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A Parent’s Guide to Understanding Retinoblastoma 1 Acknowledgements This book is dedicated to the thousands of children and families who have lived through retinoblastoma and to the physicians, nurses, technical staf and members of our retinoblastoma team in New York. David Abramson, MD We thank the individuals and foundations Chief Ophthalmic Oncology who have generously supported our research, teaching, and other eforts over the years. We especially thank: Charles A. Frueauf Foundation Rose M. Badgeley Charitable Trust Leo Rosner Foundation, Inc. Invest 4 Children Perry’s Promise Fund Jasmine H. Francis, MD The 7th District Association of Masonic Lodges Ophthalmic Oncologist in Manhattan Table of Contents What is Retinoblastoma? ..........................................................................................................3 Structure & Function of the Eye ...........................................................................................4 Signs & Symptoms .......................................................................................................................6 Genetics ..........................................................................................................................................7 Genetic Testing .............................................................................................................................8 Examination Schedule for Patients with a Family History ........................................ 10 Retinoblastoma Facts ................................................................................................................11 Diagnosis ......................................................................................................................................12 What to Expect on the Day of Your Visit.......................................................................... 14 Classification ...............................................................................................................................16 Treatment ......................................................................................................................................18 Ophthalmic Artery Chemosurgery ......................................................................................19 Coping ...........................................................................................................................................23 Long-Term Consequences ..................................................................................................... 24 Definitions ....................................................................................................................................26 References ....................................................................................................................................27 1 2 What is Retinoblastoma? Retinoblastoma (REH-tin-oh-blast-OH-ma) Retinoblastoma develops in the retina, the is a cancer of one or both eyes which occurs light-sensitive layer of the eye which enables in young children; it is the most common the eye to see. If retinoblastoma occurs in only primary cancer of the eye worldwide. There one eye, it is called unilateral retinoblastoma, are approximately 350 newly diagnosed cases and if it occurs in both eyes it is called bilateral per year in the United States. Retinoblastoma retinoblastoma. Most cases (75%) involve only afects children of all races, boys and girls one eye (unilateral), and the rest (25%) afect equally. The average age for diagnosis is both eyes (bilateral). The majority (90%) of 2.5 years when one eye is involved and patients have no family history of the disease, 1 year when both eyes are involved. and only a small percentage (10%) have other family members with retinoblastoma. This booklet will help you understand the eye and the diagnosis and treatment of retinoblastoma. 3 Structure & Function of the Eye The eye of an adult measures about one inch from the front to the back of the eye. A child’s eye measures about three-quarters of one inch. Sclera Conjunctiva Choroid Retina Ciliary body Retinal blood vessels Macula Iris Lens Optic nerve Cornea Anterior chamber Vitreous humor The eye has three layers: • Sclera – the outer protective white coating of the eye • Choroid – the middle layer which contains blood vessels to nourish the eye • Retina – the inner layer which contains the nerves that bring information to the brain for seeing. This is where a retinoblastoma starts. 4 The cornea is the clear portion of the front of The macula is the area of the retina that is the eye. The conjunctiva is a tissue which lines responsible for central vision. Its central portion the eyelids and the eyeball up to the edge of is referred to as the fovea and is responsible the cornea. The iris is the colored portion of for the sharpest vision. The macula houses the the eye. It is made up of a spongy tissue and highest concentration of the cones which are is an extension of the choroid. The pupil is the responsible for color and sharp vision. The rest opening in the iris which allows light into the eye. of the retina is composed of rods, which are The lens helps focus light rays onto the retina. more sensitive to light and are responsible for The lens can change shape, or “accommodate,” night vision and peripheral vision. to focus on near or distant objects. Attached to the outside of the wall of the eye The eye is filled with fluids which help nourish are six muscles that aid in the movement of and maintain the pressure within the eye. the eye. Movement of the eye is caused by The anterior chamber, the front portion of the shortening of the eye muscles. eye between the iris and the cornea, is filled with aqueous humor, a watery fluid, which nourishes the lens and maintains the pressure within the eye. The back portion of the eye is filled with vitreous humor, a transparent gel. The retina is made up of ten layers and contains millions of cells. The optic nerve has nerve fibers which transmit information to the brain for interpretation of objects seen and contains about a million cells. 5 Signs & Symptoms Retinoblastoma may be discovered during a A crossed eye or strabismus is the second most routine exam by a pediatrician; however, most common sign of retinoblastoma. The child’s eye often the parent is the first one to notice signs may turn outward (towards the ear) or inward of retinoblastoma. For the majority of children (towards the nose). with retinoblastoma, the sign that is noticed is a white pupil reflex or leukocoria. Leukocoria Retinoblastoma may also be noticed because of causes the pupil of the eye to reflect white, as a red painful eye, poor vision, inflammation of pictured, instead of the normal black (or normal the tissue around the eye, an enlarged (dilated) red reflection in a flash photograph). pupil, or a diferent colored iris. Retinoblastoma may cause other symptoms, like a sudden Other eye diseases can also cause this white decrease in eating or drinking. pupil reflex, so leukocoria does not always indicate retinoblastoma. An ophthalmologist can determine the correct diagnosis. 6 Genetics How can retinoblastoma be inherited? What is the chance of inheriting a gene All people, whether they have retinoblastoma mutation that may cause retinoblastoma? or not, have two copies of the retinoblastoma Both men and women can pass down a gene called RB1. An alteration (mutation) retinoblastoma gene mutation. If either parent in both copies of the RB1 gene can cause carries the hereditary mutation, there is a 50% retinoblastoma tumors. Retinoblastoma chance (1 in 2) of passing the altered RB1 gene mutations can be inherited or can happen to each future pregnancy. Roughly 90% of by chance. children who inherit a mutated RB1 gene will develop retinoblastoma. Inherited retinoblastoma: In some cases (10%) of the inherited form If bilateral tumors are present (both eyes of retinoblastoma, a mutated copy of the afected), it is assumed the child has a hereditary retinoblastoma gene is passed down from form of retinoblastoma. Only about 15% of a parent to a child. children with a tumor in one eye, and no family history of retinoblastoma, have the hereditary In other cases, a new retinoblastoma gene form. It is possible for a person who has never mutation may occur by chance at a very early been treated for retinoblastoma to have a stage in a child’s development. hereditary predisposition (to have an RB1 gene mutation in all cells of the body). 1 in 200 people Both types of inherited retinoblastoma are who carry a hereditary RB1 gene mutation, never called hereditary retinoblastoma and the develop eye tumors. For this reason, parents of retinoblastoma gene mutation is expected to a child with retinoblastoma should have detailed be present in all or most cells of the child’s retinal eye exams with an ophthalmologist body – including all of the retinal cells. to look for the presence of a cured or limited retinoblastoma, called a retinoma. Each child Non-inherited retinoblastoma: of an unafected parent with a retinoma has a 45% chance of being afected. Most often (90% of the time) retinoblastoma happens by chance and is not inherited. In Rare situations can occur where the genetic the non-inherited form of retinoblastoma status of a person’s germ cells (sperm or egg (sometimes called sporadic form), new cells) difer from other parts of the body. This retinoblastoma gene mutations occur by is called germline mosaicism. In one example of chance within a single
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