**3. Management of retinoblastoma**

The primary objective in management of retinoblastoma is survival of the child, and secondly the preservation of the globe. After safety of the patient and the globe is establish‐ ed comes the focus on maintaining visual acuity. Treatment is tailored to each individual case, and there are several options. Intraocular retinoblastoma continues to be managed with a wide range of treatment modalities including cryotherapy, laser photocoagulation, transpupillary thermotherapy, brachytherapy, external beam radiation, and enucleation. Newer treatment modalities include intra-vitreal and subconjunctival chemotherapy for advanced tumors, and the recently described technique of ophthalmic artery catheteriza‐ tion with chemotherapy infusion. [5, 6, 7]

**3.4. Intra-arterial chemotherapy**

**3.5. Focal therapy**

*3.5.2. Cryotherapy*

*3.5.3. Thermotherapy*

*3.5.1. Laser photocoagulation*

The concept of intra-arterial chemotherapy for retinoblastoma was introduced more than 50 years ago, when the alkylating agent triethylene melanamine was used via puncture

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Most recently, the technique of supraselective intraarterial chemotherapy appears to significantly improve the prognosis for eye preservation (70-80%) of group D eyes. [10, 11] Currently this treatment is employed in retinoblastoma patients as primary treatment for unilateral or bilateral retinoblastoma and as secondary treatment following failure from other treatments. This technique allows selective delivery of chemotherapy to the eye with minimal systemic absorption. The dose delivered to the eye is 10 times that achieved with systemic chemotherapy. This high dose of chemotherapy delivered to the eye accelerates regression of tumor and seeds. The chemotherapy infusion has to be repeated every 3-4 weeks for up to 3-6 injections for complete regression of tumor. Cannulation of the ophthalmic artery is difficult in children particularly in infants less than 6 months and requires surgical expertise and precision. As it is an invasive procedure the risk of

Modalities of focal therapy include laser photocoagulation, cry therapy, thermotherapy, and plaque radiotherapy. These are mostly used for small tumors, in particular those which

Laser photocoagulation is usually employed for small tumors posterior to the equator of the eye.It tends not to be used in conjunction with chemo reduction as its success de‐ pends on vascular coagulation and tumor ischemia, which is the opposite case for chemo‐ reduction. It is performed using argon or diode laser, with two rows of photocoagulation surrounding the tumor base. The tumor itelf is avoided as this could lead to vitreous

Cryotherapy was first introduced by Linkoff in 1967. It causes cell death by destroying circulation during the freeze, via damage to the vascular endothelium and decreased blood flow. This is a useful treatment for equatorial and peripheral small retinoblastomas. The tumor is destroyed with one or two sessions of triple freeze-therapy. It is an important method of tumor consolidation following chemoreduction, and is especially useful for

Thermotherapy coupled with chemoreduction is suited for tumors adjacent to the fovea and optic nerve where radiation or laser would possibly induce visual loss. It involves

sites in the carotid artery in the side of the eye to be treated.

neurological complications has to be considered though they are rare.

seeding. It is repeated at approximately 1-month intervals for 3 sessions.

management of recurrent subretinal seeds near the ora serrate

have been already reduced by chemo reduction.

The approach to retinoblastoma management has changed significantly over the last 10 years, with a move away from external beam radiation and increased use of focal treatment methods and chemoreduction. It has been well demonstrated that patients with germline tumors are at increased risk of developing secondary cancers if they receive external beam radiation. In recent years, eyes with unilateral retinoblastoma are generally managed with enucleation if the eye is classified as Reese-Ellsworth group V. For those eyes in group I-IV, chemoreduction or focal treatment is used. In bilateral cases, chemoreduction is used in most cases unless there is very asymmetric disease.

#### **3.1. Chemoreduction**

Chemoreduction is a method of reducing tumor volume to allow for focal therapeutic measures such as cryotherapy or laser photocoagulation. This approach helps to preserve vision and avoid external beam radiotherapy. Tumors may show dramatic response in the first few months of treatment, however they will recur if treatment is not consolidated with local methods. Choice of agents as well as number and frequency of cycles varies be‐ tween institutions. The main problem with chemoreduction is the recurrence of vitreous or subretinal seeds, which may respond to initial chemoreduction, but later recur.

#### **3.2. Periocular chemoreduction**

Local periocular chemotherapy can be administered in the subconjunctival or subtenons space. For children with advanced retinoblastoma, systemic chemoreduction with a local periocular boost of subconjunctival or subtenon chemotherapy can be used in advanced tumors. If used alone, recurrence is inevitable, therefore, periocular chemotherapy is combined with systemic chemotherapy for best results. For small volume intraocular retinoblastomas, focal therapy may be potentially curative but can threaten vision if the tumor is adjacent to the macula or optic nerve. In these cases, periocular chemoreduction can be effective whilst avoiding systemic chemotherapy or damaging vision using focal therapies.

