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Intravitreal Corticosteroid Implants

Policy Number: MP-451

Latest Review Date: March 2022

Category:  Pharmacology                                                      

POLICY:

FDA approved fluocinolone acetonide intravitreal implants may be considered medically necessary for their specific indications:

  • Retisert® (0.59 mg) may be considered medically necessary for the treatment of chronic non-infectious intermediate, posterior, or panuveitis, in one or both eyes.
  • Iluvien® (0.19 mg) may be considered medically necessary for the treatment of diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure.
  • Yutiq® (0.18 mg) may be considered medically necessary for the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye.

FDA approved dexamethasone intravitreal implant 0.7 mg (i.e., Ozurdex®) may be considered medically necessary for treatment of the following indications:

  • Noninfectious uveitis affecting the intermediate or posterior segment of the eye; OR
  • Macular edema following branch or central retinal vein occlusion; OR
  • Diabetic macular edema

All other uses of a corticosteroid intravitreal implant are considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

An intravitreal implant is a drug delivery system, injected or surgically implanted in the vitreous of the eye, for sustained release of a pharmacologic agent to the posterior and intermediate segments of the eye. Intravitreal corticosteroid implants are reviewed herein. Fluocinolone acetonide implants (e.g. Retisert, Iluvien, Yutiq) are non-erodible and deliver drug up to 30 to 36 months, while dexamethasone implants (e.g. Ozurdex) are bio-erodible and last up to six months.

Eye Conditions

Uveitis

Uveitis encompasses a variety of conditions, of either infectious or noninfectious etiologies, that are characterized by inflammation of any part of the uveal tract of the eye (iris, ciliary body, choroid). Infectious etiologies include syphilis, toxoplasmosis, cytomegalovirus retinitis, and candidiasis. Noninfectious etiologies include sarcoidosis, Behçet syndrome, and “white dot” syndromes such as multifocal choroiditis or “birdshot” chorioretinopathy. Uveitis may also be idiopathic, have a sudden or insidious onset, a duration that is limited (less than three months) or persistent, and a course that may be acute, recurrent, or chronic.

The classification scheme recommended by the Uveitis Study Group and the Standardization of Uveitis Nomenclature Working Group is based on anatomic location. Patients with anterior uveitis typically develop symptoms such as light sensitivity, pain, tearing, and redness of the sclera. In posterior uveitis, which comprises approximately 5% to 38% of all uveitis cases in the United States, the primary site of inflammation is the choroid or retina (or both). Patients with intermediate or posterior uveitis typically experience minimal pain, decreased visual acuity, and the presence of floaters (bits of vitreous debris or cells that cast shadows on the retina). Chronic inflammation associated with posterior segment uveitis can lead to cataracts, glaucoma, and structural damage to the eye, resulting in severe and permanent vision loss.

Treatment- Uveitis

The primary goal of therapy for uveitis is to preserve vision. Noninfectious uveitis typically responds well to corticosteroid treatment. Immunosuppressive therapy (e.g., antimetabolites, alkylating agents, T-cell inhibitors, tumor necrosis factor inhibitors) may also be used to control severe uveitis. Immunosuppressive therapy is typically reserved for patients who require chronic high-dose systemic steroids to control their disease. While effective, immunosuppressants may have serious and potentially life-threatening adverse effects, including renal and hepatic failure and bone marrow suppression.

Macular Edema after Retinal Vein Occlusion

Retinal vein occlusions are classified by whether the central retinal vein or one of its branches is obstructed. Central retinal vein occlusion and branch retinal vein occlusion differ in pathophysiology, clinical course, and therapy. Central retinal vein occlusions are categorized as ischemic or non-ischemic. Ischemic Central retinal vein occlusions are referred to as severe, complete, or total vein obstruction, and account for 20% to 25% of all central retinal vein occlusions. Macular edema and permanent macular dysfunction occur in virtually all patients with ischemic central retinal vein occlusions, and in many patients with non-ischemic central retinal vein occlusions. Branch retinal vein occlusion is a common retinal vascular disorder in adults between 60 and 70 years of age and occurs approximately three times more often than central retinal vein occlusion.

Treatment- Macular Edema after Retinal Vein Occlusion

Intravitreal injections of triamcinolone are used to treat macular edema associated with central retinal vein occlusion, with a modest beneficial effect on visual acuity. The treatment effect lasts about six months, and repeat injections may be necessary. Cataracts are a common side effect, and steroid-related pressure elevation occurs in about one-third of patients, with 1% requiring filtration surgery.

Macular photocoagulation with grid laser improves vision in branch retinal vein occlusion but is not recommended for central retinal vein occlusion. Although intravitreal injections of triamcinolone have also been used for branch retinal vein occlusion, serious adverse events have stimulated the evaluation of new treatments, including intravitreal steroid implants or the intravitreal injection of antivascular endothelial growth factor.

Diabetic Macular Edema

Diabetic retinopathy is a common microvascular complication of diabetes and a leading cause of blindness in adults.  The two most serious complications for vision are diabetic macular edema and proliferative diabetic retinopathy. At its earliest stage (non-proliferative retinopathy), microaneurysms occur. As the disease progresses, blood vessels that nourish the retina are blocked, triggering the growth of new and fragile blood vessels (proliferative retinopathy).  Severe vision loss with proliferative retinopathy arises from leakage of blood into the vitreous. Diabetic macular edema is characterized by swelling of the macula due to gradual leakage of fluids from blood vessels and breakdown of the blood-retinal barrier. Moderate vision loss can arise from the fluid accumulating in the center of the macula (macular edema) during the proliferative or nonproliferative stages of the disease. Although proliferative disease is the main blinding complication of diabetic retinopathy, macular edema is more frequent and is the leading cause of moderate vision loss in people with diabetes.

Treatment- Diabetic Macular Edema

Tight glycemic and blood pressure control is the first line of treatment to control diabetic retinopathy, followed by laser photocoagulation for patients whose retinopathy is approaching the high-risk stage. Although laser photocoagulation is effective at slowing the progression of retinopathy and reducing visual loss, it does not restore lost vision. Alternatives to intravitreal implants include intravitreal injection of triamcinolone acetonide, which is used as an off-label adjunctive therapy for diabetic macular edema.  Angiostatic agents such as injectable vascular endothelial growth factor inhibitors, which block stages in the pathway leading to new blood vessel formation (angiogenesis), have demonstrated efficacy in diabetic macular edema.

Age-Related Macular Degeneration

Age-related macular degeneration is a degenerative disease of retina that results in loss of central vision with increasing age. Two different forms of degeneration, known as dry and wet, may be observed. The dry form (also known atrophic or areolar) is more common and is often a precursor to the wet form (also known as exudative neovascular or disciform). The wet form is more devastating and characterized by serous or hemorrhagic detachment of the retinal pigment epithelium and development of choroidal neovascularization, which greatly increases the risk of developing severe irreversible loss of vision. Choroidal neovascularization is categorized as classic or occult.

