Managing Chronic Panuveitis Manifesting in a Patient With Vogt-Koyanagi-Harada Syndrome SPONSORED BY BAUSCH + LOMB ™ RETISERT ® PATIENT CASE STUDY SERIES Vogt-Koyanagi-Harada syndrome (VKH) is a granulomatous inflammatory disorder affecting ocular, auditory, meningeal, and integumentary systems, and features the development of a vision- threatening noninfectious bilateral panuveitis on a chronic course. 1-3 The exact cause of VKH is not fully understood,1,2 but the mechanism is generally agreed to be autoimmune in nature, involving the targeting of melanocytes by cytotoxic T cells in those with a genetic susceptibility. 4 VKH predominantly affects people of more-pigmented groups, such as those of Hispanic, Asian, Native American, Middle Eastern, or Asian Indian descent (but not those of sub-Saharan African descent), 1,2 and cases appear to predominate in women over men. 2 At the time of disease onset, most patients are in their second to fifth decades of life; in one study of 65 cases, the mean age was 32 years (range, 7-71 years). 2 While Lisa J. Faia, MD VKH is a multisystem disorder and diagnosis of “complete” disease requires both neurological findings Vitreoretinal Surgeon (eg, early meningism or tinnitus) and integumentary involvement (eg, later vitiligo), signs and symptoms at Associated Retina vary greatly depending on disease stage. 1 Nevertheless, evidence of bilateral diffuse posterior uveitis Consultants, PC in Royal is essential, even for probable VKH diagnosis. 1 If the early inflammation is not adequately controlled, Oak, MI, and Associate subretinal fibrosis can develop, as can glaucoma. 2,5 Months or years after disease onset, uveitis becomes Professor of Ophthalmology more diffuse and presents in the anterior segment. 1,2 Differentiation from entities such as sarcoidosis at Oakland University William Beaumont School and sympathetic ophthalmia is needed.1 High-dose systemic corticosteroids are the standard first- of Medicine line treatment for VKH; if these are not tolerated, immunomodulatory agents, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, can be employed. 6 The following case study describes a patient with previously undiagnosed, long-standing VKH who over time developed glaucoma in each Lisa J. Faia, MD, is a paid eye. This patient had irreparable vision loss in her left eye and later developed blurred vision in her right consultant of Bausch + Lomb. eye. Having hypertension, she is not a good candidate for first-line systemic corticosteroid therapy. After alternative therapies failed, the patient was treated with RETISERT (fluocinolone acetonide intravitreal implant) 0.59 mg therapy for control of her posterior uveitis associated with VKH. Case Report: Chronic Panuveitis Manifesting in Vogt-Koyanagi-Harada Syndrome BACKGROUND: A 55-year-old African American woman with hypertension and a history of bilateral glaucoma was referred to me in 2015 for diagnosis after her general ophthalmologist suspected posterior uveitis in the right eye. Indication RETISERT® (fluocinolone acetonide intravitreal implant) 0.59 mg is a corticosteroid indicated for the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye. Important Safety Information • Surgical placement of RETISERT® (fluocinolone acetonide intravitreal implant) 0.59 mg is contraindicated in active viral, bacterial, mycobacterial or fungal infections of the eye. Please see additional Important Safety Information throughout and full Prescribing Information for RETISERT® on pages 5-7. Identifying the Optimal Patient Type for RETISERT treatment Retina Today Nov/Dec 2018 Managing Chronic Panuveitis Manifesting in a November/December 2020 | Insert to Retina Today Patient With Vogt-Koyanagi-Harada Syndrome Untitled-5 1 12/4/20 2:23 PM BAUS6856_Retisert_2020_CaseStudy-3_P7.indd 1 11/6/20 10:07 AM BACKGROUND (CONT’D): In 2002, she underwent trabeculectomy and cataract surgery in her left eye; vision in this eye was later reduced WHY RETISERT? (CONT’D) The patient experienced an unacceptable to hand motion, which her doctor believed to be caused by uncontrolled, surgically exacerbated inflammation and glaucoma. In 2010, she received the adverse event following the first intraocular therapy, and there were apparently A same two surgeries in her right eye—and when the patient came to see me, she had begun to experience vision loss in her right eye. Her specialist believed diminishing outcomes from the second therapy. her glaucomatous damage was secondary to an uncontrolled posterior uveitis and response to topical ophthalmic corticosteroids, but the etiology of the The patient’s right-eye BCVA had fallen to 20/200, and uveitis of the posterior inflammation was unknown. segment was manifesting chronically in secondary macular