PIMASERTIB and SEROUS RETINAL DETACHMENTS

© by Ophthalmic Communications Society, Inc.Purpose: To report a case of multifocal serous retinal detachments associated with pimasertib. Methods: The authors report a 26-year-old patient who developed bilateral multifocal serous retinal detachments appearing 2 days after starting pimasertib (as part of a clinical trial investigating its use in low-grade metastatic ovarian cancer) and rapidly resolving 3 days after stopping it. Conclusion: The mechanism of MEK inhibitor induced visual toxicity remains unclear. The pathophysiology of multifocal serous retinal detachments as a complication of pimasertib is still poorly understood. Copyringhtpublished_or_final_versio

Presumed Idiopathic Central Serous Chorioretinopathy in a 12-Year-Old Girl

Idiopathic central serous chorioretinopathy (CSC) typically affects middle-aged males. To date, only one case of idiopathic CSC in a prepubertal subject has been reported. Atypical idiopathic CSC presentation may be challenging to diagnose. Exclusion of secondary causes of serous retinal detachment (SRD) is warranted. We describe the atypical case of a 12-year-old female with a circumscribed SRD that resolved spontaneously and with fluorescein angiography (FA) findings that were compatible with idiopathic CSC. Optical coherence tomography (OCT) and systemic assessment were performed to exclude other etiologies. FA demonstrated multiple focal leaks in early phases, with subretinal leakage and pooling in late phases. OCT showed a localized circumscribed retinal detachment. Complete blood count was within normal limits. Serum cortisol was normal (22.1 μg/dl) and mean arterial blood pressure was 100/60 mm Hg, thereby excluding secondary causes of CSC. This is the second reported case of idiopathic CSC in a prepubertal female and the first one documented by FA and OCT, as well as other studies to exclude secondary causes. Albeit rare, idiopathic CSC should be considered in the differential diagnosis of SRD in this (prepubertal) age group, after excluding secondary ocular or systemic etiologies

The Pediatric Choroidal and Ciliary Body Melanoma Study A Survey by the European Ophthalmic Oncology Group

Purpose: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. Design: Retrospective, multicenter observational study. Participants: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. Methods: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. Main Outcome Measures: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. Results: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. Conclusions: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups. (C) 2016 by the American Academy of Ophthalmology.Peer reviewe

Unusual Orange-Colored Choroidal Metastases

Purpose: To report the clinical and paraclinical features of two patients with orangecolored choroidal metastases in whom the primary cancers have not previously been associated with such lesions. Case Report: Orange-colored choroidal lesions were detected on the fundus examination of one patient with metastatic small cell neuroendocrine tumor of the larynx and oropharynx, and in another subject with metastatic alveolar soft part sarcoma of the leg. Although ultrasonographic characteristics of the choroidal masses were comparable to those of choroidal hemangiomas, fluorescein angiography revealed delayed initial fluorescence along with minimal fluorescence in subsequent phases of the angiogram which were in clear distinction from the earlier appearing and progressively intense fluorescence observed with circumscribed choroidal hemangiomas. Conclusion: Small cell neuroendocrine tumors and alveolar soft part sarcomas should be considered among the differential diagnoses for orange-colored choroidal metastases. Identifying these choroidal lesions could facilitate localizing the occult primary tumor. Fluorescein angiography may differentiate a unifocal orange choroidal metastasis from a circumscribed choroidal hemangioma

Retinal perfusion changes in radiation retinopathy.

