Iris ring melanoma: fine needle biopsy.

AIMS: To delineate the diagnostic accuracy of fine needle biopsy in iris ring melanoma and determine the tumour related mortality of this neoplasm. METHODS: A retrospective analysis of 22 patients with iris melanomas that involve the entire 360 degrees of the anterior chamber angle. RESULTS: Iris ring melanomas were correctly diagnosed in all cases. In 11 of 16 cases (69%) a fine needle biopsy performed 180 degrees away from the main mass was positive for an iris ring melanoma. The tumour related mortality in iris ring melanoma cases was four of 22 patients (18%). Actuarial survival analysis showed a 10 year mortality (Kaplan-Meier) of 15%. CONCLUSION: A fine needle aspiration biopsy can be used to diagnose an iris ring melanoma. Iris ring melanomas have significant mortality compared with focal tumours.

20 MHz high frequency ultrasound assessment of scleral and intraocular conjunctival squamous cell carcinoma.

AIM: To assess in a prospective manner, high frequency ultrasound diagnosis of deep invasion by conjunctival squamous cell carcinoma. METHODS: Prospective, non-randomised case series comparing 20 MHz high frequency ultrasonographic and clinicopathological data. RESULTS: 20 MHz high frequency ultrasound delineated the degree of deep involvement of this tumour into the sclera, globe, and orbit. The results of ultrasonography correlated with the clinicopathological results. CONCLUSIONS: High frequency ultrasound is a useful diagnostic adjunctive test in patients with possible deep involvement by a conjunctival squamous cell carcinoma.

Uveal tumour resection.

AIM: To review the ocular retention rates, visual results, and metastases in uveal tumours managed with eye wall resection techniques. METHODS: This was a retrospective analysis of consecutive local uveal tumour resections performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data were performed. RESULTS: 138 eyes were scheduled for eye wall resection surgery. The mean age was 52 years (range 11-86 years). Tumours involved predominantly the iris in 14 cases, iris-ciliary body in 57, ciliary body alone in 18 patients, and in 49 cases the choroid was involved (ciliochoroidal, iris-ciliary body-choroid, or choroid). 125 eyes harboured melanomas; posterior tumours were more likely to have epithelioid cells (p<0.05). The mean follow up was 6 years. The mean clock hours in iris and iris-ciliary body tumours was 3.5. In tumours that involved the choroid the mean largest diameter was 12.9 mm and the mean thickness 8.5 mm. 105 of 138 (76%) eyes were retained. Histological assessment of surgical margins did not correlate evidence of tumour in enucleated eyes or metastatic disease. Surgical margins of more anterior tumours were more likely to be clear on histological evaluation (p<0.05). Approximately 53% of retained eyes had a final visual acuity of > or =20/40; visual results were significantly better in more anteriorly located tumours (p<0.05). All retained iris tumour cases had > or =20/40 final visual acuity. In tumours that involved the choroid nine of 31 retained eyes kept that level of visual acuity. Eight patients developed metastases; all metastatic events developed in patients with tumours that involved the choroid, and seven of eight were mixed cell melanomas. CONCLUSIONS: 76% of eyes were retained and 53% of these had a final visual acuity of > or =20/40. Only 7% of uveal melanoma patients developed metastatic disease with a mean follow up of 6 years. Survival did not appear to be compromised with eye wall resection and in very thick, more posterior melanomas it appeared that ocular retention and visual results were better than with radiation alone.

Amelanotic corneal melanoma after a blast injury.

PURPOSE: To report a case of a corneal melanoma after trauma. METHODS: Case report. RESULTS: A 68-year-old man sustained an ocular injury from a blast furnace explosion in 1958. In 1998, he underwent a penetrating keratoplasty for a corneal scar. Histologic examination and cell markers of the host button revealed intrastromal and subepithelial melanoma. No clinical or microscopic evidence of adjacent conjunctival or uveal melanoma was found. CONCLUSION: Melanoma of the cornea can present as a stromal opacity after trauma.

Eye-wall resection.

