9 Retinoblastoma and Other Malignant Intraocular Tumors A. Linn Murphree and Laurie E. Christensen RETINOBLASTOMA Early Detection and Treatment Much of the vision loss that we as pediatric ophthalmologists accept as normal with retinoblastoma can be prevented or reversed with aggressive screening, early diagnosis, and treat- ment. In fact, we are convinced that in the coming decades detecting early disease by lowering the average age at initial diagnosis will prove to be a much more efficient and cost- effective way to manage retinoblastoma than developing exotic new drugs or gene therapy for advanced disease. For retinopathy of prematurity (ROP), we readily accept that early detection and treatment can prevent vision loss. The problem there, however, seems a bit more manageable; the children at risk for ROP all belong to a small and easily identifiable group based on low birth weight. In the absence of a family history of retinoblastoma, the problems of screening for retinoblastoma would, on first glance, appear to be a logistical nightmare. Changing practice patterns to include instillation of a mydriatic drop as a routine part of well-child care can be a simple, easy-to-perform, effective adjunct to the red-reflex exam already used by pediatricians. Unfortunately, achieving that change in practice patterns, even for something as simple as a single instillation of a drop in each eye (a 10-second, 15-cent, intervention), will require overcom- ing major conceptual hurdles. 246 chapter 9: retinoblastoma & other malignant intraocular tumors 247 The first hurdle is the rarity issue. The argument goes like this: “Retinoblastoma is so rare, that I (the pediatrician) will see only 2 to 3 cases in my 30 years of practice. Are you telling me I must screen 25,000 to 35,000 infants to find those 2 to 3 cases early?” The response to that argument is simple. Well-child care is all about screening and prevention. Most pediatricians already screen for retinoblastoma. Cur- rently they either perform, or know that they need to perform, the pupillary red-reflex exam. As a result, the proposed change in practice patterns to include pupil dilation as part of well-child care does not add a single step to the physical examination that is already a part of the well-child visit. The current practice of performing the pupillary red-reflex exam with an undilated pupil is like listening for a heart murmur without a stethoscope; it is hardly worth the trouble. It is true that retinoblastoma is rare, affecting at most only 1 in 12,000 infants. However, if the incidence of retinoblastoma is combined with congenital cataracts, the other major treatable congenital developmental anomaly of the eye, intraocular pathology that can be treated successfully before the end of the third month of life would be found in 1 of every 750 infants screened. To put these numbers in perspective, the incidence of congenital heart disease is about 1 in 500 live births; congenital dislocation of the hip affects 1 in 1,000 infants. A major reason neonatal well-child examinations exist is to screen for both these developmental disorders because early diagnosis and treat- ment is essential for the well-being of the child. During the 1- or 2-month well-child visit, pediatricians accurately listen for faint heart murmurs and competently manipulate the hip joint for evidence of a congenital dislocation. They do not, as yet, ade- quately screen for treatable intraocular pathology. The second hurdle to achieving practice pattern changes that encourage dilation of the pupil in the primary care office relates to their personal past experience screening for intraocu- lar pathology with an undilated pupil. Most pediatricians received little medical school training in ophthalmology and feel unprepared to screen for intraocular pathology. They all, however, know that the red-reflex examination is the best way to screen for retinoblastoma. They are generally now uncom- fortable, however, with the routine results they get from the undilated red-reflex screen. The pupil is so small, often 2mm or less, that the data from the test are inconclusive. The ration- ale for checking the “eyes normal” box is that because the 248 handbook of pediatric retinal disease disease is rare, the chances of being right are very high. Unfor- tunately, the chances of overlooking the presence of a large intraocular tumor are also high. The third hurdle to the concept of pupil dilation in the primary care office is the misperceived burden that a single instillation of a mydriatric drop would impose on the doctor, office staff, and office routine. Poorly or misremembered infor- mation from medical school mixed with past personal experi- ence contributes to this problem. Examples of misremembered information include (1) dilating the