(Case presented by Dr E. Torcynski at the meeting of the Eastern Ophthalmic Society, 1994. From Yanoff M, Fine BS: Ocular Pathology, 5th edn, St Louis, Mosby, 2002.)

Prognosis

poor if age of onset is over 1 year with metastases to bone; however, metastases to just liver, bone marrow, or spleen can be associated with a survival rate as high as 84%

Accounts for 15% of all childhood cancer deaths

In adults, neuroblastoma usually metastasizes to the uveal tract

Ewing’s Sarcoma

Second most frequent metastatic tumor to the orbit

Primary intermedullary malignancy of bone; originates in long bones of extremities or axial skeleton

Frequently metastasizes to bone and lungs

Occurs in 2nd-3rd decade of life

Findings

acute proptosis, hemorrhage, and inflammation from tumor necrosis

Granulocytic Sarcoma (‘Chloroma’)

Patients with myelogenous leukemia may present with orbital signs before hematologic evidence of leukemia

Findings

proptosis, may have subcutaneous periocular mass

Pathology

infiltration of involved tissues by leukemic cells

Histiocytosis X

Group of disorders resulting from abnormal proliferation of histiocytes (Langerhans’ cells) that may involve orbit

Spectrum of disease, from isolated bone lesions with excellent prognosis (eosinophilic granuloma) to systemic spread with rapid death (Letterer-Siwe disease)

Children under age 2 with multifocal disease have a poor prognosis (50% survival rate)

Findings

most frequent orbital presentation is lytic defect of orbital roof causing progressive proptosis

Pathology

granulomatous histiocytic infiltrate, Birbeck granules (central, dense core, and thick outer shell), stains positively for S-100 and vimentin

Eosinophilic granuloma

Benign, local, solitary bone lesion

Most likely to involve superior temporal bony orbit in childhood or adolescence

CT SCAN AND X-RAY: sharply demarcated osteolytic lesions

TREATMENT: incision and curettage, intralesional steroids, or radiotherapy

Hand-Schüller-Christian disease

Triad of proptosis, lytic skull defects, and diabetes insipidus

More aggressive

Multifocal bony lesions; frequently involves orbit, usually superolaterally

TREATMENT: systemic steroids and chemotherapy

PATHOLOGY: good

Letterer-Siwe disease

Most severe and malignant

Progressive and fatal

Multisystem involvement

Rarely ocular / orbital involvement

PATHOLOGY: systemic steroids and chemotherapy

Burkitt’s Lymphoma

Primarily affects the maxilla in black children, with secondary invasion of the orbit

Related to Epstein-Barr virus infection

Pathology

malignant B cells, ‘starry sky’ appearance due to histiocytes interspersed among uniform background of lymphocytes

Craniofacial Disorders

Structural development of head and face occur during 4th–8th week of gestation

Ocular motility disturbances occur in 75% of patients with craniofacial disorders

Syndromes

Treacher-Collins Syndrome (Mandibulofacial Dysostosis)

Hypoplasia of the midface

Associated with dental and ear abnormalities, microtia, micrognathia, hypoplastic malar bones, and low sideburns

Findings

lateral lid defects, absent lateral canthal tendon, absent medial lashes, antimongoloid slant, ectropion, poorly developed puncta and meibomian glands

Goldenhar’s Syndrome (Oculoauriculovertebral Dysplasia)

Abnormalities of the 1st and 2nd brachial arches

Findings

limbal dermoids and dermolipomas; may have lower lid colobomas

Other findings

hypoplastic facial bones, pretragal auricular appendages, vertebral abnormalities; may have fistulas between the mouth and ear

Associated with Duane’s syndrome

Hypertelorism

Findings

increased interpupillary distance due to increased distance between medial orbital walls

Associated with blepharophimosis, frontal meningoceles, encephaloceles, meningoencephaloceles, and fibrous dysplasia

Craniosynostoses

Premature closure of bony sutures; inhibits growth of the cranium perpendicular to the axis of the suture; growth can continue parallel to the suture

Plagiocephaly

premature closure of one-half of the coronal sutures

Skull develops normally on one side and is underdeveloped on the other side (resulting in a flattened face)

Other findings

midfacial hypoplasia, proptosis, telecanthus, V-pattern XT, oral and dental abnormalities, and respiratory problems

Crouzon’s Syndrome (Craniofacial Dysostosis) (autosomal dominant [AD] or Sporadic)

Absence of forward development of the cranium and midface

Multiple combinations of suture closure can occur

Findings

proptosis, V-pattern exotropia, nystagmus, hypertelorism; shallow orbits; optic atrophy (in 25–50%; due to narrowing of optic canal, kinking or stretching of optic nerve)

Other findings

mental retardation, hypoplasia of maxilla, parrot’s beak nose, high arched palate, external auditory canal atresia, anodonia

Apert’s Syndrome (AD)

Crouzon’s plus syndactyly

Anterior megalophthalmos

Associated with increased paternal age

Pfeiffer’s Syndrome (AD)

Findings

hypertelorism and pointy head; may have shallow orbits, syndactyly, and short digits

Carpenter’s Syndrome (autosomal recessive [AR])

Severe mental retardation

Involvement of sagittal, lambdoidal, and coronal sutures

Median Facial Cleft Syndrome

Other findings

medial cleft nose, lip, palate; widow’s peak; cranium bifidum occultum

Waardenburg’s Syndrome (AD)

Findings

lateral displacement of inner canthi / puncta, confluent eyebrows, heterochromia iridis, fundus hypopigmentation

Hemifacial Microsomia

Other findings

facial asymmetry with microtia, macrostomia, mandibular anomalies, orbital dystopia, ear tags, vertebral anomalies

Hallermann-Streiff Syndrome

Sporadic

Findings

bilateral cataracts, glaucoma, microphakia, microcornea

Pierre Robin Sequence

Findings

retinal detachment, congenital glaucoma and / or cataracts, high myopia

Other findings

micrognathia, glossoptosis, cleft palate

Associated with Stickler’s syndrome

Fetal Alcohol Syndrome

Findings

short palpebral fissures, telecanthus, epicanthal folds, comitant strabismus, optic disc anomalies; may have high myopia, anterior segment anomalies

Other findings

thin vermilion border of upper lip, variable mental retardation, small birth weight and height, cardiovascular and skeletal abnormalities

Lid Disorders

Ankyloblepharon

Partial or complete fusion of lid margins; usually temporal, often bilateral

Often AD

Associated with craniofacial abnormalities

Can be secondary to thermal or chemical burns, inflammation, ocular cicatricial pemphigoid, Stevens-Johnson syndrome

Blepharophimosis

Horizontally and vertically shortened palpebral fissures with poor levator function

Absent lid crease

May be part of autosomal dominant syndrome (chromosome 3q) with ptosis, telecanthus, epicanthus inversus, lower lid ectropion, hypoplasia of nasal bridge and superior orbital rim, anteverted ears, hypertelorism

Treatment

surgical correction requires multiple procedures

Coloboma

Embryologic cleft involving lid margin; unilateral or bilateral; partial or full thickness

Ranges from notch to absence of entire lid

Upper lid

usually medial third, not associated with systemic abnormalities, usually full thickness

Lower lid

usually lateral third, associated with other abnormalities (Treacher-Collins, Goldenhar’s syndromes), usually partial thickness

May have exposure keratitis

Treatment

method of surgical repair depends on size of defect (see section on Lid avulsion)

Congenital Horner’s Syndrome

Ptosis, miosis, anhydrosis

May cause amblyopia

Treatment

surgical repair (levator resection), severe cases require frontalis sling

Congenital Ectropion

Eversion of eyelid margin due to vertical shortening of anterior lamella

Etiology

inclusion conjunctivitis, anterior lamella inflammation, Down’s syndrome

Associated with blepharophimosis syndrome

Treatment

usually not required; otherwise, treat as the cicatricial form

Congenital Entropion

Inversion of eyelid margin

Etiology

lid retractor dysgenesis, tarsal plate defects, vertical shortening of posterior lamella

Usually involves lower eyelid

Congenital Tarsal Kink

Upper eyelid bent back and open with complete fold of tarsal plate

May cause corneal abrasion and exposure keratopathy

Distichiasis

Partial or complete accessory row of eyelashes growing from or posterior to meibomian orifices

Due to improper differentiation of pilosebaceous units

Usually well tolerated, but trichiasis may develop

Treatment

lubrication, cryoepilation, surgical epilation

Epiblepharon

Pretarsal skin and orbicularis override the lid margin, causing a horizontal fold of tissue to push cilia vertically; no entropion

Most common among Asians

Usually occurs in lower lid and resolves spontaneously

Rarely requires surgery (excision of skin and muscle for significant trichiasis)

Euryblepharon

Horizontal widening of palpebral fissure due to inferior insertion of lateral canthal tendon

Associated with ectropion of lateral third of lid

Poor lid closure with exposure keratitis

Treatment

lubrication, may require surgical repair with resection of excess lid, lateral canthal tendon repositioning, and vertical eyelid lengthening

Microblepharon

Vertical shortening of lids

May have exposure keratitis

Telecanthus

Widened intercanthal distance due to long medial canthal tendons

Associated with fetal alcohol, Waardenburg’s, and blepharophimosis syndromes

Lacrimal Disorders

Developmental Anomalies

Atresia of lacrimal puncta

ranges from thin membrane over punctal site to atresia of canaliculus

Lacrimal fistula

usually located inferonasal to the medial canthus

Dacryocystocele

Cystic swelling of lacrimal sac accompanies obstruction of lacrimal drainage system above and below the sac

Presents at birth as bluish swelling inferior and nasal to medial canthus

Infection (dacryocystitis) develops if condition does not resolve spontaneously

Common organisms: Haemophilus influenzae, S. pneumoniae, Staphylococcus, Klebsiella, Pseudomonas

Treatment

digital massage, lacrimal probing, or surgical decompression (for dacryocystitis)

Nasolacrimal Duct Obstruction (NLDO)

Up to 5% of infants have obstruction of the NLD, usually due to membrane covering valve of Hasner

Most open spontaneously within 4–6 weeks of birth; are bilateral

Findings

tearing, discharge; may develop dacryocystitis or conjunctivitis

Digital pressure over lacrimal sac producing mucoid reflux indicates obstruction of nasolacrimal duct

May have a dacryocystocele (dilated lacrimal sac), or amniotic fluid or mucus trapped in tear sac

