Case Report: Erdafitinib-induced Central Serous Chorioretinopathy.

SIGNIFICANCE: Erdafitinib is the first fibroblast growth factor receptor inhibitor approved by the U.S. Food and Drug Administration in April 2019 for the treatment of locally advanced and unresectable or metastatic urothelial carcinoma. Central serous chorioretinopathy is a common ocular adverse effect requiring frequent monitoring with ophthalmic examination. PURPOSE: This study aimed to increase awareness of erdafitinib-induced central serous chorioretinopathy, highlight erdafitinib dose management guidelines, and emphasize the importance of collaborating with oncologists to prevent adverse visual consequences. CASE REPORT: An 80-year-old patient with an advanced urothelial cancer with fibroblast growth factor receptor mutations developed central serous chorioretinopathy when he was treated with daily 8 mg of erdafitinib. The erdafitinib-induced central serous chorioretinopathy resolved completely after the discontinuation of erdafitinib. He was then treated with daily 6 mg of erdafitinib and again developed central serous chorioretinopathy, which resolved completely upon discontinuation of the medication. The patient then decided to stop treatment with erdafitinib. CONCLUSIONS: Erdafitinib, a potent tyrosine kinase receptor inhibitor of fibroblast growth factor receptors 1 to 4, demonstrates antitumor activity in advanced urothelial carcinoma with fibroblast growth factor receptor mutations with a response rate of approximately 40%. However, central serous chorioretinopathy develops in 25% of patients treated with a daily 8-mg dose of erdafitinib. Although most mild to moderate erdafitinib-induced central serous chorioretinopathies resolve with dose interruption or reduction, occasionally discontinuation of the medication is necessary. Therefore, careful coordination with oncologists is important to assess the impact of erdafitinib on vision, quality of life, and survival prognosis.

Ocular syphilis.

Syphilis is a sexually transmitted, systemic, inflammatory disease caused by the spirochaete, Treponema pallidum. The natural history of untreated syphilis progresses through four distinct stages: primary, secondary, latent, and tertiary syphilis. Ocular involvement can occur at any stage of syphilis and any part of the eye can be affected. With the exception of syphilitic posterior placoid chorioretinitis, the diverse manifestations of ocular syphilis have few distinct features that can be used to assist in clinical diagnosis. Therefore, ocular syphilis should always be a part of the differential diagnosis of most, if not all, ocular infectious and inflammatory presentations. Specifically, uveitis presentations, high-risk sexual history, illicit drug use history, treatment failure, prior history of syphilis should prompt further diagnostic workup for ocular syphilis. A presumptive diagnosis of ocular syphilis relies on serological testing, both treponemal and nontreponemal tests. All patients with ocular syphilis should have their cerebrospinal fluids tested for the co-existence of neurosyphilis and their blood tested for human immunodeficiency virus co-infection. In the United States, Centers for Disease Control and Prevention recommend that ocular syphilis be managed according to its treatment guidelines for neurosyphilis, with parenteral aqueous crystalline penicillin G the drug of choice. With the timely diagnosis and appropriate treatment, ocular syphilis is curable. However, delayed diagnosis of ocular syphilis may result in long-term visual impairment. Delayed diagnosis occurs because of its diverse presentations mimicking other ocular diseases, and failure of the clinician to order serological testing. With the recent worldwide resurgence of ocular syphilis, clinicians should be familiar with the manifestation, diagnosis, and treatment of ocular syphilis.

How Should Organizations Respond to Repeated Noncompliance by Prominent Researchers?

This article considers a case in which a prominent researcher repeatedly made protocol deviations year after year while the institutional review board and university leadership failed to adequately address his continuing noncompliance. This article argues that, in addition to reporting this researcher's pattern of noncompliance to the Office for Human Research Protections, as required by federal regulations, the university should implement a remedial action plan.

Nongranulomatous Uveitis as the First Manifestation of Syphilis.

