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Leukocoria Cite this Page

Venkata M. Kanukollu; Koushik Tripathy.

Author Information In this Page
Last Update: February 21, 2022. Continuing Education Activity

Introduction
Continuing Education Activity Go to:
Etiology
Leukocoria means ‘white pupil’ or ‘cat’s eye pupil’. Leukocoria is an abnormal pupillary reflex more clearly seen on
Epidemiology
mydriasis or photography. It is often the first sign of a range of serious intraocular disorders including congenital
Pathophysiology
cataract, Coats disease, retinoblastoma, retinopathy of prematurity, toxocariasis, Norrie disease, and retrolental
fibroplasia. Immediate diagnosis and management are mandatory as most conditions are vision-threatening, and History and Physical
some are life-threatening. This activity highlights the importance of evaluation and management of leukocoria and Evaluation
highlights the role of interprofessional teamwork in the management of patients with the underlying condition.
Treatment / Management
Objectives: Differential Diagnosis

Identify the etiology of leukocoria. Staging

Prognosis
Describe the evaluation of leukocoria
Complications
Summarize the management options available for leukocoria
Deterrence and Patient Education
Access free multiple choice questions on this topic. Enhancing Healthcare Team Outcomes

Review Questions
Introduction Go to:
References
Leukocoria means ‘white pupil’ or ‘cat’s eye pupil.’ Leukocoria is an abnormal pupillary reflex more clearly seen on
mydriasis or photography. It is often the first sign of a range of serious intraocular disorders. Leukocoria is
commonly seen in congenital cataract, Coats disease, retinoblastoma, retinopathy of prematurity, toxocariasis, Norrie Bulk Download
disease, retrolental fibroplasia, and other disorders. Immediate diagnosis and management are mandatory as most Bulk download StatPearls data from FTP
conditions are vision-threatening, and retinoblastoma may be life-threatening. Immediate referral to an
ophthalmologist, an interdisciplinary liaison with a pediatric ophthalmologist, retina specialist, and ocular oncologist
will help in the management of eyes with leukocoria in an appropriate manner. Related information
PMC
Etiology Go to:
PubMed
The normal red reflex of the human eye is due to the retro-illumination of normal choroidal vasculature reflecting
thorough the retina, vitreous, lens, pupil, and cornea. Any interference in any of these structures would give an
altered red reflex or Leukocoria. Some of the common causes of Leukocoria are: Similar articles in PubMed
[White pupil in an infant].
Retinoblastoma [Ugeskr Laeger. 2015]

Etiology of white pupillary reflex in pediatric age group.

Coats disease [Rom J Ophthalmol. 2022]

Retinopathy of prematurity (ROP) Differentials and approach to leukocoria.

[Conn Med. 2013]
Persistent fetal vasculature (PFV)
Differential diagnosis of leukocoria and strabismus, first
Ocular toxocariasis and toxoplasmosis presenting signs of retinoblastoma. [Clin Ophthalmol. 2007]

Review Don't Miss This! Red Flags in the Pediatric Eye

Astrocytic hamartoma Examination: Abnormal Red Reflex.[J Binocul Vis Ocul Motil. 2019]

Familial exudative vitreoretinopathy (FEVR) See reviews...

Vitreous hemorrhage See all...

Retinochoroidal coloboma
Recent Activity
Endogenous endophthalmitis
Your browsing activity is temporarily unavailable.
Incontinentia pigmenti (Bloch-Sulzberger syndrome)

Retinal detachment

Pediatric uveitis

Medullated retinal nerve fibers (MRNF)

Medulloepithelioma

TORCH (Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, and Herpes simplex syndrome)

Epidemiology Go to:

In a retrospective study spanning ten years, the mean age of children presenting with leukocoria was 42.5 months.
[1] Bilateral involvement was seen in 54% with a male-female sex ratio of 1.5. 76% of children were under six years
of age. 75% of the cases were caused by cataracts, and 21% were retinoblastoma. Other causes of leukocoria
included retinal detachment (1%), retinopathy of prematurity (1%), persistent pupillary membrane (1%), persistent
hyperplastic primary vitreous (0.6%), endophthalmitis (0.64%), optic nerve coloboma (0.3%), iris heterochromia
(0.3%), and ametropia (0.3%).[1]

The Third National Cancer survey data indicates an annual incidence of 11 new cases of retinoblastoma per million
children under the age of 5 years.[2] Retinoblastoma is the most common intraocular malignancy in children and
accounts for 2% of all childhood cancers. The estimated incidence ranges from 3 to 42 cases per million live births.
In the United States, the incidence is 12 cases per million live births in children less than five years of age, with a
prevalence of 6 % of all cancers in this age group.[3] Retinoblastoma affects both sexes equally. Retinoblastoma
shows the highest incidence in children less than four years of age.[4] Coats disease has an incidence of 0.09 per
100,000 population, with 85% of cases affecting the males.[5]

