Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India

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Although ocular side effects of Anti-tubercular drugs are well known, the patients generally report late in the course which can result in irreversible vision loss. The purpose of this study was to study the visual field changes during the time course of anti-tubercular therapy (ATT). Methods A total of 48 patients were studied in this prospective type of study. All patients newly diagnosed with TB and started on treatment were included in the study. Baseline examination which included visual acuity, color vision, anterior segment, IOP, Amsler grid, fundus, and visual field test were performed before starting ATT and at 6-month follow-up. Results The mean age of the study population was 35.90 ± 10.2 years. 35 (72.9%) were males and 13 (27.1%) females. 32(66.6%) had pulmonary TB and the rest 16 (33.3%) had extrapulmonary TB. MDR TB was diagnosed in 27 (56.3%) of the patients with the rest 21 (43.8%) being drug sensitive. The baseline examination was normal in all 48 patients. 3(6.3%) out of 45 patients presented with visual complaints after the treatment initiation. Altogether 7 patients out of 48, had visual field defects at the 6-month follow-up. The incidence of visual field defects in our study was 14.6% with the value being significant (0.016). 8.3% had peripheral constriction of visual fields, 2.1% with Severe generalized depression of visual fields and 2.1% with central scotoma. Out of the 45 patients with no visual complaints at 6-month follow-up, 4 (8.33%) showed peripheral field constriction. Conclusion Visual field defects caused by ATT can precede clinical symptoms. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where Visual evoked potential testing and RNFL-OCT are not available. 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F1000Research 2025, 13 :719 ( https://doi.org/10.12688/f1000research.149831.4 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Revised Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] Tejaswi Pagadala 1,2 , Gurudutt Kamath 1,2 , Teena Mariet Mendonca https://orcid.org/0000-0002-7297-386X 1,2 , Gladys Rodrigues 1,2 , Ajay Kamath 1,2 Tejaswi Pagadala 1,2 , Gurudutt Kamath 1,2 , [...] Teena Mariet Mendonca https://orcid.org/0000-0002-7297-386X 1,2 , Gladys Rodrigues 1,2 , Ajay Kamath 1,2 PUBLISHED 30 Jul 2025 Author details Author details 1 Department of Ophthalmology, Kasturba Medical College, Mangalore, India 2 Manipal Academy of Higher Education, Manipal, India Tejaswi Pagadala Roles: Data Curation, Writing – Original Draft Preparation Gurudutt Kamath Roles: Conceptualization, Supervision, Visualization Teena Mariet Mendonca Roles: Project Administration, Resources, Supervision, Writing – Review & Editing Gladys Rodrigues Roles: Methodology, Project Administration, Resources Ajay Kamath Roles: Supervision OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Manipal Academy of Higher Education gateway. This article is included in the Eye Health gateway. Abstract Objective Tuberculosis is a global health challenge with one-third of the world’s population infected by it. Although ocular side effects of Anti-tubercular drugs are well known, the patients generally report late in the course which can result in irreversible vision loss. The purpose of this study was to study the visual field changes during the time course of anti-tubercular therapy (ATT). Methods A total of 48 patients were studied in this prospective type of study. All patients newly diagnosed with TB and started on treatment were included in the study. Baseline examination which included visual acuity, color vision, anterior segment, IOP, Amsler grid, fundus, and visual field test were performed before starting ATT and at 6-month follow-up. Results The mean age of the study population was 35.90 ± 10.2 years. 35 (72.9%) were males and 13 (27.1%) females. 32(66.6%) had pulmonary TB and the rest 16 (33.3%) had extrapulmonary TB. MDR TB was diagnosed in 27 (56.3%) of the patients with the rest 21 (43.8%) being drug sensitive. The baseline examination was normal in all 48 patients. 3(6.3%) out of 45 patients presented with visual complaints after the treatment initiation. Altogether 7 patients out of 48, had visual field defects at the 6-month follow-up. The incidence of visual field defects in our study was 14.6% with the value being significant (0.016). 