Patrick De Potter

Risk factors for growth and metastasis of small choroidal melanocytic lesions.

PURPOSE To investigate the clinical features that predict growth and metastasis of an unselected group of small melanocytic choroidal tumors. METHODS A retrospective review was performed on 1329 patients with small melanocytic choroidal tumors measuring 3 mm in thickness or less. Clinical parameters of the patient and tumor were extracted and analyzed for their relationship to eventual tumor growth and metastasis using a Cox proportional hazards regression model. RESULTS Tumor growth was documented in 18% of patients. The factors predictive of tumor growth (multivariate analysis) included greater tumor thickness, posterior tumor margin touching optic disc, symptoms of flashes, floaters, and blurred vision, orange pigment on the tumor surface, and the presence of subretinal fluid. The relative risk (rr) was greatest for initial tumor thickness > 2.0 mm (rr 5.2) and posterior margin touching the optic disc (rr 2.6). After adjusting for significant tumor variables, the effect of interventional tumor treatment showed a decreasing risk for tumor growth as compared to continued observation without treatment. Of 1329 patients, 35 (3%) developed metastases. The factors predictive of metastases (multivariate analysis) included: posterior tumor margin touching the optic disc, documented growth, and greater tumor thickness. The relative risk for metastases was greatest for tumor thickness 1.1-3.0 mm (rr 8.8) and growth (rr 3.2). CONCLUSION Of small choroidal melanocytic tumors measuring 3 mm or less in thickness at the time of initial examination, 18% demonstrate growth and 3% metastasize during the period of followup. Based on this analysis, the clinical features of these tumors can be used to estimate the risk for tumor growth and metastases and assist the clinician with patient management.

Fine-needle Aspiration Biopsy of Suspected Intraocular Tumors: The 1992 Urwick Lecture

BACKGROUND Fine-needle aspiration biopsy recently has been used as a diagnostic modality for selected intraocular tumors and simulating conditions. However, the value of fine-needle aspiration biopsy for intraocular tumors previously has not been clarified. METHODS Transocular fine-needle aspiration biopsy was performed on selected patients who had intraocular lesions that were suspected clinically to be neoplasms but in which there was diagnostic uncertainty based on noninvasive clinical evaluation. These cases were analyzed to determine accuracy, complications, and limitations of the technique. RESULTS Of 6500 patients referred to the Oncology Service for evaluation of possible intraocular tumor, transocular fine-needle aspiration biopsy was used clinically in 159 cases (2.4%). It proved to be a reliable diagnostic method for intraocular malignancies such as uveal melanoma, uveal metastasis, retinoblastoma, lymphoma, and leukemia. In the 140 cases (88%) in which adequate cytologic material was obtained, the sensitivity rate was 100% and the specificity rate was 98%. In 19 cases where the cytologic material was too scant to render a diagnosis, the sensitivity rate was 84% and the specificity rate was 98%. The problem of insufficient material for cytologic diagnosis has been greatly minimized with the recent use of a 22-gauge needle. The main complication was localized intraocular hemorrhage. Retinal detachment and tumor recurrence have not been observed. CONCLUSIONS Transocular fine-needle aspiration biopsy is a safe and reliable diagnostic method for suspected intraocular tumors and inflammatory conditions in which noninvasive diagnostic modalities have failed to establish the diagnosis and in which cytologic verification of the diagnosis is necessary to institute appropriate treatment. Although the authors have had few complications with fine-needle aspiration biopsy, the technique should be reserved for selected cases where the diagnosis has not been established by less-invasive diagnostic measures.