PURPOSE: To review the ocular retention rates, visual results, and metastases in uveal tumors managed with eye-wall resection techniques. METHODS: This was a retrospective analysis of uveal tumors selected for eye-wall resection with the surgical procedures performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data was performed. RESULTS: A total of 132 eyes were scheduled for eye-wall resection surgery. Mean patient age was 52 years (range, 11 to 86 years). Tumors involved the iris alone in 17 cases, the iris-ciliary body in 53, the ciliary body alone in 16, and the choroid (ciliochoroidal, iris-ciliary body-choroid, or choroid) in 46 cases. A total of 114 eyes harbored melanomas; tumors located more posteriorly were more likely to have epithelioid cells (P < .05). Mean follow-up was 6 years. Mean number of clock hours in iris and iris-ciliary body tumors was 3.5. In tumors that involved the choroid, the mean largest diameter was 12.6 mm and the mean thickness was 8.2 mm. Ninety-three (70%) of 132 eyes were retained. Histologic assessment of surgical margins did not correlate with either evidence of tumor in enucleated eyes or metastatic disease. Surgical margins of tumors located more anteriorly were more likely to be clear on histologic evaluation (P < .05). Approximately 56% of retained eyes had a final visual acuity of 20/40 or better; visual results were significantly better in tumors located more anteriorly (P < .05). All retained eyes with iris tumors had a final visual acuity of 20/40 or better. In tumors that involved the choroid, 8 of 25 retained eyes kept visual acuity of 20/40 or better. Metastases developed in 8 patients; all metastatic events developed in patients with tumors that involved the choroid, and 7 of 8 were mixed cell melanomas. CONCLUSIONS: Seventy percent of eyes were retained, and 56% of these had a final visual acuity of 20/40 or better. Only 7% of patients with uveal melanoma developed metastatic disease (mean follow-up, 6 years). Survival did not appear to be compromised with eye-wall resection, and in very thick melanomas located more posteriorly, ocular retention and visual results appeared to be better than that attained with radiation alone.

Coats' syndrome: long term follow up.

AIM: To increase the understanding of the long term results in pseudo-retinoblastoma eyes with infantile Coats' syndrome. METHODS: This study design was a retrospective case review. 10 patients were analysed who were initially referred with a diagnosis of retinoblastoma but had Coats' syndrome on the basis of ocular oncological evaluation. Vision, fundus photography, ultrasonography, and computed tomography scans were obtained and evaluated. Changes in vision and retinal status were measured. RESULTS: The initial age at presentation was 2.4 years (range 0.25-4 years). All patients had retinal detachment at diagnosis. Nine of 10 retinas were reattached after various treatments. Reattached retinas had closure of peripheral telangiectasia and visible intraretinal crystals. Vision was dismal. At last follow up (mean 8.8 years), only two patients had 20/400 or better visual acuities. Five eyes had no light perception despite early treatment to reattach the retina. Nine of 10 eyes remain cosmetically acceptable. One patient wore a cosmetic shell. CONCLUSIONS: Long term results indicate that these eyes can be salvaged and the retina reattached but the visual outcome is poor.

Combined nevi of the conjunctiva.

OBJECTIVE: To report the clinical and histologic features of combined nevi of the conjunctiva, a type of nevus that is not uncommon in the skin but rarely has been reported in the conjunctiva. METHODS: Conjunctival nevi and melanomas in the files of the University of California at San Francisco Eye Pathology Laboratory from 1984 to 1999 were reviewed for the presence of features of both standard nevocytic nevi and blue nevi. Clinical histories and, when available, clinical photographs were obtained. RESULTS: Thirty combined nevi were discovered between 1984 and 1999. One case before 1984 had been incorrectly diagnosed as a junctional nevus. The dendritic and spindle-shaped blue nevus cells had been overlooked because they were not recognized as distinct from the standard nevocytic nevus cells. The recognition of blue as well as a brown color, a deep as well as a superficial component in the lesion, or a history of pigmentation since birth may help to establish the correct clinical diagnosis and prevent an unnecessarily deep surgical resection. Although growth of the lesion or "satellites" in some may favor a clinical diagnosis of melanoma, no lesions in this series were malignant. CONCLUSION: Despite a paucity of reports of combined nevi of the conjunctiva in the medical literature, this type of nevus, a combination of a nevocytic and a blue nevus, is common and has been overlooked in the past.

