Parents with unilateral retinoblastoma: their affected children.

BACKGROUND: A retrospective analysis of all patients with retinoblastoma on file at the Ophthalmic Oncology Center of the New York Hospital, Cornell University Medical Center was performed to examine the characteristics of retinoblastoma in children with a unilaterally affected parent. METHODS: Data were analysed for laterality of disease, age at initial diagnosis, number of tumour foci at diagnosis, ocular outcome, and patient survival. RESULTS: There were 54 patients, including nine pairs of siblings, diagnosed with retinoblastoma, each of whom had one unilaterally affected parent. The retinoblastoma was bilateral in 49 (91%) patients and unilateral in the remaining five (9%). The mean age at diagnosis was 10.5 months (range 1-36 months) and 35 patients (65%) were diagnosed within the first year of life. The mean number of initial tumour foci was 1.7 per eye; 1.6 foci per eye in bilaterally affected patients, and 3.7 foci per eye in unilaterally affected patients (p = 0.36). Retention of the eye was possible for 51 of 103 eyes affected with retinoblastoma. The mean follow up for patients was 9.0 years, with a range of 1 month to 30.5 years. There were a total of 12 deaths (22%): from retinoblastoma (two), sarcoma (five), cutaneous malignant melanoma (one), cancer type unknown (two), and cause unknown (two). CONCLUSION: Overall, the characteristics of retinoblastoma patients with a unilaterally affected parent, were similar when compared with all retinoblastoma patients with a positive family history.

Orbital rhabdomyosarcoma: treatment or overtreatment.

In 1972, the Intergroup Rhabdomyosarcoma Study standardized the classification and treatment of orbital rhabdomyosarcoma. It established chemotherapy with external beam radiotherapy as the standard of treatment, yet there was no comparison to treatment with external beam radiotherapy alone. We retrospectively examined the charts of patients with orbital rhabdomyosarcoma treated solely with external beam radiotherapy for the following data: age at diagnosis, gender, tumor recurrence, and tumor-related mortality. We followed 24 patients (mean follow-up 7.9 years) treated with external beam radiotherapy alone. The average age at diagnosis was 5.5 years; there were 15 males and 9 females. Three patients (12.5%) suffered tumor recurrence and there was one (4.2%) tumor-related death. When compared to the Intergroup Rhabdomyosarcoma Study, results suggest that chemotherapy with external beam radiotherapy may offer no advantage to external beam radiotherapy alone for the treatment of orbital rhabdomyosarcoma.

Unilateral retinoblastoma: new intraocular tumours after treatment.

A retrospective chart review of 427 eyes diagnosed with unilateral retinoblastoma was performed to determine which eyes, which patients, and when new intraocular tumours would develop after treatment. Mean follow up was 8.16 years. Twenty five (6%) of 427 unilateral retinoblastoma patients developed new intraocular tumours after treatment. Five (1%) unilateral patients who were previously treated with enucleation developed new tumours (in the fellow eye). Fifteen (24%) unilateral patients who were previously treated with external beam radiation developed new tumours (equally in either eye). New tumours did not develop in the macula of either eye. The relative risk of developing new intraocular tumours after treatment was 16% in patients diagnosed before 1 year old and 2.2% for patients diagnosed after 1 year old (p < 0.001). The mean time to onset for the development of new tumours after treatment was 0.74 years; no new tumours appeared after 7.5 years of age. Those patients who are diagnosed with unilateral retinoblastoma in the first 6 months of life and have a family history of the disease are at greatest risk of developing new intraocular tumours.

Trilateral retinoblastoma--incidence and outcome: a decade of experience.

PURPOSE: This report examines the incidence and outcome of trilateral retinoblastoma in children treated for retinoblastoma. A group of patients who are at highest risk for the development of trilateral retinoblastoma is defined. METHODS AND MATERIALS: Between 1979 and 1990, 117 children were treated with external beam radiation therapy for retinoblastoma, (97/117, bilateral). Median follow-up time was 68 months. The median age at diagnosis was 7 months. RESULTS: Six cases of trilateral retinoblastoma were identified. The incidence of trilateral retinoblastoma in children with bilateral retinoblastoma was 6% (6/97) and 10% in those with a family history of retinoblastoma. The median age at diagnosis of RB in the children with trilateral retinoblastoma, was 3 months, younger than the median age of the entire retinoblastoma group. In all cases, the pineal region was excluded from the radiotherapy fields. Treatment for the trilateral retinoblastoma consisted of craniospinal axis radiation therapy and chemotherapy in three patients, chemotherapy alone in two, and no treatment in one. All patients died from this disease. Overall, of the 117 children treated at our institution for retinoblastoma with a median follow-up of 68 months, 12 have died. Trilateral retinoblastoma was the major cause of death, accounting for 50% (6/12) of deaths. CONCLUSION: Trilateral retinoblastoma is a major and under-appreciated cause of mortality in the first 5 years after the diagnosis of bilateral retinoblastoma. A more aggressive approach toward screening a defined population of childhood retinoblastoma survivors may be warranted.

