Multiple mechanisms have been implicated in secondary glaucoma development in eyes with VKH disease. According to our findings, the angle-closure disease appears to be a significant contributor in combination with open-angle mechanisms for the development of OHT/glaucoma. We found a significantly higher prevalence of anterior (86.6%) and posterior (76.1%) synechiae in eyes with glaucoma during the follow-up period. Our findings are consistent with recent studies that found posterior and anterior synechiae in 64% of glaucoma eyes in a smaller population (n = 28) of VKH patients . However, earlier studies report a lower prevalence, with only 25% (34/136) of VKH eyes exhibiting this iris complication . The value of posterior synechiae as a predictor of VKH-related ocular complications, including glaucoma, was reported in a retrospective analysis of 87 VKH patients treated with high-dose systemic corticosteroids . The relatively high prevalence of anterior and posterior synechiae in our population suggests that VKH recurrent episodes of anterior segment inflammation may be a key mechanism in the development of glaucoma. This condition is supported by the fact that 64.2% of the eyes with glaucoma had chronic disease at presentation, probably due to a late diagnosis or inadequate control of inflammation. Our findings emphasize the importance of performing gonioscopy during routine evaluations to detect early signs of angle-closure disease.
The prevalence of glaucoma in our study (n = 67 eyes, 22%) is consistent with previous studies that have reported a rate of glaucoma in VKH eyes ranging from 2.6–45%, depending on the year and population studied [4, 8, 12–14]. However, compared to other studies, the prevalence of angle-closure glaucoma (82.1%) was higher. In a large series of 448 eyes of 224 VKH patients of India, Pandey et al. reported that angle-closure mechanisms were responsible for glaucoma development in only 29.6% of cases . This finding is similar to one of the first studies of secondary glaucoma in VKH, which found angle-closure, mainly due to pupillary block in 43.7% of the eyes in a Hispanic population . Both studies failed to provide a clear definition of angle-closure disease. Since we defined angle-closure as more than 180 degrees of irido-trabecular contact on gonioscopy, we probably found a higher prevalence of secondary angle closure in our study. Our findings are consistent with Yang et al., who discovered the angle-closure disease in 50.6% of OHT/glaucoma cases in a large study of 695 VKH eyes from China. Among the mechanisms described by these authors were pupillary-block arising from complete iris posterior synechiae (28.9%), extensive peripheral anterior synechiae (10.8%), and acute angle-closure glaucoma at onset (10.9%) .
Other inflammatory mechanisms, such as ciliary body swelling and effusion, have been implicated in uveitic glaucoma, in addition to a pupillary block from posterior synechiae, as demonstrated by ultrabiomicroscopic findings [16, 17]. In our study, 8 of the 17 glaucoma-affected eyes had acute angle-closure and an iris bombé configuration, requiring immediate iridectomy. It is likely that besides pupillary block, ciliary body edema with anterior rotation of the ciliary processes resulted in a shallow anterior chamber and acute angle-closure due to poorly controlled inflammation [16–18]. However, in the acute angle-closure, no ultrabiomicroscopy was performed.
At the time of presentation, 35.8% of eyes had acute VKH disease, and 64.2% had chronic recurrent VKH disease (p < 0.001). When considering eyes that had angle-closure glaucoma, 69.1% had the chronic VKH disease associated with recurring episodes of anterior segment inflammation. The chronic recurrent form is significantly associated with secondary glaucoma [6, 12, 14, 16, 19, 20]. Arevalo et al. reported that 58.4% and 20.7% of the eyes that developed glaucoma had the chronic recurrent and acute form of VKH disease, respectively (p ≤ 0.0001) . Abu El-Asrar et al. also reported a statistically significant association between glaucoma, cataract, or subretinal neovascular formation with the chronic recurrent form of VKH .
In our study, baseline IOP was significantly higher in glaucoma eyes (p < 0.001). Sixty-three of the eyes (94%) with glaucoma developed OHT, compared to only 26.1% in the non-glaucoma group. In VKH eyes, IOP elevation may result mainly from two mechanisms. First, topical corticosteroid use is a well-known risk factor for IOP elevation. Studies report that 13%-62% of eyes with acute and chronic uveitis of any etiology are steroid-responders [21–23]. During the acute stage of VKH, eyes usually have a low IOP secondary to low aqueous production by the ciliary body, which may protect from OHT development. However, anterior segment inflammation may damage the trabecular meshwork either by accumulation of inflammatory cells, posterior synechiae formation, and/or appositional closure . After the inflammation subsides and aqueous production restores, the damaged angle leads to a compromised aqueous outflow with subsequent IOP elevation .
Regarding treatment for VKH disease, 33 eyes (49.3%) and 61 eyes (25.6%) of glaucoma and non-glaucoma group, respectively, were on topical corticosteroids at the last visit (p < 0.001). This difference might be explained by the fact that most eyes in the glaucoma group also have the chronic recurrent form of VKH disease. In such a form, sustained inflammatory control is harder to achieve . Statistical significance was also reached in the increased use of intravenous corticosteroids in the glaucoma group (32.8% vs. 8.4%). In our study, 212 eyes (69.5%) from both groups required management with IMT to control intraocular inflammation, with no statistically significant difference between groups. The use of IMT has been widely recognized as effective in improving visual outcomes and reducing complications arising from VKH disease, such as cataracts, glaucoma, and/or subretinal neovascular membranes [11, 24, 25]. Despite the latter, prospective controlled studies are required to determine the role of IMT in glaucoma development in eyes with VKH.
Although most eyes with and without glaucoma (64.2% vs. 96.6%, p < 0.001) met our definition of IOP control, most eyes in the glaucoma group required laser and/or surgical management (61.2% vs. 9.7%, p < 0.001). Ahmed valve placement was the surgery of choice for glaucoma treatment in 17 eyes (36.2%). Previous evidence supported this finding that both Ahmed valve and trabeculectomy with mitomycin-C achieved adequate IOP control in patients with uveitic glaucoma; however, the cumulative success rate at 1-year favored significantly the Ahmed valve group . Regarding other tube implants, a study performed by Chow et al. reported no difference in IOP reduction between trabeculectomy, Ahmed, and Baerveldt implant; however, postoperative hypotony was significantly higher in the trabeculectomy group . In our study, hypotony was reported in 5 (71.4%) of the trabeculectomy eyes, with persistent choroidal detachment resulting in two eyes with no light perception. There were no cases of hypotony identified in the Ahmed valve group.
Limitations of our study include its retrospective design. Also, since many patients were referred and previously managed, data of their initial presentation and the exact moment of glaucoma development could not be obtained. Our clinical service is a tertiary referral center, and the referral bias poses some limitations on the extrapolation of the results. The relatively large sample size provides a more accurate assessment of glaucoma prevalence and mechanisms in a population of Mexican VKH patients over 18 years.