Evolution in regression patterns following chemoreduction for retinoblastoma.

OBJECTIVE: To evaluate the change in regression pattern following chemoreduction and tumor consolidation therapy (thermotherapy or cryotherapy) for retinoblastoma METHODS: Retrospective medical record analysis was completed for 557 retinoblastomas (239 eyes of 157 patients) that were treated with chemoreduction and showed regression to 1 of 5 patterns (type 0, no visible remnant; type 1, completely calcified remnant; type 2, completely noncalcified remnant; type 3, partially calcified remnant; and type 4, atrophic chorioretinal flat scar). Evolution of these regression patterns was observed over time. RESULTS: Immediately following 6 cycles of chemoreduction, types 0 (2%), 1 (30%), 2 (3%), 3 (33%), and 4 (32%) regression patterns were found. During a mean follow-up period of 56 months (median, 48 months; range, 18-145 months), there was no change in regression patterns classified as type 0, 1, or 4. However, there was evolution of regression pattern types 2 and 3. Over time, type 2 tumor scars either remained stable (41%) or evolved to type 4 (41%), 3 (9%), or 1 (9%) scars. Type 3 tumor scars remained stable (74%) or evolved to type 1 (26%) scars. CONCLUSION: Following chemoreduction and tumor consolidation therapy, retinoblastoma regression patterns types 2 and 3 can slowly evolve over time into a slightly different appearance, even without additional treatment. Ophthalmologists should be familiar with these regression patterns and their evolution.

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.

Necrotic choroidal melanoma with scleritis and choroidal effusion.

PURPOSE: To report a case of a choroidal melanoma that presented with painful scleritis and choroidal effusion. METHODS: Interventional case report with cytopathologic correlation. RESULTS: A 78-year-old otherwise healthy woman presented with sudden, severe painful ocular inflammation and marked injection of the right eye over a 3-day period, consistent with scleritis. Upon referral, 360 degrees of scleral and conjunctival injection and peripheral choroidal effusion were found. In addition, a solid hemorrhagic, choroidal mass was evident, suspicious for melanoma. Fine needle aspiration biopsy of the choroidal mass confirmed necrotic melanoma. The melanoma was treated with iodine 125 plaque radiotherapy, and during surgery, the temporal sclera was markedly edematous and the orbital tissue was fibrotic, presumed related to inflammation. Two months after radiotherapy, the scleritis and choroidal effusion had resolved. CONCLUSION: Uveal effusion can rarely occur with uveal melanoma, particularly when the tumor is necrotic.

Chemoreduction for group E retinoblastoma: comparison of chemoreduction alone versus chemoreduction plus low-dose external radiotherapy in 76 eyes.

PURPOSE: To evaluate chemoreduction (CRD) for group E retinoblastoma. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Seventy-six eyes of 56 patients with group E retinoblastoma were treated with CRD alone or CRD plus low-dose prophylactic external beam radiotherapy (CRD+P-EBR). The CRD included vincristine, etoposide, and carboplatin (6 cycles). The P-EBR was given routinely 2 months after completion of CRD at a suggested dose of 2600 cGy. Therapeutic EBR (T-EBR) was only given at the time of extensive tumor recurrence at a suggested dose of 3800 cGy. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Globe salvage. RESULTS: Of the 76 eyes, 64 received CRD alone and 12 received CRD+P-EBR. At the 2-year follow-up, globe salvage was achieved in 29 (53%) of 55 eyes in the CRD group and in 10 (91%) of 11 eyes in the CRD+P-EBR group. At 5 years, globe salvage was achieved in 20 (48%) of 42 eyes in the CRD group and in 4 (80%) of 5 eyes in the CRD+P-EBR group (P=0.347). Of the 64 eyes in the CRD group, 16 (25%) were salvaged with CRD alone and 13 (20%) with CRD+T-EBR, whereas 22 (34%) were enucleated after CRD alone and 13 (20%) were enucleated after CRD+T-EBR. Of the 12 eyes in the CRD+P-EBR group, 10 (83%) were salvaged with CRD+P-EBR, whereas 2 (17%) were enucleated and none required T-EBR. The median dose for T-EBR was 3800 cGy, and that for P-EBR was 2600 cGy. Eyes treated with CRD+P-EBR showed significantly less recurrence, leading to less chance of enucleation or therapeutic radiotherapy than that for CRD alone (P<0.001). Visual acuity was 20/100 or better or fix and follow in 9 (32%) of 28 salvaged eyes in the CRD group and in 4 (40%) of 10 in the CRD+P-EBR group. At 5 years, there were no patients in either group with metastasis of pinealoblastoma or who had died. In one patient in the CRD group, a second cancer developed. CONCLUSIONS: Group E retinoblastoma managed with CRD+P-EBR showed significantly less need for enucleation or therapeutic radiotherapy than eyes treated with CRD alone. These findings merit further study and consideration.

