Congenital glaucoma is a global problem and poses a diagnostic and therapeutic challenge to the ophthalmologist. A detailed evaluation under general anesthesia is advisable to establish the diagnosis and plan for management. Medical therapy has a limited role and surgery remains the primary therapeutic modality. While goniotomy or trabeculotomy ab externo is valuable in the management of congenital glaucoma, primary combined trabeculotomy–trabeculectomy offers the best hope of success in advanced cases. Trabeculectomy with antifibrotic agent and glaucoma drainage devices has a role in the management of refractory cases, and cyclodestructive procedures should be reserved for patients where these procedures have failed. Early diagnosis, prompt therapeutic intervention and proper refractive correction are keys to success. Management of residual vision and visual rehabilitation should be an integral part of the management of children with low vision and lifelong follow-up is a must.

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9008 Background: ALK tyrosine kinase inhibitors (TKIs) are standard of care for patients (pts) with advanced ALK+ NSCLC, and preclinical data suggest potential synergistic activity with checkpoint inhibitors in NSCLC irrespective of ALK status. Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody approved in various countries for treatment of metastatic Merkel cell carcinoma, and in the US for advanced urothelial carcinoma that has progressed following platinum therapy. We report initial results from JAVELIN Lung 101 (NCT02584634), a phase 1b/2 dose-finding trial of avelumab + crizotinib (A+C) or the next-generation ALK TKI lorlatinib (A+L) in pts with advanced/metastatic ALK-negative/wildtype (ALK−) or ALK+ NSCLC, respectively. Methods: In phase 1b, pts with previously treated ALK− NSCLC received A (10 mg/kg Q2W) + C (250 mg BID) while pts with ALK+ NSCLC received A (10 mg/kg Q2W) + L (100 mg QD) (starting dose levels in each group). The primary endpoint was dose-limiting toxicities (DLTs); secondary endpoints included adverse events (AEs) and objective responses. Results: At data cutoff on Oct 27, 2017, 12 ALK− pts had received A+C and 28 ALK+ pts had received A+L. All ALK− pts had received prior anticancer therapy; ALK+ pts had received a median 2 prior ALK TKIs (range 1-3; data not reported for 1 ALK+ pt). DLTs occurred with A+C in 5 ALK− pts (41.7%): ALT and AST increase (2 pts each), febrile neutropenia, hepatitis, QT prolongation, and rash (1 pt each). No DLTs occurred with A+L in ALK+ pts. Grade ≥3 AEs of any causality occurred with A+C in 7 ALK− pts (58.3%; most common [≥10%] was ALT increase [16.7%, n = 2]), and with A+L in 15 ALK+ pts (53.6%; most common were hypertriglyceridemia [14.3%, n = 4] and GGT increase [10.7%, n = 3]). The confirmed objective response rate with A+C in ALK− pts was 16.7% (95% CI, 2.1-48.4; partial response [PR] in 2 pts), and with A+L in ALK+ pts was 46.4% (95% CI, 27.5-66.1; PR in 12 pts; complete response in 1 pt). Conclusions: A+L showed an acceptable safety profile, distinct from A+C, and promising antitumor activity in pts with ALK+ NSCLC, and will be evaluated in treatment-naive pts in phase 2. Clinical trial information: NCT02584634.

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The ability of interferon-alpha (IFN-alpha) to induce the adhesion molecules that characterize the islets of patients with type I diabetes has been investigated. We have found that all tested recombinant IFN-as will induce major histocompatibility complex (MHC) class I on arterial endothelial cells. Some but not all IFN-as will induce intercellular adhesion molecule-1 (ICAM-1). However, there is only a transient and modest increase in VCAM on arterial endothelial cells. IFN-alpha has very little effect on endothelial MHC class II expression but will induce these proteins on monocytes. Thus, there is a close concordance between the biological actions of IFN-alpha and the appearance of those adhesion molecules induced in the islets of patients with type I diabetes. IFN-alpha is also produced in normal human islets during short-term cultures, probably as a result of the ischemia present at the center of the islet. This induction of IFN-alpha by hypoxia may explain the previously reported spontaneous induction of ICAM-1 in human islets and may also be a contributing factor to the failure of islet grafts.