Treatment

lacrimal sac massage, topical antibiotic, probing and irrigation by 13 months of age (95% cure rate); consider turbinate infracture and silicone intubation if probing unsuccessful; dacryocystorhinostomy (DCR) after multiple failures

Conjunctival Disorders

Conjunctivitis

Ophthalmia Neonatorum

Conjunctivitis within first month of life

Papillary conjunctivitis (no follicular reaction in neonate due to immaturity of immune system)

Etiology

Chemical: caused by silver nitrate 1% solution (Crede’s prophylaxis); occurs in first 24 hours, lasts 24 to 36 hours (therefore, prophylaxis is now with erythromycin or tetracycline ointment)

FINDINGS: usually bilateral, bulbar injection with clear watery discharge

No treatment necessary

Neisseria gonorrheae: days 1–2; can occur earlier with premature rupture of membranes

FINDINGS: severe purulent discharge, chemosis, eyelid edema; can be hemorrhagic; may develop corneal ulceration or perforation

DIAGNOSIS: Gram’s stain (Gram-negative intracellular diploccocci)

TREATMENT: IV ceftriaxone × 7 days; bacitracin ointment topically

High incidence of Chlamydia coinfection; therefore, also use oral erythromycin syrup and treat mother and sexual partners

Other bacteria: days 4–5; Staphylococci, Streptococci, Haemophilus, Enterococci

TREATMENT: bacitracin, erythromycin, or gentamicin ointment; fortified antibiotics for Pseudomonas

HSV: days 5–14; type 2 in 70%

FINDINGS: serous discharge, conjunctival injection, keratitis; may have vesicular lid lesions

Can have systemic herpetic infection

DIAGNOSIS: conjunctival scrapings with multinucleated giant cells; cultures take 5–7 days

TREATMENT: Zirgan 5×/d or Viroptic q2h × 1 week; acyclovir 10 mg/kg IV tid × 10 days

Chlamydia (neonatal inclusion conjunctivitis): days 5–14; most common infectious cause of neonatal conjunctivitis

FINDINGS: acute, mucopurulent, papillary (no follicles until 3 months of age); may have pseudomembranes

Associated with pneumonitis, otitis, nasopharyngitis, gastritis

DIAGNOSIS: intracytoplasmic inclusions on Giemsa stain

TREATMENT: topical erythromycin, oral erythromycin syrup × 2–3 weeks (125 mg/kg/day qid) to prevent pneumonitis (onset 3–13 weeks later); treat mother and sexual partners with doxycycline 100 mg bid × 1 week (do not use in nursing mothers)

Rule out concomitant Gonococcus infection

DDx

trauma, foreign body, corneal abrasion, congenital glaucoma, NLDO, dacryocystitis

Prophylaxis

tetracycline 1% or erythromycin 0.5% ointment at birth

Vernal Keratoconjunctivitis

Form of seasonal (warm months), allergic conjunctivitis

Male > female (2 : 1); onset by age 10 years, lasts 2–10 years, usually resolves by puberty

Associated with atopic dermatitis (75%) or family history of atopy (66%)

Findings

large upper tarsal papillae (cobblestones), minimal conjunctival hyperemia, Horner-Trantas’ dots (elevated white accumulations of eosinophils at limbus), limbal follicles (gelatinous nodules at limbus), copious ropy mucus; may have pseudomembrane, keratitis, micropannus, shield ulcer (central oval epithelial defect with white fibrin coating); high levels of histamine and IgE in tears

Pathology

chronic papillary hypertrophy, epithelial hypertrophy then atrophy, conjunctiva contains many mast cells, eosinophils, and basophils

Treatment

topical allergy medication and steroids; consider topical ciclosporin (cyclosporine)

Ligneous

Rare, bilateral, pseudomembranous conjunctivitis in children; commonly young girls

Acute onset, chronic course

Etiology

appears to be exaggerated response to tissue injury following infection, surgery, or trauma

Findings

unilateral or bilateral highly vascularized, raised, friable lesion; with continued inflammation, a white, thickened avascular woody (ligneous) mass appears above the neovascular membrane, usually on palpebral conjunctiva; easily removed but bleeds; may recur

Process affects all mucous membranes (mouth, vagina, etc)

Pathology

acellular eosinophilic hyaline material (immunoglobulins, primarily IgG), granulation tissue, cellular infiltration (T cells, mast cells, eosinophils)

Treatment

complete excision (expect significant bleeding); any remaining portion of lesion results in rapid recurrence because retained lesion acts as physical barrier to topical medications; ENT evaluation before surgery to ensure respiratory tract not involved because many require general anesthesia

Postexcision: topical steroids every hour; hyaluronidase, acetylcysteine, and α-chymotrypsin every 4 hours; topical antibiotic; topical cyclosporine (ciclosporin) 2% (applied to surgical bed with sterile cotton-tipped applicator); oral prednisone (1mg/kg/day); daily débridement of any recurrence

Kawasaki’s Disease (Mucocutaneous Lymph Node Syndrome)

Systemic childhood inflammatory disease / vasculitis with prominent mucocutaneous manifestations

Occurs in children <5 years old

More common among individuals of Japanese descent

Epidemics suggest exposure to causal agent; siblings have 10∞ increased risk

More than 50% of familial cases occur within 10 days after onset of 1st case

Diagnostic criteria (requires 5 of 6)

fever, bilateral conjunctivitis (90%), mild bilateral nongranulomatous uveitis (80%), rash, cervical lymphadenopathy, oral lesions (fissures, strawberry tongue), lesions of extremities (edema, erythema, desquamation)

Associated with polyarteritis

Treatment

aspirin; systemic steroids contraindicated (increased risk of coronary artery aneurysm)

Complications

15% develop coronary arteritis (can lead to coronary artery aneurysm or myocardial infarction)

Corneal Disorders

Anterior Megalophthalmos

Large anterior segment of eye

Associations

Marfan’s syndrome, mucolipidosis type II, Apert’s syndrome

Findings

high myopia and astigmatism; enlarged cornea, lens, iris, and ciliary ring; iris transillumination defects, lens dislocation, cataract

Congenital Corneal Staphyloma

Protuberant corneal opacity due to intrauterine keratitis

Findings

atrophic iris adheres to back of markedly thickened, scarred, and vascularized cornea; lens may be adherent to posterior cornea; cornea may perforate

Cornea Plana (AD or AR)

Mapped to chromosome 12q

Associations

sclerocornea, microcornea, and angle-closure glaucoma

Findings

flat cornea with curvature equaling that of sclera (usually 20–30 D), diffuse scarring and vascularization; may have coloboma, cataract, sclerocornea, shallow anterior chamber (AC), refractive error

Pathology

thickened epithelium, absent basement membrane, very thin Descemet’s, anterior third of stroma is scarred and vascularized

Megalocornea

Horizontal diameter of cornea greater than 12 mm in newborn (>13 mm in adult)

Nonprogressive; most commonly X-linked (associated with anterior megalophthalmos), bilateral, 90% male; also AR

Associations

Marfan’s syndrome, Alport’s syndrome, Down’s syndrome, dwarfism, craniosynostosis, facial hemiatrophy

Findings

large cornea; may have weak zonules, lens subluxation, hypoplastic iris, and ectopic pupil

Complications

ectopia lentis (enlarged limbal ring stretches the zonular fibers), glaucoma (due to angle abnormalities), cataract (PSC)

Posterior Keratoconus

Discrete posterior corneal indentation with stromal haze and thinning

Female > male

Nonprogressive, usually central and unilateral

Anterior corneal surface is normal

Vision usually good; causes irregular astigmatism

Pathology

loss of stromal substance; Descemet’s membrane may be thinned, but both it and endothelium are intact

Anterior Segment Dysgenesis (Mesodermal Dysgenesis Syndromes)

Bilateral, congenital, hereditary disorders affecting anterior segment structures

Axenfeld’s anomaly

posterior embryotoxon (anteriorly displaced Schwalbe’s line; found in 15% of normal individuals) with iris processes to scleral spur; 50% develop glaucoma; AD; mapped to chromosomes 4q25 (RIEG1), 13q14 (RIEG2), 6p25(FOXC1), 11p13 (PAX6)

Alagille’s syndrome

Axenfeld’s plus pigmentary retinopathy, corectopia, esotropia, and systemic abnormalities (absent deep tendon reflexes, abnormal facies, pulmonic valvular stenosis, peripheral arterial stenosis, biliary hypoplasia, and skeletal abnormalities); mapped to chromosome 20p12 (JAG1); ERG and EOG are abnormal

Rieger’s anomaly

Axenfeld’s plus iris hypoplasia with holes; 50% develop glaucoma; mapped to chromosomes 4q25 (RIEG1), 13q14 (RIEG2), 6p25 (FOXC1), and 11p13 (PAX6)

Rieger’s syndrome

Rieger’s anomaly plus mental retardation and systemic abnormalities (dental, craniofacial, genitourinary, and skeletal)

Peter’s anomaly

central corneal leukoma (opacity due to defect in Descemet’s membrane with absence of endothelium) with iris adhesions; lens involvement (cataract) may occur and 50% develop glaucoma; also associated with cardiac, craniofacial, and skeletal abnormalities; usually sporadic, bilateral (80%); AR or AD; mapped to chromosomes 11p13 (PAX6), 4q25-q26 (PTX2), 2p21-p22 (CYP1B1), and 6p25 (FOXC1)

Sclerocornea

Scleralized (white vascularized opacification) cornea; peripheral or entire

Nonprogressive; sporadic (50%) or hereditary (50%; AD or AR), mapped to chromosome 14; 90% bilateral

Corneoscleral limbus indistinct

Associations

persistent pupillary membrane, congenital glaucoma, cornea plana (80%)

Poor prognosis for corneal transplant

Descemet’s Tear / Rupture

May be caused by forceps trauma (vertical or oblique) or glaucoma (horizontal or concentric to limbus; Haab’s striae)

Acutely, edema occurs, scarring develops later

May cause astigmatism and amblyopia

Metabolic Disorders (Mucopolysaccharidoses, Mucolipidoses)

(see Table 5-4)

Table 5-4 Metabolic diseases with eye findings

Congenital Hereditary Stromal Dystrophy (CHSD) (AD)

Rare, nonprogressive, diffuse opacification of superficial cornea

Findings

flaky, feathery appearance of anterior stroma, clear peripherally; no corneal edema

May cause strabismus, nystagmus, and amblyopia

Dermoid

Smooth, solid, yellow-white choristoma that may extend into corneal stroma to cover visual axis or cause astigmatism

