The effect of chemoreduction on retinoblastoma-induced retinal detachment.

BACKGROUND: Retinoblastoma with total retinal detachment traditionally has been managed with enucleation. We employed a chemoreduction protocol in an effort to reduce the tumor size to allow for focal treatment and salvage of the eye. METHODS: A prospective study was performed to assess the effects of a 2-month chemoreduction regimen of vincristine, etoposide, and carboplatin on massive retinoblastoma with total retinal detachment. RESULTS: We treated 17 eyes with total retinal detachment from retinoblastoma in 13 patients over a 14-month period. At the initial examination, the mean tumor base was 15 mm and mean thickness was 10 mm. The eyes were classified as Reese-Ellsworth group V in 16 cases (94%) and group III in one case (6%). The retina was totally detached with serous subretinal fluid in all cases. After 2 months of chemoreduction, all tumors showed a response, and the tumors decreased to a mean base of 10 mm and thickness of 5 mm. Overall, a mean of 33% decrease in base and 47% decrease in thickness was noted. The subretinal fluid had resolved completely in seven eyes (41%), leaving flat retina. In three eyes (18%), partial resolution was achieved; in seven eyes (41%), minimal resolution of the subretinal fluid at the 2-month period was noted. By last follow up, at a mean of 10 months after initiation of chemoreduction, complete resolution of the subretinal fluid occurred in 13 eyes (76%) and partial resolution of subretinal fluid occurred in four eyes (24%). CONCLUSION: Preliminary observations suggest that chemoreduction may be an important tool in the initial management of retinoblastoma, even for large tumors with total retinal detachment. Tumor shrinkage may be dramatic and subretinal fluid resolution may be complete.

Ocular manifestations of the organoid nevus syndrome.

BACKGROUND: The organoid nevus (sebaceous nevus) syndrome is characterized primarily by cutaneous sebaceous nevus, seizures, and epibulbar choristomas. Based on ophthalmoscopy and computed tomography (CT), a yellow fundus lesion recently observed in this syndrome has been called a coloboma by some authors or a choroidal osteoma by others. This study was undertaken to review the authors' personal experience with the organoid nevus syndrome, to review the English language literature on the subject, and to address some misconceptions regarding its ocular manifestations. METHODS: The authors reviewed the records of patients with the organoid nevus syndrome who were personally evaluated by the authors. The ocular findings were studied in more detail, with emphasis on the epibulbar and fundus lesions. RESULTS: The authors identified five patients with the organoid nevus syndrome. Four had a classic sebaceous nevus in the facial and scalp area and two had seizures and arachnoid cysts. All five patients had an epibulbar tumor, which proved to be a complex choristoma in one case that was studied histopathologically. A characteristic ophthalmoscopic feature, observed in the four patients with clear ocular media, was a flat, yellow discoloration of the posterior fundus, of variable size and shape, that appeared to correlate with a dense plaque noted on ultrasonography and CT. In one case, histopathologic studies showed that this posterior lesion contained intrascleral cartilage. CONCLUSIONS: The authors' observations and a review of the literature indicated that the organoid nevus syndrome has varied manifestations. Just like the closely related phakomatoses, it often occurs as a forme fruste, without full expression of the syndrome. The most important ocular manifestations are an epibulbar mass, compatible with a complex choristoma, and focal, yellow discoloration in the fundus, probably related to intrascleral cartilage.

Iris juvenile xanthogranuloma studied by immunohistochemistry and flow cytometry.

An unusual large tan iris mass in a 19-month-old child was removed by iridocyclectomy and studied by light microscopy, immunohistochemistry, and flow cytometry. The excised mass consisted of granulomatous inflammation with numerous osteoclast-like giant cells and scattered atypical Touton giant cells. Immunohistochemistry studies showed that the cells were most consistent with mononuclear histiocytes. Flow cytometry showed that 90% of the cells sampled were T-lymphocytes, with a predominance of T-suppresser cytotoxic cells. Juvenile xanthogranuloma (XG) of the iris can occur as a large solitary mass, without signs of intraocular inflammation or hyphema.

