The treatment of ocular tuberculosis: A survey of published literature

Salil Mehta

doi:10.4103/0301-4738.27959

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Year : 2006 | Volume : 54 | Issue : 4 | Page : 278-280

The treatment of ocular tuberculosis: A survey of published literature

Salil Mehta
Lilavati Hospital and Research Centre, Mumbai, India

Correspondence Address:
Salil Mehta
202, Laxmi Villa, M.G.Road, Kandivali (W), Mumbai - 400 067
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/0301-4738.27959

Abstract

With an expanding awareness of ocular tuberculosis, ophthalmologists are increasingly required to participate in the care of these patients. We conducted a survey of published ophthalmic literature to identify whether the regimens of antitubercular medications prescribed conform to current guidelines. A Medline search for publications (1995-2005) was done and the data were systematically analyzed with respect to demographic features, clinical findings and the antitubercular therapy prescribed. Of the 34 papers (82 patients) available, 33 papers described the prescribed antitubercular therapy. Eighteen papers (54.5%, 46 patients) conformed to guidelines versus 15 papers (45.4%, 32 patients) did not, suggesting that a large proportion of papers do not conform to current guidelines. Wider dissemination of therapeutic guidelines is necessary to encourage rational therapy and minimize therapeutic failures, drug resistance or relapse.

Keywords: Antitubercular agents, ocular tuberculosis, survey

How to cite this article:
Mehta S. The treatment of ocular tuberculosis: A survey of published literature. Indian J Ophthalmol 2006;54:278-80

How to cite this URL:
Mehta S. The treatment of ocular tuberculosis: A survey of published literature. Indian J Ophthalmol [serial online] 2006 [cited 2023 Dec 11];54:278-80. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2006/54/4/278/27959

Table 2: The various reported clinical findings of 82 patients of ocular tuberculosis

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Table 1: The levels of evidence for the diagnosis of ocular tuberculosis

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An increasing awareness of ocular tuberculosis, often associated with systemic infection, requires ophthalmologists to be aware of and prescribe rational therapy to achieve optimal outcomes. Current literature describes numerous therapeutic regimens differing in the number of drugs prescribed,[1] dosages and duration of treatment.[2] As this primary literature is an important source of therapeutic information, we analyzed these to identify antitubercular prescribing patterns and compared them to current recommendations.

Materials and Methods

We conducted a Medline search using the search terms "ocular tuberculosis, intraocular tuberculosis and choroidal tuberculosis". We identified publications from January 1995 to May 2005 and excluded reviews, papers that focused on diagnosis, publications in any language except English or Spanish and orbital/adnexal tuberculosis. A total of 34 papers described the diagnosis and treatment of single or multiple patients and we analyzed these.

The following data were extracted: number of cases, age and sex, country of origin of the patients (if specified, otherwise it was taken to be the country of origin of the paper), ocular findings, the presence or absence of systemic tuberculosis, basis of diagnosis [Table - 1] and the antitubercular therapy given (drugs, dosages and duration of therapy).

Results

In the 34 papers analyzed,[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34] a total of 82 patients (52 males and 30 females) were described with ages ranging from 8 years to 70 years (mean 36). The majority were from India (46, 56.0%) followed by Japan (10, 12.1%). Other nationalities included patients from Malawi, Spain, the US (four each, 4.8%), Taiwan (three, 3.6%), Turkey, Mexico (two each, 2.4%), Ecuador, Brazil, Pakistan, South Korea, Sierra Leone, France and Guinea (one each, 1.2%). The described ocular manifestations are enumerated in [Table - 2].

A variety of diagnostic methods were used to diagnose intraocular tuberculosis. These included analysis of aqueous fluid in the form of smear for acid-fast bacilli, culture and polymerase chain reaction (PCR). The study of vitreous specimens or eyeball histopathology have been done in few cases. Systemic investigations included chest X-rays/computed tomography (CT) scans, bronchoscopy and Mantoux tests. Additionally, diagnosis was obtained from the culture/PCR/histopathology of sputum, lymph nodes or organ systems. The levels of evidence for the diagnosis included 36 (43.90%) patients with Level I, 16 (19.5%) with Level II and 30 (36.5%) with Level III evidence. In 31 papers (77 patients) the presence of systemic tuberculosis (usually pulmonary) was clinically suspected or proven whereas three papers described five patients with no evidence of systemic tuberculosis.[19],[21],[32] A total of six (17.6%) papers identified 12 patients with human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS).