No hereditary pattern; 25% bilateral

Findings

dermoid, layer of lipid at leading edge in cornea; may cause proptosis, astigmatism, restricted motility, amblyopia

Pathology

thickened collagen fibers covered by skin-like epithelium; contains hair, sebaceous and sweat glands, and fat; lined by squamous epithelium

Treatment

observation; excision for cosmesis or if visual axis is blocked (caution: may be full thickness; granulomatous reaction if ruptures)

Other Causes of Corneal Opacity

Interstitial keratitis

congenital syphilis causes keratitis with edema followed by stromal vascularization (’salmon patch’), blood flow stops and ‘ghost’ vessels remain with corneal haze

Riley-day syndrome (familial dysautonomia; AR)

autonomic nervous system dysfunction due to block of NE production; Eastern European Jews

Findings: decreased corneal sensation, lack of tearing, poorly reactive pupils, light-near dissociation; may develop neurotrophic keratitis with risk of perforation

Other findings: poor pain, temperature, and taste sensation; spinal curvature; increased sweating; constipation; hypotension

Crisis (lasts 1–10 days): emotional lability, profuse sweating, postural hypotension, vomiting; treat with diazepam (Valium) and hydration

Increased risk with general anesthesia: exquisite sensitivity to thiopental sodium (Pentothal) (hypotension, cardiac arrest)

Diagnosis: high urinary homo-vanillic acid (HVA) and VMA, low hexamethylphosphorous triamide (HMPT)

Infections

Syphilis

Congenital

maternal transmission after 4th month of gestation (50% for primary or secondary syphilis, 30% for untreated or late syphilis)

Findings

interstitial keratitis (33%), ectopia lentis, Argyll-Robertson pupil, optic atrophy, panuveitis with various retinal pigmentary changes (usually salt and pepper or pseudo-RP)

Other findings

Early: stillbirth, failure to thrive, rhinitis (’snuffles’), osteochondritis, pneumonia, hepatosplenomegaly

Late: Hutchinson’s teeth (peg-shaped), mulberry molars, saber shins, frontal bossing, saddle nose, deafness (5%), tabes dorsalis

Hutchinson’s triad

interstitial keratitis, Hutchinson’s teeth, deafness

Interstitial keratitis (IK): immune response to treponemal antigens

Starts between ages of 5 and 20 years; triggered by minor corneal trauma

DDx

acquired syphilis (IK usually sectoral and less severe), leprosy (superficial avascular keratitis, usually superotemporal quadrant; later, leprous pannus of blood vessels, beading of corneal nerves)

Herpes Simplex Virus (HSV)

Often an asymptomatic primary infection before age of 5 years; 3- to 5-day incubation period

Congenital

ocular involvement in 10% of disseminated cases

Findings

vesicular skin eruption, conjunctivitis, epithelial keratitis, stromal immune reaction, cataracts, necrotizing chorioretinitis

Iris Disorders

Coloboma

Iris sector defect due to incomplete closure of embryonic fissure; usually located inferonasal

May have other colobomas (lid, ciliary body, choroid, retina, and optic nerve)

Associated with trisomy 13, 18, and 22; chromosome 18 deletion; Klinefelter’s syndrome, Turner’s syndrome, CHARGE, basal cell nevus syndrome, Goldenhar’s syndrome, Meckel’s syndrome, Rubinstein-Taybi syndrome, linear sebaceous nevus syndrome

Treatment

consider surgical repair in symptomatic cases

Congenital Iris Ectropion

Ectropion uveae

ectropion of posterior pigment epithelium onto anterior surface of iris

Associated with neurofibromatosis, Prader-Willi syndrome

Congenital iris ectropion syndrome

unilateral congenital iris ectropion, high iris insertion, smooth cryptless iris surface, dysgenesis of angle, and glaucoma

Congenital Iris Hypoplasia

Thin iris stroma with transillumination of entire iris

Associated with albinism

Congenital Miosis

May be associated with other anterior segment abnormalities

Etiology

absence or malformation of dilator pupillae muscle or contracture of fibrous material on pupil margin from tunica vasculosa lentis remnant or neural crest cell abnormalities

Congenital Mydriasis

Etiology

iris sphincter trauma, pharmacologic, neurologic disease

Corectopia

Displacement of pupil

Isolated or associated with ectopia lentis et pupillae, Axenfeld-Rieger syndrome, iridocorneal endothelial syndrome, uveitis, or trauma

Dyscoria

Abnormally shaped pupil

Isolated or associated with posterior synechiae, Axenfeld-Reiger syndrome, ectopia lentis et pupillae

Persistent Pupillary Membrane

Remnants of anterior tunica vasculosa lentis that appear as fine iris strands

Common congenital ocular anomaly

Rarely visually significant

Type II

iris to lens; may have associated anterior polar cataract

Primary Iris Cysts

Due to spontaneous separation of pigmented and nonpigmented epithelium

Occur anywhere between pupil and ciliary body

Miotics can cause cysts at pupillary border

Congenital stromal cysts occur in infants and young children from sequestration of epithelium during fetal development

Brushfield’s Spots

Focal areas of iris stromal hyperplasia surrounded by relative hypoplasia

Appear as ring of peripheral, elevated, white-gray spots (10–20/eye)

Occur in 85% of Down syndrome patients

May be found in normal individuals (Kunkmann-Wolffian bodies)

Lisch Nodules

Neural crest hamartomas

Associated with neurofibromatosis type I

Number and frequency increase with age

Appear as tan nodules, usually in inferior iris

Juvenile Xanthogranuloma (JXG; Nevoxanthoendothelioma)

Histiocytic proliferation usually of skin

Yellow-orange nodules appear before 1 year of age

Orange because of vascularity (red) combined with high lipid content (yellow)

May involve iris (may cause spontaneous hyphema)

May involve muscles, salivary glands, stomach, and other internal organs

Rarely associated with an orbital granuloma (which causes proptosis)

Lesions often spontaneously regress by 5 years of age

Pathology

diffuse non-necrotizing proliferation of histiocytes with scattered touton giant cells (ring of nuclei separating a central eosinophilic cytoplasm from peripheral foamy [or clear] cytoplasm)

Treatment

iris lesions are treated with steroids, XRT, and excision

Medulloepithelioma (Diktyoma)

Primary neoplasm of ciliary body neuroectoderm (arises in nonpigmented epithelium); arises from primitive medullary epithelium that lines neural tube; can also arise in retina and ON

Occurs in both benign and malignant forms (locally invasive but limited metastatic potential)

May have heterotopic elements; no calcification

Unilateral, unifocal, usually arises before 6 years of age; no hereditary pattern

Types

Nonteratoid or simple: pure proliferation of embryonic nonpigmented ciliary epithelium

Teratoid: contains heterotopic elements such as cartilage, brain tissue, and rhabdomyoblasts

Findings

decreased vision, pain, strabismus, leukocoria, iris mass, fleshy pink to white peripheral fundus tumor; rubeosis, hyphema, glaucoma, lens coloboma occurs in some congenital cases

Pathology

undifferentiated round to oval cells containing little cytoplasm, organized into ribbon-like structures that have distinct cellular polarity; lined on one side by thin basement membrane; stratified sheets of cells are capable of forming mucinous cysts that are clinically characteristic; Flexner-Wintersteiner and Homer-Wright rosettes can be seen; called teratoid medulloepithelioma when composed of cells from 2 different embryonic germ layers; may contain cartilage, brain tissue, and rhabdomyoblasts

Treatment

resection (iridocyclectomy) or enucleation (not radiosensitive)

Prognosis

good if no extraocular extension; rarely metastasizes

Lens Disorders

Congenital Anomalies

Mittendorf’s dot

small white opacity on posterior lens capsule that represents a remnant of the posterior vascular capsule (tunica vasculosa lentis) where hyaloid artery is inserted

Chicken tracks (epicapsular star)

brown or golden flecks on anterior lens capsule; remnant of anterior tunica vasculosa lentis

Lenticonus

cone-shaped lens deformity due to central bulge in area of thin capsule; causes irregular myopic astigmatism; ‘oil-droplet’ sign on retinoscopy; associated with cataract

Anterior: bilateral, male > female; associated with Alport’s syndrome (anterior lenticonus, hereditary nephritis, and deafness)

Posterior: unilateral, sporadic, female > male, more common than anterior type, amblyopia common

Lens coloboma

focal flattening of lens edge due to absence of inferior zonules from ciliary body coloboma; not a true coloboma

Lentiglobus

generalized hemispherical deformity, very rare

Microphakia

small lens due to arrested development; associated with Lowe’s syndrome

Microspherophakia

small, spherical lens, usually bilateral; zonules visible on pupillary dilation; iridodenesis; zonule rupture is common, pupillary block may occur especially with use of miotics (treat with cycloplegic to tighten zonules, flattening the lens and pulling it posteriorly)

Associated with Weill-Marchesani syndrome, hyperlysinemia, Lowe’s syndrome, Alport’s syndrome, congenital rubella, and Peter’s anomaly

Treatment: cycloplegic (tightens zonules, flattening lens and pulling it posteriorly)

Congenital Cataracts

Characteristics

Bilateral: usually AD; consider diabetes, galactosemia, or Lowe’s syndrome; require metabolic workup and treatment by age 3 months, or irreversible nystagmus with poor visual acuity (≤20/200) occurs. Opacities greater than 3 mm can be visually significant. Surgery often performed on the better-seeing eye first: lensectomy, anterior vitrectomy, and contact lens fitting for infants; posterior capsulotomy is necessary due to significant postoperative inflammation, which causes posterior capsular opacification

Unilateral: generally not metabolic or genetic; therefore, laboratory testing is not needed. Usually local dysgenesis (PHPV, anterior polar or posterior lenticonus), often presents with leukocoria and strabismus. Requires treatment by 6–8 weeks of life

Types

classified by location or etiology

Polar (subcapsular cortex and capsule): anterior or posterior, sporadic, or AD

ANTERIOR: usually small, bilateral, symmetric, nonprogressive; good visual prognosis; 90% are idiopathic. Remnant of the hyaloid system. Associated with microphthalmos and anterior lenticonus

PATHOLOGY: fibrous plaque beneath folded anterior capsule secreted by irritated metaplastic epithelial cells

POSTERIOR: larger, usually stable, but may progress; more visually significant; AD (bilateral) or sporadic (unilateral); often with associated defect of posterior capsule

Associated with remnants of the tunica vasculosa lentis, posterior lenticonus, or lentiglobus

