Advertisement

PentaVision

Retinal Physician

Article

New Options for Intravitreal Therapy

Technological Advances in Drug Delivery to Treat Noninfectious Posterior Segment Uveitis

By: Seenu M. Hariprasad, MD
Retinal Physician January 1, 2021 Vol 18, Issue January/February 2021

ABSTRACT

Uveitis is an inflammatory ocular condition that can lead to vision loss if left untreated. Accurate diagnosis involves determining whether the uveitis is infectious or noninfectious, as the two conditions are treated differently. For patients with noninfectious uveitis, after the initial inflammation has resolved with steroid treatment, the focus must be on preventing recurrence, which can cause permanent damage to ocular structures. Further treatment can be systemic or local: however long-term systemic treatment may result in contraindications, adverse effects, or resistance to therapy. Local steroid therapy, therefore, has an important role for suppressing inflammation while mitigating the risks of systemic steroids. In the past, uveitis patients had limited options for local treatment and often required multiple medications to address recurrent symptoms. More recently new treatments have emerged that are more effective and have fewer adverse effects over the long term. These include a dexamethasone intravitreal implant, a fluocinolone acetonide intravitreal implant, and a suprachoroidal injection of triamcinolone acetonide that is expected to be approved in 2020. In addition, various biologic response modifiers are being studied for the treatment of noninfectious uveitis, only one of which, adalimumab, has so far been approved for this indication. These new therapies offer the possibility of greater control of inflammation, fewer recurrences, and enhanced safety in the many patients presenting with noninfectious uveitis.

INTRODUCTION

Uveitis is a sight-threatening ocular condition characterized by inflammation and macular edema that may or may not reflect underlying systemic disease. In the US, uveitis accounts for approximately 30,000 new cases of blindness each year.1 In up to one third of patients with uveitis, vision loss is exacerbated by the presence of macular edema.2,3

Figure 1: Photo of eye with uveitis
Figure 1: Photo of eye with uveitis

Uveitis is classified as anterior, intermediate, posterior, or pan-uveitis, according to the primary site of inflammation.4 In one study, 28% of patients with posterior uveitis developed macular edema.5

Uveitis may reflect one disease or a combination of several diseases, and the choice of treatment may depend on the type and extent of symptoms, patterns of recurrence, and the individual patient’s need and preferences.

Clearly such a complex condition presents both diagnostic and treatment challenges. An initial step in diagnosis is to determine whether the uveitis is infectious or noninfectious in origin, in order to select the appropriate treatment, as the two conditions are treated differently. In addition to clinical examination and careful history, serology and/or imaging tests may be required for an accurate diagnosis.6 Some causes of infectious uveitis, such as toxoplasmosis or endogenous endophthalmitis, may be difficult to recognize, and PCR testing of ocular fluid may be required.7

LOCAL VS SYSTEMIC THERAPY IN THE TREATMENT OF NONINFECTIOUS UVEITIS

For the practitioner caring for a patient presenting with acute uveitis, it is essential to get the inflammation and macular edema under control; secondarily, it is important to prevent recurrence of the condition, as damage to ocular structures can occur with each recurrent episode. Currently the medical management of noninfectious uveitis affecting the posterior segment includes systemic administration of immunosuppressants or systemic or local administration of steroids. All of these have the ability to suppress inflammation in the back of the eye, and all are associated with varying degrees of ocular side effects. To achieve control initially, a course of systemic steroids is effective in most patients.8 However, it should be noted that in most cases uveitis is recurrent and will require long-term treatment. The long-term effects of systemic steroids are numerous and serious. Many patients develop resistance to long-term use of systemic steroids.9 In addition, many patients have contraindications to systemic treatment, such as pregnancy, and some patients who may be candidates for systemic treatment may refuse it simply because they have a preference for local therapy. Local therapy with periocular or intravitreal administration of corticosteroid or the implantation of intraocular sustained-release delivery systems in the vitreous can provide therapeutically effective doses of drug to the posterior segment, thereby suppressing inflammation over the long term while decreasing the risks associated with systemic therapy.9

In the past, only systemic agents and off-label triamcinolone acetonide (TA) were available for the treatment of patients who required steroid therapy. Periocular or intravitreal injections had to be administered frequently, and repeated recurrences often resulted in poor long-term visual outcomes, as well as negatively impacting patients’ quality of life.10 Frequent injections also carried potential risks, such as endophthalmitis. Efforts to improve the efficacy, durability, and safety of therapy have led to the development of newer agents designed to provide local steroid therapy to the eye for an extended period of time while mitigating the side effects associated with the systemic administration of corticosteroids.

