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Ocular Immunology and Inflammation Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ioii20
Patterns of Uveitis in a University-based Tertiary Referral Center in Riyadh, Saudi Arabia a
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Huda Al Dhahri MD , Khalid Al Rubaie MD , Suhail Hemachandran MD , Ahmed Mousa PhD , a
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Priscilla W. Gikandi Bsc , Hani S. Al-Mezaine MD & Ahmed M. Abu El-Asrar MD, PhD
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Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia Published online: 24 Jul 2014.
Click for updates To cite this article: Huda Al Dhahri MD, Khalid Al Rubaie MD, Suhail Hemachandran MD, Ahmed Mousa PhD, Priscilla W. Gikandi Bsc, Hani S. Al-Mezaine MD & Ahmed M. Abu El-Asrar MD, PhD (2015) Patterns of Uveitis in a Universitybased Tertiary Referral Center in Riyadh, Saudi Arabia, Ocular Immunology and Inflammation, 23:4, 311-319, DOI: 10.3109/09273948.2014.939197 To link to this article: http://dx.doi.org/10.3109/09273948.2014.939197
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Ocular Immunology & Inflammation, 2015; 23(4): 311–319 Copyright ! Taylor & Francis Group, LLC ISSN: 0927-3948 print / 1744-5078 online DOI: 10.3109/09273948.2014.939197
ORIGINAL ARTICLE
Patterns of Uveitis in a University-based Tertiary Referral Center in Riyadh, Saudi Arabia
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Huda Al Dhahri, MD, Khalid Al Rubaie, MD, Suhail Hemachandran, MD, Ahmed Mousa, PhD, Priscilla W. Gikandi, Bsc, Hani S. Al-Mezaine, MD, and Ahmed M. Abu El-Asrar, MD, PhD Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
ABSTRACT Purpose: To investigate the referral patterns and diagnosis of uveitis in a university-based tertiary referral center in Riyadh, Saudi Arabia. Methods: We retrospectively reviewed the medical records of 642 patients (1220 eyes). Results: There were 295 (46%) males and 347 (54%) female patients, with a mean age of 36.4 ± 16.1 years at presentation. Panuveitis was most common (47.1%), followed by anterior uveitis (36.8%), posterior uveitis (10.7%), and intermediate uveitis (5.4%). Nongranulomatous (85.2%) and noninfectious (69.3%) were the most frequent types of uveitis. The most identifiable specific diagnoses were Vogt-Koyanagi-Harada (VKH) disease (19.6%), presumed tuberculous uveitis (PTU) (17.8%), Behc¸et disease (BD) (8.4%), and toxoplasmosis (6.9%). After a mean follow-up period of 31.3 ± 31.5 months, 73.5% of the eyes achieved visual acuity of 20/40 or better. Conclusions: The most common anatomic diagnosis was panuveitis. VKH disease, PTU, BD, and toxoplasmosis are the most frequently diagnosed entities. Keywords: Behc¸et disease, epidemiology, tuberculosis, uveitis, Vogt-Koyanagi-Harada disease
Uveitis includes a wide range of diverse inflammatory eye conditions affecting not only the uvea but also the retina, optic nerve, and vitreous, and is a major cause of severe visual impairment throughout the world. It may be idiopathic, associated with systemic disease, or resulting from a variety of infectious agents. Genetic, ethnic, geographic, socioeconomic, nutritional, and environmental factors influence the distribution of the types, clinical associations, and causes of uveitis in a given population.1,2 As the frequencies of disease vary in different populations, it is important to analyze and report the patterns of uveitis in the various geographic regions. Therefore, studies of the distribution of the various types and causes of uveitis and their etiology are essential in deriving a region-specific and focused approach to investigation and diagnosis as well as management. Given the continuing globalization of the world, the ethnic and geographic background of the patient should be considered as these clearly
influence the differential diagnosis. A number of small-scale studies have analyzed the pattern of uveitis in Saudi Arabia,3–5 but there is still a need for large-scale studies using consistent classification and diagnostic criteria. The aim of this study was to provide a retrospective analysis of patients with uveitis who were referred to the uveitis clinic of King Abdulaziz University Hospital, Riyadh, Saudi Arabia between January 1998 and June 2013 in order to determine the clinical patterns, causes, and systemic disease associations of uveitis.
PATIENTS AND METHODS We retrospectively reviewed the medical records of all patients with uveitis referred to the Uveitis Clinic of King Abdulaziz University Hospital, Riyadh, Saudi Arabia, between January 1998 and June 2013. Our
Received 23 January 2014; revised 16 June 2014; accepted 24 June 2014; published online 24 July 2014 Correspondence: Ahmed M. Abu El-Asrar, MD, PhD, Department of Ophthalmology, King Abdulaziz University Hospital, Airport Road, P.O. Box 245, Riyadh 11411, Saudi Arabia. E-mail: [email protected] or [email protected]
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312 H. Al Dhahri et al. hospital is a tertiary eye care center, and is the only university eye hospital in Riyadh. Patients are referred to our hospital from other centers within Saudi Arabia and the Gulf region. Patients with postoperative or traumatic endophthalmitis were not included as these patients were managed in the surgical retina division and most of them were followed up by the referring ophthalmologists. Charts were reviewed for demographic data (age, gender) and clinical data, including laterality, initial and final visual acuities, results of slit-lamp examination, results of dilated fundus examination, results of ancillary and laboratory tests, ocular complications, specific ocular cause, associated systemic diseases, and duration of follow-up. Using the International Uveitis Study Group classification system based on anatomic location, patients were categorized as having anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis.6 Uveitis was further classified as nongranulomatous if fine endothelial keratic precipitates were seen in the absence of iris nodules and/or choroidal granulomas, and granulomatous if larger keratic precipitates, including large (‘‘mutton-fat’’) keratic precipitates, Koeppe and/or Busacca iris nodules, and/or optic disc or choroidal granulomas were seen. The causative diagnoses for specific ocular uveitic entities or systemic disease associations were based on a detailed clinical history, an extensive review of systems, a complete ophthalmologic examination, and laboratory as well as ancillary tests. At presentation, all the patients had the following examination: best corrected Snellen visual acuity, applanation tonometry, slit-lamp examination of the anterior segment, fundus biomicroscopy, and indirect ophthalmoscopy. Fluorescein angiography, indocyanine green angiography, optical coherence tomography, ocular ultrasonography, and visual field testing were performed when indicated. Initial laboratory tests performed for every patient included complete blood count with differential, erythrocyte sedimentation rate, blood sugar, blood chemistry, urinalysis, tuberculin skin test (five tuberculin units), chest radiography, Venereal Disease Research Laboratory tests, and serum fluorescent treponemal antibody absorption test. A second battery of directed laboratory tests was carried out according to the suspicion of the cause (‘‘tailored approach’’). Diagnoses were made using established clinical criteria, with supporting laboratory evidence as needed. The diagnosis of presumed tuberculous uveitis (PTU) required the presence of ocular findings consistent with possible intraocular tuberculosis with no other cause of uveitis suggested by history, examination, or ancillary testing, strongly positive tuberculin skin-test results (15-mm area of induration/necrosis), and response to antituberculous therapy.7 Diagnosis of uveitis associated with
Vogt-Koyanagi-Harada (VKH) disease was based on the pattern of clinical characteristics at presentation. Patients with initial-onset acute VKH disease typically showed bilateral exudative retinal detachment and optic disc hyperemia and swelling with or without anterior uveitis. Imaging modalities, including fluorescein angiography, indocyanine green angiography, optical coherence tomography, and ocular ultrasonography, were performed to confirm the diagnosis. Patients with chronic recurrent VKH disease typically showed active granulomatous anterior uveitis with typical ‘‘sunset glow fundus,’’ nummular depigmented scars, retinal pigment epithelium clumping, and/ or migration and chorioretinal atrophy.8 Exclusion criteria were absence of previous ocular penetrating trauma or surgery. Diagnosis of Behc¸et disease (BD) was based on the International Study Group for Behc¸et’s Disease criteria.9 The diagnosis of ocular toxoplasmosis was based on the clinical observation of focal necrotizing retinochoroiditis sometimes associated with typical old pigmented scars in a patient with positive toxoplasma serology. The diagnosis of acute retinal necrosis was based on the criteria published by the American Uveitis Society.10 Diagnosis of sarcoidosis required a positive biopsy (usually transbronchial). Presumed ocular sarcoidosis was diagnosed based on high level of clinical suspicion plus chest radiographic abnormalities consistent with sarcoidosis and/or elevated serum angiotensin converting enzyme level, elevated serum lysozyme level, abnormal pulmonary function tests, and anergy on skin testing. The diagnosis of multiple sclerosis was based on a high level of clinical suspicion plus neurologic examination and brain magnetic resonance imaging abnormalities consistent with multiple sclerosis. The diagnosis of herpetic anterior uveitis was based on unilaterality, high intraocular pressure, corneal sensation depression, stromal keratitis, large keratic precipitates, and sectoral iris atrophy. Diagnoses of other etiologies were made by careful observations of ocular involvement, clinical course, and accompanying systemic disease, combined with laboratory analyses. Patients were diagnosed as having idiopathic uveitis only after laboratory tests were performed to rule out specific diagnoses consistent with the clinical presentation.
Statistical Methods Data were retrieved from medical records, reviewed, and stored in a Microsoft Access 2010 database. Data were then managed and analyzed using SPSS version 19.0 (IBM, Chicago, Illinois, USA) and StatsDirect statistical software, version 2.7.2 (StatsDirect, Cheshire, UK). Continuous variables were described as means (±SD), while categorical variables were expressed as frequency and percentages (number Ocular Immunology & Inflammation
Of the 642 patients, the diagnosis was confirmed or strongly suspected in 488 (76%) patients. VKH disease was the most frequently diagnosed entity (19.6%), Copyright ! 2015 Taylor & Francis Group, LLC
0.174 0.602 50.001* 50.001* (35.8) (5.5) (10.0) (48.6) 207 32 58 281 (45.3) (3.1) (25.0) (26.6) 29 2 16 17 0.166 0.382 50.001* 0.004* (38.1) (4.8) (5.9) (51.2) 254 32 39 341 (34.1) (6.1) (16.8) (43.0) 189 34 93 238 0.759 50.001* 0.265 0.399 (36.5) (4.1) (11.3) (48.0) 379 43 117 498 (35.0) (12.6) (8.2) (44.3) 64 23 15 81
0.295 84 (14.5) 494 (85.5) 13 (20.3) 51 (79.7) 0.007* 116 (17.4) 550 (82.6) 65 (11.7) 489 (88.3) 0.604 151 (14.6) 886 (85.4) 30 (16.4) 153 (83.6)
p Value Female (n = 666 eyes) (%) Male (n = 554 eyes) (%) p Value 418 years (n = 1037 eyes) (%)
*Statistically significant at 5% level of significance.
