Visual outcomes and factors predictive of visual loss in Behcet's disease in Sultan Qaboos University Hospital, Oman

Abstract

PURPOSE:

This study aimed to evaluate the visual outcomes and associated factors in Omani patients with Behcet's disease (BD).

METHODOLOGY:

This is a descriptive retrospective analytical cohort study. All Omani patients of age 5–65 years with a confirmed clinical diagnosis of BD having ocular manifestation who attended the Rheumatology and Ophthalmology clinics at Sultan Qaboos University Hospital, Oman from January 2018 to October 2020. The demographic data, clinical findings, systemic, and ocular examination of all the recruited patients were retrieved from the electronic patient record.

RESULTS:

The study included 31 male and 16 female participants. The median age is 29.7 ± 10.6 years. Most patients with ocular manifestations presented in the third decade of their life (21–30 years' age). The most common ocular manifestations in our study were uveitis (91.5%) followed by vitritis (40.4%), and retinal vasculitis (36.2%). The most common ocular complications in order of frequency were cataract (27.7%), posterior synechiae (23.4%), and cystoid macular edema (21.2%). In this study, 22.7% of the patients with BD-related ocular manifestations reported severe visual loss. In addition, when adding the patients with severe visual loss secondary to complications such as secondary glaucoma and optic nerve atrophy, the severe visual loss cumulatively reported being 50% for both groups.

CONCLUSION:

The clinical characteristics of ocular manifestations in BD in Oman are similar to data from studies that have been conducted in other countries. However, our study found that the severity of ocular manifestations was more dominant among females. This study finding can be helpful for clinicians to predict ocular manifestations of BD to plan a timely follow-up and subsequently prevent further severe complications or visual loss.

Introduction

Behcet's disease (BD) is a recurrent chronic inflammatory disease that affects many organs and blood vessels of all sizes and types. Due to the diversity of blood vessels affected, the manifestation of this disease can occur in different organs.[1] This disease is characterized by oral ulcers, genital ulcers, and ocular lesions.[2] The etiology and pathogenesis of BD are still unclear.[3] However, various environmental factors like; infectious agents may trigger the symptoms in some patients with a particular genetic background such as HLA B51.[4] BD was discovered by Dr. Hulusi Behcet, a Turkish dermatology professor, who defined the triple symptom cluster with chronic oral ulcers, genital ulcers, and iritis as a separate entity in 1937.[2] Historically, Dr. Adamantiades from Greece reported this disease before Hulusi Behcet therefore, it is often termed Adamantiades BD.[5] BD is more frequent along the Mediterranean, Middle, and Far Eastern areas, while Turkey has the highest prevalence rates (400: 100,000 individuals),[4] the European Union countries report low prevalence rates (from 6% to 8% of the general European population), with an estimated number of cases ranging from 6000 to 8000 cases.[6] The ratio of BD between males and females varies in different countries, (e.g., ranging from 5.37 to 1 in Egypt and 0.38 to 1 in the United States).[7,8] In most cases, BD usually develops in the third decade of life.[8] The diagnosis of BD in childhood is unusual: onset of the disease before the age of 16 years old is reported in only 3%–5.3% of cases.[9] There have been several sets of clinical diagnostic criteria used until 1990 when the International Study Group for BD introduced a new list. Recurrent oral ulcers are a necessary criterion, along with two of the other four criteria: recurrent genital ulcers, skin lesions, uveitis, and a positive pathergy test.[10] According to Standardization of Uveitis Nomenclature (SUN), the uveitis is divided into noninfectious (autoimmune) and infectious categories. The “SUN” further, subcategorized the uveitis into four groups according to the anatomical location: anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis. As well as defines the onset, duration, and course on a clinical basis.[11]

Recently in 2020, Tugal-Tutkun et al. created an algorithm based on ocular manifestations and cumulative sum of probability percentage, which is a helpful tool for early diagnosis and probability of Behcet-related uveitis.[12] Ocular manifestation is the third most common presentation. It usually has a relapsing-remitting course. Ocular involvement mainly occurs within 2–4 years from the onset of BD.