PURPOSE: The incidence of syphilis appears to be increasing in recent years. Although any structure of the eye can be involved in syphilis, isolated unilateral anterior uveitis as an initial sign of the disease is rare. We report a case of ocular syphilis presenting as a mild unilateral, nongranulomatous, anterior uveitis in an otherwise asymptomatic patient. CASE REPORT: A 64-year-old white male patient presented with a 3-day history of mildly reduced vision, photophobia, and pain in his left eye. The patient denied prior occurrences, and no contributing ocular or medical history was elicited. Entering corrected distance acuities were 20/25+ in the right eye and 20/20- in the left eye. Slit lamp examination of the left eye revealed a moderate circumlimbal flush, numerous fine keratic precipitates, and mild-to-moderate white blood cells in the anterior chamber. The patient was diagnosed as having acute, idiopathic, nongranulomatous, anterior uveitis, and topical steroid/cycloplegic treatment was initiated. Despite an initially positive, although somewhat sluggish response to treatment, the patient's uveitis suddenly worsened on day 44, exhibiting increased anterior chamber cells, several mutton-fat keratic precipitates, and elevated intraocular pressure. Systemic diagnostic workup led to the diagnosis of neurosyphilis, and the patient subsequently admitted to high-risk sexual behaviors. Treatment with intravenous aqueous penicillin-G 24 million units per day for 14 days led to complete resolution of uveitis. The case was reported to the local health department within 24 h of syphilis diagnosis. CONCLUSIONS: Syphilis, although an uncommon cause of ocular inflammation, is a highly contagious, but curable disease. Given its potentially devastating neurologic consequences, syphilis should be considered in all patients presenting with uveitis. A high index of clinical suspicion and a detailed sexual history are crucial for the accurate and timely diagnosis of ocular syphilis.

Assessment of diabetic teleretinal imaging program at the Portland Department of Veterans Affairs Medical Center.

We conducted a retrospective chart review of 200 diabetic patients who had teleretinal imaging performed between January 1, 2010, and January 1, 2011, at Portland Department of Veterans Affairs (VA) Medical Center outpatient clinics to assess the effectiveness of the diabetic teleretinal imaging program. Twenty patients (10%) had diabetic retinopathy. Ninety percent of the available teleretinal imaging studies were of adequate quality for interpretation. In accordance with local VA policy at that time, all teleretinal imaging patients should have been referred for a dilated retinal examination the following year. Image readers referred 97.5% of the patients to eye clinics for subsequent eye examinations, but the imagers scheduled appointments for only 80% of these patients. The redundancy rate, i.e., patients who had an eye examination within the past 6 mo, was 11%; the duplicate recall rate, i.e., patients who had a second teleretinal imaging performed within 1 yr of the eye examination, was 37%. Rates of timely diabetic eye examinations at clinics with teleretinal imaging programs, particularly when teleretinal imaging and eye clinics were colocated at the same community-based outpatient clinic, were higher than those without a teleretinal imaging program. We concluded that the Portland VA Medical Center's teleretinal imaging program was successful in increasing the screening rate for diabetic retinopathy.

Melanophilin and myosin Va track the microtubule plus end on EB1.

In mouse melanocytes, myosin Va is recruited onto the surface of melanosomes by a receptor complex containing Rab27a that is present in the melanosome membrane and melanophilin (Mlp), which links myosin Va to Rab27a. In this study, we show that Mlp is also a microtubule plus end-tracking protein or +TIP. Moreover, myosin Va tracks the plus end in a Mlp-dependent manner. Data showing that overexpression and short inhibitory RNA knockdown of the +TIP EB1 have opposite effects on Mlp-microtubule interaction, that Mlp interacts directly with EB1, and that deletion from Mlp of a region similar to one in the adenomatous polyposis coli protein involved in EB1 binding blocks Mlp's ability to plus end track argue that Mlp tracks the plus end indirectly [corrected] by hitchhiking on EB1. These results identify a novel +TIP and indicate that vertebrate cells possess a +TIP complex that is similar to the Myo2p-Kar9p-Bim1p complex in yeast. We suggest that the +TIP complex identified in this study may serve to focus the transfer of melanosomes from microtubules to actin at the microtubule plus end.