**1. Clinical presentation and diagnosis**

The clinical presentation of retinoblastoma can be variable depending on the stage of the tumor. However, the most common presenting symptom overall is abnormal white reflection from one or both pupils [1]. This can be observed grossly by the naked eye and is termed as leukocoria. The second most common presentation of retinoblastoma is strabismus, which results from sensory deprivation when the tumor involves the central vision [2]. Less commonly, uveitis, glaucoma, hyphema, iris heterochromia, and orbital cellulitis can also be presenting signs for retinoblastoma [3]. A more advance and late presentation may result in proptosis and orbital swelling [4]. Any of the mentioned clinical presentations in a child should prompt detailed clinical exam including dilated fundus examination. Typically, it shows unifocal or multifocal white vascularized retinal mass with or without tumor seeding. Different imaging modalities can be performed to aid in the diagnoses of retinoblastoma. The most easy and readily available modality is ultrasound. It can be helpful in the detection of intraocular mass characteristic

(height, thickness, and depth) and the presence of heterogeneity and calcification. Computed tomography (CT) is more sensitive in detecting intraocular calcification and delineating the mass. However, CT scan raises the concern of developing secondary malignancies in cases with germ line mutation due to radiations [5]. Magnetic resonance imaging (MRI) is currently the preferred imaging modality of choice for most ophthalmologists. MRI is considered the best for detecting optic nerve involvement and extraocular extension [6]. Other diagnostic procedures like cerebrospinal fluid (CSF) analysis and cytology are particularly performed when there is evidence of optic nerve involvement grossly or microscopically based on histopathologic examination after enucleation. Bone marrow biopsy is indicated for bone marrow metastasis based on clinical exam or blood work-up. Diagnosis of retinoblastoma should be based on clinical examination that is supported by imaging techniques. However, differentiating retinoblastoma from other conditions like persistent hyperplastic primary vitreous (PHPV), Coats' disease, or toxocariasis can be challenging [7–11]. Different classifications have been proposed for retinoblastoma staging throughout the past decades, including TNMH (tumor, node, metastasis, heritable trait) cancer staging for the American Joint Committee on Cancer (AJCC), Reese-Ellsworth classification system (R-E), and International Intraocular Retinoblastoma Classification (IIRC) [12–16]. The International Intraocular Retinoblastoma Classification or International Classification of Retinoblastoma (ICRB) have been widely accepted by ophthalmologists since they were first introduced in 2003, to predict the outcomes following chemoreduction for retinoblastoma [15, 16] (**Table 1** and **Figure 1**).


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*Retinoblastoma: Update on Current Management DOI: http://dx.doi.org/10.5772/intechopen.88624*

**Table 1.**

*International intraocular retinoblastoma classification.*

*Retinoblastoma - Past, Present and Future*

for retinoblastoma [15, 16] (**Table 1** and **Figure 1**).

**Group Subgroup Reference Features**

Macula Juxtapapillary Subretinal fluid

Extensive retinoblastoma

A Very low risk

C Moderate risk

E Very high risk

B Low risk Larger tumor

*International intraocular retinoblastoma classification.*

(height, thickness, and depth) and the presence of heterogeneity and calcification. Computed tomography (CT) is more sensitive in detecting intraocular calcification and delineating the mass. However, CT scan raises the concern of developing secondary malignancies in cases with germ line mutation due to radiations [5]. Magnetic resonance imaging (MRI) is currently the preferred imaging modality of choice for most ophthalmologists. MRI is considered the best for detecting optic nerve involvement and extraocular extension [6]. Other diagnostic procedures like cerebrospinal fluid (CSF) analysis and cytology are particularly performed when there is evidence of optic nerve involvement grossly or microscopically based on histopathologic examination after enucleation. Bone marrow biopsy is indicated for bone marrow metastasis based on clinical exam or blood work-up. Diagnosis of retinoblastoma should be based on clinical examination that is supported by imaging techniques. However, differentiating retinoblastoma from other conditions like persistent hyperplastic primary vitreous (PHPV), Coats' disease, or toxocariasis can be challenging [7–11]. Different classifications have been proposed for retinoblastoma staging throughout the past decades, including TNMH (tumor, node, metastasis, heritable trait) cancer staging for the American Joint Committee on Cancer (AJCC), Reese-Ellsworth classification system (R-E), and International Intraocular Retinoblastoma Classification (IIRC) [12–16]. The International Intraocular Retinoblastoma Classification or International Classification of Retinoblastoma (ICRB) have been widely accepted by ophthalmologists since they were first introduced in 2003, to predict the outcomes following chemoreduction

Small tumor • RB ≤3 mm (in basal dimension)

from the optic nerve

• RB >3 mm (in basal dimension) • Macular location (≤3 mm to foveola)

Focal seeds • Focal subretinal and/or vitreous seeds ≤3 mm from

or any of the following: • Secondary neovascular glaucoma

• Diffuse infiltrating retinoblastoma • Massive intraocular hemorrhage • Aseptic orbital cellulitis

the tumor

the lens

• Phthisis bulbi

from the tumor

D High risk Diffuse seeds • Diffuse subretinal and/or vitreous seeds >3 mm

• Al least 3 mm away from the foveola and 1.5 mm

• Juxtapapillary location (≤1.5 mm to optic nerve) • Additional subretinal fluid (≤3 mm from margin) • No vitreous or subretinal seeding is present

• Extensive retinoblastoma occupying >50% of globe

• Tumor anterior to anterior vitreous face or touching

• No vitreous or subretinal seeding is present

**56**

**Table 1.**

*Retinoblastoma: Update on Current Management DOI: http://dx.doi.org/10.5772/intechopen.88624*

**2. Management**

*response to treatments.*

**Figure 1.**

**3. Enucleation**

general health of the child, and the family desires.

Management of retinoblastoma is complex and requires a multidisciplinary team approach that includes an ophthalmologist, pediatric oncologist, radiation oncologist, pathologist, geneticist, social worker, nurses, and others. The primary goal of treatment is to save the child's life and then to salvage the globe and optimize the vision if possible. A multimodal therapeutic option for retinoblastoma is available, which ranges from focal therapies like laser photocoagulation, cryotherapy, thermotherapy, and plaque radiotherapy to enucleation or chemotherapy for more advance cases. The decision for choosing a treatment option is depending on several factors including the laterality, tumor size and histopathologic feature, the age and

*Retinoblastoma tumors, according to the international intraocular retinoblastoma classification, and their* 

Enucleation is the preferred option for most children presenting with advance tumor (group E eyes), especially if unilateral [17–21]. Other indications for enucleation are failure of all possible effective therapies, active tumor in an eye with no visual potential, anterior segment invasion, secondary neovascular glaucoma, and when the visualization of the tumor is compromised due to corneal opacity, cataract, or vitreous hemorrhage [22]. Enucleation is rarely indicated for bilateral retinoblastoma due to devastating functional limitation that follows such decision. The goal during enucleation is to obtain as much optic nerve as possible (usually 8–12 mm) to make sure that the surgical margin is free from tumor [23, 24]. Surgeons should avoid perforation of the globe during the procedure to minimize the potential risk of tumor seeding into the orbital tissue [25]. Histopathologic evaluation post enucleation allows for evaluation of high-risk features that requires additional chemotherapy. These features include retrolaminar optic nerve invasion,

#### **Figure 1.**

*Retinoblastoma - Past, Present and Future*

*Retinoblastoma tumors, according to the international intraocular retinoblastoma classification, and their response to treatments.*
