Anterior Uveitis Caused by Ocular Side Effects of Afatinib: A Case Report

Afatinib is a second-generation epidermal growth factor receptor (EGFR) inhibitor that has been shown to be effective against EGFR-mutated non-small cell lung cancer (NSCLC) resistant to conventional EGFR inhibitors such as gefitinib and erlotinib. Although ocular side effects of gefitinib and erlotinib have been reported, those for afatinib have yet to be definitively established. This report presents details on the first case of unilateral iridocyclitis associated with the side effects of afatinib therapy. A 75-year-old Japanese male ex-smoker with EGFR-mutated NSCLC underwent afatinib therapy for multiple metastases. At 2 weeks, bilateral conjunctivitis developed. Topical medication and a 1-week afatinib washout period resulted in the improvement of the conjunctivitis. However, 3 days after the resumption of afatinib, the patient developed unilateral granulomatous anterior uveitis in his right eye. Best-corrected visual acuity (BCVA) measurement indicated a decimal visual acuity of 0.2, while the slit-lamp findings were characterized by granulomatous inflammation, keratic precipitates, Koeppe nodules and posterior synechiae. There was no evidence suggesting other intraocular inflammatory disease or metastatic tumor. The left eye was intact. The use of topical medication including steroids and a washout of afatinib resulted in a gradual subsiding of the anterior uveitis. After resolution of the anterior uveitis, oral afatinib was resumed. BCVA of the right eye finally recovered to a decimal acuity of 1.0. Ophthalmologists should be aware of the possibility that side effects associated with afatinib could cause granulomatous anterior uveitis

Sustained Effect of Hyaluronic Acid in Subcutaneous Administration to the Cochlear Spiral Ganglion.

The spatiotemporal distribution of drugs in the inner ear cannot be precisely evaluated because of its small area and complex structure. In the present study, we used hyaluronic acid (HA)-dispersed luciferin to image transgenic mice and to determine the effect of HA on controlled drug delivery to the cochlea. GFAP-luc mice, which express luciferase in cochlear spiral ganglion cells, were subcutaneously administered HA-luciferin (HA-sc) or luciferin dissolved in saline (NS-sc) or intraperitoneally administered luciferin dissolved in saline (NS-ip). The bioluminescence of luciferin was monitored in vivo in real time. The peak time and half-life of fluorescence emission were significantly increased in HA-sc-treated mice compared with those in NS-sc- and NS-ip-treated mice; however, significant differences were not observed in peak photon counts. We detected differences in the pharmacokinetics of luciferin in the inner ear, including its sustained release, in the presence of HA. The results indicate the clinical potential of using HA for controlled drug delivery to the cochlea

Half-life of fluorescence emission in each group.

<p>The bar graph shows the average value of 7 mice in each group, and the error bar indicates the standard deviation. The asterisks indicate a statistically significant difference.</p

Peak photon count of each group of mice that were administered luciferin.

<p>The bar graph shows the average value of 7 mice in each group, and the error bars indicate the standard deviation.</p

Total photon counts of each group.

<p>The bar graph shows the average value of 7 mice in each group, and the error bar indicates the standard deviation.</p

Time-dependent changes of photon counts of transgenic and wild-type mice administered luciferin via different routes.

<p>The designations of the groups are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153957#pone.0153957.g001" target="_blank">Fig 1</a>.</p