019 Posterior Segment in Pediatrics

What are the five primary ocular warning signs that guide the differential diagnosis of pediatric eye disease?

• Leukocoria (white pupillary reflex)

• Macular problems

• Optic nerve problems

• Tumors

• Retinal hemorrhages

Why is it important to recognize key pediatric ocular signs rather than memorizing individual diseases?

Recognizing major signs helps generate a focused differential diagnosis and allows more efficient clinical problem-solving when a child presents with visual abnormalities.

What is leukocoria, and why is it clinically important?

Leukocoria is a white pupillary reflex. It is a major pediatric ocular red flag because it may indicate vision-threatening or life-threatening disease, including retinoblastoma.

What are the major causes of leukocoria, grouped by pathophysiology?

• Media opacity: Cataract, Persistent Hyperplastic Primary Vitreous (PHPV)

• Inflammation/Exudation: Coats disease, Toxocariasis, Posterior uveitis

• Retinal detachment: Advanced ROP, advanced Coats disease, advanced toxocariasis

• Tumor: Retinoblastoma

What tumor must always be considered in a child presenting with leukocoria?

Retinoblastoma until proven otherwise.

What is the underlying defect in Persistent Hyperplastic Primary Vitreous (PHPV)?

Failure of normal regression/development of the fetal vitreous system, resulting in persistent embryologic vitreous tissue.

How does PHPV typically present clinically?

• Usually unilateral

• Presents with leukocoria and/or strabismus

What are the characteristic anterior and posterior findings of PHPV?

• Anterior: Microphthalmia, microcornea, whitish vascularized membrane behind the lens

• Posterior: Vitreous membranes and retinal folds

What is the typical management of PHPV?

Referral for surgical management, typically lensectomy and vitrectomy.

What is Coats disease, and who is most commonly affected?

• Idiopathic, non-hereditary retinal vascular disorder

• About 75% occur in males

• Usually unilateral

What is the underlying pathophysiology of Coats disease and its major complication?

• Retinal telangiectasias (abnormal retinal vessels) cause intraretinal and subretinal exudation

• Progressive exudation can lead to exudative retinal detachment (RD)

How can Coats disease present as leukocoria?

Accumulation of retinal exudates and/or progression to exudative retinal detachment can produce a white pupillary reflex (leukocoria), making it an important differential diagnosis of retinoblastoma.

How is Coats disease treated, and why is early diagnosis important?

• Goal: treat before retinal detachment develops

• Laser photocoagulation → treats retinal telangiectasias

• Cryotherapy → used when retinal detachment is present or disease is more advanced

• Delayed treatment increases risk of neovascular glaucoma

What is the inheritance pattern of Stickler syndrome, and what are the major systemic manifestations?

• Autosomal dominant disorder

• Facial findings: flat nasal bridge, maxillary hypoplasia

• Skeletal findings: arachnodactyly, arthropathy, joint hyperextensibility

• May have Robin sequence (micrognathia, small tongue, cleft soft palate, high-arched palate)

• Associated with deafness and mitral valve prolapse

What are the characteristic ocular findings of Stickler syndrome?

• Abnormal vitreous

• High myopia

• Predisposition to retinal detachment (RD)

Why is Stickler syndrome important in pediatric ophthalmology?

It is the most common inherited cause of retinal detachment.

What is the risk and timing of retinal detachment in Stickler syndrome?

• Retinal detachments occur in approximately 65% of patients

• Can occur as early as the first 5 years of life and continue through young adulthood

What are the major risk factors for retinopathy of prematurity (ROP)?

• Prematurity: < 36 weeks gestation

• Low birth weight: < 1500 g (especially < 1250 g)

• Supplemental oxygen therapy

How does supplemental oxygen contribute to the development of ROP?

• High oxygen levels suppress normal peripheral retinal vessel development → avascular retina

• When oxygen is reduced, retinal ischemia stimulates pathologic neovascularization

What are the characteristic examination findings in ROP?

• Avascular peripheral retina

• Dilated, tortuous retinal vessels (Plus disease)

• Poor pupillary dilation

• Engorged iris vessels

• Usually bilateral

What complications can develop in advanced ROP?

• Neovascularization

• Retinal hemorrhage

• Retinal detachment (RD)

• Leukocoria

How is ROP classified anatomically by retinal zones?

• Zone I: Circle centered on the optic nerve with radius equal to 2× the disc-to-macula distance

• Zone II: Extends from Zone I to the nasal ora serrata

• Zone III: Remaining temporal crescent anterior to Zone II

Besides retinal zone, what other parameter is used to describe the severity of ROP?

Extent, measured in clock hours of retinal involvement.