Diagnoses
18 years (n = 183 eyes) (%)
Overall, 64 (10%) patients had unilateral disease and 578 (90%) patients had bilateral disease. Uveitis was chronic in 387 (60.3%) patients. At presentation to the emergency room, all the patients had active inflammation. Inflammation was nongranulomatous in 1039 (85.2%) eyes and granulomatous in 181 (14.8%) eyes. The most common anatomic diagnosis was panuveitis (47.1% [574/1220]), followed by anterior uveitis (36.8% [450/1220]), posterior uveitis (10.7% [130/ 1220]), and intermediate uveitis (5.4% [66/1220]). Table 1 shows the relationship of type of inflammation and anatomic diagnosis to age, sex, and laterality. Intermediate uveitis was significantly more common in patients who were 18 years of age or younger (p50.001). Granulomatous uveitis was significantly more common among female patients (p = 0.007). Posterior uveitis was significantly more common among male patients (p50.001). Posterior uveitis was significantly more common among patients with unilateral involvement (p = 0.001). On the other hand, panuveitis was significantly more common in patients with bilateral involvement (p = 0.001).
Age group
Classification of Disease
Variable
There were 295 (46%) males and 347 (54%) female patients. The age at presentation ranged from 4 to 87 years with a mean of 36.4 ± 16.1 years. There were 94 (14.6%) patients (183 eyes) who were 18 years of age or younger. Of the 642 patients, 517 (80.5%) were Saudi and 125 (19.5%) were non-Saudi.
Gender
Demographics
TABLE 1. Relationship of type of inflammation and anatomic diagnosis to laterality, age, and gender of patients.
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We identified 642 consecutive patients with uveitis (1220 eyes) who were referred to the Uveitis Clinic of King Abdulaziz University Hospital, Riyadh, Saudi Arabia, between January 1998 and June 2013. All patients were managed and followed up by one of the authors (AMA).
Type of inflammation Granulomatous Nongranulomatous Anatomic diagnosis Anterior Intermediate Posterior Panuveitis
Laterality
RESULTS
Unilateral (n = 64 pts.) (%)
(%)). Chi-square and comparison of proportions tests were used to detect the association/differences across different groups. Odds ratios were calculated to examine potential risk factors. A p value 50.05 was used to indicate statistical significance.
Bilateral (n = 578 pts.) (%)
p Value
Referral Patterns of Uveitis
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314 H. Al Dhahri et al. (12.0%), and PTU (8.2%). The most common diagnoses among patients aged more than 18 years were idiopathic uveitis (22.0%), VKH disease (19.8%), PTU (19.1%), and BD (9.3%). Juvenile idiopathic arthritis (p50.001) and idiopathic uveitis (p50.001) were significantly more common in patients who were 18 years of age or younger. In contrast, PTU (p50.001), BD (p = 0.041), toxoplasmosis (p = 0.048), and HLAB27-positive anterior uveitis (p = 0.02) were significantly more common in patients who were older than 18 years. Infectious uveitis accounted for 197 (30.7%) of the patients. The most common diagnosis was PTU (57.9%) followed by toxoplasmosis (22.4%) and herpetic uveitis (17.25%).
followed by PTU (17.8%), BD (8.4%), and toxoplasmosis (6.9%). Despite extensive and repeated clinical and laboratory evaluation, the diagnosis remained idiopathic in 154 (24%) patients (Table 2). Table 3 shows the prevalence of clinical entities by sex and age. The most common diagnoses among female patients were idiopathic uveitis (28.7%), VKH disease (24.0%), and PTU (18.0%). The most common diagnoses among male patients were idiopathic uveitis (18.2%), PTU (16.8%), VKH disease (16.4%), and BD (15.0%). VKH disease (p50.001), multiple sclerosis (p50.001), and idiopathic uveitis (p50.001) were significantly more common among female patients. In contrast, BD (p50.001), toxoplasmosis (p = 0.005), herpetic uveitis (p = 0.007), and HLA-B27positive anterior uveitis (p = 0.002) were significantly more common among male patients. The most common diagnoses among patients aged 18 years or younger were idiopathic uveitis (35.0%), VKH disease (25.1%), juvenile idiopathic arthritis
Diagnoses Based on Anatomical Location Table 4 shows the frequencies of various uveitic diagnoses based on anatomical location. The majority of patients with anterior uveitis (44.2%) and intermediate uveitis (71.2%) were classified as having idiopathic disease. The most common diagnoses for posterior uveitis were toxoplasmosis (56.9%), and PTU (23.1%). The most common diagnoses for panuveitis were VKH disease (41.6%), PTU (27.7%), and BD (17.1%).
TABLE 2. Diagnosis of all uveitis patients (n = 642). Type of eye disease
Number of patients (%)
Vogt-Koyanagi-Harada disease Presumed tuberculous uveitis Behc¸et disease Toxoplasmosis Fuchs uveitis Herpetic uveitis HLA-B27-positive anterior uveitis Sarcoidosis Juvenile idiopathic uveitis Multiple sclerosis Sympathetic ophthalmia Others Idiopathic TOTAL
126 (19.6) 114 (17.8) 54 (8.4) 44 (6.9) 39 (6.1) 34 (5.3) 31(4.8) 15 (2.3) 13 (2) 3 (0.9) 8 (1.2) 6 (1) 154 (24) 642 (100)
Findings at Initial Presentation At presentation 319 (26.0%) eyes had posterior synechiae of the iris. At initial slit-lamp examination, 22 (1.8%) eyes presented with hypopyon. The diagnoses among this group were BD (36.4% [8/22]), PTU (18.2% [4/22]), HLA-B27-positive anterior uveitis
TABLE 3. Prevalence of clinical entities by age and gender. Sex Diseases Vogt-Koyanagi-Harada disease Presumed tuberculous uveitis Behc¸et disease Toxoplasmosis Fuchs uveitis Herpetic uveitis HLA-B27-positive anterior uveitis Sarcoidosis Juvenile idiopathic arthritis Multiple sclerosis Sympathetic ophthalmia Others Idiopathic TOTAL
Age group
Male Female 18 years 418 years (n = 554 eyes) (%) (n = 666 eyes) (%) p Value (n = 183 eyes) (%) (n = 1037 eyes) (%) p Value 91 93 83 47 27 40 38 12 8 0 5 9 101 554
(16.4) (16.8) (15.0) (8.5) (4.9) (7.2) (6.9) (2.2) (1.4) (0.0) (0.9) (1.6) (18.2) (100)
160 120 21 29 46 24 20 17 18 16 2 2 191 666
(24.0) (18.0) (3.2) (4.4) (6.9) (3.6) (3.0) (2.6) (2.7) (2.4) (0.3) (0.3) (28.7) (100)
50.001* 0.636 50.001* 0.005* 0.179 0.007* 0.002* 0.791 0.170 0.001* 0.316 0.036* 50.001*
46 15 8 5 5 8 2 6 22 0 0 2 64 183
(25.1) (8.2) (4.4) (2.7) (2.7) (4.4) (1.1) (3.3) (12.0) (0.0) (0.0) (1.1) (35.0) (100)
205 198 96 71 68 56 56 23 4 16 7 9 228 1037
(19.8) (19.1) (9.3) (6.8) (6.6) (5.4) (5.4) (2.2) (0.4) (1.5) (0.7) (0.9) (22.0) (100)
0.125 50.001* 0.041* 0.048* 0.060 0.704 0.020* 0.523 50.001* 0.190 0.539 0.875 50.001*
*Statistically significant at 5% level of significance. Ocular Immunology & Inflammation
Referral Patterns of Uveitis
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TABLE 4. Prevalence of specific diagnoses in relation to type of anatomic diagnosis. Anatomic diagnosis
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Diseases Vogt-Koyanagi-Harada disease (n = 251 eyes) Presumed tuberculous uveitis (n = 213 eyes) Behc¸et disease (n = 104 eyes) Toxoplasmosis (n = 76 eyes) Fuchs uveitis (n = 73 eyes) Herpetic uveitis (n = 64 eyes) HLA-B27-positive anterior uveitis (n = 58 eyes) Sarcoidosis (n = 29 eyes) Juvenile idiopathic arthritis (n = 26 eyes) Multiple sclerosis (n = 16 eyes) Sympathetic ophthalmia (n = 7 eyes) Others (n = 11 eyes) Idiopathic (n = 292 eyes) TOTAL
Anterior (n = 450 eyes) (%)
Intermediate (n = 66 eyes) (%)
Posterior (n = 130 eyes) (%)
Panuveitis (n = 574 eyes) (%)
Total (n = 1220 eyes) (%)
6 (4.6)
239 (41.6)
251 (20.6)
30 (23.1)
159 (27.7)
213 (17.5)
4 (3.1) 74 (56.9)
98 (17.1) 2 (0.3)
6 (1.3) 15 (3.3)
9 (13.6)
2 (0.4) 73 (16.2) 60 (13.3) 58 (12.9)
4 (0.7)
9 (2.0) 26 (5.8)
6 (4.6)
8 (12.1)
2 (0.4) 199 (44.2) 450 (100)
104 76 73 64 58
2 (3.0) 47 (71.2) 66 (100)
4 (3.1) 6 (4.6) 130 (100)
