Leucocoria is a white pupil. It is a serious sign that requires urgent referral and assessment. The more common causes include: ( very important in the exam)
■ Infantile cataract.
■ Retinoblastoma.
other causes; Coats disease, retinal detachment from Retinopathy of prematurity
1- Retinoblastoma
The most common malignant intraocular tumour in children. Cumulative incidence at 5 years old is 9.3/million births in Jordan. Most (82%) cases are diagnosed before age 3, with males more predisposed than females, ratio 2.3 to 1. The majority of cases are unilateral.
60 % of patients with retinoblastoma are sporadic. while 40 % are inherited. Genetics Caused by mutation in the RB1 gene. A germline mutation is often associated with bilateral disease and autosomal dominant inheritance with almost complete penetrance (50% of offspring affected). Those with unilateral retinoblastoma are less likely to have a germline mutation or transmit the disease. All cases with sporadic disease have unilateral retinoblastoma.
Retinoblastoma with inherited disease:
■ 10% of cases have a family history (FH) of an inherited germline mutation; 75% of these develop bilateral tumours.
■ 30% have a negative FH and develop bilateral tumours, 95% have new germline mutations.
Sporadic disease
■ 60% have a negative FH and develop tumours unilaterally, <10% have new germline mutations.
■ Siblings with negative FH have a small risk of disease, as some (<5%) carrier parents are unaffected due to germline mosaicism.
Clinical features
Classically presents with leucocoria (55%) from a large retinal tumour mass . Secondary strabismus (25%) with decreased visual function (8%), positive FH (10%) and rarely failure to feed due to ocular pain in infants may be reported. Extraocular, fungating tumours associated with extraocular extension are rare in developed nations. Preseptal/ orbital cellulitis may occur. There may be elevated IOP (from secondary angle closure or direct tumour infiltration of the drainage angle), spontaneous hyphaema, conjunctival injection, buphthalmos, white/yellow tumour invasion into the anterior chamber or iris surface. A white/light yellow solid retinal mass is characteristic, with four growth patterns:
■ Endophytic: into the vitreous cavity.
■ Exophytic: into the subretinal space.
■ Combined endo- and exophytic.
■ Diffuse: minimally thickened, extensive tumour with retinal whitening.
Exudative retinal detachment, vitreous haemorrhage, or vitreous opacity from vitreous seeding or posterior uveitis may occur.
Differential diagnosis of retinoblastoma
A spontaneously regressed retinoblastoma (retinoma) may resemble Uveitis like Toxoplastma , Toxocara canis.
Retinal Osteoma,
Retinopathy of prematurity casing retinal detachment.
Investigations for retinoblastoma
Arrange B-scan: ultrasonography to document the presence and size of any mass lesion and any hyperechodensity within the tumour suggesting intralesional calcification (a typical finding).
Calcification in a tumor mass, means this tumor has a high metabolic rate, and calcification happens secondary to tumor necrosis and spillage of DNA in the matrix. DNA is negatively charged due to the presence of Phosphate group, this in turn will adhere to the positively charged Ca++ , causing tumor calcification.
A CT scan of the orbits may be used to confirm the presence of intralesional calcification, extent of extraocular spread, and to exclude other diagnoses. MRI is used to determine extraocular or intracranial spread. Genetic testing of blood or tumour cells is used to differentiate germline mutations.
Intraocular biopsies or other intraocular procedures must not be performed on eyes with suspected retinoblastoma.
Treatment
■ Casualty: Refer to specialty clinic that week for diagnosis.
■ Clinic: Refer to King Hussein cancer center, retinoblastoma team. Treatment is customized for each child and eye with the primary goal of local tumour control and patient survival. The secondary goal is preservation of vision.
Enucleation is used for advanced local tumours or after treatment failure.
1- Local, globe-sparing treatment options include external cryotherapy, transpupillary thermotherapy, local (sub-Tenon’s) chemotherapy, or plaque radiotherapy.
2- Systemic chemotherapy may be used alone or with local treatments as primary or salvage therapy. External beam radiotherapy is currently used only as salvage therapy in children older than 1 year who have failed all other appropriate treatments, and who still have potential vision in their only or better eye.
