Retinoblastoma (Rb) is a cancer of the retina. Retinoblastoma is the most common primary ocular malignancy of childhood. Although this disorder can occur at any age, it usually develops in young children. Most cases of retinoblastoma occur in only one eye, but both eyes can be affected. Untreated, retinoblastoma is almost always fatal, hence the importance of early diagnosis and treatment.

1. Article-
Retinoblastoma Eye (retina cancer) Surgery in
India – Full information
Index --
Retinoblastoma Eye Surgery
what causes retinoblastoma?
Genetics of Retinoblastoma
Symptoms
Diagnosis
Clinical Presentation
Investigations
Efficacy of chemo eduction
Treatment
Surgery
Radiation therapy
Cry therapy
Laser therapy
Chemotherapy
Recurrent retinoblastoma
Chemoprevention following vitrectomy
Chemotherapy for extra ocular retinoblastoma
Side Effects of Cancer and Cancer Treatment
After Treatment
Risk Factors
Conclusion
Medical tourism / health tourism India
Retinoblastoma Eye Surgery
Retinoblastoma (Rb) is a cancer of the retina. Retinoblastoma is the
most common primary ocular malignancy of childhood. Although this
disorder can occur at any age, it usually develops in young children.
Most cases of retinoblastoma occur in only one eye, but both eyes
can be affected. Untreated, retinoblastoma is almost always fatal,
hence the importance of early diagnosis and treatment.
Retinoblastoma is related to chromosome 13. Retinoblastoma occurs
when a cell of the growing retina develops a mutation in the RB gene

2. (a tumor-suppressor gene). This mutation causes the cell to grow out
of control and become cancerous.
Mutations in the RB1 gene are inherited in an autosomal dominant
pattern, which means that one copy of the altered gene in each cell is
sufficient to increase cancer risk. A person with retinoblastoma may
inherit an altered copy of the gene from one parent, or the altered
gene may be the result of a new mutation.
Retinoblastoma is the most common intraocular tumor in childhood.
In majority of early stage retinoblastoma, the eyeballs as well as
vision can be preserved with chemotherapy and local intraocular
therapy with laser or photocoagulation. However, more than half the
patients in India and other developing nations present in advanced
stage of the disease. This article reviews the genetics, clinical
approach, and treatment options for retinoblastoma focusing on
advances in chemotherapy for intraocular retinoblastoma (chemo
reduction), as well as improvement in survival in advanced
retinoblastoma with surgery, chemotherapy, radiotherapy, and bone
marrow transplantation.
What causes retinoblastoma?
In children with the genetic, i.e. the inheritable form of retinoblastoma,
we know that there is something wrong with a small piece of the
genetic material on chromosome 13, called the RB1 gene.
Chromosomes contain the genetic codes which control the way cells
grow and develop, and when a portion of the chromosome is missing

3. or one of the genetic codes is altered in some way, which is known as
a mutation, a cancer may develop...
Genetics of Retinoblastoma
Retinoblastoma may occur as nonhereditary or hereditary tumor.
Tumors in nonhereditary retinoblastoma (60% cases) are typically
solitary and unilateral with no family history and no detectable
chromosomal abnormalities. Although <10% of cases of
retinoblastoma have a positive family history, about 40% of
retinoblastoma are of hereditary origin caused by a germ line
mutation in RB1 gene on chromosome 13q14. This is due to the
majority being the result of a de novo mutation in the RB1 gene.
Amongst those with hereditary retinoblastoma (40% cases), 25%
cases have bilateral disease while 15% have unilateral disease.
Hereditary RB1 mutations are found in all cells thereby increasing risk
of other cancers, in particular, osteosarcoma and malignant
melanoma.
Inherited retinoblastoma is transmitted as an autosomal dominant
trait with high but incomplete pen trance. Children of patients with
hereditary retinoblastoma have a one in two chance of carrying the
germ cell mutation and for those who are carriers, the probability of
developing retinoblastoma is very close to 90% if parents have
bilateral retinoblastoma but probably less if they have the unilateral
form.
The probability of developing retinoblastoma in off springs and
siblings of patients is higher than in the general population because
of which they need genetic counseling so as to effectively counsel
and diagnose retinoblastoma early in high risk subjects. In bilateral
cases or those with a positive family history, one can directly perform
the genetic studies on peripheral blood sample as they would always
be due to germ line mutation in RB1 gene. In unilateral cases and
those with a negative family history, there is only 15%-20% chance
that somatic cells would also carry the mutation. Therefore, in these
cases, genetic studies for RB1 gene mutation are initially performed
in the tumor specimen, and subsequently, once the mutation has
been identified, peripheral blood is screened to determine if it is a
germ line mutation (hereditary retinoblastoma) or non hereditary
retinoblastoma.

