Arman Mashayekhi

Metastasis of Uveal Melanoma Millimeter-by-Millimeter in 8033 Consecutive Eyes

OBJECTIVE To determine the rate of metastasis of uveal melanoma on the basis of tumor thickness in millimeters. METHODS Retrospective medical record review. RESULTS The mean (median) patient age was 58 (59) years. A total of 8033 eyes were examined. Of the 285 eyes with iris melanoma, the mean tumor thickness was 2.7 mm and metastasis occurred in 0.5%, 4%, and 7% at 3, 5, and 10 years, respectively. Of the 492 eyes with ciliary body melanoma, the mean tumor thickness was 6.6 mm and metastasis occurred in 12%, 19%, and 33% at 3, 5, and 10 years, respectively. Of the 7256 eyes with choroidal melanoma, the mean tumor thickness was 5.5 mm and metastasis occurred in 8%, 15%, and 25% at 3, 5, and 10 years, respectively. For all uveal melanoma, metastasis at 5, 10, and 20 years was 6%, 12%, and 20% for small melanoma (0-3.0 mm thickness), 14%, 26%, and 37% for medium melanoma (3.1-8.0 mm), and 35%, 49%, and 67% for large melanoma (>8.0 mm). More specifically, metastasis per millimeter increment at 10 years was 6% (0-1.0 mm thickness), 12% (1.1-2.0 mm), 12% (2.1-3.0 mm), 16% (3.1-4.0 mm), 27% (4.1-5.0 mm), 28% (5.1-6.0 mm), 29% (6.1-7.0 mm), 41% (7.1-8.0 mm), 50% (8.1-9.0 mm), 44% (9.1-10.0 mm), and 51% (>10.0 mm). Clinical factors predictive of metastasis by multivariate analysis included increasing patient age, ciliary body location, increasing tumor diameter, increasing tumor thickness, having a brown tumor, and the presence of subretinal fluid, intraocular hemorrhage, or extraocular extension. CONCLUSION Increasing millimeter thickness of uveal melanoma is associated with increasing risk for metastasis.

Conjunctival Melanoma: Outcomes Based on Tumor Origin in 382 Consecutive Cases

PURPOSE To evaluate prognostic factors based on origin of conjunctival melanoma. DESIGN Interventional case series. PARTICIPANTS Three hundred eighty-two consecutive patients. METHODS Retrospective chart review. MAIN OUTCOME MEASURES Melanoma-related metastasis and death. RESULTS The melanoma arose from primary acquired melanosis (PAM; n = 284; 74%), from pre-existing nevus (n = 26; 7%), and de novo (n = 72; 19%). The mean tumor base was 11 mm for melanoma arising from PAM, 6 mm for melanoma arising from nevus, and 10 mm for those arising de novo. At 5 years (10 years), melanoma metastasis occurred in 19% (25%) in melanoma arising from PAM (P = 0.003), 10% (26%) in melanoma from nevus (P = 0.193), and 35% (49%) in those de novo. Factors predictive of metastasis by multivariable analysis included tumor origin de novo (P = 0.001), palpebral location (P<0.001), nodular tumor (P = 0.005), and orbital invasion (P = 0.022). At 5 years (10 years), melanoma-related death occurred in 5% (9%) in melanoma arising from PAM (P<0.001), 0% (9%) in melanoma arising from nevus (P<0.057), and 17% (35%) in those arising de novo. Factors predictive of death by multivariable analysis included tumor origin de novo (P<0.001), fornix location (P = 0.04), and nodular tumor (P = 0.001). CONCLUSIONS Melanoma arising de novo carries a higher risk of melanoma-related metastasis and death compared with those cases arising from PAM or nevus.

Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases.

Purpose: To evaluate clinical features and life prognosis of uveal melanoma based on age at presentation. Design: Retrospective, nonrandomized, interventional case series. Results: Of 8,033 eyes with uveal melanoma, 106 (1%) were in young patients (⩽20 years), 4,287 (53%) in mid adults (21–60 years), and 3,640 (45%) in older adults (>60 years). Based on age (young, mid adults, and older adults) at presentation, tumor epicenter was located in iris (21, 4, 2%; P < 0.0001), ciliary body (8, 5, and 7%; P = 0.0225), or choroid (71, 91, and 90%; P < 0.0001). Mean tumor diameter (10.2, 10.8, 11.5 mm; P < 0.0001), mean tumor thickness (5.0, 5.3, 5.7 mm; P < 0.0001), and extraocular extension (1, 2, and 4%; P = 0.0004) increased with age. Kaplan–Meier estimates of tumor-related metastasis at 3, 5, 10, and 20 years were 2%, 9%, 9%, and 20% in young patients (P < 0.011); 6%, 12%, 23%, and 34% in mid adults (P < 0.0001); and 11%, 19%, 28%, and 39% in older adults. Kaplan–Meier estimate of tumor-related death at 3, 5, 10, and 20 years were 0%, 2%, 5%, and 17% in young patients (P = 0.08); 3%, 6%, 11%, and 17% in mid adults (P < 0.001); and 7%, 11%, 16%, and 20% in older adults. Conclusion: Compared with mid adults and older adults, young patients manifested a higher proportion of iris melanoma. Compared with older adults, young and mid adults showed smaller melanoma basal dimension and lower tumor-related metastasis and death.