Randomized trial of radiation for age-related macular degeneration.

PURPOSE: To assess external beam radiation efficacy for subfoveal neovascularization associated with age-related macular degeneration. METHODS: All patients were evaluated in the same institution. In this prospective trial, 27 eyes (27 patients) with subfoveal neovascularization associated with age-related macular degeneration were randomized to either single fraction radiation (750 centigray) or observation. Endpoints were assessed by fluorescein angiography and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. Examiners were masked to patient treatment status. Parametric and nonparametric statistical analyses were performed. RESULTS: Twenty-seven patients were entered into the trial with a mean age of 76 years (range, 64 to 89) and a mean follow-up of 17 months (range, 7 to 32). The visual acuity loss was slightly less in the irradiated group, a finding of borderline significance (P < .046). There was no significant difference in fluorescein angiographic evidence of subretinal neovascular membrane change in the control group vs the irradiated group. CONCLUSIONS: External beam radiation, at this dose and fractionation, did not appear harmful. There was slightly less visual loss in irradiated eyes. No difference in fluorescein angiographic characteristics of subfoveal neovascularization size or progression in eyes with age-related macular degeneration was noted.

Orbital lymphangioma: an analysis of 26 patients.

AIM: To evaluate retrospective data on the clinical findings, histological features, radiological diagnosis, and management outcomes in orbital lymphangioma. METHODS: Data on 26 orbital lymphangioma patients managed over 16 years were re-evaluated. The computed tomograph and magnetic resonance scans and histological slides were reviewed. Parametric techniques were used to assess correlations among clinical, radiological, and histopathological factors. RESULTS: At presentation proptosis was present in 85%, ptosis in 73%, and restrictive eye movements in 46% of patients. The accuracy of the initial radiology interpretations was 77%. 24 cases required one or more surgeries. The mean follow up was 9.2 years (range 1-14 years). 58% of patients developed recurrences. In cases that recurred, motility restriction was significantly more frequent at initial examination than cases without recurrence (p < 0.05). After therapy, 75% of patients were satisfied with their visual function and cosmetic appearance. CONCLUSIONS: Conservative management of orbital lymphangioma with multiple partial resections may achieve satisfactory results.

Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases.

AIM: To evaluate the clinical features, treatment results, and recurrence rates in patients with either intraepithelial or invasive squamous cell carcinoma of the conjunctiva. METHODS: Retrospective analysis of 60 cases (22 conjunctival intraepithelial and 38 invasive squamous cell carcinomas) to determine patterns of clinical presentation, aetiological factors, and treatment results. The mean patient age was 64 years old. 70% of the patients were male. Patients were treated with a variety of therapies, depending on the degree of tumour involvement; most cases were treated with frozen section controlled excision and adjunctive cryotherapy. Modified eye wall resection or enucleation was done for intraocular invasion and exenteration was done for orbital involvement. RESULTS: Red eye (68%) and ocular irritation (57%) were the most common presenting symptoms. 44% of the patients had other eye findings consistent with extensive solar exposure. 20% of the patients had a history of malignant skin tumours. Visceral malignancies developed in 8%. Scleral involvement was present in 14 (37%), intraocular involvement in five (13%), and orbital invasion in four (11%) cases with invasive squamous cell carcinoma. After a mean follow up of 56 months (18-226 months) the rate of new or recurrent tumours was 4.5% for intraepithelial squamous carcinoma and 5.3% for invasive squamous cell carcinoma. No patient developed metastases or tumour related deaths. CONCLUSION: Excision with intraoperative control of the surgical margins and adjunctive cryotherapy results in good tumour control rates.

