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CASE REPORT
Ahead of print publication  

The place of dexamethasone implant in patients with Vogt–Koyanagi–Harada disease who experienced systemic treatment-related hepatic dysfunction: A case series


1 Department of Ophthalmology, Çerkezköy State Hospital, Tekirdağ, Turkey
2 Department of Ophthalmology, Dokuz Eylul University, Izmir, Turkey

Date of Submission02-Jun-2022
Date of Acceptance11-Jul-2022
Date of Web Publication04-Oct-2022

Correspondence Address:
Ali Osman Saatci,
Mustafa Kemal Sahil Bulvarı, No: 73 A Blok, Daire 9, Narlıdere-Izmir
Turkey
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2211-5056.357850

  Abstract 


We presented our observation with dexamethasone (DEX) implant in six eyes of three patients with Vogt–Koyanagi–Harada (VKH) disease who experienced hepatic dysfunction due to the systemic immunosuppressive therapy during their follow-up. Three cases who could not continue with the azathioprine (AZA) or adalimumab (ADA) treatment due to elevated liver enzymes were given consecutive bilateral DEX implant injections during the follow-up. In the first case, oral AZA was discontinued due to an elevation of the liver enzymes at the 2nd month of AZA treatment, and then she received five bilateral DEX implant administrations during the follow-up of 61 months without any intraocular pressure rise or disease recurrence. The remaining two patients had an elevation of the liver enzymes when ADA treatment was added to the prophylactic isoniazid therapy and they each received three bilateral DEX implant administrations within a year again without any complications and disease recurrence. DEX implant can be a safe and effective alternative for individuals with VKH disease whose systemic treatment is ceased due to adverse effects of the systemic treatment and intravitreal therapy with DEX implant can be beneficial to achieve a recurrence-free follow-up.

Keywords: Adalimumab, azathioprine, dexamethasone implant, hepatic dysfunction, serous retinal detachment, Vogt–Koyanagi–Harada disease



How to cite this URL:
Atas F, Kayabasi M, Saatci AO. The place of dexamethasone implant in patients with Vogt–Koyanagi–Harada disease who experienced systemic treatment-related hepatic dysfunction: A case series. Taiwan J Ophthalmol [Epub ahead of print] [cited 2023 Jan 28]. Available from: https://www.e-tjo.org/preprintarticle.asp?id=357850




  Introduction Top


Vogt–Koyanagi–Harada (VKH) disease is a multisystemic disorder that causes granulomatous panuveitis due to an autoimmune reaction against the melanocytes.[1] The Standardization of Uveitis Nomenclature Working Group[2] published classification criteria for VKH disease very recently and classified the disease into two stages as early and late stages. The key criteria for the early stage included the following: (1) Exudative retinal detachment with a characteristic appearance on fluorescein angiogram or (2) Panuveitis with two or more of five neurologic symptoms/signs. The key criteria for the late-stage VKH included the history of early-stage VKH and either (1) sunset glow fundus or (2) uveitis and one or more of three cutaneous signs.[2]

Long-term treatment options for VKH mainly include systemic corticosteroids, immunosuppressive, and biologic agents.[3] Recent case reports suggested that dexamethasone (DEX) implant may also be among the treatment options.[4],[5],[6] We present a case series of three patients with VKH disease who experienced hepatic dysfunction due to administration of the systemic therapy without any disease recurrence.


  Methods Top


Medical records of the patients between November 2014 and January 2021 with VKH disease who were treated with DEX implant administration at the Dokuz Eylul University were reviewed retrospectively. An informed consent form was signed by all of the patients.