As no recent randomized trials have been conducted to assess the optimum treatment for patients with ocular tuberculosis, we have used for discussion, the recommendations described for treatment of pulmonary and extrapulmonary tuberculosis, even though intraocular inflammation was not specifically described.

The American Thoracic Society (ATS), the Centres for Disease Control (CDC) and the Infectious Diseases Society of America (IDSA) have recommended four drugs [isoniazid (INH), pyrazinamide (PZA), ethambutol (EMB) and rifampicin (RIF)] for an initial eight weeks followed by INH and RIF either seven days a week (Regimen 1a) or twice weekly (Regimen 1b) for a minimum duration of 18 weeks.[35] The efficacy and effectiveness of these regimens has led to a rating of A 1 (A = preferred regimen; 1 = based on randomized clinical trials) and A 2 (A = preferred regimen; 2 = based on nonrandomized clinical trials) for HIV negative and positive patients respectively. These principles also apply to extrapulmonary forms of the disease or HIV-infected patients, with evidence suggesting that similar regimens of four drugs for a period of 6-9 months are effective.

The World Health Organization recommendations also require the use of four drugs (INH/RIF/PZA/ETB) for an initial two months followed by INH/RIF for four months for Category I patients (new sputum positive patients, new sputum negative patients with extensive lung parenchymal disease and those with severe extrapulmonary disease) as well patients in Category III (new smear negative patients with lesser lung parenchymal involvement and patients with less severe extrapulmonary disease).[36]

Thirty-three papers (78 patients) described the antitubercular therapy in sufficient detail and this was compared to these recommendations. The therapy in 18 papers (54.5%, 46 patients) conformed to guidelines whereas those in 15 (45.4%, 32 patients) did not.

Discussion

The aims of chemotherapy include the rapid killing of bacilli, reducing the risk of drug resistance and preventing relapse by eliminating residual bacilli. To achieve this, multiple drugs are prescribed for an adequate duration. Theoretical models describe three distinct subpopulations of bacilli. The largest subpopulation consists of fast multipliers located within cavities. INH (followed by EMB, RIF and PZA) is the most effective in killing these bacilli and reduces the risk of resistance developing within the bacillary population. The other more slowly growing bacilli subpopulations are responsible for relapses and treatment failures and need to be treated with drugs that possess a potent sterilizing ability (RIF/PZA).

All of the patients underwent clinical examination, chest X-ray and/or chest CT scan and Mantoux test to detect systemic tuberculosis with pulmonary tuberculosis being detected in the majority. Intraocular tuberculosis was suspected clinically and confirmed using smears, culture, PCR or histopathology of fluids/tissue. HIV/AIDS was frequently found in these patients and is a known risk factor.

While the majority of the reports were in accordance with recommendations, a significant proportion of the papers had regimens that are nonguideline-based. Common deviations included an inadequate number of drugs (varying from one to three) or an inadequate duration of treatment (often as little as two to three months). Only one group of authors provided a rationale for nonguideline-based therapy by highlighting a low incidence of resistance to INH and RIF (1.1 to 1.7% and 0.5 to 0.7% respectively) in their home country (Japan).[12] In our opinion, the low incidence of drug resistance should encourage the use of combination drug therapy designed to prevent its occurrence. One report described the use of rifabutin in place of RIF in an HIV positive patient that is rationally correct and overcomes deleterious RIF-antiretroviral interactions.[29]

Nonguideline-based regimens carry the risk of inadequate treatment; increase the risk of subsequent drug resistance and relapse for both the systemic and the ocular infections. Wider dissemination of this fact will enable ophthalmologists to prescribe rational therapy.

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Tables

[Table - 1], [Table - 2]

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