Purpose: To assess foveal thickness by spectral-domain optical coherence tomography (SD-OCT) during acute anterior uveitis (AAU) in HLA–B27 patients. Methods: Foveal thickness was measured at baseline and after clinical resolution of the uveitis. Data of the affected eyes of 11 patients were compared to those of a fellow, healthy eyes and to those of counterpart volunteers. Results: At baseline mean foveal thickness ± SD) was 190 ± 28 µm in affected eyes, 166 ± 20 m in fellow eyes (p &lt; 0.001), and 162±14 µm in control group (p = 0.01). On the second OCT evaluation, no significant change was observed in affected eyes while the difference versus fellow eyes and control group remained statistically significant. Conclusions: A significant increase in foveal thickness was observed in eyes with HLA –B27 AAU when compared with healthy eyes. The difference persisted for at least one month, despite full clinical and functional recover

Moschos, Marilita M

English

Medical Hypothesis, Discovery & Innovation (MEHDI) Journals

 
 
Med Hypothesis Discov Innov Ophthalmol. 2014; 3(4)  
 
 
 
Original Article 
Medical Hypothesis, Discovery &Innovation  
Ophthalmology Journal 
   
 
 
Subclinical Macular Edema Detected by Spectral-domain Optical 
Coherence Tomography (SD-OCT) in HLA-B27 Positive Anterior 
Uveitis 
Marilita M Moschos  
Department of Ophthalmology, University of Athens, Greece 
ABSTRACT 
Purpose: To assess foveal thickness by spectral-domain optical coherence tomography (SD-OCT) during acute anterior 
uveitis (AAU) in HLA–B27 patients. 
Methods: Foveal thickness was measured at baseline and after clinical resolution of the uveitis. Data of the affected eyes 
of 11 patients were compared to those of a fellow, healthy eyes and to those of counterpart volunteers. 
Results: At baseline mean foveal thickness   was 190 ± 28 µm in affected eyes, 166 ± 20 µm in fellow eyes (p < 0.001), 
and 162±14 µm in control group (p = 0.01). On the second OCT evaluation, no significant change was observed in 
affected eyes while the difference versus fellow eyes and control group remained statistically significant. 
Conclusions: A significant increase in foveal thickness was observed in eyes with HLA –B27 AAU when compared with 
healthy eyes. The difference persisted for at least one month, despite full clinical and functional recovery. 
KEY WORDS 
HLA-B27; Macula; Optical Coherence Tomography; Uveitis  
©2014, Med Hypothesis Discov Innov Ophthalmol. 
This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 
License (CC BY-NC 3.0), which allows users to read, copy, distribute and make derivative works for non-commercial 
purposes from the material, as long as the author of the original work is cited properly. 
 
Correspondence to: 
Dr Marilita M Moschos, 6, Ikarias street, Ekali,14578, Athens, Greece,Tel: ++306944887319, Fax: ++302107795347,E-Mail: 
moschosmarilita@yahoo.fr
 
INTRODUCTION 
About 50% of patients presenting with non-
granulomatous acute anterior uveitis (AAU) are HLA-B27 
antigen positive. This incidence, however, increases to 
over 70% in subjects affected by recurrent episodes of 
ocular inflammation (1). Acute anterior uveitis in HLA-
B27 positive patients present as usual; with an acute 
onset, mild to severe ocular pain, red eye, photophobia, 
and a small decrease in visual acuity (VA) (2, 3). In HLA-
B27 associated forms, men are twice more likely to be 
affected than women; the disease is most often 
unilateral with a greater risk of recurrence (1, 2). 
Posterior pole alterations occur commonly in susceptible 
patients after recurrent attacks or prolonged disease (4, 
5). Anterior vitritis, true vitritis with white exudative 
debris in the region of the ora serrata accompanied with 
retinal vasculitis and phlebitis, is seen in 30% to 63% of 
HLA-B27 positive patients, while cystoid macular edema 
 
 
Med Hypothesis Discov Innov Ophthalmol. 2014; 3(4)  
 
124 MACULAR EDEMA DETECTED BY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY 
(CME) occurs in 10 - 30% compared to 8% in HLA-B27 
negative subjects (4,6). 
Optical coherence tomography (OCT) is a contemporary 
method of obtaining high-resolution cross-section images 
of the retina, allowing precise measurement of retinal 
thickness. It uses infrared light to detect relative changes 
in reflection at optical interfaces, based on the principle 
of low-coherence interferometry (7). Optical coherence 
tomography is a safe, non-invasive technique, highly 
suitable for repeated macular measurements in 
inflammatory ocular diseases (8). Currently, available 
OCT models reach a theoretical axial resolution of 10 µm, 
with a high degree of reproducibility in localizing and 
measuring macular thickness (9). 
In order to investigate a possible increase in foveal 
thickness in cases of ocular inflammation with 
predominant anterior segment involvement, we 
prospectively evaluated a series of HLA-B27 positive 
individuals with unilateral AAU using OCT. 
 