4. If genetic testing is not pursued, then tumor surveillance for all
siblings of the affected patient is recommended, which includes
examination under anesthesia (EUA) at birth and every four months
until the age of 4 years. On the contrary, if genetic testing
demonstrates that the sibling did not inherit RB1 gene mutation, the
surveillance and anesthesia required for eye examinations can be
avoided, thereby decreasing costs and potential morbidity. Further, in
unilateral retinoblastoma, if it can be demonstrated that the child does
not carry a germ line RB1 gene mutation, then (a) the child is not at
substantial risk for second malignancies; (b) radiation therapy is
associated with less hazards and; (c) the parents and eventually the
child have a negligible risk of having another child with
retinoblastoma.
Symptoms
Children with retinoblastoma often experience the following
symptoms. Sometimes, children with retinoblastoma do not show any
of these signs or symptoms. Or, these symptoms may be similar to
symptoms of other medical conditions. If you are concerned about a
symptom on this list, please talk to your child's doctor. Sometimes, a
doctor finds retinoblastoma on a routine, well-baby examination. Most
often, however, parents notice symptoms such as:
• A pupil that looks white or red, instead of the normal black
• A crossed eye (looking either toward the ear or toward the
nose)
• Poor vision
• A red, painful-looking eye
• An enlarged pupil
• Different-colored irises
Diagnosis
Doctors use many tests to diagnose cancer and determine if it has
metastasized (spread). Some tests may also determine which
treatments may be the most effective. Although a biopsy is the only
way to make a definitive diagnosis for most types of cancer, this is
usually not possible in the case of retinoblastoma, and the doctor will
suggest other ways to make a diagnosis. Imaging tests may be used

5. to find out whether the cancer has metastasized. Your doctor may
consider these factors when choosing a diagnostic test:
• Age and medical condition
• The type of cancer
• Severity of symptoms
• Previous test results
The next step after observing the symptoms is to have the child
examined by a specialist, who will do a thorough ophthalmic
examination to check the retina for a tumor. Depending on the age of
the child, either a local or general anesthetic is used during the eye
examination.
The specialist will make a drawing or take a photograph of the tumor
in the eye to provide a record for future examinations and treatment,
and may use additional tests to confirm or detect a tumor.
If a newborn has a family history of retinoblastoma, the baby should
be examined shortly after birth by an ophthalmologist (a medical eye
doctor) who specializes in cancers of the eye.
Clinical presentation
The median age of diagnosis is 2 years. Bilateral retinoblastoma
occurs earlier than unilateral disease. Majority of retinoblastoma in
developed nations presents as an intraocular disease wherein 90% of
cases are curable. However, in the developing nations, still 65% of
patients may present with extra ocular disease. An unpublished data
from our center showed that mean age of presentation of unilateral
retinoblastoma is 34 months, while that of bilateral disease is 24
months, which is higher than that in the west. The mean duration of
symptoms was 8 months prior to visiting the tertiary care center, and
49% of patients presented with extra ocular disease. This may be due
to the lack of awareness, delayed referrals, and/or more aggressive
disease biology. From a therapeutic point of view, retinoblastoma
presentation may be divided into the following subtypes:
A. Early stage intraocular disease (preservation of eye possible)
presents most commonly with leucocoria (white reflex with an
ophthalmoscope) followed by strabismus. Therefore, a pediatrician
should always include the documentation of a red reflex with an