Combined nevi of the conjunctiva.

PURPOSE: To report the clinical and histologic features of combined nevi of the conjunctiva, a type of nevus that is not uncommon in the skin but has rarely been reported in the conjunctiva. METHODS: Conjunctival nevi and melanomas from the files of the University of California, San Francisco, eye pathology laboratory were reviewed from 1984 to 1999 for the presence of features of both standard nevocytic nevi and blue nevi. Clinical histories and, when available, clinical photographs were obtained. RESULTS: Thirty-one combined nevi were discovered during the 15-year period between 1984 and 1999. One case before 1984 had been incorrectly diagnosed as a junctional nevus. The dendritic and spindle-shaped blue nevus cells had been overlooked because they were not recognized as distinct from the standard nevocytic nevus cells. The recognition of a blue as well as a brown color, a deep as well as a superficial component in the lesion, or a history of pigmentation since birth may help to establish the correct clinical diagnosis and prevent an unnecessarily deep surgical resection. Although growth of the lesion or "satellites" in some patients may favor a clinical diagnosis of melanoma, none of the lesions in this series were malignant. CONCLUSION: Despite a paucity of reports of combined nevi of the conjunctiva in the medical literature, this type of nevus--a combination of a nevocytic and a blue nevus--is common and has been overlooked in the past.

A comparison of cause-specific melanoma mortality and all-cause mortality in survival analyses after radiation treatment for uveal melanoma.

OBJECTIVE: To determine the causes and patterns of mortality after uveal melanoma radiation. DESIGN: A cohort study from a single institution was performed. Mortality was modeled using semiparametric survival techniques. All cause and cause-specific mortality analyses were performed. Mortality was compared with expected mortality from the U.S. census data. PARTICIPANTS: A total of 731 patients were studied, and 710 (97%) of these had medium or large melanomas. The mean tumor diameter was 11.3 mm, and the mean tumor thickness was 5.8 mm. Ciliary body was involved in 122 (17%) of patients. Complete follow-up was available on 99.6% (728 of 731) of patients. MAIN OUTCOME MEASURES: The authors analyzed the distribution and causes of post-treatment mortality. RESULTS: The 5- and 10-year all-cause Kaplan-Meier survival rates were 75.6% and 62.3%, respectively. Both melanoma risk factors (older age, ciliary body involvement, and larger tumor diameter) and nonmelanoma risk factors (older age and medical condition) were significant prognostic factors of all-cause mortality. Deaths from nonmelanoma causes accounted for 91 (42.3%) of 215 deaths. The 5-year and 10-year estimates of nonmelanoma deaths were 8.3% and 15.9%, respectively. Nonmelanoma mortality was similar to that observed in the general U.S. population (91 observed, 98.1 expected). Melanoma metastases accounted for 124 (57.7%) of 215 deaths. The 5- and 10-year estimates for probability of metastatic death were 16.1% and 21.8%, respectively. The largest tumor diameter was the best predictor for melanoma mortality; ciliary body involvement, older age, and distance from the fovea also were significant in multivariate analyses. CONCLUSION: A significant proportion of patients with uveal melanoma die of nonmelanoma causes after radiation. In analyzing prognostic factors, considerable information may be lost if analyses are based on all-cause mortality rather than cause-specific mortality.

Bilateral multifocal choroidal carcinoid: long-term follow-up without treatment.

PURPOSE: To report a minimally symptomatic patient with bilateral carcinoid tumors metastatic to the choroid who was followed up for 42 months without any treatment. METHOD: Case report. RESULTS: A 54-year-old white man with a history of bronchial carcinoid tumor had bilateral multiple carcinoid tumors metastatic to the choroid. Follow-up for 42 months without treatment demonstrated no growth of the choroidal tumors, and corrected visual acuity remained RE, 20/20 and LE, 20/25. Systemic status also remained stable. CONCLUSIONS: Carcinoid tumors metastatic to the choroid may remain stationary for an extended period. Treatment may be deferred until tumor growth, exudative retinal detachment, or substantial impairment of vision develops.

