congenital glaucoma and neurofibromatosis type 1

Clinical case presentation

Dr. Samten Dorji

Chief complaint• A 6 month old male child presented with

enlargement of right eye since birth.

Parents are from Samtse Dzongkhag. Father is working in private firm and mother is house wife

History of chief complaint• 6 month old male child has enlargement of right eyes

since birth. At the same time there was tearing and irritability when exposed to bright light.

• The baby then developed brownish patches on the right side of his face and whole body at the age of 25 days.

• At the age of 3 months baby was admitted to hospital for pneumonia and had episode of focal seizures.

• For further management of the eye condition baby was referred to Kolkata

• This time baby was admitted to our ward for a therapeutic procedure.

Systemic review• CVS= no shortness of breadth• RS= no cough, history of pneumonia• GIS= no loose stool or abdominal swelling• CNS= one episode of seizures• Genitourinary system= NAD• Musculoskeletal system= no deformities

Birth historyAntenatal history

• No illness during pregnancy• No history of rubella infection• First pregnancy

Natal history

• Full term normal vaginal delivery at Paro hospital

• No obstetric trauma• Uneventful

Post natal• Birth weight=3.3 kg

Developmental assessmentSocial/emotional development

Language development

Cognitive development

Physical development

• Can recognize strangers

• Likes to play with people

• Responds to name• Makes sounds to

show happiness and discomfort

• Looks around nearby things

• Tries to get things that are out of reach due to curiosity

• Head control is poor

History cont.Family history/social history

• Non consanguineous marriage• Age of mother=25 age of father=25• Mother has same pigmented patches in her body

Examination Right eye Left eyeBuphthalmos Normal

Visual acuity Doesn’t follow the light Follows the light

Anterior segment Corneal oedema normal

Extraocular movements Normal Normal

Pupil Cannot assess Round regular and reactive

IOP by Icare 40 mmhg 8 mmhg

Dilated Funduscopy Cannot assess NAD

Systemic examination• Multiple café au lait macules in face, trunk

and limbs. >10 (biggest macule=6mm)• CVS/RS/GIS/MSS= unremarkable

Case summary• 6 month old male child has enlargement of right eye

since birth associated with tearing and irritability when exposed to bright light. The baby then developed brownish patches on the right side of his face and whole body at the age of 25 days. At the age of 3 months baby had pneumonia and had episode of focal seizures. Developmental assessment showed poor head control. His mother also have same pigmented patches like him. On general examination baby has multiple café au lait macules in face, body and limbs. On eye examination left eye is normal. In right eye baby has buphthalmos with corneal oedema and IOP 40 mmhg.

Problems 1. Right eye buphthalmos with corneal

oedema and increased IOP2. Café au lait macules in face, trunk and

limbs with first degree relative association3. Seizure disorder4. Gross motor delay

Diagnosis • Secondary congenital glaucoma

associated with neurofibromatosis type 1Differential diagnosis

• Congenital megalocornea• Trauma during birth

Investigation

Investigation • RFT and LFT= normal range• X ray upper limb and lower limb= normal • USS of whole abdomen= normal

Management • Latanoprost and timolol eye drops• Cyclocryo therapy• Paediatrcian follow up

Congenital glaucomaNeurofibromatosis

Subject review

Congenital glaucoma• Introduction• Epidemiology• Aetiology• Pathophysiology• Clinical features• Evaluation• Differential diagnosis• Management

Introduction Definition: Glaucoma that arises in children <2 years of age.

Secondary infantile glaucomaAssociated with a variety of ocularand systemic syndromes and with surgical aphakia.

Primary infantile glaucomaThe result of isolated abnormal development of the anterior chamber angle structures.

Epidemiology Country Incidence United states Between 1:10000 and 1:15000 live births

Northern Ireland 1:22000 live births

Saudi Arabia 1:2500 live births

Romania 1:1250 live births

North America and Europe More common in boys

Japan More common in girls

Secondary glaucomas > primary glaucomas

Aetiology • Primary congenital glaucoma• Aphakic glaucoma• Sturge-Weber syndrome• Anterior segment dysgenesis• Lowe syndrome• Congenital rubella• Aniridia • Neurofibromatosis, Weill-Marchesani syndrome,

Rubinstein-Taybi syndrome, Covert trauma, Steroid induced infantile glaucoma

Pathophysiology of primary congenital glaucoma

? Mutations in the gene for cytochrome P-450 1B1 (CYP1B1)

• Impaired aqueous outflow due to maldevelopment of the angle of anterior chamber

True congenital glaucoma(intra uterine

life)

Infantile glaucoma(<2 years)

Juvenile glaucoma(2 to 16 years)

Pathophysiology in secondary glaucomas

Presentation at or shortly after birth indicates a profound developmental abnormality of the anterior chamber angle, whereas presentation later in life usually suggests a different process.