Treatment- Age-Related Macular Degeneration

Effective specific therapies for exudative or wet age-related macular degeneration are intravitreous injection of a vascular endothelial growth factor inhibitor, possibly thermal laser photocoagulation (in selected patients), and photodynamic therapy.

Intravitreal Implants

Intravitreal implants deliver a continuous concentration of a pharmacologic agent to the eye over a prolonged period. The goal of therapy is to reduce inflammation in the eye while minimizing the adverse events of the therapeutic regimen.

Selection of the route of corticosteroid administration (topical, systemic, periocular, or intraocular injection) is based on the cause, location, and severity of the disease. Each therapeutic approach has drawbacks. For example, topical corticosteroids require frequent (e.g., hourly) administration and may not adequately penetrate the posterior segment of the eye due to their poor ability to penetrate ocular tissues. Systemically administered drugs penetrate poorly into the eye because of the blood-retinal barrier, and high-dose or long-term treatments may be necessary. Long-term systemic therapies can be associated with substantial adverse events such as hypertension and osteoporosis, while repeated (every 4-6 weeks) intraocular corticosteroid injections may result in pain, intraocular infection, globe perforation, fibrosis of the extraocular muscles, reactions to the delivery vehicle, increased intraocular pressure, and cataract development.

Corticosteroid implants are biodegradable or non-biodegradable. Non-biodegradable systems are thought to be preferable for treating chronic, long-term disease, while biodegradable products may be preferred for conditions that require short-term therapy. Although the continuous local release of steroid with an implant may reduce or eliminate the need for intravitreal injections and/or long-term systemic therapy, insertion or surgical implantation of the device carries risks, and the device could increase ocular toxicity due to increased corticosteroid concentrations in the eye over a longer duration. With any route of administration, cataracts are a frequent complication of long-term corticosteroid therapy.

Intraocular corticosteroid implants being evaluated include:

  • Retisert (non-biodegradable fluocinolone acetonide intravitreal implant; Bausch & Lomb) is a sterile implant that consists of a tablet containing fluocinolone acetonide 0.59 mg, a synthetic corticosteroid that is less soluble in aqueous solution than dexamethasone. The tablet is encased in a silicone elastomer cup with a release orifice and membrane; the entire elastomer cup assembly is attached to a suture tab. Following implantation (via pars plana incision and suturing) in the vitreous, the implant releases the active drug at a rate of 0.3 to 0.4 μg/d over 2.5 years.
  • ILUVIEN (non-biodegradable injectable intravitreal implant with fluocinolone acetonide; Alimera Sciences) is a rod-shaped device made of polyimide and polyvinyl alcohol. It is small enough to be placed using a 25-gauge applicator. It is expected to provide sustained delivery of fluocinolone acetonide for up to three years.
  • Ozurdex (previously known as Posurdex; biodegradable dexamethasone intravitreal implant; Allergan, Irvine, CA) is composed of a biodegradable copolymer of lactic acid and glycolic acid with micronized dexamethasone. This implant is placed into the vitreous cavity through the pars plana using a customized, single-use, 22-gauge applicator. The implant provides intravitreal dexamethasone for up to six months. The mean number of Ozurdex injections reported in the literature is 4.2 injections per year, and more than six consecutive injections have been reported.
  • Yutiq (non-biodegradable fluocinolone acetonide intravitreal implant; EyePoint Pharmaceuticals U.S., Inc.) is a sterile 3.3 mm-long implant consisting of fluocinolone acetonide 0.18 mg that is preloaded into a single-dose applicator and injected directly into the vitreous. It is designed to provide a sustained release of fluocinolone acetonide at an initial rate of 0.25 mcg/day over a 36-month period.

KEY POINTS:

The most recent update of this policy with literature review was performed through February 1, 2022.

Summary of Evidence

Uveitis

For individuals with chronic noninfectious intermediate or posterior uveitis who receive an intravitreal fluocinolone acetonide implant (0.59 mg), the evidence RCTs. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Two of the four RCTs compared two doses of implants and two trials compared implants with systemic steroids (and immunosuppression when indicated). All trials supported the efficacy of intravitreal fluocinolone acetonide implants in preventing recurrence and improving visual acuity over a four-year follow-up. The head-to-head trial comparing implants with systemic corticosteroids did not show substantial superiority in the overall effectiveness of either approach. After 24 and 54 months of follow-up, visual acuity improved from baseline in the implant groups compared to the systematic therapy groups by +6.0 and +3.2 letters (p=0.16) and +2.4 and 3.1 letters (p=0.073), respectively. However, nearly all phakic patients receiving implants developed cataracts and required cataract surgery. Further, most also developed glaucoma, with 75% of patients requiring intraocular pressure lowering medications and 35% requiring filtering surgeries. Systemic adverse events such as hyperlipidemia, diabetes, osteoporosis, fractures, and blood count/chemistry abnormalities were infrequent and not statistically distinguishable between groups. The incidence of hypertension was greater in the systemic therapy group (27%) compared to the implant group (13%), but rates of antihypertensive treatment initiation did not differ. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with noninfectious intermediate or posterior uveitis who receive an intravitreal dexamethasone implant (0.7 mg), the evidence includes an RCT. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Results of this trial at eight weeks showed that the implant was effective in reducing inflammation (the proportion of eyes with no inflammation was 47% and 12% with implant and sham, respectively) and resulted in clinically meaningful improvement in vision at week eight compared to sham controls (the proportion of patients with a gain of greater than15 letters in best-corrected visual acuity [BCVA] from baseline was greater than 40% with implants and 10% with sham). Further, at week 26, patients treated with implants reported meaningful increases in vision-related functioning. The major limitation of this trial was its lack of long-term follow-up. The use of implants resulted in higher incidences of cataracts and elevated intraocular pressure. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with chronic noninfectious uveitis affecting the posterior segment of the eye and who receive intravitreal fluocinolone acetonide implant (0.18 mg, Yutiq), the evidence includes studies listed in the table below. Relevant outcomes are symptom improvement, change in disease status, functional status and quality of life. The data establishes the efficacy of Yutiq (fluocinolone acetonide intravitreal implant) 0.18 mg by demonstrating that the recurrence rate of chronic non-infectious uveitis within six months was significantly lower in the Yutiq group compared to that in the sham group: 18% vs. 79% in Study 01 and 22% vs. 54% in Study 05. The most commonly reported adverse reactions occurring in Yutiq (fluocinolone acetonide intravitreal implant) 0.18 mg subjects were cataract development and increases in intraocular pressure. The potential benefits of Yutiq (fluocinolone acetonide intravitreal implant) 0.18 mg through reduction in the recurrence of posterior uveitis outweigh the identified risks as demonstrated in the clinical studies submitted with this drug application. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Study Identifier

Objective(s) of the Study

Study Design and Type of Control

Number of Subjects

Diagnosis of Patients

Duration of Treatment

PSV-FAI-001

Efficacy and Safety

Prospective, multi-center, randomized (2:1), double masked, comparison FAI insert to sham injection (control), followed by standard of care and 36-month follow-up.