6. ophthalmoscope in examination of newborn and at subsequent well
baby visits of a child. The absence of red reflex or strabismus merits
an examination by an ophthalmologist in order to detect early stage
intraocular retinoblastoma.
B. Advanced intraocular retinoblastoma (needs enucleation) presents
with rubeosis iridize, hyphema, hypo yon, and glaucoma. The
potential diagnosis of retinoblastoma should always be investigated in
a child presenting with spontaneous hyphema in the absence of
trauma or who presents with signs of endophthalmitis. Pain is not a
feature of intraocular retinoblastoma unless secondary glaucoma or
inflammation is present.
C. Extra ocular retinoblastoma presents with proptosis, preauricular
lymphadenopathy, and bone pain, features suggestive of bone
marrow or central nervous system involvement.
Investigations
The diagnostic work up include EUA of the eye and ultra sonography
and CT scan of the orbit and head to confirm the diagnosis of
retinoblastoma, and to detect entopic disease in the pineal gland. The
clinical presentation and ancillary radiological findings are typical for
retinoblastoma in majority of the patients, and a tissue biopsy is not
required for confirmation prior to the therapy. However, a fine needle
aspiration biopsy may be performed in select cases of pediatric
ophthalmologic disease where the diagnosis is in question.
Metastasis work up includes cerebrospinal fluid examination for
malignant cells and bone marrow biopsy and bone scan in those with
extra ocular disease. Intraocular retinoblastoma is traditionally
classified by Reese-Ellsworth (RE) classification whereas intraocular
and extra ocular retinoblastoma is classified according to Grabowski-
Abramson staging
Efficacy of chemo eduction
An early volume reduction of around 50% after two courses of VEC
can usually be expected. The overall salvage of eyes in the chemo
reduction studies is about 80%. EBRT was added in an additional
30% of the salvaged eyes. Thus, approximately 50-60% of affected

7. eyes treated with chemo reduction are successfully preserved with
avoidance of EBRT or enucleation. The rate of globe preservation is
best with less advanced eyes (85%), such as those in RE groups I to
IV whereas with more advanced eyes, such as those in RE group V,
preservation is less successful at <50%.
In a study by Shields et al. chemo eduction using six cycles of VEC
offers satisfactory retinoblastoma control for RE groups I-IV eyes,
with treatment failure necessitating additional EBRT in only 10% of
eyes and enucleation in 15% of eyes at 5-year follow-up. Patients
with RE group V eyes required EBRT in 47% and enucleation in 53%
at 5 years. Thus, all localized intraocular retinoblastoma have a
potential for eye preservation using chemo reduction. However, any
evidence for potential micrometastatic disease or overt metastasis
disease should be excluded from chemo reduction

8. Treatment
Clinical trials are the standard of care for the treatment of children
with cancer. In fact, more than 60% of children with cancer are
treated as part of a clinical trial. Clinical trials are research studies
that compare the standard treatments (the best treatments available)
with newer treatments that may be more effective. Cancer in children
is rare, so it can be hard for doctors to plan treatments unless they
know what has been most effective in other children. Investigating
new treatments involves careful monitoring using scientific methods
and all participants are followed closely to track progress.
To take advantage of these newer treatments, all children with cancer
should be treated at a specialized cancer center. Doctors at these
centers have extensive experience in treating children with cancer
and have access to the latest research. Many times, a team of
doctors treats a child with cancer. Pediatric cancer centers often have
extra support services for children and their families, such as
nutritionists, social workers, and counselors. Special activities for
children with cancer may also be available. Surgical treatment for
retinoblastoma should also be performed by specially trained
pediatric ophthalmologists.
Several types of therapies are used for retinoblastoma, and more
than 90% of children can be cured. In addition to cure, an important
goal of therapy for retinoblastoma is the preservation of vision. Many
of these treatment approaches have become available as a result of
clinical trials. The Children’s Oncology Group has recently developed
treatment protocols for which some children with retinoblastoma will
be eligible.
Treatments for retinoblastoma include:
Surgery
Surgery to remove the eye is called enucleation. Children with a
tumor in one eye only can often be cured with this treatment. In
children with a tumor in both eyes, enucleation is used only if the
ocular oncologist determines that preserving vision using other
treatment is not possible.
Radiation therapy

