Dr. Kirti Jaisingh, K15734, Dr. NidhiPanwar, Dr. Neeraj Manchanda, Dr. Shashi Nath Jha
INTRODUCTION
Uveitis is the third leading cause of worldwide blindness and currently accounts for approximately 15% of preventable vision loss worldwide.1 The Standardization of Uveitis Nomenclature (SUN) Working Group, in 2005, classified uveitis based on anatomic location into anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis2. The latter three are responsible for most visual disability in patients with ocular inflammatory disease.
In general, anterior uveitis is most often idiopathic, whereas an infectious etiology is more common among patients with posterior uveitis. Generally, infectious entities of uveitis carry a poorer overall prognosis than the noninfectious posterior uveitides. Thus, making the correct diagnosis of a specific uveitic entity is critical to its management.
The most common infectious cause of any oculargranulomatous inflammation in India is tuberculosis (TB)3. Other common causes include Toxoplasmosis, Syphilis, Cytomegalovirus (CMV), Herpes etc. as infectious entities and Sarcoidosis, Behcet disease, Wegener granulomatosis etc. as non-infectious entities. Thus, the initial diagnostic evaluation should exclude these infectious diseases, sincespecific therapy is needed and corticosteroids may be ineffective or may flare up the disease. This is particularly important in Indian subcontinent where tuberculosis is endemic.
Diagnosis of intraocular TB presents a unique challenge as the commonly employed tests for confirming TB, namely the demonstration of Mycobacteria in smear or culture in the sputum or body fluids or tissues, are seldom, if ever, positive from ocular fluids. This is explained by demonstration of paucibacillary disease in histopathological sections from autopsied eyes4. Thus indirect evidence of infection by Mycobacteria is sought after using various tests like Mantoux skin test, Quantiferon Gold, Chest X ray (CXR) etc. However, none of them have enough specificity to be considered as a gold standard. Currently contrast enhanced computerised tomography (CECT) of chest and abdomen is often used to detect the soft tissue and mediastinal changes due to TB or sarcoidosis.
Our study hereby aims to establish the utility of this technique,followed by biopsy of detected lymph nodes,in finding the etiology of posterior uveitis, in cases where conventional chest radiographs are normal.
MATERIAL AND METHODS
The observational study was conducted at eye care services of a tertiary hospital in New Delhi, India. Sixteen patients with unilateral or bilateral, intermediate or posterior or panuveitis, were included. Any patient, with known etiology or any other ocular or systemic inflammatory disease or only anterior uveitis, was excluded. Patients who refused investigations were also excluded.
All patients underwent a complete ophthalmic examination including Snellen visual acuity, Intraocular pressure (IOP) by applanation tonometry, anterior segment examination using slit lamp, posterior segment examination using slit lamp biomicroscopy, indirect ophthalmoscopy and other ancillary investigations like fundus photography, Optical Coherence Tomography (OCT) and fluorescein angiography (FA). Uveitis was diagnosed and graded according to the SUN classification.
Routine laboratory tests, including complete blood counts, erythrocyte sedimentation rate (ESR), Mantoux, Chest X ray, serum calcium, serum ACE levels, ELISA for toxoplasmosis and VDRL, were carried out in all patients. Contrast enhanced CT (CECT) of chest and abdomen was also done in all these patients. Patients, who were found to have lymphadenopathy on CECT, underwent Endobronchial ultrasound guided sampling (EBUS) along with histopathological examination of collected material.
Patients, in which the biopsy sample showed signs of tuberculosis, were started on antitubercular treatment (ATT), along with treatment of uveitis with steroids and/or other immunosuppressants.
The patients were followed up, for assessing the response to the therapy and any systemic or ocular complications, weekly for 1 month, fortnightly for next 2 months, and monthly after that. Fluorescein angiography was done 2 monthly to assess posterior segment activity. Though other parameters like visual acuity, IOP, fundoscopy, etc. were assessed at all follow up visits.
A repeat CXR was done in all those patients in which ATT was not given, at 3 months, in order to look for flaring up of latent TB in them.
RESULTS
A total of sixteen patients with posterior uveitis, including 10 males and 6 females, were included in the study. Mean age at presentation was 27.13±5.92 years. Mean visual acuity at presentation was 1.29±0.51 logMAR units. Mean visual acuity at a follow up of 6 months was 0.42±0.33 logMAR units. Table 1 shows the part of the eye affected.
All patients had a normal chest radiograph. All patients underwent CECT chest and abdomen. 10 patients were found to have hilar lymphadenopathy on CECT chest and 1 was found to have abdominal lymph nodes on CECT abdomen. All of the patients with hilar lymphadenopathy underwent lymph node biopsy using EBUS. Histopathological diagnosis of tuberculosis was confirmed in 9 cases. 1 patient was found to be suffering from sarcoidosis.Rest of the investigations are shown in tables 2-4.