129 eyes randomized

As of M6: 129 completed 0 discontinued

As of M12: 126 completed 3 discontinued

Male and female subjects age ≥18 years who had non-infectious uveitis affecting the posterior segment of the eye

Primary endpoint at Month 6

PSV-FAI-005

Efficacy and Safety

Prospective, multi-center, randomized (2:1), double masked, comparison FAI insert to sham injection (control), followed by standard of care and 36- month follow-up.

153 eyes randomized

As of M6: 151 completed 2 discontinued

Male and female subjects age ≥18 years who had non-infectious uveitis affecting the posterior segment of the eye

Primary endpoint at Month 6

 

Macular Edema

For individuals with macular edema after retinal vein occlusion who receive an intravitreal dexamethasone implant (0.7 mg), the evidence includes two RCTs. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Compared with sham controls, implants resulted in clinically meaningful improvements in visual acuity within one to three months post implant and improvement in vision occurred faster. The difference in the proportion of patients with gain of 15 or more letters in best-corrected visual acuity from baseline was more than 10% in favor of implants versus sham in both studies at 30, 60 and 90 days, but not at 180 days post implant. The use of implants resulted in higher incidences of cataracts and elevated intraocular pressure. Several additional RCTs and a meta-analysis have evaluated the comparative effects of dexamethasone intravitreal implants versus other therapies and found mixed results. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with macular edema after retinal vein occlusion who receive an intravitreal fluocinolone acetonide implant (0.59 mg), no studies were identified. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Diabetic Macular Edema

For individuals with refractory (persistent or recurrent) diabetic macular edema who receive an intravitreal fluocinolone acetonide implant (0.59 mg), the evidence includes an RCT. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Compared to standard of care (as needed laser or observation), a greater proportion of patients with implants reported clinically significant improvement in vision at six months (1.4% vs 16.8% respectively) and subsequent time points assessed but not at or beyond 30 months of follow-up. Ninety percent of patients with phakic eyes who received implants required cataract surgery and 60% developed elevated intraocular pressure. Due to the substantial increase in adverse events and availability of agents with safer tolerability profiles (e.g., anti-vascular endothelial growth factor inhibitors), implant use in diabetic macular edema is questionable. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with diabetic macular edema who receive an intravitreal fluocinolone acetonide implant (0.19 mg), the evidence includes two RCTs. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Implant-treated eyes showed in clinically meaningful improvements in vision at two and three years post implant. The percentage of patients who gained 15 letters or more was 28.7% in the implant group versus 18.9% in the sham group at three years. Subgroup analysis showed greater improvements in visual acuity in patients who were pseudophakic compared to those who were phakic (difference in mean change in number of letters at two years from baseline was 5.6 letters in pseudophakic patients vs. one letter in phakic patients). A major limitation of these implants is that nearly 80% all phakic patients will develop cataracts and will require cataract surgery. Further, intraocular pressure was elevated in 34% of patients who received this implant compared with 10% of controls. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with diabetic macular edema who receive an intravitreal dexamethasone implant (0.7 mg), the evidence includes three RCTs. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Compared to sham control, two identically designed RCTs showed clinically meaningful improvements in vision with dexamethasone implants that peaked at three months and maintained 39 months (with retreatment). The difference in proportion of patients with a gain of 15 or more letters in best-corrected visual acuity from baseline was 9.3% and 13.0% in the two trials, respectively, favoring implant versus sham at 39 months post implant. Subgroup analysis of these trials showed greater improvements in visual acuity in patients who were pseudophakic compared to those who were phakic. Additionally, evidence from various small and/or short-term trials and retrospective studies have found that, compared with primarily antivascular endothelial growth factor treatments, intravitreal dexamethasone implant (0.7 mg) was consistently associated with larger reductions in retinal thickness, but visual acuity changes were similar between treatment groups. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with diabetic macular edema who receive an intravitreal dexamethasone implant (0.7 mg) plus antivascular endothelial growth factor, the evidence includes two RCTs. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Findings from both RCTs were consistent in demonstrating that although adding dexamethasone to an antivascular endothelial growth factor treatment can lead to a greater mean reduction in central subfield thickness, it does not improve visual acuity and can lead to a higher risk of intraocular pressure elevation. Based on the consistent lack of improvement in visual acuity, increased risk of intraocular pressure elevation, and imprecision, the evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with diabetic macular edema who receive an intravitreal dexamethasone implant (0.7 mg) plus laser photocoagulation, the evidence includes an RCT. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. One RCT with one-year follow-up demonstrated that combination implants plus laser photocoagulation compared to laser photocoagulation alone resulted in better visual acuity (as measured by gain of greater than or equal to ten letters) at nine months but not at 12 months. However, the generally acceptable standard outcome measure for change is 15 or more letters and it was not used in this trial. The use of dexamethasone implants resulted in higher incidences of cataracts and elevated intraocular pressure. Further, a differential loss to follow-up, lack of power calculations for sample size estimation, and lack of intention-to-treat analysis preclude interpretation of results. A larger RCT with adequate power is needed to confirm these findings. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Age-Related Macular Degeneration

For individuals with age-related macular degeneration who receive an intravitreal dexamethasone implant (0.7 mg) plus antivascular endothelial growth factor inhibitor, the evidence includes an RCT. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Results of this trial did not demonstrate clinically meaningful reductions in the ranibizumab injection-free interval between combined treatments (34 days) and antivascular endothelial growth factor alone (29 days; p=0.016). Further, intraocular pressure was elevated in a greater proportion of patients receiving implants without any additional clinical benefit. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Other Conditions