Conjunctival metastasis as the initial manifestation of lung cancer.

PURPOSE: To report a case of conjunctival metastasis as the initial manifestation of lung cancer. METHOD: A 55-year-old man without known systemic disease developed a conjunctival mass in his right eye. He underwent excision of the tumor and systemic evaluation. RESULTS: Histopathologically, the mass was a metastatic squamous cell carcinoma. Further evaluation disclosed a primary bronchogenic carcinoma with metastasis to ribs and brain. The primary and secondary tumors were treated with chemotherapy and irradiation. CONCLUSIONS: Conjunctival metastasis may be the initial manifestation of lung cancer. It should be considered in the differential diagnosis of a deep conjunctival mass.

Transpupillary thermotherapy in the management of choroidal melanoma.

BACKGROUND: Several methods of treatment have been used for choroidal melanoma. The purpose of this report is to evaluate the effectiveness of transpupillary thermotherapy using near-infrared radiation to treat choroidal melanoma. METHODS: A prospective study was conducted to evaluate the clinical features, treatment results, and complications of patients with choroidal melanoma who were treated with transpupillary thermotherapy delivered over one to four sessions and followed for at least a 6-month period. All treated tumors had either documentation of growth or ophthalmoscopic risk factors for future growth and/or metastasis. RESULTS: There were 17 patients with choroidal melanoma treated with transpupillary thermotherapy. The mean tumor size before treatment was 6.6 mm in base and 3.0 mm in thickness. The tumor margin was a mean of 2.3 mm from the optic disc and 2.7 mm from the foveola. Seven tumors (41%) touched the optic disc margin and three (18%) were under the fovea. The tumor responded to treatment in all patients, with a decrease in thickness and resolution of associated subretinal fluid. At a minimum of 6 months of follow-up, the mean tumor thickness was 1.7 mm, and the tumor site was a residual chorioretinal scar with partial visibility of the sclera in all patients. Despite the proximity to the optic disc and foveola, the final visual acuity was the same or improved in ten eyes (59%) and decreased in seven (41%). The improved vision was due to resolution of subfoveal fluid, whereas the decreased vision was primarily the result of treatment in the fovea with ultimate retinal vascular occlusion or preretinal traction. Although long-term follow-up is not yet available, there were no patients with tumor recurrence or tumor metastases. CONCLUSIONS: This preliminary study demonstrates that transpupillary the thermotherapy appears to be an effective treatment for selected small choroidal melanomas and may be a particularly useful modality for treating those tumors near the foveola and optic disc. Longer follow-up is necessary to assess for local recurrence and the impact of treatment on survival.

External beam radiation for retinoblastoma: results, patterns of failure, and a proposal for treatment guidelines.

PURPOSE: To analyze treatment results and patterns of failure following external beam radiation for retinoblastoma and propose treatment guidelines according to specific clinical variables. METHODS AND MATERIALS: We analyzed 27 patients (34 eyes) with retinoblastoma who received external beam radiation as initial treatment at Hahnemann University Hospital from October 1980 to December 1991 and have been followed for at least 1 year. Of the 34 eyes, 14 were Groups I-II (Reese-Ellsworth classification), 7 were Group III, and 13 were Groups IV-V. Doses ranged from 34.5-49.5 Gy (mean 44.3 Gy, median 45 Gy) in 1.5-2.0 Gy fractions generally delivered through anterior and lateral wedged pair fields. RESULTS: At a mean follow up of 35.2 months (range 12-93 months), local tumor control was obtained in 44% (15 out of 34) of eyes with external beam radiation alone. Salvage therapy (plaque brachytherapy, cryotherapy, and/or photocoagulation) controlled an additional 10 eyes (29.5%), so that overall ocular survival has been 73.5%. Local tumor control with external beam radiotherapy alone was obtained in 78.5% (11 out of 14) of eyes in Groups I-II, but in only 20% (4 out of 20) of eyes in Groups III-V. A total of 67 existing tumors were identified prior to treatment in the 34 treated eyes and local control with external beam radiation alone was obtained in 87% (46 out of 53) of tumors measuring 15 mm or less and in 50% (7 out of 14) of tumors measuring more than 15 mm. When analyzing patterns of failure in the 19 eyes that relapsed, a total of 28 failure sites were identified and consisted of progression of vitreous seeds in seven instances (25% of failure sites) recurrences from previously existing tumors in 10 instances (36% of failure sites) and development of new tumors in previously uninvolved retina in 11 instances (39% of failure sites). CONCLUSIONS: 1) We find that external beam radiation to a dose of 45 Gy in fractions of 1.5 to 2.0 Gy provides adequate tumor control in retinoblastoma eyes Groups I-II (Reese-Ellsworth classification) or tumors measuring 15 mm in diameter or less. Eyes in more advanced group staging or containing tumors larger than the 15 mm seem to require higher radiation doses. We propose treatment guidelines for external beam radiation of retinoblastoma that specifically take into account the important clinical variables of tumor stage and patient age. 2) External beam radiation does not prevent the appearance of new tumors in clinically uninvolved retina. Therefore, the traditional belief that external beam radiation can treat the retina "prophylactically" should be seriously questioned. Due to this finding and their significant less morbidity, focal treatment modalities (plaque brachytherapy, photocoagulation, and/or cryotherapy), when clinically feasible, should be considered the treatment of choice for intraocular retinoblastoma. External beam radiation should be considered only when focal treatment modalities are not clinically indicated.