Combined hamartoma of the retina and retinal pigment epithelium in 77 consecutive patients visual outcome based on macular versus extramacular tumor location.

PURPOSE: To evaluate visual outcome of eyes with combined hamartoma of the retina and retinal pigment epithelium (RPE). DESIGN: Noncomparative case series. PARTICIPANTS: Seventy-nine eyes of 77 patients. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Visual outcome. RESULTS: The presenting symptoms were decreased vision (n = 32; 40%), strabismus (n = 22; 28%), both (n = 3; 4%), irritation (n = 4; 5%), and none (n = 18; 23%). The tumors had the following characteristics: a mean diameter of 7.6 mm, a mean thickness of 1.9 mm, round (n = 52; 66%) or curvilinear (n = 27; 34%) configuration, and other features including intralesional corkscrew vessels (n = 51; 65%), feeding straight vessels (n = 50; 63%), retinal traction (n = 64; 81%), fibrosis/gliosis (n = 36; 46%), and exudation (n = 10; 13%). Referring diagnosis was unknown (n = 40; 51%) or incorrect (n = 19; 24%) as retinoblastoma (n = 4), astrocytoma (n = 1), toxocariasis (n = 2), choroidal nevus (n = 5), melanoma (n = 6), and hemangioma (n = 1). The mean initial visual acuity by logarithm of the minimum angle of resolution (Snellen) for macular (n = 29) versus extramacular (n = 28) tumors was 1.2 (20/320) versus 0.61 (20/80) and at 4 years was 1.72 (20/800) versus 0.79 (20/125). Visual acuity loss of >or=3 Snellen lines was 60% versus 13%. By univariate analysis, the most important factors predictive of poor visual acuity included macular location and clock hour meridian of the tumor. CONCLUSIONS: Combined hamartoma of the retina and RPE can cause profound visual acuity loss, particularly with macular tumors. FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.

Clinical spectrum of diffuse infiltrating retinoblastoma in 34 consecutive eyes.

PURPOSE: To evaluate the clinical features and management of diffuse infiltrating retinoblastoma. DESIGN: Retrospective case series. PARTICIPANTS: Thirty-four eyes in 32 patients. METHODS: The patients' records were reviewed for patient and tumor features, ocular management, histopathologic findings, and patient survival. MAIN OUTCOME MEASURES: Clinical features, tumor management, and patient survival. RESULTS: Of 1507 patients with retinoblastoma, only 32 (2%) were classified with diffuse infiltrating retinoblastoma. The mean age at diagnosis was 4 years (range 1.5-16 years). The referring diagnoses included retinoblastoma (26 eyes, 76%), uveitis (3, 9%), Coats disease (1, 3%), trauma (1, 3%), and unspecified retinal problem (3, 9%). The anterior segment displayed tumor seeds on the corneal endothelium (8, 24%), cornea stromal edema (3, 9%), pseudohypopyon (11, 32%), hyphema (3, 9%), iris neovascularization (17, 50%), and iris tumor nodules (6, 18%). The posterior segment revealed extensive ill-defined retinoblastoma infiltrating the retina for a mean basal diameter of 20 mm and overall flat growth, sometimes with undulating retinal thickening. Overlying extensive vitreous tumor seeds (31, 91%) and vitreous hemorrhage (8, 24%) were noted. Calcification was present on ultrasonography (27/34, 79%) and computed tomography (8/9, 89%). Enucleation was performed for all 34 eyes, and there were no cases of metastases at 47 months follow-up. CONCLUSIONS: Diffuse infiltrating retinoblastoma can masquerade as uveitis or unexplained hyphema or keratic precipitates. Suspicion for retinoblastoma is important. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Primary acquired melanosis of the conjunctiva: risks for progression to melanoma in 311 eyes. The 2006 Lorenz E. Zimmerman lecture.

