EDITORIAL

Whats New in Uveitis and

Ocular Inflammation?
Timothy Y.Y. Lai, MD, FRCS, FRCOphth*

U veitis and intraocular inammation are important sight-threatening disorders worldwide, and it
has been estimated that uveitis is responsible for around 5% to 10% of blindness in the United
States and various Western countries.1 If the uveitis is not treated optimally, visual loss can develop
because of various sight-threatening complications including band keratopathy, cataract, glaucoma,
cystoid macular edema, retinal scars, and optic neuropathy.2 Among the working age group of 20 to
65 years, uveitis is second only to diabetic retinopathy as a major cause of treatable blindness.3
Therefore, uveitis is an ocular disease that carries a high socioeconomic impact.1
Recent advancements in both basic science and clinical research have greatly enhanced our
understanding in the pathogenesis, etiology, and management of uveitis and ocular inammatory
diseases. In this issue of the Asia Pacic Journal of Ophthalmology, Kedhar4 provided an excellent
literature review in research and development on ocular immunology and uveitis published in 2011 to
2012. This review gives a very comprehensive snapshot of whats new in uveitis and summarized
important ndings from various studies including the Systemic Immunosuppressive Therapy for Eye
Diseases (SITE) study and the Multicenter Uveitis Steroid Treatment (MUST) trial. Both SITE and
MUST studies were sponsored by the National Eye Institute, and the results provided important
supportive evidence to improve the management of uveitis and our understanding in the risk factors
and prognosis of uveitis.
In addition to the research topics covered in the review by Kedhar, there are 3 other areas in
uveitis with articles published in 2011Y2012 that might be of interest to clinicians. These include genetic
studies on uveitis, the use of antiangiogenesis therapy for inammatory ocular neovascularization,
and newer biologic agents for treating uveitis.
Over the past few years, a number of studies have been performed to evaluate the association of
various genes involved in the immunological system in uveitis. One of these genetic factors is the
complement factor H (CFH) gene, which is a key regulator in the alternative complement pathway of
the immune system.5,6 The CFH 184G polymorphism has been found to be associated with anterior
uveitis, and this association was specic for females.5 Moreover, the CFH I62V polymorphism was
also found to be associated with noninfectious intermediate and posterior uveitis.6 These CFH var-
iants might result in structural changes in the CFH protein and can affect the afnity of C3b binding,
which subsequently inuence the activation of the alternative pathway. Polymorphism in the com-
plement factor B (CFB) gene, an opponent of CFH, has also been found to be associated with an-
terior uveitis.7 In addition, several studies have also shown that polymorphisms in interleukin and
cytokine genes were associated with uveitis and Behcet disease.6,8Y10 These studies have enhanced
our understanding in the role of genetics in the pathogenesis of uveitis and might provide future
potential target for the treatment of intraocular inammation.
Another important recent development in the management of ocular comorbidity associated
with uveitis is the availability of antiYvascular endothelial growth factor (VEGF) agents such as
intravitreal bevacizumab and ranibizumab for choroidal neovascularization (CNV) secondary to
ocular inammation.11Y14 At present, the use of anti-VEGF agents in CNV secondary to ocular in-
ammation is considered as off-labeled use. Nonetheless, published studies have demonstrated
benecial visual outcomes following anti-VEGF therapy for inammatory CNV.11Y14 In particular,
the long-term outcome with up to 5 years of follow-up was favorable with no major complication
encountered.14 Therefore, it is reasonable to consider anti-VEGF therapy as the standard therapy
for CNV due to ocular inammation.
An area of research deciency highlighted in Kedhars4 review is the paucity of large-scale
randomized controlled trials for uveitis treatment published in 2011Y2012. Nonetheless, large-scale

From the *Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital; and 2010 Macula & Retina
Centre, Kowloon, Hong Kong.
Received for publication March 25, 2013; accepted March 29, 2013.
The authors have no funding or conicts of interest to declare.
Reprints: Timothy Y.Y. Lai, MD, FRCS, FRCOphth, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong,
Hong Kong Eye Hospital, 147K Argyle St, Kowloon, Hong Kong. E-mail: tyylai@cuhk.edu.hk.
Copyright * 2013 by Asia Pacic Academy of Ophthalmology
ISSN: 2162-0989
DOI: 10.1097/APO.0b013e318294b850

Asia-Pacic Journal of Ophthalmology & Volume 2, Number 3, May/June 2013 www.apjo.org 139

Copyright 2013 Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
Editorial Asia-Pacic Journal of Ophthalmology
clinical trials in the use of biologic agents for uveitis are be-
coming more common. For example, the results of 3 random-
ized controlled trials in the use of secukinumab, an interleukin
17A inhibitor, for the treatment of noninfectious uveitis have
just been published.15 Although the primary efcacy end points
were not met in the 3 studies, the secondary efcacy data showed
that secukinumab might reduce the use of concomitant sys-
temic immunosuppressive therapy.15 Another biologic agent,
gevokizumab, an interleukin 1AYregulating antibody, has been
shown to result in rapid and sustained reduction in uveitis and
retinal vasculitis in treatment-resistant Behcet disease.16 At pres-
ent, at least 2 large-scale, multicenter, double-masked, random-
ized controlled trials (EYEGUARD-A and EYEGUARD-C) are
being conducted to assess the efcacy and safety of gevokizumab
in the treatment of noninfectious uveitis (http://clinicaltrials.gov/
ct2/show/NCT01684345 and http://clinicaltrials.gov/ct2/show/
NCT01747538, accessed March 25, 2013). These 2 phase 3
studies will each recruit more than 300 patients, and the results
will be benecial to demonstrate whether gevokizumab is safe
and effective in treating noninfectious uveitis. Hopefully, the
research will provide a new effective treatment option that can
enhance the management of noninfectious uveitis and prevent
blindness caused by uveitis.
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for anterior uveitis in Chinese females. Mol Vis. 2011;17:2655Y2664.
Vision with action can change the world.
V Joel A. Barker
140 www.apjo.org
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& Volume 2, Number 3, May/June 2013
6. Yang MM, Lai TY, Tam PO, et al. Complement factor H and interleukin
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* 2013 Asia Pacic Academy of Ophthalmology