pupils causes glaucoma; (2) dilating the pupil takes three instillations of drops 5 min apart and then a wait of 30 min; (3) holding down a child to put in dilating drops requires three or four office staff members and totally disrupts the office routine; (4) dilating the pupils requires more work from the pediatrician that will not be separately reimbursed; and (5) dilating the pupils will obscure critical information that could be gathered from the pupil exam before dilation. Each of the five misremembered “facts” about pupil dilation commonly used by those opposed to the use of dilation as a part of the 1- or 2-month well-baby examination is pure myth. 1. Pupillary dilation causes glaucoma in older adults with narrow anterior chambers, not in infants. Iatrogenic glau- coma has not been a concern or a finding in the hundreds of thousands of tiny infants dilated for ROP screening in the last decade. 2. A single instillation of a single agent, 1% tropicamide, gives 5 to 6mm of dilation at 20min, more than adequate for red-reflex screening 3. Three or four people might be required to hold down a 3- or 4-year-old to put in eye drops, but the subjects of our inter- est are newborn infants no more than 1 to 2 months old. When they are placed supine to be weighed, the nurse makes a “lake” of 2 to 3 drops of tropicamide over the inner edge of the lid fissure. If the “lake” wets the lashes to the lateral edge of the fissure and excess runs down the temple toward the ear, the drop is “in.” There is no need or benefit of holding the lids open. If the drop does not get “in” immediately, gentle manipulation of the upper lid with the thumb on the brow will accomplish the trick. Holding the infant down is not necessary. 4. Dilating the pupil as part of the well-baby examination requires no extra effort on the part of the pediatrician. In fact, chapter 9: retinoblastoma & other malignant intraocular tumors 249 pediatricians who have been doing this routinely in their prac- tice for more than 8 years report that except that they now get a wonderfully informative red-reflex examination on virtually every baby, they are not consciously aware of the mechanics of the dilation process. They always performed the red-reflex examination. The only difference is that now they get useful information.2 5. Drops are not instilled during the first examination of the child by the pediatrician, which usually occurs before discharge from the hospital. Significant anisocoria or papillary pathology would be noted on that exam. Finally, failure to recognize the signs of retinoblastoma early can often be blamed on poor communication between parents and pediatrician. Several factors contribute to this problem: (1) parents see the leukocoria and pediatricians generally do not (because of the small pupil); (2) pediatricians find it hard to believe that the parents or other lay family members can see signs of disease that they (the trained professionals) cannot; and (3) parents accept reassurance from the pediatrician because they question their own observations of the abnormal white “glow” that is present only some times. When an irritated authority figure suggests that they might be imagining things and that they are overreacting, the parents often question the validity of their own observations and quietly acquiesce to the opinion of the professional. Clinical Presentation Any white or yellow lesion in the posterior segment of the eye in a child under 5 years of age should raise the possibility of retinoblastoma. This disease is highly curable in its early stages but can be fatal if the diagnosis is missed or delayed. When the fundus of a young child cannot be seen clearly for whatever reason, a CT scan or ocular ultrasound is essential to rule out the presence of intraocular calcium before surgically entering the eye. Retinoblastoma rarely, if ever, causes pain and discomfort unless secondary glaucoma is present. Evidence that the child does not see well is nonexistent in unilateral disease where one eye is normal. Even in bilateral disease, it is rare for the macula in both eyes to be destroyed by the tumor, although in advanced disease this can happen. 250 handbook of pediatric retinal disease Clinical signs of retinoblastoma relate to the tumor location, size, and color (Table 9-1). In the majority of cases, the diagnosis of retinoblastoma is straightforward. In a large majority of chil- dren with this disease, a parent or family member first notes the presence of a white pupillary reflection or reflex (leukocoria). A posterior pole tumor as small as 3 to 5mm in diameter has the capacity to create leukocoria. The term that parents use for the leukocoria observation is rarely the textbook-cited “cat’s eye.” Usually it is a “g” word, such as “gleam, glow, glare, or glint” (Fig.