All patients had a complete ophthalmic examination and multimodal imaging techniques such as fundus autofluorescence, fluorescein angiography (Heidelberg Retinal Angiography 2), and spectral-domain optical coherence tomography (OCT, Spectralis®, Heidelberg Engineering, Heidelberg 2, Germany) were employed whenever deemed necessary. Starting from October 2018, swept-source OCT angiography (direct regularization from images OCT Triton Plus®; Topcon Corporation, Tokyo, Japan) was also performed where appropriate. Patients were diagnosed according to the revised diagnostic criteria published in the First International Workshop on VKH (2001).[7] Viral hepatitis serology was obtained before administration of the systemic treatment. Liver enzymes were within the normal limits before the initiation of systemic treatment in all patients. Daily pulse 1-gram methylprednisolone therapy was administered by the guidance of OCT 4 to 10 days routinely at our clinic after a meticulous systemic workup in patients with VKH disease. Then either oral azathioprine (AZA) alone or together with cyclosporine A (CsA) or subcutaneous adalimumab (ADA) therapy was employed in addition to the oral steroid therapy that was then tapered slowly. Three cases who could not continue their treatment with AZA or ADA due to elevated liver enzymes were given consecutive bilateral DEX implant (0.7mg) (Ozurdex®, Allergan, Dublin, Ireland) injections during the follow-up. We preferred intravitreal DEX implant over oral corticosteroid treatment to avoid further side effects of the systemic route. All of the patients who had at least a follow-up of 1 year following the first DEX implant injections were considered for the study.


  Case Reports Top


Case 1

A 32-year-old otherwise healthy woman was diagnosed with an incomplete VKH disease in December 2015. At presentation, her best-corrected visual acuity (BCVA) was 20/200 at OU. She was initially treated with pulse methylprednisolone for 5 days. BCVA was improved to 20/20 OU following the 5-day long pulse steroid treatment. Then, oral AZA 150 mg/day and prednisone 64 mg/day were started. She presented with severe nausea and lassitude 2 months after the initiation of AZA and AZA was immediately stopped due to highly elevated liver enzymes. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) levels were 540 IU/L (range; 0–35 IU/L), 312 IU/L (range; 0–35IU/L), 894 IU/L (range; 0–38 IU/L), and 321 IU/L (range; 30–120 IU/L), respectively. At that time, oral steroid treatment was tapered to daily 16-mg methylprednisolone. Unfortunately, bilateral disease recurrence was noted 3 months later [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. After discussing the options with the patient, we injected bilateral DEX implants with the rapid resolution of the episode [Figure 1]e, [Figure 1]f, [Figure 1]g, [Figure 1]h, [Figure 1]i, [Figure 1]j. Liver enzymes returned to their normal level at the 2nd month of injections. She received a total of five bilateral DEX implant administrations during the follow-up of 61 months. No intraocular pressure rise was observed. However, she underwent bilateral phacoemulsification surgery with intraocular lens implantation a week apart at the 22nd month of the follow-up with excellent visual recovery.
Figure 1: Case 1. At the time of disease recurrence. Color fundus pictures (a: Right eye and b: Left eye) and OCT sections depicting the SRD (c: Right eye and d: Left eye). Two days after the intravitreal bilateral DEX implant injection, OCT images showing the decreased height in SRD (e: Right eye and f: Left eye). A week after the injections; OCT images delineating the lessened SRD at the right eye (g) and fully resolved SRD at the left eye (h). Three weeks after the injections, OCT sections demonstrating the almost normal-looking foveas. (i: Right eye and j: Left eye). OCT: Optical coherence tomography, SRD: Serous retinal detachment, DEX: Dexamethasone

