symptoms of redness,
ocular pain, photophobia,
cloudy vision, and seeing
haloes around lights. The
angle blockage often occurs
after the patient has been in
a dark place for several
hours (pupil dilated,
peripheral iris apposed to
trabecular meshwork).
This histologic section
through the anterior portion
of the eye demonstrates
occlusion of the anterior
chamber angle by the iris.
Note the physical blockage
of the trabecular meshwork
by the peripheral iris.
Cornea
Trabecular
meshwork
Iris
Posterior chamber
Sclera
Ciliary body
If not treated promptly,
angle-closure
glaucoma will also
cause injury to retinal
nerve fibers, but does
not typically cause deep
excavation of the optic
disc. The affected disc,
seen on the left, is pale
(especially temporally,
blue arrow) as
compared to the normal
disc on the right (black
arrow), but is flat rather
than excavated.
Primary open angle glaucoma
is the most common type,
occurring in about 4 % of the
U.S. population over 40 years
of age. It may escape detection
until advanced injury has
occurred, since it is insidious
and often asymptomatic. The
chronically increased
intraocular pressure leads to
loss of ganglion cells, the axons
of which make up the nerve
fiber layer and optic nerve. The
optic disc becomes increasingly
cupped, as shown
in this fundus photograph (rim
of cupping outlined by arrows).
A corresponding
histologic section
through the optic disc
shows the excavation of
the disc, with
undermining of the
edges (so-called
"beanpot" cup).
Cataract is an opacity of
the lens. This photograph
shows one type of
cataract, a posterior
subcapsular cataract
(arrows), often seen in
patients on prolonged
corticosteroid therapy. It
may also be seen as an
age-related phenomenon
or in diabetics. Blue
arrows indicate the
posterior surface of the
lens, yellow arrows the
anterior surface, and
white arrows outline the
cataract.
Histologically,
posterior subcapsular
cataract is
characterized by
posterior migration and
swelling of lens
epithelial cells (socalled “bladder cells of
Wedl”, blue arrows).
Lens epithelium does
not normally line the
posterior lens capsule
(black arrows) after
birth.
Cataracts involving the lens
cortex may assume a variety
of shapes, but most
commonly present as
wedge-shaped white
opacities (black arrows),
with the apices of the wedge
pointing toward the center of
the lens.
Histologically, cortical
cataracts are
characterized by the
fragmentation and
rounding up of lens fibers,
producing eosinophilic
globules (“Morgagnian
globules”). Since the lens
fibers lose their nuclei
during development,
anuclear Morgagnian
globules can be
histologically
differentiated from the
nucleated bladder cells of
Wedl.
Another type of age-related cataract is
nuclear sclerosis. The central portion
(nucleus) of the lens becomes yellowbrown (brunescent) and opaque. Nuclear
sclerosis causes an increase in the
refractive power of the eye; the elderly
patient becomes more myopic and able to
read again without bifocals or reading
glasses (so-called "second sight"). Since
the nuclear lens fibers are normally
compacted with maturation, histologic
differences between normal eyes and tbose
with nuclear sclerotic cataracts are not
readily recognizable. Yellow arrows mark
the anterior lens surface, blue arrows the
posterior lens surface, and white arrows
the nuclear cataract.
Sympathetic ophthalmia is a
granulomatous inflammation of the
choroid in the fellow eye of a patient
who has had a penetrating injury of one
eye. The immune system reacts with an
as yet undetermined antigen which was
unmasked by the injury, and attacks the
fellow ("sympathizing") uninjured eye.
Enucleation of the injured eye within
two weeks of injury will prevent the
immune response. Fundoscopy (top)
shows yellow-white subretinal nodules
with a hazy view due to cells in the
vitreous. Fluorescein angiography
(bottom) demonstrates
hyperfluorescence of the nodules due
to increased vascular permeability in
the areas of inflammation.
Histologic section of the
choroid in sympathetic
ophthalmia shows ill-defined
aggregates of epithelioid
histiocytes (i.e., granulomas,
arrows) with surrounding
lymphocytes.
The most common primary
malignant eye neoplasm in
adults is malignant melanoma
of the uvea (uvea is the
vascular layer of the eye and
consists of the iris, ciliary body
and choroid). Most melanomas
occur in the posterior aspect of
the eye (and therefore arise in
the choroid), as seen in this
fundus photograph. They
typically have a dome-shaped
or mushroom-shaped
appearance, and pigmentation
can be heavy, variable, or
nonexistent.