Follow–up Regular review including examination under anaesthesia for recurrence/new tumours to age 7 by retinoblastoma center then yearly by a local ophthalmologist.
Arrange prompt neuroimaging in older bilateral retinoblastoma patients with new-onset CNS symptoms to look for ectopic intracranial retinoblastoma (‘trilateral retinoblastoma).
2- Infantile Cataract
Bilateral or unilateral lens opacity is historically termed congenital cataract if presumed present at birth. we don’t have good studies in Jordan to get the prevalence from. However, The cumulative incidence by 1 year is 3 cases per 10,000 births. It is bilateral in 66%, with 55% being isolated cataract and 45% associated with other ocular or systemic disorders.
Inherited cataract (usually autosomal dominant) accounts for 56% of bilateral lens opacities. Associated ocular anomalies are more common with unilateral cataract, particularly persistent hyperplastic primary vitreous (PHPV), whilst systemic disease usually produces bilateral cataract, with prenatal infection and Down’s syndrome being the commonest.
History and examination
Ask the parents about the pregnancy and family history. Check the pupils for an afferent defect RAPD . A portable slit lamp makes cataract assessment easier and helps exclude associated anterior segment dysgenesis. The quality of the retinal image on direct or indirect ophthalmoscopy is another measure of severity; if the posterior pole cannot be easily seen visual deprivation is expected. Common cataract morphologies are nuclear, lamellar, anterior polar, posterior subcapsular, posterior with lenticonus, and total lens involvement.
Examine the parents, as they may have unrecognized cataract. Other signs include delayed visual development, strabismus, and nystagmus.
Investigations
B-scan ultrasonography to assess posterior structures and the globe size (including interocular asymmetry), and biometry if required. Paediatric assessment to exclude systemic causes and associations. Routine investigations include TORCH screen (maternal infection), urinary reducing sugars (galactosaemia), and urinary amino acids (Lowe’s syndrome). Electrodiagnostic testing may be indicated if retinal dysfunction is
suspected.
Treatment
■ Casualty: refer to a specialty clinic the same week, as visually significant unilateral or bilateral cataracts are ideally removed within 6 weeks of birth, to avoid deprivational amblyopia.
■ Clinic: the decision to operate is made by the parents, after discussion with a surgeon experienced in infant cataract surgery. Bilateral cataracts detected early are treated by
lensectomy and anterior vitrectomy, with the resulting aphakia treated with glasses or contact lenses.
Unilateral cataract is managed the same way but with a contact lens, rather than glasses, postoperatively. Because of the presence of anisokonia, it is preferred to use a contact lens. Intraocular lens implants can be used from 4 months of age, but are associated with an increased complication rate, and posterior capsular thickening will require YAG or surgical capsulotomy. Lens implantation before age 4 months is possible, but controversial. The lens power depends on the age of the child, with infants and younger children left hyperopic to allow for later ‘myopic shift’ as the eye grows.
Aphakic glaucoma is a significant complication, particularly for children undergoing early surgery when the risk can be up to 50%. It would appear to reduce when surgery is performed later, even by waiting until over 4 weeks of age.
Strabismus and amblyopia occur in virtually all cases of unilateral cataract, whether treated or not. Amblyopia is also common with bilateral cataracts. In children undergoing lens implantation, primary posterior capsulorrhexis or later capsulotomy will be required. After unilateral surgery, failure to patch the nonaffected eye is the leading cause of poor vision. Also, discuss the more general risks of cataract surgery.
Follow–up
Even if no surgery is undertaken, clinic review is required to ensure that the good eye develops normally, and to review the cataractous eye. Long-term, regular follow-up after surgery is mandatory to monitor for complications. Children should be seen at 1 day, then 1, 2, and 4 weeks after surgery, and regularly thereafter. Refract at the second postoperative visit and prescribe contact lenses or glasses initially for near vision (give the retinoscopy with no subtraction for working distance). Refraction should be regularly updated, and glasses or contact lenses altered accordingly, with bifocal or varifocal correction from about 2 years of age. Check IOP at every visit. Increased corneal thickness may give falsely elevated IOP readings and examination under anaesthesia may be required. Patching will be required for amblyopia. Postoperative therapy includes topical antibiotic, steroid and mydriatic.