PURPOSE: To evaluate the clinical features and risks for transformation of conjunctival primary acquired melanosis (PAM) into melanoma. DESIGN: Noncomparative case series. PARTICIPANTS: Three hundred eleven eyes with conjunctival PAM without melanoma at initial examination from a single-center tertiary referral center. METHODS: Retrospective chart review with evaluation of the clinical features of PAM at initial presentation and follow-up. Times to PAM enlargement, recurrence, and transformation into melanoma were assessed using Kaplan-Meier estimates. Risk factors for these outcomes were analyzed using Cox proportional hazards regressions. MAIN OUTCOME MEASURES: Primary acquired melanosis enlargement, recurrence, and transformation into melanoma. RESULTS: Mean patient age at diagnosis of PAM was 56 years (range, 15-90), 62% were female, and 96% were Caucasian. The conjunctival quadrant(s) affected by PAM were temporal (57%), inferior (45%), nasal (42%), and superior (37%). The anatomic location(s) of PAM included bulbar conjunctiva (91%), limbal conjunctiva (55%), cornea (23%), forniceal conjunctiva (13%), palpebral conjunctiva (12%), and caruncle (11%). Primary acquired melanosis extended for a mean of 3 clock hours (range, 1-12). Initial management included observation (n = 194 eyes [62%]), biopsy combined with cryotherapy (n = 107 eyes [34%]), and topical chemotherapy and/or cryotherapy without biopsy (n = 10 [4%]). Of PAM that was observed, Kaplan-Meier estimates at 10 years revealed PAM enlargement in 35% and transformation into melanoma in 12%. Of those that underwent incisional or excisional biopsy, 10-year estimates of PAM recurrence and transformation into melanoma were 58% and 11%, respectively. Progression to melanoma occurred in 0% of cases of PAM without atypia, 0% of cases of PAM with mild atypia, and 13% of cases of PAM with severe atypia. Of the 9 patients with PAM who developed melanoma, none have developed systemic metastasis. Multivariable analysis revealed that the most significant factor for both PAM recurrence and progression to melanoma was extent of PAM in clock hours. CONCLUSION: Primary acquired melanosis without atypia or with mild atypia shows 0% progression to melanoma, whereas PAM with severe atypia shows progression to melanoma in 13%. The greater the extent of PAM in clock hours, the greater the risk for transformation to melanoma.

Iris cavernous hemangioma associated with multiple cavernous hemangiomas in the kidney, brain, and skin.

PURPOSE: To document the relationship of iris cavernous hemangiomas with multiorgan hemangiomas in a child. METHODS: A 7-year-old girl with kidney hemangiomas, brain hemangiomas, and skin hemangiomas developed blurred vision and darkening of the right iris. She had undergone 6 previous brain surgeries and multiple revisions of a ventriculoperitoneal shunt for hydrocephalus beginning at age 3 months. RESULTS: Examination revealed visual acuity of 20/30 in the right eye and 20/20 in the left eye. There was a reddish-purple lobulated cystic mass along the superior iris pupillary margin measuring 2 mm in greatest diameter confirmed by ultrasound biomicroscopy. The remainder of the ocular examination was unremarkable. The diagnosis was iris cavernous hemangioma in a patient with multiorgan cavernous hemangiomatosis. By 1-year follow-up, the iris hemangioma deflated, leaving a fibrotic, involuted scar. CONCLUSIONS: Iris cavernous hemangioma can be associated with multiorgan hemangiomas that can be life threatening.

Primary acquired melanosis of the conjunctiva: experience with 311 eyes.

PURPOSE: To evaluate clinical features and risks for transformation of conjunctival primary acquired melanosis (PAM) into melanoma. METHODS: Retrospective chart review and Kaplan-Meier estimates of times to PAM enlargement, recurrence, and transformation into melanoma. MAIN OUTCOME MEASURES: PAM enlargement, recurrence, and transformation into melanoma. RESULTS: The mean patient age at diagnosis of PAM was 56 years; 62% were female and 96% Caucasian. The conjunctival quadrant(s) affected by PAM and its extent in clock hours were recorded. Initial management included observation in 62%, biopsy combined with cryotherapy in 34%, and other methods in 4%. Of PAM that was observed, Kaplan-Meier estimates at 10 years revealed PAM enlargement in 35% and transformation into melanoma in 12%. Of those that underwent incisional or excisional biopsy, 10-year estimates of PAM recurrence and transformation into melanoma were 58% and 11%, respectively. Progression to melanoma occurred in 0% of PAM without atypia, 0% of PAM with mild atypia, and 13% of PAM with severe atypia. Multivariable analysis revealed that the most significant factor for both PAM recurrence and progression to melanoma was extent of PAM in clock hours. CONCLUSION: PAM without atypia or with mild atypia shows 0% progression into melanoma, whereas PAM with severe atypia shows progression into melanoma in 13%. The greater the extent of PAM in clock hours, the greater the risk for transformation into melanoma.