8.3% had peripheral constriction of visual fields, 2.1% with Severe generalized depression of visual fields and 2.1% with central scotoma. Out of the 45 patients with no visual complaints at 6-month follow-up, 4 (8.33%) showed peripheral field constriction. Conclusion Visual field defects caused by ATT can precede clinical symptoms. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where Visual evoked potential testing and RNFL-OCT are not available. READ ALL READ LESS Keywords Mycobacterium tuberculosis, Drug toxicity, DOTS, visual field defects, toxic optic neuropathy, Ethambutol, Linezolid Corresponding Author(s) Teena Mariet Mendonca ( [email protected] ) Close Corresponding author: Teena Mariet Mendonca Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Pagadala T et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Pagadala T, Kamath G, Mendonca TM et al. Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.12688/f1000research.149831.4 ) First published: 01 Jul 2024, 13 :719 ( https://doi.org/10.12688/f1000research.149831.1 ) Latest published: 30 Jul 2025, 13 :719 ( https://doi.org/10.12688/f1000research.149831.4 ) Revised Amendments from Version 3 In accordance with the reviewer’s feedback, substantial revisions have been made in the third version of the manuscript. The methods section now includes the rationale for excluding participants over the age of 50. Additionally, the discussion has been updated to address the color vision abnormalities observed in our patients. All typographical errors have also been corrected. In accordance with the reviewer’s feedback, substantial revisions have been made in the third version of the manuscript. The methods section now includes the rationale for excluding participants over the age of 50. Additionally, the discussion has been updated to address the color vision abnormalities observed in our patients. All typographical errors have also been corrected. See the authors' detailed response to the review by Gordon T Plant See the authors' detailed response to the review by Karthik Vinay Mahesh See the authors' detailed response to the review by Sanjeeta Sitaula READ REVIEWER RESPONSES Introduction Tuberculosis (TB) is one of the ancient diseases known to mankind that has co-evolved with humans for many decades 1 and is a global health challenge. TB is one of the top three infectious killing diseases in the world and is also the leading cause of death from a single infectious agent. 2 India is a country with the world’s largest TB burden, accounting for one-fourth of global TB incidence. 3 According to the India TB Report 2022, there is a 19% increase in cases (new and relapse) in 2021 from 2020. 4 Interrupting its transmission is central to achieving the reduction in its incidence required to meet the End TB targets. 4 DOT (Directly observed therapy) is widely accepted and followed in many other countries and is the most effective. It is the fastest expanding and most extensive growing strategy and the second largest based on people initiated on treatment and population coverage, respectively. 1 The standard treatment plan for tuberculosis usually is six months; however, for resistant cases, it may even extend to 2 years with less potent and less toxic drugs 1 with treatment change based on the drug resistance. The first line of drugs includes ethambutol, isoniazid, pyrazinamide, and rifampicin, and these are part of DOTS (Directly Observed Treatment Short course). Despite the increased availability of medical treatment, new challenges have developed with the growing incidences of drug-resistant tuberculosis that include DR-TB (drug-resistant), MDR-TB (multidrug-resistant), and XDR-TB (extensively drug-resistant). 6 ATT-associated ocular toxicity was first established in the 1960s. 7 Ethambutol and linezolid are the most common anti-TB drugs responsible for ocular side effects. 4 , 8 Rare cases of Isoniazid-induced toxic optic neuropathy have also been reported. 9 , 10 The toxic neuropathies associated with Ethambutol and linezolid account for about 1% and normally occur after 4-6 months of treatment. 11 Optic nerve head and retinal nerve fiber layer changes are minimal in the early stages. 