The global prevalence of childhood cataract ranges from 0.3% to 23% per 10,000, with a median of 1 per 10,000 and
0.6% to 9.8% per 10,000 for congenital cataract with a median of 1.7 per 10,000 based on many studies that reported
congenital cataract.[6] In a study involving 602 newborns, the incidence of retinopathy of prematurity (ROP) at any
stage was 34%, and Type 1 pre threshold ROP was 5% with a mean gestational age of 31 weeks.[7] The incidence of
neonatal endophthalmitis in the United States is 4.2 cases/1000000 live births.[8]

Pathophysiology Go to:

Leukocoria is a whitish or altered pupillary reflex that appears due to obstruction of the normal retinochoroidal
vasculature, which reflects through the pupil. The various causes of leukocoria, their etiopathogenesis, and clinical
features are as follows:

Retinoblastoma: Retinoblastoma (RB) results from malignant transformation of the primitive retinal cells,
most likely a multipotent retinoblast. 48% of cases show autosomal dominant transmission with 90%
penetrance at birth and maps to chromosome 13q14.[9] 95% of cases are sporadic, while only 5% of cases
have a family history of RB. RB is caused by a mutation in the RB1 tumor suppressor gene located on sub-
band 13q14.2. 75% of RB is caused by a mutation in a single retinal cell by inactivation of both alleles of the
RB1gene. These are unilateral and unifocal—60% of cases present with leukocoria within two years of age.
Pathological microscopy shows Flexner-Wintersteiner rosettes (ring of nuclei surrounding a clear central
lumen, also seen in Medulloepithelioma), Homer-Wright rosettes (neural filaments with no clear, distinct
lumen, also seen in adrenal neuroblastoma and medulloblastoma), pseudo-rosettes, and fleurettes (bouquet of
pink bulbous neoplastic photoreceptor inner segments; highly specific for RB). Intratumoral calcification
(90%) is common. Retinoblastoma presents as leukocoria (60%), squint (20%), and decreased vision (5%).
Clinical features are yellowish-white retinal mass, rubeosis iridis, pseudohypopyon, hyphema, angle-closure
glaucoma, and uveitis. Two types are seen: endophytic type: starts at the inner retina and grows into vitreous
simulating endophthalmitis and causes pseudohypopyon, and exophytic type: starts from the outer retina and
grows towards choroid extending into sclera simulating Coats disease or traumatic retinal detachment.
Intratumoral calcification is seen along with tumor necrosis when it outgrows its blood supply—trilateral
retinoblastoma (3%) in the presence of pinealoblastoma or parasellar neuroblastoma along with bilateral RB.
Retinocytoma or retinoma is a benign tumor composed of fleurettes.

Coats disease: Coats disease is a retinal telangiectatic condition that commonly affects one eye of young
males. Though it is mostly a sporadic condition multiple genetic changes have been described. Chromosomes
involved are 3 and 13 with the involvement of NDP (Norrie disease protein), CRB1, and PANK2 genes.
Clinical features are mid-peripheral or peripheral telangiectasia, retinal exudation, exudative retinal
detachment, neovascular glaucoma, and bulb-like microaneurysms (Leber’s military aneurysms). The choroid
and sclera remain unaffected. The most devastating complication is neovascular glaucoma, seen in 10% of
cases, which might often require enucleation. The timely intervention of the retinal detachment can prevent
this.

Persistent fetal vasculature: Persistent fetal vasculature (PFV) or Persistent hyperplastic primary vitreous
(PHPV)is a congenital condition due to failure of regression of the intraocular fetal vasculature. It’s the second
most common cause of infantile leukocoria.[10] It is non-heritable and commonly causes unilateral
involvement. Leukocoria results from a complete pupillary membrane, cataract, fibrovascular sheath attached
to the posterior lens capsule, strabismus, and a rarely cloudy cornea due to glaucoma. Anterior PFV presents
with microphthalmia, cataract, elongated ciliary process, shallow anterior chamber, retrolental fibrovascular
membranes, dilated iris vessels, glaucoma, and ectropion uveae. Posterior PFV presents with microphthalmia,
tractional retinal detachment, hypoplastic optic nerve and macula, vitreous membranes and stalk, clear lens,
and strabismus.