What are the stages of Retinopathy of Prematurity (ROP)?

• Stage 1: Flat demarcation line between vascular and avascular retina

• Stage 2: Elevated ridge

• Stage 3: Ridge with fibrovascular proliferation

• Stage 4A: Partial retinal detachment, macula on

• Stage 4B: Partial retinal detachment, macula off

• Stage 5: Total retinal detachment

What is Plus Disease in ROP, and why is it important?

• Dilated, tortuous retinal vessels

• May have retinal hemorrhages

• Indicates more severe/active disease

• Can occur at any stage of ROP

Which ROP stages involve retinal detachment?

• Stage 4A: RD with macula attached

• Stage 4B: RD with macula detached

• Stage 5: Total RD

When are infants at risk for ROP typically screened?

Before discharge from the NICU or children's hospital.

What follow-up schedule is recommended for very low birth weight infants (<2 lb 12 oz / <1250 g)?

• Every 2 weeks until 14 weeks

• Every 1 month until 6 months

• Every 6 months thereafter

How is ROP managed based on stage?

• Stages 1-2: Observation; 80–90% regress spontaneously

• Stage 3: Laser photocoagulation and/or anti-VEGF therapy

• Stages 4-5: Surgical repair (scleral buckle, vitrectomy, or both)

Which ROP stages usually do not require treatment?

Stages 1 and 2, because most cases (80-90%) regress without intervention.

When are laser photocoagulation and anti-VEGF therapy indicated in ROP?

Stage 3 ROP, when fibrovascular proliferation develops and risk of progression increases.

What surgical options are used for advanced ROP?

For Stages 4-5 with retinal detachment:

• Scleral buckle

• Vitrectomy

• Combination of both

What are the major long-term visual sequelae seen after treatment for Retinopathy of Prematurity (ROP)?

• High myopia

• Reduced peripheral vision

• Reduced central visual acuity (from macular dragging)

• Strabismus and amblyopia

• Cataracts

Why can patients treated for ROP have decreased vision even if the retina is preserved?

Visual impairment may result from:

• Macular dragging → decreased central visual acuity

• Loss of peripheral retina → decreased peripheral vision

• Associated refractive errors, especially high myopia

• Development of amblyopia or strabismus

What is the newest major medical treatment for ROP?

Intravitreal anti-VEGF therapy (bevacizumab/Avastin)

• Used particularly for severe neovascular ROP

• Suppresses VEGF-driven pathologic retinal neovascularization

What is the mechanism of action of bevacizumab (Avastin) in ROP?

Bevacizumab is an anti-VEGF monoclonal antibody that inhibits VEGF-mediated abnormal retinal vessel growth, reducing neovascularization and disease progression.

What are the major concerns with anti-VEGF treatment in premature infants?

Because VEGF is important for normal development throughout the body:

• Systemic absorption may occur

• Potential impact on neurodevelopment and organ development

• Reported concerns include:

  • Increased risk of motor impairment in some studies

  • Possible association with pulmonary hypertension

Why is there interest in using very low doses of bevacizumab for ROP?

To maintain retinal efficacy while minimizing systemic VEGF suppression and potential developmental side effects.

What are the three major inherited macular disorders commonly considered in pediatric patients?

• X-linked (Juvenile) Retinoschisis

• Best Vitelliform Macular Dystrophy

• Stargardt Disease

What is the inheritance pattern and typical age of presentation of X-linked juvenile retinoschisis?

• X-linked inheritance

• Prevalence: ~1:5,000 to 1:25,000

• Usually presents between 5 to 10 years of age

What is the characteristic macular finding in X-linked juvenile retinoschisis?

Macular "spoke-wheel" pattern caused by splitting (schisis) of the retinal layers.

What are the major retinal complications of X-linked juvenile retinoschisis?

• Approximately 50% develop peripheral retinoschisis

• May develop:

  • Retinal tears (RT)

  • Retinal detachment (RD)

What is the classic ERG finding in X-linked juvenile retinoschisis?

Reduced b-wave with relatively normal a-wave ("electronegative ERG").

What is the typical visual acuity range in X-linked juvenile retinoschisis?

Variable vision loss, typically around 20/60 to 20/200.

What are the key features of Best (Vitelliform) macular dystrophy?

• Autosomal dominant

• Onset before driving age (childhood)

• Vision often remains relatively preserved early (~20/40–20/200)

• Tritan (blue-yellow) color vision defect

What are the characteristic electrophysiologic findings in Best disease?

• Normal ERG

• Reduced EOG

What is the classic fundus appearance of Best disease?

Vitelliform ("egg-yolk") lesion in the macula.

What are the stages of Best vitelliform dystrophy?

