Hypopigmented Retinal Lesions

Alex V. Levin



• Lesions characterized by reduced or absent pigment in or absence of the retinal pigmented epithelium or choroid present at birth.

• Includes, but is not limited to: Tumors (retinoblastoma, astrocytic hamartoma of tuberous sclerosis, congenital benign gliotic tumors), infections (cytomegalovirus, toxoplasmosis, varicella), retinal dystrophies (torpedo maculopathy, Leber congenital amaurosis), and congenital abnormalities (coloboma, Aicardi syndrome)


Retinoblastoma should be considered in the differential diagnosis of any white retinal lesion in infancy.


• Family history of retinoblastoma or tuberous sclerosis

• Congenital infections: Cytomegalovirus (CMV), toxoplasmosis, varicella

• Chromosomal aberration

• Parental consanguinity leading to autosomal recessive disease


• Retinoblastoma is an autosomal dominant disease associated with loss of heterozygosity of the RB1 gene (13q14).

• Tuberous sclerosis is autosomal dominant (associated with TSC1 or TSC2 gene mutations)

• Coloboma-CHARGE syndrome (CHD7, SEMA3E, CHX10, OTX2, SHH genes and others, del22q11.2 and other chromosomal aberrations. Multiple systemic syndromes associated with coloboma

• Isolated coloboma can be either autosomal dominant or autosomal recessive.

• Aicardi syndrome-X-linked dominant inheritance

• Leber congenital amaurosis- autosomal recessive (GUCY2D, RPE65, RDH12, AIPL1, LRAT, RPGRIP1, SPATA7, CRX, CRB1, RPGR1P1, CEP290, IMPDH1 and other genes)


• For conditions with genetic associations, genetic counseling, and/or prenatal testing (if mutated gene is known or congenital abnormalities are identified in family members)

• For infections:

– Toxoplasmosis-pregnant women should not eat undercooked meat and avoid exposure to cat litter. With confirmed maternal infection, systemic treatment may prevent infection of fetus.

– Varicella-women should be vaccinated no later than 1 month before pregnancy. If a nonimmunized previously noninfected mother is exposed to varicella virus, consider administration of prophylactic treatment with varicella zoster immune globulin (VZIG) or acyclovir or valacyclovir to prevent fetal infection.

– Cytomegalovirus-good hygiene is essential to prevent maternal infection. If mother becomes infected, consider treatment with CMV immune globulin to protect fetus.


• Hypopigmented retinal epithelium due to a wide range of disease processes; cell may contain a low amount of melanin or there may be a complete absence of RPE.

• In coloboma, a failure of complete closure of the choroid fissure results in a gap in the choroid and overlying dysplastic retina (intercalary membrane).

• Infections result in RPE destruction.

• Retinoblastoma and astrocytic hamartoma are neoplastic processes.


• Genetic mutation (two-hit mechanism in retinoblastoma and astrocytic hamartoma)

• Cytomegalovirus, Toxoplasma gondii spread through the placenta in utero.


• Retinoblastoma may also affect pineal gland or bone marrow, later secondary tumors especially if radiated.

• Astrocytic hamartoma of tuberous sclerosis

– may have seizures, skin lesions, subependymal periventricular tubers, developmental delay

• Prenatal varicella

– Microphthalmia, optic atrophy, cataracts, cicatricial skin lesions, atrophy/hypoplastic lesions of limbs

• Cytomegalovirus

– Jaundice, thrombocytopenia/purpura/

• Petechia, hepatosplenomegaly, porencephalic cyst

• Toxoplasmosis

– Intracranial calcifications, uveitis, hydrocephalus

• Coloboma

– Systemic abnormalities (e.g., Coloboma + Heart + Atresia choanae + Retardation + Genitourinary + Ear defines full expression of CHARGE syndrome)

• Aicardi syndrome

– Central nervous system malformation (absent corpus callosum), seizures, developmental delay, skeletal abnormalities

• Leber congenital amaurosis

– Renal disease, deafness, developmental delay



• Family history of retinoblastoma, tuberous sclerosis, coloboma, Aicardi syndrome, or Leber congenital amaurosis

• History of prior fetal loss with infection or Aicardi (male fetuses)

– Known exposure to infection in utero

– Other known associated anomalies


• Complete ophthalmologic and systemic exam

• In retinoblastoma, Tumors may be endophytic or exophytic, unilateral or bilateral, single or multiple, may have vitreous seeding, or rarely inflammatory involvement of anterior segment or orbit

• Coloboma may also affect iris and/or optic nerve, retinal detachment caused by breaks in dysplastic retina within coloboma.