Currently three new generation therapies offer improved options for local treatment. Two of these agents are relative newcomers to the uveitis market; the third is in development and is expected to be approved this year.

DEXAMETHASONE INTRAVITREAL IMPLANT (ABBVIE)

The dexamethasone intravitreal implant was the first steroid approved by the US Food and Drug Administration (FDA) for administration in the office setting.11 It was approved in 2010 for the treatment of noninfectious uveitis affecting the posterior segment of the eye.12 It is also indicated for the treatment of diabetic macular edema, as well as for macular edema following branch retinal vein occlusion or central retinal vein occlusion. It consists of a rod-shaped intravitreal implant that contains 0.7 mg dexamethasone in a sustained-release drug delivery system. The implant is preloaded into a single-use applicator and injected directly into the vitreous.

Figure 2: Illustration of the device and/or application procedure
Figure 2: Illustration of the device and/or application procedure

The efficacy and safety of the dexamethasone intravitreal implant were established in a single 26-week multicenter, double-masked randomized clinical study that included 229 patients with noninfectious ocular inflammation of the posterior segment, vitreous haze grade of > +1.5 on the 0-4 classification scale, and best corrected visual acuity (BCVA) of 10 to 75 letters on the Snellen eye chart.9 2011 Seventy-seven patients received the a 0.7 mg dexamethasone intravitreal implant, 76 received a dexamethasone 0.35 mg implant, and 76 received sham injections. After a single injection, at the Week 8 primary end point, 47% of patients receiving the study drug reached a vitreous haze score of zero (no inflammation) vs 12% of patients in the sham injection group (P <0.001). In addition, the percentage of eyes achieving at least a 15-letter improvement from baseline BCVA was 2- to 6-fold greater in both dexamethasone implant groups than in the sham group throughout the study period and was statistically significant at all time points compared with sham.9

Contraindications to the dexamethasone intravitreal implant include ocular or periocular infections including most viral diseases of the cornea and conjunctiva, glaucoma, torn or ruptured lens capsule, and hypersensitivity. Adverse effects include those associated with ophthalmic steroids, including elevated intraocular pressure (IOP), and cataract formation.12

The dexamethasone intravitreal implant is a highly effective drug for controlling inflammation, but its effect peaks in the first 2 weeks post-injection; it has a relatively short duration of action, and symptoms may recur after approximately 4 months. For this reason, it is often used as initial treatment and then replaced by the fluocinolone acetonide (FAc) insert for longer-term maintenance.

FLUOCINOLONE ACETONIDE (EYE POINT PHARMACEUTICALS, WATERTOWN, MA)

Fluocinolone acetonide (FAc) 0.18 mg is a sustained-release corticosteroid intravitreal implant that was approved in 2018 for the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye.13 This medication is not to be confused with an FAc 0.19 mg implant, Iluvien, licensed by Alimera Sciences, which is not currently FDA approved for treatment of uveitis. The implant discussed here , Yutiq, is the successor to an FAc implant (14) that was approved in 2005. The older implant had a higher dose (0.59 mg) and had to be implanted surgically in the operating room.15 It is rarely used today because is invasive, has a poor side effect profile, and is very expensive. The newer compound is supplied in a preloaded 25-gauge needle applicator. It is designed to release 0.18 mg FAc into the eye at an initial rate of 0.25 mcg/day for a period of 36 months.34 The FAc intravitreal implant can be administered in the physician’s office.

The efficacy and safety of the FAc 0.18 mg implant were assessed in two parallel phase 3 double-masked, randomized prospective studies.16,17 In both studies, patients with recurrent noninfectious posterior segment uveitis were randomized to the FAc 0.18 mg implant or sham injections. The primary endpoint was recurrence rate at 6 and 12 months. Both studies met their primary efficacy endpoint at both timepoints with statistical significance.