0. Abnormal EOG, no retinal findings

1. Pigment mottling

2. Vitelliform ("egg-yolk") lesion

3. Lesion begins to reabsorb

4. "Scrambled egg" stage with vision decline

5. Atrophy

How is Best disease managed?

• Genetic counseling

• Vision rehabilitation/supportive care

• Long-term monitoring

When does Stargardt disease typically present, and how does vision change over time?

• Onset in the 1st or 2nd decade

• Progressive central vision loss

• Vision may decline to ~20/200

What are the characteristic fundus findings in Stargardt disease?

• Early foveal mottling

• "Beaten bronze" appearance of the macula

• Yellow-white pisciform flecks surrounding the macula

• Eventual geographic atrophy

What angiographic finding is classically associated with Stargardt disease?

Dark choroid on fluorescein angiography.

What are the inheritance patterns and typical presentation of cone dystrophy?

• May be autosomal dominant, autosomal recessive, or X-linked

• Presents from teenage years through adulthood

• Progressive decrease in visual acuity (often to ~20/200)

What are the hallmark symptoms of cone dystrophy?

• Decreased central vision

• Abnormal dark adaptation

• Hemeralopia (poor vision in bright light)

What are the characteristic electrophysiologic findings in cone dystrophy?

• Abnormal photopic (cone) ERG

• Scotopic (rod) responses relatively preserved until late disease

What retinal findings are associated with cone dystrophy?

• Early macular mottling

• Bull's-eye maculopathy

• Fluorescein angiography may show a hyperfluorescent window defect surrounding a hypofluorescent center

How do X-linked retinoschisis, Best disease, Stargardt disease, and cone dystrophy differ?

• X-linked retinoschisis: Spoke-wheel macula, ↓ b-wave with normal a-wave.

• Best disease: Egg-yolk lesion, normal ERG + abnormal EOG, AD.

• Stargardt disease: Beaten-bronze macula, yellow flecks, dark choroid.

• Cone dystrophy: Hemeralopia, abnormal photopic ERG, bull's-eye maculopathy.

What are the key inheritance patterns and epidemiology of retinitis pigmentosa (RP)?

• Most common hereditary fundus disorder

• Can be autosomal dominant, autosomal recessive, or X-linked

• Symptoms typically begin in the 1st to 3rd decades of life

What is the classic fundus triad of retinitis pigmentosa?

• Bone-spicule pigmentation

• Arteriolar attenuation

• Waxy optic disc pallor

What are the characteristic electrophysiologic findings in retinitis pigmentosa?

• Early: abnormal scotopic (rod) ERG

• Photopic ERG relatively preserved initially

• Reduced EOG

What future treatment strategy is being explored for retinitis pigmentosa?

Gene therapy, with multiple ongoing efforts targeting inherited retinal disorders.

What are the major congenital and acquired optic nerve disorders covered in pediatric ophthalmology?

• Optic nerve pit

• Optic nerve hypoplasia

• Optic atrophy

• Optic nerve coloboma

What is an optic nerve pit and where is it typically located?

• Congenital excavation of the optic disc

• Appears as a round or oval pit

• Usually located in the inferotemporal (lower temporal) quadrant of the optic disc

What visual findings can occur with an optic nerve pit?

• Visual field defects

• May mimic glaucoma on visual field testing

• Optic disc is often larger than normal

What is the most important complication of an optic nerve pit?

Serous macular retinal detachment

• Occurs in approximately 45% of patients

• Median age of occurrence ≈ 30 years

What is optic nerve hypoplasia, and how common is it?

• Congenital underdevelopment of the optic nerve

• Incidence ≈ 2 per 100,000 births

• May be unilateral or bilateral

Why is bilateral optic nerve hypoplasia particularly important to recognize?

Bilateral disease may be associated with central nervous system abnormalities and warrants neuroimaging.

Classic association:

• Septo-optic dysplasia (de Morsier syndrome)

  • Absence of the septum pellucidum

  • Agenesis of the corpus callosum

What maternal exposures have been associated with optic nerve hypoplasia?

Possible association with medications or alcohol exposure during gestation.

How does visual function vary in optic nerve hypoplasia?

• Visual acuity ranges widely:

  • Near normal vision

  • To NLP (no light perception)

• Visual field defects may also occur

What is the classic fundus appearance of optic nerve hypoplasia?

Small optic nerve with a "double-ring sign"

• Inner ring = chorioretinal atrophy

• Outer ring = expected normal disc margin

How is optic nerve hypoplasia assessed using the disc-macula/disc-diameter ratio?

Measure:

DM:DD = Disc-Macula distance : Disc Diameter

• Ratio > 3:1 suggests optic nerve hypoplasia

What are the two major pediatric intraocular tumors emphasized in this section?