PATHOLOGY: posterior migration of lens epithelium

Sutural (AR): bilateral opacities of Y sutures; rarely affects vision. Occurs during development of fetal lens nucleus

Nuclear (usually AD): bilateral, opacification of embryonic / fetal nucleus; typically axial, dense, bilateral, and larger than 3 mm. Associated with small eye

Anterior pyramidal: congenital anterior subcapsular

Lamellar / zonular: bilateral, symmetric, appears like a sand dollar; circumscribed zone of opacity within lens, surrounding the nucleus. May be due to transient toxic exposure during embryogenesis (neonatal tetany); can be AD. Usually does not interfere with vision

Complete: no red reflex; unilateral or bilateral

Membranous: lens proteins resorb following trauma; anterior and posterior capsules fuse into a dense white membrane

Crystalline: rare, bilateral congenital cataract, with refractile, rhomboid crystals (containing tyrosine and cysteine) radiating outward from the center of the lens into the juvenile nucleus

Anterior axial embryonic: most common type of congenital / infantile cataract. White, clustered, punctate opacities near the Y sutures; not visually significant

Pulverulent (AR): central, translucent, ovoid, and cluster of dot-like opacities in the fetal nucleus

Coronary (AR): wreath of peripheral cortical opacities that encircle the nucleus in a radial fashion; smaller punctate bluish opacities within the nucleus. Associated with Down’s syndrome

Etiology

hereditary; associated with systemic syndromes; of unknown origin

Etiology of bilateral cataracts

Idiopathic (60%)

Intrauterine infection (3%): TORCH syndromes (Toxoplasmosis, Other infections (syphilis; also hepatitis B, Varicella-Zoster virus, HIV, parvovirus B19), Rubella, CMV, HSV) the alternate acronym is TORCHES (TOxoplasmosis, Rubella, CMV, HErpes simplex, Syphilis)

Associated with ocular disorders: Leber’s congenital amaurosis, retinitis pigmentosa (RP), PHPV, retinopathy of prematurity (ROP), aniridia, Peter’s anomaly, ectopia lentis, posterior lenticonus, uveitis, tumors (retinoblastoma, medulloepithelioma)

Metabolic: galactosemia, hypocalcemia, Lowe’s syndrome, congenital hemolytic jaundice, hypoglycemia, mannosidosis, Alport’s syndrome, Fabry’s disease

Hereditary (30%, usually AD):

WITHOUT SYSTEMIC ABNORMALITIES: AD, AR, X-linked

WITH CHROMOSOMAL ABNORMALITIES: trisomy 18, trisomy 21 (Down’s syndrome), Turner’s syndrome, trisomy 13 (Patau’s syndrome), ‘cri-du-chat’ syndrome

CRANIOFACIAL SYNDROMES: Crouzon’s syndrome, Apert’s syndrome, Hallermann-Streiff syndrome, Pierre Robin sequence

CNS ABNORMALITIES: Zellweger syndrome, Torsten-Sjögren syndrome, Marinesco-Sjögren syndrome, Lawrence-Moon-Biedl-Bardet syndrome, Norrie’s disease, neurofibromatosis

SKIN ABNORMALITIES: Cockayne’s syndrome, Rothmund-Thomson syndrome, Werner’s syndrome, atopic dermatitis, ichthyosis, incontinentia pigmenti

Maternal drug ingestion / malnutrition

Trauma

Specific entities

Galactosemia (AR): defect in 1 of 3 enzymes (galactose-1-P-uridyl transferase [most common], galactokinase, or uridine diphosphate [UDP] galactose-4-epimerase) causes inability to convert galactose into glucose; galactose is converted into galactitol, which serves as osmotic agent for influx of fluid

FINDINGS: oil-droplet cataract (reversible early on)

OTHER FINDINGS: mental retardation, hepatomegaly, jaundice, and malnutrition within 1st few weeks of life

TREATMENT: eliminate lactose from diet; fatal if untreated

Mannosidosis: α-mannosidase deficiency causes Hurler-like syndrome

FINDINGS: posterior spoke-like opacity; no corneal changes (unlike Hurler’s)

OTHER FINDINGS: mental retardation, short stature, skeletal changes, hepatosplenomegaly

Fabry’s disease: α-galactosidase A deficiency

FINDINGS: cornea verticillata; spoke-like cataract in 25%

OTHER FINDINGS: angiokeratomas, cardiovascular abnormalities, renal disorders, bouts of pain in digits

Hypocalcemia: either idiopathic or following surgery of parathyroid glands

Punctate iridescent opacities in anterior and posterior cortex

Lowe’s (oculocerebrorenal) syndrome (X-linked): defect of amino acid metabolism; male > female

FINDINGS: congenital cataract (100%), usually bilateral; small, thin, discoid lens (microphakic) associated with retained lens nuclei; glaucoma (50%); congenital cataract and glaucoma are very rare

Female carriers have white, punctate cortical opacities and subcapsular plaque-like opacities

OTHER FINDINGS: renal tubular acidosis, aminoaciduria, renal rickets, mental retardation, muscular hypotonia, failure to thrive

Alport’s syndrome (X-linked): triad of anterior lenticonus, deafness, and hemorrhagic nephropathy / renal failure

FINDINGS: conjunctival calcium crystals, corneal endothelial pigment, juvenile arcus, spherophakia, anterior polar cataract, retinal changes similar to retinitis pigmentosa or fundus albipunctatis, optic nerve drusen

Female carriers have lenticular changes

DIAGNOSIS: renal or skin biopsy (lack of α-5 type IV collagen in glomerular and epidermal basement membranes)

Hallermann-Streiff syndrome (mandibulo-oculofacial dysmorphia): hypoplasia of mandible with bird-like facies; one of the few syndromes with combined cataract and glaucoma

FINDINGS: microphakia, microcornea, glaucoma, and cataract (can develop within 1st few weeks of life); spontaneous rupture of lens capsule with absorption of lens proteins can occur; immune response to lens proteins resembles phacoanaphylactic uveitis

Intrauterine infections: usually occur early in first trimester because lens capsule is formed during week 5 of embryogenesis; rubella, HSV, mumps, toxoplasmosis, vaccinia, CMV

Hypoglycemia during pregnancy: congenital lenticular opacities; associated with optic atrophy, mental retardation

Down’s syndrome: snowflake cataract, keratoconus

Diagnosis of bilateral cataracts

if AD pattern determined, no workup is necessary

Urinalysis: amino acids (Lowe’s syndrome), reducing substance after milk feeding (galactosemia)

Blood tests: calcium (hypocalcemia / hyperparathyroidism), glucose (hypoglycemia), red blood cell galactokinase, TORCH titers

Karyotyping: trisomy 13 (Patau’s syndrome), 18, and 21 (Down’s syndrome); Turner’s syndrome, ‘cri-du-chat’ syndrome

Bilateral audiograms: congenital rubella, Alport’s syndrome

B-scan ultrasound: if no view of fundus

Etiology of unilateral cataracts

Idiopathic (80%):

Ocular abnormalities (10%): PHPV, posterior lenticonus (90% unilateral), anterior segment dysgenesis, tumors (retinoblastoma, medulloepithelioma)

Trauma (9%):

Intrauterine infection: rubella; 33% unilateral

Diagnosis of unilateral cataracts

rule out trauma (child abuse), TORCH titers

DDx of leukocoria (white pupil)

cataract, retinoblastoma, toxoplasmosis, toxocariasis, RD, ROP, PHPV, Coats’ disease, coloboma, myelinated nerve fibers, retinal dysplasia, Norrie’s disease, incontinentia pigmenti, retinoschisis, cyclitic membrane, medulloepithelioma

DDx of congenital cataracts and glaucoma

Lowe’s syndrome, rubella, Hallermann-Streiff syndrome

Rubella: due to maternal infection late in the first trimester of pregnancy

FINDINGS (in 50%): cataract (usually bilateral, pearly white nuclear opacification; retention of lens nuclei in embryonic nucleus; virus remains viable in lens for years: viral shedding following cataract surgery can lead to intense and persistent AC inflammation), salt and pepper fundus (normal ERG), glaucoma (usually either cataract or glaucoma, rarely both), microphthalmos (15%), necrotizing iridocyclitis, corneal clouding

OTHER FINDINGS (especially during 1st trimester): cardiac defects (patent ductus arteriosis), deafness (infection of the organ of Corti [90%]), and mental retardation

Complications of surgery

chronic aphakic glaucoma (15%). Usually discovered 5–6 years after surgery; increased risk with trauma, microcornea, PHPV, preexisting anterior segment abnormalities, and retained lens material

Prognosis

Good: lamellar cataracts (later onset and less risk of glaucoma)

Intermediate: nuclear cataracts

Poor: total cataracts (high incidence of microcornea, poor pupillary dilation, and increased risk of glaucoma). Microphthalmos, strabismus, nystagmus, and amblyopia; 90% of patients with visually significant congenital bilateral cataracts will develop nystagmus if not treated by 2 months of age; nystagmus and amblyopia may not resolve even after cataract surgery

Glaucoma

Childhood Glaucoma

Several types of glaucoma typically categorized by age of onset

Congenital (occurs in infants <3 months old; may be primary, secondary, or associated with a syndrome)

Infantile (between 3 months and 3 years of age)

Juvenile (between 3 and 35 years of age)

Types (Figure 5-6)

Figure 5-6 Classification of the congenital and infantile glaucomas.

