Congenital Retinal Anomalies

Embryology
• Neural ectodermal cells – first month of development
• Ganglion cell layer – first – sixth week of gestation
• Cones – 5 months
• Rods – 7 months
• Growth after birth too – RB
• Vitreous develops in 3 stages
– First – 2-3 month
– Second and Tertiary – 3-4 month
– Supply from – Hyaloid artery
 Epidemiology
• Rare anomalies
• Diseases With Specific Retinal Findings That
Suggest a Diagnosis
■ Egg yolk—Best disease
■ Lacunae—Aicardi syndrome
■ Cherry-red spot—metabolic diseases
■ Retinal necrosis and hemorrhage—
Cytomegalovirus
■ Astrocytic hamartoma—Tuberous sclerosis
 Pathogenesis
• Congenital defects (e.g., coloboma),
• Vascular abnormalities (e.g., retinopathy of
prematurity [ROP]),
• Infections
• Tumors,
• Trauma, and
• Metabolic diseases
 Clinical Presentation
• Unilateral abnormalities may be difficult to detect, because
the children function well if the vision is good in the other
eye.
• The vision loss may not be noticed until the child has a
vision test or if the child occludes the normal eye
• Strabismus may develop in eyes with unilateral vision loss
• In some lesions, such as retinoblastoma or large
colobomas, an abnormality of the red reflex may be noted.
• If the vision loss is bilateral, decreased vision will usually be
evident.
• In infants, significant bilateral vision loss initially manifests
as nystagmus that develops within the first 2 to 3 months
of life.
 CONGENITAL
• Coloboma
– incomplete closure of the embryonic fissure
– inferonasal quadrant
– white defects, because the sclera is directly visible due to
the absence of normal retina and retinal pigment
epithelium
– Prognosis – Foveal involovement
– Isolated or may withsystemic disorders, such as CHARGE
(Coloboma, Heart defects, Atresia choanae, Retardation of
growth, Genitourinary anomalies, and Ear anomalies)
syndrome.
– Not progressive.
– Difficult to treat.
 Congenital Retinal Fold
• Rare anomalies
• A fold of retinal tissue extends from the optic
nerve to the retinal periphery, usually in the
inferotemporal portion of the eye
• May be inherited in an autosomal dominant
• associated with marked vision loss, and are
not amenable to treatment.
 Persistent Fetal Vasculature
• incomplete regression of the hyaloid blood
vessel during embryological development
 Aicardi Syndrome
• X-linked – Distinctive retinal changes.
• Females
• maternal spontaneous abortions
• Systemic findings
– absence of the corpus callosum,
– developmental delay, and
– seizures.
• Retinal findings
– multiple round depigmented areas (lacunae),
primarily in the posterior portion of the retina
 Albinism
• Decreased pigment (oculocutaneous albinism
[OCA])
• Isolated to the eye (ocular albinism).
• Neonatal period with decreased vision and
nystagmus.
• Decreased skin and hair pigment.
– Transillumination defects of the iris
– Decreased peripheral retinal pigmentation,
– Hypoplasia of the fovea
– VA Range : 20/100 - 20/200
 Foveal Hypoplasia
• The normal foveal reflex is missing and the retinal
blood vessels are not organized around the
fovea.
• The abnormal foveal anatomy causes decreased
vision in patients with foveal hypoplasia.
• Albinism
• Aniridia
• May be suspected of having amblyopia or
factitious visual loss unless the retina is carefully
examined.
 ABNORMALITIES OF
VASCULAR DEVELOPMENT
• Retinopathy of Prematurity
• Abnormal neovascular tissue develops. This
tissue may proliferate and cause bleeding and
traction, which can progress to retinal
detachment.
• Major cause of morbidity in premature infants.
• The risk increases with decreasing birth weight
and gestational age, occurring almost exclusively
in infants born at 30 weeks gestation or less.
• The presence of plus disease is a key indicator
of risk. Plus disease describes increased
tortuosity and dilation of the posterior blood
vessels which reflects the abnormal retinal
vascular development.
 Stages
• 1 - Demarcation line
• 2 – Elevated ridge at border of demarcation
• 3 – Elevated Ridge with abnormal blood
vessels
• 4 – Partial Tractional Retinal Detachment
• 5 – Total Retinal Detachment ( closed funnel)
 Treatment of ROP