COMBINED CHEMOREDUCTION AND ADJUVANT TREATMENT FOR INTRAOCULAR RETINOBLASTOMA

OBJECTIVE The purpose of the study is to investigate chemoreduction and adjuvant treatment (AT) for retinoblastoma and its effect on complete retinal tumor control, vitreous seed control, and subretinal seed control. DESIGN The study design was a prospective, nonrandomized clinical trial. PARTICIPANTS There were 130 intraocular retinoblastomas in 52 eyes of 32 consecutive patients observed for at least 1 year after initiation of treatment. INTERVENTION Treatment with chemoreduction using vincristine, etoposide, and carboplatin (VEC) and adjuvant treatment (+ AT) (cryotherapy, laser photocoagulation, thermotherapy, chemothermotherapy, plaque radiation therapy, or external beam radiation therapy) were assessed. MAIN OUTCOME MEASURES The effect of chemoreduction for 6 cycles (VEC x 6) versus fewer than 6 cycles (VEC x <6) on retinoblastoma control was analyzed. Furthermore, the impact of adjuvant treatment (+ AT) versus no adjuvant treatment (no AT) on retinoblastoma control was analyzed. RESULTS Retinal tumors showed favorable initial regression with chemoreduction. Adjuvant treatment was applied to 93% of the retinal tumors after chemoreduction and only 2% recurred over the mean follow-up of 17 months (range 13-27 months). Vitreous seeds and subretinal seeds showed initial regression and often complete disappearance with chemoreduction. In those eyes with seeds before treatment, the addition of AT to VEC for 6 cycles decreased the vitreous seed recurrence from 75% to 0% (P = 0.04) and also decreased the subretinal seed recurrence from 67% to 0% (P = 0.003). More important, when considering that enucleation or external beam radiation therapy was the only other treatment option for these 52 eyes, the authors were successful in avoiding these methods in 42% of cases. Of the 36 eyes classified as Reese-Ellsworth group 5, there was 78% ocular salvage, and external beam radiation therapy was avoided in 25% of these eyes. There was a 100% ocular salvage in the group 5 eyes that received VEC for 6 cycles + AT to retinal tumors and seeds. CONCLUSIONS Chemoreduction and AT to intraocular retinoblastoma and its seeds provides good retinal tumor control, even in eyes with advanced disease. Chemoreduction alone generally is not adequate to achieve complete tumor seed control. Cautious follow-up of affected patients is recommended because the risk for recurrent vitreous and subretinal seeds is substantial and proper treatment is critical for salvaging the eye.

Metastatic Tumors to the Iris in 40 Patients

PURPOSE Metastatic cancer to the iris is rare, and the best approaches to clinical recognition and treatment of this neoplasm are not widely known. We reviewed a series of patients with metastatic cancer to the iris and elucidated the clinical variations, diagnostic approaches, and treatment of this neoplasm. METHODS The files of the Wills Eye Hospital Ocular Oncology Service were surveyed, and cases of metastatic cancer to the iris were extracted for further analysis. General data, systemic data, tumor characteristics, diagnostic methods used, treatment, and prognosis were tabulated. RESULTS Of 512 patients with uveal metastasis, the iris was involved in 40 (7.8%). The metastasis originated from breast carcinoma in 16 cases, lung carcinoma in 11, carcinoid tumor in three, melanoma in three, colonic carcinoma in two, and esophageal, laryngeal, prostate, and kidney carcinoma in one case each. In one case the primary tumor was never identified. There was no history of primary cancer in 13 (32%) of 40 patients. All iris metastases were unilateral, and secondary glaucoma was present in 15 (38%). Fine-needle aspiration biopsy of the iris lesion helped to establish the diagnosis in 11 cases. Treatment with chemotherapy, radiotherapy, or both, achieved local tumor control in all patients. The overall mean survival was 20 months and the median survival was 13 months after diagnosis of the iris metastasis. CONCLUSIONS Iris metastasis can show a spectrum of clinical variations, but its features are generally distinctive enough to differentiate it from other intraocular neoplasms and inflammations. Treatment consists of chemotherapy, which was sometimes combined with ocular irradiation. The visual prognosis was good but the systemic prognosis was generally poor.

Histopathologic Evidence of Fibrovascular Ingrowth Four Weeks After Placement of the Hydroxyapatite Orbital Implant

We studied the histopathologic findings after placement of an orbital hydroxyapatite implant in a patient. The implant was placed after enucleation for a choroidal melanoma and was removed four weeks later because histopathologic examination of the enucleated globe disclosed tumor invasion of the optic nerve that necessitated further orbital tissue removal. Our histopathologic findings confirm that there is significant ingrowth of fibrovascular tissue in these implants, even within weeks of implantation.

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.

Fine-needle aspiration biopsy of suspected intraocular tumors.

Background: Fine-needle aspiration biopsy recently has been used as a diagnostic modality for selected intraocular tumors and simulating conditions. However, the value of fine-needle aspiration biopsy for intraocular tumors previously has not been clarified. Methods: Transocular fine-needle aspiration biopsy was performed on selected patients who had intraocular lesions that were suspected clinically to be neoplasms but in which there was diagnostic uncertainty based on noninvasive clinical evaluation. These cases were analyzed to determine accuracy, complications, and limitations of the technique. Results: Of 6500 patients referred to the Oncology Service for evaluation of possible intraocular tumor, transocular fine-needle aspiration biopsy was used clinically in 159 cases (2.4%). It proved to be a reliable diagnostic method for intraocular malignancies such as uveal melanoma, uveal metastasis, retinoblastoma, lymphoma, and leukemia. In the 140 cases (88%) in which adequate cytologic material was obtained, the sensitivity rate was 100% and the specificity rate was 98%. In 19 cases where the cytologic material was too scant to render a diagnosis, the sensitivity rate was 84% and the specificity rate was 98%. The problem of insufficient material for cytologic diagnosis has been greatly minimized with the recent use af a 22-gauge needle. The main complication was localized intraocular hemorrhage. Retinal detachment and tumor recurrence have not been observed. Conclusions: Transocular fine-needle aspiration biopsy is a safe and reliable diagnostic method for suspected intraocular tumors and inflammatory conditions in which noninvasive diagnostic modalities have failed to establish the diagnosis and in which cytologic verification of the diagnosis is necessary to institute appropriate treatment. Although the authors have had few complications with fine-needle aspiration biopsy, the technique should be reserved for selected cases where the diagnosis has not been established by less-invasive diagnostic measures. Ophthalmology 1993;100:1677-1684

