Intravitreal and Punctum Corticosteroid Implants Form

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EFFECTIVE DATE: 08|01|2025 POLICY LAST REVIEWED: 04|16|2025

OVERVIEW An intravitreal implant is a drug delivery system, injected or surgically implanted in the vitreous of the eye, for sustained release of drug to the posterior and intermediate segments of the eye. Four intravitreal corticosteroid implants, ie, fluocinolone acetonide 0.59 mg (Retisert), fluocinolone acetonide 0.19 mg (Iluvien), fluocinolone acetonide 0.18 mg (Yutiq), and dexamethasone 0.7 mg (Ozurdex) are reviewed herein. Fluocinolone acetonide implants are nonerodible and deliver drug up to 30 to 36 months while dexamethasone implants are bioerodible and last up to 6 months. A punctum implant is a drug delivery device that is inserted through the lower lacrimal punctum into the canaliculus, for sustained release of a pharmacologic agent to the ocular surface. Dexamethasone ophthalmic insert 0.4 mg (Dextenza) is the first corticosteroid intracanalicular insert and is reviewed herein.

MEDICAL CRITERIA Not applicable

PRIOR AUTHORIZATION
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POLICY STATEMENT Medicare Advantage Plans and Commercial Products A fluocinolone acetonide intravitreal implant 0.59 mg (Retisert®) may be considered medically necessary for the treatment of: • Chronic non-infectious intermediate, posterior, or panuveitis.

A fluocinolone acetonide intravitreal implant 0.19 mg (Iluvien®) may be considered medically necessary for the treatment of: • Diabetic macular edema in individuals who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure.

A dexamethasone intravitreal implant 0.7 mg (Ozurdex™) may be considered medically necessary for the treatment of: • Noninfectious ocular inflammation, or uveitis, affecting the intermediate or posterior segment of the eye, OR • Macular edema following branch or central retinal vein occlusion, OR • Diabetic macular edema.

A punctum dexamethasone insert 0.4 mg (Dextenza®) may be considered medically necessary for the treatment of: • Ocular inflammation and pain following ophthalmic surgery.

A punctum dexamethasone insert 0.4 mg (Dextenza) is considered not covered for Medicare Advantage Plans and not medically necessary for Commercial Products as the evidence is insufficient to determine that the technology results in an improvement in the net health outcomes: • Ocular itching associated with allergic conjunctivitis

A fluocinolone acetonide intravitreal implant 0.59 mg (Retisert®) or 0.19 mg (Iluvien®) or dexamethasone intravitreal implant 0.7 mg (Ozurdex™) is considered not covered for Medicare Advantage Plans and not Medical Coverage Policy | Intravitreal and Punctum Corticosteroid Implants

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medically necessary for Commercial Products as the evidence is insufficient to determine that the technology results in an improvement in the net health outcomes for the treatment of any of the following: • Birdshot retinochoroidopathy • Cystoid macular edema related to retinitis pigmentosa • Idiopathic macular telangiectasia type 1 • Postoperative macular edema • Circumscribed choroidal hemangiomas • Proliferative vitreoretinopathy • Radiation retinopathy. • Prophylaxis of cystoid macular edema in individuals with noninfectious intermediate uveitis or posterior uveitis and cataract undergoing cataract surgery The following are not covered for Medicare Advantage Plans and not medically necessary for Commercial Products as the evidence is insufficient to determine that the technology results in an improvement in the net health outcomes: • A fluocinolone acetonide intravitreal implant 0.18 mg (Yutiq) for the treatment of chronic noninfectious posterior uveitis affecting the posterior segment of the eye • All other uses of a corticosteroid intravitreal implants

COVERAGE Benefits may vary between groups and contracts. Please refer to the appropriate Evidence of Coverage or Subscriber Agreement for applicable physician administered injectable drug benefits/coverage.

BACKGROUND Eye Conditions Uveitis Uveitis encompasses various conditions, of infectious and 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 be idiopathic, have a sudden or insidious onset, a duration that is limited (<3 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 in 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 The primary goal of therapy for uveitis is to preserve vision. Noninfectious uveitis typically responds well to corticosteroid treatment. Immunosuppressive therapy (eg, 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 nonischemic. Ischemic central retinal

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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 occlusion, and in many patients with nonischemic central retinal vein occlusion. Branch retinal vein occlusion is a common retinal vascular disorder in adults between 60 and 70 years of age and occurs approximately 3 times more often than central retinal vein occlusion.

