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PURPOSE: Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. MATERIALS AND METHODS: This study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). RESULTS: 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/PRAME(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/PRAME(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. CONCLUSION: In the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.

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BACKGROUND: Extremes in perioperative blood pressures are known risk factors for adverse outcomes after surgical interventions. There is scarce literature studying these parameters as predictors of outcomes after ocular surgery. METHODS: This was a retrospective single-centre interventional cohort analysis to evaluate the relationship between perioperative (preoperative and intraoperative) blood pressure value and variability and postoperative visual and anatomic outcomes. Included were patients who underwent primary 27-gauge (27g) vitrectomy for repair of diabetic tractional retinal detachment (DM-TRD) with at least 6 months of follow-up. Univariate analyses were conducted via independent two-sided t-tests and Pearson's χ2 tests. Multivariate analyses were conducted via generalised estimating equations. RESULTS: 71 eyes of 57 patients were included in the study. Higher preprocedure mean arterial pressure (MAP) was associated with fewer Snellen lines of improvement at postoperative month 6 (POM6) (p<0.01). Higher mean intraoperative systolic blood pressure (SBP), diastolic blood pressure and MAP were associated with visual acuity 20/200 or worse at POM6 (p<0.05). Patients with sustained intraoperative hypertension had 1.77 times the risk of visual acuity 20/200 or worse at POM6 compared with those without sustained intraoperative hypertension (p=0.006). Higher SBP variability was associated with worse visual outcomes at POM6 (p<0.05). Blood pressure was not associated with macular detachment at POM6 (p>0.10). CONCLUSIONS: Higher average perioperative blood pressure and blood pressure variability are associated with worse visual outcomes in patients undergoing 27g vitrectomy for DM-TRD repair. Patients with sustained intraoperative hypertension were approximately twice as likely to have visual acuity 20/200 or worse at POM6 compared to those without sustained intraoperative hypertension.

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Infantile Refsum disease is a rare peroxisomal biogenesis disorder characterized by impaired alpha-oxidation and accumulation of phytanic acid in the tissues. Patients often present with fundus changes resembling retinitis pigmentosa, developmental delay, sensorineural hearing loss, ataxia, and hepatomegaly. Traditionally, mainstay treatment for this condition has been a phytanic acid-restricted diet, although supplementation with either docosahexaenoic acid or cholic acid has rarely been described in the literature. We present a case of infantile Refsum disease in a child with retinitis pigmentosa-like ocular findings, sensorineural hearing loss, and self-resolving hepatic disease, who developed novel findings of macular edema refractory to carbonic anhydrase inhibitors. We describe management with a phytanic acid-restricted diet and combination docosahexaenoic acid, and cholic acid therapy, which helped to limit progression of her disease.

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