7 The most common visual field defects associated with ethambutol and linezolid are central and centro-caecal scotomas, 12 whereas bitemporal hemianopic scotomas are more commonly seen with isoniazid toxicity. 9 Timely detection of ATT-induced optic neuropathy is essential since sight-threatening complications can be reversed if the drug causing the toxicity is discontinued. The purpose of this study was to evaluate visual function in patients receiving ATT and to evaluate the visual field changes caused due to ATT. Methods This was a prospective observational study done in a tertiary health care center in South India, conducted from December 2020 to October 2022. The study was approved by the Institutional Ethics Committee (Kasturba Medical College, Mangalore, affiliated to Manipal Academy of Higher Education, Manipal, India, Approval No: IEC KMC MLR 12-2020/441) and abided by the tenets of the Helsinki Protocol. Inclusion criteria were patients above 15 years of age, newly diagnosed with TB who were to be started on anti-tubercular therapy. A written informed consent was taken from all the patients. Patients above 50 years of age, previously on Anti-Tubercular Therapy, patients with a previous history of retinal and optic nerve pathologies, diabetics, patients with renal dysfunction, those with previously documented visual field defects, patients with nutritional optic neuropathy, including vitamin B12 deficiency, and patients with TB arachnoiditis were excluded. Individuals over the age of 50 were excluded from the study, as the risk of glaucoma increases with age and may result in alterations to the visual field. The following tests were done at baseline (beginning of ATT) and at 6 months from the date of starting ATT. Baseline ocular examination which included best corrected visual acuity using Snellen chart and Jaeger chart, color vision using Ishihara plates (38 plates, 2021 edition), Slit lamp examination, IOP with Goldman Applanation Tonometer, Amsler grid, Dilated fundus examination using slit lamp biomicroscopy and indirect ophthalmoscopy, and Humphrey visual field analysis 30-2 were done. Patients were advised to continue with their ATT and to review immediately in case of any visual symptoms. The occurrence of any visual disturbances supported by diminished visual acuity, colour vision disturbances with or without visual field defects, was considered as toxic optic neuropathy. Visual evoked potential testing (pattern reversal VEP, black and white checkerboard pattern) was done to prove the diagnosis in patients suspected to have toxic optic neuropathy, and the drug responsible was identified and stopped. The data was analyzed using IBM SPSS version 25. The nominal variables-type of color vision and fields at baseline and follow-up were compared using the Mc Nemer test for nominal variables, whereas the visual acuity was compared at baseline and follow-up using the Wilcoxon sign rank test for ordinal variables. A p-value of <0.05 was considered significant for all analyses. Results A total of 48 patients participated in this study. 7 patients who were above the age of 50 years were excluded from the study. The mean age of the study population was 35.90 years ± 10.2 years. Among the 48 patients, 4 (8.3%) were 15-20 years of age, 13 (27%) in the age group of 21-30 years, and 8 (16.6%) in the age group of 31-40. Rest 23 (47.9%) patients are in the age group of 41-50 years.35 (72.9%) out of 48 were male and 13 (27.1%) were female. Of the total 48 patients included, 32(66.6%) patients had a diagnosis of pulmonary tuberculosis. Out of the 15 patients with extrapulmonary tuberculosis 4(8.3%) had disseminated tuberculosis, 4(8.3%) with TB lymphadenitis, 6(12.5%) with pleural effusion, 1(2.1%) with abdominal tuberculosis and 1(2.1%) with pott’s spine ( Figure 1 ). Figure 1. Pi chart showing various indications in the study population for receiving ATT. TB REGIMEN: MDR tuberculosis, mainly rifampicin-resistant tuberculosis was found in 27(56.3%) at the time of their diagnosis and the rest 21 (43.8%) were drug-sensitive. The average dosage of ethambutol received by the patients in our study was 20 mg/kg body weight for 6 months. The average dosage of INH(Isoniazid) was 5 mg/kg body weight for 6 months. Of the 27 with drug resistance, 25 patients were initiated on a shorter bedaquiline regimen and 3 on all oral longer MDR TB regimens ( Table 1 ). For the longer MDR TB regimen patients received Linezolid 600 mg for 6 months. Table 1. Treatment regimen followed among the study group. Sensitivity Drug sensitive MDR TB Rifampicin resistant Shorter bedaquiline Longer MDR TB regimen Number 21 22 2 3 Percentage 43.8% 45.8% 4.2% 6.3% Visual acuity at baseline for all the 48 patients included in the study was 6/6. 