Intravitreal triamcinolone acetonide for radiation maculopathy after plaque radiotherapy for choroidal melanoma.

Objective: To evaluate the effect of intravitreal triamcinolone acetonide on patients with visually symptomatic radiation-induced maculopathy after plaque radiotherapy for choroidal melanoma. Design: In this prospective, nonrandomized, single-center case series of 31 patients with visually symptomatic radiation-induced maculopathy after plaque radiotherapy for choroidal melanoma at the Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University, triamcinolone acetonide (4 mg/1 mL) was injected through the pars plana into the vitreous cavity using sterile technique. Status of radiation maculopathy and final visual acuity were the main outcome measures. Results: At the time of diagnosis of choroidal melanoma, visual acuity was 20/20 to 20/50 in 90% (n = 28), 20/60 to 20/200 in 10% (n = 3), and 20/400 or worse in none of the patients. The mean radiation dose to the foveola was 5,122 cGy (median, 3,280 cGy; range, 1,000–16,100 cGy). Radiation maculopathy developed at a mean of 22 months (median, 16 months; range, 6–96 months) after plaque radiotherapy. In all cases, the choroidal melanoma was regressed, and there was no retinal detachment or neovascularization of the retina, optic disk, or iris. At the time of diagnosis of radiation maculopathy, visual acuity was 20/20 to 20/50 in 19% (6/31), 20/60 to 20/200 in 58% (18/31), and 20/400 or worse in 23% (7/31) of patients. After intravitreal injection of triamcinolone acetonide, visual acuity was stable or improved in 91% (20/22) of patients by 1 month and 45% (14/31) by 6 months. Mean foveal thickness by optical coherence tomography was 417 μm at injection and 207 μm at 1 month and 292 μm at 6 months after injection. Conclusions: Intravitreal triamcinolone acetonide can stabilize or improve visual acuity in some patients with radiation-induced maculopathy, but its effect might not be lasting.

Optical coherence tomography of choroidal nevus in 120 patients.

Objective: To describe the optical coherence tomography (OCT) findings of choroidal nevi. Methods: Retrospective, single-center case series of 120 eyes of 120 consecutive patients with choroidal nevi who were evaluated by OCT. Diagnostic imaging was performed with a Zeiss StratusOCT Model 3000 (Carl Zeiss Ophthalmic Systems, Dublin, CA) using scan acquisition protocols of 6 radial lines and retinal thickness analysis overlying the nevus. Results: The mean patient age was 59 years (median, 60 years; range, 14–87 years). The choroidal nevus was a mean of 5.2 mm in basal dimension and 1.7 mm in thickness and was located a mean of 2.7 mm from the optic disk and 2.5 mm from the foveola. Related retinal findings by ophthalmoscopic evaluation included overlying retina edema (3%), subretinal fluid (16%), retinal thinning (0%), drusen (58%), and retinal pigment epithelium (RPE) detachment (2%). In comparison, related retinal findings at the site of the nevus by OCT included overlying retina edema (15%), subretinal fluid (26%), retinal thinning (22%), drusen (41%), and RPE detachment (12%). Furthermore, OCT permitted classification of the overlying retinal edema as focal cystoid (3%), diffuse cystoid (8%), coalescent cystoid (3%), and noncystoid edema (1%). By OCT, the overlying retina was normal thickness (32%), thinned (22%), or thickened (45%), and photoreceptor loss or attenuation was noted in 51% of cases. Specific OCT findings of the choroidal nevus were limited to its anterior surface with minimal penetration into the mass. These findings included increased thickness of the RPE/choriocapillaris layer (68%) and optical qualities within the anterior portion of the nevus of hyporeflectivity (62%), isoreflectivity (29%), and hyperreflectivity (9%). Hyporeflectivity was observed in 68% of pigmented nevi and 18% of nonpigmented nevi. When comparing OCT with clinical examination, OCT was more sensitive in the detection of related retinal edema, subretinal fluid, retinal thinning, photoreceptor attenuation, and RPE detachment. Conclusions: OCT is a useful diagnostic modality for imaging the retina overlying a choroidal nevus. Numerous overlying changes such as subretinal fluid, retinal edema, retinal thinning, and photoreceptor attenuation are visible by OCT.