#### **3.3. Intravitreal chemotherapy**

The use of intravitreal chemotherapy was pioneered by Ericson and Rosengren, [8] and has been studied extensively in animal models. It is widely used in Japan but has largely been avoided elsewhere due to concerns regarding tumor seeding. A recent technique has described combining the intravitreal injection with a bleb of subconjunctival chemothera‐ py to avoid tumor seeding.[9]

#### **3.4. Intra-arterial chemotherapy**

with a wide range of treatment modalities including cryotherapy, laser photocoagulation, transpupillary thermotherapy, brachytherapy, external beam radiation, and enucleation. Newer treatment modalities include intra-vitreal and subconjunctival chemotherapy for advanced tumors, and the recently described technique of ophthalmic artery catheteriza‐

The approach to retinoblastoma management has changed significantly over the last 10 years, with a move away from external beam radiation and increased use of focal treatment methods and chemoreduction. It has been well demonstrated that patients with germline tumors are at increased risk of developing secondary cancers if they receive external beam radiation. In recent years, eyes with unilateral retinoblastoma are generally managed with enucleation if the eye is classified as Reese-Ellsworth group V. For those eyes in group I-IV, chemoreduction or focal treatment is used. In bilateral cases, chemoreduction is used in most cases unless there

Chemoreduction is a method of reducing tumor volume to allow for focal therapeutic measures such as cryotherapy or laser photocoagulation. This approach helps to preserve vision and avoid external beam radiotherapy. Tumors may show dramatic response in the first few months of treatment, however they will recur if treatment is not consolidated with local methods. Choice of agents as well as number and frequency of cycles varies be‐ tween institutions. The main problem with chemoreduction is the recurrence of vitreous or

Local periocular chemotherapy can be administered in the subconjunctival or subtenons space. For children with advanced retinoblastoma, systemic chemoreduction with a local periocular boost of subconjunctival or subtenon chemotherapy can be used in advanced tumors. If used alone, recurrence is inevitable, therefore, periocular chemotherapy is combined with systemic chemotherapy for best results. For small volume intraocular retinoblastomas, focal therapy may be potentially curative but can threaten vision if the tumor is adjacent to the macula or optic nerve. In these cases, periocular chemoreduction can be effective whilst avoiding systemic chemotherapy or damaging vision using focal

The use of intravitreal chemotherapy was pioneered by Ericson and Rosengren, [8] and has been studied extensively in animal models. It is widely used in Japan but has largely been avoided elsewhere due to concerns regarding tumor seeding. A recent technique has described combining the intravitreal injection with a bleb of subconjunctival chemothera‐

subretinal seeds, which may respond to initial chemoreduction, but later recur.

tion with chemotherapy infusion. [5, 6, 7]

is very asymmetric disease.

**3.2. Periocular chemoreduction**

**3.3. Intravitreal chemotherapy**

py to avoid tumor seeding.[9]

therapies.

**3.1. Chemoreduction**

32 Telemedicine

The concept of intra-arterial chemotherapy for retinoblastoma was introduced more than 50 years ago, when the alkylating agent triethylene melanamine was used via puncture sites in the carotid artery in the side of the eye to be treated.

Most recently, the technique of supraselective intraarterial chemotherapy appears to significantly improve the prognosis for eye preservation (70-80%) of group D eyes. [10, 11] Currently this treatment is employed in retinoblastoma patients as primary treatment for unilateral or bilateral retinoblastoma and as secondary treatment following failure from other treatments. This technique allows selective delivery of chemotherapy to the eye with minimal systemic absorption. The dose delivered to the eye is 10 times that achieved with systemic chemotherapy. This high dose of chemotherapy delivered to the eye accelerates regression of tumor and seeds. The chemotherapy infusion has to be repeated every 3-4 weeks for up to 3-6 injections for complete regression of tumor. Cannulation of the ophthalmic artery is difficult in children particularly in infants less than 6 months and requires surgical expertise and precision. As it is an invasive procedure the risk of neurological complications has to be considered though they are rare.

#### **3.5. Focal therapy**

Modalities of focal therapy include laser photocoagulation, cry therapy, thermotherapy, and plaque radiotherapy. These are mostly used for small tumors, in particular those which have been already reduced by chemo reduction.

#### *3.5.1. Laser photocoagulation*

Laser photocoagulation is usually employed for small tumors posterior to the equator of the eye.It tends not to be used in conjunction with chemo reduction as its success de‐ pends on vascular coagulation and tumor ischemia, which is the opposite case for chemo‐ reduction. It is performed using argon or diode laser, with two rows of photocoagulation surrounding the tumor base. The tumor itelf is avoided as this could lead to vitreous seeding. It is repeated at approximately 1-month intervals for 3 sessions.