Pediatric cataract: Over 60% of children presenting with leukocoria have congenital cataracts [unilateral
(18%) and bilateral (42%)]. Unilateral cataracts are usually sporadic, while bilateral cataracts are often
associated with other systemic diseases like intrauterine infections (rubella, toxoplasmosis, cytomegalovirus,
and herpes simplex virus infections), metabolic disorders (galactosemia), and chromosomal anomalies
(trisomy 21, Stickler syndrome and myotonic dystrophy).

Pediatric uveitis: Pars-planitis with its ‘snowball’ or ‘snow-banking’ in the vitreous commonly presents as
leukocoria. Most children have bilateral symmetry. Other causes of uveitis in children are juvenile idiopathic
arthritis (JIA), tubulointerstitial nephritis, and uveitis (TINU), leukemia, retinoblastoma, juvenile
xanthogranuloma, and Blau syndrome.

Toxocariasis: Toxocariasis is caused by a nematode Toxocara canis, which causes both systemic and ocular
toxocariasis. Definitive hosts are dogs and cats, so close contact with domestic pet dogs and cats is an
important risk factor for children. Ocular toxocariasis is mostly unilateral and presents with blurred vision,
floaters, leukocoria, and strabismus. Toxocariasis clinically presents as retinal granuloma (localized at the
posterior pole or peripheral), endophthalmitis, vitreous abscess, temporal dragging of the macula, and
tractional retinal detachment.

Astrocytic hamartoma: Retinal astrocytic hamartoma is a benign retinal tumor composed of glial cells,
especially astrocytes, and is frequently associated with tuberous sclerosis. Other features are hamartomas of
iris and ciliary body with neovascular glaucoma and giant retinal astrocytoma with exudative retinal
detachment.[11] Tuberous sclerosis transmits autosomal dominantly and results from mutation of either of the
two genes, TSC1 (encoding hamartin) and TSC2 (encoding tuberin).[12]

Retinopathy of prematurity (ROP): This is also known as Retrolental Fibroplasia. ROP results from
abnormal proliferation of retinal vessels in premature infants weighing less than 1250 gm or under 32 weeks of
gestation. These children usually receive oxygen therapy and present signs of ROP between 35 and 45 weeks
of post-conceptional age. Children under 1000 gm pose the highest risk for blindness, while most cases regress
spontaneously over 3 to 4 months. ROP shows four stages, as mentioned below. Leukocoria might present
from stage 3 onwards.

Endogenous endophthalmitis: Endogenous endophthalmitis is rare and occurs commonly in premature, very
low birth weight neonates. Klebsiella pneumoniae, Methicillin-resistant Staphylococcus aureus, Pseudomonas
aeruginosa, and Candida albicans are the common causative organisms.[13] The pathogen most commonly
reaches the eye through the posterior circulation in the form of a septic embolus. The infection then extends
from the Retinochoroidal circulation into the vitreous cavity and then to anterior chamber of the eye.

Retinochoroidal coloboma: Coloboma is a congenital defect in the iris, ciliary body, choroid, retina, and optic
nerve due to a failed or incomplete closure of the embryonic fissure. It usually involves the inferonasal
quadrant of the eye. Retinochoroidal coloboma usually presents as leukocoria. Rhegmatogenous Retinal
detachment is the most common complication.

Familial exudative vitreoretinopathy (FEVR): Familial exudative vitreoretinopathy (FEVR) is a hereditary

retinal vascular disorder characterized by avascular peripheral retina especially temporal quadrant with a ‘V’
shaped demarcation, temporal dragging of retinal vessels and macula, retinal falciform folds, retinal ischemia
with neovascularization, subretinal exudates, and retinal detachment. Inheritance is Autosomal Dominance
with 100% penetrance. FEVR develops as a consequence of a genetic abnormality (Wnt signaling) that affects
the growth and development of retinal blood vessels. An important differential is ROP, but cases with ROP
have a history of preterm birth and low birth weight. FEVR cases have a family history of a similar
disease, and clinical examination or fundus fluorescein angiogram (FFA) may reveal peripheral avascular
retina in the family members.

Retinal detachment: Pediatric retinal detachments account for 3.2% to 6.6% of all cases of retinal
detachment.[14] Pediatric retinal detachments are commonly secondary to ocular trauma, ROP, Myopia,
Stickler’s syndrome, X-linked retinoschisis, Persistent hyperplastic primary vitreous, FEVR, retinochoroidal
coloboma, Marfan’s syndrome, Coats disease, uveitis, and following intraocular surgery.

Medulloepithelioma: Medulloepithelioma (diktyoma) is a non-hereditary tumor of the non-pigmented ciliary

epithelium. These slow-growing tumors present with the visual decline, raised intraocular pressure, localized
angle closure, leukocoria, cataract, and red-eye. It appears in the region of the ciliary body as a whitish-pink
mass and is associated with the DICER-1 gene. 5% of cases are associated with pleuropulmonary blastoma
family tumor and dysplasia Syndrome (PPB-FTDS). Ultrasound biomicroscopy (UBM) and anterior segment
optical coherence tomography (OCT) would help assess the size and extent of the tumor.