In the first study, 129 participants with noninfectious uveitis affecting the posterior segment in 6 countries were randomized to treatment; 87 patients were randomized to the FAc implant and 42 to sham injection. At 6 months, 27.6% of patients in the FAc group had a recurrence, compared with 95.5% in the sham group. Between 6 and 12 months, there was a slight increase in the recurrence rate in both groups, but it remained significantly lower in the FAc insert group compared with the sham group (P <0.001). At 12 months, patients in the FAc group had an average of 1.3 mm Hg IOP rise, compared with 0.2 mm Hg in the sham group. Cataract surgery was required in 33.3% of phakic patients in the FAc group compared with 5% in the sham group.16

Results were comparable in the second parallel phase 3 study. This was a prospective, multicenter, multinational, randomized, double-masked, sham-controlled 36-month trial.17 Eligible patients were randomized in a 2:1 ratio to receive either the FAc insert 0.18 g (N = 87) or sham injection (N = 42). The primary efficacy endpoint was the recurrence of uveitis within 6 months. The 6-month uveitis recurrence rate was 18.4% in the FAc group vs 78.6% in sham (P < 0.001). By 12 months, 27.6% of patients in the FAc group had a recurrence of inflammation, compared with 85.7% of patients in the sham group (P <0.001). In the FAc group, at 12 months there was a mean IOP increase of 1.3 ±3.6 mm Hg, compared with 0.2 ± 4.2 mm Hg in the sham group. By 12 months, ocular hypertensive medication had been used by 26.4% of patients treated with FAc, compared with 26.2% in the sham group. One patients receiving FAc required glaucoma surgery during the first 12 months. At 12 months, cataract surgery was required in 33.3% of phakic patients treated with FAc, compared to 5.0% in the sham group. The most common adverse events reported in the FAc treatment group were cataract formation and increases in IOP. In the sham group, they were macular edema and noninfectious endophthalmitis.17

SUPRACHOROIDAL ADMINISTRATION OF OCULAR CORTICOSTEROID (CLEARSIDE BIOMEDICAL, ALPHARETTA, GA AND BAUSCH & LOMB, BRIDGEWATER, NJ)

An investigational technique for delivering ocular corticosteroids is via suprachoroidal administration of triamcinolone acetonide (TA), known as CLS-TA.14 TA reduces inflammation in the eye as well as ocular edema and improves visual outcomes.18 The drug is provided with a prepackaged syringe containing a needle approximately 1000 μm in length.19 In this technique, 4 mg TA is injected into the suprachoroidal space 4 mm posterior to the limbus. The drug is quickly absorbed into posterior segment tissue, with no depot at the injection site, which allows for high concentrations at the target site while minimizing concentrations at anterior sites, thereby minimizing side effects. In preclinical studies, there were no adverse effects and no evidence of drug toxicity in a porcine model,20 while in a study in New Zealand white rabbits, no toxic minimal amounts of TA were found in the lens and anterior segment following suprachoroidal injection compared with intravitreal administration, suggesting fewer ocular side effects. Systemic exposure also remained very low.21

In a small pilot study in patients with uveitis (N = 9), no ocular hypertension was seen over a 26-week observation period with the suprachoroidal injection.22 All eight efficacy-evaluable subjects had improvements in visual acuity. Four subjects, who did not need additional therapy, had on average a greater than 2-line improvement in visual acuity through week 26. Among the seven subjects who had macular edema at baseline, all had at least a 60-μm reduction in central subfield thickness (CST) at week 8 (mean reduction of 154 μm). Overall, a simple suprachoroidal injection of TA was well tolerated and no increases in IOP were observed.22 Results of this study suggested that suprachoroidal TA injection has the potential for good control of inflammation with less risk for cataract and glaucoma development. This hypothesis was tested in the PEACHTREE study, with 160 patients.

PEACHTREE was a phase 3 randomized, controlled, double-masked multicenter trial.23 The primary efficacy endpoint was the proportion of patients in each arm gaining ≥15 ETDRS letters in BCVA from baseline at week 24. The secondary endpoint was reduction from baseline in CST at week 24. There were 96 patients in the CLS-TA study arm and 64 patients received the sham procedure. Patients received two injections, at day 0 and week 12. Suprachoroidal CLS-TA met the primary study endpoint, with a significantly greater proportion of subjects vs control having ≥15 ETDRS BCVA gain at 6 months (P <0.001) at week 24, meaning that patients were able to read ETDRS letters half the size after study therapy compared with study entry. At week 24, CST was reduced from baseline in CLS-TA patients by 153 μm compared with a reduction of 18 μm in the control group, a difference of 135 μm (P < 0.001). The overall safety profile was favorable, with low rates of IOP and cataract and no serious adverse events attributable to suprachoroidal CLS-TA. Longer-term outcomes are being assessed in the extension MAGNOLIA study (Clinical-Trials.gov identifier, NCT02374060). Two smaller studies, AZALEA and DOGWOOD,24 showed similar results. Food and Drug Administration approval is pending for this new treatment for noninfectious uveitis, which is expected to be indicated as well for macular edema, the principal cause of vision loss in uveitis.23

It is important to know how, when, and for which patients each of these new therapies is appropriate. The table below may be helpful in comparing them.

