•Bilateral cases:

−−Enucleation is advisable for a Group D eye when the fellow eye is Group A, which can be cured with focal therapy, avoiding the morbidity of systemic chemotherapy.

−−Enucleation is indicated for all Group E eyes to avoid a trial of chemotherapy or radiation that can create a false sense of security by obscuring adverse risk factors that predispose to difficult- to-treat and poor-prognosis systemic metastasis. A futile trial of radiation therapy may predispose to fatal second primary tumor development in the long term.

•Exceptional circumstances:

−−Bilateral primary enucleation is needed when both the eyes present with Group E disease. Attempts to save such eyes may put the child’s life in jeopardy from systemic metastasis. Only rarely can these eyes be cured; visual potential is extremely poor in such severely compromised eyes.

•Enucleation is also indicated for recurrent tumors when all the other treatment modalities have failed, or when complications (retinal detachments, media opacities, hyphema) prevent evaluation and treatment of progressive disease.

9.7.5  Procedure

Clinical observations and imaging is used to determine the IIRC classification and evaluate extraocular disease, after which the Retinoblastoma Team discusses all treatment options with the family, to determine when enucleation is the best choice.

9.7.6  Consequences

Delay in indicated enucleation puts the child at risk for extraocular retinoblastoma and causes unnecessary suffering when the eye is painful and has no useful vision.

9.7.7  Related SOPs

OPHTH classification; OPHTH extraocular retinoblastoma; OPHTH enucleation indications; OPHTH enucleation technique.

9.8  Enucleation Technique SOP

9.8.1  Objectives

To standardize the surgical technique with least risk of tumor dissemination, avoid intraoperative and postoperative complications, and obtain a better cosmetic outcome.

9.8.2  Applicability

Ophthalmologist, operating room nurse.

9.8.3  Scope

Technical procedure.

9.8.4  Clinical Significance

Enucleation of the eye with retinoblastoma is a carefully considered procedure to save the child from extraocular spread of tumor. Utmost attention is paid not to inadvertently open the eye or cut across tumor in an involved optic nerve.

9.8.5  Procedure

•Enucleation procedure:

−−After standard preparation and appropriate exposure with a lid speculum, a 360° limbal peritomy is performed with a temporal extension.

−−The four recti muscles are isolated and detached from the globe. Depending on the surgeon’s preference and experience, each recti muscle could be isolated after passing a double armed 5-0 Vicryl suture at its insertion, and a 6-0 Vicryl for the obliques. If preferred, and to avoid inadvertent penetration of the globe and spreading tumor with the cutting needle, each muscle could be clamped with a straight snap to control bleeding, and separated near the insertion, placing sutures in the muscles after the removal of

the eye. It is preferable to leave the superior rectus free in the orbit, to reduce the incidence of upper lid ptosis when this muscle is dragged anteriorly beyond its anatomical position on the spiral of Tilleaux. The medial rectus is cut last, leaving a clamp on the muscle at the globe to facilitate the manipulation of the globe when cutting the optic nerve.

−−The eye is gently prolapsed forward and rotated temporally while the enucleation scissors are placed medially to localize the optic nerve. The scissors are opened to straddle the optic nerve and slid towards the medial orbital wall and orbital apex. Optimally, between 8 and 12 mm of the optic nerve is removed with the globe to avoid incomplete tumor excision.

−−Immediately after the globe is prolapsed, finger pressure is applied to the orbital apex for at least 10 min. The oblique muscles and Tenons’ attachments are excised carefully after the nerve is cut and the globe prolapsed. Special care is taken to avoid damaging the lids or accidentally recutting the optic nerve.

•Tumor specimen collection (Fig. 9.1) procedure:

−−The enucleated eye is moved to a separate sterile table. The optic nerve length is measured from the globe to the cut end. The globe is opened on the papillary-optic nerve plane to harvest the tumor for genetic studies of the RB1 gene mutations causing the tumor, while maintaining the globe for pathological examination. The surgeon regowns and regloves to avoid tumor contamination of the surgical field.

•Orbital Implant:

−−The orbital implant serves to partially fill the void left by removing the globe of its content, reducing the potential for a volume deficit within the socket. The attachment of the extraocular muscles to the implant or its wrapping material is believed to improve implant motility and reduce the risk of implant migration; the efficiency of transmitting this movement determines the degree of motility.