Metastatic tumours to the conjunctiva: report of 10 cases.

AIMS/BACKGROUND: Ten patients with metastatic tumours to the conjunctiva and the clinical aspects of this rare form of ocular metastasis are described in this study. METHOD: All patients with ocular and adnexal metastatic tumours referred to an ocular oncology service were reviewed and those having conjunctival metastases were studied for the site of their primary tumour, clinical features, and treatment of the conjunctival tumour, associated ocular and systemic findings, and the patients' outcome. RESULTS: The primary malignancy was carcinoma of the breast in four, lung cancer in two, laryngeal carcinoma in one, cutaneous melanoma in two, and unknown in one patient. The conjunctival metastases appeared after the primary tumour over a mean period of 44 (8-130) months. They were solitary in eight cases, located in bulbar conjunctiva in six, palpebral conjunctiva in two, and in limbus and forniceal conjunctiva in one patient each. The tumour was yellow in colour in seven patients, red in two, and brown in one. Eight patients also had metastases to other ocular structures. Seven patients received external beam radiotherapy to the affected eye, two were managed by excisional biopsy, and one with chemotherapy. The mean survival after the diagnosis of conjunctival metastasis was nine (range 2-26) months. CONCLUSION: Metastatic tumours to the conjunctiva appear at an advanced stage of the systemic disease when there are other ocular and organ metastases. The presence of a conjunctival mass in a patient with a prior systemic cancer should alert the ophthalmologist to the possibility of a conjunctival metastasis and evaluation should be pursued.

Mail consultations in ophthalmology. The Tenth Richard E. Hoover Lecture.

BACKGROUND: Although a number of diagnostic and therapeutic methods are available to assist the ophthalmologist, relatively little attention has been given to mail consultations. By this method, a clinical summary and photographs, fluorescein angiograms, ultrasonograms, and/or other relevant materials are mailed to a consultant who then renders an opinion by telephone and/or return mail. MATERIALS AND METHODS: The records of all mail consultations that were sent to the senior author and his colleagues during a 20 year period were reviewed to determine the total number of mail consultations, the reasons for the consultations, and the diagnoses and therapeutic recommendations that were made by the consultant. RESULTS: A total of 1357 mail consultations were received during the 20 year period, with a progressively increasing number of consultations each year. Consultations were received from 757 physicians representing all 50 states in the United States and 32 other countries. Because of the authors' subspecialty in ocular oncology and medical retinal diseases, the majority of the consultations received were related to those topics. In many cases, the initial diagnosis and treatment plan were altered based on our opinion through mail consultation. Based on the material received, the recommendations that we made included observation in 635 cases, enucleation in 152, surgical excision of a lesion in 120, plaque radiotherapy in 102, laser photocoagulation in 81, systemic evaluation in 40, external beam irradiation in 36, fine needle aspiration biopsy in 33, orbital exenteration in 25, chemotherapy in 21, and cryotherapy in 14. CONCLUSION: Although not as ideal as direct patient examination, mail consultation can be an effective method of making or confirming a diagnosis and obtaining a therapeutic opinion. Although the authors have received mail consultations related to ocular oncology, this method may be applicable to other subspecialties in ophthalmology and to general medicine.