Therapies may be individualized according to particular patients’ needs and preferences. For example, a patient who has done well on shorter acting steroids and did not have an uncontrollable IOP response may respond well to FAc 0.18 mg. Moreover, these agents are not necessarily mutually exclusive. Some patients may require a combination of local and systemic therapies, and even when local therapies alone are chosen, the practitioner may select one therapy to initiate treatment and another for longer-term treatment.

The experienced ophthalmologic surgeon should not find any of the intravitreal agents difficult to administer. However, before administering any of these agents for the first time, it may be useful to review on-line videos showing administration techniques or even to practice administering the agent using dummy eyes.

Table 1
Drug Indication Duration of Action Costs*** Other Comments
Dexamethasone intravitreal implant 0.7 mg Noninfectious uveitis affecting the posterior segment of the eye; diabetic macular edema 4-6 months $2000 Effective in achieving early resolution of symptoms
Fluocinoline acetonide intravitreal implant 0.18 mg Chronic noninfectious uveitis affecting the posterior segment of the eye 12-36 months $7000 Has the longest duration of action and can be used for long-term maintenance
CLS-TA triamcinolone intravitreal implant 4 mg Macular edema associated with uveitis* Up to 12 months ** $40 Appears to be effective in resolving macular edema, the primary cause of vision loss in noninfectious uveitis.
*Pending FDA approval.
**6 months in the PEACHTREE trial, and an additional 6 months in MAGNOLIA; pending FDA approval.
***Published prices, does not reflect insurance or Medicare coverage cost

BIOLOGICS

The aim of therapy with biologic response modifiers (biologics) is to regulate the inflammatory process by suppressing immune effector responses. Biologics are used off-label for uveitis, except for adalimumab (AbbVie), which was approved in 2016 for the treatment of noninfectious uveitis.25 Several biologics have been proposed for noninfectious uveitis. These include monoclonal antibodies, soluble receptors, cytokines, and natural cytokine antagonists.

TNF-α is a pro-inflammatory cytokine that exacerbates immune disease including uveitis. Molecules that block TNF-α have been found to be effective in modulating the immune response and in reducing inflammation in patients with uveitis.26 The most commonly used TNR-α inhibitors are infliximab and adalimumab. Infliximab, a chimeric lgG1 monoclonal antibody, impairs the binding of TNF-α to its receptor. The efficacy and safety of infliximab for uveitis have been investigated in patients with refractory uveitis27 and with Behcet’s disease28. In the refractory uveitis trial, remission of uveitis was achieved in 60% of patients treated with infliximab in the first year and was maintained by 60% of those patients in the second year.27 However, intravitreal infliximab causes immunogenic reactions and may cause retinotoxicity.29

Adalimumab is a humanized recombinant lgG1 monoclonal antibody that binds to human TNF-α with high affinity. It has been studied in patients with juvenile idiopathic uveitis, in which it has been shown to be more efficacious than infliximab at maintaining remission.30 A 2016 study showed adalimumab and infliximab to have comparable efficacy and incidence of serious adverse effects in refractory uveitis.31 However, while they show promise, TNF inhibitors may also increase risk of infections, including tuberculosis, and may reactivate chronic viral infections, as well as malignancy, and congestive heart failure.32

In addition to the TNF inhibitors, biologics that have been investigated for this disease include the lymphocyte inhibitors daclizumab, rituximab, abatacept, basiliximab, and specific receptor antagonists, including anakinra, canakinumab, gevokizumab, tocilizumab, alemtuzumab, and efalizumab.33 Rituximab has been studied in uveitis patients with juvenile idiopathic arthritis.34 The IL-2 receptor daclizumab has been successful in treating patients with uveitis refractory to standard therapy.35

Biologics may benefit some but not all patients with uveitis. They appear to be most useful in treating concomitant ophthalmic and systemic inflammation, such as in patients with rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, Behçet’s disease, or inflammatory bowel disease.33 However, biologics are currently not considered to be first-line treatment because of the lack of long-term safety data. In addition their high cost is prohibitive.33 Further randomized controlled trials evaluating the use of biologics in noninfectious uveitis are needed before they can be considered the optimal therapy for this condition.

