Purpose: To present the molecular mechanisms involved in the pathogenesis of conjunctival melanoma (CM) and review the existing literature on targeted molecular inhibitors as well as immune checkpoint inhibitors for the management of locally advanced and metastatic disease. Methods: A comprehensive review of the literature was performed using the keywords "conjunctival melanoma", "immune checkpoint inhibitors", "BRAF inhibitors", "MEK inhibitors", "CTLA4 inhibitors", "PD1 inhibitors", "c-KIT mutations", "BRAF mutations", "NRAS mutations", "dabrafenib", "trametinib", "vemurafenib", "ipilimumab", "pembrolizumab", and "nivolumab". A total of 250 articles were reviewed and 120 were included in this report. Results: Mutations of mediators in the MAP kinase pathway, such as RAS, BRAF, MEK and ERK, and mutations of the PI3K/AKT/mTOR pathway play a major role in the pathogenesis of conjunctival melanoma. In addition, alterations of c-KIT, NF1, TERT, chemokine receptors as well as chromosomal copy number alterations and micro RNAs are thought to have a causative association with CM development. Targeted molecular inhibitors, such as BRAF and MEK inhibitors, are currently being implemented in the therapy of BRAF-mutated CM. Furthermore, immune checkpoint PD-1 and CTLA4 inhibitors with favorable clinical outcomes in the treatment of cutaneous melanoma have increased recurrence-free survival and reduced metastatic spread in CM cases. Conclusion: The complex molecular mechanisms that contribute to the development of CM can be targeted both by molecular inhibitors of oncogenic pathways as well as immune checkpoint inhibitors in order to halt progression of the disease and increase survival.

BACKGROUND AND OBJECTIVE: To report the clinical outcomes of the use of a novel, specially designed, scleral-fixated intraocular lens (IOL) for the correction of aphakia in the absence of capsular support of variable etiology in children. PATIENTS AND METHODS: This is a retrospective, noncomparative, interventional case series of five eyes of five consecutive patients who underwent three-port pars plana vitrectomy and scleral fixation of the IOL. Inclusion criteria were at least 6 months of follow-up in children who underwent vitrectomy and IOL placement for aphakia and inadequate capsular support. Patients were excluded from the analysis if there was a previous open globe injury or any other ocular comorbidity such as macular pathology or previous surgery for retinal detachment, glaucoma, corneal transplantation, or strabismus. RESULTS: The median follow-up period was 9 months (range: 7–13 months). The median age was 8 years (range: 2–10 years), and the male-to-female ratio was 5 to 0. Mean postoperative best-corrected visual acuity (VA) at the last follow-up visit was 20/32 (0.26 ± 0.32 logMAR [mean ± standard deviation]), improving from a mean baseline uncorrected VA of 20/800 (1.6 ± 0.7 logMAR), a statistically significant change ( P = .003). The uncorrected postoperative VA was 20/63 (0.54 ± 0.37 logMAR). No significant postoperative complications were noted and all patients had good IOL position at the end of the follow-up without IOL capture. The mean tilt in four eyes (the 2-year-old was excluded from the analysis) was 2.1 ± 1.9 degrees. None of the patients required reoperation. CONLCUSIONS: The present study represents the first to date in evaluating the use of a scleral-fixated IOL in patients with aphakia and in pediatric patients with inadequate capsular support. The technique is safe and provides excellent postoperative IOL fixation without IOL capture in any of the patients studied. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:94–101.]

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Melanoma is the most rapidly increasing cancer in the world. Associated morbidity and mortality are mainly related to metastatic potential. Metastases to the breast from malignant melanoma are rare and represent only 1.3%–2.7% of reported cases. The aim of this study was to present a rare case of metastatic malignant melanoma to the breast. A 51-year-old woman was admitted for management of a palpable mass of the left breast. The past medical history referred to a sizable nodular melanoma that was removed from her back. Classification of the breast lesion was BI-RADS 5. Core needle biopsy was compatible with the diagnosis of malignant melanoma. Immunohistochemical evaluation was positive for Mart1 and Ki67. Subsequent staging was indicative of multiple secondary foci in the liver and bones. The patient was administered a combination of PD L1 inhibitor nivolumab with the anti-CTLA4 inhibitor ipilimumab followed by additional targeted therapy with the BRAF inhibitor vemurafenib. Metastasis to the breast from malignant melanoma is extremely rare. Nevertheless, breast metastases must be suspected in patients with a history of malignant melanoma. Moreover, recent breakthroughs in the Braf and MEK inhibitors and immune checkpoint inhibition therapies have impressively improved prognosis in patients affected by melanoma.