(8.5) (6.2) (6.0) (5.2) (4.8)
14 (2.4)
29 (2.4) 26 (2.1)
8 (1.4) 7 (1.2)
16 (1.3) 7 (0.6)
3 (0.5) 40 (7.0) 574 (100)
11 (1.0) 292 (23.9) 1220 (100)
TABLE 5. Prevalence of findings at initial presentation by uveitic diagnoses. Clinical indices Diagnosis
Hypopyon (n = 22 eyes) (%)
Vogt-Koyanagi-Harada disease Presumed tuberculous uveitis Behcet disease Toxoplasmosis Fuchs uveitis Herpetic uveitis HLA-B27-positive anterior uveitis Sarcoidosis Juvenile idiopathic arthritis Multiple sclerosis Sympathetic ophthalmia Others Idiopathic TOTAL
0 4 8 0 0 0 3 0 0 0 0 0 7 22
Fibrinous reaction (n = 27 eyes) (%)
(0) (1.9) (7.7) (0) (0) (0) (5.2) (0) (0) (0) (0) (0) (2.4) (1.8)
(13.6% [3/22]), and idiopathic uveitis (31.8% [7/22]). A total of 27 (2.2%) eyes presented with fibrinous reaction in the anterior chamber. The diagnoses among this group were HLA-B27-positive anterior uveitis (37.1% [10/27]), VKH disease (22.2% [6/27]), PTU (14.8% [4/27]), BD (7.4% [2/27]), sarcoidosis (3.7% [1/27]), and idiopathic uveitis (14.8% [4/27]). At presentation, 105 (8.6%) eyes had macular edema. The anatomic diagnoses among this group were anterior uveitis (9.5% [10/105]), intermediate uveitis (17.1% [18/105]), posterior uveitis (12.4% [13/ 105), and panuveitis (61.1% [64/105]). The diagnoses among these eyes were PTU (50.5% [53/105]), idiopathic uveitis (21.8% [23/105]), BD (12.4% [13/105]), toxoplasmosis (4.8% [5/105]), multiple sclerosis (3.8% [4/105]), HLA-B27-positive anterior uveitis (1.9% [2/ Copyright ! 2015 Taylor & Francis Group, LLC
6 4 2 0 0 0 10 1 0 0 0 0 4 27
(2.4) (1.9) (1.9) (0) (0) (0) (17.2) (3.4) (0) (0) (0) (0) (1.4) (2.2)
Posterior synechiae (n = 319 eyes) (%) 79 61 20 6 0 8 15 9 14 5 1 4 97 319
(31.5) (28.6) (19.2) (7.9) (0) (12.5) (25.9) (31) (53.8) (31.3) (14.3) (36.4) (33.2) (26.1)
Macular edema (n = 105 eyes) (%) 1 53 13 5 0 0 2 1 0 4 0 3 23 105
(0.4) (24.9) (12.5) (6.6) (0) (0) (3.4) (3.4) (0) (25) (0) (27.3) (7.9) (8.6)
Total 251 213 104 76 73 64 58 29 26 16 7 11 292 1220
105]), VKH disease (1.0% [1/105]), sarcoidosis (1.0% [1/105]), and others (2.9% [3/105]). Table 5 shows the prevalence of findings at initial presentation by uveitic diagnoses. Our analysis demonstrated that findings at initial presentation including presence of posterior synechiae of the iris (p50.0001), hypopyon (p = 0.0005), anterior chamber fibrinous reaction (p50.0001), and macular edema (p50.0001) were significantly associated with uveitic diagnoses.
Results of Tuberculin Skin Test Among the 114 patients with PTU, tuberculin skin-test results were strongly positive. The mean area of
316 H. Al Dhahri et al. TABLE 6. Prevalence of complications by uveitic diagnoses.
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Diagnosis Vogt-Koyanagi-Harada disease Presumed tuberculous uveitis Behc¸et disease Toxoplasmosis Fuchs uveitis Herpetic uveitis HLA-B27-postive anterior uveitis Sarcoidosis Juvenile idiopathic arthritis Multiple sclerosis Sympathetic ophthalmia Others Idiopathic Total
Cataract (n = 209) (%) 46 41 17 3 14 11 6 2 7 0 3 2 57 209
(18.3) (19.2) (16.3) (3.9) (19.2) (17.2) (10.3) (6.9) (26.9) (0) (42.9) (18.2) (19.5) (17.1)
Glaucoma (n = 169) (%) 41 18 6 1 17 13 16 2 6 0 0 0 49 169
(16.3) (8.5) (5.8) (1.3) (23.3) (20.3) (27.6) (6.9) (23.1) (0) (0) (0) (16.8) (13.9)
induration was 24.4 ± 10 mm (range, 20–80 mm). The uveitis in these patients responded to antituberculous therapy with no recurrences after stopping treatment. Twelve additional patients had positive tuberculin skin-test results (10-mm area of induration)11 (p50.0001). Their diagnoses included toxoplasmosis (33.3% [4/12]), BD (25.0% [3/12]), HLA-B27-positive anterior uveitis (25.0% [3/12]), multiple sclerosis (8.3% [1/12]), and sympathetic ophthalmia (8.3% [1/12]).
Epiretinal membrane (n = 40) (%) 3 13 6 1 0 4 3 2 2 0 0 2 4 40
Choroidal Neovascular membrane (n = 16) (%)
Hypotony (n = 26) (%)
(1.2) (6.1) (5.8) (1.3) (0) (6.3) (5.2) (6.9) (7.7) (0) (0) (18.2) (1.4) (3.3)
5 5 2 0 1 3 4 1 1 0 0 0 4 26
(2) (2.3) (1.9) (0) (1.4) (4.7) (6.9) (3.4) (3.8) (0) (0) (0) (1.4) (2.1)
14 2 0 0 0 0 0 0 0 0 0 0 0 16
Retinal vein occlusion (n = 10) (%)
(5.6) (0.9) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (1.3)
0 3 6 0 0 0 0 0 0 0 0 0 1 10
(0) (1.4) (5.8) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0.3) (0.8)
Total 251 213 104 76 73 64 58 29 26 16 7 11 292 1220
TABLE 7. Comparison between initial visual acuity and visual acuity at 1 year follow-up for 854 eyes. Visual acuity at 1 year follow-up
Initial visual acuity 20/200 20/50–20/100
20/40 73 20/50–20/100 46 20/200 61 TOTAL 180 (21.1)
110 66 19 195 (22.8)
20/40
Total
431 614 (71.9) 39 151 (17.7) 9 89 (10.4) 479 (56.1) 854 (100)
Visual Outcome Complications Overall, 357 (29.3%) eyes developed at least one complication. Cataract was the most common, occurring in 17.1% of eyes, followed by glaucoma, occurring in 13.9% of the eyes (Table 6). Table 6 shows the prevalence of complications by uveitic diagnoses. Our analysis demonstrated a significant association between the uveitic diagnoses and the development of cataract (p = 0.02) and the development of glaucoma (p50.001). There were significant associations between the presence of posterior synechiae of the iris at presentation and the development of cataract (odds ratio = 3.1; 95% confidence interval (CI) = 2.23–4.24) and the development of glaucoma (odds ratio = 2.96; 95% CI = 2.09–4.19). Inflammatory retinal vein occlusion occurred in 10 eyes. The diagnoses included BD (6), PTU (3), and idiopathic (1). Band keratopathy was detected in 24 eyes at presentation. Of the 183 eyes from patients who were 18 years of age or younger, 18 (9.8%) had band keratopathy. Of the 1037 eyes from patients who were older than 18 years of age, 6 (0.6%) had band keratopathy. The difference between the two percentages was statistically significant (p50.001).
The follow-up period ranged from 3 to 192 months with a mean of 31.3 ± 31.5 months. The distribution of initial and visual acuity at 1-year follow-up is illustrated in Table 7. Initial and visual acuity at 1year follow-up were available for 854 eyes. Of the 854 eyes, 614 (71.9%) achieved visual acuity of 20/40 or better. The prevalence of poor visual acuity of 20/200 or less significantly reduced from 180 (21.1%) eyes at presentation to 89 (10.4%) eyes at last follow-up (p50.0001). The prevalence of visual acuity of 20/40 or better significantly increased from 479 (56.1%) eyes at presentation to 614 (71.9%) eyes at final follow-up (p50.0001). Initial visual acuity and visual acuity at 1year follow-up for the more frequently seen cases of uveitis classified by diagnosis are summarized in Table 8.
DISCUSSION In the current study, we have elucidated the current etiology of uveitis in a university-based referral center in Riyadh, Saudi Arabia. The most common specific diagnoses seen among our study population were VKH disease, PTU, and BD. The most common Ocular Immunology & Inflammation
Referral Patterns of Uveitis
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TABLE 8. Comparison of initial visual acuity and visual acuity at 1 year follow-up in eyes with various uveitic diagnoses. Type of eye disease Visual acuity 20/200 Initial Final p Value 20/40 Initial Final p Value
Vogt-Koyanagi-Harada disease (n = 195 eyes) (%)
Presumed tuberculous uveitis (n = 155 eyes) (%)
Behc¸et disease (n = 89 eyes) (%)
Idiopathic uveitis (n = 186) (%)
59 (30.3) 21 (10.8) 50.001*
40 (25.8) 26 (16.8) 0.085
25 (28.1) 12 (13.5) 0.031*
20 (10.8) 16 (8.6) 0.496
84 (43.1) 160 (82.1) 50.001*
68 (43.9) 100 (64.8) 0.013*
49 (55.1) 72 (80.9) 0.035*
132 (70.9) 157 (84.4) 0.139
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*Statistically significant at 5% level of significance.