Uveitis is the most frequent ocular symptom of BD, but it may also present with episcleritis, conjunctival ulcerations, scleritis, keratoconjunctivitis, keratitis, myositis, extraocular muscle palsies, orbital inflammation, isolated optic neuritis, and lacrimal gland involvement. Behcet's uveitis is usually bilateral in the majority of the patients (63%–100%).[13] Ocular involvement may be considered one of the most disabling manifestations in BD.

Aim and rationale of the study

In this study, we evaluated the ocular manifestations and visual outcomes and associated risk factors in Omani patients with BD who attended the Rheumatology and Ophthalmology clinics at Sultan Qaboos University Hospital (SQUH). This study is crucial as it would help to implement a more appropriate protocol for patient follow-up and management plan to reduce ocular morbidity. So far, no study about ocular manifestation in Omani population with BD is published.

Methodology

This descriptive retrospective analytical cohort study was performed at the SQUH in Muscat, Oman, from January 2018 to October 2020 based on retrospective data between January 2006 and October 2020. The institutional approval from the Medical Research Ethics Committee was obtained (SQU-EC/205/2020) and conformed to the provision of the Declaration of Helsinki.

This study included a total of 47 Omani patients with ocular manifestations out of 108 clinically confirmed and diagnosed cases of BD between the age of 5 and 65 years, who attended the Rheumatology and Ophthalmology clinics at SQUH. This includes 31 males (66.0%) and 16 females (34.0%); the male-to-female ratio was 2:1.

Patients with other autoimmune diseases, systemic infectious diseases, or ocular inflammatory pathology was excluded from the study.

Demographic data (age, sex, and region), disease onset, initial systemic manifestations of the disease, ocular manifestations, laterality, and ocular examination of all cases were retrieved from the electronic patient record. The record was kept confidential by assigning unique identifiers to each participant and was only accessible to principal investigators.

Consent was not obtained due to the retrospective nature of the review. A comprehensive ophthalmic examination was done on all patients which included assessment of visual acuity (VA), intraocular pressure measurement, anterior segment, and dilated fundus examination. Fundus fluorescein angiography was carried out when indicated.

Statistical analysis

The collected data were recorded and analyzed using Statistical Package for Social Sciences (version 20.0, SPSS Inc., Chicago, IL, USA). Data were presented as mean ± standard deviation (SD), range, and percentages. Categorical variables were analyzed by Chi-squared test and Continuous data were analyzed using the analysis of variation or unpaired t-test to determine the association between different variables being investigated.

Results

A total of 47 (43.5%) patients were identified with ocular manifestations out of 108 with BD between January 2006 and October 2020. The mean duration of the disease was 15.89 years (SD ± 8.28). The mean age at presentation to the ophthalmology clinic was 29.72 years with a SD ± 10.62 years (range, 12–62 years).

There were eight (17.0%) patients below or at age of 20 years, 21 (44.7%) patients at 21–30 years of age, 10 (21.3%) patients at 31–40 years of age, 6 (12.8%) at 41–50 years of age, and 2 (4.3%) patients above or at age of 51 years.

The geographical distribution of patients in various governorates is presented in Figure 1. Al Batinah was the highest percentage of BD patients with ocular manifestation; 19 (40.4%), followed by Muscat, Ad Dakhliyah, Al Sharqiya, and Ad Dhahirah.

Figure 1.

Patients' distribution in governorates. (Each vertical Blue bar indicates patient count from particular region and white box inside each blue bar shows number of patients in digits and percentage)

Clinical manifestations

Table 1 shows the prevalence of male and female patients distributed based on ocular manifestations. Results suggest that the most common ocular manifestations are uveitis (91.5%), vitritis (40.4%), and retinal vasculitis (36.2%). Male patients had a higher frequency of such manifestations (65.1%), (78.9%), and (70.5%), respectively. Moreover, some patients developed retinitis (12.8%). The anterior uveitis group comprised 15 (31.9%) patients, and 28 (59.6%) patients where in the posterior segment or panuveitis groups.

Table 1.

The prevalence of ocular manifestations of behcet's in male and female patients[14,15,16]

Manifestation	Number of each manifestation		Number of 47 patients
	Male, n (%)	Female, n (%)	Total, n (%)
Uveitis	28 (65.1)	15 (34.8)	43 (91.5)
Vitritis	15 (78.9)	4 (21.1)	19 (40.4)
Retinal vasculitis	12 (70.5)	5 (29.5)	17 (36.2)
Retinitis	5 (83.3)	1 (16.7)	6 (12.8)
Vascular occlusion	4 (80.0)	1 (20.0)	5 (10.6)
Epiretinal membrane	2 (50.0)	2 (50.0)	4 (8.5)
Retinal hole	1 (66.6)	2 (33.3)	3 (6.4)
Optic nerve involvement	1 (33.4)	2 (66.6)	3 (6.4)
Periphelipitis	1 (50.0)	1 (50.0)	2 (4.3)
Conjuctivitis	0	2 (100.0)	2 (4.3)
Choroditis	0	1 (100.0)	1 (2.1)

In addition, our results show a low prevalence of epiretinal membrane (8.5%), periphlebitis (4.3%), retinal hole (6.4%), optic nerve involvement (6.4%), conjunctivitis (4.3%), and choroiditis (2.1%). A higher percentage of anterior uveitis was seen in males.

Complications were also observed in the results and are mentioned in Table 2. Cataract was the most frequent complication presented in 13 (27.7%) patients, followed by posterior Synechiae in 11 (23.4%) patients, cystoid macular edema (CME) in 10 (21.2%) patients, glaucoma in 8 (17.0%) patients, and optic atrophy in 4 (8.4%) patients. Retinal neovascularization elsewhere (NVE) in three (6.4%) patients and retinal detachment in two (4.3%) patients. Ocular involvement was bilateral in 47.7% and unilateral in 52.3% (29.5% in the left eye and 22.7% in the right eye) patients.

Table 2.

The prevalence of ocular complication among the patients[2,8,17,18]

Complications	Number of 47 patients, n (%)
Cataract	13 (27.7)
Posterior synechiae	11 (23.4)
CME	10 (21.2)
Glaucoma	8 (17.0)
Optic atrophy	4 (8.4)
Retinal NVE	3 (6.4)
Retinal detachment	2 (4.3)

CME: Cystoid macular edema, NVE: Neovascularization elsewhere

Visual loss [Table 3] was categorized into four different groups according to VA, namely normal or mild visual loss (1-0.4 VA), moderate visual loss (0.3-0.1 VA), severe visual loss (0.05, Counting finger, Hand Motion or Light Perception), and blind (no light perception [NLP]).

Table 3.

Classification of visual loss according to visual acuity[19,20]

Classifications of visual loss	Number of 44 patients
	VOD, n (%)	VOS, n (%)
Normal/mild visual loss	29 (65.9)	24 (54.5)
Moderate visual loss	5 (11.4)	10 (22.7)
Severe visual loss	9 (20.4)	9 (20.4)
Blind	1 (2.2)	1 (2.2)

Number: Number of patients, VOD: Visual acuity in right eye, VOS: Visual acuity in left eye

The majority of patients in this study had normal to mild vision loss, 65.9% in the right eye and 54.5% in the left eye. In addition, severe visual loss and blindness are considered poor visual outcomes. Our study revealed that 44 (22.7%) patients with ocular manifestations developed poor visual outcome with an equal percentage in each eye, among them, one (2.2%) patient had NLP, in both eyes.

Overall, (50.0%) of patients were get stabilized to baseline or improved during the follow-up. Eventually, risk factors associated with poor visual outcomes (severe visual loss or blindness) were young patients between the ages 21 and 30 years (25%), the female gender more likely to develop poor visual outcomes (31%), and unilateral ocular involvement in (26%) of patients.

However, it was observed that the more severe the intraocular inflammation, the higher the risk of visual loss. The most common complications responsible for poor visual outcomes were glaucoma, optic atrophy, cataract, and posterior segment involvement or panuveitis.

Discussion

The clinical course of BD patients in this sample is similar to that of previous research in other countries. Since BD is comparatively uncommon in Oman, it is difficult to estimate the exact incidence rates and clinical features based on only 108 cases.

