Adverse events after intravitreal infliximab (Remicade).
OBJECTIVE
To determine the tolerability of intravitreal infliximab (Remicade) in patients with refractory diabetic macular edema or choroidal neovascularization secondary to age-related macular degeneration.


METHODS
This is a prospective, interventional, noncomparative, open-label, 12-week pilot study of intravitreal infliximab in four patients who failed conventional therapies. Two had diabetic macular edema and two had choroidal neovascularization secondary to age-related macular degeneration. All patients received 0.5 mg/0.05 mL intravitreal infliximab and were eligible for a second injection at 6 weeks if reinjection criteria were met. Outcome measures were best-corrected visual acuity using standard Early Treatment Diabetic Retinopathy Study refraction, central retinal thickness on optical coherence tomography, fluorescein angiography, standard electroretinography, and microperimetry. Patients were evaluated at Days 0 and 1 and Weeks 2, 6, and 12. Six months after study completion, all patients were tested for human antimouse and human antichimeric antibodies.


RESULTS
At Week 12, visual acuity scores had declined in three patients. All patients had persistence of cystoid macular edema on optical coherence tomography, although two had a decrease in central retinal thickness. Three patients had an overall worsened appearance on angiography. On the final electroretinography, all patients had a decrease in maximal combined responses, from 7% to 24% from baseline, which may have been within expected variability of electroretinography data. To photopic flicker stimulus, three patients had slower latency of response, and all had decreased amplitudes. All patients declined on microperimetry. The first patient entered in the study met the criteria for a second injection because of improved standard electroretinography and microperimetry at Week 6. However, 2 weeks after the second injection, he developed panuveitis. Two other patients, after one injection only, had evidence of inflammation (vitritis or panuveitis) on examination at Week 6. Three patients developed systemic antibodies against infliximab (human antichimeric antibodies).


CONCLUSIONS
Low-dose intravitreal infliximab was not well tolerated in this small group of patients and was both immunogenic and probably retinotoxic.
Giganti
Monica
M
Retina Consultants PLLC, Slingerlands, NY, USA. drgiganti@retinaconsultant.org
Beer
Paul M
PM
Lemanski
Nicole
N
Hartman
Coby
C
Schartman
Jerome
J
Falk
Naomi
N
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology; D002678:Chimera / Q000276:immunology; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000209:etiology; D003930:Diabetic Retinopathy / Q000150:complications / Q000188:drug therapy; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D007267:Injections; D008268:Macular Degeneration / Q000150:complications / Q000188:drug therapy; D008269:Macular Edema / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D015864:Panuveitis / Q000139:chemically induced* / Q000175:diagnosis; D010865:Pilot Projects; D011446:Prospective Studies; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D041623:Tomography, Optical Coherence; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014822:Vitreous Body
D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab