New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease

Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and meningeal and auditory manifestations. The disease affects pigmented races with a predisposing genetic background. Evidence has been provided that the clinical manifestations are caused by a T-lymphocyte-mediated autoimmune response directed against antigens associated with melanocytes in the target organs. Alongside of T lymphocytes, autoreactive B cells play a central role in the development and propagation of several autoimmune diseases. The potential role of B lymphocytes in the pathogenesis of granulomatous uveitis associated with VKH disease is exemplified within several studies. The early initial-onset acute uveitic phase typically exhibits granulomatous choroiditis with secondary exudative retinal detachment and optic disc hyperemia and swelling, subsequently involving the anterior segment if not adequately treated. The disease eventually progresses to chronic recurrent granulomatous anterior uveitis with progressive posterior segment depigmentation resulting in “sunset glow fundus” appearance and chorioretinal atrophy if not properly controlled. Chronically evolving disease is more refractory to treatment and, consequently, vision-threatening complications have been recognized to occur in the chronic recurrent phase of the disease. Conventional treatment with early high-dose systemic corticosteroids is not sufficient to prevent chronic evolution. Addition of immunomodulatory therapy with mycophenolate mofetil as first-line therapy combined with systemic corticosteroids in patients with acute initial-onset disease prevents progression to chronic evolution, late complications, vitiligo, and poliosis. Furthermore, patients under such combined therapy were able to discontinue treatment without relapse of inflammation. These findings suggest that there is a therapeutic window of opportunity for highly successful treatment during the early initial-onset acute uveitic phases, likely because the underlying disease process is not fully matured. It is hypothesized that early and aggressive immunosuppressive therapy will prevent remnant epitope generation in the initiation of the autoimmune process, the so-called primary response. B cell depleting therapy with the anti-CD20 monoclonal antibody rituximab is effective in patients with refractory chronic recurrent granulomatous uveitis. The good response after rituximab therapy reinforces the idea of an important role of B cells in the pathogenesis or progression of chronic recurrent uveitis associated with VKH disease.

Long-Term Outcomes of Initial Trabeculectomy in Glaucoma Associated with Granulomatous and Non-Granulomatous Uveitis

Purpose To evaluate the outcomes of initial trabeculectomy in granulomatous and non-granulomatous uveitis. Methods Retrospective comparative study of 68 eyes that underwent an initial trabeculectomy. Results The mean follow-up was 74.18 and 74.86 months in both groups (p = 0.95). The intraocular pressure decreased from 40.03 mmHg (± 7.2) and 36.48 mmHg (± 11.3) to 14.00 mmHg (± 6.2) and 13.48 mmHg (± 5.7), the number of medications decreased from 3.73 (± 0.7) and 3.58 (± 0.9) to 1.00 (± 1.4) and 1.13 (± 1.4) on the last follow-up (p < 0.01) in the granulomatous and non-granulomatous groups, respectively. More eyes in the granulomatous uveitis group developed delayed postoperative complications like cataract, transient hypotony and glaucoma progression. Success rates were 64.9 and 71.0%, while failure rates were 35.1 and 29.0% in both groups (p = 0.84). Conclusions Trabeculectomy seems to have comparable IOP control and survival in granulomatous and non-granulomatous uveitis. Nevertheless, more eyes in the granulomatous uveitis group developed late onset complications.

Granulomatous uveitis and choroidal detachment in a patient after topical treatment with Bimatoprost: A case report

Background: Bimatoprost 0.03% is an intraocular pressure (IOP) lowering prostaglandin analog with different adverse side effects such as potential ocular inflammatory effect and ocular hyperemia. Case presentation: We report a case of 80-year-old woman diagnosed with bilateral glaucomatous uveitis, and choroidal detachment in the left eye after topical bimatoprost administration. During the patient’s hospitalization, Bimatoprost treatment was discontinued and local steroid therapy was administrated. After 1 week we reported a marked improvement of visual acuity, IOP measurement was 12 mmHg in both eyes. Anterior segment examination showed complete resolution of conjunctival and pericheratic hyperemia with significant reduction of endothelial precipitates in both eyes. Conclusions: In our case, the anterior granulomatous uveitis occurred in both pseudophakic eyes and the choroidal detachment (CD) in the eye that previously had trabeculectomy. Probably the scar tissue of the trabeculectomy allowed a better penetration of the Bimatoprost or a greater sensitivity due to an altered trabecular tissue. This work confirms that the onset physiopathology mechanism of granulomatous uveitis and CD following instillation of Bimatoprost remains uncertain.

Vogt-Koyanagi-Harada Disease

Vogt-Koyanagi-Harada (VKH) is a multisystem autoimmune disease characterized by bilateral, diffuse granulomatous uveitis associated with neurological, auditory, and integumentary findings. Multimodal imaging is crucial for both the initial diagnosis and monitoring the treatment response. Although it is a severe disease with several complications, the visual prognosis is good if treated promptly and aggressively.

Diagnostic value of lymphopaenia and elevated serum ACE in patients with uveitis

AimTo evaluate the diagnostic worth of elevated serum ACE (sACE) and lymphopaenia, singly or combined, in diagnosing sarcoid uveitis.MethodsMonocentric retrospective study, on a cohort of 996 adult patients referred to our department between March 2001 and December 2018 for a diagnostic work-up of uveitis. The sensitivity (SE), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the two biomarkers were calculated in different contexts.ResultsEight hundred and sixty-eight patient cases were reviewed. The mean age at uveitis onset was 49.4 (±18.6) years. Of them, 144 patients had a diagnosis of sarcoid uveitis. An elevated sACE had SE of 45.8%, Sp of 88.8%, PPV of 44.9% and NPV of 89.2% in diagnosing sarcoid uveitis. For lymphopaenia, SE was 15.3%, Sp was 96.7%, PPV was 47.8% and NPV was 85.2%. For the combination of elevated sACE and lymphopaenia, SE was 18.9%, Sp was 99.0%, PPV was 73.9% and NPV was 89.5%. The value of this combination varied according to patient age at diagnosis plus anatomoclinical entities: for patients aged ≤50 years, SE was 31.3%, Sp was 99.7%, PPV was 90.9% and NPV was 94.3%. For granulomatous uveitis, SE was 26.2%, Sp was 97.3%, PPV was 73.3% and NPV was 82.5%.ConclusionA combination of elevated serum ACE and lymphopaenia more convincingly suggests sarcoid uveitis than these investigational tests used alone, especially in patients with granulomatous uveitis, while a lack of these markers corresponds to a high NPV.Trial registration numberNCT03863782.