afatinib is a second - generation epidermal growth factor receptor ( egfr ) inhibitor that blocks erbb - family receptors . this inhibitor has been reported to be effective against egfr - mutated non - small cell lung cancer ( nsclc ) and can be used as an alternative to conventional egfr inhibitors such as gefitinib and erlotinib , or as a first - line treatment [ 2 , 3 ] . previously reported ocular side effects of gefitinib and erlotinib include dry eye symptoms , blepharitis / meibomitis , trichomegaly , eyelid skin rash and anterior uveitis [ 4 , 5 , 6 , 7 , 8 ] . however , little is known about the ocular side effects associated with afatinib . in this report , we describe the first case of unilateral anterior uveitis , which was highly suspected to be secondary to the afatinib therapy . a 75-year - old japanese male ex - smoker underwent four different video - assisted thoracoscopic surgeries for egfr - mutated nsclc and a pancreaticoduodenectomy for metastatic pancreatic tumor in 2006 . in september 2014 , he was diagnosed with metastatic thyroid tumor and received afatinib therapy in november 2014 . two weeks after the initiation of an oral 40-mg afatinib dose , the patient developed bilateral conjunctival injection without discharge and was referred to ophthalmologists . the best - corrected visual acuity ( bcva ) measurements showed there was a decimal visual acuity of 0.9 in the right eye and 1.0 in the left eye . slit - lamp examination revealed there was bulbar conjunctival injection and incipient senile cataract in both eyes . during these examinations the conjunctivitis resolved shortly after the instillation of bromfenac 0.1% eye drops twice a day and a 1-week afatinib washout period . on the 3rd day after the patient resumed taking afatinib , he developed blurred vision in his right eye and once again visited his ophthalmologists . bcva had decreased to a decimal acuity of 0.2 in his right eye , while it remained at 1.0 in his left eye . slit - lamp examination revealed keratic precipitates , cells ( 1 + ) in the anterior chamber , two small koeppe nodules on the nasal iris , posterior synechiae and mild vitreous haze in the right eye ( fig . intraocular pressure elevation , dendritic or pseudo - dendritic corneal epithelial lesion , iris atrophy , or histories of recurrent hsv infection or skin eruption were absent . the results of a serologic test including full blood counts , liver enzymes , kidney function , electrolytes , fasting plasma glucose and hemoglobin a1c revealed only mild anemia . serologic tests for syphilis were negative . a chest x - ray and ct scan showed no hilar or mediastinal lymphadenopathy , and no signs of tuberculosis . human leukocyte antigen ( hla ) typing revealed that the patient was hla - b27 negative . since the unexplained uveitis that developed after the administration of afatinib was similar to that which has been observed for erlotinib , we considered the possibility of afatinib - induced uveitis . based on these findings , we stopped the general afatinib treatment and then restarted topical betamethasone 0.1% four times per day and mydriatics once per day . after the inflammation gradually subsided , the topical betamethasone 0.1% was then tapered to twice per day and the mydriatics were discontinued . although oral afatinib at a dose of 30 mg was resumed after a 3-week washout period , the anterior uveitis in the right eye did not recur . egfr is a transmembrane receptor that is ubiquitously distributed and constitutively expressed in normal epithelial tissues that include the skin , glands , hair follicles , and the conjunctival and corneal epithelium [ 9 , 10 ] . however , it is unknown whether the egfr is expressed in the human iris pigment epithelium . ocular side effects of egfr inhibitors , such as dry eye symptoms , blepharitis / meibomitis , trichomegaly , and eyelid skin rashes , are understandable , as egfrs are distributed in both the epidermal and epithelial tissues . however , both the mechanism and the reason why egfr inhibitors rarely cause intraocular inflammation remain unknown . a mutation in the intracellular domain of the receptor not only results in overexpression , but has also been shown to be associated with tumor growth and progression . since first - generation egfr inhibitors , which include gefitinib and erlotinib , are able to reversibly block only the egfr , they are used as first - line chemotherapeutic agents for nsclc with egfr mutation [ 11 , 12 , 13 ] . recently , afatinib , which irreversibly inhibits erbb family members including egfr , her2 and her4 , has become available for use in treating the progression of nsclc . moreover , despite the availability of gefitinib and erlotinib , afatinib is now considered to be the first - line treatment for egfr - mutated nsclc [ 2 , 3 ] . various ocular side effects secondary to gefitinib and erlotinib have been previously reported when using these inhibitors [ 4 , 5 , 6 , 7 , 8 ] . among them , bilateral anterior uveitis secondary to erlotinib has been shown to be a rare ocular side effect [ 6 , 7 , 8 ] . however , ocular side effects associated with afatinib have yet to be clearly established . here , we report the details of the first case of unilateral anterior uveitis associated with afatinib therapy . a number of medications have been shown to cause drug - induced uveitis , which can be quantitatively assessed by using the naranjo algorithm [ 14 , 15 ] . based on a naranjo score of 5 , probable due to the following findings : there are previous conclusive reports on their reaction ( + 1 ) ; the adverse event appeared after the suspected drug was administered ( + 2 ) ; the adverse reaction improved when the drug was discontinued ( + 1 ) ; the adverse reaction did not reappear when the drug was re - administered ( 1 ) , and there were no alternative causes that , on their own , could have caused the reaction ( + 2 ) . although afatinib - induced uveitis has not been previously reported , a prior study by kawaguchi et al .   did report a case of bilateral erlotinib - induced uveitis that showed granulomatous inflammation accompanying koeppe nodules . thus , granulomatous anterior uveitis with iris nodules could possibly be a characteristic of egfr inhibitor - induced uveitis . although our current case only showed unilateral involvement , all other previous reports of uveitis secondary to erlotinib have been reported to be bilateral . in our current case , the patient developed bilateral conjunctival injection prior to the uveitis , which might be a symptom of anterior uveitis . if we had we not stopped the afatinib treatment , the possibility exists that uveitis might have developed in his left eye . however , the specific reason why only the right eye was involved remains unknown at present . after we stopped the afatinib treatment , our results showed that the topical use of steroid and mydriatics were effective in treating the afatinib - caused anterior uveitis . while the exact reason why the patient did not develop uveitis upon re - administration of the drug is unknown , one possibility might be that the dose was lower and/or there was continuation of the topical steroid . in conclusion , ophthalmologists need to be aware of the possibility that drug - induced uveitis could occur during the treatment of cancer in patients , even when the uveitis is unilateral . written informed consent was obtained from the patient for publication of this case report and any accompanying images .
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 .