anatomic diagnosis was panuveitis (47.1%), followed by anterior uveitis (36.8%), posterior uveitis (10.7%), and intermediate uveitis (5.4%). VKH disease is a chronic, bilateral, granulomatous panuveitis and exudative retinal detachment associated with poliosis, vitiligo, alopecia, and central nervous system and auditory signs. The prevalence of the disease varies among different populations of the world, and it commonly affects pigmented races and people of certain genetic predispositions.12,13 In the current study, VKH disease was the most common identifiable specific diagnosis, accounting for 19.6% of all uveitis cases, and was the most common cause of panuveitis (42.3%). VKH disease was also a common cause of uveitis in previous studies from Saudi Arabia,3–5 Japan,14–18 China,19 and Thailand.20,21 However, VKH disease is rarely seen in Caucasian.1,2 In patients with panuveitis, VKH disease was the most common specific diagnosis in a study from Japan,14 and the second most common specific diagnosis in a study from China.19 In our series, PTU was the second most common identifiable specific diagnosis (17.8%) and the second most common cause of posterior uveitis (23.1%) and panuveitis (27.7%). Several previous studies suggested that there may be a resurgence of ocular tuberculosis throughout the world.3,4,14,22–25 In our service, tuberculin skin testing is routinely performed in the workup of uveitis, and a high index of suspicion of the diagnosis is maintained in patients with unexplained chronic uveitis.6,26 All the patients with PTU were treated with antituberculous therapy combined with systemic corticosteroids.6,26 In our series, all patients with PTU had strongly positive tuberculin skin test results. In contrast, only 2.3% of patients with other specific diagnoses had a positive test. Our findings suggest that the presence of a strongly positive tuberculin skin test results with no other specific causes of uveitis should raise the suspicion of a tuberculous etiology. In a previous study, Llorenc¸e et al. emphasized the importance of tuberculin skin test as indirect evidence of PTU.27 Interestingly, 4 (1.9%) eyes with PTU presented with Copyright ! 2015 Taylor & Francis Group, LLC
hypopyon. Presence of hypopyon at presentation in patients with tuberculous uveitis is rare, but 2 cases were previously reported.28,29 In the current study, BD was the third most common identifiable specific diagnosis, accounting for 8.4% of all uveitis cases and for 17.1% of eyes with panuveitis. Our findings support the previous observations of the geographical distribution of BD between the northern latitude of 30 and 45 in the Mediterranean, Asian, and Eurasian populations, coinciding with the ancient silk route.1,2 Similar to our study, a high frequency of BD as a cause of uveitis has been reported in studies from Turkey,30 Japan,14–18 Saudi Arabia,3–5 Tunisia,31 Iran,32 Korea,33 China,19 and Italy.22,23 BD was the leading cause of panuveitis in these studies. In our study, toxoplasmic retinochorioditis was the fourth most common identifiable specific diagnosis, accounting for 6.9% of all uveitis cases, and was the most common cause of posterior uveitis, accounting for 56.9% of eyes with posterior uveitis. The results of previous studies indicated that toxoplasmic retinochoroiditis was the leading cause of posterior uveitis,23,30–32,34–36 accounting for 24.6–60.2% of cases. In previous studies from Saudi Arabia, toxoplasmosis accounted for 6–8.2% of all uveitis cases.3–5 In the current study, sarcoidosis accounted for only 2.3% of all cases. Our findings are similar to that reported in previous reports from Tunisia,31 Saudi Arabia,4 Iran,32 Italy,22 and China.19 However, in Japan, sarcoidosis is the most frequent intraocular inflammatory disease.18 Similarly, in studies from Western countries, sarcoidosis was among the most frequently observed systemic diseases associated with uveitis.34,36,37 In the current study, the frequency of specific disease was analyzed by age and gender. Idiopathic uveitis was the most common diagnosis in patients who were 18 years of age or younger, followed by VKH disease and juvenile idiopathic arthritis. In contrast, studies from Western countries identified juvenile idiopathic arthritis as the most common specific diagnosis for uveitis in children.38 In our study, juvenile idiopathic arthritis accounted for only
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318 H. Al Dhahri et al. 2.0% of all uveitis cases. Our findings are in agreement with studies from Japan14–18 that demonstrated that juvenile idiopathic arthritis is a rare association for uveitis in Japan. In the current study, idiopathic uveitis was the most common diagnosis among patients aged more than 18 years, followed by VKH disease, PTU, and BD. Our analysis of diagnosis based on gender revealed that idiopathic uveitis was the most common diagnosis in male patients followed by PTU, VKH disease, and BD. In female patients, the most common diagnosis was idiopathic uveitis followed by VKH disease, and PTU. Our analysis also revealed a significant male preponderance in BD, toxoplasmosis, herpetic uveitis, and HLA-B27positive anterior uveitis, and a significant female preponderance in VKH disease, multiple sclerosis, and idiopathic uveitis. These findings are compatible with previous reports.16,17 The high prevalence of panuveitis in our study could be explained by the high frequency of VKH disease, PTU, and BD, all of which manifest mainly as panuveitis. The fact that panuveitis was the most common anatomic type in our study reflects also the referral character of our hospital; most patients with acute anterior uveitis are treated by local ophthalmologists and are not referred. A shift in the relative frequency of uveitis cases away from anterior uveitis and toward posterior uveitis and panuveitis was seen in tertiary referral centres.1,2 Panuveitis is also predominant in Japan,14–18 which would be expected as sarcoidosis, VKH disease, and BD are the most common specific diagnoses in Japan.14–18 Panuveitis is also relatively frequently observed in other parts of Asia, South America, Africa, and the Mediterranean basin.1,2 In contrast, anterior uveitis is by far the most common form of uveitis in Western countries, accounting for at least half of the total uveitis cases.1,2 Thus, compared to studies from Western countries,1,2 there were comparatively lower frequencies of anterior uveitis and higher frequencies of panuveitis in our study. In eyes with anterior uveitis, idiopathic uveitis was the most common cause, accounting for 44.2% of all anterior uveitis eyes. The most common clinical associations of anterior uveitis in this study were Fuchs uveitis (16.2%), herpes (13.3%), and HLA-B27positive-anterior uveitis (12.9%). Similar findings were previously reported.1,2 In the present study, intermediate uveitis accounted for only 5.4% of all uveitis cases. Similarly, intermediate uveitis was reported to be the least common form of uveitis in all different geographic regions.1,2 In this series, 71.2% of intermediate uveitis eyes were classified as idiopathic, 13.6% were associated with tuberculosis, and 12.1% were associated with multiple sclerosis. Consistent with our results, most previous studies showed that the great majority of intermediate uveitis cases were idiopathic.30–32,34–36 We also demonstrated
that intermediate uveitis was significantly more common in patients who were 18 years of age or younger consistent with a previous report.32 In this study, at least one complication occurred in 29.3% of the eyes. The leading complications observed in our study were cataract and glaucoma. Our observations are consistent with previous reports showing that glaucoma and cataract were the most frequent complications.3,4,30,39 In our study, band keratopathy was significantly more common in patients who were 18 years of age or younger. This finding supports the previous observation that band keratopathy is more common in children with uveitis, and it tends to be a particular feature in those with early-onset severe type of inflammation.40 In the current study, we assessed the visual acuity at 1-year follow-up. Overall, visual acuity of 20/40 or better was achieved in 71.9% of all eyes. The limitations of this study are that the data were collected retrospectively and that it is likely that more severe cases of uveitis were observed at this university-based tertiary referral center. Therefore, disease frequencies must be considered in light of such referral bias toward more complicated panuveitis. These limitations mean that our data are not representative of the general population. Nevertheless, this study adds additional data to the clinical spectrum of uveitis referred to a tertiary eye care center in Saudi Arabia. In conclusion, our data indicate a predominance of panuveitis, which would be expected, as VKH disease, PTU, and BD were the most common specific diagnoses, all of which manifest as panuveitis. Furthermore, VKH disease, multiple sclerosis, and idiopathic uveitis were significantly more common in female patients, and BD, toxoplasmosis, herpetic uveitis, and HLA-B27-positive anterior uveitis were significantly more common in male patients. Juvenile idiopathic arthritis and idiopathic uveitis were significantly more common in patients aged 18 years or younger, and PTU, toxoplasmosis, and HLA-B27positive anterior uveitis were significantly more common in patients aged more than 18 years.
ACKNOWLEDGEMENTS The authors thank Michelle B. Rasonabe and Connie B. Unisa-Marfil for secretarial work. Ahmed M. Abu El-Asrar holds the Dr. Nasser Al-Rasheed Research Chair in Ophthalmology.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. Ocular Immunology & Inflammation
Referral Patterns of Uveitis This work was supported by Dr. Nasser AlRasheed Research Chair in Ophthalmology (Abu ElAsrar AM).