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Case 2

A 35-year-old otherwise healthy woman was diagnosed to have an incomplete VKH disease in November 2014 [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d]. BCVA was 20/400 at the first examination bilaterally. She was treated with pulse methylprednisolone for 4 days. BCVA was improved to 20/20 following the 4-day pulse steroid treatment OU. Then, oral prednisolone 64 mg/day, CSA 200 mg/day, and AZA 150 mg/day were commenced. At the 24th month of follow-up, CSA was stopped. However, at the 72nd month of follow-up, she was diagnosed to have disease recurrence. BCVA was 20/20 in the right eye and 20/25 at the left eye at the recurrence. Slit-lamp examination revealed the presence of 2+ cells in both eyes. OCT analysis showed an increased choroidal thickness in both eyes and subretinal fluid at the parafoveal region of the macula in the left eye [Figure 2]e, [Figure 2]f, [Figure 2]g, [Figure 2]h. This time, we decided to put her on ADA following the 7-day duration of pulse methylprednisolone treatment. As her QuantiFERON-TB Gold test was positive during the preparatory work up, we first initiated antituberculosis prophylaxis (isoniazid (INH), 100 mg/day) for 1 month before ADA administration as recommended. Then, ADA treatment was added. We tapered the oral steroid when ADA treatment was started. However, elevated liver enzymes were noted 1 month after the initiation of ADA. The serum ALT, AST, GGT, and ALP levels were 1179 IU/L, 1270 IU/L, 224 IU/L, and 160 IU/L, respectively. All of her systemic therapy including AZA, ADA, and INH were stopped and bilateral DEX implant was administrated to prevent a possible recurrence. Liver enzymes returned to their normal limit a month later. She received a total of three bilateral DEX implant injections with excellent control of the disease almost within a year. However, she developed moderate cataracts and will need cataract surgery in near future. No intraocular pressure rise was noted.
Figure 2: Case 2. At the first initiation. Color fundus pictures (a: Right eye and b: Left eye) and OCT images showing the serous retinal detachment (c: Right eye and d: Left eye). At the recurrence. Late venous phase of fluorescein angiographic images (e: Right eye and f: Left eye). OCT images demonstrating the increased choroidal thickness in both eyes and the serous retinal detachment in left eye (g: Right eye and h: Left eye). OCT: Optical coherence tomography, SRD: Serous retinal detachment

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Case 3

A 50-year-old otherwise healthy woman received the diagnosis of incomplete VKH disease in December 2020 [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d. BCVA was 20/200 in OD and 20/400 in OS at the presentation. She received 9-day long pulse methylprednisolone treatment initially. After the completion of the pulse steroid treatment, BCVA returned to 20/20 in both eyes and we put the patient on oral steroid and planned to commence the ADA treatment. During the preparatory tests, the QuantiFERON-TB Gold test was found to be positive. Following the INH prophylaxis of 1 month (100mg/day), ADA was started and oral steroid was tapered. However, at the 3rd month, she developed severe nausea and laboratory tests showed that liver enzymes increased dramatically. The serum ALT, AST, GGT, and ALP levels were 238 IU/L, 171 IU/L, 837 IU/L, and 239 IU/L, respectively. ADA and INH were stopped, and we decided to inject the DEX implant bilaterally for the maintenance of remission. Overall, she received three bilateral DEX implants 3 to 4 months apart. Liver enzymes returned to their normal level a month after the cessation of the systemic therapy. No intraocular pressure rise was experienced but there was mild cataract formation at the last visit.
Figure 3: Case 3. At the first visit. Color fundus pictures (a: Right eye and b: Left eye). Optical coherence tomography images depicting the serous retinal detachment with bacillary layer detachment and increased choroidal thickness (c: Right eye and d: Left eye)

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  Discussion Top


DEX implant was approved for the treatment of noninfectious posterior uveitis in 2011,[8] and since then, it is successfully employed in uveitic eyes with macular edema. In a very recent review on the place of intravitreal DEX implant for the treatment of noninfectious uveitic macular edema, we concluded that DEX implant can either be used as a single therapeutic agent in some selected cases or as an adjunct agent to an already ongoing systemic therapy or as a bridging treatment option while changing the systemically administered agents.[9] We successfully administered intravitreal unilateral DEX implant and simultaneous ranibizumab injection in addition to systemic oral mycophenolic acid in a 46-year-old woman with active serpiginous choroiditis complicated with a extrafoveolar macular neovascularization in order for both to control the inflammation and treat the macular neovascularization.[10] Recently, DEX implant has been reported as an alternative local agent to control the inflammation in patients with active VKH.[4],[5],[6]