9. Radiation therapy uses high-energy x-rays or other particles to kill
cancer cells. The most common type of radiation treatment is called
external-beam radiation therapy, which is radiation therapy given
from a machine outside the body. Radioactive plaque therapy, also
called internal radiation therapy, is the delivery of radiation therapy
directly to the eye with a disc containing radiation.
Fatigue, drowsiness, nausea, vomiting, and headache are common
temporary side effects of radiation therapy. Radiation therapy in
young children can interfere with normal growth, including growth of
the orbital bones, depending on the dose. The increased risk of
additional tumors later in life for children with the hereditary form of
retinoblastoma is further increased following radiation therapy. These
effects are not seen after radioactive plaque therapy.
Cry therapy
Cry therapy uses extreme cold to destroy cancer cells.
Laser therapy
Laser therapy uses heat in the form of a laser to shrink smaller
tumors. It may be called thermotherapy (or TTT for transpupillary
thermotherapy), and it may be used alone or in addition to cry therapy
or radiation therapy. Photocoagulation is a different type of laser
therapy that uses light to shrink tumors.
Chemotherapy
Chemotherapy uses drugs to kill cancer cells, and may be used to
shrink tumors in the eye. It is administered by a pediatric oncologist
and often makes it possible to completely eliminate any remaining
smaller tumors with the following focal (localized) measures:
• Thermotherapy or photocoagulation (laser therapy)
• Cry therapy
• Radioactive plaque therapy
Chemo reduction is a treatment approach that is often used in
children with bilateral disease in the hope of avoiding enucleation and
preserving vision in at least one eye. The ophthalmologist, in
consultation with the pediatric oncologist, will determine if this
treatment is appropriate. Both doctors will monitor the response to

10. treatment regularly and may recommend additional treatment to
prevent the cancer from returning.
The drugs used most often are incrusting (Oncovin), carboplatin
(Paraplatin), and etoposide (VePesid, Etopophos, and Toposar).
Depending on the extent of the tumor, a combination of two or more
drugs will be recommended. All chemotherapy has side effects that
occur during the period of treatment. Some drugs have the potential
for specific long-term complications. Your doctor will discuss these
before treatment begins.
The medications used to treat cancer are continually being evaluated.
Talking with your child's doctor is often the best way to learn about
the medications they've been prescribed, their purpose, and their
potential side effects or interactions with other medications.
Recurrent retinoblastoma
Treatment of recurrent retinoblastoma depends on where the cancer
recurred and how aggressive the new tumor is. The doctor may
recommend surgery, radiation therapy, chemotherapy, or focal
measures (photocoagulation, thermotherapy, or cry therapy).
Chemoprevention following vitrectomy
Retinoblastoma may present with atypical features such as vitreous
hemorrhage or signs of vitreous inflammation, particularly in older
children. Vitrectomy should be avoided in these cases until the
possibility of underlying retinoblastoma is excluded. If vitrectomy is
performed in an eye with unsuspected retinoblastoma, enucleation
combined with chemotherapy, radiotherapy or both without delay is
advised to prevent systemic tumor dissemination.
Chemotherapy for extra ocular retinoblastoma
Metastasis retinoblastoma is seen in less than 10% cases in
developed nations whereas almost two-third of cases of
retinoblastoma in developing countries. Chemotherapy is indicated in
all these situations and is used in the following two fashions:
1. Conventional chemotherapy wherein the same drugs are used as