MATERIALS AND METHODS 
In this prospective, controlled study, patients were 
recruited between January 2012 and July 2013 from the 
Department of Ophthalmology of the University of 
Athens (Greece). 
Inclusion criteria were the occurrence of unilateral AAU 
and the presence of HLA-B27 antigen (any subtype). 
Exclusion criteria were the presence of any opacities of 
the media (cornea, lens, aqueous and vitreous humor) 
sufficient to prevent fundus examination and/or OCT 
scanning, any previous ocular surgery (cataract, 
glaucoma, vitreoretinal), any ongoing topical treatment 
for glaucoma, the presence of macular hole and 
epiretinal membranes or the presence of age-related 
macular disease and diabetic retinopathy. 
Eyes of affected patients were first examined by OCT 0 to 
five days after the onset of AAU; then 4±1 weeks later, 
with obvious clinical signs of healing. Clinical 
measurements were taken at least 5 days after 
discontinuation of therapy. Best corrected VA (Logarithm 
of the Minimum Angle of Resolution -- log MAR units) 
was recorded; intra ocular pressure (IOP) was measured 
in all patients, and they were all examined by the slit 
lamp. Gonioscopy and funduscopy (after dilatation with 
1% tropicamide) were performed. Optical coherence 
tomography was performed simultaneously in both eyes 
while age-matched healthy volunteers were examined as 
an external control group. Treatment consisted of an 
hourly administration of topical 1% prednisolone, a 
cycloplegic agent (3% scopolamine or 1% atropine) twice 
a day and a steroid ointment at night. Therapy was 
progressively tapered every four to five days until 
complete resolution of the uveitis. 
All patients underwent macular OCT scanning (Spectral-
domain OCT (Spectralis SD-OCT, Heidelberg Engineering), 
carried out by an experienced hand (MM). To measure 
foveal thickness, images were obtained with a 5 mm 
horizontal and vertical scan line, analyzed by the 
software function “retinal thickness”. The caliper was 
positioned at the lowest point of the foveal profile, and 
the two measurements averaged for each patient. 
Finally, the results were compared using the paired and 
unpaired student “t” test. Consistency of localization and 
the scanning process, together with the coefficient of 
variation were thus assessed. 
 
RESULTS 
Eleven patients (seven men and four women, mean age 
40 ± 16 yrs.) presenting with unilateral AAU displaying a 
positive HLA-B27 antigen were included in the study. 
Fourteen healthy volunteers (seven men and seven 
women, mean age 39 ± 11 yrs., 22 eyes) established the 
control group. 
The coefficients of variation were assessed in the two 
centers, measuring 5.3% (SD: 5 µm) and 6.1% (SD: 6 µm), 
respectively. Study group’s initial and final VA, as well as 
the OCT results of the affected and of the healthy fellow 
eyes are all detailed in Table I (data of the control group 
not shown). 
Mean foveal thickness  at the baseline were 190±28 µm 
in the affected and 166 ± 20 µm in the fellow eyes (p < 
0.001), in addition to 162 ± 14 µm in the control group (p 
= 0.01). In the study group eyes, mean VA increased from 
0.16 ± 0.06 log MAR, to 0.05 ± 0.18 log MAR at the last 
OCT examination. Acute anterior uveitis clinically healed 
in all patients after 26 ± 9 days from the beginning of 
treatment. One patient developed persistent CME 
despite the fact that anterior segment inflammation had 
resolved. This subject was excluded from the second 
 
 
Med Hypothesis Discov Innov Ophthalmol. 2014; 3(4)  
 
125 MACULAR EDEMA DETECTED BY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY 
examination data due to the continuation of local and 
systemic anti-inflammatory treatment. At the second 
OCT evaluation (4 ± 1 weeks after the diagnosis), results 
for mean foveal thickness in the study eyes revealed 179 
± 21 µm, with no significant difference in the baseline (p 
= 0.35). Conversely, the difference between this latter 
cohort when compared to both the healthy fellow eyes, 
and the control eyes remained statistically significant (p = 
0.02 and 0.05, respectively). 
 