TORCH syndrome: TORCH syndrome includes toxoplasmosis, other agents (Treponema pallidum, Varicella-
zoster virus, Parvovirus B19), rubella, cytomegalovirus, and herpes simplex. It’s a neonatal infection which
spreads transplacentally from an infected mother and presents with leukocoria.

Medullated retinal nerve fibers: Normal retinal nerve fibers usually are devoid of myelin sheath anterior to
lamina cribrosa. Medullated retinal nerve fibers are those fibers which still possess the myelin sheath anterior
to lamina cribrosa. They are asymptomatic except for causing Leukocoria and are associated with myopia,
amblyopia, and strabismus. They appear as a white or yellowish striated patch with feathered borders in the
peripapillary area or around the macula.

Incontinentia pigmenti (IP): Incontinentia Pigmenti (Bloch-Sulzberger syndrome) is a rare X-linked

dominant disorder caused by mutation of NEMO/IKK gene located at the Xq28 loci. It affects mostly females,
and the disease is lethal for males in-utero. IP is characterized by skin, ocular, neurological, and dental
abnormalities. Ocular findings are retinal non-perfusion areas, tractional retinal detachment, vitreoretinal
fibrosis, and retinal pigment epithelial defects. IP may clinically resemble retinoblastoma and presents as
leukocoria due to vitreoretinal fibrosis. Skin lesions initially present as erythematous vesicular rashes, which
are later replaced with verrucous lesions, swirling macular hyperpigmentation, and linear hypopigmentation.
[15][16][17][18]

History and Physical Go to:

A thorough medical history of present illness, past ocular history, medical history, and family history should be
elicited. A family photograph would help know if the leukocoria was present from birth or later in childhood.
Persistent fetal vasculature is most often present at birth. A history of prematurity would lead us to investigate in line
with retinopathy of prematurity, which presents as leukocoria due to retinal detachment and retrolental fibroplasia.
Birth trauma can lead to hyphema or vitreous hemorrhage, which presents as an altered pupillary reflex. Family
history is essential in retinoblastoma, FEVR, and coloboma.

The color of the pupillary reflex also gives a hint of the diagnosis. Retinoblastoma presents as a whitish pupillary
reflex, while congenital cataracts show a blue-grey reflex. Coats disease and retinal detachment show a yellowish
reflex. In 20% of cases, retinoblastoma presents as strabismus. Retinal detachments, vitreous hemorrhage, Coats
disease, and retinoblastoma (60%) usually presents as unilateral disease, while FEVR, endogenous endophthalmitis,
astrocytic hamartomas, and 40% of retinoblastomas are bilateral.[19]

Evaluation Go to:

Any child presenting with leukocoria should be evaluated for vision, pupillary reflexes, slit-lamp examination of
both anterior segment and fundus, indirect ophthalmoscopy, FFA, OCT of the retina, and B scan ultrasonography.
Neuroimaging, blood workup, genetic testing, and fine-needle aspiration cytology are other ancillary tests done to
confirm the diagnosis.

Pupillary reflex: In a dark room, looking through the direct ophthalmoscope set at ‘0’ from a distance of 18
inches away from the eye, when light is projected on to the eyes, a normal red reflex should emanate from both
eyes and should be symmetrical in color and contrast. A markedly diminished reflex, a white reflex, dark spots
in the reflex, or an asymmetry (Bruckner reflex) are all considered to be abnormal. When in doubt, dilate the
pupil with dilating drops to examine the reflex in detail. For infants, less than nine months of age, a
combination of Cyclopentolate 0.2% with Phenylephrine 1% eye drops are used 45 minutes prior to the
examination.[20] Atropine drops may be avoided due to its anticholinergic side effects. For infants, more than
nine months of age, either Tropicamide 1% with Phenylephrine 2.5% combination or Cyclopentolate 0.2%
with Phenylepherine1% combinations drops can be used 45 minutes prior to examination.

Bruckner reflex: When viewed through a direct ophthalmoscope, when strabismus is present, the fixating eye
has a darker reflex than the deviating eye. This test would help differentiate leukocoria from altered reflex
produced in small-angle deviations and amblyopia (anisometropia).

