Editorial
Recent Advancements in Management
of Uveitis
Uveitis is a sort of “umbrella term” that encompasses
many different diseases, with different etiologies, treatment and prognosis.
However, there is a common denominator among them: the potential, more or less
important, to produce severe and permanent deficit in visual acuity and/or
visual function.1 This concept should be kept in mind whenever we face a
patient with uveitis and need to establish the treatment modality. This patient
will be most of times young and in working age. Disease’s impact on his life
and his social circle should not be underestimated, nor the impact of uveitis
as a cause of morbidity and socio-economic blindness within the society.2
In recent years, much emphasis has been put to define,
specifically, each clinical entity. Results of this effort are the criteria for
the diagnosis of Behcet's disease3,4, sarcoidosis5 or
Vogt-Koyanagi-Harada syndrome.6 The SUN criteria (Standardization of Uveitis
Nomenclature), although wider, also help in defining a particular clinical
picture, esential step before choosing diagnostic and therapeutic strategies
and comparing results among different centers.7
Speaking the same "language"
shortens distances and facilitates
experience exchanges.
Different uveal diseases appear in different geographic
regions and genetic backgrounds; epidemiological knowdelge about uveitis in the
part of the world we are working will render our task easier. Major emphasis
should be put on epidemiologic research
everywhere, but specially in
countries of the so called developing world: appraisal of our patient population
is key when taking decisions, mainly in a context where resources are far to be
unlimited.
During the last years, we have been privileged witness of
a breakthrough in ancillary tests for disease diagnosis. Just as an example, in
1948, Posner and Schlossman described for the first time the clinical picture
of hypertensive cyclitis that bears their names.8 Their original description of a benign and recurrent
syndrome is far from the current understanding of this form of infectious,
hypertensive and severe uveitis. Sixty years passed and thousands of molecular
techniques were developed and applied to aqueous humor analysis. Our knowledge
of uveitic entities moved steadily from the description of biomicroscopic
findings to the molecular and imaging
characterization of each syndrome. The arrival of Spectral Domain
Optical Coherence Tomography (SD-OCT) shed light on various posterior uveitic
diseases, mainly the group of the so called white dot syndromes: the almost
histological resolution of images combined with the non-invasive acquisition
mode render this tool esential in the diagnosis and monitoring of the disease.9
The near future is the Enhanced Depth Imaging
OCT (EDI-OCT), which will “remove the veil” from the choroid, a so frequent
target within the spectrum of uveitis.10
How to define the active or quiescent nature of uveitis
remains crucial and difficult to implement. How to predict which patients will
have a more torpid evolution or will develop complications more often, how to
know who will respond less to treatment.... The quantification of proteins in
the anterior chamber using the laser flare meter (LFM) technology represents a
great improvement for disease activity assesment, objectively measured in terms
of blood-aqueous barrier rupture.11 The method proved to be useful in the management of
juvenile idiopathic arthritis (JIA) – associated uveitis and was a good
predictor of progression to more severe forms of the disease.12 Similarly, the
indocyanine green (ICGA) angiography allowed us to "see" choroidal inflammation, to
defined choroidal tissue as the primary site of inflammation in many entities
and to monitor treatment response.13
The concept of recurrence in VKH syndrome,
for example, traditionally considered as an anterior uveitis requiring topical
treatment, radically changed due to ICG angiography: we know now that disease
reactivation involves also the primary site of the autoimmune insult and that
treatment should be systemic.14
Perhaps the greatest progress (and also the next
frontier) has to do with treatment. The
development of biological drugs in the field of rheumatology and oncology
allowed us to benefit our patients with a better treatment targetted to the
molecular level. The shift from systemic to intraocular delivery, whenever
possible, is by far our great contribution. The family of tumor necrosis factor
(TNF) alpha blockers proved to be important agents in the treatment of uveitis
and showed interesting differences between uveal inflammation and inflammation
affecting elsewhere in the body: Etanercept,
for example, although very useful in cases of arthritis, spondylitis, or
psoriasis, presents few advantages (if any) in the management of uveitis.15 Is the intraocular approach really superior to systemic
immunosuppression? Even though it seems its advantages are clear, this issue is
still a matter of discussion. Surprisingly, the MUST (Multicenter Uveitis
Steroid Treatment Trial) study did not find clear benefits from local therapy
with the Retisert implant compared to systemic corticosteroid administration
(with immunosuppressants if needed).16 The goal of therapy is to achieve as many periods of
remission as possible with the lowest doses and the least adverse effects
(ocular or systemic). Keeping this in mind, we are still waiting for more
results of the Ozurdex implant.17
In short time, uveitis has moved from being considered a
purely infectious disease, mainly linked to tuberculosis or syphilis, to
represent a wide and diverse group of diseases, infectious, autoimmune or
autoimmune infectiously - triggered. From being considered a guarded prognosis
disease, where the balance between the damage from disease itself and the one
related to steroid therapy was difficult to establish, to be thought as a group
of very different entities, each one with specific challenges and molecularly
targeted treatments. The genetic pathway (and the differences in treatment
response according to genetic polymorphisms in each different patient) is still
waiting to be explored. And even more important, in the era of globalization of
disease management, in a world where frontiers are difficult to establish and
knowledge is global, resources are far away of being homogeneously distributed.
How to bring the gold standard of care to every patient suffering from uveitis,
regardless where he is, represents definitely our next big challenge.
REFERENCES
16. Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Louis TA, Sugar EA, Thorne JE. Randomized comparison of systemic
anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate,
posterior, and panuveitis: The multicenter uveitis steroid treatment trial. Ophthalmology. 2011; 118 (10): 1916-1926.
Karina Julian,
MD
Uveitis
– Instituto de la Visión
Ophthalmology
Department, Austral University Hospital
Austral
University – School of Medicine
Buenos
Aires – Argentina