**2. Presentation, evaluation, and diagnosis**

## **2.1 Clinical presentation**

The initial signs and symptoms of retinoblastoma (RB) are usually noticed by friends or family members, or at times from an abnormal "red reflex", more specifically, a white reflex or (leukocoria) from a photograph. Medical professionals, such as pediatricians during a routine examination, or a pediatric ophthalmologist, may also notice signs and symptoms consistent with RB, however less often. In very rare circumstances the intraocular mass may be picked up on head imaging for non-ophthalmic reasons. In developed nations such as the United States, the most common presenting finding for intraocular retinoblastoma is leukocoria or "cats eye reflex" (43%), followed by strabismus (22%), pseudo cellulitis, (9%), microphthalmia (5%), routine screening examination (17%), and rarely the presence of an intraocular mass on non-ophthalmic imaging (<1%) [10].

On average the ophthalmic oncologist is the third medical professional to evaluate a child suspicious for having RB. According to a large study on referral patterns there is an average delay of 1.1 months between initial symptoms and evaluation with any medical professional, and 2.0 months before an appointment with an ophthalmic oncologist [10]. As of 2014, mortality from retinoblastoma in the United States is approximately 3%, however in developing countries is close to 60%. Although our treatment has improved greatly, in many parts of the world access to care is a large barrier to successful therapy. Mean age at diagnosis in Asia is 22 months, compared to North America and Europe which are 12 and 9 months, respectively. On a more significant note, there are approximately 3000 new cases of retinoblastoma in Asia compared to only 300 new cases in North America, even further highlighting the need for improved access to care. As there are relatively few specialists and centers who treat such a rare condition, it is important to use the internet, telemedicine, and other social services to help train ancillary staff and improve access to triage services to improve prognosis for children.

#### **2.2 Misdiagnosis and differential diagnosis**

A review of the literature demonstrates a historic misdiagnosis rate of 11–40% based on histopathologic analysis of enucleated specimens, and a clinical misdiagnosis rate from 16 to 53% [10]. Fortunately the accuracy in diagnosis at specialized ophthalmic oncology centers in the United States is believed to exceed 99%. In a recent review of referring physician patterns the most common simulating lesions (>5% of analyzed lesions) were: Persistent fetal vasculature, Coat's Disease, Astrocytic Hamartoma, Intraretinal hemorrhage, and retinal detachment. Retinopathy of prematurity and congenital cataract were previously misdiagnosed often, but increased awareness of these conditions and better examination practices are likely the cause of reduced misdiagnosis of these two entities. Misdiagnosis of RB may be due to the fact that the condition is exceedingly rare, large differential diagnosis, and the challenges of examining children. Thus, any suspicion for the condition should warrant prompt referral to specialized care [11].

#### **2.3 Evaluation and diagnosis of retinoblastoma**

We will describe an organized approach in a stepwise manner for evaluating and properly diagnosis of RB. This will consist of: detailed history, initial office examination, ultrasonographic testing, examination under anesthesia, and current

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*Retinoblastoma: Presentation, Evaluation, and Diagnosis DOI: http://dx.doi.org/10.5772/intechopen.85744*

*2.3.1 History*

able to elicit this finding.

*2.3.2 Office examination*

leukocoria can be noted at that time.

patient encounters should be left to the treating physician.

consensus on imaging and genetic testing. Modifications dependent on specific

For any child with suspicion of retinoblastoma, a very detailed history is the most useful step in establishing an appropriate differential diagnosis and accurate examination, and in cases may establish the diagnosis. History should be taken prior to examination to ensure an appropriate focused examination. It should include details of the pregnancy, labor, and delivery of the child. History of birth weight, birth trauma, maternal infection, history of prematurity, oxygen therapy, and whether leukocoria was present at birth or developed later. Also, history of hearing abnormalities at birth or during young childhood should be taken into consideration as well. History of animal/pet exposure should also be elicited. These questions should help direct the clinician to the diagnosis of cataract, retinopathy of prematurity, persistent fetal vasculature, toxocariasis, and congenital rubella, which all can mimic retinoblastoma. The time course of when parents or clinicians first noticed an abnormality and the course of their visits with other health care providers should be carefully elicited. Most children with retinoblastoma do not have an obvious ocular abnormality at birth. They tend to develop signs such as esotropia, visual disturbances, or other strabismus between 6 months and 2 years of age. Leukocoria is also unlikely to be present at birth and will occur around the same time frame as the strabismus. For children suspected to have retinoblastoma a detailed family history including number and health of their siblings should be noted, along with any history of family medical conditions. A history of poor vision, blindness, or loss of an eye should be requested. A positive history of retinoblastoma in parents should point to the diagnosis, as simulating lesions do not usually occur in patients with a positive family history. If the child's parents or siblings have not had recent dilated fundus examinations they should be performed as soon as possible [12]. About 1% of patients with history of retinoblastoma may develop spontaneous regression with retinoma/ retinocytoma present on dilated examination [13]. Some parents may be unaware that they were treated for retinoblastoma as children and examination may be

The initial examination of the child should occur while history taking, by watching the child's behavior, visual interaction with the world, and evaluating for any abnormalities in size of the child, proportions, or for any facial abnormalities. The external examination of a child with retinoblastoma should be otherwise normal except for the ocular exam unless the child has a 13q deletion syndrome. Before the formal examination, the ability to notice leukocoria, decreased visual function, strabismus, or periorbital swelling should be noted upon gross examination. Assessment of vision is obviously dependent on age of patient, and his or her individual cooperation, but the size and symmetry of each eye should be recorded, as asymmetric size can suggest other diagnoses as well as retinoblastoma. Presence or absence of heterochromia should be noted during this portion of the examination as well [12]. Pupil response should also be documented. Using a direct ophthalmoscope or retinoscope, the pupillary light reflex should be noted in both eyes and

The next step should be instillation of dilating eyedrops (0.5% tropicamide and 2.5% phenylephrine). Cyclopentolate is not necessary for this examination. If the

consensus on imaging and genetic testing. Modifications dependent on specific patient encounters should be left to the treating physician.