Ultrasonography: This is recommended in all patients presenting with leukocoria. It is highly specific for
detecting intraocular calcifications (90%) in retinoblastoma. Retinoblastoma is seen as a solid retinal mass
with high reflectivity due to calcification. Coats disease is seen as a retinal detachment, and point echoes in the
subretinal fluid with no retinal mass lesion. Toxocariasis shows an elevated granuloma with no calcification.
Astrocytic hamartomas present as glistening yellow calcification in contrast to dull, chalky white calcification
of retinoblastoma. Ultrasonography helps in differentiating an isolated retinal detachment from one associated
with a retinal mass lesion. Medulloepithelioma shows a pattern of heterogeneous areas of high internal
reflectivity. Clear cysts are visible within the mass.

Fundus fluorescein angiography (FFA): Retcam photography with FFA is very useful in evaluating
leukocoria in infants. Coats disease shows retinal telangiectasia as a ‘lightbulb’ appearance with late leakage
and peripheral non-perfusion areas. Retinoblastoma shows a rapid homogenous hyperfluorescence.
Toxocariasis granulomas show reticular hyperfluorescence with retinal traction. ROP and FEVR demonstrate a
peripheral avascular zone.

Optical coherence tomography (OCT): It is a noninvasive test to assess fluid, edema, or fibrosis in the
posterior pole lesions. Anterior segment OCT (AS-OCT) would help delineate the size and extent of
Medulloepithelioma.

Computerized tomography (CT): CT is avoided in children due to high exposure to radiation but can be
useful if intraocular calcification is doubtful.

Magnetic resonance imaging (MRI): It is a diagnostic modality of choice to detect the intracranial spread of
retinoblastoma and other secondary tumors like pinealoblastoma or parasellar neuroblastoma. Retinoblastoma
is seen as an isointense to a hyperintense lesion on T1 weighted images and hypointense on T2 weighted
images.

Blood investigations: These are helpful in toxocariasis, TORCH infections, and endogenous endophthalmitis.

Fine needle aspiration cytology (FNAC): Vitreous tap helps in endogenous endophthalmitis and chronic
endophthalmitis secondary to toxocariasis. It is contraindicated in retinoblastoma as it leads to seeding and
metastasis. Anterior chamber tap shows eosinophils in toxocariasis. The ratio of aqueous to plasma lactate
dehydrogenase (LDH) is more than 1.0 in retinoblastoma. It is usually less than 1.0 in ocular disease other than
RB. Aqueous LDH serves as a histologic tumor marker and correlates with the severity of retinoblastoma (type
4 and 5). Isoenzymes LDH4 and LDH5 are characteristically elevated.

Genetic testing: This helps in the diagnosis and genetic counseling in retinoblastoma, FEVR, astrocytic
hamartoma, and Coats disease (NDP gene). Analysis of the retinoblastoma gene is done by direct and indirect
methods. The direct method aims to detect the initial mutation that formed the tumor and subsequently finds
out whether the mutation is in the germline of the patient. Indirect methods are used if the initial mutation
cannot be located. DNA can be evaluated from the tumor cells or from leukocytes. The deletion of the RB gene
is detected by karyotyping and Southern blot technique. Point mutations are detected by ribonuclease
protection, gel electrophoresis, and direct DNA sequencing.

Treatment / Management Go to:

Leukocoria is a sign of an underlying ocular disease. The management of common ocular conditions causing
leukocoria is as follows:

Retinoblastoma: Chemoreduction followed by adjuvant consolidative treatment (laser photocoagulation,

thermotherapy, cryotherapy, chemotherapy) has replaced external beam radiotherapy as the primary mode of
treatment for intraocular retinoblastoma.[21] The following are the various methods of treatment of retinoblastoma:

Enucleation: Treatment of choice for unilateral group E and D intraocular retinoblastoma and in all blind and
painful eyes. This involves minimal manipulation with the ‘no-touch’ technique and excision of at least 10 mm
of the optic nerve to prevent the intracranial spread.

Chemoreduction: Six monthly cycles of vincristine (0.05mg/kg), etoposide (5mg/kg), and carboplatin
(18.6mg/kg) (VEC) are used to reduce the tumor size.

Thermotherapy: Heating up to 42 to 60 degrees C is indicated in tumors with a basal diameter of less than 3
mm without any vitreous seeding. It has a synergistic effect with chemotherapy.

External beam radiation therapy (EBRT) is indicated in Large tumors with vitreous seeding, salvageable eyes,
multifocal tumors, and in eyes that failed coagulation therapy. RB is a very radiosensitive tumor. A dose of
4000 cGy is used with 200 cGy fractions.

Episcleral Plaque brachytherapy: Episcleral application of ruthenium-106 or iodine-125 plaque is made. This
is indicated in single medium-sized tumors not involving optic nerve or macula.

Photocoagulation/Cryotherapy is used for small posteriorly located tumors, not involving optic nerve or
macula.