11. is used in chemo reduction or chemoprevention, but for a longer
duration of 6-12 months.
2. High dose chemotherapy (HDT) wherein after initial conventional
chemotherapy, the patient is consolidated with high doses of the
same agents and bone marrow rescued with an autologous stem cell
transplantation (ASCT).
Two different subgroups of patients with extra ocular retinoblastoma
with different outcome can be distinguished as follows:
A. Extra ocular disease limited to orbit alone (invasion up to or
beyond the cut end of optic nerve; sclera invasion up to the orbital
contents) or with concomitant lymph node invasion. These patients
have a 5-year progression free survival of >80% using initial
exenteration followed by intensive chemotherapy and radiotherapy.
Similar results have also been obtained using initial neoadjuvant
chemotherapy followed by limited surgery (enucleation or resection of
residual orbital mass) and adjuvant therapy and radiotherapy.
Comparable results have been reported using HDT with ASCT. Thus,
HDT in these two situations seems to be a therapeutic alternative
with the advantage of shorter duration of therapy. Further, most of the
failures or recurrences are in the CNS, and thus, intrathecal
chemotherapy is used by some centers along with chemotherapy.
B. Those with systemic and/or CNS dissemination (bones, bone
marrow, positive CSF cytology, or mass lesion in brain) are seldom
cured with conventional chemotherapy. However, HDT using
carboplatin, etoposide, and cyclophosphamide is effective in patients
with chemo sensitive retinoblastoma patients with distant metastasis
disease, except those with CNS disease. Prognosis is extremely poor
in those with CNS disease. CNS irradiation, as is currently employed,
does not cure CNS disease. Role of intrathecal therapy using
methotrexate, cytosine arabinoside, and hydrocortisone, as is
employed in CNS leukemia, is debatable. Thus, more effective
therapeutic strategies are required to cure CNS disease in
retinoblastoma.
Side Effects of Cancer and Cancer Treatment
Cancer and cancer treatment can cause a variety of side effects;
some are easily controlled and others require specialized care. Below

12. are some of the side effects that are more common to retinoblastoma
and its treatments.
Fatigue (tiredness). Fatigue is extreme exhaustion or tiredness, and
is the most common problem that people with cancer experience.
More than half of patients experience fatigue during chemotherapy or
radiation therapy, and up to 70% of patients with advanced cancer
experience fatigue. Patients who feel fatigue often say that even a
small effort, such as walking across a room, can seem like too much.
Fatigue can seriously impact family and other daily activities, can
make patients avoid or skip cancer treatments, and may even impact
the will to live.
Nausea and vomiting. Vomiting, also called emesis or throwing up,
is the act of expelling the contents of the stomach through the mouth.
It is a natural way for the body to rid itself of harmful substances.
Nausea is the urge to vomit. Nausea and vomiting are common in
patients receiving chemotherapy for cancer and in some patients
receiving radiation therapy. Many patients with cancer say they fear
nausea and vomiting more than any other side effects of treatment.
When it is minor and treated quickly, nausea and vomiting can be
quite uncomfortable but cause no serious problems. Persistent
vomiting can cause dehydration, electrolyte imbalance, weight loss,
depression, and avoidance of chemotherapy.
After Treatment
All children cured of cancer, including those with retinoblastoma,
require life-long, follow-up care. Once a child has been free of
retinoblastoma for two to four years following treatment, and is
considered cured, the emphasis during periodic follow-up visits
changes. Pediatric oncologists will focus on the quality of the child's
life, including developmental and psychosocial concerns.
Most young children adapt well to the loss of one eye if enucleation
took place. Rarely, both eyes will require removal to save the child's
life. If both eyes are removed, the local educational system is
required to provide special services. Parents are encouraged to
investigate the school's services and advocate on their child's behalf.
Based on the therapy the child received and whether the child has
the genetic form of retinoblastoma, the doctor will determine what