These 9 patients were started on category 1 ATT. All patients received oral steroids in the dose of 1mg/kg alongwith starting ATT. Immunosuppressives (mostly methotrexate, azathioprine in 1 patient only) were begun 5 weeks after starting ATT. Rest of the patients were managed with oral steroids and other immunosuppressives, mostly methotrexate.
A repeat chest X-ray at 3 months in rest of the 9 patients, did not show any flaring up of latent pulmonary TB. All patients improved markedly.
Complications:
Steroid induced cataract occurred in 1 patient. Glaucoma occurred in 2 patients and both underwent glaucoma filtering surgery later. Vitreous hemorrhage developed in 1 patient who subsequently underwent vitrectomy and laser photocoagulation in both eyes. (table 5)
DISCUSSION
Tuberculosis is the most common single cause of morbidity and mortality worldwide, with an annual incidence of about 8.7 million and causing nearly 3 million deaths each year5.Incidence of ocular tuberculosis in India has been variably reported, ranging between 1.3 and 20%6-7.Usually a primary infection of the eye is found to be rare and ocular TB is more or less secondary in origin8. This justifies making the diagnosis of ocular TB by scanning the most common parts affected by Mycobacteria.
The large variations in clinical presentation and the lack of uniformity in diagnostic criteria make the diagnosis of intraocular tuberculosis difficult.CECT involves the use of special computed tomography scanning techniques to detect and assess the acute and chronic changes in lung parenchyma and lymphadenopathy in mediastinum.Mediastinal lymphadenopathy has been well described in numerous conditions including systemic infections (tuberculosis), autoimmune disorders (sarcoidosis) and lymphoproliferative disorders (lymphomas, leukemia). Conventional X-rays images can miss detecting this lymphadenopathy due to the interference of the sternum and soft tissue such as trachea and the oesophagus.
In one large series Kaiser et al found that CT scans were able to detect sarcoidosis in 14 of 17 cases that were missed on routine X-rays9. Chung et al studied 60 uveitis patients with biopsy proven sarcoidosis , of which CXR was abnormal in 50% whereas HRCT was abnormal in 95% cases10.
Ganesh et al in a recent study found abnormal HRCT in 52 patients as compared to 27 patients with abnormal CXR in 58 patients with granulomatous uveitis. Of the patients with posterior uveitis, 94.4% had HRCT findings of TB as compared to 38.8% patients with abnormal CXR3.
Similarly in our study, all patients had a normal Chest X-Ray. However, CECT showed abnormality in 68.75% patients clearly demonstrating its superiority in finding the diagnosis.
Although clinical findings on CECT have been related to their specific abnormalities like TB, sarcoidosis, etc. yet a definitive diagnosis as in any mass lesion should always be biopsy proven. This can further reduce the burden of giving ATT in non-proven cases.
As far as known, none of the studies done yet, in this field, have employed biopsy for the definitive diagnosis of etiology of posterior uveitis. This is the 1st study showing the utility of doing an extraocular biopsy to make a definitive diagnosis of uveitis, especially to exclude TB, in an endemic area like INDIA.
In our study all patients had normal chest radiograph. If CT wouldn’t have been performed these patients would have been managed with oral steroids alone which could have led to flaring up of tuberculosis.
in conclusion, CECT due to its better mediastinal imaging allows us to detect and assess previously undetected pathology and leads to a better final outcome. However, the cost and radiation hazards have to be compared with the potential benefit of therapy to the patients.
| TYPE OF UVEITIS | PANUVEITIS | CHOROIDITIS | VASCULITIS | INTERMEDIATE UVEITIS |
| NO. OF PATIENTS (16) | 3 (18.75%) | 7 (43.75%) | 5 (31.25%) | 1 (6.25%) |
Table 1: Types of uveitis in all patients
| MANTOUX POSITIVITY | ˂10mm | 10-20mm | ˃20mm |
| NO. OF PATIENTS (16) | 2 (12.5%) | 11 (68.75%) | 3 (18.75%) |
Table 2: Results of Mantoux skin testing in study patients
| NO. OF PATIENTS | CHEST X RAY | POSITIVE LYMPHNODES ON CECT
|
CECT NEGATIVE | |
| CHEST | ABDOMEN | |||
| 16 | 0 | 10 (6.25%) | 1 (6.25%) | 6 (37.5%) |
Table 3: Radiological findings in study patients
| EBUS FINDINGS | NON NECROTIZING LYMPHADENITIS | CASEOUS NECROSIS | REACTIVE LYMPHADENITIS | ZN STAINING POSITIVE |
| 10 | 1 (10%) | 9 (90%) | 0 | 1 (10%) |
Table 4: Histopathological findings in study patients
| COMPLICATIONS | NO. OF PATIENTS |
| Vitreous hemorrhage | 1 |
| Cataract | 1 |
| Glaucoma | 2 |
| Weight gain | 15 |
| Rashes on face and body | 2 |
| Hoarseness of voice | 1 |
| Psychosis | 1 |
Table 5: List of complications in study patients
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