Cryotherapy is used for small anteriorly located tumors.

Coats disease: Mild cases may be observed. Other management options include laser treatment of telangiectatic
vessels, microaneurysms, and capillary nonperfusion areas, cryotherapy for exudation with subretinal fluid,
intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents, and retinal surgery for retinal detachment are
other available therapy.

PFV: The anterior PFV is treated with observation, cataract, and glaucoma management. Treatment is aimed at
preventing amblyopia and correcting strabismus by treating cataracts and glaucoma. Severe intraoperative bleeding
should be anticipated from persistent tunica vasculosa lentis. Retinal lesions of posterior PFV are managed by
lensectomy, membranectomy, and vitrectomy through either anterior limbal or pars-plana approach.

Pediatric cataract: Cataracts operated between 2 months to 6 months yield good results. Emmetropization of an eye
generally is achieved by nine years of age.[22] Unilateral cataracts should be operated before six weeks and bilateral
cataracts before eight weeks of age.[23] Surgery is advised for visually significant cataracts (more than 3 mm of
opacity).

Pediatric uveitis: Corticosteroids are the mainstay of treatment of noninfectious uveitis in children. Periocular or
sub-tenons corticosteroid injections are used in pars planitis, especially in unilateral cases. Steroid-induced glaucoma
and cataract are potential complications of corticosteroid therapy and should always be looked for. Methotrexate is
the most commonly used first-line immunomodulatory drug in children with uveitis. Second-line agents are
azathioprine, cyclosporine, and mycophenolate. Anti-TNF (tumor necrosis factor) agents like infliximab and
adalimumab are successfully used in the treatment of resistant pediatric uveitis.[24]

Toxocariasis: Topical or systemic corticosteroids are the mainstay of treatment in the control of the inflammation.
The role of anti-helminthic therapy in ocular toxocariasis is controversial and should always accompany steroids.[25]
Pars plana Vitrectomy is the most common surgical treatment for ocular toxocariasis.

Astrocytic hamartoma should be observed. Glaucoma should be treated accordingly. Tuberous sclerosis should be
ruled out.

Retinopathy of prematurity: Observation, retinal laser, cryotherapy, and retinal surgery are the different treatment
modalities for ROP. Immature retinal vessels alone can be observed, and screening repeated. The cryo-ROP study
showed positive results of cryotherapy for the entire avascular retina in the threshold ROP. Early treatment of the
ROP study (ETROP) recommended the ablation of the peripheral avascular retina for type 1 ROP.

Endogenous endophthalmitis: Management depends on the causative organism and the severity of the infection.
Empirical treatment includes intravitreal injection of vancomycin (1 mg/0.1 ml) plus either ceftazidime (2.25 mg/0.1
ml) or Amikacin (0.4 mg/0.1 ml). Vancomycin covers for gram-positive organisms while ceftazidime and amikacin
cover for gram-negative organisms.[26][27][28] For fungal vitritis, vitrectomy with intravitreal injection of
amphotericin (5-10 mcg/0.1 ml) or voriconazole (100 to 200 mcg/0.1 ml) and systemic antifungal therapy are
indicated. Pars plana vitrectomy is indicated for all severe sight-threatening endophthalmitis. Systemic antifungal or
antibacterial therapy should be started depending on the blood and vitreous culture reports.

Retinochoroidal coloboma: Retinal detachment and cataract are the most common associations of retinochoroidal
coloboma. Poor vision, amblyopia, and strabismus may be noted. Prophylactic barrage laser along the coloboma
margin creates a strong chorioretinal adhesion and reinforces the margins, thereby may reduce the occurrence of
extra-colobomatous retinal detachment.[29] Pars-plana vitrectomy with or without scleral buckling, drainage of
subretinal fluid, and endotamponade with long-acting gas or silicone oil is the treatment of choice for retinal
detachment. The exact localization of the retinal breaks that cause the retinal detachment may be very difficult to
localize because of the thin atrophic retina, transparent intercalary membrane, nystagmus, small cornea, and cataract.

Familial exudative vitreoretinopathy: Stage 1 FEVR without exudation can be observed. Stage 2 with exudation is
treated with a laser to the avascular retina. Surgery is indicated for stages 3 to 5 and is aimed at relieving traction by
excision or incising the scar tissue, thereby encouraging reattachment of the retina.

Retinal detachment: Two surgical options for pediatric rhegmatogenous retinal detachments are scleral buckle with
or without encircling band and vitrectomy. This is the preferred surgery, even in Grade C proliferative
vitreoretinopathy (PVR). Vitrectomy with or without encirclage is done in retinal detachment with more than PVR
Grade C. In tractional retinal detachment, the scleral buckle may be sufficient if the break is in the periphery.