3(6.3%) out of 45 patients presented with visual complaints at 6 months. 1 patient (2.1%) had vision of 6/18 with the other two patients (4.2%) below 6/60 ( Table 2 ). Table 2. Visual acuity at baseline and at follow-up. Visual acuity baseline 6-month follow-up P value 6/6 48 (100%) 45 (93.8%) .102 6/18-6/9 0 0 6/36-6/18 0 1 (2.1%) <6/60 0 2 (4.2%) Color vision examination was normal in all 48 patients during baseline evaluation. 3(6.3%) developed color vision abnormalities at follow-up with all of them being red-green deficient ( Table 3 ). P value was 0.250 which is not significant. Table 3. Color vision at baseline and follow-up. Color vision baseline 6-month follow-up P value Normal 48 (100%) 45 (93.8%) .250 (NS) Red-green deficit 0 3 (6.3%) Anterior segment examination findings and IOP were normal in all patients at baseline and follow-up. Fundus examination was found to be within normal limits in all 48 patients at baseline. However, 3(6.3%) had abnormal findings at follow-up. 1(2.1%) had bilateral temporal disc pallor with the other two patients (4.2%) having bilateral hyperaemic disc. Visual fields at baseline for all 48 patients were normal. Out of the 45 patients with no visual complaints at 6-month follow-up, 4 (8.33%) showed peripheral field constriction. Out of the 8.33%, Constriction in one quadrant was observed in 2.1% whereas constriction in 2 quadrants was observed in 6.3%. 3(6.3%) patients developed visual symptoms during the treatment course, out of them, peripheral field constriction was noted in one patient (2.1%), one showed severe generalized depression of visual fields (2.1%) and the other patient had central scotoma (2.1%). p-value of 0.16 was calculated which was found to be significant ( Table 4 ). Table 4. Comparison of baseline visual field with 6month follow-up. Visual fields Baseline 6-month follow-up P value Normal 48 (100%) 41 (85.4%) .016 (sig) Central scotoma 0 1 (2.1%) Peripheral constriction in only 1 quadrant 0 1 (2.1%) Peripheral constriction in 2 quadrants 0 3 (6.3%) Peripheral constriction in all 4 quadrants 0 1 (2.1%) Severe generalized depression of visual fields 0 1 (2.1%) All three of these patients with visual complaints were on linezolid as part of their all-oral long bedaquiline regimen. The three patients with visual symptoms were immediately advised to stop the linezolid and even the TB center had been notified of the same. To confirm the diagnosis in the three patients with visual symptoms VEP and RNFL OCT was done which showed prolonged P100 latency and thinning of the RNFL layer. RNFL OCT and VEP were not done in the patients with only visual field abnormalities without any symptoms. The visual acuity, color vision, and visual field defects improved in two of the three patients within 1-2 months with the average being 1.5 months post-stopping linezolid. Visual symptoms of one patient however did not improve even after stopping linezolid which can be attributed to a longer duration of drug intake. Discussion Baseline visual acuity was normal in all patients; however, 3 (6.3%) patients complained of visual symptoms with 2 reported vision less than 6/60. This is similar to Garg et al, 13 at 8.69%, Ashraf et al, 14 at 10.6%, Panchal et al, 4 7.44%, and Goyal et al, 15 at 3.3% incidence of visual complaints. However, no patient in studies done by Saxena et al, 16 Menon et al, 17 Kandel et al, 18 Kim et al, 19 Jin et al, 8 had any visual complaints. Color vision abnormality was noted in 6.3% of our patients similar to 5.32% as seen in a study done by Panchal et al. 4 All patients in our study exhibited red-green color vision deficiency, as the Ishihara plates used do not detect blue-yellow color vision anomalies. Out of 48 people in our study on fundus examination, 4.2% had disc edema and 2.1% had temporal disc pallor. The findings in these patients were bilateral. Similar findings were noted by Panchal et al 4 who had 2.12% with bilateral disc edema and 2.12% with bilateral disc pallor. A study done by Ambika et al, 20 showed 44.14% with disc pallor and <1% showed disc edema. The incidence of visual field defects in our study was 14.6% with the value being significant (0.016). 