• Prevent retinal distortion and detachment by stopping the abnormal

vascular activity
• The presence of any plus disease or stage 3 disease in zone 1, or the
presence of stages 2 or 3 and plus disease in zone 2
• The peripheral retina in patients with ROP produces vascular endothelial
growth factor (VEGF), which stimulates the growth of abnormal vessels.
• Treatment
– laser or cryotherapy
– The goal is to decrease production of VEGF and induce regression of the
abnormal vessels.
• Develop scars in the fovea after treatment, which may impair visual acuity
• If patients develop progressive retinal detachments, retinal surgery (such
as vitrectomy) may be indicated.
• Visual Prognosis – Poor
intraventricular hemorrhage
 Other Disorders of Peripheral
Retinal Vascularization
• Norrie disease.
– An X-linked disorder characterized by the retinal
abnormalities, hearing loss, and developmental
delay.

• Familial exudative vitreoretinopathy (FEVR).

– An autosomal dominant disorder caused by
mutation of the FEVR1 gene on chromosome 11
• Incontinentia pigmenti.
– An X-linked disorder that is usually lethal in males.
– Affected patients develop bullous erythematous skin
lesions in the neonatal period, followed by verrucous
changes, and subsequently hyperpigmented macules.
– Developmental delay and dental changes occur in
some patients.
– Approximately one-third of patients develop retinal
changes similar to ROP. Many patients also develop
cataracts.
• Coat’s disease.
– An idiopathic disorder of retinal vasculature that
occurs in older children.
– Unilateral.
– Peripheral abnormal telangiectatic retinal blood
vessels proliferate and leak exudative fluid
produce large collections of yellow subretinal fluid
and retinal detachments
• Von-Hippel-Lindau disease (VHL).
– An autosomal dominant disorder in which
patients develop vascular tumors of the retina and
central nervous system.
– Systemic manifestations include renal cell
carcinoma, pheochromocytoma, and lesions in
multiple other organs
Peripheral retinal
angiomas
• Sickle cell disease.
– Develop peripheral retinal abnormalities secondary to
decreased vascular perfusion.
– Caused by arteriolar occlusion induced by sickling of
the abnormal red blood cells.
– Patients with hemoglobin SC disease and sickle
thalassemia have the highest risk of retinal
complications.
– If untreated, this may progress and cause vitreous
hemorrhage and retinal detachments.
– Laser treatment is used to treat these lesions
 INFECTIOUS DISEASES
• Herpes Simplex Virus
• Congenital HSV is usually acquired during passage
through the birth canal.
• systemic involvement, including the skin, central
nervous, liver, lungs, and eyes.
• Ocular findings include conjunctivitis and keratitis. If the
retina is involved, patients may develop massive retinal
necrosis with marked visual loss.
• Treatment includes systemic medication, such as
acyclovir.
• Cytomegalovirus
– common congenital infection in humans.
– Asymptomatic.
– Systemic manifestations liver, hematological, hearing, and
central nervous system abnormalities.
– Ophthalmic manifestations retinochoroiditis, which is
characterized by focal areas of retinal necrosis and
hemorrhages.
– Infants with systemic involvement and older
immunocompromised children with CMV are usually treated
with ganciclovir.
• Syphilis
– Congenital syphilis may cause a wide variety of
systemic and ocular problems.
– Ocular abnormalities may develop in infancy or
later in childhood.
– Retinal involvement consists of chorioretinitis,
which may appear similar to retinitis pigmentosa.
• Toxoplasmosis
– Toxoplasma gondii, an obligate intracellular
parasite.
– Exposure to cats or through contaminated meat
or drinking water.
– Congenital infections are associated with liver,
spleen, central nervous system, and ocular
involvement.
• Characterized by inactive circumscribed pigmented
retinal scars.
• If the lesions reactivate, focal areas of retinitis with
inflammation and overlying vitritis are seen
• selflimited, but reactivation may occur.
• Treatment is generally reserved for active lesions that
may impair vision, such as those in the fovea.
• combination of antimicrobials for the infection and
corticosteroids to decrease inflammation.
Inactive scar