Medulloepithelioma: Enucleation is the standard treatment for advanced ciliary body tumors. Exenteration of the
orbit is required when the orbit is involved. Local excision can be done for small tumors involving 3 to 4 clock
hours.

Incontinentia pigmenti: Laser ablation of retinal non-perfusion areas and cryotherapy may be helpful.

Differential Diagnosis Go to:

Leukocoria is an altered pupillary reflex presenting as a white/greying reflex when compared to the bright red/orange
reflex of the fellow eye. The following conditions mimic leukocoria, but they haven't actually altered pupillary
reflexes instead a differently looking eye which the parents bring it to the doctor's attention:

Pediatric glaucoma

Strabismus and Bruckner reflex

Hypopyon

Hyphema

Corneal opacities

Foreign body

Causes of Intraocular calcification:

Calcified cataract

Asteroid hyalosis

Retinoblastoma

Calcified drusen

Astrocytic hamartomas

Retinocytoma

Astrocytomas

Optic nerve meningioma

Optic nerve head drusen

Phthisis

Staging Go to:

Tartarella et al have classified leukocoria as below:

Pre-lenticular leukocoria

Lenticular leukocoria

Retrolenticular leukocoria

Mixed presentation leukocoria

International Classification of Retinoblastoma (ICRB)[30]

Group A: Small intraretinal tumors (less than 3 mm) away from the foveola and the disc.

Group B: Tumors more than 3 mm, macular or juxtapapillary in location, or with subretinal fluid.

Group C: Tumor with focal subretinal or vitreous seeding more than 3 mm from the tumor.

Group D: Tumor with diffuse subretinal or vitreous seeding more than 3 mm from the tumor.

Group E: Extensive retinoblastoma occupying more than 50 percent of the globe volume with or without
neovascular glaucoma, hemorrhage, tumor extension to the anterior chamber, or optic nerve.

International Classification of Retinopathy of Prematurity[31]

Zones:

Zone 1: a small circle of the retina around the disc with a radius twice the distance from the macula to the
center of the disc.

Zone 2: circle surrounding zone 1 which extends to the nasal ora Serrata

Zone 3: crescent-shaped area of the Temporal retina

Extent: involved areas measured in clock hours

Stages:

Stage 1: Demarcation ‘line’ between the vascular and avascular retina

Stage 2: Capillary growth over the demarcation line forms a ‘Ridge’

Stage 3: Tufts of extraretinal blood vessels grow over the ridge

Stage 4: Subtotal retinal detachment (4A-extrafoveal,4B-foveal)

Stage 5: Total retinal detachment.

‘Plus’ disease: Dilated tortuous retinal vessels surrounding the optic disc, vitreous haze, and iris vascular congestion.

Aggressive posterior ROP(AP-ROP): ‘Plus’ disease in zone 1 or posterior zone 2 with vascular loops. Such
aggressive disease may worsen rapidly and may not follow the typical stages of ROP.

Staging of Persistent hyperplastic primary vitreous (FEVR)[32][33]

Stage 1: Avascular retinal periphery

Stage 2: Retinal neovascularization (2A-without exudate,2B-with exudate)

Stage 3: Extramacular retinal detachment (3A-without exudate,3B-with exudate)

Stage 4: Subtotal retinal detachment involving the macula (4A-without exudate,4B-with exudate)

Stage 5: Total retinal detachment.

Classification of retinochoroidal coloboma[34]

Type 1: Coloboma extending above the disc

Type 2: Coloboma extending up to the superior border of the disc

Type 3: coloboma extending below the inferior border of the disc

Type 4: Coloboma involving the disc

Type5: Coloboma present inferior to the disc with normal retina above and below the coloboma

Type 6: pigmentation present in the periphery

Type 7: coloboma involving only the periphery

Prognosis Go to:

Retinoblastoma (RB) has a survival rate of 90% to 95% with a good prognosis, although the affected eye might lose
vision. Poor prognostic signs of retinoblastoma are optic nerve/extra-scleral/uveal invasion, multifocal tumors,
delayed diagnosis, and degree of differentiation. Bilateral involvement doesn’t worsen the prognosis, while the
degree of necrosis and calcification does not influence the prognosis. The prognosis of RB depends on the status of
the tumor is the worst eye. High-risk features for recurrence are optic nerve invasion, massive choroidal
involvement, orbital spread, and involvement of anterior segment and uveal tissue.

Congenital cataract has a good prognosis if diagnosed early and if operated before six weeks. Developmental cataract
has a better prognosis than congenital cataract. Bilateral cataracts have a better prognosis than unilateral cataracts.
Even a mild opacity can cause significant amblyopia. Unilateral cataracts also pose a higher risk of anisometropia.