2.1% had a peripheral constriction in all 4 quadrants, 2.1% with Severe generalized depression of visual fields, and 2.1% with central scotoma. In our study, 4 patients (8.3%) showed Peripheral field constriction in different quadrants making it the most common field defect similar to the study done by Ashraf et al, 14 in which 13.3% had field defects with 8.15% being peripheral field defects in different quadrants. However, visual field defects in patients receiving anti-tubercular therapy varied in different studies. Bitemporal field defects were observed by Kho et al 12 in his study, centro-caecal scotomas (2.12%) were observed by Panchal et al. 4 Garg et al 13 in their study concluded that 8.69% (8 eyes of 4 patients) with visual field defects with centro-caecal scotoma in one patient and the rest with peripheral constriction. Few studies like Kandel et al, 18 Kim et al, 19 Jin et al, 8 Saxena et al, 16 observed no visual field changes in any of their patients on anti-tubercular therapy. The higher incidence of MDR TB in our cohort could be because the study location is the District TB Center and referral center for drug resistant tuberculosis. The limitations of this study include that reaching a definite conclusion by extrapolation of results to the general population was not possible due to the small sample size. The patients were not followed up at shorter intervals, the accurate time of onset of the side effects could not be studied. Visual field defects caused by ATT can precede clinical symptoms. In our study only 6.3% of the patients presented with decreased vision, whereas 14.6% of the patients had subclinical visual field defects. Subclinical visual field abnormalities could be the first signs of impending optic neuropathy in patients receiving ATT. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where visual evoked potential testing and RNFL-OCT are not available. Patients on ATT should be regularly screened for ocular adverse effects preferably every month. Routine examinations like visual acuity, color vision, and fundus examination must be carried out to look for any subclinical effects of the treatment and monitor their progression. The limitations of the study are as follows. The study population is heterogeneous since all the newly diagnosed tuberculosis patients were included along with those having MDR TB. The patients received the medications according to their body weight. Since fixed drug combinations were prescribed, it is difficult to pinpoint the offending drug. Secondly, we did not compare the Mean deviation and Pattern standard deviation before and after the ATT was started, which could have given us the information regarding cumulative retinal sensitivity. Chest physicians, ophthalmologists, and healthcare workers need to be aware of potentially sight-threatening side effects of ATT. Prompt diagnosis and timely intervention are the keys to optimal visual outcomes in patients with toxic optic neuropathy due to ATT. Declarations Institutional Ethical Committee clearance for the study was obtained. Data availability Underlying data Open Science Framework: Visual field changes in patients receiving antitubercular therapy, https://doi.org/10.17605/OSF.IO/SAQMC . 21 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgments None References 1. Sandhu GK: Tuberculosis: Current situation, challenges, and overview of its control programs in India. J. Global Infect. Dis. 2011; 3 : 143–150. PubMed Abstract | Publisher Full Text | Free Full Text 2. Gupta V, Testi I, Agrawal R, et al. : Ocular tuberculosis: Where are we today? Indian J. Ophthalmol. 2020; 68 : 1808–1817. PubMed Abstract | Publisher Full Text | Free Full Text 3. Global TB Report 2022 Geneva World Health Organization. 2022. License CC BY-NC-SA 3.0 IGO. 4. Ministry of Health & Family Welfare-Government of India. Home: Central TB Division; [Accessed 16 Nov 2022]. Reference Source 5. Panchal K, Solu TM: Ocular side effects of anti-tubercular drugs in patients receiving Anti-Tb treatment at Tertiary Care Center. Int. J. Ocul. Oncol. Oculoplasty. 