Retinal Vasculitis in Patients with Positive TB Testing in Aceh

(Indonesia): A Case Series

Lia Meuthia Zaini

1,2

Department of Opthalmology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

Department of Opthalmology, Dr.Zainoel Abidin Hospital, Banda Aceh, Indonesia

Keywords: Retinal Vasculitis, Vitreous hemorrhage, Eales disease

Abstract: Retinal vasculitis is a group of diseases characterized by inflammation of the retinal blood vessels. Although

many retinal vasculitis are unknown, many systemic diseases are associated with this diseases such as

tuberculosis (TB), Lyme disease, syphilis, toxoplasmosis, or viral infection. Retinal vasculitis can also be

part of posterior uveitis. One of the most frequent cause of retinal vasculitis is TB, which often referred to as

Eales disease. This disease is very rare in developed countries and more often found in countries with poor

economic levels. In Aceh (Indonesia), the disease is quite common, but it has never been reported. Several

theories have been proposed to explain the etiology of this diseases. Hypersensitivity to tuberculo-protein is

the most common theory reported about the possible etiology of Eales disease. It is based on the positive

results of Mantoux reactions in Eales patients. However, Mantoux examination can be positive in 67-90% of

healthy adults in India (and possibly other developing countries including Indonesia). The author report 3

cases of Eales diseases with recurrent vitreous hemorrhage as the first manifestation, in patients with

positive TB testing in Aceh. We also provide a brief review of the literature.

1 INTRODUCTION

Retinal vasculitis is a group of diseases

characterized by inflammation of the retinal blood

vessels. Although many retinal vasculitis are

unknown (idiopathic), many systemic diseases are

associated with this diseases such as tuberculosis

(TB), Lyme disease, syphilis, toxoplasmosis, or viral

infection. In addition, retinal vasculitis can also be

part of posterior uveitis. One of the most frequent

cause of retinal vasculitis is TB, and Eales disease is

a vasculitic disease of the retina that is often

associated with TB.

2 CASE 1

A 40-year-old male presented to our outpatient

department with blurred vision of the left eye for 1

week. He had a history of hypertension. There were

no history of trauma, other systemic diseases, or

long-term drug use. Visual acuity was normal on

right eye and 5 CF on left eye. Ocular examination

revealed normal anterior segment of both eyes with

vitreous bleeding on the left eye.

We suggested the patient to have laboratory

testing and chest x-ray with no initial treatment. The

patient came a week later with a strong positive

result of Mantoux test (induration of more than 15

mm). We thought about Eales disease, and provided

oral steroid therapy as well as photocoagulation

lasers. One week later, vitreous bleeding began to

subside. We continued steroid treatment, and ask the

patient to come within 1 month.

One month later, bleeding has reduced. Visual

acuity of the both eyes were 6/6. Slit lamp bio

microscopic examination with super field lens

showed minimal hemorrhage and vasculitis on the

peripheral retina.

Six months later, the patient came again,

complaining of floaters on both eyes. Ocular

examination revealed minute vitreous bleeding in

the right eye. Minimal retinal hemorrhage and

vasculitis were found on the peripheral retina.

178

Zaini, L.

Retinal Vasculitis in Patients with Positive TB Testing in Aceh (Indonesia): A Case Series.

DOI: 10.5220/0008788501780182

In Proceedings of the 2nd Syiah Kuala International Conference on Medicine and Health Sciences (SKIC-MHS 2018), pages 178-182

ISBN: 978-989-758-438-1

Figure 1. Vitreous hemorrhage of the left eye; right eye

was within normal limit

Figure 2. Vitreous hemorrhage of the left eye begins to

subside

Figure 3. Minimal vitreous bleeding of the right eye six

months later, the left eye was clear

Figure 4. Retinal hemorrhage and vasculitis in far

periphery of the retina detected after vitreous hemorrhage

resolved

We again prescribed oral steroid therapy and

planned PCR test. One week after that vision

improve with minimal vitreous hemorrhage. We

referred the patient to Jakarta for diagnosis

confirmation and PCR test. The patient returned 3

weeks later with 6/6 visual acuity on both eyes.

Vitreous was clear with retinal hemorrhage. PCR

results for TB was negative and OCT examination

revealed normal foveal contour of the both eyes. We

suggested bimonthly examination to the patient.

Two months later the patient came with vitreous

hemorrhage on the left eye. We decided to observe

him for 1 one month before prescribing anti-

tuberculosis drug. The condition improved on the

following 6 months with minimal complaint for

floaters.

3 CASE 2

A 19-year-old male patient came with complaint of

recurrent blurred vision of the right eye about 1

month earlier. No history of trauma and other

systemic disease. The patient noted that condition

always improved without medications.