(From Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Primary Congenital Glaucoma

Etiology

mapped to chromosomes 1p36 (GLC3B), 2p21-p22 (GLC3A, CYP1B1); a mutation in the CYP1B1 gene accounts for ∼85% of congenital glaucoma. AR in 10%; affected parent has 5% chance of having a child with infantile glaucoma

Epidemiology

occurs in 1 of 12,500 births; 40% present at birth; 86% present during first year of life; 70% bilateral; 70% males

Symptoms

tearing, photophobia, blepharospasm, eye rubbing. If younger than age 3 months, usually presents with corneal clouding or tearing; older than 3 years of age, usually asymptomatic with progressive myopia and insidious VF loss

Findings

IOP >21 mmHg; C/D ratio >0.3 (present in only 2.6% of normal infants; cupping is reversible in childhood); buphthalmos (‘bull’s-eye’; horizontal corneal diameter >13 mm; limbal ectasia; stretching of zonules can lead to lens subluxation; irreversible); corneal clouding / edema / Haab’s striae (circumferential or horizontal Descemet’s ruptures [vs oblique or vertical with forceps injury]; may result in chronic corneal edema, scarring, and astigmatism); myopia

Angle is of neural crest origin, as are facial bones, teeth, cartilage, and meninges; therefore, congenital glaucoma may be associated with malformation of these structures

Other ocular associations

microcornea, cornea plana, sclerocornea, Axenfeld’s / Reiger’s / Peter’s anomaly (50%), aniridia (50–75% develop glaucoma by teens due to increased episcleral venous pressure, iris stump blocking TM, or angle malformation or agenesis), microspherophakia, nanophthalmos, PHPV, ROP, tumors (retinoblastoma [RB], JXG, medulloepithelioma), inflammation, trauma, steroid-induced

Associated syndromes

Lowe’s syndrome (50%); Sturge-Weber syndrome (50%, especially if nevus flammeus involves upper lid, due to primary defect in angle and increased episcleral venous pressure); neurofibromatosis (25% if plexiform neurofibroma involves upper lid; may have hamartomatous infiltration of angle); congenital rubella (2–15%); also Marfan’s syndrome, homocystinuria, Weill-Marchesani syndrome, Rubenstein-Taybi, Pierre Robin, nevus of Ota, trisomy 13 (Patau’s), Hallermann-Streiff, Stickler’s syndrome, mucopolysaccharidoses (Hurler’s and Hunter’s)

Diagnosis

Examination under anesthesia (EUA): usually required for complete evaluation. Remember, ketamine and succinylcholine raise IOP, general anesthesia (halothane, thiopental, tranquilizers, and barbituates) lowers IOP. Best time for IOP measurement is just as patient goes under and is not too deep

Gonioscopy: landmarks are often poorly recognized due to ‘Barkan’s membrane’ covering TM (but no histologic evidence of such a structure)

1 Open-angle with anterior iris insertion above scleral spur (usual configuration is flat iris insertion into trabecular meshwork; less commonly, concave insertion with plane of iris posterior to scleral spur and anterior iris sweeping upward and inserting into TM)

2 Thickening of TM

3 Peripheral iris stromal hypoplasia

Treatment

definitive treatment is surgical; medication is a temporizing measure

Goniotomy: perform in child <

years of age; TM incised under direct gonioscopic visualization; requires clear cornea; 77% success rate

Trabeculotomy (ab externo): if cornea hazy, if >

years old, or if goniotomy fails twice; Schlemm’s canal is entered via an external incision, and the trabeculotome rotates into the AC and tears the TM; 77% success rate

If goniotomy and trabeculotomy fail, consider trabeculectomy with mitomycin C, drainage implant, cycloablation of CB

Uveitis

Anterior Uveitis

DDx

JRA, trauma, infection, tumor, sympathetic ophthalmia, sarcoidosis, phacoantigenic

Juvenile Rheumatoid Arthritis (JRA)

Most common cause of uveitis in children: seronegative (RF−), ANA-positive, pauciarticular (<5 joints) arthritis in children <16 years old; mostly girls

Types (Table 5-2)

Pauciarticular (<5 joints), early onset: 80% female; 30% with chronic iridocyclitis; 25% of all JRA; RF−; 60% ANA+

Pauciarticular, late onset: 90% male; 15% of all JRA; RF−; ANA−; 75% HLA-B27; 15% acute iridocyclitis

Polyarticular (<5 joints): 85% female; iridocyclitis rare; 40% of all JRA; 75% are RF−

Still’s disease: throughout childhood; 60% male; small and large joints; iridocylitis rare; 20% of all JRA; RF−; ANA−; high fever, rash, organomegaly, polyserositis

Table 5-2 Classification of JRA

Findings

chronic anterior uveitis (30%, usually bilateral; eyes are white and quiet even with active ocular inflammation [lots of flare]), glaucoma (20%), cataract (40%), band keratopathy (40%)

Other findings (30%)

arthritis, fever, lymphadenopathy, maculopapular rash, myocarditis, hepatosplenomegaly

Treatment

topical steroids and cycloplegic; consider systemic steroids or sub-Tenon’s steroid injection; treat complications. May require immunosuppressive agents, EDTA chelation for band keratopathy, treatment of secondary glaucoma, cataract surgery (eyes should be without AC reaction for at least 3 months; intraoperatively, anterior vitrectomy, synechialysis, removal of cyclitic membranes; no IOL; may be complicated by hypotony)

Posterior Uveitis

DDx

toxoplasmosis, toxocariasis, presumed ocular histoplasmosis syndrome (POHS), HSV, syphilis, Lyme disease, sympathetic ophthalmia, masquerade syndromes (RB, leukemia, lymphoma, melanoma, JXG, intraocular foreign body, RD, RP, MS)

Toxoplasmosis

Due to infection with Toxoplasma gondii, usually congenital (maternal infection during gestation)

70% of women are seronegative

Primary retinal infection with coagulative necrosis and secondary granulomatous choroiditis with vitritis; intraretinal cysts cause recurrent disease

Most common cause of posterior uveitis (25%); 98% congenital

Most common cause of pediatric uveitis (50% of posterior uveitis in children)

Tachyzoite form is responsible for inflammation

Congenital infection

transplacental transmission of T. gondii

First-trimester infection: neonatal convulsions, intracerebral calcifications, retinitis

Later infection: may have retinitis only

inactive chorioretinal scar in posterior pole, often in macula (Figure 5-7); active focal white fluffy lesion (‘headlight in fog’ appearance) occurs adjacent to old scar with granulomatous uveitis and vitritis; may have white spots along arterioles (Kyrieleis’ plaques); may have microphthalmia, nystagmus, strabismus

In AIDS: head CT may show ring-enhancing lesions; minimal AC reaction and vitritis because immunocompromised host is unable to mount normal immune response

Figure 5-7 Congenital toxoplasmic retinitis. Note inactive satellite scars at the macula, the inferior juxtapapillary scar, and the temporal pallor of the disc.

(From Khanna A, Goldstein DA, Tessler HH: Protozoal posterior uveitis. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Other findings

Congenital toxoplasmosis: stillbirth, mental retardation, seizures, hydrocephalus, microcephaly, intracranial calcifications, hepatosplenomegaly, vomiting, diarrhea

Acquired toxoplasmosis: rash, meningoencephalitis, flu-like syndrome

Pathology

round Toxoplasma cysts (Figure 5-8); chronic granulomatous choroiditis

Figure 5-8 Viable and necrotic cysts of Toxoplasma gondii in the necrotic retina.

(From Khanna A, Goldstein DA, Tessler HH: Protozoal posterior uveitis. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Diagnosis

ELISA or immunofluorescence assay (IFA) for Toxoplasma IgG or IgM

Toxocariasis (Table 5-3)

Due to infection with 2nd-stage larval form of dog roundworm Toxocara canis (ocular larva migrans)

Table 5-3 Clinical presentations of toxocariasis

Acquired by ingestion of contaminated soil

Ocular larva migrans

usually unilateral, solitary lesion; does not complete life cycle (stool examination unnecessary), no other findings

Visceral larva migrans

fever, lymphadenopathy, hepatomegaly, pneumonitis, eosinophilia, no eye involvement

Findings

3 clinical presentations depending on patient age (endophthalmitis, localized granuloma, or peripheral granuloma); vitreous abscess; dragging of macula temporally owing to peripheral lesion results in apparent XT; often presents with leukocoria; traction RD can occur (Figure 5-9)

Figure 5-9 Typical toxocara granuloma located over the optic nerve.

(In: Yanoff M, Duker JS [eds]: Ophthalmology (Ch. 173), London, Mosby, 1999.)

Other findings

may affect lungs and liver

DDx

as for leukocoria

Diagnosis

AC tap for eosinophils; ELISA for Toxocara antibody titers; no ova / parasites in stool

Treatment

topical steroid and cycloplegic for active uveitis; vitrectomy, may require surgical repair of RD

Metabolic Disorders

(Table 5-4 and Box 5-2)

Box 5-2 Ocular manifestations of childhood cerebral degenerations

Conjunctival telangiectasia: ataxia telangiectasia, Fabry’s disease

Glaucoma: MPS I-Scheie, Zellweger’s disease (rare)

Corneal opacity: MPS I, III, IV, VI; mucolipidoses III, IV; Fabry’s disease, sialidosis with chondrodystrophy, Cockayne’s disease, xeroderma pigmentosum, Zellweger’s disease (occasionally), Wilson’s disease (Kayser-Fleischer ring)

Lens opacity: Wilson’s disease, galactosemia, Marinesco-Sjögren syndrome, Lowe’s disease, cerebrocutaneous xanthomatosis, sialidosis, mannosidosis

Cherry red spot: Tay-Sachs disease, sialidosis, Niemann-Pick disease (50%), GM gangliosidosis (50%), Farber’s disease, multiple sulfatase deficiency (metachromatic leukodystrophy variant)

Macular and pigmentary degeneration: ceroid lipofuscinosis, MPS 1-H, 1-S, II, III; mucolipidoses IV, Refsum’s disease (phytanic acid lipidosis), Bassen-Kornzweig (abetalipoproteinemia), Kearns-Sayre syndrome

Optic atrophy: Krabbe’s disease, metachromatic leukodystrophy, sphingolipidoses, adrenoleukodystrophy, Alexander’s disease, spongy degeneration, Pelizaeus-Merzbacher disease, neuraxonal dystrophy, Alpers’ disease, spinocerebellar degeneration, diseases with retinal pigmentary degeneration

Nystagmus: diseases with poor vision (searching nystagmus), Pelizaeus-Merzbacher disease, metachromatic leukodystrophy, Friedreich’s ataxia, other spinocerebellar degenerations and cerebellar atrophies, neuraxonal dystrophy, ataxia telangiectasia, Leigh’s syndrome, Marinesco-Sjögren syndrome, opsoclonus-myoclonus syndrome, Chédiak-Higashi disease

Ophthalmoplegia: Leigh’s syndrome, Kearns-Sayre syndrome, Niemann-Pick variant with vertical ophthalmoplegia, Gaucher’s disease, Bassen-Kornzweig syndrome, ataxia-telangiectasia, Tangier’s disease

Retinal Disorders

Persistent Hyperplastic Primary Vitreous (PHPV)

Unilateral microphthalmia with spectrum of findings from prominent hyaloid vessel remnant with large Mittendorf’s dot and Bergmeister’s papillae to angle-closure from fibrovascular invasion of lens through posterior lens capsule

Due to incomplete regression of tunica vasculosa lentis and primary vitreous

Sporadic, 90% unilateral

Findings

microphthalmia, vascularized retrolental plaque (may contain cartilage), elongated ciliary processes, prominent radial vessels on iris surface, shallow AC, iris vascularization; may have cataract, angle-closure glaucoma, vitreous hemorrhage, retinal detachment