• Astrocytic hamartoma in infancy presents with gray–white and translucent with a smooth surface, in retina or optic nerve.

• Toxoplasmosis chorioretinal scars are large and up to 5 optic disc diameters in size. Uni or multifocal, preferential involvement of macula, hyperpigmented margins

• Chorioretinal scars of congenital varicella are similar to those of toxoplasmosis.

• Leber congenital amaurosis examination in infancy can have yellow–white “macular coloboma”, may or may not have other signs of retinal dystrophy, poor vision.

• In Aicardi syndrome, hypopigmented lacunar lesions are multiple, bilateral, and characterized by pigmented borders with preferential involvement of posterior pole.

• Cytomegalovirus lesions are usually necrotic/inflammatory macular lesions (maculitis) in one or both eyes.



Initial lab tests

• Karyotype for congenital abnormalities

• Gene analysis based on diagnosis

• Serology test for toxoplasmosis, varicella, cytomegalovirus

Follow-up & special considerations

• Consult genetics counselor if genetic disorder

• Low vision support, as needed

• Evaluation of family members if genetic disease


Initial approach

• Ultrasound to confirm tumor in retinoblastoma (calcification)

• MRI or CT to confirm diagnosis of retinoblastoma, tuberous sclerosis, Aicardi, congenital infection

Follow-up & special considerations

For progressive conditions, continue to monitor patients.

Diagnostic Procedures/Other

• Bone marrow test or lumbar puncture if retinoblastoma

• Electroretinogram to assess for Leber’s amaurosis (ERG severely reduced or isoelectric)

Pathological Findings

• See Retinoblastoma chapter

• Cytomegalovirus infections: Retinal necrosis and edema with nuclear viral inclusions

• Astrocytic hamartomas of tuberous sclerosis: Elongated fibrous astrocytes with interlacing cytoplasmic processes in the nerve fiber layer of retina (1)

• Toxoplasmosis: Tachyzoites appear as crescent shapes and stain well with Giemsa or Wright stain.

• Leber congenital amaurosis: Underdeveloped and hypomelanized retinal pigmented epithelium and photoreceptors

• Aicardi syndrome: Thinned out RPE and decreased number and size of vessels


Astrocytic hamartoma of tuberous sclerosis.

• Retinoblastoma

• Coloboma

• Cytomegalovirus

• Toxoplasmosis

• Varicella

• Leber congenital amaurosis

• Aicardi syndrome

• Astrocytic hamartoma of tuberous sclerosis

• Torpedo maculopathy



• For active congenital toxoplasmosis lesions (overlying vitreitis, active retinitis): Systemic pyrimethamine, sulfadiazine, trisulfapyrimidine, folinic acid

• For cytomegalovirus retinitis usually no treatment is needed – self-limiting, if infant immune system normal

• For varicella lesions – no treatment needed (inactive scars)

• Chemotherapy for retinoblastoma (see chapter Retina Retinoblastoma)


General Measures

Low vision early intervention.

Issues for Referral

• Genetic consultation

• Oncology for retinoblastoma

• Enucleation may be indicated in retinoblastoma patients followed by ocularist.

Additional Therapies

• See Retinoblastoma chapter

• Seizure management in Aicardi


None known.


• Surgery for retinal detachment in coloboma patients.

• Enucleation for some retinoblastoma patients.


Initial Stabilization

See Retinoblastoma chapter.



• Long-term follow-up is recommended for all retinoblastoma patients (see Retinoblastoma chapter).

• Low vision support and intervention

• Monitor coloboma every 6–12 months for detachment

• Monitor toxoplasmosis for activation of lesions







• Retinoblastoma has variable prognosis depending on size and extent of tumor.

• Ocular lesions of tuberous sclerosis usually not visually significant

• Leber congenital amaurosis usually blindness but gene therapy now becoming available for certain gene mutations

• Aicardi syndrome usually complicated by cortical visual impairment

• Toxoplasmosis may or may not reactivate, poor vision if fovea involved

• CMV maculitis self-limited

• Varicella lesions rarely progress.

• Coloboma may be asymptomatic or visually devastating.


• Retinoblastoma; death, visual loss

• Coloboma: Retinal detachment

• Toxoplasmosis: Reactivation


1. Shields JR, Eagle RC, Shields CL, et al. Aggressive retinal astrocytomas in four patients with tuberous sclerosis complex. Trans Am Ophthalmol Soc 2004;102:139–148.

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Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Hypopigmented Retinal Lesions

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