# Childhood Uveitic Glaucoma: Complex Management in a Fragile Population
## 3 Pathogenesis of IOP Dysregulation in Uveitis Glaucoma  
The pathogenesis of IOP dysregulation in uveitis is not fully understood yet. Uveitis can compromise the delicate balance between secretion and outflow of aqueous humor; therefore, in patients with uveitis, both ocular hypotony and hypertension can occur. It has been reported that ocular hypertension develops in up to 46% of uveitis patients and that it is more common in patients with chronic inflammation than in those with acute uveitis [32; 33]. Ocular hypotony is less common in uveitis, affecting up to 10% of patients and is more common in young patients, mainly those with JIA uveitis [34]. IOP reduction is frequently due to ciliary body inflammation, resulting in decreased aqueous production [35] and can occur as a complication following glaucoma surgery. Interestingly, raised IOP in uveitis can be documented in eyes with either closed or open iridocorneal angle. In uveitis glaucoma, open-angle is more common than angle closure [36]. Several pathogenetic mechanisms have been hypothesized to cause IOP rise in both closed- and open-angle uveitic glaucoma. In the closed angle UG, IOP rise can be secondary to three mechanisms: (1) pupillary block caused by posterior synechiae, (2) presence of peripheral anterior synechiae, and (3) forward rotation of the ciliary body, described in VKH Syndrome [37]. In open-angle UG, the disruption of the blood-aqueous barrier due to inflammation increases the level of proteins in the aqueous humor in uveitis eyes. This great amount of proteins (up to 1308 mg vs. 30-50 mg in normal eyes) can interfere with the aqueous outflow. [PERSON] et al., characterized the protein pattern of the aqueous humor of patients with and without uveitis. The results were very similar to those of serum proteins, supporting the theory that the increased blood-aqueous barrier permeability may be involved in the pathogenesis of uveitis [38]. [PERSON] et al., demonstrated a relationship between aqueous humor protein concentration and aqueous humor outflow. Specifically, the outflow was significantly reduced in uveitis with high aqueous humor protein levels and appeared to be normal in active uveitis with low flare levels [39]. In addition, mechanical clogging of the Trabecular Meshwork (TM) can result from the high concentration of inflammatory cells and debris in the anterior chamber [38]. The inflammation of the TM, known as trabeculinis, is also supposed to be involved in the development of uveitis open-angle glaucoma. Trabeculinis is frequently characterized by an acute IOP increase, as in the Fuchs heterochromic uveitis (FHU), herpetic uveitis (HU), and Posner-Schlossman syndrome (PSS) subtypes [39]. [PERSON] et al., collected aqueous samples during cataract surgery from 22 patients with inactive uveitis and 24 subjects without uveitis. Patients with uveitis showed a greater expression of interleukin 2 (IL-2), interferon-gamma (INF-\(\gamma\)), and tumor necrosis factor-alpha (TNF-\(\alpha\)), related to T-helper 1 inflammatory response, compared to patients without uveitis [40]. Current evidence shows that the T-helper response is involved in uveitis pathogenesis, and the cytokine response may differ in infectious and non-infectious unveitis [41; 42]. However, there is still debate whether a specific cytokine pattern may be linked to a higher risk of developing uveitis glaucoma. \begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Diagnosis** & **Type of Uveitis** & **Prevalence (\%)** & **Relative Risk of Glaucoma** \\ \hline JIA & anterior & 26.19 & 2.49 \\ \hline VKH & panuveitis & 3.96 & 2.71 \\ \hline CMV & anterior & 4.76 & 1.46 \\ \hline BD & panuveitis & 4.76 & 1.46 \\ \hline Idiopathic & all & 30.15 & 1.28 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Type of uveitis and prevalence of pediatric uveitis with the corresponding relative risk (RR) of UG. JIA: Juvenile Idiopathic Arthritis; VKH: Vogt–Koyanagi–Harada; CMV: Cytomegalovirus; BD: Behcet’s disease.