Authors: Kendra Brett, Melissa Severn
CADTH identified 1 non-Canadian guideline that includes recommendations on the frequency of visual examinations for people with active tuberculosis who take ethambutol as part of their treatment. The guideline recommends testing for visual acuity and colour vision before starting treatment and at every health care visit throughout the course of treatment with ethambutol (recommendations based on clinical experience).
In Canada, a recommended treatment for active tuberculosis (TB) disease includes a regimen of isoniazid, rifampin, pyrazinamide, and ethambutol.1 A common adverse effect of ethambutol is eye toxicity (i.e., visual impairment),1 which can cause changes in visual acuity, visual fields, and colour vision. Given this side effect of ethambutol, there is an interest in knowing whether there is any guidance regarding monitoring for these adverse effects in people taking ethambutol as part of treatment for active TB disease.
In June 2020, CADTH searched the literature for evidence-based guidelines regarding the frequency of visual examination for people taking ethambutol as part of a TB treatment.2 This report identified 5 evidence-based guidelines that met the inclusion criteria based on their title and abstract. The purpose of the current report is to review the full texts of these guidelines and to summarize and critically appraise the eligible publications.
This report is a component of a larger CADTH condition-level review on TB. A condition-level review is an assessment that incorporates all aspects of a condition, including prevention, detection, treatment, and management. For more information on CADTH’s condition-level review on TB, please visit the project page (https://www.cadth.ca/tuberculosis).
What are the evidence-based guidelines regarding the frequency of visual examination for people taking ethambutol as part of a TB treatment regimen?
A limited literature search was conducted for a previous CADTH report2 by an information specialist on key resources, including MEDLINE via Ovid, the Cochrane Library, the University of York Centre for Reviews and Dissemination (CRD) databases, the websites of Canadian and major international health technology agencies, as well as a focused internet search. The search strategy comprised both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were ethambutol and visual impairment. Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, and guidelines. The search was also limited to English-language documents published between January 1, 2010, and June 4, 2020. Internet links were provided, where available.
The evidence in this report was identified in a previous CADTH report,2 in which 1 reviewer screened citations and abstracts. For this report, the full-text articles were reviewed by 1 reviewer, and the final selection of full-text articles was based on the inclusion criteria presented in Table 1.
Criteria | Description |
Population | People taking ethambutol as part of a tuberculosis treatment regimen |
Intervention | Visual examination (e.g., visual field test, colour vision test, dilated fundus and optic nerve examination, visual acuity testing) |
Comparator | Not applicable |
Outcomes | Recommendations regarding frequency and duration of testing |
Study designs | Health technology assessments, systematic reviews, evidence-based guidelines |
Articles were excluded if they did not meet the selection criteria outlined in Table 1, were duplicate publications, or were published before 2010. Guidelines with unclear methodology were also excluded.
The included publication was critically appraised by 1 reviewer using the following tool as a guide: the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.3 Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included publication were described narratively.
A total of 144 citations were identified in the literature search for the previous CADTH report2 and 4 potentially relevant publications were retrieved from the grey literature. Five potentially relevant reports were identified and retrieved for full-text review. Of these potentially relevant articles, 4 guidelines were excluded as they did not include recommendations regarding visual examination,1,4-6 and 1 evidence-based guideline7 met the inclusion criteria and was included in this report.
One evidence-based guideline7 was identified and included in this report. This guideline was developed by the Singapore Ministry of Health in 2016,7 and it is intended to be used by health care professionals in Singapore who work with individuals with TB. The population and interventions covered by this guideline (i.e., prevention, diagnosis, and management of TB) were broader than the eligible population and interventions for this report, and recommendations relevant to this report covered testing for visual acuity and colour vision in individuals with TB who will receive or who are receiving treatment with ethambutol. The guidelines were developed by a committee of experts by adapting a previous guideline and a review of relevant literature, but no other details were reported on the methods used to search for evidence or develop the recommendations.7 The strength of the evidence informing the recommendations was graded from 1++ (highest) to 4 (lowest; expert opinion), and the recommendations were graded from A (highest) to D (lowest) based on the level of evidence. In cases where no relevant evidence (i.e., scientific literature or expert opinion) was identified, recommendations were developed based on the clinical experience of the guideline development group and graded as a “good practice point.”
Additional details regarding the study characteristics are provided in tables in Table 2 in Appendix 1.