13. evaluations are needed to check for long-term effects. This may
include imaging studies (CT scan or MRI) and blood work.
Counseling will also be provided in the case of children who have an
increased risk of additional tumors later in life, such as those with
bilateral disease and those with unilateral disease who have a family
history of the disease. Annual visits to specialized ophthalmologic
and medical oncologists are necessary in order to fully monitor the
child's recovery, and to increase the probability that a second cancer
will be detected in its earliest stages.
Children who have had cancer can also enhance the quality of their
future by following established guidelines for good health into and
through adulthood, including not smoking, maintaining a healthy
weight, and avoiding drinking alcohol in excess.
Risk Factors
A risk factor is anything that increases a person's chance of
developing a disease, including cancer. There are risk factors that
can be controlled, such as smoking, and risk factors that cannot be
controlled, such as age and family history. Although risk factors can
influence disease, for many risk factors it is not known whether they
actually cause the disease directly. Some people with several risk
factors never develop the disease, while others with no known risk
factors do.
When retinoblastoma affects both eyes, it is always a genetic
condition, even though only 10% to 15% of children with
retinoblastoma have a family history of the disease. Rarely, the
genetic form occurs in only one eye. The genetic form of the disease
always occurs in younger children (rarely beyond one year old) and
increases the child's risk of developing another cancer later in life.
About 60% of children with retinoblastoma do not have the genetic
form. They develop a single tumor in only one eye, and there is no
increased risk of additional tumors later in life.
Children who have had bilateral retinoblastoma or the hereditary form
of unilateral retinoblastoma are at increased risk for developing other
types of cancer; the risk of additional tumors is higher in those
children who receive radiation therapy to the orbit (eye socket) to
preserve vision or to other parts of the body where the tumor has
spread.

14. Conclusion
Retinoblastoma is a chemo sensitive disease but cannot be cured
with chemotherapy alone. It is a very effective mode of therapy in
preserving vision and the long-term complications of enucleation and
EBRT, especially in intraocular retinoblastoma. Metastasis
retinoblastoma to the orbit can be treated with good results with
combination chemotherapy, radiotherapy, and possibly, conservative
eye surgery as well. Distant metastasis disease cannot be cured with
conventional chemotherapy in majority of the cases; however, HDT
with ASCT appears to be a promising therapy for such cases.
Retinoblastoma with CNS metastases continues to have dismal
prognosis despite HDT with SCT and/or cranial radiation.
Medical tourism / health tourism India
India is one of the best places for the medical treatment or any other
health care in India. Every year thousand of visitors are coming to
India from around the world just for the medical check up and other
type of cancer and cardiac surgery or others diseases.
India is giving Thailand stiff competition in healthcare services for
overseas patients with cost of surgery lower by over 30% and in fact
cheapest in entire south Asia. Medical tourism in fast emerging as a
big opportunity for India with its low cost advantage, high quality
healthcare providers and an English speaking populace.
Medical tourism has become a common form of vacationing, and
covers a broad spectrum of medical services. Medical tourism mixes
leisure, fun and relaxation together with wellness and healthcare.
A combination of many factors has lead to the recent increase in
popularity of medical tourism. Exorbitant cost of healthcare and
medical facilities in advanced countries, ease and affordability of
international travel, favorable currency exchange rates in the global
economy, rapidly improving technology and high standards of
medical care in the developing countries has all contributed their
share to this rapid development of medical tourism.
India has originated as one of the most important hubs for medical
tourism. Many people from the developed countries come to India for
the rejuvenation promised by yoga and Ayurvedic massage however,
a nice blend of top-class medical expertise at attractive prices is
helping more and more Indian corporate hospitals to lure foreign
patients, including patients from developed nations such as the UK

15. and the US, for high end surgeries like Cardiac By Pass Surgery or
the various cancer surgeries.
As more and more patients from Europe, the USA and other affluent
nations with high medical costs look for effective options, healthcare
tourism in India is definitely on the cards for most of them and the fast
growing Indian corporate health sector is fully geared to meet that
need.
Not just cost savings or the high standard of medical care facility, but
also the waiting time is much lower for any treatment in India than in
any other country. Medical help is often an emergency and situations
can turn worse if the treatment is delayed. While you might have to
wait for several months to get a surgical operation done in the US, in
India things can be arranged within a week. For further details on the
Retinoblastoma Eye (retina cancer) Surgery in India at an
economic cost feel free to visit us at
www.indiancancersurgerysite.com or mail your queries at
info@indiancancersurgerysite.com or talk to us at
+91 9579034639.