Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Bilateral Chorioretinal Inflammation And Bilateral Panuveitis Of The Eye
Treatment: Intravenous Immunoglobulin (IVIG) Code J1569
The insurer denied the Intravenous Immunoglobulin (IVIG) Code J1569.
The denial is overturned. 

The patient is a female with bilateral chorioretinal inflammation and panuveitis for whom coverage of IVIG (intravenous immunoglobulin) therapy is the subject of review. Coverage was previously denied as experimental/investigational per Aetna Clinical Policy Bulletin (Parenteral Immunoglobulins) for this patient's indication. 

Upon appeal, the patient is identified as having autoimmune retinopathy/acute zonal occult outer retinopathy (AZOOR) - a rare form of posterior uveitis.  The provider states that the inflammation affects the patient's retina and optic nerve with potential to cause permanent blindness. Reportedly, she has tried and failed methotrexate, azathioprine, Cellcept, Humira, triamcinolone injections and Ozurdex implants. The patient is currently on oral prednisone along with Humira and methotrexate. The provider states that the patient has seen the world's expert on this condition who confirmed the diagnosis and recommended treatment with IVIG (intravenous immunoglobulin).  The patient is currently taking prednisone at levels which are leading to significant comorbidity. The provider states that the only other options for the patient include rituximab and Actemra, but he has not observed significant in patient's treated with rituximab and there is not much literature on the subject to support such use.  

An exam documents vision as currently corrected to 20/20 OU (both eyes). Intraocular pressures were 19 mm (millimeters) Hg (mercury) OU (both eyes). Visual field restriction was noted bilaterally.    

Yes, the health plan should cover the treatment with IVIG (intravenous immunoglobulin) Therapy (J1569).

Yes, the requested IVIG (intravenous immunoglobulin) Therapy (J1569) is likely to be more beneficial than any of the remaining treatment options identified considering that standard treatments for the insured's condition have been exhausted.

In this case, IVIG (intravenous immunoglobulin) is proposed for a patient with presumed autoimmune retinopathy/acute zonal occult outer retinopathy who has failed more conventional therapies including methotrexate, azathioprine, Cellcept, Humira, triamcinolone injections and Ozurdex implants as well as oral and topical steroids. 

Autoimmune retinopathies (AIRs) are a group of inflammatory-mediated diseases characterized by the presence of antiretinal antibodies (ARAs), visual field deficits, and photoreceptor dysfunction in the setting of progressive unexplained vision loss.  The AIRs (autoimmune retinopathies) encompass the better-studied paraneoplastic syndromes, such as cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), and a larger group of AIRs (autoimmune retinopathies) that have similar clinical and immunologic features but that are not associated with an underlying malignancy. The term non-paraneoplastic autoimmune retinopathy (npAIR) was coined to describe this latter group, which has previously been called recovering-associated retinopathy, autoimmune retinopathy in the absence of cancer, or, simply, autoimmune retinopathy.

There are no standard guidelines for the management of AIR (autoimmune retinopathy). The rarity of AIRs (autoimmune retinopathies), and the difficulty in firmly establishing the diagnosis, has limited investigations that evaluate treatment outcomes. According to Grange et al, common approaches to both paraneoplastic and non-paraneoplastic autoimmune retinopathy include systemic or local corticosteroids, intravenous immunoglobulin or plasmapheresis. Additionally, antimetabolites, such as mycophenolate mofetil and azathioprine, and T-cell inhibitors such as cyclosporine have been used. Less frequently, targeted B-cell therapy, such as anti-CD20 (cluster of differentiation 20) monoclonal antibody (rituximab), has also been used. Unfortunately, therapy is not helpful once widespread retinal degeneration has occurred. 

According to a more recent review by Sen, "Most evidence in the treatment of AIR [autoimmune retinopathy) relies on reports of pAIR [paraneoplastic autoimmune retinopathy] and includes corticosteroids, plasmapheresis, intravenous immunoglobulin (IVIG), and other immunomodulators...There is no consensus on the best approach or whether treatment is beneficial. Of the 45 members who responded to a more detailed question about treatment approaches, 46.7% selected systemic or local corticosteroids as the first step in treatment of npAIR [non-paraneoplastic autoimmune retinopathy], whereas IVIG [intravenous immunoglobulin] (8.9%), plasmapheresis (8.9%), nonbiologic immunosuppressives (20.0%), and biologics (13.3%) were chosen as the first step by a minority."

A review of the literature shows that treatment results with IVIG (intravenous immunoglobulin) are found primarily as case reports/case series. Guy et al reported three cases of pAIR (paraneoplastic autoimmune retinopathy) treated with IVIG (intravenous immunoglobulin). In one patient, visual acuity improved dramatically within 24 hours of taking the first dose, but visual field improved two weeks later. In the second patient, there was no improvement, although ARA (antiretinal antibody) levels declined. In the third patient, the visual field improved. Treatment was started in early stages of disease for all patients. 

More recently, Fekri et al reported a 12-year-old male with npAIR (non-paraneoplastic autoimmune retinopathy) stabilized with intravenous immunoglobulin (IVIG).

As this patient has exhausted more conventional therapies for this rare condition, and a review of the literature support the use of IVIG (intravenous immunoglobulin) as among second-line treatments of this patient's condition, the medical appropriateness of IVIG (intravenous immunoglobulin) is established.