Therapeutic window of opportunity in the acute uveitic phase of Vogt–Koyanagi–Harada disease: Prevention of late autoimmune complications by early intervention

Abstract

Purpose To determine relationship between timing of treatment initiation and disease outcomes and whether a therapeutic window of opportunity exists in initial‐onset acute uveitis associated with Vogt–Koyanagi–Harada disease. Methods Retrospective analysis of 112 patients (224 eyes). Main outcome measures were final visual acuity, progression to chronic recurrent evolution, development of complications, particularly ‘sunset glow fundus’, and drug‐free remission cure of uveitis. Results Forty‐six patients (92 eyes) presented in the phase preceding anterior segment (AS) inflammation (early presentation) and 66 patients (132 eyes) had AS inflammation at presentation (late presentation). In significantly more eyes in the early presentation group (85.9%), final visual acuity of 20/20 was achieved compared with those in the late presentation group (66.7%) (p = 0.001). None of the eyes in the early presentation group progressed to chronic recurrent evolution and none developed ‘sunset glow fundus’, whereas in the late presentation group, 28.8% of the eyes progressed to chronic recurrent evolution (p < 0.001) and 56.1% developed ‘sunset glow fundus’ (p < 0.001). Patients in the early presentation group were able to discontinue treatment without relapse of inflammation at significantly shorter time intervals compared to patients in the delayed presentation group (p < 0.001). In the late presentation group, logistic regression analysis demonstrated that presenting clinical features predicting unfavourable outcomes were posterior synechiae (odds ratio = 4.03; 95% confidence interval [CI] = 1.29–12.23), bullous exudative retinal detachment extending to the periphery (odds ratio = 3.35; 95% CI = 1.53–7.32) and female gender (odds ratio = 2.05; CI = 1.08–3.90). Conclusions Our findings suggest that the window of opportunity lies in the phase preceding AS inflammation and initiation of effective treatment during this phase results in cure of uveitis and prevents blinding complications.

Prognostic value of pretreatment indocyanine green angiography in the acute uveitic phase of Vogt‐Koyanagi‐Harada disease

“…Previous studies also demonstrated that subretinal pooling of fluorescein over the posterior pole was more frequently observed in patients who presented early within 2 weeks of symptoms compared to those presenting after 2 weeks (Chee et al., 2010; Yang et al., 2007). These findings suggest that the absence of peripapillary punctate choroidal hyperfluorescence, punctate choroidal hyperfluorescence elsewhere and patches of hypofluorescence that corresponded to areas of exudative retinal detachment on pretreatment ICGA are poor prognostic factors as it suggests that the choroidal inflammation is no longer within the therapeutic window of opportunity (Abu El‐Asrar et al., 2023).…”

“…The diagnosis of VKH disease in the acute uveitic phase was based on the pattern of clinical characteristics at presentation. Patients with initial‐onset uveitis associated with VKH disease typically showed bilateral exudative retinal detachment and optic nerve head hyperaemia and swelling with (delayed presentation) or without (early presentation) AS inflammation (Abouammoh et al., 2016; Abu El‐Asrar, Al Mudhaiyan, et al., 2017; Abu El‐Asrar et al., 2012, 2023; Abu El‐Asrar, Dosari, et al., 2017) (Figure 1). We only included the patients who had ICGA performed before initiating treatment with a minimum follow‐up of 12 months.…”

“…All patients were managed and followed up by one of the authors (AMA). Patients received treatment according to a standardized protocol, as described previously (Abouammoh et al., 2016; Abu El‐Asrar, Al Mudhaiyan, et al., 2017; Abu El‐Asrar et al., 2012, 2023; Abu El‐Asrar, Dosari, et al., 2017). All patients received systemic corticosteroids combined with immunomodulatory drugs as first‐line therapy.…”

“…At initial presentation, 38 patients (76 eyes) presented in the phase preceding AS inflammation (early presentation). Forty-six patients (92 eyes) had AS inflammation at presentation (late presentation), as previously described (Abu El-Asrar et al, 2023). The immunomodulatory drugs used in this group included mycophenolate mofetil in 78 patients, cyclosporine in 5 patients and methotrexate in one patient.…”

“…Recently, we demonstrated the presence of a therapeutic window of opportunity in initial‐onset acute uveitis associated with VKH disease in the phase preceding AS inflammation (early presentation). This is an early critical period during which effective suppression of inflammation alters the disease course as none of the eyes in the early presentation group developed SGF or progressed into chronic recurrent granulomatous inflammation (Abu El‐Asrar et al., 2023).…”