To investigate retinal blood flow and oxygen saturation changes in patients diagnosed with retinopathy following plaque radiation treatment to treat choroidal melanoma. Eight patients (mean age 55.75?years, SD 12.58?years) who have developed unilateral ischaemic radiation-related retinopathy as confirmed by wide-field fluorescein angiography were recruited for the study. The fellow eye with no other ocular or retinal pathology was used as control. Both eyes underwent measurement of total retinal blood flow (TRBF) and retinal blood oxygen saturation using prototype methodologies of Doppler Spectral Domain Optical Coherence Tomography (OCT) and Hyperspectral Retinal Camera, respectively. The average TRBF in the retinopathy eye was significantly lower compared to the fellow eye (33.48???12.73??l/min versus 50.37???15.26??l/min; p?=?0.013). The arteriolar oxygen saturation (SaO2 ) and venular oxygen saturation (SvO2 ) were higher in the retinopathy eye compared to the fellow eye (101.11???4.26%, versus 94.45???5.79%; p?=?0.008) and (62.96???11.05% versus 51.24???6.88%, p?=?0.051), respectively. The ionizing radiation seems to have an impact on the TRBF, SaO2 and SvO2 , clinically presenting similar to a rapidly developing diabetic retinopathy. The results show an altered retinal vascular physiology in patients with radiation-related retinopathy

Development of a Metastatic Uveal Melanoma Prognostic Score (MUMPS) for Use in Patients Receiving Immune Checkpoint Inhibitors

Metastatic uveal melanoma (mUM) is a rare disease. There are limited data on prognostic clinical factors for overall survival (OS) in patients with mUM treated with immune checkpoint inhibitors (ICI). Retrospective and non-randomized prospective studies have reported response rates of 0–17% for anti-PD1/L1 ± anti-CTLA4 ICI in mUM, indicating a potential benefit only in a subset of patients. This study evaluates the characteristics associated with ICI benefit in patients with mUM. We performed a single-center retrospective cohort study of patients with mUM who received anti-PD1/L1 ± anti-CTLA4 ICI between 2014–2019. Clinical and genomic characteristics were collected from a chart review. Treatment response and clinical progression were determined by physician assessment. Multivariable Cox regression models and Kaplan–Meier log-rank tests were used to assess differences in clinical progression-free survival (cPFS) and OS between groups and identify clinical variables associated with ICI outcomes. We identified 71 mUM patients who received 75 lines of ICI therapy. Of these, 54 received anti-PD1/L1 alone, and 21 received anti-PD1/L1 + anti-CTLA4. Patient characteristics were: 53% female, 48% were 65 or older, 72% received one or fewer lines of prior therapy. Within our cohort, 53% of patients had developed metastatic disease <2 years after their initial diagnosis. Bone metastases were present in 12% of patients. The median cPFS was 2.7 months, and the median OS was 10.0 months. In multivariable analyses for both cPFS and OS, the following variables were associated with a good prognosis: ≥2 years from the initial diagnosis to metastatic disease (n = 25), LDH < 1.5 × ULN (n = 45), and absence of bone metastases (n = 66). We developed a Metastatic Uveal Melanoma Prognostic Score (MUMPS). Patients were divided into 3 MUMPS groups based on the number of the above-mentioned prognostic variables: Poor prognosis (0–1), Intermediate prognosis (2) and Good prognosis (3). Good prognosis patients experienced longer cPFS (6.0 months) and OS (34.5 months) than patients with intermediate (2.3 months cPFS, 9.4 months OS) and poor prognosis disease (1.8 months cPFS, 3.9 months OS); p < 0.0001. We developed MUMPS—a prognostic score based on retrospective data that is comprised of 3 readily available clinical variables (time to metastatic diagnosis, presence of bone metastases, and LDH). This MUMPS score has a potential prognostic value. Further validation in independent datasets is warranted to determine the role of this MUMPS score in selecting ICI treatment management for mUM

Conjunctival melanoma treatment outcomes in 288 patients: a multicentre international data-sharing study

Background To relate conjunctival melanoma characteristics to local control. Methods Retrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. Results 288 patients had a mean initial age of 59.7 +/- 16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2-8.9%), 19.3% (14.4-25.5%) and 36.9% (26.5-49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence. Conclusion This multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management.OV

The Pediatric Choroidal and Ciliary Body Melanoma Study A Survey by the European Ophthalmic Oncology Group

Purpose: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. Design: Retrospective, multicenter observational study. Participants: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. Methods: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. Main Outcome Measures: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. Results: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. Conclusions: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups. (C) 2016 by the American Academy of Ophthalmology