A Strange Case of Post-injection Uveitis Todd J. Purkiss, M.D., Ph.D. Retina Associates of Kentucky May 19, 2016

History 78 year old white male with NVAMD OU: 78 year old white male with NVAMD OU: OS diagnosed 2011, treated with monthly Avastin, PDT, then monthly Eylea beginning 2/2014 OS diagnosed 2011, treated with monthly Avastin, PDT, then monthly Eylea beginning 2/2014 OD diagnosed 10/2014 and treated from the start with monthly Eylea OD diagnosed 10/2014 and treated from the start with monthly Eylea PMH: PMH: Arthritis, HTN, PPH, s/p CABG 2012, s/p PCIOL (2/2015 OS, 4/2015 OD) Arthritis, HTN, PPH, s/p CABG 2012, s/p PCIOL (2/2015 OS, 4/2015 OD)

Presentation Injection visit 4/2015, was symptomatic for new floaters OS, and PVD confirmed on exam; no other abnormalities noted Injection visit 4/2015, was symptomatic for new floaters OS, and PVD confirmed on exam; no other abnormalities noted Eylea injected OU, as scheduled Eylea injected OU, as scheduled Two days later, presented with red, painful OS Two days later, presented with red, painful OS Exam demonstrated 2+ cell, trace flare Exam demonstrated 2+ cell, trace flare Diagnosed with iritis, started on PF QID Diagnosed with iritis, started on PF QID

Course Three days later, improved, but some vitreous debris Three days later, improved, but some vitreous debris Switched to Durezol TID Switched to Durezol TID Two days later, OS was quiet Two days later, OS was quiet Two weeks following onset, remained quiet Two weeks following onset, remained quiet Began Durezol taper (BID x 1 week, daily x 1 week, then stop) Began Durezol taper (BID x 1 week, daily x 1 week, then stop)

Course At scheduled 1 month exam, OS worse with small KP and small hypopyon At scheduled 1 month exam, OS worse with small KP and small hypopyon Injection held OU, and Durezol OS TID restarted Injection held OU, and Durezol OS TID restarted No significant improvement after 24 hours, so concerned for endophthalmitis No significant improvement after 24 hours, so concerned for endophthalmitis Injected Vancomycin and Ceftazidime Injected Vancomycin and Ceftazidime

Course A week later, significantly improved OS, but NVAMD again active OD A week later, significantly improved OS, but NVAMD again active OD Eylea injected OD Eylea injected OD Two weeks post antibiotics OS, only mild vitreous debris remained Two weeks post antibiotics OS, only mild vitreous debris remained Durezol taper initiated Durezol taper initiated Uncertain whether was endophthalmitis or inflammation Uncertain whether was endophthalmitis or inflammation

Course Follow-up visit 6/2015, OS remained quiet off Durezol, but NVAMD active OU Follow-up visit 6/2015, OS remained quiet off Durezol, but NVAMD active OU Eylea injected OU Eylea injected OU

Course Two days later, trace injection and trace cell OS! Two days later, trace injection and trace cell OS! Presumed inflammatory response to Eylea Presumed inflammatory response to Eylea Started Durezol QID with planned taper over next month Started Durezol QID with planned taper over next month At scheduled monthly visit, OS nearly quiet again At scheduled monthly visit, OS nearly quiet again Eylea injected OD, but held OS Eylea injected OD, but held OS

Course At scheduled monthly visit, OS quiet, but NVAMD active At scheduled monthly visit, OS quiet, but NVAMD active Eylea injected OD per schedule Eylea injected OD per schedule Lucentis injected OS Lucentis injected OS

Course Two days later, patient again developed symptoms OS, but did not call in, due to holiday weekend Two days later, patient again developed symptoms OS, but did not call in, due to holiday weekend When seen 4 days following injection, 4+ injection, K edema, 4+ cell with trace hypopyon When seen 4 days following injection, 4+ injection, K edema, 4+ cell with trace hypopyon Durezol QID and Atropine BID started Durezol QID and Atropine BID started

Course At scheduled monthly visit, OS again improved At scheduled monthly visit, OS again improved Eylea injected OD Eylea injected OD Continue Durezol QID OS Continue Durezol QID OS Next monthly visit, OS quiet Next monthly visit, OS quiet Eylea injected OD Eylea injected OD Continue Durezol QID OS with plan to suppress inflammation from future injection Continue Durezol QID OS with plan to suppress inflammation from future injection

Course Two weeks later, NVAMD active OS Two weeks later, NVAMD active OS Eylea injected Eylea injected Remained on Durezol QID Remained on Durezol QID The next month, OS with mild KP, trace cell, but moderate vitreous debris The next month, OS with mild KP, trace cell, but moderate vitreous debris Eylea OD per schedule Eylea OD per schedule Remained on Durezol QID OS Remained on Durezol QID OS

Course Two weeks later, patient bothered by lingering vitreous debris OS Two weeks later, patient bothered by lingering vitreous debris OS Decision made to perform PPV Decision made to perform PPV Vancomycin, Ceftazidime, and Voriconazole injected Vancomycin, Ceftazidime, and Voriconazole injected Vitreous biopsy sent for testing Vitreous biopsy sent for testing

Course Vitreous biopsy results: Vitreous biopsy results: Gram stain negative Gram stain negative Bacterial cultures negative Bacterial cultures negative Fungal cultures negative Fungal cultures negative Acid-fast bacillus negative Acid-fast bacillus negative Flow cytometry Flow cytometry CD % CD % CD % CD % Normal inflammatory cells Normal inflammatory cells

Course Has continued Eylea OD Has continued Eylea OD Has received Triescence twice OS for CME, with good response Has received Triescence twice OS for CME, with good response Mild SR hemorrhage at inferior border of PED OS, but has been improving Mild SR hemorrhage at inferior border of PED OS, but has been improving VA last month: VA last month: 20/20 OD 20/20 OD 20/30 OS 20/30 OS

Summary Recurrent inflammation OS Recurrent inflammation OS Symptoms always began 2 days following injection Symptoms always began 2 days following injection Seen with Eylea and Lucentis, but not with Triescence Seen with Eylea and Lucentis, but not with Triescence No evidence of infection or malignancy No evidence of infection or malignancy Never a reaction OD, despite regularly scheduled Eylea throughout Never a reaction OD, despite regularly scheduled Eylea throughout

Etiology? Reaction to medication? Reaction to medication? Eylea and Lucentis different molecules Eylea and Lucentis different molecules Reaction to vehicle? Reaction to vehicle? Only common component is polysorbate 20, which has never had a reported hypersensitivity in the literature Only common component is polysorbate 20, which has never had a reported hypersensitivity in the literature Reaction to silicone in syringe? Reaction to silicone in syringe? Reaction to mechanical stimulation of injection? Reaction to mechanical stimulation of injection?

Future Plan? If NVAMD becomes active again OS: If NVAMD becomes active again OS: Repeat Eylea? Repeat Eylea? Concurrent Ozurdex? Concurrent Ozurdex? PDT? PDT?

Update! NVAMD again became active OS: NVAMD again became active OS: Repeated Eylea, per patient request Repeated Eylea, per patient request Patient had Durezol, in case of inflammation Patient had Durezol, in case of inflammation Patient reported some inflammatory symptoms post-injection and started Durezol Patient reported some inflammatory symptoms post-injection and started Durezol At monthly follow-up, had tapered Durezol and no signs of inflammation, so not sure eye was actually inflamed At monthly follow-up, had tapered Durezol and no signs of inflammation, so not sure eye was actually inflamed