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20. Pathanapitoon K, Kunavisarut P, Ausayakhun S, et al. Uveitis in a tertiary ophthalmology centre in Thailand. Br J Ophthalmol. 2008;92:474–478. 21. Sittivarakul W, Bhurayanontachai P, Ratanasukon M. Pattern of uveitis in a university-based referral center in southern Thailand. Ocul Immunol Inflamm. 2013; 21:53–60. 22. Mercanti A, Parolini B, Bonora A, et al. Epidemiology of endogenous uveitis in north-eastern Italy: analysis of 655 new cases. Acta Ophthalmol Scand. 2001;79:64–68. 23. Cimino L, Aldigeri R, Salvarani C, et al. The causes of uveitis in a referral centre of northern Italy. Int Ophthalmol. 2010;30:521–529. 24. Rathinam SR, Namperumalsamy P. Global variation and pattern changes in epidemiology of uveitis. Indian J Ophthalmol. 2007;55:173–183. 25. Singh R, Gupta V, Gupta A. Pattern of uveitis in a referral eye clinic in north India. Indian J Ophthalmol. 2004;52: 121–125. 26. Al-Mezaine HS, Al-Muammar A, Kangave D, et al. Clinical and optical coherence tomographic findings and outcome of treatment in patients with presumed tuberculous uveitis. Int Ophthalmol. 2008;28:413–423. 27. Llorenc¸ V, Gonzalez-Martin J, Keller J, et al. Indirect supportive evidence for diagnosis of tuberculosisrelated uveitis: from the tuberculin skin test to the new interferon gamma release assays. Acta Ophthalmol. 2013;91: e99–e107. 28. Chatziralli IP, Keryttopoulos P, Papazisis L, et al. Hypopyon in the context of tuberculous uveitis. Clin Exp Optom 2012;95:241–243. 29. Velu J, Agarwal S, Gupta V, et al. Hypopyon uveitis—a rare presentation of intraocular tuberculosis. Ocul Immunol Inflamm. 2013;21:251–253. 30. S ¸ engu¨n A, Karadag˘ R, Karakurt A, et al. Causes of uveitis in a referral hospital in Ankara, Turkey. Ocul Immunol Inflamm. 2005;13:45–50. 31. Khairallah M, Yahia SB, Ladjimi A, et al. Patterns of uveitis in a referral centre in Tunisia, North Africa. Eye. 2007;21: 33–39. 32. Soheilian M, Heidari K, Yazdani S, et al. Patterns of uveitis in a tertiary eye care center in Iran. Ocul Immunol Inflamm. 2004;12:297–310. 33. Chung H, Choi DG. Clinical analysis of uveitis. Korean J Ophthalmol. 1989;3:33–37. 34. Rodriguez A, Calonge M, Pedroza-Seres M, et al. Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol. 1996;114:593–599. 35. Oruc S, Kaplan AD, Galen M, et al. Uveitis referral pattern in Midwest University Eye Center. Ocul Immunol Inflamm. 2003;11:287–298. 36. Rothova A, Buitenhuis HJ, Meenken C, et al. Uveitis and systemic disease. Br J Ophthalmol. 1992;76:137–141. 37. Merrill PT, Kim J, Cox TA, et al. Uveitis in the southeastern United States. Curr Eye Res. 1997;16:865–874. 38. Kump LI, Cervantes-Castan˜eda RA, Androudi SN, et al. Analysis of pediatric uveitis cases at a tertiary referral center. Ophthalmology. 2005;112:1287–1292. 39. Miyanaga M, Shimizu K, Kawaguchi T, et al. A clinical survey of uveitis in HTLV-1 endemic region. Ocul Immunol Inflamm. 2009;17:335–341. 40. Woreta F, Thorne JE, Jabs DA, et al. Risk factor for ocular complications and poor visual acuity at presentation among patients with uveitis associated with juvenile idiopathic arthritis. Am J Ophthalmol. 2007;143: 647–655.
Ocular Immunology and Inflammation Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ioii20
Patterns of Uveitis in a University-based Tertiary Referral Center in Riyadh, Saudi Arabia a
a
a
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Huda Al Dhahri MD , Khalid Al Rubaie MD , Suhail Hemachandran MD , Ahmed Mousa PhD , a
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Priscilla W. Gikandi Bsc , Hani S. Al-Mezaine MD & Ahmed M. Abu El-Asrar MD, PhD
a
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Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia Published online: 24 Jul 2014.
Click for updates To cite this article: Huda Al Dhahri MD, Khalid Al Rubaie MD, Suhail Hemachandran MD, Ahmed Mousa PhD, Priscilla W. Gikandi Bsc, Hani S. Al-Mezaine MD & Ahmed M. Abu El-Asrar MD, PhD (2015) Patterns of Uveitis in a Universitybased Tertiary Referral Center in Riyadh, Saudi Arabia, Ocular Immunology and Inflammation, 23:4, 311-319, DOI: 10.3109/09273948.2014.939197 To link to this article: http://dx.doi.org/10.3109/09273948.2014.939197
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Ocular Immunology & Inflammation, 2015; 23(4): 311–319 Copyright ! Taylor & Francis Group, LLC ISSN: 0927-3948 print / 1744-5078 online DOI: 10.3109/09273948.2014.939197
ORIGINAL ARTICLE
Patterns of Uveitis in a University-based Tertiary Referral Center in Riyadh, Saudi Arabia
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Huda Al Dhahri, MD, Khalid Al Rubaie, MD, Suhail Hemachandran, MD, Ahmed Mousa, PhD, Priscilla W. Gikandi, Bsc, Hani S. Al-Mezaine, MD, and Ahmed M. Abu El-Asrar, MD, PhD Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
ABSTRACT Purpose: To investigate the referral patterns and diagnosis of uveitis in a university-based tertiary referral center in Riyadh, Saudi Arabia. Methods: We retrospectively reviewed the medical records of 642 patients (1220 eyes). Results: There were 295 (46%) males and 347 (54%) female patients, with a mean age of 36.4 ± 16.1 years at presentation. Panuveitis was most common (47.1%), followed by anterior uveitis (36.8%), posterior uveitis (10.7%), and intermediate uveitis (5.4%). Nongranulomatous (85.2%) and noninfectious (69.3%) were the most frequent types of uveitis. The most identifiable specific diagnoses were Vogt-Koyanagi-Harada (VKH) disease (19.6%), presumed tuberculous uveitis (PTU) (17.8%), Behc¸et disease (BD) (8.4%), and toxoplasmosis (6.9%). After a mean follow-up period of 31.3 ± 31.5 months, 73.5% of the eyes achieved visual acuity of 20/40 or better. Conclusions: The most common anatomic diagnosis was panuveitis. VKH disease, PTU, BD, and toxoplasmosis are the most frequently diagnosed entities. Keywords: Behc¸et disease, epidemiology, tuberculosis, uveitis, Vogt-Koyanagi-Harada disease
Uveitis includes a wide range of diverse inflammatory eye conditions affecting not only the uvea but also the retina, optic nerve, and vitreous, and is a major cause of severe visual impairment throughout the world. It may be idiopathic, associated with systemic disease, or resulting from a variety of infectious agents. Genetic, ethnic, geographic, socioeconomic, nutritional, and environmental factors influence the distribution of the types, clinical associations, and causes of uveitis in a given population.1,2 As the frequencies of disease vary in different populations, it is important to analyze and report the patterns of uveitis in the various geographic regions. Therefore, studies of the distribution of the various types and causes of uveitis and their etiology are essential in deriving a region-specific and focused approach to investigation and diagnosis as well as management. Given the continuing globalization of the world, the ethnic and geographic background of the patient should be considered as these clearly
influence the differential diagnosis. A number of small-scale studies have analyzed the pattern of uveitis in Saudi Arabia,3–5 but there is still a need for large-scale studies using consistent classification and diagnostic criteria. The aim of this study was to provide a retrospective analysis of patients with uveitis who were referred to the uveitis clinic of King Abdulaziz University Hospital, Riyadh, Saudi Arabia between January 1998 and June 2013 in order to determine the clinical patterns, causes, and systemic disease associations of uveitis.
PATIENTS AND METHODS We retrospectively reviewed the medical records of all patients with uveitis referred to the Uveitis Clinic of King Abdulaziz University Hospital, Riyadh, Saudi Arabia, between January 1998 and June 2013. Our
Received 23 January 2014; revised 16 June 2014; accepted 24 June 2014; published online 24 July 2014 Correspondence: Ahmed M. Abu El-Asrar, MD, PhD, Department of Ophthalmology, King Abdulaziz University Hospital, Airport Road, P.O. Box 245, Riyadh 11411, Saudi Arabia. E-mail: [email protected] or [email protected]
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312 H. Al Dhahri et al. hospital is a tertiary eye care center, and is the only university eye hospital in Riyadh. Patients are referred to our hospital from other centers within Saudi Arabia and the Gulf region. Patients with postoperative or traumatic endophthalmitis were not included as these patients were managed in the surgical retina division and most of them were followed up by the referring ophthalmologists. Charts were reviewed for demographic data (age, gender) and clinical data, including laterality, initial and final visual acuities, results of slit-lamp examination, results of dilated fundus examination, results of ancillary and laboratory tests, ocular complications, specific ocular cause, associated systemic diseases, and duration of follow-up. Using the International Uveitis Study Group classification system based on anatomic location, patients were categorized as having anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis.6 Uveitis was further classified as nongranulomatous if fine endothelial keratic precipitates were seen in the absence of iris nodules and/or choroidal granulomas, and granulomatous if larger keratic precipitates, including large (‘‘mutton-fat’’) keratic precipitates, Koeppe and/or Busacca iris nodules, and/or optic disc or choroidal granulomas were seen. The causative diagnoses for specific ocular uveitic entities or systemic disease associations were based on a detailed clinical history, an extensive review of systems, a complete ophthalmologic examination, and laboratory as well as ancillary tests. At presentation, all the patients had the following examination: best corrected Snellen visual acuity, applanation tonometry, slit-lamp examination of the anterior segment, fundus biomicroscopy, and indirect ophthalmoscopy. Fluorescein angiography, indocyanine green angiography, optical coherence tomography, ocular ultrasonography, and visual field testing were performed when indicated. Initial laboratory tests performed for every patient included complete blood count with differential, erythrocyte sedimentation rate, blood sugar, blood chemistry, urinalysis, tuberculin skin test (five tuberculin units), chest radiography, Venereal Disease Research Laboratory tests, and serum fluorescent treponemal antibody absorption test. A second battery of directed laboratory tests was carried out according to the suspicion of the cause (‘‘tailored approach’’). Diagnoses were made using established clinical criteria, with supporting laboratory evidence as needed. The diagnosis of presumed tuberculous uveitis (PTU) required the presence of ocular findings consistent with possible intraocular tuberculosis with no other cause of uveitis suggested by history, examination, or ancillary testing, strongly positive tuberculin skin-test results (15-mm area of induration/necrosis), and response to antituberculous therapy.7 Diagnosis of uveitis associated with
Vogt-Koyanagi-Harada (VKH) disease was based on the pattern of clinical characteristics at presentation. Patients with initial-onset acute VKH disease typically showed bilateral exudative retinal detachment and optic disc hyperemia and swelling with or without anterior uveitis. Imaging modalities, including fluorescein angiography, indocyanine green angiography, optical coherence tomography, and ocular ultrasonography, were performed to confirm the diagnosis. Patients with chronic recurrent VKH disease typically showed active granulomatous anterior uveitis with typical ‘‘sunset glow fundus,’’ nummular depigmented scars, retinal pigment epithelium clumping, and/ or migration and chorioretinal atrophy.8 Exclusion criteria were absence of previous ocular penetrating trauma or surgery. Diagnosis of Behc¸et disease (BD) was based on the International Study Group for Behc¸et’s Disease criteria.9 The diagnosis of ocular toxoplasmosis was based on the clinical observation of focal necrotizing retinochoroiditis sometimes associated with typical old pigmented scars in a patient with positive toxoplasma serology. The diagnosis of acute retinal necrosis was based on the criteria published by the American Uveitis Society.10 Diagnosis of sarcoidosis required a positive biopsy (usually transbronchial). Presumed ocular sarcoidosis was diagnosed based on high level of clinical suspicion plus chest radiographic abnormalities consistent with sarcoidosis and/or elevated serum angiotensin converting enzyme level, elevated serum lysozyme level, abnormal pulmonary function tests, and anergy on skin testing. The diagnosis of multiple sclerosis was based on a high level of clinical suspicion plus neurologic examination and brain magnetic resonance imaging abnormalities consistent with multiple sclerosis. The diagnosis of herpetic anterior uveitis was based on unilaterality, high intraocular pressure, corneal sensation depression, stromal keratitis, large keratic precipitates, and sectoral iris atrophy. Diagnoses of other etiologies were made by careful observations of ocular involvement, clinical course, and accompanying systemic disease, combined with laboratory analyses. Patients were diagnosed as having idiopathic uveitis only after laboratory tests were performed to rule out specific diagnoses consistent with the clinical presentation.