Active scar with inflammation

Adjacent to scar
• Rubella
• Systemic involvement includes cardiac, hearing, and
central nervous system abnormalities.
• Ocular findings include cataracts and glaucoma.
• Retinal manifestations include pigmentary changes that
may mimic retinitis pigmentosa.
• The spotty areas of pigmentation are sometimes
described as salt-and-pepper retinopathy
• Lymphocytic Choriomeningitis Virus
– Transmitted by exposure to rodents.
– Systemic manifestations primarily involve the central nervous system,
including hydrocephalus, microcephaly, calcifications, and
developmental delay.
– Ocular manifestations consist of chorioretinal scars, primarily in the
posterior retina.
– The appearance of these scars may be similar to those seen in
toxoplasmosis and Aicardi syndrome.
• Toxocariasis
• Toxocara canis, a parasite - exposure to dog or cat
feces or unclean food.
• Systemic involvement includes visceral larval migrans,
usually in infants and toddlers. It may present with
flulike symptoms.
• Ocular involvement - focal retinal granulomas,
associated with inflammation and bands of traction
tissue.
• Treatment is indicated if the vision is threatened.
• Bacterial Endophthalmitis
• Rare and potentially devastating infection of the
vitreous and retina.
• commonly occurs as a result of penetrating ocular
injury or as a complication of ophthalmic surgery.
• Rarely, endogenous endophthalmitis may develop in
patients with endocarditis or other systemic disease.
• marked ocular inflammation with hypopyon.
• Prompt treatment with systemic and intravitreal
antibiotics is usually necessary if vision is to be
preserved.
 INHERITED DISORDERS OF
RETINAL FUNCTION
• Retinitis Pigmentosa
– Characterized by dysfunction of the retinal
photoreceptors (rods and cones).
– Patients with RP typically develop pigmentary
changes in the retina, with clumps of
hyperpigmented tissue that appear like bone
spicules.
• Leber Congenital Amaurosis
• A congenital form of RP - an autosomal recessive fashion
• It presents within the first few months of life with poor
or absent visual fixation and nystagmus.
• Poorly reactive pupils and marked farsightedness are
usually present.
• The retina initially appears normal, but most patients
develop pigmentary changes with age.
• Systemic Disorders Associated with Retinitis
Pigmentosa
– Bardet-Biedl syndrome is associated with
developmental delay, extra digits on the hands
and feet, obesity, and hypogonadism.
– Usher syndrome is associated with sensorineural
hearing loss.
• Stargardt Disease (Juvenile Macular Degeneration)
– Autosomal recessive
– Unexplained vision loss, usually during the second decade.
– Caused by a mutation of the retina-specific ATP-binding
transporter protein (ABCR). The retina often initially appears
normal, and the child may be suspected of malingering.
– “beaten metal” appearance of the macula
– Some patients have a characteristic dark appearance of the
choroid on fluorescein angiography of the retina.
• Neuronal Ceroid Lipofuscinosis (Batten
Disease)
– Autosomal recessive - abnormal deposits develop
in neuronal lysosomes.
– Present with decreased vision, developmental
delay, and seizures.
– Ophthalmic findings include optic nerve atrophy
and pigmentary deposits within the retina
• Disorders Associated With Cherry-red Spots
– Tay-Sachs,
– Niemann-Pick,
– Sialidosis, and
– Sandhoff disease.
• The appearance is due to accumulation of
abnormal material in the ganglion cells
surrounding the fovea
 Other Inherited Disorders
of Retinal Function
• Best vitelliform dystrophy.
– An autosomal dominant - mutation of the
vitelliform macular dystrophy gene.
– Yellow cystic structure in the macula that may
look like an egg yolk.
– The diagnosis is established by an abnormal
electrooculogram, which reflects dysfunction of
the retinal pigment epithelium.
• Achromatopsia (rod monochromatism).
– Characterized by absent cone function.
– Infants present in a similar fashion to LCA, with
minimal fixation and nystagmus in early infancy.
– Usually photophobic.
– Absence of cone responses - ERG
• Congenital stationary night blindness.
– Less severe form of congenital RP.
– Infants typically present with nystagmus in the
first few months of life, but visual function is not
markedly impaired.
– Diagnosis - ERG
• Juvenile retinoschisis
– An X-linked disorder - inner layers of the retina
separate.
– Initially –fovea and Older develop peripheral
retinal detachments
– Progressive vision loss.
– A characteristic ERG abnormality (a decreased
scotopic b-wave with preserved a-wave) is
diagnostic.
• Joubert syndrome.
• maldevelopment of the cerebellar vermis,
• Imaging - “molar tooth sign.”
• It frequently presents with abnormal breathing in
infancy.
• Other systemic features include hypotonia, ataxia, and
developmental delay.
• Some patients with Joubert syndrome have a congenital
form of retinal dystrophy that presents with poor visual
responses and nystagmus in infancy.
• Ocular motor apraxia is a common feature.
 Retinoblastoma
• Most common intraocular malignancy of infancy and childhood

