Ocular surface complications following biological therapy for cancer.

Novel and highly effective biological agents developed to treat cancer over the past two decades have also been linked to multiple adverse outcomes, including unanticipated consequences for the cornea. This review provides an overview of adverse corneal complications of biological agents currently in use for the treatment of cancer. Epidermal growth factor receptor inhibitors and immune checkpoint inhibitors are the two classes of biological agents most frequently associated with corneal adverse events. Dry eye, Stevens-Johnson syndrome, and corneal transplant rejection have all been reported following the use of immune checkpoint inhibitors. The management of these adverse events requires close collaboration between ophthalmologists, dermatologists, and oncologists. This review focuses in depth on the epidemiology, pathophysiology, and management of ocular surface complications of biological therapies against cancer.

Case Report: Multiple Sclerosis Presenting as Unilateral Gaze-evoked Nystagmus.

SIGNIFICANCE: Unilateral gaze-evoked nystagmus is a rare neurologic finding that is largely diagnosed in connection with ischemic stroke. Gazed-evoked nystagmus is also a rare initial presentation of multiple sclerosis. PURPOSE: This study aimed to report a rare presentation of gaze-evoked nystagmus in a patient with multiple sclerosis and review the mechanism underlying the gaze-evoked nystagmus. CASE REPORT: A 32-year-old man presented with a 1-week history of diplopia. Neurologic examination revealed right-sided gaze-evoked nystagmus and right-sided ataxia. Laboratory test revealed a positive result for oligoclonal bands. Contrast brain MRI revealed multiple hyperintense T2 lesions including a hyperintense patch at the right inferior cerebellar peduncle. A diagnosis of multiple sclerosis was made. The patient received methylprednisolone 500 mg intravenously for 14 days. The diplopia and gaze-evoked nystagmus resolved and remained stable 2 months later. CONCLUSIONS: Our case demonstrates that damage to the inferior cerebellar peduncle may result in ipsilesional gaze-evoked nystagmus and ipsilesional ataxia, in contrast to ipsilesional gaze-evoked nystagmus and contralesional ataxia.

Case report: Early onset Marin-Amat syndrome after receiving ChAdOx1 nCoV-19 vaccination.

While vaccination against COVID-19 is still ongoing, some rare adverse events temporally related to vaccinations have been reported, particularly with ChAdOx1 nCoV-19. Here, a 77-year-old male presented to our outpatient department with persistent ptosis of his left eye for 1 month. He initially received vaccination with ChAdOx1 nCoV-19 and developed symptoms of Bell's palsy 3 days later. He received a 14-day course of prednisolone, but the ptosis persisted. Marin-Amat syndrome was compatible with his symptoms of ptosis exacerbation during orbicularis oris exertion. A temporal correlation between ChAdOx1 nCoV-19 vaccination and Bell's palsy without infectious or autoimmune diseases was delineated. Further studies are needed to clarify the possible relationship between these two events.

Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells.

Mutations of SPINT2, the gene encoding the integral membrane, Kunitz-type serine inhibitor HAI-2, primarily affect the intestine, while sparing many other HAI-2-expressing tissues, causing sodium loss in patients with syndromic congenital sodium diarrhea. The membrane-bound serine protease prostasin was previously identified as a HAI-2 target protease in intestinal tissues but not in the skin. In both tissues, the highly related inhibitor HAI-1 is, however, the default inhibitor for prostasin and the type 2 transmembrane serine protease matriptase. This cell-type selective functional linkage may contribute to the organ-selective damage associated with SPINT 2 mutations. To this end, the impact of HAI-2 deletion on matriptase and prostasin proteolysis was, here, compared using Caco-2 human colorectal adenocarcinoma cells and HaCaT human keratinocytes. Greatly enhanced prostasin proteolytic activity with a prolonged half-life and significant depletion of HAI-1 monomer were observed with HAI-2 loss in Caco-2 cells but not HaCaT cells. The constitutive, high level prostasin zymogen activation observed in Caco-2 cells, but not in HaCaT cells, also contributes to the excessive prostasin proteolytic activity caused by HAI-2 loss. HAI-2 deletion also caused increased matriptase zymogen activation, likely as an indirect result of increased prostasin proteolysis. This increase in activated matriptase, however, only had a negligible role in depletion of HAI-1 monomer. Our study suggests that the constitutive, high level of prostasin zymogen activation and the cell-type selective functional relationship between HAI-2 and prostasin renders Caco-2 cells more susceptible than HaCaT cells to the loss of HAI-2, causing a severe imbalance favoring prostasin proteolysis.