Statistical Methods Data were retrieved from medical records, reviewed, and stored in a Microsoft Access 2010 database. Data were then managed and analyzed using SPSS version 19.0 (IBM, Chicago, Illinois, USA) and StatsDirect statistical software, version 2.7.2 (StatsDirect, Cheshire, UK). Continuous variables were described as means (±SD), while categorical variables were expressed as frequency and percentages (number Ocular Immunology & Inflammation
Of the 642 patients, the diagnosis was confirmed or strongly suspected in 488 (76%) patients. VKH disease was the most frequently diagnosed entity (19.6%), Copyright ! 2015 Taylor & Francis Group, LLC
0.174 0.602 50.001* 50.001* (35.8) (5.5) (10.0) (48.6) 207 32 58 281 (45.3) (3.1) (25.0) (26.6) 29 2 16 17 0.166 0.382 50.001* 0.004* (38.1) (4.8) (5.9) (51.2) 254 32 39 341 (34.1) (6.1) (16.8) (43.0) 189 34 93 238 0.759 50.001* 0.265 0.399 (36.5) (4.1) (11.3) (48.0) 379 43 117 498 (35.0) (12.6) (8.2) (44.3) 64 23 15 81
0.295 84 (14.5) 494 (85.5) 13 (20.3) 51 (79.7) 0.007* 116 (17.4) 550 (82.6) 65 (11.7) 489 (88.3) 0.604 151 (14.6) 886 (85.4) 30 (16.4) 153 (83.6)
p Value Female (n = 666 eyes) (%) Male (n = 554 eyes) (%) p Value 418 years (n = 1037 eyes) (%)
*Statistically significant at 5% level of significance.
Diagnoses
18 years (n = 183 eyes) (%)
Overall, 64 (10%) patients had unilateral disease and 578 (90%) patients had bilateral disease. Uveitis was chronic in 387 (60.3%) patients. At presentation to the emergency room, all the patients had active inflammation. Inflammation was nongranulomatous in 1039 (85.2%) eyes and granulomatous in 181 (14.8%) eyes. The most common anatomic diagnosis was panuveitis (47.1% [574/1220]), followed by anterior uveitis (36.8% [450/1220]), posterior uveitis (10.7% [130/ 1220]), and intermediate uveitis (5.4% [66/1220]). Table 1 shows the relationship of type of inflammation and anatomic diagnosis to age, sex, and laterality. Intermediate uveitis was significantly more common in patients who were 18 years of age or younger (p50.001). Granulomatous uveitis was significantly more common among female patients (p = 0.007). Posterior uveitis was significantly more common among male patients (p50.001). Posterior uveitis was significantly more common among patients with unilateral involvement (p = 0.001). On the other hand, panuveitis was significantly more common in patients with bilateral involvement (p = 0.001).
Age group
Classification of Disease
Variable
There were 295 (46%) males and 347 (54%) female patients. The age at presentation ranged from 4 to 87 years with a mean of 36.4 ± 16.1 years. There were 94 (14.6%) patients (183 eyes) who were 18 years of age or younger. Of the 642 patients, 517 (80.5%) were Saudi and 125 (19.5%) were non-Saudi.
Gender
Demographics
TABLE 1. Relationship of type of inflammation and anatomic diagnosis to laterality, age, and gender of patients.
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We identified 642 consecutive patients with uveitis (1220 eyes) who were referred to the Uveitis Clinic of King Abdulaziz University Hospital, Riyadh, Saudi Arabia, between January 1998 and June 2013. All patients were managed and followed up by one of the authors (AMA).
Type of inflammation Granulomatous Nongranulomatous Anatomic diagnosis Anterior Intermediate Posterior Panuveitis
Laterality
RESULTS
Unilateral (n = 64 pts.) (%)
(%)). Chi-square and comparison of proportions tests were used to detect the association/differences across different groups. Odds ratios were calculated to examine potential risk factors. A p value 50.05 was used to indicate statistical significance.
Bilateral (n = 578 pts.) (%)
p Value
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313
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314 H. Al Dhahri et al. (12.0%), and PTU (8.2%). The most common diagnoses among patients aged more than 18 years were idiopathic uveitis (22.0%), VKH disease (19.8%), PTU (19.1%), and BD (9.3%). Juvenile idiopathic arthritis (p50.001) and idiopathic uveitis (p50.001) were significantly more common in patients who were 18 years of age or younger. In contrast, PTU (p50.001), BD (p = 0.041), toxoplasmosis (p = 0.048), and HLAB27-positive anterior uveitis (p = 0.02) were significantly more common in patients who were older than 18 years. Infectious uveitis accounted for 197 (30.7%) of the patients. The most common diagnosis was PTU (57.9%) followed by toxoplasmosis (22.4%) and herpetic uveitis (17.25%).
followed by PTU (17.8%), BD (8.4%), and toxoplasmosis (6.9%). Despite extensive and repeated clinical and laboratory evaluation, the diagnosis remained idiopathic in 154 (24%) patients (Table 2). Table 3 shows the prevalence of clinical entities by sex and age. The most common diagnoses among female patients were idiopathic uveitis (28.7%), VKH disease (24.0%), and PTU (18.0%). The most common diagnoses among male patients were idiopathic uveitis (18.2%), PTU (16.8%), VKH disease (16.4%), and BD (15.0%). VKH disease (p50.001), multiple sclerosis (p50.001), and idiopathic uveitis (p50.001) were significantly more common among female patients. In contrast, BD (p50.001), toxoplasmosis (p = 0.005), herpetic uveitis (p = 0.007), and HLA-B27positive anterior uveitis (p = 0.002) were significantly more common among male patients. The most common diagnoses among patients aged 18 years or younger were idiopathic uveitis (35.0%), VKH disease (25.1%), juvenile idiopathic arthritis
Diagnoses Based on Anatomical Location Table 4 shows the frequencies of various uveitic diagnoses based on anatomical location. The majority of patients with anterior uveitis (44.2%) and intermediate uveitis (71.2%) were classified as having idiopathic disease. The most common diagnoses for posterior uveitis were toxoplasmosis (56.9%), and PTU (23.1%). The most common diagnoses for panuveitis were VKH disease (41.6%), PTU (27.7%), and BD (17.1%).