Ten-year follow-up of helium ion therapy for uveal melanoma.

PURPOSE: To examine the results of helium ion irradiation in 218 patients with uveal melanoma treated more than 10 years ago. METHOD: A retrospective review was made of 218 patients (218 eyes) treated with helium ion radiation for uveal melanoma between 1978 and 1984. RESULTS: After helium ion irradiation, 208 (95.4%) of 218 eyes had local tumor control. Ten years after irradiation, 46 (22.4%) of 218 eyes had been enucleated; the majority of enucleations (37 of 46) resulted from anterior ocular segment complications. Ten years after radiation, 102 (46.8%) of the 218 patients were dead; 51 had non-melanoma-related deaths and 51 had died of metastatic melanoma. Best-corrected visual acuity after radiation was greater than 20/40 in 21 (23%) of 93 eyes of the patients who were alive and who had retained their eyes 10 or more years after treatment. In patients with tumors less than 6 mm in height and more than 3 mm distant from the nerve or the fovea, 13 (72%) of 18 retained visual acuity greater than 20/40. In contrast, only 11% of the patients with either thicker tumors or those close to the nerve or fovea retained that level of visual acuity. CONCLUSIONS: Helium ion irradiation of uveal melanoma is associated with good local tumor control and reasonable retention of the treated eye 10 years after treatment. In eyes with tumors less than 6 mm in thickness and more than 3 mm distant from the optic nerve and fovea, many retain excellent vision.

Metastatic risk for distinct patterns of postirradiation local recurrence of posterior uveal melanoma.

OBJECTIVE: The purpose of the study is to compare the prognostic significance of horizontal/marginal versus vertical/diffuse patterns of postirradiation local recurrence of posterior uveal melanoma. DESIGN: The study design was a nonrandomized, retrospective clinical study. Semiparametric and nonparametric statistical techniques were used. PARTICIPANTS: Seven hundred sixty-six posterior uveal melanoma patients were studied. INTERVENTION: Either iodine-125 plaque or helium ion radiation therapy was performed. MAIN OUTCOME MEASURES: Local tumor recurrence and systemic metastasis were measured. RESULTS: Local tumor recurrence was detected in 66 (8.6%) of 766 irradiated tumors. The 5-year actuarial rate of local recurrence was 10%. The recurrence pattem was horizontal/marginal in 27 patients (41%) and vertical/diffuse in 39 patients (59%). Systemic metastasis was detected in 5 patients (19%) with horizontal/marginal recurrence and in 19 patients (49%) with vertical/diffuse recurrence. After known metastatic risk factors were controlled, the relative risk for metastasis was 2.2 for horizontal/marginal recurrence and 5.1 for vertical/diffuse recurrence (P = 0.05). The actuarial rate of systemic metastasis was 2.9% per year for all patients, 6.3% per year for patients with horizontal/marginal recurrence, and 15.5% per year for patients with vertical/diffuse recurrence. CONCLUSIONS: Postirradiation local recurrence of posterior uveal melanoma is a risk factor for systemic metastasis. Vertical/diffuse recurrences may be associated more strongly with metastatic disease than horizontal/marginal recurrences.

15 years experience with helium ion radiotherapy for uveal melanoma.

