Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Neurotrophic Keratitis.
Treatment: Oxervate, Pre-service.
The insurer denied the Oxervate, Pre-service.
The denial is upheld. 

The patient is a male with neurotrophic keratitis for whom coverage of Oxervate is the subject of review.  According to the provider, the patient has extreme neurokeratitis and dry eyes and is in danger of perforating corneal ulcers. 

Coverage was previous denied per policy criteria as the patient has previously received an eight-week course of Oxervate. 

An exam documents the patient is complaining that his eyes have been red and itchy after stopping Oxervate. He was continuing to take Refresh and Cequa. Previous treatment also included punctal plugs, Lipiflow/Blephex and placement of amniotic membranes. On exam, vision was 20/25-1 right eye (OD) and 20/25-2 left eye (OS).  An anterior segment exam found decreased tear lakes and two-plus filaments in both eyes (OU). Decreased corneal sensation was noted bilaterally. An amniotic membrane was placed in the left eye (OS). The patient was instructed to complete the course of Oxervate (six times per day for two months) prior to bandage contact lens use. 

Upon appeal, it is reported that the patient has a severe case of neurotrophic keratitis (NK) that improved after the first round but needs a second round to enjoy clinically significant benefits.

Based on the information provided, the proposed second eight-week course of Oxervate is not established as medically necessary per standard of care.

Neurotrophic keratitis (NK) is a corneal degenerative disease characterized by a reduction or absence of corneal sensitivity. In neurotrophic keratitis, corneal innervation by the trigeminal nerve is impaired. Partial or complete loss of corneal sensation may result in epithelial keratopathy, epithelial defect, stromal ulceration, and eventually corneal perforation. Clinical presentation of neurotrophic keratitis ranges from subtle corneal surface irregularities to corneal melting and perforation. Neurotrophic keratitis is usually graded in three different stages according to the "Mackie classification".

Stage I is characterized by epithelial irregularity most commonly in the form of punctate keratopathy without epithelial defect.

Stage II is defined by recurrent or persistent epithelial defects (PED) without stromal involvement. The persistent epithelial defects (PED) is usually oval in shape and its margins are characteristically smooth and rolled due to impaired epithelial healing. Descemet's folds and anterior chamber inflammation may be observed.

Stage III is characterized by stromal involvement leading to corneal ulcer, melting, and perforation

The management of neurotrophic keratitis airs to promote corneal healing and avoid complications. Patients with neurotrophic keratitis should use preservative-free medications, as epithelial drug toxicity could complicate the disease. Ocular surface diseases other than /associated with neurotrophic keratitis (i.e., dry eye, blepharitis, exposure keratitis, limbal stem cell deficiency) should be properly treated. Therapy of neurotrophic keratitis depends on the disease stage. With stage I neurotrophic keratitis, frequent application of preservative-free artificial eye drops and lubricant ointment is suggested punctal occlusion may be beneficial. In cases of persistent keratopathy, autologous serum tears may be helpful. Therapeutic soft contact lenses or amniotic membrane grafts may also be helpful. With stage II neurotrophic keratitis, the aim of therapy is to promote persistent epithelial defect healing and prevent the development of a corneal ulcer. Treatment includes the use of unpreserved artificial tears, lubricant ointments, therapeutic soft contact lenses or patching, topical autologous serum, amniotic membrane grafts tarsorrhaphy or botulinum induced ptosis and topical recombinant human nerve growth factor treatment. Antibiotic eye drops can be prescribed to prevent bacterial infections. Topical corticosteroids can be used to control inflammation cautiously, as they could induce stromal melting. With stage III disease, therapy focuses on ulcer healing and prevention of corneal perforation. 

The Food and Drug Administration (FDA) approved Oxervate (cenegermin) for the treatment of neurotrophic keratitis. Recommended dosage and administration is one drop of Oxervate in the affected eye(s), six times per day at two-hour intervals, for eight weeks.

The safety and efficacy of Oxervate, a topical eye drop containing cenegermin, was studied in a total of 151 patients with neurotrophic keratitis in two, eight-week, randomized controlled multi-center, double-masked studies. In the first study, patients were randomized into three different groups. One group received Oxervate, a second group received an eye drop with a different concentration of cenegermin, and the third group received an eye drop without cenegermin. In the second study, patients were randomized into two groups. One group was treated with Oxervate eye drops and the other group was treated with an eye drop without cenegermin. All eye drops in both studies were given six times daily in the affected eye(s) for eight weeks. In the first study, only patients with the disease in one eye were enrolled, while in the second study, patients with the disease in both eyes were treated in both eyes (bilaterally). Across both studies, complete corneal healing in eight weeks was demonstrated in 70 percent of patients treated with Oxervate compared to 28 percent of patients treated without cenegermin (the active ingredient in Oxervate).

Oxervate is usually reserved for the treatment of stage II (moderate) or stage III (severe) neurotrophic keratitis. A second course of Oxervate may be considered medically necessary if the patient continues to have stage II or stage III keratitis while demonstrating some beneficial response to treatment.

In this case, the records provided for review document that the patient has decreased corneal sensation in both eyes (OU). There is no documentation of epithelial defects or corneal ulcers. There is no documentation of the patient's response to the initial eight-week course of Oxervate other than are report that it "improved after 1st round." Therefore, a second eight-week course of Oxervate is not established as medically necessary.