Anterior uveitis often associated with Zika virus infection
Click Here to Manage Email Alerts
Anterior uveitis may be present in a high percentage of patients infected by Zika virus and is often associated with increased IOP, according to a study.
Zika virus (ZIKV) infection is transmitted by Aedes mosquitoes. The first cases were reported in Uganda and Tanzania in the late 1940s, and in subsequent years, outbreaks were identified in several other African and Asian nations, Pacific islands and, later, several countries within Latin America and the Caribbean. Ocular manifestations reported in the literature were limited to conjunctivitis until 2016, when an outbreak affecting 1.3 million people occurred in Brazil. Since then, with the expanded understanding of the clinical manifestation of ZIKV, several cases of uveitis were reported.
At an island referral center in the French West Indies, the Pointe-à-Pitre University Hospital in Guadeloupe, the medical records of patients with confirmed ZIKV infection were reviewed. Patients who were referred for a red eye were included in the study. All patients underwent further virologic and serologic testing for ZIKV, best corrected visual acuity and IOP measurement, and slit lamp and fundoscopy examination. Uveitis was defined as active or inactive based on the standardization of uveitis nomenclature criteria.
Out of 62 patients with red eye, 30 (48.4%) had anterior nongranulomatous uveitis without synechiae, which was bilateral in all cases. Ocular hypertension, defined as IOP greater than 21 mm Hg, was reported in 50 of 60 eyes (83.3%).
“Ocular hypertension is thought to occur when the cells of the ZIKV-infected trabecular meshwork trigger an inflammatory cascade, which in turn causes trabeculitis,” the authors wrote.
Ocular pain was reported by 60% of patients. Visual acuity was rarely and only mildly affected. No case of posterior uveitis or retinal lesions was observed.
All eyes were treated with dexamethasone eye drops from diagnosis, leading to complete recovery after 1 year of treatment. However, despite the use of glaucoma medications, IOP was still high at 1 year in 50% of eyes. This led the authors to recommend thorough clinical examination in any patient positive for ZIKV presenting with a red eye.
“Although the findings of this study suggest that anterior uveitis responds well to corticosteroid eye drops, it is often associated with raised IOP that, if left untreated, could be sight threatening. Therefore, clinicians attending to those with acute ZIKV infection should have a low threshold for considering ZIKV-associated uveitis and arrange slit lamp biomicroscopy and IOP measurement for any of their patients presenting with a red eye,” they wrote.
Reference:
Agrawal R, et al. JAMA Ophthalmol. 2021;doi:10.1001/jamaophthalmol.2020.5138.
Perspective
Back to Top
This study goes back to the 2 years between 2016 and 2017, in which Zika virus (ZIKV) infection was a huge problem in Brazil and a lot of attention had gone to transmission of Zika from mother to fetus, causing microcephaly and retinal lesions. Fewer studies, such as this study, investigated the effects on the eye of systemic ZIKV infections in adults. There were some case reports on uveitis, but this is a larger study on 62 patients with positively confirmed systemic ZIKV infection and a history of red eye, half of which were found to have uveitis.
One interesting point was that 15 of these patients also had ocular hypertension, leading the authors to conclude that in patients with ZIKV infection who develop uveitis, this is often associated with raised IOP and that slit lamp biomicroscopy and IOP measurement should therefore be performed in patients with acute ZIKV infection presenting with a red eye.
In this study, subjects with other infectious diseases, including dengue fever virus (DFV) and chikungunya virus (CHIKV), were excluded. DFV, CHIKV and ZIKV belong to the same family of RNA arthropod-borne viruses, and it would be interesting to investigate whether all three of them increase IOP. We could then make a statement that these arthropod-borne viruses, transmitted by the Aedes mosquito, have the capability to induce ocular hypertension.
This human study supports what we had previously found in an animal model. The statement “Ocular hypertension is thought to occur when the cells of the ZIKV-infected trabecular meshwork trigger an inflammatory cascade, which in turn causes trabeculitis” clearly refers to the paper we published in 2019, although this is not cited at that point. In that study, we discovered that ZIKV infects trabecular meshwork cells and evokes inflammatory responses causing trabeculitis. We hypothesized that ZIKV likely enters the eye crossing the blood-aqueous humor barrier through the iris, which is highly vascularized. Then, through aqueous humor flow, it reaches the trabecular meshwork, infecting the cells and inducing trabeculitis. Using a mouse model, we demonstrated that ZIKV infection resulted in raised IOP and eventually retinal ganglion cell loss and optic nerve damage, the hallmarks of glaucoma.
There are two important key messages arising from this study. First, ZIKV infection is potentially a global problem. Due to climate changes and the global circulation of people, viruses such as Zika, but also chikungunya and dengue, are likely to spread also in areas that were not affected previously, evolving and adapting to other climates. If ophthalmologists see a uveitis case they cannot explain, Zika infection could be one of the causes, and they should do serology testing for ZIKV.
The second key message is that the role of these RNA viruses in ocular infections is underreported. The chances of getting high IOP and then possibly glaucoma from ZIKV should be investigated. We have seen IOP rise as a consequence in this study, but does this infection predispose to glaucoma? We need to look into this possibility.
Reference:
Singh PK, et al. mSphere. 2019;doi:10.1128/mSphere.00173-19.
Collapse
Read more about
Click Here to Manage Email Alerts