For individuals with birdshot retinochoroidopathy refractory or intolerant to standard therapy who receive an intravitreal fluocinolone acetonide implant (0.59 mg) or intravitreal dexamethasone implant (0.7 mg), the evidence includes multiple observational studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Multiple observational studies have noted improvements in anatomic and visual acuity outcomes. Long-term follow-up for efficacy and safety is limited. RCTs are needed to permit conclusions on the efficacy of corticosteroid implants in refractory or intolerant patients with birdshot retinopathy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with cystoid macular edema who receive an intravitreal dexamethasone implant (0.7 mg), the evidence includes one observation-controlled RCT (N=14), three comparative observational studies and numerous case series. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The RCT found improved mean visual acuity and eye anatomy outcomes with intravitreal dexamethasone compared to the control eyes, but these differences were not sustained at six months. The comparative observational studies included 269 patients (range, 60 to 135) and also lacked responder analysis of the proportion of patients with a 15-or-more letter improvement. One case series evaluated the proportion of patients with a three-line improvement in best-corrected visual acuity; although 88% of patients achieved this outcome at two months, the proportion with improvement was not sustained at six months (27.8%). Additional blinded, multicenter RCTs are needed that compare intravitreal dexamethasone to another established treatment. The trials should be adequately powered for measuring proportion of patients in whom vision had improved by 15 letters or more. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with idiopathic macular telangiectasia type 1 who receive an intravitreal dexamethasone implant (0.7 mg), the evidence includes multiple case reports. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Case reports have noted mix results for visual acuity and inflammation-related outcomes. Long-term follow-up for efficacy and safety is limited. Better quality studies with long-term follow-up are needed to permit conclusions on the efficacy of corticosteroid implants in patients with idiopathic macular telangiectasia type 1. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with postoperative chronic macular edema (pseudophakic cystoid macular edema, Irvine-Gass syndrome) who receive an intravitreal dexamethasone implant (0.7 mg), the evidence includes one RCT (N=29) that compared dexamethasone intravitreal implant, 0.7 mg to triamcinolone intravitreal injection 4 mg, two comparative observational studies and numerous case series. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The RCT found no statistically significant difference between treatments in mean visual acuity improvement at three or six months. The proportion of patients in whom vision had improved by 15 letters or more was not reported. The comparative observational studies included only small numbers of patients and also lack responder analysis of the proportion of patients with a 15-or-more letter improvement. In the largest case series (N=100), two of every five patients experienced clinically meaningful improvements in visual acuity after one year of follow-up. Additional RCTs are needed that have clearly defined and representative populations (i.e., for chronic and refractory patients, documentation of intensity and duration of the first-line therapy regimens) and are adequately powered for measuring proportion of patients in whom vision had improved by 15 letters or more. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with circumscribed choroidal hemangiomas who receive an intravitreal dexamethasone implant (0.7 mg) plus photodynamic therapy, the evidence includes a case report. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Results of the case report do not permit conclusions about the efficacy and safety of adding dexamethasone implants for circumscribed choroidal hemangiomas to photodynamic therapy. RCTs are needed to permit conclusions on the efficacy of corticosteroid implants in this population. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals with proliferative vitreoretinopathy who receive an intravitreal dexamethasone implant (0.7 mg), the evidence includes a case series and a case report. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. These studies have reported multiple interventions, including dexamethasone implants in conjunction with surgery and laser for preventing proliferative retinopathy after retinal detachment surgery. RCTs are needed to permit conclusions on the efficacy of corticosteroid implants in patients with proliferative retinopathy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with radiation retinopathy who receive an intravitreal dexamethasone implant (0.7 mg), the evidence includes multiple observational studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Multiple observational studies have noted improvements in anatomic and visual acuity outcomes. Long-term follow-up for efficacy and safety is limited. RCTs are needed to permit conclusions on the efficacy of corticosteroid implants in patients with radiation retinopathy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with noninfectious intermediate uveitis or posterior uveitis and cataract undergoing cataract surgery who receive prophylaxis with intravitreal dexamethasone 0.7 mg (Ozurdex), the best evidence includes one single-center, open-label RCT of 43 patients in India. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Compared with oral corticosteroids, intravitreal dexamethasone 0.7 mg had similar benefits and avoided need for early steroid taper due to adverse effects on blood glucose, but potentially increased risk of developing intraocular pressure. Due to important study limitations including its small sample size, unclear allocation concealment methods and lack of blinding, evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

American Academy of Ophthalmology

In 2019, the American Academy of Ophthalmology published its preferred Practice Pattern® for retinal vein occlusions. These stated: “Macular edema may complicate both central retinal vein occlusions and branch retinal vein occlusions. The first line of treatment for associated macular edema is anti-vascular endothelial growth factors. Intravitreal corticosteroids, with the associated risk of glaucoma and cataract formation, have demonstrated efficacy. Also, laser photocoagulation surgery in branch retinal vein occlusion has a potential role in treatment. 

In 2019, the American Academy of Ophthalmology also published its preferred Practice Pattern® for diabetic retinopathy. Related to therapy with intravitreal corticosteroids, the Academy stated: "Because of their side-effect profile, including cataract progression and elevated IOP [intraocular pressure], they [intravitreal corticosteroids] are generally used as second-line agents for DME [diabetic macular edema], especially for phakic patients."

National Institute for Health and Care Excellence

In 2019, the National Institute for Health and Care Excellence (NICE) released guidance on the use of fluocinolone acetonide intravitreal implant 0.19 mg (Iluvien) for treating chronic diabetic macular edema that is insufficiently responsive to available therapies in an eye with a natural lens (phakic eye).The NICE guidance states, “Fluocinolone acetonide intravitreal implant is not recommended as an option for treating chronic diabetic macular edema that is insufficiently responsive to available therapies in an eye with a natural lens (phakic eye).” The NICE committee reached this conclusion based on their interpretation that “results from [Fluocinolone Acetonide in Diabetic Macular Edema] FAME may not be generalizable to people with chronic diabetic macular oedema in phakic eyes with symptomatic cataract seen in the NHS” because “in FAME, very few people had symptomatic cataract at baseline” and that the type of rescue therapy used in FAME is not used in NHS clinical practice.

In 2019, the NICE released guidance on the use of fluocinolone acetonide intravitreal implant for treating recurrent non-infectious uveitis. NICE's guidance stated, "Fluocinolone acetonide intravitreal implant is recommended, within its marketing authorization, as an option for preventing relapse in recurrent non-infectious uveitis affecting the posterior segment of the eye."

In 2017, the NICE released guidance on the use of dexamethasone intravitreal implant (with adalimumab) for the treatment of noninfectious uveitis. NICE recommended the implant only in cases of “active disease” with “worsening vision” and the “risk of blindness.”

In 2011, the NICE provided guidance on the use of the dexamethasone intravitreal implant for macular edema secondary to retinal vein occlusion. The dexamethasone implant was recommended as an option for the treatment of macular edema following central retinal vein occlusion. NICE also recommended it as an option for the treatment of macular edema following branch retinal vein occlusion when treatment with laser photocoagulation has not been beneficial or suitable.

In 2015, the NICE provided guidance on the dexamethasone intravitreal implant (Ozurdex) for treating diabetic macular edema. Ozurdex was recommended as a possible treatment for diabetic macular edema if there is “an artificial lens” and the edema either has “not improved with non-corticosteroid treatment, or such treatment is not suitable.”