Conservative treatment of retinoblastoma. The use of plaque brachytherapy.

Retinoblastoma is the most common intraocular malignancy in childhood. The tumor arises from multipotential retinal cells. Treatment options include enucleation, external beam radiotherapy, episcleral plaque radiotherapy, photocoagulation, cryotherapy or a combination of these modalities. In retinoblastoma 10% have a positive family history and of the remaining 90%, 35% represent germinal chromosomal mutations while 65% represent somatic chromosomal mutations. Therefore, approximately 40% of all retinoblastomas are hereditary and are transmitted as a highly penetrant autosomal dominant trait. In the Wills Eye/Hahnemann University experience an analysis of 400 consecutive patients, 103 tumors in 103 eyes were treated with solitary plaque radiotherapy. Tumor regression was observed in all patients initially. After 40 months mean follow-up, persistent regression was observed in 89 cases (87%) and recurrences in 13 cases (13%). Of the 13 recurrences, five were in the group treated primarily (5/31) and eight in the group treated after failing other modalities (8/72). Plaque brachytherapy is an important tool in the management of retinoblastoma. Our preliminary data suggest that plaque brachytherapy is an effective treatment modality for primary treatment as well as after failure using other modalities.

Retinoblastoma manifesting as orbital cellulitis.

Five children with previously undiagnosed retinoblastoma had signs of unilateral orbital cellulitis and were treated with systemic antibiotics, corticosteroids, or both. When retinoblastoma was finally diagnosed clinically, radiologists believed in every case that, on the basis of the soft-tissue swelling seen with computed tomography, there was orbital extension of the tumor. However, intraoperative and histopathologic observations disclosed no demonstrable orbital tumor involvement. The affected eyes all had neovascular glaucoma, and all harbored highly necrotic tumors that were contained within the eye. We concluded that orbital inflammation can occur with retinoblastoma confined to the eye and that signs of orbital cellulitis do not necessarily imply orbital extension of the tumor.

Magnetic resonance imaging in choroidal osteoma.

High resolution magnetic resonance imaging (MRI) with surface coil and contrast material was used to demonstrate the presence of bone in choroidal osteoma. Contrary to initial impressions, choroidal osteoma does not show typical negative image of the bone in MRI scans. The ossifying tumor of the choroid appears as a bright (hyperintense) signal on T1-weighted images and as an area of relative low intensity on T2-weighted images. On contrast T1-weighted scans, the tumor showed gadolinium-DPTA (Gd-DPTA) enhancement. These MRI findings are discussed in relation with histopathologic features of choroidal osteoma and the presence of fat marrow in the intertrabecular spaces of the bone at the level of the choroid.

Current alternatives in the management of posterior uvea melanomas.

The management of malignant melanomas of the posterior uvea recently has become a topic of great controversy. The traditional treatment by enucleation of the tumor-containing eye has recently been challenged by a number of authorities, and clinicians more frequently are using alternative methods of management when possible. Current management can range from periodic observation and fundus photography of selected small lesions that appear dormant, to photocoagulation, radiotherapy, or local resection in the case of growing tumors in eyes with useful or salvageable vision. In cases where the tumor is far advanced and there is no hope of useful vision, enucleation is often inevitable. The choice of therapy is a complex issue and each case must be individualized. In selecting a therapeutic approach certain factors must be carefully weighed. These include the size of the melanoma, its extent and location, its apparent activity, the condition of the opposite eye and the age, general health, and psychological status of the patient. Based on personal experience with approximately 3000 cases, the authors discuss their current indications for the various therapeutic techniques for posterior uvea melanomas.