The eye is the most commonly affected organ in BD, according to literature search.[14,15] The percentages of ocular manifestations recorded in studies conducted in Iran, Korea, China, Japan, and Germany were (55%), (51%), (35%), (69%), and (55%), respectively. Furthermore, Arab countries such as Morocco (67%) and Jordan have recorded high rates of eye involvement (60%).[16] While this study detected 43.50% (n = 47 cases out of n = 108) developed ocular manifestation.

The mean age of ocular involvement in this cohort was 29.7 years of age (third or fourth decade of life), which is similar to that reported in other research: 36 years in Jordan, 34 years in Japan, and 30 years in Turkey.[2,13,21] In our study, the male-to-female ratio was 2:1 that reveals male predominance similar to other studies. In Iran, Japan, China, Korea, and Germany different male-to-female ratios were recorded 1.19:1, 0.98:1, 1.34:1, 0.63:1, and 1.40:1, respectively.[16] This may indicate that Behcet's pathogenesis is probably associated with environmental, genetic, or ethnic factors.

This research revealed that the most common ocular manifestation is uveitis (91.5%), vitritis (40.4%), and retinal vasculitis (36.2%), but in a study conducted in Jordan, the results revealed vitritis (55.6%) as the most common symptom among Jordanian patients then uveitis (50%).[2] Diffuse vitritis is usually the sign of posterior segment involvement, and its resolution is an important diagnostic marker.[21] A nongranulomatous necrotizing obliterative vasculitis may consequently result in vascular occlusions causing significant damage in the posterior segment. During the disease, the retina, and optic nerve is frequently damaged, end up with significant visual impairment in patients.

In our study, we found that (31.9%) had anterior uveitis and a higher percentage of patients (59.6%) demonstrated posterior segment involvement or panuveitis. Similarly, a study from Iran reported (40%) of patients with anterior uveitis and (44%) in Morocco whereas reported from China revealed (18%) has anterior uveitis. Also in Iran, posterior uveitis was seen in (44%) of patients, (44%) in Morocco, and (19%) in China.[13,16]

One study from Jordan revealed that the most common ocular complications among their patients were cataract (44.4%), followed by CME (33.3%), then posterior synechiae (11.1%) and glaucoma in (5.6%) cases.[2] In contrast, previous studies showed the most common ocular complications in BD was cataract followed by posterior synechiae.[17,22] Our study reflected, cataract in (27.7%) patients, followed by posterior synechiae (23.4%). In order to avoid any possible confounding variables, we only included patients with cataracts that are aged ≤30 years to eliminate age-related cataracts (senile cataract).

Neovascularization either at the disc (NVD) or NVE in the retina results from retinal ischemia secondary to vascular occlusion. Retinal ischemia has been shown to cause NVD (13%) in BD.[18] Our study detected five (10.6%) patients with vascular occlusion.

Three (6.4%) of them developed NVE, which is similar to the results of the Jordan study.[2] In our study, more than half (52.2%) of the patients had a unilateral ocular involvement, which is higher than other studies ranging from 0% to 35%.[21,23,24]

Poor visual outcomes were reported in this cohort to be (22.7%). Similarly, the United Kingdom and North America revealed (21%) and (25%), respectively.[19,20] Our findings indicate that patients in Oman are at a high risk of losing their VA. This study showed that (50%) of them stabilized or improved at subsequent visits.

Finally, this study highlighted the risk factors associated with poor visual outcomes. This includes patients' age of early thirties, (21–30 years), female gender, and unilateral ocular involvement. There were general agreements with findings from previous research related to risk factors except for gender. Furthermore, the involvement of the posterior segment is significantly associated with worse visual outcome. In addition, the presence of glaucoma was associated with an increased risk of developing poor visual outcomes.

Therefore, early recognition and timely treatment of ocular manifestation particularly uveitis can prevent complications that result in permanent visual loss.

Conclusion

This study demonstrated that the ocular manifestations of BD are similar to data from studies conducted in other countries. Ocular involvements predominantly occurred in the third decade of life. Almost one-quarter of patients developed poor visual outcomes with female gender and unilaterality as a risk factor. The retrospective nature and the small sample size are limitations of this study. To evaluate the prevalence of this disease in Oman, further research involving multiple centers on a larger sample is required.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.