DDx of intraocular cartilage

PHPV, medulloepithelioma, teratoma, trisomy 13

Treatment

observation, lensectomy with or without vitrectomy

Prognosis

depends on degree of amblyopia; visual prognosis variable after surgery, often depends on status of posterior segment

Coloboma

Yellow-white lesion with pigmented margins due to incomplete closure of embryonic fissure; usually located inferonasal

Retina is reduced to glial tissue; no RPE; may have colobomas of other ocular structures

Retinopathy of Prematurity (Retrolental Fibroplasia)

Vasoproliferative retinopathy occurring almost exclusively in premature infants; occasionally in full-term infants

Risk factors

low birth weight (<1.5 kg; if <1.25 kg, 65% develop some degree of ROP), early gestational age (<33 weeks), supplemental oxygen (>50 days; controversial), coexisting illness

Risk increases exponentially the more premature and the smaller the infant: <2000 g (4 pounds, 7 ounces), earlier than 36 weeks (at 36 weeks, nasal retina is completely vascularized; at 40 weeks, temporal retina is fully vascularized)

2 phases

Acute: abnormal vessels develop in association with fibrous proliferation; >85–90% spontaneously regress

Chronic: retinal detachment, temporal displacement of macula, severe vision loss; occurs in 15%

Classification

(International Classification of ROP [ICROP])

Zone:

1 Posterior pole, area enclosed by 60° diameter circle centered on optic nerve

2 Area between edge of zone 1 and circle centered on optic disc and tangent to nasal ora serrata

3 Remaining crescent of temporal peripheral retina anterior to zone 2

Extent: measured in clock hours of involvement

Figure 5-10 Stage 1 retinopathy of prematurity. The flat, white border between the avascular and vascular retina seen superiorly is called a demarcation line.

(Reproduced from Earl A. Palmer, MD, and the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. From Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Figure 5-11 Stage 2 retinopathy of prematurity. The elevated mesenchymal ridge has height. Highly arborized blood vessels from the vascularized retina dive into the ridge.

(Reproduced from Palmer EA, MD, and the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity: In: Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Figure 5-12 Stage 3 retinopathy of prematurity. Vessels on top of the ridge project into the vitreous cavity. The extraretinal proliferation carries with it a fibrovascular membrane. Note the opalescent avascular retina anterior to the ridge.

(From Sears J, Capone A: Retinopathy of primaturity. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Figure 5-13 Stage 3 retinopathy of prematurity. Note finger-like projections of extraretinal vessels into the vitreous cavity. Hemorrhage on the ridge is not uncommon.

(From Sears J, Capone A: Retinopathy of prematurity. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Figure 5-14 Stage 4a detachment spares the fovea. Stage 4b detachment involves the fovea.

(From Sears J, Capone A: Retinopathy of prematurity. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Plus disease

engorged, tortuous vessels around disc, vitreous haze, and iris vascular congestion; progressive vascular incompetence throughout eye; poor prognostic sign

Threshold disease

(level at which 50% go blind without treatment) = stage 3 in zone 1 or 2 with Plus disease and at least 5 contiguous or 8 cumulative clock hours of involvement; usually develops at 27 weeks’ postgestation (Figure 5-15)

Figure 5-15 Definition of ‘threshold’ retinopathy of prematurity.

(From Sears J, Capone A: Retinopathy of prematurity. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Aggressive posterior (AP) ROP or Rush disease

plus disease in zone 1 or posterior zone 2; rapidly progressive

Prethreshold

1 Zone 1, any stage

2 Zone 2, stage 2+ or 3

3 Zone 2, stage 3+ for >5 clock hours

DDx of peripheral vascular changes and retinal dragging

FEVR, incontinentia pigmenti (Bloch-Sulzberger syndrome), X-linked retinoschisis

DDx of temporally dragged disc

FEVR, Toxocara, congenital falciform fold

Diagnosis

screen infants <1250 g, on supplemental oxygen during first 7 days of life, or <27 weeks’ gestation

Treatment

observation, laser, cryo, surgery

Cryotherapy for ROP Study (Cryo-ROP): determined whether treatment for ROP would prevent poor outcomes (see below)

Treat with ablation of peripheral avascular retina: when patient reaches type 1 ROP, defined as:

Zone 1, any stage with Plus disease

Zone 1, stage 3

Zone 2, stage 2 or 3 with Plus disease

(Early Treatment of ROP Study [ETROP])

Indirect argon green or diode laser photocoagulation: 500 µm spots to entire avascular retina in zone 1 and peripheral zone 2 (at least as effective as cryotherapy; Laser-ROP study)

Cryotherapy: to entire avascular retina in zone 2, but not ridge (cryo-ROP study)

Serial exams: with type 2 ROP, defined as:

Zone 1, stage 1 or 2

Zone 2, stage 3

Surgery: vitrectomy with or without lensectomy, membrane peel, and possible scleral buckle for tractional retinal detachment (TRD) or rhegmatogenous retinal detachment (RRD) (cicatricial ROP, stages 4 and 5)

Prognosis

depends on extent of disease; most cases resolve spontaneously without visible residua

Some develop cicatricial changes: (retrolental fibroplasia)

GRADE I: myopia and peripheral glial scar (VA >20/40)

GRADE II: dragged retina, macular heterotopia (VA 20/50-20/200)

GRADE III: retinal fold (VA <20/200)

GRADE IV: partial retrolental membrane and RD (VA = HM or LP)

GRADE V: complete retrolental membrane and RD (VA = LP or NLP)

Complications

Grade I-II: myopia (80%; due to forward displacement of lens–iris diaphragm), anisometropia, strabismus, amblyopia, macular heterotopia, pseudo-XT (change in angle κ due to macular dragging from peripheral cicatrization), increased risk of retinal tear or RD

Grade III-V: nystagmus, glaucoma, cataracts, heterochromia irides, rubeosis iridis, anterior uveitis, RD, band keratopathy, phthisis bulbi

Major clinical study

Cryotherapy for ROP Study (Cryo-ROP)

Objective: to evaluate whether cryotherapy for ROP in preterm infants with birth weights <1251 g prevents unfavorable outcomes (posterior retinal fold, stage 4B or 5 retinal detachment, or visual acuity of 20/200 or worse)

Results

The more posterior the zone and the greater the extent of stage 3+ ROP, the poorer is the outcome

All unfavorable fundus structural outcomes and almost all unfavorable visual acuity outcomes occurred in eyes with zone 1 or 2 ROP and >6 sectors of stage 3+ disease

Fewer unfavorable outcomes occurred in treated vs control eyes (44.4% vs 62.1% for visual acuity; 27.2% vs 47.9% for fundus status)

Retinal detachments remained stable in treated eyes (22%) but continued to occur in control eyes (from 38.6% at 5.5 years to 41.4% at 10 years)

After 10 years, treated eyes were much less likely than control eyes to be blind

Conclusions

Cryotherapy preserves visual acuity in eyes with threshold disease

Initial examination: 4–6 weeks after birth or at 30 weeks’ gestational age (whichever is later), then every 2 weeks until vessels reach zone 3

Prethreshold disease: examine every week until regression or threshold disease develops

Threshold disease: perform cryotherapy within 72 hours of diagnosis

Laser photocoagulation or cryotherapy to avascular retina, 90% regression rate

After 1 week, plus disease is usually less if treatment will work, fibrovascular proliferation often takes 2 weeks to begin regressing; consider retreatment if ROP is worse after 1 week; retreat untreated areas

Stage 4 disease: 60% reattachment rate with scleral buckle; 5% obtain useful vision

Stage 5 disease: vitrectomy (very poor success rate)

Familial Exudative Vitreoretinopathy (FEVR) (AD or X-Linked Recessive)

Mapped to chromosome 11q13-q23 (EVR1), 11p13-p12 (EVR3)

Most are unaware that they have this disorder

Rare, progressive developmental abnormality of peripheral retinal vasculature (especially temporally)

Findings

similar to ROP (Figures 5-16 and 5-17)

Stage 1: avascular peripheral retina, white without pressure, vitreous bands, peripheral cystoid degeneration, microaneurysms, telangiectasia, straightened vessels, vascular engorgement; may have strabismus or nystagmus; most asymptomatic; may progress to stage 2

Stage 2: fibrovascular proliferation with neovascularization, exudates, dragging of disc and macula, retinal folds and detachments; visual loss after 2nd–3rd decade of life rare unless progression to stage 3

Stage 3: cicatrization with rhegmatogenous retinal detachments (10–20%; usually in 3rd–4th decade of life), may develop proliferative vitreoretinopathy; prognosis poor

Figure 5-16 Fundus view of a patient who has familial exudative vitreoretinopathy. Note abnormally straightened retinal vasculature.

(From Kimura AJ: Hereditary vitreoretinopathies. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Figure 5-17 Fluorescein angiogram of a patient who has familial exudative vitreoretinopathy.

(From Kimura AJ: Hereditary vitreoretinopathies. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Treatment

prophylactic laser treatment to avascular retina (controversial); may require RD repair

Coats’ Disease (Leber’s Miliary Aneurysms)

Nonhereditary, proliferative exudative vascular disease

More common in males (10 : 1); bimodal distribution (peak in 1st decade and small peak in young adulthood [associated with hypercholesterolemia])

90% unilateral; 50% progressive

Findings

usually presents with leukocoria and strabismus; telangiectatic blood vessels leak (with large amount of subretinal lipid in outer plexiform layer), noncalcified yellow subretinal lesions, exudative RD in 66% (especially in patients <4 years old), microaneurysms, capillary nonperfusion

Pathology

triad of retinal vascular anomalies, subretinal and intraretinal cholesterol deposits, and intraretinal PAS-positive deposits; loss of vascular endothelium and pericytes; gliotic retina over subretinal fluid with cholesterol clefts and hemosiderin-laden macrophages. Aspiration of subretinal exudates reveals cholesterol and pigment-laden macrophages

DDx

retinoblastoma, angiomatosis retinae (von Hippel-Lindau syndrome), PHPV

B-scan ultrasound

consider ruling out retinoblastoma

Fluorescein angiogram (FA)

blood-fluid levels; saccular aneurysms (‘light bulb’ dilatations) of retinal arterioles and venules (Figure 5-18)

Figure 5-18 A, The classic fundus picture of Coats’ disease with massive lipid exudation that causes an exudative retinal detachment. B, Fluorescein angiogram from the same patient with large telangiectatic vessels and numerous leaking aneurysms.