Solitary Congenital hypertrophy of the retinal pigment epithelium: Clinical features and frequency of enlargement in 330 patients

OBJECTIVE To describe the clinical features of solitary congenital hypertrophy of the retinal pigment epithelium (CHRPE) and to determine the frequency of enlargement of this lesion DESIGN Retrospective, observational, noncomparative case series. PARTICIPANTS Three hundred thirty consecutive patients with solitary CHRPE. MAIN OUTCOME MEASURES The 3 main outcome measures included flat lesion enlargement, intralesional lacunae enlargement, and development of an elevated nodule within the lesion. The clinical features at the time of presentation were analyzed for their impact on the main outcomes using a series of Cox proportional hazards regressions. RESULTS The most common referring diagnosis included choroidal nevus (26%), choroidal melanoma (15%), CHRPE (9%), and unspecified lesion (48%). The median age at diagnosis was 45 years (range, 1-80 years), and there were no patients with familial adenomatous polyposis or related colon cancer, although a history of cancer was noted in 8% of patients, most commonly breast cancer (3%). The lesion most frequently was located inferotemporally (31%) and at the equatorial region (45%). Rarely, it was located in the macula (1%) or peripapillary region (1%). The median largest basal diameter was 4.5 mm, and the lesion was flat in all cases except in 5 (1.5%), in which there was an intralesional lesion nodule. The lesion was pigmented in 88% of cases and nonpigmented in 12%. Lacunae were noted in 43% of the pigmented CHRPE, and the lacunae showed gradual enlargement in 32%. Factors related to lacunae enlargement included number and relative size of lacunae. Flat enlargement of the lesion was documented in 46% of patients with comparative photographic follow-up and in 83% of those followed up for more than 3 years. The median rate of enlargement was 10 micro m per month. The most important factor associated with flat lesion enlargement was relative size of the lacunae within CHRPE. There were no cases of CHRPE in which a nodule developed while the patient was being followed up. Of the 5 lesions that had a nodule, progressive enlargement of the nodule was found in 3. CONCLUSIONS Congenital hypertrophy of the retinal pigment epithelium generally has been regarded as a benign, stable lesion, but subtle, flat enlargement was noted in most patients (83%) followed up for 3 or more years using meticulous photographic comparison. Flat enlargement of the lesion appeared to be related to percentage of the mass occupied by lacunae.

Pseudomelanomas Of The Posterior Uveal Tract: The 2006 Taylor R. Smith Lecture

Purpose: To determine the types and frequency of lesions that clinically simulate choroidal or ciliary body melanoma (posterior uveal melanoma; PUM). Patients and Methods: A review was conducted on cases of patients referred to the ocular oncology service from October 1978 through September 2003 with the diagnosis of possible PUM but who were subsequently diagnosed by the authors to have a simulating lesion rather than PUM. The type and percent of pseudomelanomas were tabulated and compared with findings of a similar study from our service on data collected before 1978. Results: There were ≈12,000 patients referred because of a lesion believed to be a PUM during the 25 years included in the data collection. Of these patients, 1,739 (14%) were found to have a simulating condition. There were 54 different conditions that simulated melanoma. The most frequent condition was choroidal nevus, accounting for 851 cases (49%) of the pseudomelanomas. This was followed by peripheral exudative hemorrhagic chorioretinopathy (139 cases; 8%), congenital hypertrophy of the retinal pigment epithelium (108 cases; 6%), hemorrhagic detachment of the retina or pigment epithelium (86 cases; 5%), circumscribed choroidal hemangioma (79 cases; 5%) and age-related macular degeneration (76 cases; 4%). Compared with the 1980 report, the rate of pseudomelanomas diagnosed as choroidal nevus increased from 26% to 49%. Conclusion: A variety of lesions can simulate PUM. Suspicious choroidal nevus is still the lesion most difficult to differentiate from PUM. Most other pseudomelanomas account for a lower percent compared with findings from the prior study, suggesting that clinicians are now more familiar with the other pseudomelanomas and less likely to refer them to rule out PUM.

Circumscribed choroidal hemangioma.