• Autosomal dominant inheritance

• Affects 1:20,000 live births

• Mean age of presentation is 18 months (unilateral at 24 months, bilateral

at 13 months)

• 13q14 chromosome defect

• Unilateral or bilateral (70% unilateral)

Genetics of RB
 Clinical Description
• Leukocoria
• Strabismus
• Rubeosis
• Hypopyon
• Hyphema
• Buphthalmia
• Orbital cellulitis
 Clinical Diagnosis
• Fundoscopy
• Ultrasound imaging
• Magnetic resonance imaging
• Computed tomography
Ultrasound of RB
Grouping of Retinoblastoma
 Group A
– small tumors with round configuration.

– tumors greater than 3 mm from fovea and

greater than 1.5 mm from optic disc.

– No intraocular tumor dissemination

 Group B

– Tumors still discrete but larger or closer

to critical structures than group A.

– Subretinal fluid extending no further

than 5 mm from tumor base.

– No intraocular tumor dissemination

 Group C
» Tumors that have progressed
through group A and B.

» Tumor dissemination located

near the originating site.

» Focal, fine, localized vitreous

or subretinal seeding.
 Group D
» More extensive dissemination of
intraocular tumor than in group C.
» SRF occupying more than one
quadrant of retina.
» Upto total RD.

» Massive and / or diffuse vitreous

seeding extending at distance from
tumor
 Group E

» Tumors include any or all

characteristics of group A through D.

» Tumor features of effects associated

with irreversible ocular morbidity
Choice of treatment depends on…
• Tumor size
• Location
• Laterality
• Presence of vitreous or subretinal seeding
• Potential visual acuity
• Tolerance of child for various therapies
• Risk for second cancers
 Current therapies for
retinoblastoma
• Enucleation
• External beam radiotherapy
• Brachy therapy
• Transpupillary thermotherapy
• Chemotherapy (local and systemic)
• Laser photocoagulation
• Cryotherapy
• Observation (for spontaneously regressed tumors)
Regression patterns in
Retinoblastoma
Type 0 – regression with no
tumor remnant