Changing trends in the management of retinoblastoma: 1951-1965 vs 1966-1980.

A retrospective analysis of the records of 1253 retinoblastoma patients (567 females, 665 males, and sex of one unknown) seen in the years 1951-1965 (575 patients, Interval I) and 1966-1980 (678 patients, Interval II) was conducted to determine changes in the manner of presentation of the disease, the treatment modalities employed, and their subsequent outcomes following treatment. There was no significant difference between the two 15-year time intervals in the age at presentation (mean, range), laterality, gender, family history, laterality vs gender distribution, family history vs laterality, employment of chemotherapy in unilateral cases or the use of external beam radiation (EBR) in bilateral cases. Changing trends in the management of retinoblastoma were observed as a result of the introduction of new treatment modalities, such as cryotherapy, light coagulation, and radioactive plaque therapy. Bilateral patients have received chemotherapy less frequently in interval II. The use of photocoagulation, cryotherapy, and brachytherapy for bilaterals, and cryotherapy for unilaterals increased significantly during Interval II. During both time intervals, a significantly higher percentage of unilaterally affected eyes were enucleated compared with bilaterally affected eyes; in addition, there was a decrease in the percentage of enucleations performed on both unilaterally and bilaterally affected eyes. In Interval II, 87% of unilateral patients and 91% of the bilateral patients had an enucleation performed.

Retinoblastoma aqueous humor: aromatic amino acids.

Aqueous humor from children with retinoblastoma obtained at enucleation and from eyes with adult cataracts were assayed with electrochemical liquid chromatography (Model 5500 Coulochem electrode array system) for metabolites of tyrosine, tryptophan metabolic pathways, catecholamine degradation pathways and ascorbate. More than 20 metabolites were identified in human aqueous for the first time. High levels of ascorbate were found in aqueous of eyes with adult cataracts (254, 336 ng/ml). Tyrosine metabolism in both sets of eyes was through dopamine. Vandylmandelic acid (VMA), homovanillic acid (HVA), and 3-methoxy, 4-hydroxyphenylglycol (MHPG) were all detected in retinoblastoma eyes. Although eyes with either adult cataracts or childhood retinoblastoma convert tryptophan through the serotonin pathway, retinoblastoma eyes metabolize tryptophan through the kynurenine pathway to a greater degree than adult cataract eyes.

Mortality from second tumors among long-term survivors of retinoblastoma.

BACKGROUND: Children diagnosed with retinoblastoma, a rare cancer of the eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into adulthood. Retinoblastoma is frequently caused by inherited mutations of the RB1 tumor suppressor gene. Most patients with germline (hereditary) mutations have bilateral disease. PURPOSE: We sought to quantify the mortality from second malignancies among long-term survivors of retinoblastoma and to identify factors that predispose to these deaths. METHODS: A retrospective cohort study examined mortality among 1603 patients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblastoma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the corresponding expected figure based on U.S. mortality data for the general population for 1925-1990. RESULTS: Follow-up was complete for 1458 patients (91%) for a median of 17 years after retinoblastoma diagnosis. A total of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 from other known causes (RR = 1.0), and 21 from ill-defined or unknown causes. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma and benign and malignant neoplasms of brain and meninges. Among 919 children with bilateral retinoblastoma, 90 deaths from second primary tumors occurred (RR = 60). Deaths from second tumors were more frequent among females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer deaths occurred thereafter. Radiotherapy for retinoblastoma further increased the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interval = 1.0-7.3). CONCLUSIONS: These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy treatment for retinoblastoma appears to further enhance the inborn susceptibility to development of a second cancer. IMPLICATIONS: Patients with retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mortality from a second cancer.

Nursing implications of visual fields in successfully treated retinoblastoma patients.

Very little data has been published on the long term peripheral vision of patients diagnosed and successfully treated for retinoblastoma. Nursing should address the patient's response to vision-conserving treatment and their adaptation to decreased peripheral vision. Computerized Humphrey's Central 30/Peripheral 30-60 visual fields were performed on ten patients (all with greater than ten year follow-up) who were successfully treated for retinoblastoma. All ten visual fields revealed an absolute and relative scotoma in the affected eye. Visual field loss was always worse than one would have predicted based upon the fundus examination of the tumor(s). Decisions for treatment must be based upon an interdisciplinary approach of nursing and medicine to evaluate patient survival and visual outcome. Nursing interventions include utilizing the visual field as a teaching aid, preparing the patient and the family for potential future visual loss and adaptation of lifestyle, and providing emotional support and realistic reassurance.

Bilateral retinoblastoma. Correlations between age at diagnosis and time course for new intraocular tumors.