 
Table1: Visual Acuities and the Oct Assessment Results in the Study and in the Fellow Eyes 
Patient initial VA AE
1 
(logMAR)
final VA AE
1 
(logMAR)
1
st
 OCT AE
2 
(m)
2
nd
 OCT AE
2 
(m)
1
st
 OCT FE
3 
(m)
2
nd
 OCT FE
3 
(m)
1 0,24 0,00 212 169 183 145
2 0,18 0,00 208 164 175 144
3 0,12 0,00 201 191 185 181
4 0,08  - 236  - 201  -
5 0,12 -0,10 181 189 153 185
6 0,30 0,02 157 181 149 137
7 0,22 0,04 171 144 159 157
8 0,10 0,00 134 161 130 135
9 0,16 0,56 207 498 157 162
10 0,12 0,10 188 201 175 168
11 0,14 0,00 192 210 161 149  
¹ Initial and final VA. AE = Affected Eye. FE = Fellow healthy Eye. 
² OCT values in the affected eyes at the baseline and at the second evaluation. 
³ OCT values in the fellow healthy eyes at the baseline and at the second evaluation. 
 
DISCUSSION 
Changes in macular profile have been extensively 
documented in posterior uveitis. To detect early macular 
changes in AAU, we used OCT investigation of macular 
thickness in HLA-B27 related AAU. Mean foveal thickness 
of 11 eyes affected by uveitis was significantly increased 
in the inflamed eye during unilateral AAU when 
compared to the contralateral eye or to normal subjects 
(collected as external controls). A new OCT scan was 
performed in those same eyes after 4 ± 1 weeks. At this 
time, inflammation was clinically resolved in 10 eyes; VA 
improved, and treatment stopped for at least five days. 
One eye developed clinical CME, confirmed by 
angiography. This patient was excluded from the next 
round of the examination statistics as the steroid therapy 
could not be discontinued. At the second evaluation, 
mean foveal thickness decreased in both the study and 
the fellow eye groups even though the former still 
showed higher values (179 ± 21µm vs. 156 ± 18µm). 
Surprisingly, the change between the initial and final OCT 
evaluation was not significant in the study eyes. The 
difference between the affected and fellow eyes did, 
however, remain significant (p = 0.02). The coefficients of 
variation and standard deviation found in this study are 
very similar to earlier results where macular evaluation 
was performed by OCT (7, 8). Moreover, our patients had 
sufficient VA to allow good fixation, with no significant 
retinal alterations except in one case, thus allowing 
accurate localization of the fovea. Usually, CME occurs in 
10-30% of HLA-B27 positive patients (4, 8). The presence 
of retinal edema is classically suspected in the presence 
of a decrease in VA. Nussenblatt et al. found a strong 
correlation between angiographic evidence of macular 
thickening in uveitis and VA (logMAR) (10). Whatsoever, 
Antcliff et al. were unable to observe this association 
using OCT (8). Macular edema results from diseases 
causing rupture of the inner and/or outer blood-retinal 
barrier. Edema may develop from flooding of the 
extracellular space by proteins and fluids or from 
insufficient depletion of albumin and other osmotically 
 
 
Med Hypothesis Discov Innov Ophthalmol. 2014; 3(4)  
 
126 MACULAR EDEMA DETECTED BY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY 
active molecules. Such molecules bind water to cause 
edema (11). Their intricate depletion might be due to the 
external limiting membrane and entanglements in 
extracellular traffic flow within the retina. Contrary to 
surgical trauma, which triggers a transient inflammatory 
response, endogenous uveitis produces a constant 
release of inflammatory mediators. The course of 
inflammatory macular edema is not; therefore, 
necessarily self-limited, and can develop and persist long 
after the onset of the inflammation (12). Data collected 
in this series show that a significant increase of foveal 
thickness appeared in eyes of patients with AAU when 
compared with the fellow, healthy eye. This difference 
persisted for at least one month, despite full clinical and 
functional resolution of the disease suggesting that some 
changes occur in the retinal osmotic equilibrium during 
typical anterior uveitis. Given the absence of any 
ophthalmoscopic sign and the complete recovery of VA, 
this macular edema should be considered subclinical. The 
increase in the extent of study group and the 
prolongation of follow up are mandatory to better define 
whether and when the correspondence between the two 
eyes can be restored. 
 
DISCLOSURE 
Conflicts of Interest: None declared. 
 
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Subclinical Macular Edema Detected by Spectral-domain Optical Coherence Tomography (SD-OCT) in HLA-B27 Positive Anterior Uveitis

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Subclinical Macular Edema Detected by Spectral-domain Optical Coherence Tomography (SD-OCT) in HLA-B27 Positive Anterior Uveitis

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