retinoblastoma. By formalizing SOPs, patient care will be organized and simplified, so that retinoblastoma management is improved in many aspects. Multidisciplinary teamwork will be facilitated. Clinicians, trainees, auxiliary caregivers, and the families will perceive and understand the treatment options clearly. Each individual child’s “menu of care” will include selected SOPs at certain times during the course of treatment. Therefore, the overall process can be viewed as a “language for retinoblastoma,” with each of the SOPs constituting the “words” of different “sentences,” in the narrative describing the child’s and the family’s experience with retinoblastoma.

SOPs also provide a standard of care in ocular oncology, allowing the assessment of the efficacy and performance of the team. Each SOP specifies the objectives, scope, applicability, team member responsibilities, clinical significance, and consequences if the SOP is not followed, specimen collection guidelines, required materials, and analysis of the technical details. SOPs are linked and connected with each other. Therefore, the SOP process is dynamic and evolving. New concepts will be developed through ongoing discussions, updates, and inclusion of new information and ideas. These new concepts can be formalized in the SOP process and consensus to seek changes based on evidence. Worldwide

systematic development of such guidelines may offer a common background for clinical trials, and facilitate a standard of optimal care for retinoblastoma families.

Each section of this chapter is presented in the format of a brief SOP, with specific fields addressed and links to related SOPs. However, this is only an illustration: the entire set of Retinoblastoma Management SOPs at the Hospital for Sick Children is actually much more extensive, focused, and concise.

9.2  Retinoblastoma Presentation SOP

9.2.1  Objective

To ensure that the patients suspected to have retinoblastoma are diagnosed as soon as possible to optimize the outcome.

9.2.2  Applicability

Family physicians or pediatricians, referring optometrists or ophthalmologists, retinoblastoma specialists.

9.2.3  Scope

To immediately refer any suspected child to the appropriate specialist, for confirmation or exclusion of retinoblastoma.

9.2.4  Clinical Significance

•Leukocoria [3]: varies depending on the source of light in line with the viewer’s gaze; most often detected by parents and/or relatives in sporadic nonfamilial cases (Figs. 9.1a and 9.2a).

•“Photoleukocoria”: often noticed retrospectively in the photographs of the child [4]; public and medical knowledge of retinoblastoma and awareness of the importance of leukocoria will improve the rates of early diagnosis.

•Unilateral and constant strabismus [5]: second most frequent presentation in sporadic cases involving the macula.

•Painful glaucomatous eye, aseptic orbital cellulitis secondary to extensive necrosis of intraocular tumor [6], anisocoria, uveitis, heterochromia, hyphema, hypopyon, searching nystagmus [5], phthisis bulbi [7]: less frequent presenting signs, often associated with late diagnosis.

Fig. 9.1  (a) Unilateral sporadic retinoblastoma presenting as a right leukocoria noticed by the child’s parents shortly after birth. When the child was referred at the age of 25 months, the right eye presented IIRC Group D: massive tumor with calcification, total retinal detachment, shallow anterior chamber and high intraocular pressure of 40 mmHg. (b) B-scan ultrasound showed calcification in a single tumor. (c) UBM showed anterior tumor behind the iris and ciliary body, but no ciliary body invasion. The right eye was enucleated and was opened to obtain live

tumor cells (d) to determine the two RB1 mutations (M1: heterozygous deletion of the entire copy of the RB1 gene, M2: hemizygous deletion of exons 18–27). These mutations were not detected in the DNA extracted from the child’s blood, eliminating the risk for her parents and siblings. Her future offspring will be checked for the mutations identified in her tumor, since she could still have germline mosaicism (images by Dr. Alejandra Valenzuela and Lindsay Hampton)

Fig. 9.2  (a) An 11-month- old baby girl presented with unilateral leukocoria with a small esotropia, first noticed by her parents at the age of 9 months. (b) B-ultrasound showed a large calcified mass, shadowing posterior surfaces and orbit, occupying the vitreous cavity. (c, d) CT scan showed calcification in a single tumor located supero-nasally with a normal size optic nerve in the right eye. (e) RetCam® image of the tumor with subretinal and vitreous seeding that extended up to the ora serrata. (f) Compression dressing reduces postoperative swelling (images by Carmelina Trimboli, Lindsay Hampton and Dr. Alejandra Valenzuela)

a

c

e

b

d

f

Fig. 9.3  (a) Family tree: father was cured by the enucleation of both eyes. (b–e) His son was born before his RB1 mutation was identified. At birth, the boy’s right eye had one superotemporal tumor, and developed three more tumors over the next year. (b) Two tumor scars are evident with a newly detected tumor immediately above the optic nerve (box, insert enlargement), seen as a blurring of the choroidal pattern. (c) Six months later, two tumors are controlled by laser, and the inferior laser scar shows reactivation; repeat laser treatment controlled all right eye tumors, with final visual acuity 20/20. (d) At birth, the boy’s left eye had a medium-sized macular tumor. (e) After chemotherapy and laser therapy, the macular tumor still recurred and showed a vitreous hemorrhage from the reactivating central tumor. Since

the right eye was essentially cured with good vision, the left eye was enucleated at 2 years of age. (f, g) The daughter was conceived after the RB1 mutation of her father and brother was found to be an 11 base pair deletion of exon 14. Amniocentesis showed that she also carried the mutant RB1 allele, and so she was delivered at 36 weeks of gestation to facilitate early treatment of tumors. She had one paramacular tumor in the left eye at birth, and over the next year, developed 12 tumors between the two eyes. (f, g) All her tumors were controlled with focal therapy (laser and cryotherapy) with a final visual acuity of 20/20 in each eye, with regular amblyopic patching of the right eye to force development of the left eye vision

children are at risk and require surveillance ­screening (Fig. 9.3).

9.2.6  Consequences

•Timely referral when tumors are small facilitates cure by short courses of focal therapy and/or chemotherapy.

•Late referral when tumors are big either necessitates prolonged courses of chemotherapy with focal

therapy or results in failure despite chemotherapy and/or radiotherapy, resulting in loss of both eyes.

•Very late referral incurs the risk of extraocular orbital, central nervous system, bone marrow, bone, or other metastatic disease.

9.2.7  Related SOPs

OPHTH referral; OPHTH initial presentation; OPHTH initial examination; OPHTH differential diagnosis; GENE surveillance; GENE mutation identification.