A retrospective analysis of 355 eyes from 325 patients with bilateral retinoblastoma followed for at least five years was analyzed for the development of new ocular tumors. Eighty-eight eyes (24.8%) developed new tumors with more than 95% of these seen in patients diagnosed before the age of two years. Excluding one patient, no new tumors were seen in patients who were initially diagnosed after 33 months of age. The relative risk for developing new tumors was greater (45.1%) for patients diagnosed within the first six months of life than for patients diagnosed after the age of six months (14.2%). The highest percentage of patients (58%) to develop new tumors were those diagnosed before the age of three months. In patients initially treated before two years of age, new tumors were noted to develop up to 4.5 years later, whereas among eyes diagnosed after the age of two years, 100% of all new tumors were seen before 1.5 years of follow-up. Regardless of the age at diagnosis, however, the upper age limit for new tumor development ranged from 4.0-6.25 years, with a mean of 5.1 years. All new tumors were managed with either photocoagulation/cryotherapy or plaques.

Ultrasonic tissue characterization of uveal melanoma and prediction of patient survival after enucleation and brachytherapy.

We performed survival studies on 136 patients with uveal malignant melanoma who were examined with ultrasonic tissue characterization before treatment with cobalt-60 brachytherapy (74 patients) or enucleation (62 patients). Mean follow-up time was 58.7 months for the brachytherapy group and 59.0 months for the enucleated group. The maximal follow-up time was nearly ten years. Univariate survival analysis showed that patients with small tumors (less than 250 mm3, 49 patients) had a higher five-year survival when treated with brachytherapy than when treated with enucleation. No patients in this study with tumor volumes greater than 1,500 mm3 (13 patients) were treated with brachytherapy. For tumors of intermediate size (74 patients), survival analysis did not indicate appreciable differences between the treatment options. However, multivariate models including two ultrasonic tissue characterization variables, scatterer size and concentration, showed appreciable intergroup differences in the dependence of survival on these factors. Results suggest that tissue properties detectable with ultrasonic techniques are related to differences in patient survival and may be used for treatment planning for tumors of intermediate size.

Retinoblastoma. The long-term appearance of radiated intraocular tumors.

A retrospective analysis of 50 patients with retinoblastoma was undertaken to determine the appearance of intraocular retinoblastoma that had received external beam radiation a minimum of 10 years previously. Of the 91 tumors found in 59 eyes, 76 (84%) continued to be ophthalmoscopically visible after 10 years. The most common ophthalmoscopic appearance was a Type III regression pattern. The type of radiation regression pattern correlated with the pretreatment volume of the tumor. The largest tumors (mean, 10.0 disc diameter [dd]) became Type I regression patterns, whereas the smallest tumors (mean, 1.0 dd) completely disappeared. This represents the first long-term follow-up of the intraocular status of radiated retinoblastoma.

Radiation regression patterns in treated retinoblastoma: 7 to 21 years later.

A retrospective review of cases on file at the Ophthalmic Oncology Center of The New York Hospital-Cornell Medical Center, New York was performed in order to examine the appearance of radiation regression patterns 7 or more years after successful treatment of retinoblastoma with external beam radiotherapy. Forty-eight patients were found to have 89 tumors in 57 eyes which were treated solely with external beam radiation; they were followed for a minimum of 7 years and had sufficient information available for analysis. All but five of the patients had bilateral retinoblastoma. Seventy-four of the 89 tumors continued to be ophthalmoscopically visible after 7 or more years. Taking into account those that did change between the time of first evaluation (usually at the completion of treatment) and final evaluation (7 or more years after treatment), the number of Type I regressions increased by 10.1%, Type IIs decreased by 19.1%, Type IIIs fell by 7.8%, Type IVs rose by 10.1%, and the number of tumors that disappeared increased by 6.8%. Type II remained the most common regression throughout the follow-up. The regression with the greatest potential for change was the Type II regression. The pretreatment volume of the tumor correlated with long-term radiation regression patterns. The smallest tumors (mean size 1.1 dd [disc diameter] or less in size) completely disappeared, while the largest (mean 9.9 dd) became Type I regressions.

Endophytic vs exophytic unilateral retinoblastoma: is there any real difference?

A retrospective review of 297 cases of enucleated and histologically proven unilateral retinoblastoma with a minimum of 5-year follow-up was analyzed to see if there were any clinical or prognostic differences between endophytic and exophytic type retinoblastoma. Endophytic retinoblastoma (181 cases) was found more often than exophytic (116 cases). The following features were not associated with the clinical appearance of either endophytic or exophytic tumors: sex of patient, right vs left eye, propensity for bilateral development, initial sign or symptom, presence of rubeosis, preoperative metastasis, optic nerve invasion, orbital recurrence, survival of the patient, length of follow-up, or age at diagnosis. Three features were found that correlated with type: a disproportionately higher percentage of patients with endophytic retinoblastoma had a positive family history; a disproportionately high percentage of patients with exophytic retinoblastoma developed glaucoma; and choroidal invasion occurred significantly more often in patients who had exophytic retinoblastoma than in those who had endophytic retinoblastoma.

