Outcomes Associated With Sustained-Release Intraocular Fluocinolone Implants in a Case of Melanoma-Associated Retinopathy Treated Without Systemic Immunosuppression

Abstract

IMPORTANCE Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome in which antiretinal antibodies crossreact with retinal ON-bipolar cells, resulting in night blindness and progressive visual field loss. Current therapeutic options include cytoreductive surgery in combination with immunoglobulin, corticosteroids, or plasmapheresis, but their effectiveness is limited and may be contraindicated, given the possible protective role of circulating autoantibodies against metastatic spread. We report 3-year follow-up of the first case (to our knowledge) of MAR treated with intravitreal long-acting steroid implants.OBJECTIVE To report on a patient with MAR who was treated with intravitreal fluocinolone acetonide implants in the absence of systemic immunosuppression. DESIGN, SETTING, AND PARTICIPANTSThis is a 3-year follow-up of a 73-year-old woman with a history of surgical excision of a malignant melanoma of the left pinna who presented with visual symptoms of shimmering and nyctalopia. Fundus examination, fundus autofluorescence, and optical coherence tomography were normal, with no evidence of cystoid macular edema. Automated perimetry showed a reduction in visual field and full-field electroretinography (ERG) demonstrated findings consistent with generalized ON-bipolar cell dysfunction, typical of MAR. The patient was treated with bilateral fluocinolone acetonide intravitreal implants. MAIN OUTCOMES AND MEASURESVisual acuity, visual field, and electroretinography testing for 3 years after treatment. RESULTSVisual fields improved in this 73-year-old patient from 20/30 (Snellen measured as 6/9) OD and 20/16 (6/5) OS at baseline to 20/20 OU within 1 week of treatment. Detailed electroretinography monitoring indicated characteristic abnormalities that partly resolved after treatment, consistent with improved inner retinal ON-bipolar cell function. Bilateral cataracts developed approximately 2 years after injection; cataract surgery was performed uneventfully. At 3 years posttreatment, the patient remained visually stable and in systemic disease remission, with best-corrected visual acuity remaining at 20/20 OU. CONCLUSIONS AND RELEVANCEWe report what is, to our knowledge, the first case of MAR treated with intravitreal slow-release corticosteroid implants, which shows improvements in visual symptoms, visual fields, and retinal function. Sustained-release intraocular steroid implants may offer an effective and safe alternative to systemic immunosuppression in MAR, although results from 1 case should be generalized with abundant caution.

Evaluation of fluocinolone acetonide 0.19 mg intravitreal implant in the management of birdshot retinochoroiditis

“…We analysed the choroidal response to Iluvien ® implant of 15 eyes in 11 patients, and in all patients the choroid inflammatory involvement seemed to persist despite the steroid implant. Choroidal thickness has been mentioned in the literature as an indirect measure of choroidal activity, and can discriminate between active BRC patients and controls [19]. Case 1 in our series is illustrative, as choroidal thickening persisted after the Iluvien ® implant and was associated with progressive peripapillary RPE changes.…”

“…The therapeutic role of local ocular corticosteroids in non-infectious posterior uveitis is well established [19][20][21][22][23][24][25][26][27]. Slow-release, sustained-delivery intravitreal corticosteroid implants are approved for non-infectious uveitis, including the FAc 0.19 mg intravitreal implant (Iluvien®; Alimera Sciences Limited, Aldershot, UK).…”

An update on autoimmune retinopathy

“…There is no standard treatment protocol currently but the various therapeutic options described for AIRs, in the previous literature[ 7 10 21 22 23 39 40 51 59 60 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 ] are (1) immunosuppression through systemic and/or topical (intravitreal/sub-tenon/depot) corticosteroids, (2) immunomodulators like cyclosporine (calcineurin inhibitor which prevents IL-2 transcription), infliximab (anti-TNFα antibody), mycophenolate mofetil (IMP dehydrogenase inhibitor, preventing purine synthesis), azathioprine (purine antimetabolite), (3) biologics such as monoclonal antibodies like rituximab (anti-CD20 antibody), alemtuzumab (anti-CD52 antibody), ipilimumab (antagonist antibody against cytotoxic T-lymphocyte antigen-4), tocilizumab (anti-IL-6 receptor antibody), sarilumab (anti-IL-6 receptor antibody), (4) and others like intravenous immunoglobulin (IVIG), plasmapheresis. IVIG has been hypothesized to have several mechanisms of action like neutralization of autoantibodies, binding of complement components, inhibition of dendritic cells maturation, modulation of intercellular adhesion, and contribution of IgG4.…”

“…Once a diagnosis of AIR is established, the best approach is to first reduce the tumor burden using chemotherapy, radiotherapy, and/or surgery[ 10 59 70 ] as indicated, in paraneoplastic retinopathies. For all cases of AIR, it is generally suggested to begin with steroids (local or systemic) and/or with antimetabolites/T-cell inhibitors, as the first or second-line treatment respectively,[ 21 25 51 62 63 66 73 74 79 90 92 ] after systemic management of the underlying autoimmune disease, if present. A short-term treatment trial with intravitreal or sub-tenon triamcinolone (40-80 mg, two injections over 8 months) has been suggested, before starting systemic steroids (60-80 mg oral prednisone daily), to both confirm the diagnosis as well as to avoid the adverse effects of treatment.…”

“…[ 74 ] More recently, a case report describes improvement in visual acuity, visual field, and retinal function with bilateral intravitreal sustained-release fluocinolone acetonide implant in a patient with MAR, in the absence of any systemic therapy. [ 90 ] Since AIR has an autoimmune basis, long-term treatment was initially advocated (4 months to a year or more) for both stabilization and regain of the lost visual function,[ 25 ] but there is still a controversy on the potential benefit of the same[ 21 69 98 ] and hence a prospective randomized placebo-controlled clinical trial is warranted. [ 51 ]…”