(From Mittra RA, Mieler WF, Pollack JS: Retinal arterial macroaneurysms. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Treatment

cryo or laser to stop leaking blood vessels

Norrie’s Disease (X-Linked Recessive)

Defect of retinal development

Findings

bilateral leukocoria (white, often hemorrhagic retrolental mass), retinal dysplasia, peripheral NV, hemorrhagic RD, and retinal necrosis

Other findings

deafness, mental retardation

Shaken Baby Syndrome

30–40% of children subjected to child abuse will have ophthalmic sequelae

Most common in children <3 years old

Findings

diffuse retinal hemorrhages, papilledema, vitreous hemorrhage, retinal tissue disruption (retinoschisis, retinal breaks, folds); may resemble CRVO, Terson’s syndrome, or Purtscher’s retinopathy

Associated with other injuries

subdural hematoma, subarachnoid hemorrhage, bruises, fracture of long bones or ribs

Prognosis

poor due to macular scarring, vitreous hemorrhage, RD

Inherited Retinal Diseases

Fundus Flavimaculatus (AR)

Mapped to chromosome 1p21-p13 (ABCA4)

Findings

bilateral pisciform, yellow-white flecks at level of RPE

Predominantly involves peripheral retina with macula involved to a lesser degree; flecks, then macular degeneration

Central vision preserved until macula involved

Pathology

lipofuscin deposits within hypertrophied RPE cells

ERG

degree of abnormality correlates with amount of fundus involvement

Stargardt’s Disease

AR or less often AD; mapped to chromosomes 1p21-p22 (STGD1), 4p (STGD4), 6q14 (STGD3)

Juvenile macular degeneration with flecks

Most common hereditary macular dystrophy

Onset in first 2 decades of life with decreased vision

Symptoms

decreased vision, nyctalopia

Findings

bilateral pisciform, yellow-white flecks at level of RPE; change with time (new ones appear, others disappear); beaten-metal appearance of fundus; foveal atrophy; bull’s-eye maculopathy; may have salt and pepper pigmentary changes of peripheral retina (Figure 5-19)

Figure 5-19 Stargardt’s disease.

(From Kaiser PK, Friedman NJ, Pineda II, R: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn, Philadelphia, WB Saunders, 2004.)

Pathology

RPE massively thickened by accumulation of lipofuscin

FA

dark choroid (85%) due to accumulation of lipofuscin in RPE; areas of hyperfluorescence do not directly correspond to flecks; pigmentary changes in macula appear as window defects (Figure 5-20)

Figure 5-20 Fluorescein angiogram of Stargardt’s disease demonstrating dark choroid and hyperfluorescent pisciform flecks.

(From Kaiser PK, Friedman NJ, Pineda II, R: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn, Philadelphia, WB Saunders, 2004.)

ERG and EOG

normal or subnormal

Prognosis

50% have at least 20/40 vision in one eye by age 19; only 22% have 20/40 vision by age 39; rapid progression to 20/200 – Counting fingers (CF)

Best’s Disease (Vitelliform Dystrophy) (AD)

Variable penetrance; mapped to chromosome 11q13 (VMD2 [bestrophin])

Second most common hereditary macular dystrophy

Progressive with onset in 1st decade of life

Macular dystrophy in which RPE is primarily affected; form of exudative central macular detachment in which pigmentation can occur in end stages with atrophic scarring and / or CNV

Associated with strabismus and hyperopia

Symptoms

none or mild decreased vision initially; later decreases to 20/50-20/100; better vision than expected by clinical appearance

Findings

progressive macular changes; can get CNV

Previtelliform stage: small round submacular yellow dot

Vitelliform stage: yellow-orange egg yolk / fried egg appearance; can be multiple; usually between ages 3 and 15 (Figure 5-21)

Scrambled egg stage: irregular subretinal spots; vision usually still good

Cyst stage

Pseudohypopyon stage: RPE atrophy

Round chorioretinal atrophy stage: atrophic scar; vision usually stabilizes at 20/100

Figure 5-21 Best’s disease. Vitelliform stage.

(Courtesy of Ola Sandgren, University Hospital of Umea, Sweden. From Parnell JR, Small KW: Macular dystropies. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

DDx

central serous chorioretinopathy, RPED, toxoplasmosis, macular coloboma, solar retinopathy, old foveal hemorrhage, adult vitelliform macular dystrophy, syphilis

FA

blockage by egg yolk lesion; window defect when cyst ruptures

ERG

normal

EOG

abnormal (Arden ratio <1.6; also in carriers)

Dark adaptation

normal

Prognosis

good vision (20/30-20/100 range)

Familial Drusen (Doyne’s Honeycomb Dystrophy) (AD)

Mapped to chromosome 2p16-p21 (EFEMP1)

Small yellow-white, round to oval deposits on Bruch’s membrane; decreased vision after age 40

Complications

macular edema, hemorrhage, CNV

North Carolina Macular Dystrophy (AD)

Mapped to chromosome 6q14-q16 (MCDR1)

Onset in 1st decade with drusen progressing to chorioretinal atrophy with staphyloma of macula (Figure 5-22)

Figure 5-22 North Carolina macular dystrophy.

(From Parnell JR, Small KW: Macular dystrophies. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

May develop CNV

ERG, EOG, and dark adaptation

normal

Pseudoinflammatory Macular Dystrophy (Sorsby’s) (AD)

Mapped to chromosome 22q12-q13 (SFD [TIMP-3])

Atrophy, edema, hemorrhage, and exudate

Decreased acuity and color vision occurs between ages 40 and 50

ERG and EOG

subnormal late

Dark adaptation

delayed

Pattern Dystrophies (Usually AD)

Group of diseases with central pigmentary disturbance, good central vision, normal ERG, abnormal EOG

May develop CNV

Sjögren’s reticular

fishnet configuration; fishnet is hypofluorescent on FA

Butterfly

gray-yellow butterfly lesion with surrounding depigmentation; onset between ages 20 and 50 with slightly reduced vision; mapped to chromosome 6p21 (RDS [peripherin])

Adult vitelliform

onset between ages 30 and 50; early ring-like area of RPE clumping that develops into symmetric, solitary yellow macula lesions (like Best’s egg yolk lesions but smaller [1/2 DD in central fovea] and do not break up); often have central area of pigment; CNV is more common than in Best’s disease; normal EOG

Progressive Cone Dystrophy

Autosomal dominant or less often X-linked; mapped to chromosomes 6p21 (COD3), Xp21 (COD1) [RPGR]), Xq27 (COD2)

Progressive dysfunction of cones with normal rod function

Onset during first 3 decades of life with decreased vision, dyschromatopsia, photophobia

Symptoms

visual loss, photophobia (usually precede visible macular changes)

Findings

decreased vision (to 20/200), decreased color vision, central scotoma, nystagmus (25%), NFL loss, optic atrophy, macular degeneration (granular appearance early, then beaten-metal appearance); can have fine, golden subretinal deposits, bull’s-eye maculopathy (Figure 5-23); can develop a pattern that mimics Stargardt’s or fundus flavimaculatus

Figure 5-23 The ‘bull’s-eye’ maculopathy in this 5-year-old male who has a cone–rod dystrophy is not found in all cases of this entity.

(From Sieving PA: Retinis pigmentosa and related disorders. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

VF

normal

FA

may show window defects early

ERG

absent photopic, normal scotopic

EOG

normal

Dark adaptation

rod phase only

Prognosis

poor vision (20/200 level) by 4th decade of life

Tapetoretinal Degeneration

Processes that involve the outer half of the retina (photoreceptor / RPE); RPE = tapetum nigran (black carpet)

Retinitis Pigmentosa (RP)

Group of progressive dystrophies caused by abnormal photoreceptor protein production

Most common hereditary degeneration, incidence 1 : 5000

RP type I (rod–cone)

Inheritance patterns:

AR (37%): most common form; may be due to defects in 2 RPE genes (which provide instructions for vitamin A transport proteins): RPE 65, CRALBP

X-LINKED RECESSIVE (4%): rarest and most severe form; poor prognosis; vision <20/100 by 3rd decade of life; carriers may have fundus changes

AD (20%): least severe form, later onset; most likely to retain good vision

SPORADIC (30–50%)

Associations: keratoconus, macular cystoid degeneration, Coats’ disease, optic disc drusen, astrocytic hamartoma of ON, myopia

Symptoms: nyctalopia, ‘blue blindness,’ decreased vision late

Findings: pigmentary retinal changes (bone spicules), attenuated arteries, waxy pallor of optic nerve (due to glial membrane formation over disc), retinal atrophy with increased visibility of choroidal vessels, vitreous cells, cataract; some forms can have prominent subretinal exudation (Coats’-like disease) (Figure 5-24)

Pathology: photoreceptor atrophy including outer nuclear layer; inner retina well preserved; RPE cells invade retina and surround retinal vessels (bone spicules)

VF: inferotemporal scotoma, enlarges to form ring / annular scotoma; constricted

ERG: early, increased rod threshold with normal cone response and decreased scotopic b-wave; late, nonrecordable; abnormalities precede retinal changes and visual complaints

EOG: abnormal

Dark adaptation: prolonged

RP carriers:

FUNDUS: bone spicules, salt and pepper changes, bronze sheen in macula

ERG: decreased scotopic amplitude and delayed cone B-wave implicit time in X-linked carriers

VITREOUS FLUOROPHOTOMETRY: abnormal in X-linked carriers

DDx of tunnel vision: glaucoma, functional, gyrate atrophy, vitamin A toxicity, occipital lobe stroke

DDx of nyctalopia: uncorrected myopia, vitamin A deficiency, zinc deficiency, choroideremia, gyrate atrophy, congenital stationary night blindness (CSNB), Goldman-Favre disease

DDx of salt and pepper fundus: rubella retinopathy, Leber’s congenital amaurosis, carrier states (albinism, RP, choroideremia), syphilis, cystinosis, phenothiazine toxicity, pattern dystrophy, following resolution of an exudative RD

Macular complications: CME (no leakage on FA), epiretinal membrane, atrophy

Figure 5-24 ’Typical’ retinitis pigmentosa changes.