CONCLUSION

Chronic noninfectious posterior uveitis can lead to permanent impairment or loss of vision. In the past, patients with chronic uveitis in the posterior segment were burdened with multiple medications, frequent office visits, often to more than one specialist, and high co-pays for those visits. While management of chronic noninfectious posterior uveitis remains challenging, new generation implants offer greatest efficacy and minimal adverse events compared with earlier treatment modalities. New medications and new administration techniques make it possible to continue local treatment without having to advance to systemic steroids or immunological options, with their greater potential for adverse effects over the long term. With the new generation of medications, we are closer to the goal of achieving effective control of inflammation, reducing recurrences, and enhancing safety, thereby improving ocular outcomes and quality of life in patients with chronic posterior uveitis.

REFERENCES

  1. Allergan Receives FDA Approval for OZURDEX® as Treatment Option for Noninfectious Uveitis Affecting the Posterior Segment of the Eye. Press Release. Available at: https://www.businesswire.com/news/home/20100924005874/en/Allergan-Receives-FDA-Approval-OZURDEX%C2%AE-Treatment-Option . Accessed April 14, 2020.
  2. Al-Rayes H, Al-Swailem R, Al-Balawi M, et al. Safety and efficacy of infliximab therapy in active Behcet’s uveitis: an open-label trial. Rheumatol Int. 2008;29(1):53-57.
  3. Bispo PJM, Davoudi S, Sahm ML, et al. Rapid detection and identification of uveitis pathogens by qualitative multiplex real-time PCR. Invest Ophthalmol Vis Sci. 2018;59:582–589.
  4. Callanan D, Nguyen QD, Suhler EB, et al. Reduced risk of recurrence of noninfectious posterior segment uveitis after 0.18 mg fluocinolone acetonide insert: Randomized Trial. Am J Ophthalmol. 2020; S0002-9394(20)30064-7.
  5. Clearside Biomedical. Data on file. April 2018.
  6. Dick AD. The treatment of chronic uveitic macular oedema. Br J Ophthalmol. 1994;78:1–2.
  7. Edelhauser HF, Verhoeven RS, Burke B, et al. Intraocular distribution and targeting of triamcinolone acetonide suspension administered into the suprachoroidal space. Invest Ophthalmol Vis Sci. 2014 ; 55: 5259.
  8. EyePoint Pharmaceuticals Receives FDA Approval of YUTIQ™ (fluocinolone acetonide intravitreal implant) 0.18 mg. Available at: http://investors.psivida.com/news-releases/news-release-details/eyepoint-pharmaceuticals-receives-fda-approval-yutiqtm Accessed April 14, 2020.
  9. Giganti M, Beer PM, Lemanski N, et al. Adverse events after intravitreal infliximab (Remicade). Retina. 2010;30:71-80.
  10. Gilger BC, Abarca EM, Salmon JH, Patel S. Treatment of acute posterior uveitis in a porcine model by injection of triamcinolone acetonide into the suprachoroidal space using microneedles. Invest Ophthalmol Vis Sci. 2013;54: 2483–2492.
  11. Goldstein DA, Do D, Noronha G, et al. Suprachoroidal corticosteroid administration: a novel route for local treatment of noninfectious uveitis. Transl Vis Sci Technol. 2016; 5:14.
  12. Heiligenhaus A, Miserocchi E, Heinz C, et al. Treatment of severe uveitis associated with juvenile idiopathic arthritis with anti-CD20 monoclonal antibody (rituximab). Rheumatology. 2011;50: 1390-1394.
  13. HUMIRA (adalimumab). Prescribing Information. AbbVie Inc. N Chicago, IL; 2020.
  14. Jabs DA. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol. 2005;140:509–516.
  15. Jabs DA, Akpek EK. Immunosuppression for posterior uveitis. Retina. 2005;25(1):1-18.
  16. Kok H, Lau C, Maycock N, et al. Outcome of intravitreal triamcinolone in uveitis. Ophthalmology. 2005;112:1916-1921.
  17. Lardenoye CW, van Kooij B, Rothova A. Impact of macular edema on visual acuity in uveitis. Ophthalmology. 2006;113:1446–1449.