Endogenous endophthalmitis doesn’t have a favorable prognosis. Most cases result in retinal detachment and
uncontrolled infection, eventually requiring enucleation or evisceration.

FEVR is a lifelong disease and can reactivate at any time. Following treatment, patients with FEVR should be
followed up every six months with fundus examination and fluorescein angiography. Prognosis of retinal detachment
surgery is very poor because children often present with poor visual acuity with a higher percentage of macular
involvement. Besides these, the child possesses a lifelong risk of cataracts, glaucoma, and recurrence in retinal
detachment.[35]

Medulloepithelioma that is confined to the globe has an excellent prognosis with a 5-year survival rate of 90-95%
after enucleation.[36]

The prognosis for retinochoroidal coloboma is reasonably good if amblyopia is managed in time and if the
prophylactic laser is done to prevent retinal detachment. Foveal involvement in coloboma causes severe loss of
vision.

Complications Go to:

Retinoblastoma:

Choroidal and scleral invasion

Metastasis

Vitreous seeding

Tumor invasion into the anterior chamber

Rubeosis iridis and glaucoma

Recurrence of the tumor and subsequent neoplasms

Elevated intracranial pressure

Phthisis

Death

Pediatric uveitis:

Amblyopia

Cataracts

Band shaped keratopathy

Glaucoma

Cystoid macular edema

Retinochoroidal coloboma:

Cataract

Retinal detachment

Amblyopia

Zonular weakness

Cataract and cataract surgery:

Amblyopia

Anisometropia

Secondary capsular opacification

Secondary glaucoma

Postoperative uveitis and endophthalmitis

Retinal detachment

Coats disease:

Neovascular glaucoma

Orbital cellulitis

Anterior chamber cholesterolosis

Vitreous hemorrhage

Neovascularization of disc and retina

Intraretinal microcysts

Secondary vasoproliferative tumor

Deterrence and Patient Education Go to:

Leukocoria is a pediatric manifestation. So parents of the child should be properly educated about investigating the
child fully to know the cause for the leukocoria. It could be as benign as an altered Bruckner reflex to most sinister
retinoblastoma, which could be sight or life-threatening. The family doctor or the pediatrician or the primary care
physician are the first to diagnose leukocoria, and thus they play an essential role in the outcome of the eye
condition. Any complaint of altered pupil reflex should be taken seriously and thoroughly investigated.

Parents should be reassured and counseled appropriately about the cumbersome process of the full investigation,
including neuroimaging and also screening siblings for a hereditary disorder. Genetic counseling of retinoblastoma is
complex and very much essential. Only 5 percent of retinoblastoma patients have a family history of RB. Bilateral
retinoblastoma survivor parent has a 45 percent chance of having an affected child. A unilateral retinoblastoma
survivor parent has a 7 percent chance of having an affected child. Normal parents of a child with bilateral RB has
less than 5 percent risk of having another child with RB. If two or more siblings are affected, then the chance of
another child having RB is 45 percent.

Enhancing Healthcare Team Outcomes Go to:

Primary care physicians, pediatricians, and optometrists are the first to assess leukocoria. Early diagnosis and referral
to an ophthalmologist are mandatory for a successful outcome. Inter sub-specialty liaison between a general
ophthalmologist, pediatric ophthalmologist, ocular oncologist, and a retinal surgeon is essential in a faster diagnosis
and management of the child as conditions like retinoblastoma are life-threatening in addition to being a vision-
threatening disease. Siblings and parents should all be involved in care management as some of the conditions
causing leukocoria are hereditary. Involving a geneticist early in the care management helps int the genetic
counseling of the parents. American Academy of Pediatrics has laid down the following recommendations in
children with leukocoria:[37]

Pediatricians or other primary care clinicians should check the red reflex of all neonates, infants, and children
before discharging them from their care.

The result of red reflex examination should be rated as normal if color, intensity, and clarity are the same in
both eyes when checked simultaneously.

All infants or children with altered Bruckner reflex or absent red reflex should be referred to a pediatric
ophthalmologist immediately.

The referring practitioner must communicate directly with the ophthalmologist and chart a plan for proper
follow up.

Relatives of children with high-risk disorders like retinoblastoma, cataracts, glaucoma, and retinal dysplasia
should be examined for red reflex and must be referred to a pediatric ophthalmologist.

The pediatric ophthalmologist should examine for subtle retinal lesions when the children are brought by
parents with a complaint of leukocoria.

Review Questions Go to:

Access free multiple choice questions on this topic.

Comment on this article.

Figure

Example of Leukocoria. Contributed by Rian Kabir, MD

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