Ultrasonography of
melanomas will demonstrate
their shape and relative
density. On the left is a Bscan, showing a mass (white
arrow) in the posterior aspect
of the eye. On the right is an
A-scan which shows the high
peak (blue arrow) at the
surface of the tumor, with
low internal reflectivity
(lower peaks following the
initial spike).
MRI is also useful in
documenting the shape and
internal characteristics of
uveal melanoma
(hypointense to vitreous on
T1-weighted image [yellow
arrow]; hyperintense on T2weighted image [blue
arrow]), but most importantly
may demonstrate extraocular
extension (not seen here).
T1
Vitreous
A gross photograph
of a mushroom or
collar-button shaped
choroidal
melanoma situated
at the equator of the
eye. When the tumor
breaks through
Bruch's membrane to
expand into the
subretinal space, the
elastic nature of
Bruch's membrane
causes the focal
constriction and
mushroom shape of
the tumor.
Along with size and extraocular
extension, a major prognostic factor
in melanoma is the histologic cell
type. Uveal melanomas can be
divided into spindle (good
prognosis), epithelioid (poor
prognosis) and mixed spindleepithelioid (intermediate prognosis)
categories. Spindle cells have
elongate nuclei, longitudinal
nuclear grooves and/or punctate
nucleoli, and indistinct cell borders,
as seen here
Epithelioid cells, in
contrast to spindle cells,
are polygonal cells with
rounded nuclei, prominent
central nucleoli, and
distinct cell borders.
Mitotic figures are usually
more evident in
epithelioid melanomas
than in their spindle cell
counterparts.
Melanomas gain access out of
the eye principally through
emissaria, channels carrying
vessels and nerves that
penetrate the sclera to supply
the intraocular tissues. In this
histologic section, melanoma
cells are exiting the eye along
an emissarial canal (arrows)
containing an artery, the lumen
of which is at the lower right.
The vortex veins are the most
common point of egress for
choroidal melanomas.
Metastasis of uveal melanomas
is usually hematogenous, and
the liver is the site most
commonly involved.
The most common
intraocular malignancy in
adults is not primary, but
secondary, i.e. metastasis.
Lung and breast carcinomas
are the most likely to spread
to the eye. In contrast to
primary uveal melanomas,
metastases are often placoid
(flat or shallowly elevated),
as seen in this fundus
photograph, and multiple.
They typically are a nearterminal event; the average
life expectancy after
diagnosis of an intraocular
metastasis
is 6-9 months.
This histologic section
demonstrates a choroidal
metastasis of squamous cell
carcinoma (lung primary).
Commonly, metastatic lung
cancer may present in the eye
without the primary tumor
being known, making the
clinical distinction between
primary and secondary
tumors in the eye difficult.
Any patient presenting with
an intraocular mass should
have a systemic workup to
exclude metastasis from
another site.
Cytomegalovirus
retinitis typically
occurs in
immunocompromised
patients, particularly
AIDS. The infection
usually tracks along
retinal vasculature
(left), causing
opacification and
hemorrhage; variant
clinical
manifestations may
include macular
disease (right).
Histologic section of a
retina infected with
CMV. Note the large
cells with prominent
basophilic "owl's eye"
intranuclear inclusion
(arrows).
Background diabetic
retinopathy is characterized
by numerous
microaneurysms, dot
hemorrhages and hard
exudates, and occasional
cotton-wool spots (blue
arrow) in the posterior
fundus. Most of the red dots
seen in this picture represent
hemorrhages;
microaneurysms are more
easily seen on fluorescein
angiography.
Fluorescein angiography
(same field as the previous
fundus photograph) is
much more sensitive in
identifying
microaneurysms and is the
method of choice for
following patients. It will
also highlight areas of
capillary nonperfusion and
any neovascularization.
Trypsin digested (to
remove nonvascular
tissue) ink injected
whole mount
preparations of retina
highlight
microaneurysms (blue
arrows) of the capillary
bed and areas of
nonperfusion (yellow
arrows). The initial
pathologic alteration is
loss of pericytes in the
capilary walls, followed
by loss of endothelial
cells and lack of blood
flow.