PURPOSE: To review the long-term experience of helium ion therapy as a therapeutic alternative to enucleation for uveal melanoma, particularly with respect to survival, local control, and morbidity. METHODS AND MATERIALS: 347 patients with uveal melanoma were treated with helium ion RT from 1978-1992. A nonrandomized dose-searching study was undertaken, with doses progressively reduced from 80 GyE in five fractions to 48 GyE in four fractions, given in 3-15 days, mean of 7 days. RESULTS: Local control was achieved in 96% of patients, with no difference in the rate of local control being seen at 80, 70, 60, or 50 GyE in five fractions. At the lowest dose level of 48 GyE in four fractions, the local control rate fell to 87%. Fifteen of 347 patients (4%) had local regrowth in the eye requiring enucleation (12 patients), laser (1 patient) or reirradiation (2 patients). The time of appearance of local regrowth ranged from 4 months to 5 years posttreatment, with 85% occurring within 3 years. Of the 347 patients, 208 are alive as of May 1, 1997. The median follow up of all patients is 8.5 years, range 1-17 years. Kaplan-Maier (K-M) survival is 80% at 5 years, 76% at 10 years, and 72% at 15 years posttreatment. Patients with tumors not involving the ciliary body have a 15-year K-M survival of 80%. The results for patients whose tumors involved the ciliary body are poor, with a 15-year K-M survival of 43%. Seventy-five percent of patients with tumors at least 3.0 mm from the fovea and optic nerve, and initial ultrasound height less than 6.0 mm, retained vision of 20/200 or better posttreatment. Patients with tumors larger than 6 mm in thickness, or with tumors lying close to the optic nerve or fovea, have a reduced chance of retaining useful vision. The enucleation rate is 19%, 3% for local failure and 16% because of complications of the helium RT, particularly neovascular glaucoma, which occurred in 35% of patients. CONCLUSIONS: Local control and retention of the eye are excellent. Complications of therapy reduce vision and eye preservation. Twenty-four percent of patients manifested distant metastases 6 to 146 months posttreatment, mean of 43 months, median of 36 months. Late-appearing distant metastases do not appear to be caused by persistent tumor in the eye. The risk of metastases is high for patients with tumors greater than 7 mm in initial ultrasound height (37%), anterior tumors involving the ciliary body (47%), and in those with local failure (53%). Patients with tumors not involving the ciliary body and initial dimensions less than 10 mm had only an 8% chance of death from melanoma. A search for effective adjuvant therapy is needed for patients at high risk of metastases (large tumors, ciliary body involved, local regrowth in eye).

Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma.

PURPOSE: The purpose of this investigation is to delineate the risk factors in the development of neovascular glaucoma (NVG) after helium-ion irradiation of uveal melanoma patients and to propose treatment technique that may reduce this risk. METHODS AND MATERIALS: 347 uveal melanoma patients were treated with helium-ions using a single-port treatment technique. Using univariate and multivariate statistics, the NVG complication rate was analyzed according to the percent of anterior chamber in the radiation field, tumor size, tumor location, sex, age, dose, and other risk factors. Several University of California San Francisco-Lawrence Berkeley National Laboratory (LBNL) patients in each size category (medium, large, and extralarge) were retrospectively replanned using two ports instead of a single port. By using appropriate polar and azimuthal gaze angles or by treating patients with two ports, the maximum dose to the anterior segment of the eye can often be reduced. Although a larger volume of anterior chamber may receive a lower dose by using two ports than a single port treatment. We hypothesize that this could reduce the level of complications that result from the irradiation of the anterior chamber of the eye. Dose-volume histograms were calculated for the lens, and compared for the single and two-port techniques. RESULTS: NVG developed in 121 (35%) patients. The risk of NVG peaked between 1 and 2.5 years posttreatment. By univariate and multivariate analysis, the percent of lens in the field was strongly correlated with the development of NVG. Other contributing factors were tumor height, history of diabetes, and vitreous hemorrhage. Dose-volume histogram analysis of single-port vs. two-port techniques demonstrate that for some patients in the medium and large category tumor groups, a significant decrease in dose to the structures in the anterior segment of the eye could have been achieved with the use of two ports. CONCLUSION: The development of NVG after helium-ion irradiation is correlated to the amount of lens, anterior chamber in the treatment field, tumor height, proximity to the fovea, history of diabetes, and the development of vitreous hemorrhage. Although the influence of the higher LET deposition of helium-ions is unclear, this study suggests that by reducing the dose to the anterior segment of the eye may reduce the NVG complications. Based on this retrospective analysis of LBNL patients, we have implemented techniques to reduce the amount of the anterior segment receiving a high dose in our new series of patients treated with protons using the cyclotron at the UC Davis Crocker Nuclear Laboratory (CNL).