CHOROIDAL MELANOMA IN PHAKOMATOSIS PIGMENTOVASCULARIS WITH OVERLAPPING STURGE-WEBER SYNDROME AND KLIPPEL-TRENAUNAY SYNDROME.

PURPOSE: To present the rare occurrence of choroidal melanoma in an adult patient with phakomatosis pigmentovascularis and an overlap of Sturge-Weber syndrome and Klippel-Trenaunay syndrome. METHODS: Observational case report. RESULTS: A 75-year-old White woman with nevus flammeus involving the left forehead, periorbital area, cheek, chin, upper limb, and trunk, along with hemihypertrophy of the left side of the face and left upper limb, presented for evaluation of an intraocular mass in the left eye. Anterior examination of the left eye showed diffuse episcleral and iris melanocytosis. Fundus examination of the left eye showed diffuse choroidal melanocytosis and an elevated choroidal lesion. B-scan ultrasonography demonstrated a hollow lesion, and the patient was diagnosed with choroidal melanoma in the left eye in the setting of phakomatosis pigmentovascularis with overlap of Sturge-Weber syndrome and Klippel-Trenaunay syndrome. Fine-needle aspiration biopsy confirmed the diagnosis, and Iodine 125 plaque radiotherapy was performed. CONCLUSION: Individuals with clinical features suggestive of phakomatosis pigmentovascularis, Sturge-Weber syndrome, or Klippel-Trenaunay syndrome should undergo a complete ophthalmological evaluation for the presence of ocular melanocytosis and uveal melanoma.

Massive spontaneous subconjunctival hemorrhage in a patient on therapeutic warfarin: A case report.

PURPOSE: To describe a case of massive spontaneous subconjunctival hemorrhage in a patient taking warfarin with a therapeutic international normalized ratio (INR). OBSERVATIONS: Massive circumferential hemorrhagic chemosis, extensive periorbital and facial ecchymosis, and active arterial extravasation in the subconjunctiva which required cessation and reversal of anticoagulation. Findings gradually resolved over several months after discharge. CONCLUSIONS AND IMPORTANCE: While subconjunctival hemorrhage, even in anticoagulated patients, is usually benign, rare examples of severe presentations exist. We present, to our knowledge, the first documented case of a subconjunctival hemorrhage necessitating cessation and reversal of anticoagulation in the setting of a therapeutic INR.

Nanoparticle mediated increased insulin-like growth factor 1 expression enhances human placenta syncytium function.

INTRODUCTION: Placental dysfunction is an underlying cause of many major obstetric diseases and treatment options for complications like fetal growth restriction (FGR) are limited .We previously demonstrated nanoparticle delivery of the human insulin-like growth factor 1 (hIGF1) transgene under control of the trophoblast-specific PLAC1 promoter maintains normal fetal growth in a surgically-induced FGR mouse model. However, uptake by human placental syncytiotrophoblast has yet to be determined. METHODS: An ex vivo human placenta perfusion model, term placenta villous fragments, and other in vitro syncytiotrophoblast models were used to determine nanoparticle uptake, transgene expression, and functional responses under oxidative stress conditions. RESULTS: In the ex vivo perfusion, fluorescence from a Texas-Red conjugated nanoparticle increased in maternal perfusate upon nanoparticle addition and declined by the conclusion of the experiment (P < 0.001. Fluorescent histology confirmed localization in the syncytiotrophoblasts. No Texas-Red fluorescence was detected in the fetal perfusate. Transgene expression of hIGF1 in differentiated BeWo cells, isolated primary trophoblasts and fragments was increased compared to untreated (55,000-fold, P = 0.0003; 95-fold, P = 0.003; 400-fold, P < 0.001, respectively). Functionally, increased hIGF1 expression in villous fragments resulted in translocation of glucose transporter 1 to the syncytiotrophoblast cell membrane and under conditions of oxidative stress in BeWo cells, protected against increased cell death (P < 0.01) and decreased mitochondrial activity (P < 0.01). CONCLUSION: The current study confirms that our nanoparticle is capable of uptake in human placental syncytium which results in enhanced transgene expression, functional changes to cellular activity and protection against increased oxidative stress.

Clinical Features, Metastasis, and Survival in Patients Younger Than 21 Years With Posterior Uveal Melanoma.

Importance: Given the rarity of posterior uveal melanoma in patients younger than 21 years, reporting clinical experience in this area has relevance. Objective: To describe the baseline clinical features, treatment, and clinical course of a group of patients younger than 21 years who have primary posterior uveal melanoma. Design, Setting, and Participants: This retrospective descriptive case series of patients younger than 21 years who have a primary choroidal or ciliochoroidal melanoma was conducted at a single-center subspecialty referral practice. Patients in the relevant age group who were treated in a single practice between July 1980 and December 2013 were included; clinical data collected through December 2017 were captured to permit adequate follow-up time in all cases. Main Outcomes and Measures: Conventional descriptive statistics of relevant clinical variables (eg, demographic, tumor, treatment, and outcome variables) of each patient were recorded. Actuarial metastasis-free and overall survival curves were computed and plotted, as was a postdetection survival curve of patients who developed metastasis during available follow-up. Results: Of 2265 patients with posterior uveal melanoma encountered by the authors during the study interval, 18 (0.8%) were younger than 21 years when diagnosed and treated. Ten were female and 8 male, and the mean (SD) age was 16.6 (4.2) years. Through available follow-up, 8 of these patients had developed metastatic uveal melanoma (44%). All 8 died of metastasis. Actuarial survival analysis showed that the cumulative probability of metastatic death in this group exceeded 50%. The median overall survival time after treatment of the primary intraocular tumor was 11.9 (95% CI, 7.3-16.5) years. The median survival time after detection of metastasis in the 8 patients who developed metastasis was 2.3 months (95% CI, 0.0-5.2) months. Conclusions and Relevance: Posterior uveal melanoma in patients younger than 21 years appears to have a similar if not worse prognosis than patients with PUM in the population overall. Owing to the later onset of metastasis observed, patients younger than 21 years should continue to have surveillance tests for more than 10 years after treatment.

Posterior uveal melanoma in adolescents and children: current perspectives.

Recognizing that <1% of all uveal melanomas occur in young persons, and that very few clinicians encounter more than a few such cases over an extended career, we felt that a retrospective review of literature and sharing of our clinical experience would be appropriate to remind readers about this age subgroup of patients with posterior uveal melanoma. This interest stems from the increase in reported cases of uveal melanoma in younger individuals and recent advances in the field.