Subretinal Fibrosis in Uveitis

As recognized more than 70 years ago by Adalbert Fuchs, son of acclaimed eye pathologist Ernst Fuchs,¹ subretinal fibrosis (SRF) in eyes with uveitis is an uncommon complication that occurs most frequently in the setting of serious retinal detachment (SRD) or chorioretinitis.² Fuchs called this condition ‘choroiditis proliferans,’³ whereas others have referred to ‘progressive subretinal fibrosis and uveitis,’ ‘subretinal fibrosis syndrome,’ and ‘subretinal fibrosis and uveitis syndrome.^4–6 Rojas provided a very thorough and thoughtful review of this topic nearly 20 years ago⁷ and agreed with the original observations of Fuchs; specifically that uveitic SRD, occurring most often in the setting of Vogt-Koyanagi-Harada (VKH) disease or sympathetic ophthalmia (SO), and chorioretinitis, due most frequently to multifocal choroiditis/punctate inner choroiditis (MFC/PIC), are the most common clinical causes of uveitic SRF.⁸ Disease-specific risk factors for the development of SRF in eyes with SRD or chorioretinitis have yet to be fully explored.

In this issue of Ocular Immunology & Inflammation (OII), Golzarri et al.⁹ reported the results of a retrospective case-control study of 92 Mexican mestizo patients with VKH disease with (cases; n = 39) and without (controls; n = 53) SRF followed for at least 12 months in their tertiary referral patient population in Mexico City. The overall prevalence of SRF in the cohort was 42.4%, compared to 64.8% in an earlier study from the same group,¹⁰ 40% from a cohort seen at the National Eye Institute,¹¹ 13% from The Francis I. Proctor Foundation-UCSF,¹² and 7% from the Doheny Eye Institute -USC.¹² Bivariate analysis performed by Golzarri et al⁹ suggested that a therapeutic response time of longer than 1 month was associated with a 4.5-fold increased risk in the development of SRF (95% CI 1.5–13.4; p = .01), whereas the occurrence of a large or bullous SRD, defined as extending beyond the arcade vessels, increased the risk of SRF formation by 7.8 fold (95% CI 2.6–23.4; p = .001). Both a delay in medical attention of greater than 4 weeks (OR 2.2, 95% CI 0.8–6.2; p = .1) and the occurrence of any SRD (OR 2.1, 95% CI 0.8–6.6; p = .1) showed trends toward an increased risk of SRF formation. Logistic regression that adjusted for age, best-corrected visual acuity (BCVA) at presentation, and a therapeutic response time of greater than 4 weeks showed that both a delay in medical attention of 4 weeks or greater (adjusted OR 5.3, 95% CI 1.0–27.9; p = .05) and the occurrence of a bullous SRD (OR 8.9, 95% CI 1.9–41.1; p = .005) were associated with increased SRF risk. Eyes with SRF within the macula at last visit tended to have worse BCVA (median 20/80) than eyes with SRF outside of the macula or around the disc (median 20/40) – although these differences failed to achieve statistical significance (p = .08; Mann Whitney test). The authors concluded that Mexican mestizo patients with VKH disease are at particularly high risk of SRF formation, a notion supported by their previous study¹⁰ and by the high proportion of Latino VKH patients reported to develop SRF from referral centers in California.¹² A multiracial VKH study that controlled for non-racial risk factors for SRF formation would be required to address the issue more definitively, however. While the authors found no optical coherence tomography abnormalities associated with an increased risk of SRF formation, they did not show enhanced depth imaging or report on the influence of choroidal thickness at presentation, a finding that could be expected to be correlated with the presence and extent of SRD, which, as noted above, appear to influence the rate of SRF formation.

The report by Golzarri et al.⁹ in this issue of OII supports earlier suggestions^10–14 that Latino heritage, a delay in diagnosis, severity of inflammation at presentation, and time to control that inflammation all contribute to increased risk of developing SRF in patients with VKH disease, and that macular SRF formation, in particular, might portend more limited long-term recovery of vision. Together, such findings highlight the importance of prompt diagnosis, treatment, and control of active VKH disease so as to minimize the risk of developing SRF and other vision-threatening complications of condition.^15–18

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The authors reported there is no funding associated with the work featured in this article.