Evaluation of the Glucocorticoid Receptor as a Biomarker of Treatment Response in Vogt-Koyanagi-Harada Disease

Abstract

The evaluation of clinical predictive factors and determination of the change in expression of GR isoforms as potential biomarkers can contribute to the early identification of GC-resistant patients with VKH.

Catching the therapeutic window of opportunity in early initial-onset Vogt–Koyanagi–Harada uveitis can cure the disease

“…These results indicate that early, combined, sustained, and if possible ICGA-monitored treatment is able to modify the VKH disease phenotype, avoiding SGF and achieving cure, much in the same fashion as early and sustained therapy changes the phenotype of birdshot retinochoroiditis [36]. Treatment duration is variable and individually different, depending on the time-point of treatment initiation, disease severity, and individual susceptibility to treatment, which may include biomarkers indicating therapy response in the future [37]. Treatment should not be stopped if subclinical ICGA-detected choroiditis remains present, and the duration should be 15 months at minimum, and ideally closer to 24 months [29].…”

Initial-onset acute and chronic recurrent stages are two distinctive courses of Vogt-Koyanagi-Harada disease

“…However, this classification did not consider time from the onset of symptoms, and specific findings observed at certain time point from the symptoms presentation and outcomes related to the stage of VKH disease were not introduced [ 13 , 16 ]. Moreover, as an attempt to introduce a categorization of VKH patients in clinical studies, different intervals of time have been used [ 5 , 14 , 17 – 20 ]. Another major shortcoming of these revised criteria is the fact that highly sensitive diagnostic modalities, such as indocyanine green angiography (ICGA) [ 21 ], measurement of choroidal thickness using enhanced depth imaging optical coherence tomography (EDI-OCT) [ 22 ] or swept source optical coherence tomography (SS-OCT) [ 23 ], and high-frequency ultrasound biomicroscopy (UBM) for in vivo visualization of the anterior segment [ 24 ], especially crucial for early identification of the inflammatory process, diagnosis of atypical cases and follow up of the disease, are missing.…”

“…In that regard, since prognosis is significantly affected by the stage of the disease and the presence of subclinical inflammation [ 5 , 8 – 12 ], the use of a more comprehensive classification that considers ancillary testing and a clear distinction between initial-onset acute and chronic recurrent disease courses, is advisable. The poor response to therapy, among patients with a chronic recurrent granulomatous AS inflammation has been described [ 20 , 25 ]. Moreover, this subset of patients has more complications [ 8 , 26 ] and a trend to have more severe ocular and systemic manifestations of the disease.…”

Vogt-Koyanagi-Harada disease

“…Some significant developments have been published regarding potential biomarkers of treatment response based on the glucocorticoid receptor (GR), which is a ligand-dependent transcriptional factor [30]. Urzua et al have found a distinct expression profile of GR isoforms that allows to categorize GC response as early as 2 weeks [26]. This laboratory-based approach is based on the quantification of mRNA levels of GR isoforms in two time points and a ratio calculation between both measurements.…”