This guideline was previously included in a CADTH report8 on guidelines for the identification of TB. The detailed critical appraisal of the guideline can be found in that report8 and summarized in Table 3 in Appendix 1. In brief, it was unclear whether this guideline by the Singapore Ministry of Health7 used a systematic approach to search for and evaluate the evidence because insufficient methodological details were reported in the guideline.
The specific recommendations and the strength of the recommendations are provided in Table 4 in Appendix 1.
One evidence-based guideline7 included recommendations regarding visual examinations for people taking ethambutol as part of a TB treatment regimen.
The guideline from the Singapore Ministry of Health recommends that adults should have their visual acuity and colour vision checked before starting a TB treatment regimen that includes ethambutol; this recommendation is considered a “good practice point” because it is based off the clinical experience of the guideline development group (i.e., no supporting evidence).7
The guideline from the Singapore Ministry of Health recommends that adults who are taking ethambutol as part of their TB treatment regimen should have their visual acuity and colour vision checked at each visit; this recommendation is considered a “good practice point” because it is based off the clinical experience of the guideline development group (i.e., no supporting evidence).7
The findings in this report are limited by the quantity and quality of the evidence. One guideline7 was identified that included 2 relevant recommendations; however, the guideline did not report the methods used to search for evidence or to develop the recommendations, limiting the reliability of the guideline. In addition, the relevant recommendations were based on the clinical experience of the members of the guideline development group rather than evidence from the literature, which reduces the certainty of the recommendations. It was not reported in the guideline whether a literature review was conducted on visual examination in people taking ethambutol, thus it is unknown whether the decision to base these recommendations on the clinical experience of the guideline development group was due to a lack of available evidence on the topic (e.g., literature review did not identify any relevant evidence) or for another reason.
The guideline7 identified in this report is meant to apply to Singapore, and the recommendations were based off the clinical experience of the members of the guideline development group. Therefore, it is unknown whether the recommendations are generalizable to the Canadian clinical practice.
This report comprised 1 low-quality evidence-based guideline that included 2 recommendations regarding visual examinations in people taking ethambutol as part of a TB treatment regimen. Overall, in adults with TB, testing for visual acuity and colour vision was recommended before starting treatment with ethambutol and at every health care visit throughout the course of treatment with ethambutol. However, these recommendations are based solely off the clinical experience of the guideline development group with no supporting scientific evidence, and this limitation should be considered when interpreting the findings of this report.
1.Public Health Agency of Canada. Chapter 5: Canadian Tuberculosis Standards 7th Edition: 2014 – Treatment of Tuberculosis disease. https://www.canada.ca/en/public-health/services/infectious-diseases/canadian-tuberculosis-standards-7th-edition/edition-17.html. Accessed April 30 2021.
2.Visual Examination Frequency for People Taking Ethambutol for Tuberculosis: Guidelines. Ottawa: CADTH; 2020 Jun. (CADTH rapid response report: summary of abstracts). https://www.cadth.ca/visual-examination-frequency-people-taking-ethambutol-tuberculosis-guidelines. Accessed 2021 May 17.
3.Agree Next Steps C. The AGREE II Instrument. [Hamilton, ON]: AGREE Enterprise; 2017: https://www.agreetrust.org/wp-content/uploads/2017/12/AGREE-II-Users-Manual-and-23-item-Instrument-2009-Update-2017.pdf. Accessed 2021 Apr 21.
4.British HIV Association. British HIV Association guidelines for the management of tuberculosis in adults living with HIV 2018 (2019 interim update); 2019. https://www.bhiva.org/file/5c485f3dc7c17/BHIVA-TB-guidelines.pdf. Accessed 2021 May 17.
5.Nahid P DS, Alipanah N, et al. . Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016;63(7):e147-e195. 2016.
6.World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. 2014; https://apps.who.int/iris/bitstream/handle/10665/112360/9789241548748_eng.pdf;jsessionid=83E9F94E594142AAA3DAE3B6E09CD6B8?sequence=1 Accessed 2021 Feb 26.
7.Ministry of Health, Singapore. Prevention, Diagnosis and Management of Tuberculosis; 2016. https://www.moh.gov.sg/docs/librariesprovider4/guidelines/moh-tb-cpg-full-version-for-website.pdf Accessed 2021 May 21.
8.Identification of Tuberculosis: A Review of the Guidelines. Ottawa: CADTH; 2020 February. (CADTH rapid response report: summary with critical appraisal). https://cadth.ca/sites/default/files/pdf/htis/2020/RC1236%20TB%20identification%20Final.pdf. Accessed 2021 May 17.