Ophthalmological examination revealed visual

acuity of hand motion on the right eye and 6/6 on the

left eye. Anterior segment of both eyes was within

normal limits. We found severe vitreous hemorrhage

of the right eye. Ultrasound examination showed no

retinal detachment.

Figure 5. Dense vitreous hemorrhage in the right eye

We performed radiological and laboratory tests

available at our hospital, provided anti thrombolytic,

and advised him to rest in semi-fowler position. One

week later the patient came with normal laboratory

results and chest x-rays, except for positive Mantoux

test with induration of more than 15 mm. Vitreous

bleeding remains the same, there was no significant

increase in vision. We diagnosed the patient with

Eales' disease and prescribed prednisone 1 mg / BW

with 10 mg tapering off weekly. After 1 month

observation, there was no improvement. The patient

was referred to undergo vitrectomy surgery. He

returned two months later with clear vitreous,

attached retina with giant vessels, minimal retinal

hemorrhage, and laser scars on peripheral retina.

Retinal Vasculitis in Patients with Positive TB Testing in Aceh (Indonesia): A Case Series

179

The patient returned two years later with the

same complaint but on the left eye. Visual acuity

was hand movement with dense vitreous

hemorrhage found on the left eye. We proposed

diagnostic workup that he eventually refused

because he preferred to consult overseas.

4 CASE 3

A 38-year-old man presented with 1 week of blurred

vision of the left eye. Initially he saw black spots.

He reported no pain, redness, and lacrimation. There

is no history of trauma and other systemic diseases.

The patient had a history of gradually blurred vision

and metamorphopsia of his other eye about one year

earlier. He was diagnosed with Branch Retinal Vein

Occlusion (BRVO) of the right eye and received

intravitreal anti-Vascular Endothelial Growth Factor

(VEGF) injection twice. He did not undergo any

laboratory test at that time. As the complaint

improves, the patient never regains control to the

ophthalmologist until symptoms appear in the left

eye.

Visual acuity at the time of examination was 6/6

on the right eye and 6/20 on the left eye. Anterior

segments were within normal limits. There were

minimal vitreous hemorrhages, retinal hemorrhage

in the supero-temporal quadrant accompanied by

cotton wool spots.

Figure 6. Retinal hemorrhage, sheating, and cotton wool

spot in the supero-temporal left eye

OCT examination showed normal foveal contour of

the right eye, and minimal sub retinal fluid and

exudate on the left eye.

Figure 7. OCT examination of the right and left eye

The patient underwent laboratory tests and chest x-

ray, and all the results were negative. Mantoux test

could not be done due to technical problems in our

Hospital. We performed sub tenon injection of

triamcinolone acetonide, systemic

metylprednisolone, and laser photocoagulation on

the left eye. The condition improved but rebleeding

occurred after 1 month, so did the complaint for

black spots. Due to the recurrence, we referred the

patient to a pulmonary specialist to determine the

possibility of latent tuberculosis infection. They

performed IFN-Gamma Release Assay (IGRA)

examination, and revealed a positive result for

tuberculosis.

5 DISCUSSION

Retinal vasculitis is a group of diseases

characterized by inflammation of the retinal blood

vessels. Consensus of the Standardization of Uveitis

Working Group in November 2004 described retinal

vasculitis as an inflammation and changes in retinal

blood vessels, including perivascular sheathing,

vascular leakage , or occlusion (Mir et al., 2017; Ku

et al., 2012).

Although many retinal vasculitis are unknown

(idiopathic), many systemic diseases are associated

with this diseases such as tuberculosis, Lyme

disease, syphilis, toxoplasmosis, or viral infection

(Ku et al., 2012; Mesquida et al., 2017; Sharief et

al., 2017). Retinal vasculitis can also be associated

with other diseases like Behcet, sarcoidosis, multiple

sclerosis, collagen-vascular disease, and sympathetic

ophthalmia. In addition, retinal vasculitis can also be

part of posterior uveitis (Pelegrin et al., 2017; Do et

al., 2016).

Retinal vasculitis associated with tuberculosis is

Eales diseases. It is a primary idiopathic occlusive

vasculopathy, characterized by venous inflammation

(vasculitis), occlusion, and retinal

neovascularization that usually involves the

peripheral retina. In the early stages, Eales disease

often has no symptoms. Some patients may

experience black spots on the eyes (floaters) 75%, or

blurred vision due to vitreous bleeding (60%). Eales

disease is very rare in developed countries and more

SKIC-MHS 2018 - The 2nd Syiah Kuala International Conference on Medicine and Health Sciences

180

often found in countries with poor economic levels.

India is one of the countries that quite often reported

the case. They found that 1 of 200-250 eye diseases

patients suffering from Eales. The number is also

significant in Aceh (Indonesia), but has never been

thoroughly reported (American, 2014; Das et al.,

1994; Dalvin & Smith, 2017; Patnaik, et al., 1998).

