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Saudi Journal of Ophthalmology (2013) 27, 295—298
Case Report
Nongranulomatous anterior uveitis in a patient with Usher
syndrome
Sultan Abdulaziz S. Alzuhairy, MD a,⇑; Abdullah Alfawaz, MD b
Abstract
A 34-year-old female with Usher syndrome, but no family history of similar illness, presented with complaints of vision reduction,
redness, and photophobia. Biomicroscopic examination showed mildly injected conjunctivae bilateral, small, round keratic precipitates; bilateral +2 cells with no flare reaction in the anterior chamber; and bilateral posterior subcapsular cataracts. No associated
posterior synechiae, angle neovascularization, or iris changes were detected; normal intraocular pressures were obtained. Fundus
examination demonstrated waxy pallor of both optic nerves, marked vasoconstriction in retinal vessels, and retinal bone spicule
pigment formation, with a normal macula. Electroretinography confirmed the diagnosis of retinitis pigmentosa, optical coherent
tomography was normal and otolaryngology consultation was conducted.
To our knowledge, an association between Usher syndrome and bilateral nongranulomatous anterior uveitis has not been previously reported, and our purpose is to report this association.
Keywords: Retinitis pigmentosa, Usher syndrome, Uveitis: Anterior uveitis
Ó 2013 Production and hosting by Elsevier B.V. on behalf of Saudi Ophthalmological Society, King Saud University.
http://dx.doi.org/10.1016/j.sjopt.2013.06.001
Introduction
Usher syndrome is an association of retinitis pigmentosa
(RP) and congenital sensorineural hearing loss. The exact incidence of Usher syndrome has been difficult to determine, but
surveys of RP patients have suggested that about 10% are
profoundly deaf, and ophthalmic examinations of children
in deaf schools have revealed that approximately 6% have
RP. Usher syndrome is the most common cause of deafness
and blindness and is responsible for half of all cases of combined deafness and blindness. The prevalence of Usher syndrome is thought to be 3 cases per 100,000 people.1–3
Uveitis is commonly subdivided histologically and clinically
into two main categories: granulomatous and nongranulomatous. Nongranulomatous uveitis typically has an infiltration of
lymphocytes and plasma cells, whereas granulomatous reac-
tions also include epithelioid and giant cells. The most common form of nongranulomatous anterior uveitis is acute
anterior uveitis (AAU), which is associated with the HLA-B27
allele in half to two thirds of patients. Although the cause is
usually unknown, certain ocular and systemic diseases may
be the underlying cause of the iritis, or iridocyclitis.2
Here, we report after PUBMED search a case of Usher syndrome with bilateral nongranulomatous anterior uveitis,
which was not reported before.
Case report
A 32-year-old female with a known case of Usher syndrome has been followed up in the clinic since the age of
17 years. At her initial hospital presentation, she had
Received 15 January 2013; received in revised form 20 May 2013; accepted 1 June 2013; available online 19 June 2013.
a
b
Ophthalmology Department, Faculty of Medicine, Qassem University, Buridah, Saudi Arabia
Anterior Segment and Uveitis Division, Ophthalmology Department, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
⇑ Corresponding author. Tel.: +966 63800050.
e-mail address: [email protected] (S.A.S Alzuhairy).
Peer review under responsibility
of Saudi Ophthalmological Society,
King Saud University
Production and hosting by Elsevier
Access this article online:
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296
S.A.S. Alzuhairy, A. Alfawaz
decreased vision, especially at night, and partial deafness.
Her eye examination at that time revealed the following: visual acuity of 20/40 in the right eye and 20/30 in the left
eye and intraocular pressure (IOP) measurements within a
normal range in both eyes. Slit lamp examination showed
the following in both eyes: a quiet conjunctiva, a clear cornea,
a deep and quiet anterior chamber, a clear lens, a pale disk,
arteriolar attenuation, and the presence of bone spicules
(Fig. 1). The diagnosis was confirmed by electroretinography
using flash stimuli (no reproducible response could be obtained in both eyes) (Fig. 2).Visual field testing was performed, showing generalized field constriction in both eyes.
The patient was referred to the Ear, Nose, and Throat
(ENT) clinic for an assessment of her hearing problem. A
diagnosis of Usher syndrome was confirmed in the patient.
Thirteen years later, the patient presented with complaints
of redness, photophopia and blurred vision. On examination,
the visual acuity was the same, the IOP measurements were
within the normal range in both eyes, the conjunctivae were
mildly injected, and the corneas were clear in both eyes.
Bilateral +2 cells with no flare reaction in the anterior chamber (SUN working group classification) 4 and early bilateral
posterior subcapsular cataracts (Fig. 3A) were detected. Fine
keratic precipitates (KPs) (i.e., corneal endothelial deposits)
were found in both eyes (Fig. 3B). The iris appeared normal,
and no posterior synechiae were detected. The retina was
the same as before, with no evidence of vitritis, vasculitis, or
retinitis. Based on these examination results, the patient was
diagnosed with bilateral nongranulomatous anterior uveitis.
A uveitis workup was performed, including a complete blood
count (CBC), erythrocyte sedimentation rate (ESR), C-reactive
protein level, antinuclear antibody test, HLA-B27 test, HLA-B5
test, angiotensin-converting enzyme (ACE) test, a chest X-ray,
computerized tomography of the chest, tuberculine or purified
protein derivative (PPD) test, Venereal Disease Research Laboratory (VDRL) test, and toxoplasma serology. The results of all these
tests were within normal limits. The patient was treated with a
topical corticosteroid, prednisolone acetate1% (Pred Forte), 4
times a day and was followed up in the clinic. Steroid tapering
was carried out with subsequent follow-up.