Table 2: Characteristics of Included Guideline
Intended users, target population | Relevant interventions and outcomes considered | Evidence collection, selection, and synthesis | Evidence quality assessment | Recommendation development and evaluation | Guideline validation |
Singapore Ministry of Health (2016)7 | |||||
Intended users: Health care practitioners Target population: Individuals with TB | Interventions: Visual acuity, colour vision Outcomes: Not reported | Developed by adapting existing guidelines and a review of relevant literature. No other details provided. | Methods for assessing the evidence were not reported. “Level of evidence: 1++ = High quality meta-analyses, SRs of RCTs, or RCTs with a very low risk of bias 1+ = Well conducted meta-analyses, SRs of RCTs, or RCTs with a low risk of bias 1– = Meta-analyses, SRs of RCTs, or RCTs with a high risk of bias 2++ = High quality SRs of case control or cohort studies. High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal 2+ = Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal 2– = Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal 3 = Non-analytic studies, e.g., case reports, case series 4 = Expert opinion (p. 2).” | Recommendations were appraised by scoring the strength of the evidence, and grade of recommendation (no other details provided) Grade of recommendation: A = At least 1 study with evidence level 1++, or a body of evidence that is primarily rated at 1+, with consistency in the results B = Body of evidence with studies rated 2++, with consistency in results C = Body of evidence rated 2+, with consistency of results D = Evidence rated as level 3 or 4 GPP = Recommended best practice based on the clinical experience of the guideline development group | Not reported |
GPP = good practice point; RCT = randomized controlled trial; SR = systematic review; TB = tuberculosis.
Table 3: Strengths and Limitations of the Included Guideline Using AGREE II3
Item | Singapore Ministry of Health (2016)7 |
Domain 1: Scope and purpose | |
1. The overall objective(s) of the guideline is (are) specifically described. | Yes |
2. The health question(s) covered by the guideline is (are) specifically described. | No |
3. The population (e.g., patients, public) to whom the guideline is meant to apply is specifically described. | Partially |
Domain 2: Stakeholder involvement | |
4. The guideline development group includes individuals from all relevant professional groups. | Partially |
5. The views and preferences of the target population (e.g., patients, public) have been sought. | No |
6. The target users of the guideline are clearly defined. | Yes |
Domain 3: Rigour of development | |
7. Systematic methods were used to search for evidence. | No |
8. The criteria for selecting the evidence are clearly described. | No |
9. The strengths and limitations of the body of evidence are clearly described. | Partially |
10. The methods for formulating the recommendations are clearly described. | No |
11. The health benefits, side effects, and risks have been considered in formulating the recommendations. | No |
12. There is an explicit link between the recommendations and the supporting evidence. | Partially |
13. The guideline has been externally reviewed by experts before its publication. | No |
14. A procedure for updating the guideline is provided. | Yes |
Domain 4: Clarity of presentation | |
15. The recommendations are specific and unambiguous. | Yes |
16. The different options for management of the condition or health issue are clearly presented. | Yes |
17. Key recommendations are easily identifiable. | Yes |
Domain 5: Applicability | |
18. The guideline describes facilitators and barriers to its application. | No |
19. The guideline provides advice and/or tools on how the recommendations can be put into practice. | No |
20. The potential resource implications of applying the recommendations have been considered. | No |
21. The guideline presents monitoring and/or auditing criteria. | Partially |
Domain 6: Editorial independence | |
22. The views of the funding body have not influenced the content of the guideline. | No |
23. Competing interests of guideline development group members have been recorded and addressed. | No |
AGREE = Appraisal of Guidelines for Research and Evaluation.
Table 4: Summary of Recommendations in Included Guideline
Recommendations and supporting evidence | Quality of evidence and strength of recommendations |
Singapore Ministry of Health (2016)7 | |
Recommendation 1: “Before starting tuberculosis treatment, baseline liver enzymes should be performed in those over 15 years old. Adult patients to be commenced on ethambutol must have their visual acuity and colour vision checked at baseline (p. 50).” No supporting evidence reported. | Recommendation 1: Good practice point |
Recommendation 2: “The patient’s weight should be documented at each visit and the drug dosages adjusted accordingly. Adult patients on ethambutol must have their visual acuity and colour vision checked at each visit. Those with risk factors for drug-induced hepatitis must be closely monitored (p. 64).” No supporting evidence reported. | Recommendation 2: Good practice point |
ISSN: 2563-6596
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