TABLE 2. Diagnosis of all uveitis patients (n = 642). Type of eye disease
Number of patients (%)
Vogt-Koyanagi-Harada disease Presumed tuberculous uveitis Behc¸et disease Toxoplasmosis Fuchs uveitis Herpetic uveitis HLA-B27-positive anterior uveitis Sarcoidosis Juvenile idiopathic uveitis Multiple sclerosis Sympathetic ophthalmia Others Idiopathic TOTAL
126 (19.6) 114 (17.8) 54 (8.4) 44 (6.9) 39 (6.1) 34 (5.3) 31(4.8) 15 (2.3) 13 (2) 3 (0.9) 8 (1.2) 6 (1) 154 (24) 642 (100)
Findings at Initial Presentation At presentation 319 (26.0%) eyes had posterior synechiae of the iris. At initial slit-lamp examination, 22 (1.8%) eyes presented with hypopyon. The diagnoses among this group were BD (36.4% [8/22]), PTU (18.2% [4/22]), HLA-B27-positive anterior uveitis
TABLE 3. Prevalence of clinical entities by age and gender. Sex Diseases Vogt-Koyanagi-Harada disease Presumed tuberculous uveitis Behc¸et disease Toxoplasmosis Fuchs uveitis Herpetic uveitis HLA-B27-positive anterior uveitis Sarcoidosis Juvenile idiopathic arthritis Multiple sclerosis Sympathetic ophthalmia Others Idiopathic TOTAL
Age group
Male Female 18 years 418 years (n = 554 eyes) (%) (n = 666 eyes) (%) p Value (n = 183 eyes) (%) (n = 1037 eyes) (%) p Value 91 93 83 47 27 40 38 12 8 0 5 9 101 554
(16.4) (16.8) (15.0) (8.5) (4.9) (7.2) (6.9) (2.2) (1.4) (0.0) (0.9) (1.6) (18.2) (100)
160 120 21 29 46 24 20 17 18 16 2 2 191 666
(24.0) (18.0) (3.2) (4.4) (6.9) (3.6) (3.0) (2.6) (2.7) (2.4) (0.3) (0.3) (28.7) (100)
50.001* 0.636 50.001* 0.005* 0.179 0.007* 0.002* 0.791 0.170 0.001* 0.316 0.036* 50.001*
46 15 8 5 5 8 2 6 22 0 0 2 64 183
(25.1) (8.2) (4.4) (2.7) (2.7) (4.4) (1.1) (3.3) (12.0) (0.0) (0.0) (1.1) (35.0) (100)
205 198 96 71 68 56 56 23 4 16 7 9 228 1037
(19.8) (19.1) (9.3) (6.8) (6.6) (5.4) (5.4) (2.2) (0.4) (1.5) (0.7) (0.9) (22.0) (100)
0.125 50.001* 0.041* 0.048* 0.060 0.704 0.020* 0.523 50.001* 0.190 0.539 0.875 50.001*
*Statistically significant at 5% level of significance. Ocular Immunology & Inflammation
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TABLE 4. Prevalence of specific diagnoses in relation to type of anatomic diagnosis. Anatomic diagnosis
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Diseases Vogt-Koyanagi-Harada disease (n = 251 eyes) Presumed tuberculous uveitis (n = 213 eyes) Behc¸et disease (n = 104 eyes) Toxoplasmosis (n = 76 eyes) Fuchs uveitis (n = 73 eyes) Herpetic uveitis (n = 64 eyes) HLA-B27-positive anterior uveitis (n = 58 eyes) Sarcoidosis (n = 29 eyes) Juvenile idiopathic arthritis (n = 26 eyes) Multiple sclerosis (n = 16 eyes) Sympathetic ophthalmia (n = 7 eyes) Others (n = 11 eyes) Idiopathic (n = 292 eyes) TOTAL
Anterior (n = 450 eyes) (%)
Intermediate (n = 66 eyes) (%)
Posterior (n = 130 eyes) (%)
Panuveitis (n = 574 eyes) (%)
Total (n = 1220 eyes) (%)
6 (4.6)
239 (41.6)
251 (20.6)
30 (23.1)
159 (27.7)
213 (17.5)
4 (3.1) 74 (56.9)
98 (17.1) 2 (0.3)
6 (1.3) 15 (3.3)
9 (13.6)
2 (0.4) 73 (16.2) 60 (13.3) 58 (12.9)
4 (0.7)
9 (2.0) 26 (5.8)
6 (4.6)
8 (12.1)
2 (0.4) 199 (44.2) 450 (100)
104 76 73 64 58
2 (3.0) 47 (71.2) 66 (100)
4 (3.1) 6 (4.6) 130 (100)
(8.5) (6.2) (6.0) (5.2) (4.8)
14 (2.4)
29 (2.4) 26 (2.1)
8 (1.4) 7 (1.2)
16 (1.3) 7 (0.6)
3 (0.5) 40 (7.0) 574 (100)
11 (1.0) 292 (23.9) 1220 (100)
TABLE 5. Prevalence of findings at initial presentation by uveitic diagnoses. Clinical indices Diagnosis
Hypopyon (n = 22 eyes) (%)
Vogt-Koyanagi-Harada disease Presumed tuberculous uveitis Behcet disease Toxoplasmosis Fuchs uveitis Herpetic uveitis HLA-B27-positive anterior uveitis Sarcoidosis Juvenile idiopathic arthritis Multiple sclerosis Sympathetic ophthalmia Others Idiopathic TOTAL
0 4 8 0 0 0 3 0 0 0 0 0 7 22
Fibrinous reaction (n = 27 eyes) (%)
(0) (1.9) (7.7) (0) (0) (0) (5.2) (0) (0) (0) (0) (0) (2.4) (1.8)
(13.6% [3/22]), and idiopathic uveitis (31.8% [7/22]). A total of 27 (2.2%) eyes presented with fibrinous reaction in the anterior chamber. The diagnoses among this group were HLA-B27-positive anterior uveitis (37.1% [10/27]), VKH disease (22.2% [6/27]), PTU (14.8% [4/27]), BD (7.4% [2/27]), sarcoidosis (3.7% [1/27]), and idiopathic uveitis (14.8% [4/27]). At presentation, 105 (8.6%) eyes had macular edema. The anatomic diagnoses among this group were anterior uveitis (9.5% [10/105]), intermediate uveitis (17.1% [18/105]), posterior uveitis (12.4% [13/ 105), and panuveitis (61.1% [64/105]). The diagnoses among these eyes were PTU (50.5% [53/105]), idiopathic uveitis (21.8% [23/105]), BD (12.4% [13/105]), toxoplasmosis (4.8% [5/105]), multiple sclerosis (3.8% [4/105]), HLA-B27-positive anterior uveitis (1.9% [2/ Copyright ! 2015 Taylor & Francis Group, LLC
6 4 2 0 0 0 10 1 0 0 0 0 4 27
(2.4) (1.9) (1.9) (0) (0) (0) (17.2) (3.4) (0) (0) (0) (0) (1.4) (2.2)
Posterior synechiae (n = 319 eyes) (%) 79 61 20 6 0 8 15 9 14 5 1 4 97 319
(31.5) (28.6) (19.2) (7.9) (0) (12.5) (25.9) (31) (53.8) (31.3) (14.3) (36.4) (33.2) (26.1)
Macular edema (n = 105 eyes) (%) 1 53 13 5 0 0 2 1 0 4 0 3 23 105
(0.4) (24.9) (12.5) (6.6) (0) (0) (3.4) (3.4) (0) (25) (0) (27.3) (7.9) (8.6)
Total 251 213 104 76 73 64 58 29 26 16 7 11 292 1220
105]), VKH disease (1.0% [1/105]), sarcoidosis (1.0% [1/105]), and others (2.9% [3/105]). Table 5 shows the prevalence of findings at initial presentation by uveitic diagnoses. Our analysis demonstrated that findings at initial presentation including presence of posterior synechiae of the iris (p50.0001), hypopyon (p = 0.0005), anterior chamber fibrinous reaction (p50.0001), and macular edema (p50.0001) were significantly associated with uveitic diagnoses.
Results of Tuberculin Skin Test Among the 114 patients with PTU, tuberculin skin-test results were strongly positive. The mean area of
316 H. Al Dhahri et al. TABLE 6. Prevalence of complications by uveitic diagnoses.
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Diagnosis Vogt-Koyanagi-Harada disease Presumed tuberculous uveitis Behc¸et disease Toxoplasmosis Fuchs uveitis Herpetic uveitis HLA-B27-postive anterior uveitis Sarcoidosis Juvenile idiopathic arthritis Multiple sclerosis Sympathetic ophthalmia Others Idiopathic Total
Cataract (n = 209) (%) 46 41 17 3 14 11 6 2 7 0 3 2 57 209
(18.3) (19.2) (16.3) (3.9) (19.2) (17.2) (10.3) (6.9) (26.9) (0) (42.9) (18.2) (19.5) (17.1)
Glaucoma (n = 169) (%) 41 18 6 1 17 13 16 2 6 0 0 0 49 169
(16.3) (8.5) (5.8) (1.3) (23.3) (20.3) (27.6) (6.9) (23.1) (0) (0) (0) (16.8) (13.9)
induration was 24.4 ± 10 mm (range, 20–80 mm). The uveitis in these patients responded to antituberculous therapy with no recurrences after stopping treatment. Twelve additional patients had positive tuberculin skin-test results (10-mm area of induration)11 (p50.0001). Their diagnoses included toxoplasmosis (33.3% [4/12]), BD (25.0% [3/12]), HLA-B27-positive anterior uveitis (25.0% [3/12]), multiple sclerosis (8.3% [1/12]), and sympathetic ophthalmia (8.3% [1/12]).
Epiretinal membrane (n = 40) (%) 3 13 6 1 0 4 3 2 2 0 0 2 4 40
Choroidal Neovascular membrane (n = 16) (%)
Hypotony (n = 26) (%)
(1.2) (6.1) (5.8) (1.3) (0) (6.3) (5.2) (6.9) (7.7) (0) (0) (18.2) (1.4) (3.3)
5 5 2 0 1 3 4 1 1 0 0 0 4 26
(2) (2.3) (1.9) (0) (1.4) (4.7) (6.9) (3.4) (3.8) (0) (0) (0) (1.4) (2.1)
14 2 0 0 0 0 0 0 0 0 0 0 0 16
Retinal vein occlusion (n = 10) (%)
(5.6) (0.9) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (1.3)
0 3 6 0 0 0 0 0 0 0 0 0 1 10
(0) (1.4) (5.8) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0.3) (0.8)
Total 251 213 104 76 73 64 58 29 26 16 7 11 292 1220
TABLE 7. Comparison between initial visual acuity and visual acuity at 1 year follow-up for 854 eyes. Visual acuity at 1 year follow-up
Initial visual acuity 20/200 20/50–20/100
20/40 73 20/50–20/100 46 20/200 61 TOTAL 180 (21.1)
110 66 19 195 (22.8)
20/40
Total
431 614 (71.9) 39 151 (17.7) 9 89 (10.4) 479 (56.1) 854 (100)
Visual Outcome Complications Overall, 357 (29.3%) eyes developed at least one complication. Cataract was the most common, occurring in 17.1% of eyes, followed by glaucoma, occurring in 13.9% of the eyes (Table 6). Table 6 shows the prevalence of complications by uveitic diagnoses. Our analysis demonstrated a significant association between the uveitic diagnoses and the development of cataract (p = 0.02) and the development of glaucoma (p50.001). There were significant associations between the presence of posterior synechiae of the iris at presentation and the development of cataract (odds ratio = 3.1; 95% confidence interval (CI) = 2.23–4.24) and the development of glaucoma (odds ratio = 2.96; 95% CI = 2.09–4.19). Inflammatory retinal vein occlusion occurred in 10 eyes. The diagnoses included BD (6), PTU (3), and idiopathic (1). Band keratopathy was detected in 24 eyes at presentation. Of the 183 eyes from patients who were 18 years of age or younger, 18 (9.8%) had band keratopathy. Of the 1037 eyes from patients who were older than 18 years of age, 6 (0.6%) had band keratopathy. The difference between the two percentages was statistically significant (p50.001).
The follow-up period ranged from 3 to 192 months with a mean of 31.3 ± 31.5 months. The distribution of initial and visual acuity at 1-year follow-up is illustrated in Table 7. Initial and visual acuity at 1year follow-up were available for 854 eyes. Of the 854 eyes, 614 (71.9%) achieved visual acuity of 20/40 or better. The prevalence of poor visual acuity of 20/200 or less significantly reduced from 180 (21.1%) eyes at presentation to 89 (10.4%) eyes at last follow-up (p50.0001). The prevalence of visual acuity of 20/40 or better significantly increased from 479 (56.1%) eyes at presentation to 614 (71.9%) eyes at final follow-up (p50.0001). Initial visual acuity and visual acuity at 1year follow-up for the more frequently seen cases of uveitis classified by diagnosis are summarized in Table 8.