Uveal Melanoma in Teenagers and Children: A Report of 40 Cases

A review of 3706 consecutive patients with uveal melanoma revealed that 40 patients (1.1%) were age 20 years or younger at the time of diagnosis. The youngest patient was age 6 years but the majority of patients (78%) were between 15 and 20 years old. The tumor occurred in the iris in 5 cases (12%) and in the posterior uvea in 35 cases (88%). The mean largest tumor dimension and thickness was 10 mm and 5 mm, respectively. In all cases, the diagnosis of uveal melanoma was suspected before referral, and misdirected treatment was avoided. The tumor was initially treated by enucleation in 24 cases (60%), local resection in 7 (18%), plaque radiotherapy in 3 (8%), and observation in 6 (15%). Secondary treatment was required in 7 cases in the form of enucleation (4 cases), ablative laser (1 case), plaque radiotherapy (1 case), and exenteration (1 case). The mean follow-up period was 68 months (median, 48 months) from the time of treatment, and only one patient died of metastases (from a massive ciliochoroidal melanoma 33 months after treatment). The remainder of the group of young patients are alive and healthy. Cumulative survival rates show that 96% of young patients with uveal melanoma survive at the 5-year period.

Clinical variations of trilateral retinoblastoma: A report of 13 cases

Of 440 consecutive children with retinoblastoma whom we treated between April 1972 and April 1992, 13 (3%) developed a midline intracranial neoplasm. Four of these 13 patients had bilateral familial retinoblastoma, 7 had bilateral sporadic retinoblastoma, and 1 patient had unilateral familial retinoblastoma. The twin brother of the latter patient developed pinealoblastoma without retinoblastoma. In this series, the incidence of trilateral retinoblastoma was 8% of all bilateral familial retinoblastoma and 5% of all bilateral sporadic retinoblastoma. The retinoblastoma was diagnosed at a mean age of 4.5 months and the midline intracranial tumor was diagnosed at a mean age of 23 months. The mean time interval between the diagnosis of retinoblastoma and the intracranial tumor was 22 months (range, 0 to 48 months). Seven patients (55%) were asymptomatic and their intracranial neoplasm was found on routine brain-imaging studies. The primary intracranial neoplasm had a pineal location in 10 cases and parasellar location in three cases. Despite aggressive combined treatment, 12 patients (92%) have died at a mean interval of 11 months after the diagnosis of intracranial malignancy. The mean survival of patients with midline intracranial neoplasm who were asymptomatic was significantly longer than that of symptomatic patients (P = .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Magnetic Resonance Imaging in the Evaluation of the Hydroxyapatite Orbital Implant

The role of magnetic resonance imaging (MRI) in the assessment of fibrovascular ingrowth in the integrated hydroxyapatite orbital implant is evaluated. Fifteen patients who underwent enucleation and placement of a hydroxyapatite orbital implant were evaluated for degree of implant vascularity with gadolinium-DPTA-enhanced MRI with surface coil before drilling the implant. On T1-weighted images, the hydroxyapatite sphere appeared with intermediate signal. After gadolinium-DPTA administration, all patients showed an enhancement in the implant consistent with the presence of fibrovascular ingrowth. The enhancement was most notable in the peripheral portions of the sphere and was seen as early as 5 months after implantation. Comparison of gadolinium-DPTA-enhanced MRI with contrast-enhanced computed tomography, ultrasonography, and color Doppler imaging suggests that these latter techniques are not as helpful in the detection of the fibrovascular tissue in the orbital implant. Bone scan, a technique used by many surgeons, demonstrates fibrovascular ingrowth, but it is limited by its one-dimensional low-resolution image. Because of its three-dimensional capability and its highest resolution, contrast-enhanced MRI with surface coil appears to be the best imaging method for evaluating the hydroxyapatite orbital implant and its fibrovascular ingrowth.