−−Adequate size and type of the orbital implant: The normal volume of an average globe is 7 mL. When the decision has to be made in relation to the size of the orbital implant, it is important to consider the volume provided by the most commonly used spherical implants: 18 mm = 3.05 mL and 20 mm = 4.19 mL. When using a wrap, it

adds 1–1.5 mm to the overall diameter of the implant, and the ocular prosthesis adds 1.5–2 mL. Therefore, the most advisable size is a 20 mm wrapped implant with an artificial eye, which provides a similar volume as the normal globe.

−−Nonporous orbital implants (such as acrylic and silicone) are cheaper and present lower incidence of exposure and/or extrusion when compared to porous implants (Porous polyethylene, natural and synthetic HA, aluminum oxide, and polyethylene).

−−A variety of wrapping materials could be used depending on the type of implant selected and the availability, including homologous donor tissue (sclera, fascia, dura pericardium); autogenous fascia tissue (fascia lata, temporalis fascia, rectus abdominis sheath, post auricular muscle); heterologous tissue (bovine pericardium); and synthetic materials (polyglactin 910, polyglycolic acid mesh, polyester mesh).

−−Ideally, the muscle should be sutured in an anatomical fashion following the spiral of Tillaux; it is important to avoid dragging muscles too anteriorly, since this will reduce the range of movement and can induce lid malposition.

−−Tenon’s capsule may be closed in two planes (deep and superficial) to avoid long-term exposure using interrupted 6-0 absorbable sutures (poliglactin). The conjunctiva is closed with a running 6-0 plain gut suture. Saline solution irrigation may help to identify these two layers at suturing, as Tenon’s fascia tends to become more whitish in color when soaked with saline solution.

−−A single dose of prophylactic endovenous antibiotic (such as cephalosporin) and topical antibioticointment,onceadayforthefirstpostoperative week, may be given to reduce the risk of perioperative infection.

−−A preliminary prosthetic conformer is inserted under the lids [36]. Although the conformer may not fit perfectly, the family usually feels better because the child appears to have both eyes. A firm pressure dressing is applied ideally for the first postoperative 48 h to keep lid swelling and hematoma formation to a minimum (Fig. 9.2f). A definitive prosthetic eye can be made specifically for the child approximately 6 weeks postenucleation.

•Inadvertent spilling of tumor into the orbit leads to recurrent retinoblastoma and may endanger the child’s life. Potential cure may require extensive therapy (chemotherapy, radiation therapy, stem cell/ bone marrow transplantation).

•Complications of enucleation related to the surgical technique, type of implant or its wrapping material, orbital or tissue characteristics, and/or prior radiation: Common problems are:

−−Persistent noninfectious mucous discharge, often related to upper airway infection or inadequate prosthetic fitting, which requires testing for bacterial cultures and subsequent treatment, and a better-fitting prosthesis.

−−Extrusion and/or exposure of the orbital implant that might require oculoplastic/orbital repair.

9.8.7  Related SOPs

OPHTH enucleation indication; OPHTH orbital implant; OPHTH prosthetic conformer; GENE Tumor harvest.

9.9  Collection of Tumor

for DNA Analysis SOP

9.9.1  Objectives

To identify the two mutant RB1 alleles in order to determine if the child with unilateral nonfamilial retinoblastoma has a germline mutation; allow retinoblastoma tumor to be donated for research with consent and ethics approval.

All unilateral nonfamilial retinoblastoma enucleations; bilateral retinoblastoma only with research consent.

9.9.4  Clinical Significance

Genetic counseling for the family is more accurate with molecular analysis of the tumor from the unilateral nonfamilial retinoblastoma [16].

9.9.5  Procedure

•The globe is opened with a razor incision with a pupil- lary-optic nerve section at the level of the main tumor mass to access intraocular viable tumor (Fig. 9.1d).

•Tumor for RB1 gene analysis is harvested from the center of the tumor mass and placed in sterile tissue culture medium (RPMI 1640 with 100 mg/mL of penicillin/streptomycin and 10–15% serum).

•A 10-mL ACD (yellow-top tube) or EDTA (laven- der-top tube) blood sample is sent with the tumor for RB1 mutation analysis.

•Special care is taken in harvesting the tumor to avoid interference with the optic nerve or choroid, which must be pathologically assessed for the risk of extraocular spread.

9.9.6  Consequences

Inadequate retinoblastoma tumor collection precludes accurate molecular diagnosis for unilateral retinoblastoma patients; careless opening of the globe may confuse the pathological interpretation of the extent of disease.