(From Sieving PA: Retinis pigmentosa and related disorders. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

RP type II (cone–rod)

AD, AR, or X-linked

Findings: less pigment deposition; 50% are sine pigmento

ERG: cones more affected than rods

Treatment

low vision aids, dark glasses; vitamin A slows reduction of ERG (controversial)

Prognosis

poor

RP Variants

Treatable RP

Bassen-Kornzweig (abetalipoproteinemia), Refsum’s (elevated phytanic acid), gyrate atrophy (elevated ornithine)

Leber’s congenital amaurosis (AR)

mapped to chromosomes 1p31 (LCA2), 14q11 (RPGRIP1), 17p13 (LCA1,LCA4), 19q13 (CRX)

Infantile form of RP; blind or severe visual impairment in infancy or early childhood; responsible for approximately 10% of childhood blindness

Associations: keratoconus, hyperopia, cataract, macular coloboma, mental retardation, deafness, seizures, renal and musculoskeletal abnormalities

Findings: decreased vision (HM-CF [hand movements–counting fingers]), nystagmus, hyperopia, poorly reactive pupils, range of fundus appearance from normal (most common) to variety of pigmentary changes (granular, fleck, salt and pepper, sheen, or atrophic)

OCULODIGITAL SIGN: child rubs eyes to elicit entopic stimulation of retina

Pathology: diffuse absence of photoreceptors

ERG: low or completely flat

Sector RP (AD or AR)

retinal changes limited to focal area, usually inferonasal quadrant

VF: abnormal

ERG: abnormal; normal b-wave implicit time reflects nonprogression

Prognosis: good

Unilateral RP

very rare

Inverse RP

posterior pole affected (rather than midperiphery): bone spicules in macula, normal periphery

FA: dark choroid (probably a variant of Stargardt’s)

Retinitis punctata albescens (AR): small white spots in midperiphery of retina, no bone spicules

RP sine pigmento

no retinal pigmentary changes

Pseudoretinitis pigmentosa

migration of RPE melanin into sensory retina leading to bone spicule pattern

Etiology: trauma, drug toxicity (chloroquine, chlorpromazine), infection / inflammation (syphilis, toxoplasmosis, measles, rubella), post-CVO, resolved exudative RD, ophthalmic artery occlusion

RP Syndromes

Usher’s syndrome (AR)

most common syndrome associated with RP; mapped to chromosome 1q41 (USH2A)

Findings: RP and deafness; ataxia, MR, low phosphate (rickets), muscle wasting 10–20% of RP patients are deaf; 5% of congenitally deaf individuals have Usher’s type I

TYPE 1: night blindness (1st–2nd decade), profound deafness, unintelligible speech, ataxia

TYPE 2: night blindness (2nd–4th decade), partial deafness, intelligible speech, no ataxia

DDx of deafness and RP: Usher’s, Hallgrenn’s, Alstrom’s, Laurence-Moon-Biedl-Bardet, and Cockayne’s syndromes

Other eye syndromes associated with hearing loss: Cogan’s (IK + hearing loss), Stickler’s (vitreous changes, joint and orofacial abnormalities, hearing loss), Waardenburg-Klein (iris heterochromia, white forelock), Duane’s (15% have hearing loss)

Refsum’s disease (AR)

deficiency of phytanic acid oxidase interferes with fatty acid metabolism

Phytanic acid accumulates in RPE cells, sensory retina deteriorates; onset in childhood

Mapped to chromosomes 7q21-q22 (PEX1), 10p15-p12 (PNYH)

Findings: atypical RP (often sine pigmento or starts in macula), cataracts, prominent corneal nerves

Other findings: ataxia, peripheral neuropathy, deafness, anosmia, ichthyosis, cardiac abnormalities, hypotonia, hepatomegaly, mental retardation

Diagnosis: increased serum copper and ceruloplasmin; increased CSF protein without pleocytosis

Treatment: dietary restriction of animal fats, milk products, leafy green vegetables

Bassen-Kornzweig syndrome (AR)

hereditary abetalipoproteinemia; mapped to chromosome 4q24 (MTP)

Inability to transport and absorb lipids because apolipoprotein B is a major protein of chylomicrons; deficiency in fat-soluble vitamins (A, D, E, and K)

Findings: RP (usually without bone spicules); may have Bitot’s spots on conjuctiva

Other findings: ataxic neuropathy, growth retardation, coagulopathy

Diagnosis: CBC, cholesterol (low), stool sample; elevated CSF protein; no apolipoprotein B-48 (low chylomicrons) or apolipoprotein B-100 (low LDL and VLDL)

Treatment: vitamin A and E supplements

Other causes of treatable RP due to vitamin A deficiency: chronic pancreatitis, cirrhosis, bowel resection

Lawrence-Moon-Bardet-Biedl syndrome (AR)

mapped to chromosomes 2q31 (BBS5), 3p13-p12 (BBS3), 11q13 (BBS1), 15q22-q23 (BBS4), 6q21 (BBS2), 20p12 (BBS6)

L-M and B-B: pigmentary retinopathy with flat ERG, mental retardation, hypogonadism, short stature

B-B: polydactyly and obesity (Figure 5-25)

L-M: spastic paraplegia

Figure 5-25 Bardet-Biedl syndrome with extensive peripheral retinal pigment epithelium and parafoveal retinal pigment epithelium atrophy.

(From Sieving PA: Retinis pigmentosa and related disorders. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Spielmeyer-Vogt-Batten-Mayou syndrome

neuronal ceroid lipofuscinosis

Onset between 2 and 4 years of age in Jewish females

Findings: RP-like retinal degeneration with bull’s-eye maculopathy

Other findings: seizures, progressive dementia, ataxia

Pathology: vacuolization of peripheral lymphocytes; metachromasia of skin fibroblasts in cell culture (carriers only)

Chronic progressive external ophthalmoplegia (CPEO)

mitochondrial inheritance; 50% with positive family history

Findings: retinal degeneration (salt and pepper changes with normal retinal function; progresses to RP-like disease), ptosis, ophthalmoplegia, strabismus

Other findings: facial weakness, dysphagia, small stature, limb girdle myopathy, cardiac conduction defects (Kearns-Sayre syndrome)

Olivopontocerebellar atrophy

retinal degeneration; tremors, ataxia, dysarthria

Alstrom’s disease

mapped to chromosome 2p13 (ALMS1)

RP with profound visual loss in 1st decade of life; diabetes, obesity, deafness, renal failure, baldness, acanthosis nigricans, hypogenitalism

Cockayne’s syndrome

RP with profound visual loss by 2nd decade of life; dwarfism, deafness, mental retardation, premature aging, psychosis, intracranial calcifications

Neuronal ceroid lipofuscinosis (Batten’s disease)

juvenile or adult onset of seizures, dementia, ataxia, mental retardation

Central Areolar Choroidal Dystrophy (AD)

Mapped to chromosome 6p (RDS [peripherin]), 17p13 (CACD)

Decreased vision in 4th decade

Findings

RPE mottling in macula progressing to geographic atrophy (choroidal vessels visible) (Figures 5-26, 5-27)

Figure 5-26 Central geographic atrophy in a patient with central areolar choroidal dystrophy.

(From Kaiser PK, Friedman NJ, Pineda II, R: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn, Philadelphia, WB Saunders, 2004.)

Figure 5-27 Left eye of same patient as shown in Figure 5-26 demonstrating similar central geographic atrophy.

(From Kaiser PK, Friedman NJ, Pineda II, R: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn, Philadelphia, WB Saunders, 2004.)

FA

window defect of central lesion

ERG

normal or subnormal

EOG, dark adaptation

normal

Bietti’s Crystalline Retinopathy (AR)

Decreased vision in 5th decade

Findings

yellow-white refractile spots throughout fundus, geographic atrophy; may have crystals in peripheral corneal stroma (Figure 5-28)

Figure 5-28 Bietti’s crystalline retinopathy.

(From Kaiser PK, Friedman NJ, Pineda II, R: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn, Philadelphia, WB Saunders, 2004.)

FA

crystals hyperfluoresce, window defects and areas of blockage

ERG

reduced

Congenital Stationary Night Blindness (CSNB)

Poor night vision (nyctalopia)

Group of nonprogressive rod disorders classified by fundus appearance

Findings

normal vision, VF, and color vision; may show paradoxical pupillary dilation to light; no Purkinje shift (always most sensitive to 550 nm)

ERG

scotopic and photopic implicit times are identical; decreased scotopic ERG; photopic ERG almost normal

Normal fundus

Nougaret type (AD): no rod function; mapped to chromosome 3p21 (GNAT1)

Riggs type (AR): some rod function

Schubert-Bornschein type (X-linked or AR): some or no rod function, myopia

Abnormal fundus

Fundus albipunctatus (AR): mapped to chromosome 12q13-q14

FINDINGS: midperipheral deep yellow-white spots spare macula (Figure 5-29)

ERG: normalization of scotopic after 4–8 hours of dark adaptation

ALPORT’S SYNDROME (AD): kidney failure, deafness, anterior lenticonus with anterior polar cataract; may have retinal appearance similar to fundus albipunctatus

Oguchi’s disease: mapped to chromosomes 2q37 (Oguchi 1, Arrestin, SAG), 13q34 (Oguchi 2 [RHOK])

MIZUO-NAKAMURA PHENOMENON: golden-brown fundus (yellow / gray sheen) in light-adapted state, normal-colored fundus in dark-adapted state (takes about 12 hours) (Figure 5-30)

ERG: absent b-wave; only scotopic a-wave

Kandori’s flecked retina (AR): yellow-white spots scattered in equatorial region; spares macula

Figure 5-29 Fundus albipunctatus. This posterior pole and beyond show multiple small, discrete, round, white dots that spare the fovea.

(From Noble KG: Congenital stationary night blindness. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Figure 5-30 Oguchi’s disease. A, The yellowish metallic sheen is apparent nasal to the optic disc. B, After 3 hours of dark.

(From Noble KG: Congenital stationary night blindness. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Gyrate Atrophy (AR)

Mapped to chromosome 10q26

Deficiency of ornithine aminotransferase; elevated ornithine levels (10–20× normal), low lysine levels; chorioretinal dystrophy itself is not due to high ornithine levels

Progressive retinal degeneration; starts peripherally and spreads toward posterior pole

Onset by 2nd decade of life with decreased vision, nyctalopia, and constricted visual fields

Findings

scalloped areas of absent choriocapillaris and RPE in periphery with abrupt transition between normal and atrophic areas (Figure 5-32); eventually lose choriocapillaris and medium-sized choroidal vessels; myopia (90%), cataracts, vitreous degeneration, CME

Figure 5-32 Gyrate atrophy.

(From Kaiser PK, Friedman NJ, Pineda II, R: Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edn, Philadelphia, WB Saunders, 2004.)

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