edema. When we DIAGNOSIS: The patient’s left eye had only hand-motion vision and was soft in applanation tonometry. Band keratopathy, which has been observed in discussed RETISERT once again, the patient was more engaged, and her glaucoma B cases of VKH,7 was present, and the pseudophakic lens had dense posterior capsule opacification. Color fundus imaging showed subretinal fibrosis and optic specialist agreed that the treatment was viable. We talked through the risks disc pallor in a “sunset glow” effect (Figure 1), consistent with VKH.2 The right eye had a BCVA of 20/150 and an IOP of 13 mm Hg; the anterior chamber had associated with RETISERT. The patient had been unhappy with the blurred vision trace cell and flare, and the vitreous had grade 1 + haze and cell. Fluorescein angiography (FA) revealed diffuse leakage in the macula and around the optic that occurred after her preservative-free triamcinolone acetonide injection; and nerve (Figure 2A-B), and macular edema shown in OCT (Figure 2C), which has been reported in cases of VKH,7 suggested a posterior uveitis. while her vision was already so reduced, I advised her that nearly all RETISERT C patients experience a temporary decrease in visual acuity in the implanted eye The patient reported a previous case of hearing loss. She also had ongoing headaches (managed with over-the-counter drugs) and vitiligo (managed with immediately after surgery.11 Corticosteroids should also be used with caution in a steroid cream). Of note regarding ancestry, the patient mentioned that she has Native American relatives. Laboratory findings from a combination of patients with glaucoma; after RETISERT placement, eyes must be monitored for treponemal and non-treponemal tests were negative for syphilis, and an interferon gamma release assay for tuberculosis also returned a negative result— elevated IOP.11 Corticosteroids can also cause cataracts; based on RETISERT lowering the probability of uveitis secondary to such infections.8 Unremarkable serum levels of lysozyme and angiotensin converting enzyme helped D clinical trials, nearly all phakic eyes are expected to develop cataracts.11 My differentiate the patient’s condition from sarcoidosis.9 The patient also denied a history of ocular trauma or penetrating ocular surgery prior to the onset of patient’s eyes, however, had been pseudophakic since 2002 (left eye) and 2010 her earliest symptoms. Coupled with her glaucoma specialist’s belief that uncontrolled posterior uveitis was one of the causes of her glaucoma (for which (right eye). Caution needs to be exercised to ensure completeness of healing, if she later received trabeculectomies), this history permitted a differentiation from sympathetic ophthalmia.1,10 Based on the summary of findings, I diagnosed placing RETISERT following cataract surgery, as the use of steroids may delay my patient’s posterior uveitis as a feature of VKH. Figure 3. OCT scans following first RETISERT placement. healing and increase the incidence of bleb formation.11 Imaging demonstrates resolution of macular edema and improvement TREATMENT: Aggressive treatment with systemic corticosteroids was not FOLLOW-UP: One month following placement of her first RETISERT implant in the ellipsoid zone 1 month (A), 12 months (B), 24 months (C), and advised given the patient’s hypertension, so we tried low-dose corticosteroids with in the right eye, the patient began a slow taper off methotrexate, which was 34 months (D) after implantation. The patient was slowly tapered off an immunomodulator, oral mycophenolate mofetil—but therapeutic effect was methotrexate from the beginning of month 2 through month 12. completed 12 months post surgery. To manage the anterior portion of her panuveitis, not seen. She then began treatment with oral methotrexate 25 mg per week. In the patient took prednisolone acetate ophthalmic suspension, 1%, twice daily for follow-up, there were some improvements in the patient’s visual acuity as well as her 36 months following RETISERT placement. IOP-lowering medications were considered as well. RETISERT is designed to release fluocinolone acetonide neurological and integumentary symptoms, but she was not tolerating the therapy over approximately 30 months, initially at a rate of 0.6 µg per day, then decreasing to a steady state of between 0.3 and 0.4 µg after the first month.11 In well and admitted to lapses in regimen adherence. clinical trials, IOP-lowering medications were required in 77% of RETISERT patients, and filtration surgeries were needed in 37%.11 My patient had previously The patient wanted to stop taking systemic medications, so while continuing received a trabeculectomy. After RETISERT placement, she also took an IOP-lowering medication (dorzolamide hydrochloride,