In this paper, the first and second patients come

with the main complaints of floaters, and blurred

vision caused by vitreous hemorrhage. While the

third patient came with metamorphopsia associated

with macular edema caused by Branch Retinal Vein

Occlusion (BRVO). BRVO in this case can occur

because of the inflammation (retinal phlebitis),

which is the underlying disorder of the disease. The

inflammatory cells found in the branches of central

retinal vein cause blockage of the blood vessels,

resulting in the occurrence of BRVO. Sometimes

inflammation occurs in the central retinal vein

causing the occurrence of Central Retinal Vein

Occlusion (CRVO) (Patnaik et al., 1998).

Etiopathogenesis of Eales disease remains

controversial. Wardsworth described Eales disease

as a primary vasculitis with an unknown etiology in

young adults. Retinal vasculitis and peripheral

retinal revascularization associated with various

systemic and ocular diseases may resemble Eales

disease in the inflammatory and proliferative

phases.

Our three patients have no symptoms of

tuberculosis infection seen from chest x-ray

examination. However, Mantoux tests were strongly

positive (induration more than 15 mm) in the first

and second patients. This test is one of the major

tuberculin skin tests used around the world and

widely used in patients with Eales disease. Mantoux-

positive rate has been reported in 42-98% of Eales

disease. However, Mantoux examination can be

positive in 67-90% of healthy adults in India (and

possibly other developing countries including

Indonesia). Therefore, the role of this examination in

Eales disease still a questioned, in addition this

disease has also been reported in patients with

Mantoux negative (Patnaik et al., 1998; Biswas &

Verma, 2007; Biswas et al., 2002; Talat et al., 2014;

Murugeswari et al., 2014). In our first and second

cases, the Mantoux examination results were

strongly positive with induration of more than 15

mm. The third patient underwent IGRA due to

technical problem in performing Mantoux test in our

hospital and all hospitals in Aceh at the time. This

examination is considered to have better specificity

than tuberculin skin test (Banaei et al., 2016; Katyal

et al., 2018). So far, we have not found a literature

report about IGRA on Eales disease. In our case this

test helped us establish the diagnosis. Utilization of

IGRA is therefore an interesting idea.

The three major signs of Eales disease are

inflammation characterized by periphlebitis or

vasculitis in the periphery retina, ischemia caused by

blood vessel blockage, and retinal

neovascularization (in optic disc or retina) which

responsible for recurrent vitreous haemorrhage (Das

et al., 2010; Gadkari, 2007). In the first patient we

found vitreous bleeding and signs of inflammation in

the peripheral retina. Although bleeding and

inflammation are not severe, an excellent response

to corticosteroids coupled with strong positive

Mantoux results helped us to guide the diagnosis. In

the second patient, the retina couldn’t be evaluated

more detail due to dense vitreous hemorrhage. It is

unfortunate that so difficult for us to follow up the

course of the disease because the patient has

undergone vitrectomy abroad, and not so good

record system in our hospital at that time. The

diagnosis of Eales became doubtful because there

was no confirmation of the inflammatory process in

the peripheral retina, until the patient came again

about 1 year later and there was a severe vitreous

bleeding occurred in the other eye. Male with

productive age, recurrent vitreous hemorrhage, and

strong positive results of Mantoux test guide us to

make the most possible diagnosis of the patient. The

third patient presented with symptoms characteristic

with inflammation of the peripheral retina,

accompanied by complications of BRVO in both

eyes that do not occur simultaneously. Positive lab

testing is only IGRA tests and a slight increase in

total cholesterol and LDL, as well as decreased

HDL. The literature suggests that young adult males

with BRVO or CRVO who do not have hypertension

and diabetes, and who have no signs of

arteriosclerosis, and indicate the presence of

phlebitis can be diagnosed as Eales. Response to oral

corticosteroids helps us to confirm the diagnosis.

With all the limited facilities, we have, the first

and third patients can still be well managed. The

disease records describe that the retina and vision is

still stable with corticosteroid and laser therapy in

the first patient, as well as corticosteroids and

intravitreal anti-VEGF injection in the third patient.

The second patient had to undergo overseas

vitrectomy surgery due to severe vitreous

hemorrhage. The absence of vitrectomy machine in

our province at that time made it difficult for us to

manage it here. We recognize that the financial

problems facing our country, especially in the

province of Aceh, causes difficulties and sometimes

lead to a bit of frustration in terms of diagnosing and

Retinal Vasculitis in Patients with Positive TB Testing in Aceh (Indonesia): A Case Series

181

managing. So, it is our responsibility as an

ophthalmologist, and also local governments to

continuously strive to improve the facilities and

human resources in our province, in order to perform

good management for our patients later.

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