• Retinoblastoma (malignant)

• Choroidal hemangioma (benign vascular tumor)

What are the key epidemiologic and clinical features of retinoblastoma?

• Occurs in approximately 1 in 20,000 births

• Most common intraocular malignancy of childhood

• Mean age at diagnosis: 18 months

• Almost all cases diagnosed before 4 years of age

How does retinoblastoma typically present?

• Leukocoria (white pupillary reflex) – most common presentation

• Strabismus

• Occasionally decreased vision or other signs of intraocular mass

What imaging characteristic helps identify retinoblastoma?

Calcification within the tumor

• High calcium content

• Highly reflective on B-scan ultrasonography

What percentage of retinoblastoma cases are bilateral, and what is the prognosis?

• Approximately 30% are bilateral

• Survival rate exceeds 90% with modern treatment

What are the two major growth patterns of retinoblastoma?

• Endophytic: Growth toward the vitreous with vitreous seeding

• Exophytic: Growth into the subretinal space

What are the major vision- and life-threatening complications of retinoblastoma?

• Optic nerve invasion

• Metastatic spread

Why is RB1 genetic testing important in retinoblastoma?

• Identifies hereditary disease

• Helps guide family counseling

• Patients with germline RB1 mutations have increased risk of additional non-ocular malignancies

What treatment modalities are used for retinoblastoma?

• Chemotherapy

• Radiation therapy

• Cryotherapy

• Laser photocoagulation

• Enucleation

Treatment depends on tumor size, laterality, vision potential, and extent of spread.

What are the key features of a choroidal hemangioma?

• Benign vascular tumor of the choroid

• Appears as a reddish-orange lesion

• Usually observed unless vision is threatened

When should a choroidal hemangioma be treated and how?

Treat only if it:

• Affects vision

• Causes retinal detachment

What are the major causes of retinal hemorrhages in children?

• Abuse (nonaccidental trauma)

• Anemia

• Diabetic retinopathy

• Leukemia

What systemic diseases should be considered when retinal hemorrhages are identified?

• Hematologic disease (anemia, leukemia)

• Vascular disease (diabetic retinopathy)

• Trauma, especially child abuse

Why are retinal hemorrhages particularly concerning in children younger than 2 years?

In children < 2 years old, retinal hemorrhages should raise strong concern for nonaccidental trauma (abuse).

What retinal hemorrhage findings increase suspicion for child abuse?

• Retinal hemorrhages in a young child

• Bilateral retinal hemorrhages

• Hemorrhages that are difficult to explain by accidental trauma

What alternative causes of retinal hemorrhages should be considered before concluding abuse?

• Birth-related retinal hemorrhages (typically resolve within 1 month)

• Falls

• Accidental trauma

• Medical causes (anemia, leukemia, diabetic retinopathy)

How can anemia present in a pediatric patient with retinal hemorrhages?

• Low red blood cell count

• May cause retinal hemorrhages

• Systemic symptoms include:

  • Lethargy

  • Pallor

When retinal hemorrhages are seen with pallor and lethargy, what hematologic condition should be considered?

Anemia

Key clues:

• Low RBC count

• Pallor

• Fatigue/lethargy

• Retinal hemorrhages

How common is diabetic retinopathy in children, and when should screening begin?

• Rare before 10 years of age

• Children should receive annual eye examinations after age 10

How does diabetic retinopathy behave in pediatric patients?

If present, diabetic retinopathy in children tends to be:

• More severe

• More rapidly progressive than in many adult patients

What retinal findings are commonly seen in leukemia?

• Intraretinal hemorrhages

• Roth spots

• Cotton-wool spots

• Dilated and tortuous retinal vessels

What is the most common childhood leukemia, and how frequently does ocular involvement occur?

Acute Lymphocytic/Acute Lymphoblastic Leukemia (ALL)

• Accounts for approximately 90% of childhood leukemias

• Ocular involvement occurs in about 75–80% of cases

What are the major systemic signs and symptoms of childhood leukemia?

• Pallor

• Fever

• Easy bruising

• Recurrent infections

• Joint pain

• Petechial hemorrhages

Why is early recognition of childhood leukemia important?

• Can be rapidly fatal if untreated

• Often responds well to:

  • Chemotherapy

  • Bone marrow transplantation

What are the major causes of retinal hemorrhages in children, and what clues help distinguish them?

• Abuse: Infant <2 years, often bilateral hemorrhages

• Anemia: Pallor, lethargy, low RBC count

• Diabetic retinopathy: Usually after age 10; can progress rapidly

• Leukemia: Roth spots, pallor, fever, bruising, infections