  18. Lin P. Infectious uveitis. Curr Ophthalmol Rep. 2015;3(3):170-183.
  19. Lowder C, Belfort R Jr, Lightman S, et al. Ozurdex HURON Study Group. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011; 129:545-553.
  20. Nguyen QD, Callanan D, Dugel P, et al. Treating chronic noninfective posterior segment uveitis: the impact of cumulative damage. Proceedings of an expert panel round table discussion. Retina. 2006; suppl 1:1-16.
  21. Nussenblatt RB. The natural history of uveitis. Int Ophthalmol. 1990; 14: 303–308.
  22. Nussenblatt RB, Peterson JS, Foster CS, et al. Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series. Ophthalmology. 2005;112(5):764-770.
  23. OZURDEX (dexamethasone intravitreal implant) Highlights of Prescribing Information. Allergan USA, Inc. Madison, NJ; 2018.
  24. Pasadhika S, Rosenbaum JT. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis. Biologics: Targets and therapy. 2014;8:67-81.
  25. Rabinovich CE. Use of tumor necrosis factor inhibitors in uveitis. Curr Opin Rheumatol. 2007; 19(5):482-486.
  26. RETISERT® (fluocinolone acetonide intravitreal implant) 0.59 mg prescribing information. Bausch & Lomb Inc. Bridgewater, NJ; 2019.
  27. Rifkin LM, Birnbaum AD, Goldstein DA. TNF inhibition for ophthalmic indications: current status and outlook. BioDrugs. 2013 Aug;27(4):347-57.
  28. Rothova A, Suttorp-van Schulten MSA, Treffers WF, et al. Causes and frequency of blindness in patients with intraocular inflammatory disease. Brit J Ophthalmol. 1996;80:332-336.
  29. Simonini G, Taddio A, Cattalini M, et al. Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res. 2011;63(4):612-618.
  30. Suhler EB, Smith JR, Giles TR, et al. Infliximab therapy for refractory uveitis: 2-year results of a randomized, prospective clinical trial. Arch Ophthalmol. 2009;277(6):819-822. Research letter.
  31. Vallet H, Seve P, Biard L, et al. Infliximab versus adalimumab in the treatment of refractory inflammatory uveitis: a multicenter study from the French Uveitis Network. Arthritis Rheumatol. 2016;68(6):1522-1530.
  32. Yeh S, Khurana RN, Shah M, et al, for the PEACHTREE Study Investigators. Efficacy and safety of suprachoroidal CLS-TA for macular edema secondary to noninfectious uveitis: Phase 3 randomized trial. Ophthalmology. 2020; e-pub ahead of print.
  33. Yeh S, Kurup SK, Wang SC, et al. DOGWOOD Study Team. Retina. 2019;39(10):1880-1888.
  34. YUTIQ™ (fluocinolone acetonide intravitreal implant) 0.18 mg, for intravitreal injection. Full Prescribing Information. EyePoint Pharmaceuticals US, Inc. Watertown, MA. 2018.
  35. Yeh S, Khurana RN, Shah M, et al, for the PEACHTREE Study Investigators. Efficacy and safety of suprachoroidal CLS-TA for macular edema secondary to noninfectious uveitis: Phase 3 randomized trial. Ophthalmology. 2020; e-pub ahead of print.
  36. Yeh S, Kurup SK, Wang SC, et al. DOGWOOD Study Team. Retina. 2019;39(10):1880-1888.
  37. YUTIQ™ (fluocinolone acetonide intravitreal implant) 0.18 mg, for intravitreal injection. Full Prescribing Information. EyePoint Pharmaceuticals US, Inc. Watertown, MA. 2018.

EXAMINATION QUESTIONS

Technological Advances in Drug Delivery to Treat Noninfectious Posterior Segment Uveitis

This CME activity is sponsored by the University of Florida College of Medicine and is supported by an unrestricted educational grant from AbbVie. Participants must score at least 80% on this exam in order to receive credit. The University of Florida College of Medicine designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. To take this exam and obtain credit, please take the test online at https://cme.ufl.edu/online-cme/tadd/ . Expires: January 31, 2022.

Supported by an unrestricted educational grant from ABBVIE.

What to Read Next