In 2013, the NICE updated its guidance on the intravitreal fluocinolone acetonide implant (Iluvien), recommending Iluvien as an option for treating chronic diabetic macular edema that is insufficiently responsive to available therapies only if:

  • “the implant is to be used in an eye with an intraocular (pseudophakic) lens and
  • Their diabetic macular oedema has not got better with other treatments.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Intravitreal implant, fluocinolone acetonide, Retisert®, Ozurdex®, dexamethasone intravitreal implant, Iluvien™, Yutiq

APPROVED BY GOVERNING BODIES:

In 2009, Ozurdex® (dexamethasone 0.7 mg intravitreal implant; Allergan) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of macular edema following branch retinal vein occlusion or central retinal vein occlusion. Subsequently, in 2010, the indication was expanded to include treatment of noninfectious uveitis affecting the posterior segment of the eye. In 2014, the indication was again expanded to include treatment of diabetic macular edema.

In September 2014, Iluvien® (fluocinolone acetonide 0.19 mg intravitreal implant; Alimera Sciences) was approved by FDA for the treatment of diabetic macular edema in patients previously treated with a course of corticosteroids and without a clinically significant rise in intraocular pressure.

In 2005, Retisert™ (fluocinolone acetonide 0.59 mg intravitreal implant; Bausch & Lomb) was approved by FDA for the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye.

In October 2018, Yutiq (fluocinolone acetonide 0.18 mg intravitreal implant; EyePoint Pharmaceuticals) was approved by the FDA for the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan.  FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.

CURRENT CODING:

CPT codes

67027

Implantation of intravitreal drug delivery system (e.g., ganciclovir implant), includes concomitant removal of vitreous

67028

Intravitreal injection of a pharmacologic agent (separate procedure)

HCPCS codes

J7311

Injection, fluocinolone acetonide, intravitreal implant (Retisert), 0.01 mg

J7312

Injection dexamethasone, intravitreal implant (Ozurdex), 0.1mg

J7313

Injection, fluocinolone acetonide, intravitreal implant (Iluvien), 0.01 mg

J7314

Injection, fluocinolone acetonide, intravitreal implant (Yutiq), 0.01 mg

REFERENCES:

  1. Alimera Sciences Inc. Iluvien (fluocinolone acetonide intravitreal implant) 0.19 mg for Intravitreal Injection: Prescribing Label. 2014; https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201923s002lbl.pdf. Accessed February 8, 2022.
  2. Allergan Inc. Ozurdex (dexamethasone intravitreal implant): Prescribing Label 2014; https://media.allergan.com/actavis/actavis/media/allergan-pdf-documents/product-prescribing/20180515-OZURDEX-USPI-v1-0USPI3348.pdf. Accessed February 8, 2022.
  3. Baillif S, Maschi C, Gastaud P, et al. Intravitreal dexamethasone 0.7-mg implant for radiation macular edema after proton beam therapy for choroidal melanoma. Retina. Oct 2013; 33(9):1784-1790.
  4. Bajwa A, Aziz K, Foster CS. Safety and efficacy of fluocinolone acetonide intravitreal implant (0.59 mg) in birdshot retinochoroidopathy. Retina. Nov 2014; 34(11):2259-2268.
  5. Bansal P, Agarwal A, Gupta V, et al. Spectral domain optical coherence tomography changes following intravitreal dexamethasone implant, Ozurdex(R) in patients with uveitic cystoid macular edema. Indian J Ophthalmol. May 2015; 63(5): 416-22.
  6. Bausch & Lomb Incorporated. Retisert (fluocinolone acetonide intravitreal implant) 0.59 mg: Prescribing Label. 2019;https://www.bausch.com/Portals/69/-/m/BL/United%20States/USFiles/Package%20Inserts/Pharma/retisert-prescribing-information.pdf?ver=2018-04-23-125740-133. Accessed February 8, 2022.
  7. Bazin L, Gambrelle J. [Combined treatment with photodynamic therapy and intravitreal dexamethasone implant (Ozurdex ((R))) for circumscribed choroidal hemangioma]. J Fr Ophtalmol. Dec 2012; 35(10):798-802.
  8. Bellocq D, Pierre-Kahn V, Matonti F, et al. Effectiveness and safety of dexamethasone implants for postsurgical macular edema including Irvine-Gass syndrome: the EPISODIC-2 study. Br J Ophthalmol. May 17 2016.
  9. Bezatis A, Spital G, Hohn F, et al. Functional and anatomical results after a single intravitreal Ozurdex injection in retinal vein occlusion: a 6-month follow-up -- the SOLO study. Acta Ophthalmol. Aug 2013; 91(5): e340-7.
  10. Bolukbasi S, Cakir A, Erden B, et al. Comparison of the short-term effect of aflibercept and dexamethasone implant on serousretinal detachment in the treatment of naive diabetic macular edema. Cutan Ocul Toxicol. Dec 2019; 38(4): 401-405.
  11. Boyer DS, Yoon YH, Belfort R Jr, et al. Three-Year, Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema. Ophthalmology. 2014 Jun 4.
  12. Brady CJ, Villanti AC, Law HA, et al. Corticosteroid implants for chronic non-infectious uveitis. Cochrane Database Syst Rev. Feb 12 2016; 2:CD010469.
  13. Bui KM, Chow CC, Mieler WF. Treatment of recalcitrant radiation maculopathy using intravitreal dexamethasone (Ozurdex) implant. Retin Cases Brief Rep. Summer 2014; 8(3):167-170.
  14. Burkholder BM, Wang J, Dunn JP, et al. Postoperative outcomes after fluocinolone acetonide implant surgery in patients with birdshot chorioretinitis and other types of posterior and panuveitis. Retina. Sep 2013; 33(8):1684-1693.
  15. Callanan DG, Gupta S, Boyer DS, et al. Dexamethasone intravitreal implant in combination with laser photocoagulation for the treatment of diffuse diabetic macular edema. Ophthalmology. Sep 2013; 120(9):1843-1851.
  16. Callanan DG, Loewenstein A, Patel SS, et al. A multicenter, 12-month randomized study comparing dexamethasone intravitreal implant with ranibizumab in patients with diabetic macular edema. Graefes Arch Clin Exp Ophthalmol. Mar 2017; 255(3): 463-473.
  17. Cakir A, Erden B, Bolukbasi S, et al. Comparison of the effect of ranibizumab and dexamethasone implant in diabetic macular edema with concurrent epiretinal membrane. J Fr Ophtalmol. Sep 2019; 42(7): 683-689.
  18. Caminal JM, Flores-Moreno I, Arias L, et al. Intravitreal dexamethasone implant for radiation maculopathy secondary to plaque brachytherapy in choroidal melanoma. Retina. Sep 2015; 35(9):1890-1897.
  19. Campochiaro PA, Brown DM, Pearson A et al. Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology 2011; 118(4):626-35 e2.
  20. Campochiaro PA, Brown DM, Pearson A et al. Sustained delivery fluocinolone acetonide vitreous inserts provides benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology 2012; 119(10):2125-32.
  21. Center for Drug Evaluation and Research. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210331Orig1s000SumR.pdf. Accessed March 10, 2022.
  22. Coelho J, Malheiro L, Melo Beirao J, et al. Real-world retrospective comparison of 0.19 mg fluocinolone acetonide and 0.7 mg dexamethasone intravitreal implants for the treatment of diabetic macular edema in vitrectomized eyes. Clin Ophthalmol. 2019; 13: 1751-1759.
  23. Comyn O, Lightman SL, Hykin PG. Corticosteroid intravitreal implants vs. ranibizumab for the treatment of vitreoretinal disease. Curr Opin Ophthalmol 2013; 24(3):248-54.
  24. Csaky KG, Richman EA, Ferris FL. Report from the NEI/FDA Ophthalmic Clinical Trial Design and Endpoints Symposium. Invest Ophthalmol Vis Sci. Feb 2008; 49(2): 479-89.
  25. Cunha-Vaz J, Ashton P, Iezzi R, et al. Sustained Delivery Fluocinolone Acetonide Vitreous Implants: Long-Term Benefit in Patients with Chronic Diabetic Macular Edema. Ophthalmology. Jun 13 2014.
  26. Dang Y, Mu Y, Li L, et al. Comparison of dexamethasone intravitreal implant and intravitreal triamcinolone acetonide for the treatment of pseudophakic cystoid macular edema in diabetic patients. Drug Des Devel Ther. 2014; 8: 1441-9.
  27. Degoumois A, Akesbi J, Laurens C, et al. [Efficacy of intravitreal dexamethasone implants in macular edema excluding venous occlusions: results for a cohort of 80 patients]. J Fr Ophtalmol. Feb 2015; 38(2):126-133.
  28. Donati S, Gandolfi C, Caprani SM, et al. Evaluation of the Effectiveness of Treatment with Dexamethasone Intravitreal Implantin Cystoid Macular Edema Secondary to Retinal Vein Occlusion. Biomed Res Int. 2018; 2018: 3095961.
  29. Dutra Medeiros M, Navarro R, Garcia-Arumi J, et al. Dexamethasone intravitreal implant for treatment of patients with recalcitrant macular edema resulting from Irvine-Gass syndrome. Invest Ophthalmol Vis Sci. May 07 2013; 54(5):3320-3324.
  30. Erdogan G, Aydogan T, Unlu C, et al. Dexamethasone Implant for the treatment of type 1 idiopathic macular telangiectasia. J Ocul Pharmacol Ther. May 2016; 32(4):211-215.
  31. Flaxel CJ, Adelman RA, Bailey ST, et al. Diabetic Retinopathy Preferred Practice Pattern(R). Ophthalmology. Jan 2020; 127(1): P66-P145.
  32. Flaxel CJ, Adelman RA, Bailey ST, et al. Retinal Vein Occlusions Preferred Practice Pattern(R). Ophthalmology. Feb 2020; 127(2): P288-P320.
  33. Fortoul V, Denis P, Kodjikian L. Anatomical and functional recurrence after dexamethasone intravitreal implants: a 6-month prospective study. Eye (Lond). Jun 2015; 29(6): 769-75.
  34. Fraser-Bell S, Kang HK, Mitchell P, et al. Dexamethasone intravitreal implant in treatment-naive diabetic macular oedema: findings from the prospective, multicentre, AUSSIEDEX study. Br J Ophthalmol. Aug 25 2021.
  35. Freissinger S, Vounotrypidis E, Wolf A, et al. Evaluation of Functional Outcomes and OCT-Biomarkers after Intravitreal Dexamethasone Implant for Postoperative Cystoid Macular Edema in Vitrectomized Eyes. J Ophthalmol. 2020; 2020: 3946531.
  36. Gado AS, Macky TA. Dexamethasone intravitreous implant versus bevacizumab for central retinal vein occlusion-related macular oedema: a prospective randomized comparison. Clin Experiment Ophthalmol. Mar 10 2014.
  37. Gillespie BW, Musch DC, Niziol LM, et al. Estimating minimally important differences for two vision-specific quality of life measures. Invest Ophthalmol Vis Sci. Jun 06 2014; 55(7):4206-4212.
  38. Grover D, Li TJ, Chong CC. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev 2008; (1):CD005656.
  39. Grzybowski A, Sikorski BL, Ascaso FJ, et al. Pseudophakic cystoid macular edema: update 2016. Clin Interv Aging. NA 2016; 11: 1221-1229.
  40. Guclu H, Pelitli Gurlu V. Comparison of topical nepafenac 0.1% with intravitreal dexamethasone implant for the treatment of Irvine-Gass syndrome. Int J Ophthalmol. 2019; 12(2): 258-267.
  41. Haller JA, Bandello F, Belfort R, Jr. et al. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology 2011; 118(12):2453-60.
  42. Haller JA, Bandello F, et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010; 117(6):1134-46.e3.
  43. Holbrook JT, Sugar EA, Burke AE, et al. Dissociations of the Fluocinolone Acetonide Implant: The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. Am J Ophthalmol. Apr 2016; 164:29-36.
  44. Hollo G, Aung T, Cantor LB, et al. Cystoid macular edema related to cataract surgery and topical prostaglandin analogs: Mechanism, diagnosis, and management. Surv Ophthalmol. Sep 2020; 65(5): 496-512.
  45. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  46. Jaffe GJ, Branchaud B, Hahn P, et al. Quality of Life and Risks Associated with Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, or Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment Trial and Follow-up Study. Ophthalmology. Oct 2015; 122(10): 1976-86.
  47. Jaffe GJ, Foster CS, Pavesio CE, et al. Effect of an Injectable Fluocinolone Acetonide Insert on Recurrence Rates in Chronic Noninfectious Uveitis Affecting the Posterior Segment: Twelve-Month Results. Ophthalmology. Apr 2019; 126(4): 601-610.
  48. Jaffe GJ, Martin D, Callanan D et al. Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical study. Ophthalmology 2006; 113(6):1020-7.
  49. Jaffe GJ, Pavesio CE. Effect of a Fluocinolone Acetonide Insert on Recurrence Rates in Noninfectious Intermediate, Posterior, or Panuveitis: Three-Year Results. Ophthalmology. Oct 2020; 127(10): 1395-1404.