Circumscribed choroidal hemangioma is an uncommon, benign vascular tumor manifesting as an orange-red mass in the posterior pole of the eye. Serous retinal detachment accounts for decreased vision in most patients. Diagnosis of this tumor is challenging with many patients initially misdiagnosed with choroidal melanoma or metastasis. Several ancillary tests such as ultrasonography, fluorescein angiography, indocyanine green angiography, and magnetic resonance imaging help differentiate this tumor from other simulating lesions. Asymptomatic lesions should be observed, but visually threatening or visually impairing lesions require treatment. Photodynamic therapy, laser photocoagulation, and transpupillary thermotherapy may be used for primary management of this tumor. Patients who fail to respond to previous treatment or those with extensive serous retinal detachment can be treated using radiotherapeutic modalities. Long interval between onset of symptoms and treatment, poor visual acuity at presentation, and presence of chronic retinal or retinal pigment epithelial changes are associated with poor long-term vision.

Plaque Radiotherapy for Juxtapapillary Choroidal Melanoma: Tumor Control in 650 Consecutive Cases

PURPOSE To evaluate treatment of juxtapapillary choroidal melanoma with plaque radiotherapy and to investigate the role of supplemental transpupillary thermotherapy (TTT). DESIGN Retrospective, comparative case series. PARTICIPANTS We included 650 consecutive eyes with juxtapapillary choroidal melanoma within 1 mm of the optic disc. METHODS Eyes with juxtapapillary choroidal melanoma receiving plaque radiotherapy over a 31-year period from October 1974 to November 2005 were included in the study. The TTT and no TTT groups were analyzed separately and compared. MAIN OUTCOME MEASURES Local tumor control, metastasis, and tumor-related mortality. RESULTS The median basal tumor diameter was 10 mm (range, 1.5-21) and median thickness was 3.5 mm (range, 0.5-14.8). In 481 eyes (74%), the tumor was directly adjacent to the optic disc and in 169 eyes (26%) the posterior tumor margin was between 0.1 and 1.0 mm from the optic disc. The circumpapillary extent of the tumor was <4 clock-hours in 321 eyes (50%), 4-8 clock-hours in 250 eyes (38%), and >8 clock-hours in 79 eyes (12%). Plaque radiotherapy using iodine-125 in 616 eyes (95%), cobalt-60 in 19 eyes (3%), iridium-192 in 12 eyes (2%), and ruthenium-106 in 3 eyes (<1%) delivered a median radiation dose of 8000 cGy (range, 3600-15 500) to the tumor apex and adjunctive TTT was used in 307 eyes (56%). Kaplan-Meier estimates for tumor recurrence, metastasis, and death were 14%, 11%, and 4% at 5 years and 21%, 24%, and 9% at 10 years, respectively. Eyes treated with additional TTT showed slight (statistically nonsignificant) reduction in recurrence and metastasis. Using multivariable analysis, factors predictive of tumor recurrence included foveolar tumor requiring TTT (hazard ratio, 5.07; P<0.001) and greater tumor thickness (hazard ratio, 1.29 per mm increase; P<0.001). Factors predictive of metastasis included greater tumor base (hazard ratio, 1.21 per mm increase; P<0.001) and increasing intraocular pressure (hazard ratio, 1.11 per mmHg increase; P = 0.020). CONCLUSIONS Plaque radiotherapy for juxtapapillary melanoma provides local tumor control in approximately 80% of eyes at 10 years. In subjects who received TTT, there was slight but nonsignificant improved local tumor control and lower metastatic rate.

Classification and treatment of radiation maculopathy.

Purpose of review Radiation maculopathy is a sight-limiting consequence of radiotherapy in the management of uveal melanoma and other intraocular tumors. In this review, we consider clinical, fluorescein angiographic and optical coherence tomographic findings, propose a classification for radiation maculopathy and discuss the management of this condition. Recent findings Radiation macular edema (RME) can be classified by optical coherence tomography into noncystoid or cystoid edema, with foveolar or extrafoveolar involvement. Optical coherence tomographic grading of RME has been found to correlate with visual acuity. Focal argon laser might have some limited benefit in the treatment of RME. Intravitreal triamcinolone and intravitreal antivascular endothelial growth factor agents can be of short-term benefit in the treatment of RME. In a randomized controlled trial, periocular triamcinolone significantly reduced rates of RME and vision loss up to 18 months following plaque radiotherapy for uveal melanoma. Summary Currently, there is no proven treatment for established RME, though periocular triamcinolone has been shown to have a preventive benefit. An accepted classification system for radiation maculopathy would be of benefit in planning and comparing future treatment trials.