Treatment 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 6 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 2 most serious complications for vision are diabetic macular edema and proliferative diabetic retinopathy. At its earliest stage (nonproliferative 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 the 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 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 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 the 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 as 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 the 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 Effective specific therapies for exudative or wet age-related macular degeneration are an intravitreous injection of a vascular endothelial growth factor inhibitor, possibly thermal laser photocoagulation (in selected patients), and photodynamic therapy.

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Intravitreal and Punctum Implants Intravitreal and punctum 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 (eg, 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 to 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 nonbiodegradable. Nonbiodegradable 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 the following: • Retisert (nonbiodegradable 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 (nonbiodegradable 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 3 years. • Ozurdex (previously known as Posurdex; biodegradable dexamethasone intravitreal implant; Allergan ) 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 6 months. The mean number of Ozurdex injections reported in the literature is 4.2 injections per year, and more than 6 consecutive injections have been reported.1,2, • Dextenza (biodegradable dexamethasone intracanalicular insert; Ocular Therapeutix) is a rod-shaped hydrogel device that is designed to deliver a sustained and tapered release of 0.4 mg of dexamethasone over 4 weeks. Following ophthalmic surgery, it is inserted through the inferior punctum into the canaliculus of the operative eye. To allow for visualization and retention monitoring, the hydrogel device is conjugated with fluorescein. No removal is required as the device is designed to resorb and exit the nasolacrimal system independently. • Yutiq (nonbiodegradable 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.

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 includes 4 randomized controlled trials (RCTs).

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Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Two of the 4 RCTs compared 2 doses of implants, and 2 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 4- 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 with the systematic therapy groups by +6.0 and +3.2 letters (p=.16) and +2.4 and 3.1 letters (p=.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%) than in 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 8 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 8 compared with sham controls (the proportion of patients with a gain of ≥15 letters in best-corrected visual acuity from baseline was >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 posterior uveitis affecting the posterior segment of the eye and who receive intravitreal fluocinolone acetonide implant (0.18 mg), the evidence includes 2 pivotal RCTs. Relevant outcomes are symptom improvement, change in disease status, functional status, and quality of life. Harmful outcomes of interest are treatment-related morbidity. Both RCTs consistently found statistically significantly lower uveitis recurrence rates for intravitreal fluocinolone acetonide implant (0.18 mg) at both 6 and 12 months. However, serious limitations of these findings include inconsistency in the magnitude of the benefit at 12 months (odds ratio [OR], 67.09; 95% confidence interval [CI], 8.81 to 511.06 in published RCT and OR, 3.04; 95% CI, 1.52 to 6.08 in the unpublished RCT) and, with more imputed recurrences in the sham groups than the treatment groups, we also can’t rule out an overestimation of the treatment effect. For the remainder of key outcomes, results were inconsistent between RCTs, appearing more favorable in the published trial. Most notable were the differences between RCTs in mean change in best-corrected visual acuity at 12 months (higher for fluocinolone acetonide in the published trial, lower in the unpublished trials) and risk of increased intraocular pressure within 12 months (increased risk in the unpublished trial, but not in the published trial). Due to these inconsistencies and serious methodological limitations, the evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Macular Edema For individuals with macular edema after retinal vein occlusion who receive an intravitreal dexamethasone implant (0.7 mg), the evidence includes 2 RCTs, systematic reviews, and observational studies. 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 1 to 3 months postimplant, and improvement in vision occurred faster. The difference in the proportion of patients with a 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 postimplant. The use of implants resulted in higher incidences of cataracts and elevated intraocular pressure. Several additional RCTs, systematic reviews, and observational studies have evaluated the comparative effects

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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 relevant 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 with the standard of care (as needed laser or observation), a greater proportion of patients with implants reported clinically significant improvement in vision at 6 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 better tolerability profiles (eg, antivascular endothelial growth factor ), 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 2 RCTs and several observational studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. In RCTs, implant-treated eyes showed clinically meaningful improvements in vision at 2 and 3 years postimplant. 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 3 years. Subgroup analysis showed greater improvements in visual acuity in patients who were pseudophakic compared with those who were phakic (difference in mean change in the number of letters at 2 years from baseline was 5.6 letters in pseudophakic patients vs. 1 letter in phakic patients). Similar results were seen in observations studies with follow up to 2 years. A major limitation of these implants is that nearly 80% of 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 RCTs and additional nonrandomized comparative studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Compared with sham control, 2 identically designed RCTs showed clinically meaningful improvements in vision with dexamethasone implants that peaked at 3 months and were maintained at 39 months (with retreatment). The difference in the 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 2 trials, respectively, favoring implant versus sham at 39 months postimplant. Subgroup analysis of these trials showed greater improvements in visual acuity in patients who were pseudophakic compared with 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 therapy, the evidence includes 2 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.