  50. Ji K, Zhang Q, Tian M, et al. Comparison of dexamethasone intravitreal implant with intravitreal anti-VEGF injections for the treatment of macular edema secondary to branch retinal vein occlusion: A meta-analysis. Medicine (Baltimore). May 2019; 98(22): e15798.
  51. Keilani C, Halalchi A, Wakpi Djeugue D, et al. Evaluation of best corrected visual acuity and central macular thickness after intravitreal dexamethasone implant injections in patients with Irvine-Gass syndrome: A retrospective study of six cases. Therapie. Oct 2016; 71(5):457-465.
  52. Kempen JH, Altaweel MM, Drye LT, et al. Benefits of Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, and Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. Ophthalmology. Oct 2015; 122(10): 1967-75. PMID 26298715
  53. Kempen JH, Altaweel MM, Holbrook JT et al.  Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial. Ophthalmology 2011; 118(10):1916-26.
  54. Klamann A, Bottcher K, Ackermann P, et al. Intravitreal dexamethasone implant for the treatment of postoperative macular edema. Ophthalmologica. 2016; 236(4):181-185.
  55. Kumar P, Sharma YR, Chandra P, et al. Comparison of the Safety and Efficacy of Intravitreal Ranibizumab with or without Laser Photocoagulation Versus Dexamethasone Intravitreal Implant with or without Laser Photocoagulation for Macular Edema Secondary to Branch Retinal Vein Occlusion. Folia Med (Plovdiv). Jun 01 2019; 61(2): 240-248.
  56. Kuppermann BD, Blumenkranz MS, Haller JA et al. Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol 2007; 125(3):309-17.
  57. Kuppermann BD, Goldstein M, Maturi RK, et al. Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial. Ophthalmologica. Sep 2015; 234(1):40-54.
  58. Laine I, Lindholm JM, Ylinen P, et al. Intravitreal bevacizumab injections versus dexamethasone implant for treatment-naive retinal vein occlusion related macular edema. Clin Ophthalmol. 2017; 11: 2107-2112.
  59. Landre C, Zourdani A, Gastaud P, et al. [Treatment of postoperative cystoid macular edema (Irvine-Gass syndrome) with dexamethasone 0.7 mg intravitreal implant]. J Fr Ophtalmol. Jan 2016; 39(1):5-11.
  60. Lei S, Lam WC. Efficacy and safety of dexamethasone intravitreal implant for refractory macular edema in children. Can J Ophthalmol. Jun 2015; 50(3):236-241.
  61. Lightman S, Belfort R, Jr., Naik RK, et al. Vision-related functioning outcomes of dexamethasone intravitreal implant in noninfectious intermediate or posterior uveitis. Invest Ophthalmol Vis Sci. Jul 2013; 54(7):4864-4870.
  62. Loutfi M, Papathomas T, Kamal A. Macular oedema related to idiopathic macular telangiectasia type 1 treated with dexamethasone intravitreal implant (ozurdex). Case Rep Ophthalmol Med. 2014; 2014:231913.
  63. Lowder C, Belfort R, Jr., Lightman S et al. Dexamethasone Intravitreal Implant for Noninfectious Intermediate or Posterior Uveitis. Arch Ophthalmol 2011; 129(5):545-53.
  64. Massin P, Erginay A, Dupas B, et al. Efficacy and safety of sustained-delivery fluocinolone acetonide intravitreal implant in patients with chronic diabetic macular edema insufficiently responsive to available therapies: a real-life study. Clin Ophthalmol. 2016; 10:1257-1264.
  65. Maturi RK, Bleau L, Saunders J, et al. A 12-month, single-masked, randomized controlled study of eyes with persistent diabetic macular edema after multiple anti-VEGF injections to assess the efficacy of the dexamethasone-delayed delivery system as an adjunct to bevacizumab compared with continued bevacizumab monotherapy. Retina. Mar 30 2015; 35(8):1604-1614.
  66. Maturi RK, Chen V, Raghinaru D, et al. A 6-month, subject-masked, randomized controlled study to assess efficacy of dexamethasone as an adjunct to bevacizumab compared with bevacizumab alone in the treatment of patients with macular edema due to central or branch retinal vein occlusion. Clin Ophthalmol. 2014; 8:1057-1064.
  67. Maturi RK, Glassman AR, Liu D, et al. Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. Jan 01 2018; 136(1): 29-38.
  68. Mayer WJ, Kurz S, Wolf A, et al. Dexamethasone implant as an effective treatment option for macular edema due to Irvine-Gass syndrome. J Cataract Refract Surg. Sep 2015; 41(9):1954-1961.
  69. Mylonas G, Georgopoulos M, Malamos P, et al. Comparison of Dexamethasone Intravitreal Implant with Conventional Triamcinolone in Patients with Postoperative Cystoid Macular Edema. Curr Eye Res. Apr 2017; 42(4): 648-652.
  70. National Institute for Health and Care Excellence (NICE). Fluocinolone acetonide intravitreal implant for treating chronic diabetic macular edema in phakic eyes after an inadequate response to previous therapy Technology appraisal guidance [TA613], 2019. https://www.nice.org.uk/guidance/ta613 Accessed February 5, 2022.
  71. National Institute for Health and Care Excellence (NICE). Fluocinolone acetonide intravitreal implant for treating recurrent non-infectious uveitis Technology appraisal guidance [TA590] 2019; https://www.nice.org.uk/guidance/TA590/chapter/1-Recommendations Accessed February 6, 2022.
  72. National Institute for Health and Care Excellence (NICE). Adalimumab and dexamethasone for treating non-infectious uveitis [TA460]. 2017; https://www.nice.org.uk/guidance/ta460. Accessed February 1, 2022.
  73. National Institute for Health and Care Excellence (NICE). Dexamethasone intravitreal implant for treating diabetic macular oedema [TA349]. 2015; www.nice.org.uk/guidance/ta349. Accessed February 3, 2022.
  74. National Institute for Health and Clinical Excellence (NICE). Dexamethasone intravitreal implant for the treatment of macular oedema secondary to retinal vein occlusion. NICE [TA229]. 2011. Available online at: www.nice.org.uk/nicemedia/live/13541/55590/55590.pdf. Accessed February 2, 2022.
  75. National Institute for Health and Care Excellence (NICE). Fluocinolone acetonide intravitreal implant for treating chronic diabetic macular oedema after an inadequate response to prior therapy [TA301]. 2013; https://www.nice.org.uk/guidance/ta301. Accessed February 4, 2022.
  76. Novais EA, Maia M, Filho PA, et al. Twelve-Month Follow-Up of Dexamethasone Implants for Macular Edema from Various Diseases in Vitrectomized and Nonvitrectomized Eyes. J Ophthalmol. 2016; 2016: 7984576.
  77. Ozkok A, Saleh OA, Sigford DK, et al. THE OMAR STUDY: Comparison of Ozurdex and Triamcinolone Acetonide for Refractory Cystoid Macular Edema in Retinal Vein Occlusion. Retina. Jul 2015; 35(7): 1393-400.
  78. Park UC, Park JH, Ma DJ, et al. A Randomized Paired-Eye Trial of Intravitreal Dexamethasone Implant for Cystoid Macular Edema In Retinitis Pigmentosa. Retina. Jul 2020; 40(7): 1359-1366.
  79. Pavesio C, Zierhut M, Bairi K et al. Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis. Ophthalmology 2010; 117(3):567-75, 75 e1.
  80. Pearson PA, Comstock TL, Ip M et al. Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial. Ophthalmology 2011; 118(8):1580-7.
  81. Pichi F, Specchia C, Vitale L et al. Combination therapy with dexamethasone intravitreal implant and macular grid laser in patients with branch retinal vein occlusion. Am J Ophthalmol 2014; 157(3):607-15 e1.
  82. Pulido JS, Flaxel CJ, Adelman RA, et al. Retinal vein occlusions Preferred Practice Pattern ((R)) Guidelines. Ophthalmology. Jan 2016; 123(1):P182-208.
  83. Regnier SA, Larsen M, Bezlyak V, et al. Comparative efficacy and safety of approved treatments for macular oedema secondary to branch retinal vein occlusion: a network meta-analysis. BMJ Open. 2015; 5(6):e007527.
  84. Reibaldi M, Russo A, Longo A, et al. Rhegmatogenous retinal detachment with a high risk of proliferative vitreoretinopathy treated with episcleral surgery and an intravitreal dexamethasone 0.7-mg implant. Case Rep Ophthalmol. Jan 2013; 4(1):79-83.
  85. Rittiphairoj T, Mir TA, Li T, et al. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev. Nov 17 2020; 11: CD005656.
  86. Rush RB, Goldstein DA, Callanan DG, et al. Outcomes of birdshot chorioretinopathy treated with an intravitreal sustained-release fluocinolone acetonide-containing device. Am J Ophthalmol. Apr 2011; 151(4):630-636.
  87. Sherif M, Wolfensberger TJ. Intraocular dexamethasone implant as adjunct to silicone oil tamponade for proliferative vitreoretinopathy. Klin Monbl Augenheilkd. Feb 01 2017.
  88. Spaide RF. RETINAL VASCULAR CYSTOID MACULAR EDEMA: Review and New Theory. Retina. Oct 2016; 36(10): 1823-42.
  89. Srour M, Querques G, Leveziel N, et al. Intravitreal dexamethasone implant (Ozurdex) for macular edema secondary to retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol. Jun 2013; 251(6):1501-1506.
  90. Sudhalkar A, Chhablani J, Vasavada A, et al. Intravitreal dexamethasone implant for recurrent cystoid macular edema due to Irvine-Gass syndrome: a prospective case series. Eye (Lond). Dec 2016; 30(12):1549-1557.
  91. Sudhalkar A, Vasavada A, Bhojwani D, et al. Intravitreal dexamethasone implant as an alternative to systemic steroids as prophylaxis for uveitic cataract surgery: a randomized trial. Eye (Lond). Mar 2020; 34(3): 491-498.
  92. Thorne JE, Sugar EA, Holbrook JT, et al. Periocular Triamcinolone vs. Intravitreal Triamcinolone vs. Intravitreal Dexamethasone Implant for the Treatment of Uveitic Macular Edema: The PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema(POINT) Trial. Ophthalmology. Feb 2019; 126(2): 283-295.
  93. Tyson SL, Bafna S, Gira JP, et al. Multicenter randomized phase 3 study of a sustained-release intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. Feb 2019; 45(2): 204-212.
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  100. Williams GA, Haller JA, Kuppermann BD et al. Dexamethasone posterior-segment drug delivery system in the treatment of macular edema resulting from uveitis or Irvine-Gass syndrome. Am J Ophthalmol 2009; 147(6):1048-54, 54 e1-2.
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POLICY HISTORY:

Medical Policy Panel, June 2010

Medical Policy Group, September 2010 (2)

Medical Policy Administration Committee, October, 2010

Available for comment October 21 through December 6, 2010

Medical Policy Administration Committee, October, 2010

Available for comment November 4 – December 20, 2010

Medical Policy Group, December 2010; 2011 Coding update (1): added J7312

Medical Policy Group, May 2011 (1): Update to Policy, Key Points and References

Medical Policy Administration Committee, May 2011

Available for comment May 11 – June 27, 2011

Medical Policy Group, April 2012 (1): Update to Policy, Key Points and References related to MPP update to include coverage criteria for Retisert for intermediate and panuveitis and for Ozurdex to include coverage criteria for uveitis affecting the intermediate segment of the eye

Medical Policy Administration Committee, May 2012

Medical Policy Panel, March 2013

Medical Policy Group, June 2013 (1): Update to Key Points, Governing Bodies, Coding, with the addition of CPT code 67028, and References; no change to policy statements

Medical Policy Administration Committee, July 2013

Medical Policy Panel, March 2014

Medical Policy Group, March 2014 (1): Update to Key Points, Governing Bodies and References; no change to policy statement

Medical Policy Group, July 2014 (1): Update to Policy statement, Key Points, Governing Bodies and References related to addition of new criteria for coverage for Ozurdex for DME, effective 06/28/14.

Medical Policy Administration Committee, September 2014

Available for comment August 21 through October 4, 2014

Medical Policy Panel, October 2014

Medical Policy Group, October 2014 (1): Updated Policy statement, Key Points, Governing Bodies, Key Words, Coding and References related to addition of coverage criteria for FDA approved drug Iluvien for DME, effective 09/26/14 using codes J3490 and 67028; also noted that Ozurdex is now approved for general DME population

Medical Policy Administration Committee, November 2014

Available for comment October 24 through December 4, 2014

Medical Policy Panel, October 2015

Medical Policy Group, October 2015 (6):  Updates to Key Points and References; no change to policy statement.

Medical Policy Group, November 2015: 2016 Annual Coding Update.  Added J7313 to current coding.

Medical Policy Panel, March 2016

Medical Policy Group, March 2016 (6): Updates to Key Points, Coding, and References; no change to policy statement.

Medical Policy Panel, March 2017

Medical Policy Group, May 2017 (6): Updates to Description, Key Points, Approved by Governing Bodies, and References. Policy intent unchanged.

Medical Policy Panel, March 2018

Medical Policy Group, April 2018 (6): Updates to Description, Key Points, Practice Guidelines, and References. Policy intent unchanged.

Medical Policy Panel, March 2019

Medical Policy Group, April 2019 (6): Updates to Key Points; title edited “Intravitreal Corticosteroid Implants” no changes to policy statement.

Medical Policy Group, July 2019 (6): Updated Description, Policy statement, Coding, Key Words and Governing Bodies to include Yutiq.

Medical Policy Group, September 2019: October 2019 quarterly coding update.  Added new CPT code J7314 to Current Coding.  Moved Yutiq’s previous unclassified code J3490 to Previous Coding section.

Medical Policy Group, December 2019 (6): 2020 Annual Coding Update, Revised codes J7311, J7313.

Medical Policy Panel, March 2020

Medical Policy Group, April 2020 (6): Updates to Description, Key Points, Practice Guidelines and Governing Bodies.

Medical Policy Panel, March 2021

Medical Policy Group, March 2021 (6): Updates to Description, Key Points and References.

Medical Policy Panel, March 2022 (9): 2022 Annual updates to Description, Key Points, References. Removed previous coding section that includes HCPCS code J3490 (unclassified drugs) for Yutiq and Iluvien prior to 10/1/19. No change to policy statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.