• Angle closure: persistent hyperplastic primary vitreous, retinopathy of prematurity, or retinoblastoma

• Open angle: corticosteroid-induced and chronic uveitic glaucomas

Aphakic glaucoma: Retained lens material and presence of a small cornea

Clinical features

Corneal oedema Acute corneal hydrops

epiphora

blepharospasmphotophobia

Haab’s striae

Corneal diameter(>12mm)

Children >2 years

• Decreased visual acuity • Strabismus • Progressive unilateral myopia

Evaluation Under general anaesthesia

IOPOptic disc Corneal diameter Gonioscopy

Koeppe diagnostic lens

• CDR >0.3• Asymmetry

USS for axial length

Differential diagnosisCorneal oedema or clouding

Epiphora/red eye

Photophobia Corneal enlargement

Obstetric birth trauma (“forceps injury”)

Nasolacrimal duct obstruction

Conjunctivitis Axial myopia

Rubella keratitis Conjunctivitis Iritis Megalocornea (X-linked or sporadic)

Metabolic disorders Trauma Microphthalmic fellow eye

Congenital hereditary endothelial dystrophy

Treatment Medical Surgical

• Oral carbonic anhydrase inhibitor• Topical carbonic anhydrase inhibitor• Topical beta- blocker• Prostaglandin analogs

• Goniotomy• Trabeculotomy• Trabeculectomy• Drainage implant surgery• Cyclocryotherapy or laser

cyclophotocoagulation

Course and outcome• Buphthalmos at birth= poor prognosis• Glaucoma in few months after birth= good prognosis and outcome

Neurofibromatosis • Introduction• Epidemiology and pathogenesis• Characteristics• Ocular manifestation• Mechanism of glaucoma• Investigation• Treatment

Introduction

Neurofibromatosis type 1 (von Recklinghausen’s

disease)Neurofibromatosis type 2

(central neurofibromatosis)

• Is a inherited disorder characterized by neuroectodermal tumours that arise within multiple organs

Epidemiology and pathogenesisNF type 1 NF type 2

Incidence 1 person per 3500-400 people 1 person per 40000-50000 people

Sex Male=female Male=female

Gene 17q11 22q12

Inheritance Autosomal dominant Autosomal dominant

Characteristics NF type 1At least 2 of the followingAt least six café au lait spots• 5mm pre pubertal or• 15mm post pubertalNeurofibromas • One plexiform neurofibroma• At least 2 of any other type

Intertrigenous freckling(axilla or groin)Optic nerve gliomaAt least two Lisch nodules (iris hamartomas)

Distinctive osseous dysplasia(sphenoid or tibial)Affected first-degree relative

NF type 2Either A or B

A. Bilateral acoustic nerve masses(CT or MRI)

B. Affected first-degree relative and

1. unilateral acoustic nerve mass2. at least two of the following• Neurofibroma• Meningioma• Glioma• Schwannoma• Juvenile posterior subcapsular

cataract

Café au lait spots Neurofibromas Lisch nodules

Intertrigenous frecklingOptic nerve glioma

Ocular manifestation

• Lisch nodules- melanocytic hamartomas of iris stroma

• Subcutaneous pedunculated and plexiform neurofibromas of the eyelids

• Optic nerve glioma- frequently involve optic chiasm causing bilateral visual loss and intracranial mass effects, in the orbit can cause progressive proptosis and optic atrophy

• Pulsating proptosis• Glaucoma • Multifocal choroidal nevi• Retinal tumors

NF type 1 NF type 2

• Hamartomas of the retina• Juvenile posterior subcapsular or• Cortical lens opacities

Mechanism of glaucoma• Obstruction of aqueous outflow by

neurofibromatous tissue in the angle• Developmental angle which maybe

associated with congenital ectropion uveae• Secondary angle-closure caused by forward

displacement of peripheral iris associated with neurofibromatous thickening of ciliary body

• Secondary synechial angle-closure caused by contraction of a fibrovascular membrane.

Investigation

MRI and CT of orbit and brain

EEG and audiography

Treatment

• Neonates with an eyelid plexiform neurofibroma should be followed up frequently

According to findings

Course and outcome

• Reduced life expectancy• systemic hypertension, cancer, and expansive growth of benign intracranial

neoplasms• neurofibrosarcoma, other sarcomas, leukemias, and lymphomas, occur with

increased frequency in patients who have NF-1• In patients with NF-2, the main cause of early death is expansion of a CNS

neoplasm• Unilateral or bilateral blindness

Thank you