DISCUSSION In the current study, we have elucidated the current etiology of uveitis in a university-based referral center in Riyadh, Saudi Arabia. The most common specific diagnoses seen among our study population were VKH disease, PTU, and BD. The most common Ocular Immunology & Inflammation
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TABLE 8. Comparison of initial visual acuity and visual acuity at 1 year follow-up in eyes with various uveitic diagnoses. Type of eye disease Visual acuity 20/200 Initial Final p Value 20/40 Initial Final p Value
Vogt-Koyanagi-Harada disease (n = 195 eyes) (%)
Presumed tuberculous uveitis (n = 155 eyes) (%)
Behc¸et disease (n = 89 eyes) (%)
Idiopathic uveitis (n = 186) (%)
59 (30.3) 21 (10.8) 50.001*
40 (25.8) 26 (16.8) 0.085
25 (28.1) 12 (13.5) 0.031*
20 (10.8) 16 (8.6) 0.496
84 (43.1) 160 (82.1) 50.001*
68 (43.9) 100 (64.8) 0.013*
49 (55.1) 72 (80.9) 0.035*
132 (70.9) 157 (84.4) 0.139
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*Statistically significant at 5% level of significance.
anatomic diagnosis was panuveitis (47.1%), followed by anterior uveitis (36.8%), posterior uveitis (10.7%), and intermediate uveitis (5.4%). VKH disease is a chronic, bilateral, granulomatous panuveitis and exudative retinal detachment associated with poliosis, vitiligo, alopecia, and central nervous system and auditory signs. The prevalence of the disease varies among different populations of the world, and it commonly affects pigmented races and people of certain genetic predispositions.12,13 In the current study, VKH disease was the most common identifiable specific diagnosis, accounting for 19.6% of all uveitis cases, and was the most common cause of panuveitis (42.3%). VKH disease was also a common cause of uveitis in previous studies from Saudi Arabia,3–5 Japan,14–18 China,19 and Thailand.20,21 However, VKH disease is rarely seen in Caucasian.1,2 In patients with panuveitis, VKH disease was the most common specific diagnosis in a study from Japan,14 and the second most common specific diagnosis in a study from China.19 In our series, PTU was the second most common identifiable specific diagnosis (17.8%) and the second most common cause of posterior uveitis (23.1%) and panuveitis (27.7%). Several previous studies suggested that there may be a resurgence of ocular tuberculosis throughout the world.3,4,14,22–25 In our service, tuberculin skin testing is routinely performed in the workup of uveitis, and a high index of suspicion of the diagnosis is maintained in patients with unexplained chronic uveitis.6,26 All the patients with PTU were treated with antituberculous therapy combined with systemic corticosteroids.6,26 In our series, all patients with PTU had strongly positive tuberculin skin test results. In contrast, only 2.3% of patients with other specific diagnoses had a positive test. Our findings suggest that the presence of a strongly positive tuberculin skin test results with no other specific causes of uveitis should raise the suspicion of a tuberculous etiology. In a previous study, Llorenc¸e et al. emphasized the importance of tuberculin skin test as indirect evidence of PTU.27 Interestingly, 4 (1.9%) eyes with PTU presented with Copyright ! 2015 Taylor & Francis Group, LLC
hypopyon. Presence of hypopyon at presentation in patients with tuberculous uveitis is rare, but 2 cases were previously reported.28,29 In the current study, BD was the third most common identifiable specific diagnosis, accounting for 8.4% of all uveitis cases and for 17.1% of eyes with panuveitis. Our findings support the previous observations of the geographical distribution of BD between the northern latitude of 30 and 45 in the Mediterranean, Asian, and Eurasian populations, coinciding with the ancient silk route.1,2 Similar to our study, a high frequency of BD as a cause of uveitis has been reported in studies from Turkey,30 Japan,14–18 Saudi Arabia,3–5 Tunisia,31 Iran,32 Korea,33 China,19 and Italy.22,23 BD was the leading cause of panuveitis in these studies. In our study, toxoplasmic retinochorioditis was the fourth most common identifiable specific diagnosis, accounting for 6.9% of all uveitis cases, and was the most common cause of posterior uveitis, accounting for 56.9% of eyes with posterior uveitis. The results of previous studies indicated that toxoplasmic retinochoroiditis was the leading cause of posterior uveitis,23,30–32,34–36 accounting for 24.6–60.2% of cases. In previous studies from Saudi Arabia, toxoplasmosis accounted for 6–8.2% of all uveitis cases.3–5 In the current study, sarcoidosis accounted for only 2.3% of all cases. Our findings are similar to that reported in previous reports from Tunisia,31 Saudi Arabia,4 Iran,32 Italy,22 and China.19 However, in Japan, sarcoidosis is the most frequent intraocular inflammatory disease.18 Similarly, in studies from Western countries, sarcoidosis was among the most frequently observed systemic diseases associated with uveitis.34,36,37 In the current study, the frequency of specific disease was analyzed by age and gender. Idiopathic uveitis was the most common diagnosis in patients who were 18 years of age or younger, followed by VKH disease and juvenile idiopathic arthritis. In contrast, studies from Western countries identified juvenile idiopathic arthritis as the most common specific diagnosis for uveitis in children.38 In our study, juvenile idiopathic arthritis accounted for only
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318 H. Al Dhahri et al. 2.0% of all uveitis cases. Our findings are in agreement with studies from Japan14–18 that demonstrated that juvenile idiopathic arthritis is a rare association for uveitis in Japan. In the current study, idiopathic uveitis was the most common diagnosis among patients aged more than 18 years, followed by VKH disease, PTU, and BD. Our analysis of diagnosis based on gender revealed that idiopathic uveitis was the most common diagnosis in male patients followed by PTU, VKH disease, and BD. In female patients, the most common diagnosis was idiopathic uveitis followed by VKH disease, and PTU. Our analysis also revealed a significant male preponderance in BD, toxoplasmosis, herpetic uveitis, and HLA-B27positive anterior uveitis, and a significant female preponderance in VKH disease, multiple sclerosis, and idiopathic uveitis. These findings are compatible with previous reports.16,17 The high prevalence of panuveitis in our study could be explained by the high frequency of VKH disease, PTU, and BD, all of which manifest mainly as panuveitis. The fact that panuveitis was the most common anatomic type in our study reflects also the referral character of our hospital; most patients with acute anterior uveitis are treated by local ophthalmologists and are not referred. A shift in the relative frequency of uveitis cases away from anterior uveitis and toward posterior uveitis and panuveitis was seen in tertiary referral centres.1,2 Panuveitis is also predominant in Japan,14–18 which would be expected as sarcoidosis, VKH disease, and BD are the most common specific diagnoses in Japan.14–18 Panuveitis is also relatively frequently observed in other parts of Asia, South America, Africa, and the Mediterranean basin.1,2 In contrast, anterior uveitis is by far the most common form of uveitis in Western countries, accounting for at least half of the total uveitis cases.1,2 Thus, compared to studies from Western countries,1,2 there were comparatively lower frequencies of anterior uveitis and higher frequencies of panuveitis in our study. In eyes with anterior uveitis, idiopathic uveitis was the most common cause, accounting for 44.2% of all anterior uveitis eyes. The most common clinical associations of anterior uveitis in this study were Fuchs uveitis (16.2%), herpes (13.3%), and HLA-B27positive-anterior uveitis (12.9%). Similar findings were previously reported.1,2 In the present study, intermediate uveitis accounted for only 5.4% of all uveitis cases. Similarly, intermediate uveitis was reported to be the least common form of uveitis in all different geographic regions.1,2 In this series, 71.2% of intermediate uveitis eyes were classified as idiopathic, 13.6% were associated with tuberculosis, and 12.1% were associated with multiple sclerosis. Consistent with our results, most previous studies showed that the great majority of intermediate uveitis cases were idiopathic.30–32,34–36 We also demonstrated
that intermediate uveitis was significantly more common in patients who were 18 years of age or younger consistent with a previous report.32 In this study, at least one complication occurred in 29.3% of the eyes. The leading complications observed in our study were cataract and glaucoma. Our observations are consistent with previous reports showing that glaucoma and cataract were the most frequent complications.3,4,30,39 In our study, band keratopathy was significantly more common in patients who were 18 years of age or younger. This finding supports the previous observation that band keratopathy is more common in children with uveitis, and it tends to be a particular feature in those with early-onset severe type of inflammation.40 In the current study, we assessed the visual acuity at 1-year follow-up. Overall, visual acuity of 20/40 or better was achieved in 71.9% of all eyes. The limitations of this study are that the data were collected retrospectively and that it is likely that more severe cases of uveitis were observed at this university-based tertiary referral center. Therefore, disease frequencies must be considered in light of such referral bias toward more complicated panuveitis. These limitations mean that our data are not representative of the general population. Nevertheless, this study adds additional data to the clinical spectrum of uveitis referred to a tertiary eye care center in Saudi Arabia. In conclusion, our data indicate a predominance of panuveitis, which would be expected, as VKH disease, PTU, and BD were the most common specific diagnoses, all of which manifest as panuveitis. Furthermore, VKH disease, multiple sclerosis, and idiopathic uveitis were significantly more common in female patients, and BD, toxoplasmosis, herpetic uveitis, and HLA-B27-positive anterior uveitis were significantly more common in male patients. Juvenile idiopathic arthritis and idiopathic uveitis were significantly more common in patients aged 18 years or younger, and PTU, toxoplasmosis, and HLA-B27positive anterior uveitis were significantly more common in patients aged more than 18 years.
ACKNOWLEDGEMENTS The authors thank Michelle B. Rasonabe and Connie B. Unisa-Marfil for secretarial work. Ahmed M. Abu El-Asrar holds the Dr. Nasser Al-Rasheed Research Chair in Ophthalmology.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. Ocular Immunology & Inflammation
Referral Patterns of Uveitis This work was supported by Dr. Nasser AlRasheed Research Chair in Ophthalmology (Abu ElAsrar AM).
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