The patient has received regular follow-up examinations in
the uveitis clinic for the past 3 years. During this time period,
she has had 4 episodic exacerbations of bilateral nongranulomatous anterior uveitis and has responded nicely to topical
steroid treatment each time. Her best-corrected visual acuity
at the most recent follow-up examination was 20/80 in the
right eye, which improved to 20/60 with pinhole testing,
and 20/100 in the left eye, which improved to 20/60 with pinhole testing. The decreased visual acuity was attributed to
the presence of +2 posterior subcapsular cataract in both
eyes. No active inflammation has occurred during the past
3 months. The patient is currently undergoing treatment with
topical prednisolone acetate1% (Pred Forte) once daily for
both eyes. Neither vitritis nor macular edema has been detected. She is booked for cataract surgery in 2 months, providing that her condition remains under control and an
exacerbation of uveitis does not occur.
Discussion
Figure 1. Color fundus photos showing classic features of retinitis
pigmentosa (RP), pale disk, arteriolar attenuation, and bone-spicule
retinal pigment epithelial changes in both eyes.
Usher syndrome is the name given to the association of RP
and congenital sensorineural hearing loss, whether partial or
profound, Ophthalmologists should be attuned to patients
with RP who present with a nasal intonation to their speech
or wear hearing aids and should ask these patients when
Figure 2. Electroretinograms (ERGs) for both eyes, showing that no reproducible response could be obtained.
Nongranulomatous anterior uveitis in a patient with Usher syndrome
Figure 3A. Slit lamp examination showing posterior subcapsular
cataract.
Figure 3B. Showing fine keratic precipitates (KPs) in the corneal
endothelium.
exactly the vision and hearing loss began. In contrast to classical Usher syndrome, slowly progressive deafness has been
identified in one subgroup of Usher patients (gene USH3A),
which is caused by mutations in clarin-1, a transmembrane
protein with a possible role in cochlear hair cell and photoreceptor synapses. However, the hearing level of most Usher
patients is typically stable over time.1,5,6
Currently, there are 11 types of Usher syndrome in which
the chromosomal location is known; of these, 9 have cloned
genes. The proteins encoded by these genes are part of a dynamic protein complex that is present in hair cells of the inner
ear and in photoreceptor cells of the retina. For example,
Usher syndrome type 2A is caused by mutations in the gene
USH2A. These mutations in turn cause changes in the usherin
protein (at chromosome 1q41), which encodes a basement
membrane protein found in many tissues, including structural
basement membranes in the retina and inner ear.1,2
In addition to Usher syndrome, a number of other genetic
conditions and environmental insults may lead to pigmentary
retinopathy and hearing loss, including Alport syndrome, Alström and Cockayne syndromes, dysplasia spondyloepiphysaria congenita, Hurler syndrome, and Refsum disease. By a
careful study of individual patients and families, the diagnosis
of Usher syndrome can be made with relative certainty.
Molecular testing for specific forms of Usher syndrome help
confirm the diagnosis.3,6
Several research articles have reported and described the
association between Usher syndrome and Fuchs’ heterochromic uveitis (FHU).7–9,11–14 In their 2010 study, Lichtinger et al.
7
confirmed the association between FHU and RP and found
297
a particularly stronger association of FHU with Usher syndrome type 2; the causes for this significant association are
not yet clear, but patients with RP and those with uveitis exhibit several common clinical and laboratory inflammatory
features .In addition, Turan-Vural et al. 9 reported a case of
Usher syndrome in association with unilateral FHU.
Lichtinger et al. 7 also demonstrated that some patients
with RP have circulating B cells that are reactive with the retinal antigens, especially the S antigen. This finding may explain the tendency for immune reactions in patients with
RP, which could increase their susceptibility for developing
uveitis.10 A study by Chowers et al. 8 described the association between FHU and RP and showed that patients with
RP can develop autoimmune reactions to anterior chamber
antigens that bear some similarity to retinal antigens, leading
to the clinical manifestation of FHU. Other studies have also
described the association between RP and FHU.7,11–14
In our case, all possible causes of anterior uveitis were excluded, either by clinical examinations or by negative investigations. A herpetic cause of iridocyclitis is less likely in this
case because of the presence of bilaterality, which is rare in
herpetic uveitis. In addition, no herpetic corneal signs and
no glaucoma or iris atrophy were detected. The patient also
possessed normal corneal sensation. Fuchs’ heterochromic
iridocyclitis is less likely in this case because the KPs were
round (not stellate shaped), there was no evidence of heterochromia, and, more importantly, there was a complete response to topical steroid treatment, which is not typical in
cases of FHU.
To the best of our knowledge, this is the first reported
case of Usher syndrome associated with chronic bilateral
nongranulomatous anterior uveitis. Therefore, it is important
for ophthalmologists to recognize that, although rare, nongranulomatous anterior uveitis can be found in association
with RP and, more specifically, with Usher syndrome. This
may influence the follow-up and management plan for these
patients, especially if complications have occurred.
Conflict of interest
The authors declared that there is no conflict of interest.
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