Preproliferative
diabetic retinopathy is
heralded by venous
beading and tortuosity,
numerous cotton-wool
spots (arrows), and
intraretinal microvascular
abnormalities
("IRMA's"). Patients who
develop these changes
are at high risk for
subsequent
neovascularization, and
should be treated with
panretinal
photocoagulation.
Formations of new vessels
(neovascularization,
"NV") at the
optic disc ("NVD") or
elsewhere in the retina
("NVE") are the hallmark
of proliferative diabetic
retinopathy. The new
vessels may grow on the
surface of the retina, but
often grow into the
vitreous. These vessels are
abnormal and bleed easily,
leading to reparative
fibrovascular tissue
ingrowth, contraction, and
tractional retinal
detachment.
NVD
Photomicrograph of
neovascularization
along the surface of
the retina (black
arrow). Note the
wrinkling of the
retina, particularly the
photoreceptors (white
arrows), resulting in
focal tractional retinal
detachments.
Proliferative diabetic
retinopathy with early
(left) and established
(right) fibrovascular
tissue ingrowth (socalled “retinitis
proliferans”).
A gross photograph (left)
of a complete funnelshaped retinal
detachment extending
forward from the optic
disc in an enucleated eye.
A higher magnification
(right) of an in vivo
fibrovascular tissue
membrane (arrows) into
the vitreous in a patient
with proliferative diabetic
retinopathy.
A low power histologic
section demonstrates a
closed funnel-shaped
complete retinal
detachment. The
subretinal space (blue
arrows) is filled with
serosanguinous fluid.
Contracture of the
fibrovascular tissue has
pulled the retina forward
to occupy the retrolental
space (black arrows). The
choroid and ciliary body
are artifactually separated
from the sclera (yellow
double arrows).
Panretinal laser
photocoagulation inhibits
neovascularization by
obliterating the ischemic
retina and circumventing
production of angiogenic
factors. The fundus photo on
the left shows the results of
laser burns in a grid pattern
shortly after treatment; at a
later date the retinal pigment
epithelium has
hypertrophied and caused
the spots to become
pigmented.
A histologic section through
a photocoagulation burn
shows focal loss of
photoreceptors [PR] and
outer nuclear layer [ONL],
with chorioretinal adhesion
(curved blue arrows)and
retinal pigment epithelial
hypertrophy (straight blue
arrows).
ONL
PR
Even in advanced
proliferative
diabetic
retinopathy (left)
(“retinitis
proliferans”),
vitrectomy
(surgical removal
of vitreous and
fibrovascular
tissue) may allow
the retina to
become
reattached and
recover some
degree of vision
(right).
The fundus picture in
accelerated
("malignant")
hypertension is similar
to that in central retinal
vein occlusion,
although it is bilateral
and predominantly
localized to the
posterior fundus. In
addition, hard exudates
(small yellow dots) are
present in the macula.
Histologic sections of
cotton-wool spots
show microinfarcts
with swelling of nerve
fibers ("cytoid
bodies") in the nerve
fiber layer (left). The
swelling results from
axoplasmic stasis and
accumulation of
intracellular
organelles such as
mitochondria. On the
right the cytoid bodies
(arrows) are
highlighted by ink
injected into the
ganglion cells.
Histologic section of a
hard exudate (blue
arrow) shows its
characteristic location
in the outer plexiform
layer of the retina. It is
the result of leakage of
lipids and proteins into
the retina without
complete
resorption.[ONL=outer
nuclear layer;
OPL=outer plexiform
layer; INL=inner
nuclear layer]
INL
OPL
ONL
Fundus appearance in
central retinal artery
occlusion shows a
cherry red spot in the
fovea (arrow) due to
edema (without
hemorrhage) of the
surrounding retina. The
fovea, being the
thinnest area of the
retina, allows the red
reflex of the choroid to
show through. Central
retinal artery occlusion
causes immediate,
complete blindness and
is irreversible if
untreated within hours.
Histologic cross section of an
optic nerve demonstrates a
thrombo-embolus occluding
the central retinal artery
(blue arrow), and
recanalization of the central
retinal vein (black arrow)
indicating prior occlusion of
that vessel. Vein occlusions
most commonly are due to
compression by a diseased
artery (hypertension,
atherosclerosis), since the two
share a common adventitial
sheath. This histologic section,
therefore, shows features
indicating both central retinal
artery and vein occlusion.