Type 1 – regression with

completely calcified
remnant

Type 2 – regression with

noncalcified remnant
 Regression patterns in
Retinoblastoma

Type 3 – regression with Type 4 - regression with flat

partially calcified tumor chorioretinal scar
remnant
 RETINAL HEMORRHAGE
• Parturition-related Hemorrhage
– Most common following vacuum-assisted
delivery, occasionally following caesarean section.
– Vary from scattered posterior hemorrhages to
diffuse bleeding in all quadrants of the eye.
– Usually resolve without sequela during the first
few weeks of life.
• Nonaccidental Trauma
– Child abuse,
– Often associated with intracranial hemorrhages and other signs of abuse.
– The hemorrhages may occur in any layer of the retina and vitreous hemorrhage may
also occur.
– The presence of retinal hemorrhages is an important finding in the evaluation of
patients suspected of abuse.
– Diffuse multilayered retinal hemorrhages, particularly in the absence of external signs of
trauma, are highly suspicious for nonaccidental injury
– In severe cases of shaking injury the layers of the retina may split (retinoschisis). This
produces a dome-shaped elevation overlying the macula, often with folds of retinal
tissue bordering the lesion
– Blood layering may occur within this cavity, with the position of the blood dependent on
how the patient’s head is positioned.
– This finding has been very rarely reported in infants with severe crush head injuries. In
the absence of such a history and associated findings, retinoschisis cavities are
essentially pathognomonic for nonaccidental injuries.
Retinoschisis with premacular folds
 OTHER SYSTEMIC DISEASES
ASSOCIATED WITH SPECIFIC
RETINAL ABNORMALITIES
• Tuberous Sclerosis (Bourneville disease)
– An autosomal dominant phakomatosis.
– Most cases represent new mutations.
– Systemic abnormalities include developmental delay, seizures, and
tumors of the central nervous system, kidney, and heart.
– Characteristic skin lesions include ash-leaf spots, adenoma sebaceum,
and subungual fibromas.
– Approximately one-third to one-half of patients with TS have retinal
astrocytic hamartomas.
– In young patients these are typically smooth, elevated grayish nodules
that are found in the posterior retina.
Adenoma sebaceum

Ash-leaf spot
Tuberous sclerosis.
Retinal astrocytic hamartomas
(arrows), with appearance similar to
retinoblastoma
• Retinal astrocytic
hamartoma with
lobulated
appearance, more
commonly seen in
older affected
children.
• Neurofi bromatosis Type 2
– Less common than neurofi bromatosis type 1
– An autosomal dominant fashion.
– Patients uniformly develop acoustic neuromas.
– They do not have iris Lisch nodules.
– Posterior subcapsular cataracts may occur.
– A specific retinal abnormality associated with NF2 is an epiretinal
membrane.
– These arise on the inner retinal surface and may cause a wrinkled
appearance of the retina when they contract.
– Epiretinal membranes occur relatively commonly in adults,
particularly the elderly.
• Chronic Granulomatous Disease
– A disorder of phagocytosis - An X-linked fashion.
– Patients develop severe recurrent infections in
multiple organ systems.
– Patients may develop idiopathic retinal pigment
epithelial scarring along the course of the retinal
blood vessels
 Pigment
ed
perivasc
ular
lesions
• Familial Adenomatous Polyposis (Gardner Syndrome)
– An autosomal dominant disorder in which affected individuals
develop polyps in the colon with a high potential for malignant
conversion.
– Congenital hypertrophy of the retinal pigmented epithelium is a
fairly common retinal finding in normal individuals,
characterized by circular areas of dark retinal pigmentation.
– Patients with Gardner syndrome develop similar lesions, but
they are increased in number and have an ovoid appearance
– This retinal finding may be useful in identifying patients in
families with Gardner syndrome who are at risk for the
development of colon cancer.
areas of congenital hypertrophy
of the retinal pigment epithelium
Thank you