Ocular melanoma: total dose and dose rate effects with Co-60 plaque therapy.

From 1968 to 1987, 123 consecutive patients with nonmetastatic choroidal melanoma were treated with cobalt-60 plaques. One hundred sixteen patients were followed up for a mean of 3.8 years. Twenty patients had local failure, and 14 patients had distant failure. Complications included 32 cataracts, and seven enucleations were required. Local recurrence did not correlate with tumor height, tumor volume, dose, or dose rate. Increased volume (P = .004) and height (P = .01) correlated with increased rates of distant metastases. Dose adjusted for volume did not correlate with the rate of metastases.

Reconstruction of the anophthalmic socket: lower eyelid malposition and canthal tendon laxity.

There are a number of etiologies underlying the development of socket deformity with associated lower eyelid malposition, lateral canthal tendon laxity, and/or contraction of the inferior fornix. In addition to cosmetic considerations, each of these anatomic problems can interfere with comfortable wear and retention of a prosthesis. This chapter gives an overview of these problems and details our preferred surgical approaches to repair of these anatomic deformities. Specifically discussed are techniques for: mucous membrane and ear cartilage grafting to repair lower lid inner lamellar tissue shortage, reconstruction of the inferior fornix/cul-de-sac, direct lower eyelid lateral canthal resuspension, and resuspension using a periosteal flap or autogenous fascia lata from the iliotibial tract.

Ophthalmic neoplasms in infancy and childhood.

The most common ocular and orbital tumors presenting in infancy, childhood and adolescence are presented and discussed in this review. It has been prepared specifically for the clinical pediatrician and focuses on the clinical recognition of ophthalmic neoplasms, their diagnostic evaluation employing the use of advanced imaging techniques, biopsy when indicated and extent of disease workup. In addition, current treatment modalities are discussed. Ocular tumors addressed include: retinoblastoma, capillary hemangioma, lymphangioma, dermoid and epidermoid cysts, teratoma, glioma, astrocytic hamartoma, neurofibroma, rhabdomyosarcoma and fibrous tumors. Two aggressive and potentially fatal tumors, rhabdomyosarcoma and retinoblastoma, are presented in detail. In addition, the ocular tumors associated with the phakomatoses (von Hippel-Lindau, tuberous sclerosis and neurofibromatosis) are reviewed.

Optic nerve involvement in retinoblastoma.

This retrospective review of 814 retinoblastoma patients discloses 240 cases of tumor extension into the optic nerve. Optic nerve involvement was classified according to the degree of invasion; grade I is superficial invasion of the optic nerve head only, grade II is involvement up to and including the lamina cribrosa, grade III is involvement beyond the lamina cribrosa, and grade IV is involvement up to and including the surgical margin. The incidence of optic nerve involvement was 29.5% (240/814). The mortality rate of patients with optic nerve involvement with grade I was 10%; grade II, 29%; grade III, 42%; and grade IV, 78%. Actuarial life-table analysis shows an increased mortality rate with increasing grade of optic nerve involvement. Multivariate statistical analysis shows that the grade of optic nerve involvement and the age at diagnosis of optic nerve involvement are the factors most significantly associated with survival.

Neuron-specific enolase and retinoblastoma. Clinicopathologic correlations.

Neuron-specific enolase (a glycolytic, ubiquitous, intracellular enzyme) has recently been reported to be detectable in the aqueous humor of eyes containing retinoblastoma. Aqueous humor from 17 patients with histologically proven retinoblastoma was assayed for the presence of neuron-specific enolase (NSE). NSE was detectable in 17 out of 17 patients with levels between 619 and 60,000 ng/ml. A multitude of clinocopathological parameters were examined for statistically significant correlations with levels of aqueous humor NSE. This investigation demonstrated that only two parameters, the presence of tumor invasion into the anterior chamber, and inflammation significantly correlated with aqueous NSE levels. Histological parameters which did not correlate with aqueous NSE levels included tumor necrosis, calcification, Flexner-Wintersteiner rosettes, exophytic/endophytic tumor type, tumor extent relative to the equator, and optic nerve/choroidal invasion. Clinical parameters which showed no correlation included patient sex (M/F), enucleation age, presentation age, family history, laterality, prior treatment, and presence of metastatic disease. Neuron-specific enolase is present in the anterior chamber of eyes enucleated for retinoblastoma, but additional testing is necessary to determine the normal levels of neuron-specific enolase in children's eyes and the levels in eyes with lesions simulating retinoblastoma.