Abstract
Retinoblastoma is the most common intraocular malignancy of infancy which frequently manifests with a white pupillary reflex. We report a case of delayed presentation of a child with retinoblastoma in his left eye because parents thought the change in iris colour in this eye was due to the innocent heterochromia irides that was previously diagnosed in his elder sibling. This late presentation necessitated enucleation of the affected eye followed by chemotherapy.
Keywords: ophthalmology, glaucoma, retina, head and neck cancer, paediatric oncology
Background
Retinoblastoma is the most common primary ocular malignancy in childhood which frequently presents with a white reflex in the pupil. The development of heterochromia of the iris in a young child may also signal the presence of an underlying retinoblastoma. On occasion, however, a parent may pay little attention to this potentially serious abnormal sign of heterochromia if they have been previously reassured by the medical fraternity of an innocent cause of sectoral heterochromia irides present in an older sibling thus leading to a possible delay in presentation for a life-threatening retinoblastoma . Raising awareness and emphasising the seriousness of this sign/symptom might enable parents/clinicians to early seek specialised ophthalmology care for early diagnosis and treatment of possible underlying devastating sight and life-threatening malignancy.
Case presentation
A 14-month-old boy presented to our eye department after being referred from peripheral eye unit with 2-week history of red and watery left eye which has been worsening and not responding to topical antibiotics and steroids. There was no history of mucopurulent discharge, watering of the eye or a previous history of ocular trauma. His parents reported that he had no visual problems but they noticed that there was a recent change in colour of his left eye. He was a product of full term normal delivery and had no previous medical or ophthalmic problems.
The parents were keen to point out that his older brother was diagnosed with benign sectoral hetrerochromia irides by an ophthalmologist (figure 1). Further, they volunteered that they noticed a change in colour of the affected child’s eye 3 months prior to presentation but ignored this as they thought it would be similar diagnosis as his older sibling (figure 2). A family history and systems history was normal.
Figure 1.
An older brother with sectoral heterochromia irides involving the lower half of the iris of right eye.
Figure 2.
The patient at age of 10 months; 3 months before presentation, showing clear white pupillary reflex in the left affected eye.
On examination, the left eye was watery and showed ‘angry’ ciliary injection with hazy cornea and poor iris and pupil details. The right eye was normal on examination. Red reflex was normal in the right eye but absent in the left eye. There was marked left relative afferent pupillary defect. The corneal haze precluded any view of the retinal details in the left eye. An ultrasound scan of the left eye revealed a large mass protruding from the retina and filling the vitreous cavity (figure 3).
Figure 3.
(A,B) B scan U/S of the left eye of the patiet showing (A); a mass filling most of the vitreous cavity (B) arising from the retina.
An examination under anaesthesia including an ultrasound examination of the child’s eyes confirmed the above findings. In addition, the peripheral iris of the left eye showed vascular engorgement and a hyphaema (figure 4). The cornea was hazy and the intraocular pressure was elevated in the left eye (34 mmHg). There was no view of the retina of the left eye but the right eye was completely normal.
Figure 4.
(A,B) Left eye examination under anesthesia (EUA) showing (A) conjunctival chemosis with cilicary injection and cloudy cornea, (B) hyphema in the anterior chamber.
An urgent paediatric consultation and workup including an orbital MRI scan excluded leukaemia as a differential diagnosis and the MRI confirmed the presence of the intravitreal mass with retinal origin (figure 5).
Figure 5.
MRI without contrast showing left dense intraocular mass filling the whole vitreous cavity.
Investigations
B scan ultrasound was done (figure 2).
MRI scan of brain and orbit was done (figure 5).
Full blood count; within normal.
Differential white blood cell count was normal.
Liver function test was normal.
Kidney function test was normal.
Inflammatory markers; erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) within normal.
CT scan was not done as might increase the risk of developing second tumours in these patients.
Differential diagnosis
The most likely diagnosis was advanced retinoblastoma of the left eye extending to the anterior segment which was confirmed by clinical examination and investigations. Other diagnoses considered were lymphoma, leukaemia and other causes of anterior uveitis.
Treatment
Based on the clinical signs and the investigations, the child was classified as having a large (group E) intraocular retinoblastoma. The child was treated with an enucleation of the left eye with a long segment of optic nerve (figure 6). The histology revealed intraocular retinoblastoma with no invasion of the tumour at the cut margin of the optic nerve with no scleral invasion.
Figure 6.
Enucleated left eye harbouring the retinoblastoma with long optic nerve segment.
The patient had chemotherapy for possible submicroscopic seeding.
Outcome and follow-up
The child has been followed up for 6 months after surgery with a healthy left eye socket and no evidence of local tumour recurrence. As per protocol the right eye continued to have regular follow-up examinations and was normal. The older siblings were also examined and found to have a normal eye examination.
Discussion
Retinoblastoma, though uncommon occurring in 1:18 000 live births, still considered to be the most common ocular malignancy in children.1 A white pupillary reflex is the most common presentation and accounts for ~60% of cases (figure 3). Other presentations include strabismus (20%), painful red eye (glaucoma 7%), orbital cellulitis, heterochromia irides and hyphema.2 Other differential diagnoses of white pupillary reflex include important but less serious causes like congenital cataract, toxoariasis, persistent hyperplastic primary vitreous, cicatricial retinopathy of prematurity, optic disc and choroidal coloboma, and mylelinated nerve fibres of the retina.3 The earlier retinoblastoma is detected the more favourable the outcome and hence awareness campaigns of the ‘white pupillary reflex’ have been established to increase public awareness of this potentially serious sign. Though the parents of our patient were keen to seek medical advice in his older brother regarding his sectoral heterochromia irides, this was an unfortunate for his younger brother (our patient) whose change in colour of his eye was mistaken by the parents as innocent cause in the child eye that harboured a retinoblastoma. We believe parental and public education on the diverse presentation of retinoblastoma would lead to prompt referral and diagnosis of a potentially life-threatening retinoblastoma
Learning points.
‘White pupillary reflex’ is the most common presenting sign of retinoblastoma. All physicians and optometrists must be aware of the importance of this sign and the seriousness of the possible underlying pathology that it could present.
The public, as well, must be made aware of the need to seek experienced opinion if they ever noticed this sign in their children.
Other non-specific eye symptoms like heterochromia irides; sectoral or complete, must not be ignored and should be reviewed by an ophthalmologist who would be able to explain these symptoms to parents trying to clarify the need of similar or other eye symptoms to be reviewed by ophthalmologists.
The earlier detection and presentation of such lesions is the most important factor which impacts the visual, cosmetic and survival outcomes.
The use of smartphone cameras could be an available tool to be used by parents for early detection of this serious sign.4
Footnotes
Contributors: MSA-A, the main author of the case. I have received the case after being seen by my colleague, I have made the clinical evaluation, examination and further referral for specialised center and contacted the family for have further evaluation of other members of the family as well as consenting and photographing. I have written the initial manuscript and further modification after being revised by my coauthors and I have submitted the case. RS: he has received the case in his clinic and intiated the managemennt process. He has examined the case in the clinic and further initiated the management plan. He ordered the initial investigations. YAY: he is the ocular oncologist and the surgeon who performed the surgery and enucleated the involved eye. He is following up the case. PW: he is my supervising consultant who I have consulted him in regard to the case who helped in further explaining and writing up the case. He made the final edition of the case report.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Patient consent for publication: Parental/guardian consent obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.
References
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