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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 1-year follow-up demonstrated that combination implants plus laser photocoagulation compared with laser photocoagulation alone resulted in better visual acuity (as measured by a gain of ≥10 letters) at 9 months but not at 12 months. However, the generally accepted standard outcome measure for change is 15 or more letters, and this standard 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 the 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=.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 patients with refractory or intolerant birdshot retinochoroidopathy. 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 1 observation controlled RCT (N=14), 3 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 6 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 3-line improvement in best-corrected visual acuity; although 88% of patients achieved this outcome at 2 months, the proportion with improvement was not sustained at 6 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 the 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 mixed results for visual acuity and inflammation-related outcomes. Long-term follow-up for efficacy and

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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 1 RCT (N=29) that compared dexamethasone intravitreal implant 0.7 mg to triamcinolone intravitreal injection 4 mg, 2 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 3 or 6 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), 2 of every 5 patients experienced clinically meaningful improvements in visual acuity after 1 year of follow-up. Additional RCTs are needed that have clearly defined and representative populations (ie, for chronic and refractory patients, documentation of intensity and duration of the first-line therapy regimens) and are adequately powered for measuring the 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 or 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 that the technology results in an improvement in the net health outcome.

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 ocular inflammation and pain following ophthalmic surgery who receive punctum dexamethasone implant (0.4 mg), the evidence includes 3 RCTs. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. All 3 trials noted significant improvements with the punctum dexamethasone insert (0.4 mg) across both coprimary efficacy endpoints of an absence of pain at 8 days and absence of anterior chamber cells at day 14. Adverse events were generally similar between punctum dexamethasone insert (0.4 mg) and sham. Based on the consistent benefits and lack of important increases in adverse event risk, evidence is sufficient 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 implant (0.7 mg) , the best evidence includes

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1 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 the 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.

For individuals with ocular itching associated with allergic conjunctivitis who receive punctum dexamethasone implant (0.4 mg), the evidence includes 3 RCTs, 2 of which has been published. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Compared with the sham insert, punctum dexamethasone implant (0.4) demonstrated a significant decrease in patient- reported ocular itching after 1 week post-implant, and throughout most time points up to 30 days. Adverse events were similar in both groups and were all considered mild to moderate. However, limitations of these trials prevent evaluation of therapeutic use. It was not described if included participants had previously failed first-line therapies or if they were treatment-naive, making the intended use population unclear. If intended for use in treatment-naive patients, comparison to first-line topical agents is necessary for therapeutic evaluation. Additionally, the modified symptom scoring model used by investigators is typically only used in controlled, research settings, and not typically used for evaluation of therapeutic outcomes in real-world environments. The remaining approval trial (NCT02988882) also found improved ocular itching with the punctum dexamethasone insert compared with vehicle control on day 8. However, the differences were generally smaller than those seen in the published trials and failed to reach significance. Due to the limitations of the published literature, and the lack of predefined clinically meaningful difference in symptom scores, the clinical significance of the primary outcome is unclear. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

CODING Medicare Advantage Plans and Commercial Products The following HCPCS/CPT code(s) are covered for Medicare Advantage Plans and Commercial Products when filed with one of the ICD-10* Diagnosis Code(s) listed below: J1096 Dexamethasone, lacrimal ophthalmic insert, 0.1 mg J7311 Injection, fluocinolone acetonide, intravitreal implant (Retisert), 0.01 mg J7312 Injection, dexamethasone, intravitreal implant, 0.1 mg J7313 Injection, fluocinolone acetonide, intravitreal implant (Iluvien), 0.01 mg
J7314 Injection, fluocinolone acetonide, intravitreal implant (Yutiq), 0.01 mg
68841 Insertion of drug-eluting implant, including punctal dilation when performed, into lacrimal

canaliculus, each

*ICD-10 Diagnosis Code(s) E08.37X1-E08.37X9
E09.37X1-E09.37X9 E10.37X1-E10-37X9 E11.37X1-E11.37X9 E13.37X1-E13.37X9
H20.10-H20.13
H30.90-H30.93
H34.8110-H34.8192
H34.8310-H34.8392
H35.031-H35.039
H35.30-H35.3294
H35.81

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