A fundus photograph of
central retinal vein
occlusion shows marked
hemorrhage and cotton-wool
spots throughout the retina
(so-called "strawberry
sundae”appearance), with
edema of the optic nerve
head.
A histologic section in
vein occlusion shows
intraretinal
hemorrhages in nearly
all layers of the retina
and in the subretinal
space, resulting in a
hemorrhagic retinal
detachment.
Retina
Choroid
Rhegmatogenous retinal
detachments refer to
detachments due to tears in the
retina (arrow), with leakage of
liquefied vitreous through the
tear into the subretinal space.
Tears are caused by vitreoretinal
adhesions. When the vitreous
exerts traction on these
adhesions, as when the posterior
vitreous detaches and falls
forward, tears may result.
Detachments may be bullous
and billowing[left photograph]
or shallow and rippling [right
photograph].
Histologic sections of
normal (left side) and
detached (right side)
retina, demonstrating
degeneration of
photoreceptor outer
and inner segments
with separation from
the retinal pigment
epithelium [RPE] by
serous fluid
containing pigmentladen cells.
Subretin
RP
Age-related macular
degeneration, a
common cause of legal
blindness
in the elderly in the
U.S., may occur in two
forms. Pictured here is
the atrophic ("dry")
form, in which yellowwhite subretinal
deposits accumulate in
the macula. In this form,
visual acuity is
decreased somewhat
[20/40 to 20/400 range],
but peripheral vision is
maintained.
Histologic section of
drusen (hyalinized
deposits along Bruch's
membrane, arrows) lifting
up the retinal pigment
epithelium. Coalescence
of drusen form the
macroscopically visible
subretinal deposits in the
fundus.
The "wet" form of age-related
macular degeneration, as seen in this
fundus photograph, is far more
visually disabling. Breaks in Bruch's
membrane form, and
neovascularization occurs, growing
from the choriocapillaris through the
breaks, into the subretinal space.
Bleeding and organization ensues,
leading to a disciform scar separating
the macula from its metabolic supply.
In this fundus photograph, the blue
arrow points to the neovascular
membrane. Surrounding it is subretinal
hemorrhage (white arrows), with some
exudates inferiorly at the edge of the
hemorrhagic retinal detachment
(yellow arrows).
Histologic sections demonstrate
the fibrovascular tissue
ingrowth into the subretinal
space, and the lower section
shows marked architectural
disruption of the retina as an end
result.
Retina
Subretinal space
Choroid
Retinoblastoma is caused by mutation
or deletion of the retino-blastoma gene
on chromosome 13q14. The normal
gene product suppresses tumor
formation; the altered gene product
allows tumor growth. Both alleles of the
chromosome must be altered in order to
allow tumor formation. If one allele is
inherited from a parent, or mutates in the
germ cell, all somatic cells will carry the
mutation and the chances of multiple
cells acquiring the second allelic
mutation is increased, so that multifocal
and bilateral retinoblastomas usually
result. If there is no germline mutation,
then the chance of more than one cell
having both alleles altered is remote, and
a solitary retinoblastoma is the norm.
Retinoblastoma
typically occurs in
children age 4 or less;
in inherited or germline
mutations the average
age at diagnosis is
around 1 year. Tumors
may grow into the
visual axis and be
visible as whitish
masses in the pupil
(leukocoria), as in this
case of bilateral
retinoblastoma.
The tumor originates within
primitive retinal neural cells, and
proliferates rapidly, often
outstripping its blood supply so
that the tumors are often partially
necrotic and calcified. The
principal prognostic factor for
patient survival is extraocular
involvement (tumor outside the
eye portends a bad prognosis).
Retinoblastomas typically exit
the eye through the optic nerve
[ON], as is show in this low
power histologic section. Once in
the nerve, the tumor may gain
access to the subarachnoid space
and disseminate throughout the
central nervous system.
ON
Flexner-Wintersteiner
rosettes (arrows) are comprised
of tumor cells forming a ring
about an empty central lumen.
The luminal lining recapitulates
the external limiting membrane
of the normal retina.
Fleurettes are architectural
forms indicating even more
photoreceptor differentiation:
putative attempts at forming
rod or cone inner segments.
These are characterized by
bulbous protrusions of
cytoplasm into the empty
central lumen (arrow).