#### *3.5.2. Cryotherapy*

Cryotherapy was first introduced by Linkoff in 1967. It causes cell death by destroying circulation during the freeze, via damage to the vascular endothelium and decreased blood flow. This is a useful treatment for equatorial and peripheral small retinoblastomas. The tumor is destroyed with one or two sessions of triple freeze-therapy. It is an important method of tumor consolidation following chemoreduction, and is especially useful for management of recurrent subretinal seeds near the ora serrate

#### *3.5.3. Thermotherapy*

Thermotherapy coupled with chemoreduction is suited for tumors adjacent to the fovea and optic nerve where radiation or laser would possibly induce visual loss. It involves heating the tumor using a diode infrared laser system, and is usually performed in conjunction with chemoreduction.

tion is appropriate. Also best considered for enucleation, are children with secondary glauco‐ ma, pars plana seeding, or anterior chamber seeding, Over 99% of patients with unilateral retinoblastoma without microscopic or macroscopic extraocular disease are cured by enuclea‐ tion. The technique of enuclation is to gently remove the eye intact without seeding any

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35

Telemedicine can be defined as the delivery of healthcare and sharing of medical knowledge over distance using telecommunication means. It is used to support health care between participants who are separated from each other.[14] It has the potential to improve the accessibility, quality, and cost of healthcare, and may also contribute to medical education and research. The concept of telemedicine was introduced about 30 years ago through the use of telephones and facsimile machines. However today, telemedicine has advanced, integrating medical and network technology, comprising remote diagnosis, expert consultation, informa‐

Telemedicine can be broadly divided into two categories: synchronous telemedicine uses telecommunications for real-time interactions between participants (i.e. Videoconferencing), as compared to store-and-forward telemedicine which captures patient data for subsequent

The potential benefits of an effective telemedicine system in ophthalmology are many. Telemedicine has a variety of possible applications in ophthalmology, from community screening to the provision of expertise in areas where it is otherwise not available. Broad-based applications of telemedicine could greatly enhance screening efforts for potentially blinding conditions such as diabetic retinopathy, macular degeneration, glaucoma, retinopathy of prematurity and retinoblastoma to name but a few. Telemedicine can bring subspecialty

Tele-medicine applications in ophthalmology comprise both clinical and educational process‐

expertise to small or rural communities, as well as to the developing world.

**•** professional development through group discussion, lectures, and tutorials

malignant cells into the orbit.

**4.1. Telemedicine**

**4. Telemedicine in management of retinoblastoma**

tion service, online checkups, and remote communication.

interaction with a remote expert (i.e. Digital radiology)

es between the send and receive sites. These can include:

**•** formulation of a diagnosis and clinical management plan;

**•** secondary advice and support in clinical management plan;

**4.2. Applications in ophthalmology**

**•** screening of a disease;

**•** peer supervision and support;

#### *3.5.4. Plaque radiotherapy*

This is a form of brachytherapy in which a radioactive implant is placed on the sclera over the base of a retinoblastoma. An average of 2 to 4 days of treatment time is required to deliver the total radiation dose to the tumor. It is useful for tumors less than 8mm thick and 16mm in base. Plaque radiotherapy can be used as a primary or secondary treatment. In the majority of cases it is used as a secondary treatment to salvage a glove after prior failed treatment. The visual outcome varies with tumor size and location as well as side effects such as radiation retinop‐ athy and papillopathy. Overall following 1 application of plaque radiotherapy there is an approximately 80% tumor control rate at 4 years.[13]

#### **3.6. External beam radiotherapy**

Retinoblastoma is generally a radiosensitive tumor. External bean radiotherapy is a method of delivering whole eye irradiation to treat advanced retinoblastoma, particularly when there is advanced vitreous seeding. Recurrence of retinoblastoma after external beam radiation is a problem that can develop in the first 1 -4 years after treatment. Radiation damage to the retina, optic nerve, and lens can be challenging to manage.

External beam radiation was once employed in a large percentage of patients but has fallen out of favor, largely because external beam radiation has the potential to increase the risk of the development of additional nonocular cancers in survivors of germline retinoblastoma. It is estimated that the risk approximates 1% per year of life.[13] Patients who develop a second cancer and then survive that cancer have an increased risk for the development of nonocular tumors of approximately 2% per year from the time of the second tumor diagnosis. The average latency period between subsequent tumor diagnoses becomes progressively less with each additional cancer that develops. Children radiated during the first year of life are between 2-8 times as likely to develop second cancers as those radiated after the age of 1 year.

Nonetheless external beam radiation remains an excellent method of preserving vision in a child with retinoblastoma, and certain clinical situation demand its use. Unlike focal therapies, external beam radiation can provide an excellent opportunity for useful vision in a macula that is not affected by tumor. It may be considered as a primary option in children with small tumors located within the macula, or for multifocal tumors where focal therapies are ineffective. External beam radiation also continues to be the salvage treatment of choice after focal treatments have failed. For children with advanced extraoculaar or metastatic disease, radiation can also play a role in palliation along with chemotherapy.

#### **3.7. Enucleation**

Enucleation continues to be a frequently used and important method for managing retino‐ blastoma If there is advanced disease with no hope for useful vision in the affected eye, or there is concern regarding tumor invasion into the optic nerve, choroid or orbit, then enuclea‐ tion is appropriate. Also best considered for enucleation, are children with secondary glauco‐ ma, pars plana seeding, or anterior chamber seeding, Over 99% of patients with unilateral retinoblastoma without microscopic or macroscopic extraocular disease are cured by enuclea‐ tion. The technique of enuclation is to gently remove the eye intact without seeding any malignant cells into the orbit.
