Safety of systemic therapy for noninfectious uveitis

Ormaechea, Maria Soledad; Hassan, Muhammad; Onghanseng, Neil; Park, Jung Hyun; Mahajan, Sarakshi; Al-Kirwi, Khalid Yusuf Yaseen; Uludağ, Günay; Halim, Muhammad Sohail; Schlaen, Ariel; Sepah, Yasir J.; Diana, V.; Nguyen, Quan Dong

doi:10.1080/14740338.2019.1692810

Cited by 12 publications

(8 citation statements)

References 232 publications

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“…Once the acute inflammation is controlled, the long-term management of uveitis is challenging and depends on several aspects, including disease severity, association with a systemic condition and patient's particularities (Ref. 92 ). A stepwise approach is typically employed, introducing different immunomodulatory agents, either alone or in combination, to reduce the CS burden and their attendant ocular and systemic adverse events, especially in prolonged use.…”

Section: Uveitismentioning

confidence: 99%

AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?

Castro,

Steel,

Layton

2024

Expert Rev. Mol. Med.

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Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.

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Section: Uveitismentioning

confidence: 99%

AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?

Castro,

Steel,

Layton

2024

Expert Rev. Mol. Med.

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“…The first-line treatment for noninfectious posterior uveitis with or without ME includes systemic and local corticosteroids. [ 8 ] Systemic steroids have multiple ocular and systemic dose-limiting side effects often associated with the development of other comorbidities. [ 8 ] Local steroid includes topical drops and periocular and intravitreal injection.…”

Section: Introductionmentioning

confidence: 99%

Single Low-dose Suprachoroidal Triamcinolone Acetonide Injection in Macular Edema Secondary to Noninfectious Posterior Uveitis

Anand,

Sinha,

Gupta

et al. 2023

Middle East African Journal of Ophthalmology

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PURPOSE: The purpose was to study the anatomical and functional outcome following single low-dose suprachoroidal triamcinolone acetonide (LD-SCTA) (2 mg) injection in noninfectious posterior uveitis. METHODS: Eleven patients with macular edema (ME) more than 280 μ secondary to noninfectious uveitis were included in the study. A single LD-SCTA (0.5 ml) injection was performed in the study eye with the help of a novel suprachoroidal microneedle (Pricon, Iscon Surgicals, Jodhpur, Rajasthan, India). The study parameters were noted at 4 and 12 weeks post LD-SCTA injection. RESULTS: Ten of 11 patients had a significant decrease in central macular thickness (CMT). The mean CMT measurement at baseline was 513.6 ± 191.73 μm for the 10 patients who responded to the treatment, which reduced significantly to 265.1 ± 34.72 μm (P < 0.003) and 260.6 ± 34.72 μm (P < 0.002) at 4 and 12 weeks, respectively. The mean best-corrected visual acuity (BCVA) at baseline was 0.84 ± 0.41 logMAR unit which improved to 0.52 ± 0.33 (P < 0.001) and 0.25 ± 0.22 (P < 0.000) at weeks 4 and 12, respectively. The mean intraocular pressure at baseline recorded was 16.36 ± 2.97 mmHg, 19.45 ± 4.80 mmHg (P = 0.06) at 4 weeks, and 17.27 ± 2.53 mmHg (P = 0.35) at 12 weeks. One eye which did not respond to LD-SCTA was a case of recurrent Vogt–Koyanagi–Harada disease. CONCLUSION: Single LD-SCTA injection is efficacious in reducing CMT in ME, improving BCVA, and controlling the inflammation in noninfectious posterior uveitis. LD-SCTA can be used as a first-line therapy in noninfectious uveitis over other routes of steroid administration with a favorable outcome and safety profile.

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“…Intraocular injection of therapeutic agents is, therefore, proposed to circumvent this problem ( Hosoya and Tachikawa, 2009 ). Intravitreal steroid injections are also propagated to avoid the systemic side effects of steroids ( Nayak and Misra, 2018 ; Ormaechea et al, 2019 ). Intravitreal steroids are currently used in the clinic and include intravitreal triamcinolone acetonide (IVTA), the dexamethasone (DEX) intravitreal implant, and the fluocinolone acetonide (FA) intravitreal implant.…”

Section: Introductionmentioning

confidence: 99%

Comparative Efficacy and Safety of Advanced Intravitreal Therapeutic Agents for Noninfectious Uveitis: A Systematic Review and Network Meta-Analysis

Liao

Zhong

et al. 2022

Front. Pharmacol.

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Background: To compare the efficacy and safety of advanced intravitreal therapeutic regimens, including a dexamethasone implant at 350 and 700 μg; a fluocinolone acetonide (FA) implant, 0.2 µg/day, 0.59 and 2.1 mg; intravitreal bevacizumab, 1.25 mg; intravitreal ranibizumab, 0.5 mg; intravitreal triamcinolone acetonide (IVTA), 2 and 4 mg; and standard of care (SOC, systemic therapy) for noninfectious uveitis.Methods: We searched the Cochrane Library database, EMBASE, Medline, clinicaltrials.gov until April 2021 with 13 RCTs (1806 participants) identified and conducted a pairwise and Bayesian network meta-analysis with random effects.Results: No specific regimen showed a statistically significant advantage or disadvantage to another treatment regimen with regard to efficacy. However, the FA implant, 0.59 mg was associated with a higher risk of cataract (RR 4.41, 95% CI 1.51–13.13) and raise in intraocular pressure (IOP) (RR 2.53 95% CI 1.14–6.25) compared with SOC at 24 months. IVTA, 4 mg at 6 months was associated with lower risk of IOP rising compared with FA implant, 0.2 µg/day at 36 months (RR 3.43 95% CI 1.12–11.35).Conclusion: No intravitreal therapeutic regimens showed a significant advantage or disadvantage with regard to efficacy. However, SOC was associated with lower risk of side effects compared with FA implants. IVTA, 4 mg, might be the best choice with lowest risk of IOP rising.Systematic Review Registration:clinicaltrials.gov, identifier CRD42020172953

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Safety of systemic therapy for noninfectious uveitis

Cited by 12 publications

References 232 publications

AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?

AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?

Single Low-dose Suprachoroidal Triamcinolone Acetonide Injection in Macular Edema Secondary to Noninfectious Posterior Uveitis

Comparative Efficacy and Safety of Advanced Intravitreal Therapeutic Agents for Noninfectious Uveitis: A Systematic Review and Network Meta-Analysis

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