Recently, there has been a trend away from enucleation and toward more conservative treatment modalities in patients with advanced retinobiastoma. Traditionally, unilateral cases had been managed with enucleation while bilateral cases required enucleation of the more severely affected eye with subsequent radiation therapy of the remaining eye.1'3 As radiation therapy became more successful in preserving eyes with retinobiastoma, the indications for its use have broadened.4 At present, proposed indications for external beam radiation usage include treatment of the second eye hi bilateral cases after the worse eye has been enucleated, treatment of both eyes in symmetrical bilateral disease, and treatment of posterior pole tumors in unilateral cases. In each instance, the reason for electing treatment versus enucleation is that the eye is felt to have "visual potential." Unfortunately, it is often difficult to predict the visual outcome of these eyes. This is especially true with tumors involving the macula. A review of the literature revealed little visual acuity information on such patients who were treated conservatively.5'8 Therefore, we reviewed our experience with patients who underwent radiation treatment for large macular retinobiastoma and report their visual results.
PATIENT SELECTION AND METHODS
The medical records and fundus photographs of all patients with advanced retinobiastoma invoiving the macula and fovea seen at the Duke University Eye Center from 1983 to 1990 were reviewed retrospectively. Those patients who were treated with external beam radiation and had a Reese-Ellsworth classification of group III or greater were included in this study. In each case, the initial diagnosis and Reese-Ellsworth classification were assessed with an examination using anesthesia. A detailed fundus drawing, fundus photographs, computerized tomography (CT) scan, lumbar puncture, and bone marrow aspiration were performed. Each child was followed up with serial examinations under anesthesia, fundus photography, and CT scans. Other studies were performed periodically as medically indicated. Each patient received 4000 rads of external beam radiation in divided dosages of 180 rads per day over 5 weeks. In addition, seven patients received chemotherapy which included vincristine and cyclophosphamide (Cytoxan). The chemotherapy was administered under a protocol for advanced group IV and V retinobiastoma or any patient with a positive surgical margin. Chemotherapy was given for 1 year and then discontinued if the patient remained stable with no evidence of recurrence.
Visual acuity was assessed by various methods determined by the child's age and level of cooperation. In all but three eyes, Snellen acuities were obtained. In the remaining three patients, preferential looking techniques were used to evaluate vision. Both distance and near vision were evaluated when possible. The development of strabismus, amblyopia, and cataract were closely monitored and treatment was initiated if necessary.
FIGURE 1: Treated macular retinoblastoma visual results. Visual acuity of patients grouped by Reese-Ellsworth classification (III = group III, IV = group IV, V = group Vf.
A total of 20 eyes in 17 patients with large macular and foveal tumors were identified and treated primarily with external beam radiation (Table). Based on the ReeseEllsworth classification, 8 were group III, 8 were group IV, and 4 were group V. The average age at diagnosis was 10 months (range, 1 to 36 months). Bilateral retinoblastoma occurred in 75%, and 24% had a positive family history. Patients 6, 8, and 14 had bilateral disease which was symmetrical and both eyes received identical treatment.
Distance visual acuity ranged from 5/200 to 20/50 with all eyes retaining useful vision (Fig 1). All eyes remained comfortable and none required further treatment. In addition to the macular location of the tumor, additional factors which limited the final level of visual acuity included cataract in 3 eyes, partial retinal detachment in 1 eye, and amblyopia in 2 eyes (Table). Four eyes have undergone cataract extraction without complications.
The visual prognosis in advanced retinoblastoma involving the macula has generally been regarded as poor, thereby supporting the traditional practice of enucleation in such cases.5"7 Conservative methods of management including external beam radiation, scierai plaques, cryotherapy, and laser treatment do not appear to adversely affect the patient's overall systemic prognosis and, therefore, it seems reasonable to salvage these eyes if "useful* vision can be preserved. Several studies support the finding that tumor localization is the best predictor of the final visual acuity, with macular tumors demonstrating the poorest results.6,7 However, Lam et al recently reported a series of patients with macular retinoblastoma in which three patients eventually obtained 20/20 vision.8 While there was no direct foveal involvement by the tumor in these patients, their studies support the concept that with conservative management excellent results are possible.
FIGURE 2: Fundus drawings of patient 6 prior to treatment. Note large bilateral macular retinoblastoma tumors.
FIGURE 3: Fundus photographs of macular and disc area of patient 6 prior to treatment.
All of our patients had advanced retinoblastoma with large tumors involving the macula and fovea. It was impossible to determine prior to treatment what the final visual outcome would be. Some of the worst looking cases actually had surprisingly good visual outcomes. It is very difficult to tell by observing the tumor where the active center is located. As patient 6 illustrates (Figs 2-5), after treatment the regression pattern often is away from the macula and foveal area. Retina in this area may survive, resulting in good visual function. Not unexpectantly, the Reese-Ellsworth classification was not found to be useful in predicting visual outcome in these cases.
Other factors also played a role in the final visual outcome. Seven patients developed a cataract, which became significant enough to require extraction in four cases. In the four unilateral cases, amblyopia certainly must have had an effect on the final visual outcome and may explain why these patients, as a group, had the poorest results.
FIGURE 4: Fundus photographs of the right eye of patient 6 after treatment. Note marked regression of the tumor and disturbance of the retinal architecture after radiation therapy Visual function of this eye was 20 /400.
FIGURE 5: Fundus photograph of the left eye of patient 6 after treatment. Note the marked regression of the macular tumor to a temporal location. The parafoveal function was preserved, and visual acuity is 20/50.
Seven patients had chemotherapy in addition to external beam radiation. This was done under a protocol for patients with group IV or V disease who were felt to have a high potential for metastatic disease or any patient with a positive surgical margin. The role of chemotherapy in the treatment of intraocular disease in retinoblastoma is controversial, and we do not feel that it played a significant role in the preservation of vision in these patients. Further work in this area will need to be done to establish the efficacy of chemotherapy.
Based on these findings, we feel it is reasonable to consider patients with large macular retinoblastomas for conservative treatment rather than enucleation. We found it impossible to determine the final visual outcome based on the appearance of the tumors prior to treatment. If it is not contraindicated for other reasons, a trial of radiation therapy may allow the patient to retain a functioning eye and thereby improve quality of life. In unilateral cases, amblyopia must be considered and a trial of patching initiated to ascertain the full potential of the treated eye. Cataract extraction, when appropriate, appeared to be safe and afforded marked improvement in visual function. However, we did delay as long as possible before entertaining lens removal because of the recent report of tumor growth and metastatic spread postcataract surgery.9
Caution still must be exercised in selecting patients for radiation therapy. A recent report has indicated that there is a greater chance of developing a second cancer in the field of radiation.10 While these data were collected over a period from 1922 to 1973, and do not represent current methods of administering radiation, they still indicate that the treatment is not without risks. As we become more sophisticated and confident in our treatment modalities, further emphasis should be placed on the potential for preserving sight in these young patients.
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