Latronico et al.[6] reported a 15-year-old girl with a recurrent VKH disease while she was on oral steroids and cyclosporine. They initially administered a DEX implant in the left eye following a 3-day long intravenous pulse methylprednisolone treatment. The inflammation in the left eye subsided but as the inflammation was still persisting in the right eye, DEX implant was also administered intravitreally in the right eye. Two weeks after, inflammation was also under control in the right eye. However, follow-up duration was not mentioned in the text. Myung et al.[5] reported a 49-year-old male with a probable VKH disease who received two DEX implants in the OS in association with oral steroid treatment. No immunosuppressive therapy was prescribed, and the follow-up was only 4 months. Recently, Chen et al.[4] reported two patients with acute VKH disease and DEX implant was employed in addition to systemic steroid treatment. Both patients received intravenous methylprednisolone at the diagnosis, followed by oral prednisolone and cyclosporine. One patient received bilateral DEX implant 2 weeks after the diagnosis while the other received DEX implant unilaterally just at the time of diagnosis. The patients did not experience any recurrences during the follow-up of 6 and 13 months. They suggested that DEX implant administration in the acute phase of disease could enhance the short-term and long-term control of intraocular anti-inflammation.

Nowadays, in patients with acute VKH disease, systemic immunosuppressives in association with oral steroid treatment are the general practice pattern following a course of pulse methylprednisolone therapy. However, DEX implant can be a safe and effective alternative for individuals with VKH disease whose systemic treatment is ceased due to adverse effects of the systemic treatment and intravitreal therapy with DEX implant can be helpful to prevent the disease recurrences. Repetition of DEX implant treatment is certainly open to discussion and the decision to stop injecting DEX implant should be judged individually for each case.

Ethics statement

This study was a retrospective case series and therefore did not require ethical board approval. Written informed consent was obtained from all the individuals for this case series information and for the images of the case report to be published anonymously for educational and research purposes.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors declare that there are no conflicts of interest of this article.



 
  References Top

1.
O'Keefe GA, Rao NA. Vogt-Koyanagi-Harada disease. Surv Ophthalmol 2017;62:1-25.  Back to cited text no. 1
    
2.
Standardization of Uveitis Nomenclature (SUN) Working Group. Classification criteria for Vogt-Koyanagi-Harada disease. Am J Ophthalmol 2021;228:205-11.  Back to cited text no. 2
    
3.
Abu El-Asrar AM, Van Damme J, Struyf S, Opdenakker G. New perspectives on the immunopathogenesis and treatment of uveitis associated with Vogt-Koyanagi-Harada disease. Front Med (Lausanne) 2021;8:705796.  Back to cited text no. 3
    
4.
Chen PL, Chen SN. Efficacy of intravitreal dexamethasone implant in patients with Vogt-Koyanagi-Harada disease and bilateral panuveitis: Two case reports. Medicine (Baltimore) 2021;100:e27394.  Back to cited text no. 4
    
5.
Myung JS, Aaker GD, Kiss S. Treatment of noninfectious posterior uveitis with dexamethasone intravitreal implant. Clin Ophthalmol 2010;4:1423-6.  Back to cited text no. 5
    
6.
Latronico ME, Rigante D, Caso F, Cantarini L, Costa L, Nieves-Martín L, et al. Bilateral dexamethasone intravitreal implant in a young patient with Vogt-Koyanagi-Harada disease and refractory uveitis. Clin Rheumatol 2015;34:1145-8.  Back to cited text no. 6
    
7.
Read RW, Holland GN, Rao NA, Tabbara KF, Ohno S, Arellanes-Garcia L, et al. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: Report of an international committee on nomenclature. Am J Ophthalmol 2001;131:647-52.  Back to cited text no. 7
    
8.
Hunter RS, Lobo AM. Dexamethasone intravitreal implant for the treatment of noninfectious uveitis. Clin Ophthalmol 2011;5:1613-21.  Back to cited text no. 8
    
9.
Karti O, Saatci AO. Intravitreal dexamethasone implant in the treatment of non-infectious uveitic macular edema. Med Hypothesis Discov Innov Ophthalmol 2018;7:169-75.  Back to cited text no. 9
    
10.
Saatci AO, Ayhan Z, Engin Durmaz C, Takes O. Simultaneous single dexamethasone implant and ranibizumab injection in a case with active serpiginous choroiditis and choroidal neovascular membrane. Case Rep Ophthalmol 2015;6:408-14.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

 
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