2020; 6 : 187–191. Publisher Full Text 6. Pezzella AT: History of pulmonary tuberculosis. Thorac. Surg. Clin. 2019; 29 : 1–17. Publisher Full Text 7. Kim YK, Hwang JM: Serial retinal nerve fiber layer changes in patients with toxic optic neuropathy associated with antituberculosis pharmacotherapy. J. Ocul. Pharmacol. Ther. 2009; 25 : 531–536. PubMed Abstract | Publisher Full Text 8. Jin KW, Lee JY, Rhiu S, et al. : Longitudinal evaluation of visual function and structure for detection of subclinical ethambutol-induced optic neuropathy. PLoS One. 2019; 14 (4): e0215297. PubMed Abstract | Publisher Full Text | Free Full Text 9. Sharma R, Sharma P: Toxic optic neuropathy. Indian J. Ophthalmol. 2011; 59 : 137–141. PubMed Abstract | Publisher Full Text | Free Full Text 10. Ommurugan B, Bhattacharjee D, Patil N: Isoniazid the culprit behind toxic optic neuropathy. Asian J. Pharm. Clin. Res. 2017; 10 : 1. Publisher Full Text 11. Libershteyn Y: Ethambutol/linezolid toxic optic neuropathy. Optom. Vis. Sci. 2016; 93 : 211–217. PubMed Abstract | Publisher Full Text 12. Kho RC, Al-Obailan M, Arnold AC: Bitemporal visual field defects in ethambutol-induced optic neuropathy. J. Neuroophthalmol. 2011; 31 : 121–126. PubMed Abstract | Publisher Full Text 13. Garg P, Garg R, Prasad R, et al. : A prospective study of ocular toxicity in patients receiving ethambutol as a part of directly observed treatment strategy therapy. Lung India. 2015; 32 : 16–19. PubMed Abstract | Publisher Full Text | Free Full Text 14. Mahrukh AA, Bhat MA: Visual field changes in patients receiving antitubercular drug therapy at tertiary care hospital: an analytical observational study. Int. J. Contemp. Med. Res. 2017; 4 : 346–349. 15. Goyal JL, Sarmi D, Singh NP, et al. : Evaluation of visual functions in patients on ethambutol therapy for tuberculosis: a prospective study. J. Commun. Dis. 2003; 35 : 230–243. PubMed Abstract 16. Mandal S, Saxena R, Dhiman R, et al. : Prospective study to evaluate incidence and indicators for early detection of ethambutol toxicity. Br. J. Ophthalmol. 2020; 105 : 1024–1028. 17. Menon V, Jain D, Saxena R, et al. : Prospective evaluation of visual function for early detection of ethambutol toxicity. Br. J. Ophthalmol. 2009; 93 : 1251–1254. PubMed Abstract | Publisher Full Text 18. Kandel H, Adhikari P, Shrestha GS, et al. : Visual function in patients on Ethambutol therapy for tuberculosis. J. Ocul. Pharmacol. Ther. 2012; 28 : 174–178. Publisher Full Text 19. Kim KL, Park SP: Visual function test for early detection of ethambutol induced ocular toxicity at the subclinical level. Cutan. Ocul. Toxicol. 2015; 35 : 228–232. 20. Ambika S, Kp L, Gopal M, et al. : Visual outcomes of toxic optic neuropathy secondary to Ethambutol: A retrospective observational study from India, an endemic country. Indian J. Ophthalmol. 2022; 70 : 3388. 21. Mendonca TM, et al. : Visual field changes in patients receiving antitubercular therapy. [Datatset]. Open Science Framework. 2024. Publisher Full Text Comments on this article Comments (0) Version 4 VERSION 4 PUBLISHED 01 Jul 2024 ADD YOUR COMMENT Comment Author details Author details 1 Department of Ophthalmology, Kasturba Medical College, Mangalore, India 2 Manipal Academy of Higher Education, Manipal, India Tejaswi Pagadala Roles: Data Curation, Writing – Original Draft Preparation Gurudutt Kamath Roles: Conceptualization, Supervision, Visualization Teena Mariet Mendonca Roles: Project Administration, Resources, Supervision, Writing – Review & Editing Gladys Rodrigues Roles: Methodology, Project Administration, Resources Ajay Kamath Roles: Supervision Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (4) version 4 Revised Published: 30 Jul 2025, 13:719 https://doi.org/10.12688/f1000research.149831.4 version 3 Revised Published: 26 Feb 2025, 13:719 https://doi.org/10.12688/f1000research.149831.3 version 2 Revised Published: 01 Aug 2024, 13:719 https://doi.org/10.12688/f1000research.149831.2 version 1 Published: 01 Jul 2024, 13:719 https://doi.org/10.12688/f1000research.149831.1 Copyright © 2025 Pagadala T et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Pagadala T, Kamath G, Mendonca TM et al. Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.12688/f1000research.149831.4 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 4 VERSION 4 PUBLISHED 30 Jul 2025 Revised Views 0 Cite How to cite this report: Plant GT. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.184006.r401598 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v4#referee-response-401598 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 25 Oct 2025 Gordon T Plant , University College London, London, UK Approved VIEWS 0 https://doi.org/10.5256/f1000research.184006.r401598 The authors have responded to my ... Continue reading READ ALL The authors have responded to my comments and corrections in a satifactory manner Competing Interests: No competing interests were disclosed. Reviewer Expertise: Neuro-Ophthalmology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Plant GT. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.184006.r401598 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v4#referee-response-401598 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Sitaula S. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.184006.r401599 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v4#referee-response-401599 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 23 Aug 2025 Sanjeeta Sitaula , Department of Ophthalmology, Tribhuvan University, Kirtipur, Central Development Region, Nepal Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.184006.r401599 Thank you for the authors responses. There are still a number of concerns in the study. 1. TB regimen- In MDR TB the authors have stated "27 with drug resistance, 25 patients were initiated on a shorter bedaquiline regimen ... Continue reading READ ALL Thank you for the authors responses. There are still a number of concerns in the study. 1. TB regimen- In MDR TB the authors have stated "27 with drug resistance, 25 patients were initiated on a shorter bedaquiline regimen and 3 on all oral longer MDR TB regimens" the total adds upto 28! The table 1 however shows 3 groups of MDR treatment- 1. MDR TB Rifampicin resistant 2. Shorter bedaquiline 3.Longer MDR TB regimen. The authors have stated that " longer MDR TB regimen patients received Linezolid 600 mg for 6 months." Did the other groups of MDR TB not receive Linezolid? Did any groups of treatment contain both ethambutol and linezolid? Please elaborate on the drugs used for different regimens of ATT. 2. Among the 3 patients with visual impairment, what was the average duration of ethambutol and or linezolid? Were the patients on only linezolid or both linezolid and ethambutol? Did none of the patient present prior to 6 month follow up for visual symptoms? 3. In the findings of RNFL OCT among the 3 patients with visual impairment- 2 cases had hyperemic discs where we would expect increase in RNFL thickness, rather that thinning. Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sitaula S. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.184006.r401599 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v4#referee-response-401599 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 3 VERSION 3 PUBLISHED 26 Feb 2025 Revised Views 0 Cite How to cite this report: Plant GT. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.177486.r387392 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v3#referee-response-387392 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 03 Jun 2025 Gordon T Plant , University College London, London, UK Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.177486.r387392 The study is addressing an important issue. Traditionally we have relied upon patients reporting visual symptoms as the trigger for taking action to avoid optic neuropathy. However if perimetry can be utilised to detect "preclinical" optic nerve damage this will ... Continue reading READ ALL The study is addressing an important issue. Traditionally we have relied upon patients reporting visual symptoms as the trigger for taking action to avoid optic neuropathy. However if perimetry can be utilised to detect "preclinical" optic nerve damage this will prevent permanent damage as it is clear that it is delay in management that gives rise to permanent damage Detailed comments: Page Para Line 1 4 6 should read: ? should read "whereas bitemporal hemianopic scotomas are more commonly seen with izoniazid toxicity" 1 5 "at the earliest" is vague. Is there any evidence regarding the incidence of full recovery related to the time since onset of symptoms? If not it would be helpful to say so here 1 7 What was the reason for excluding patients above 50? This should be stated. Also state how many such patients were excluded which edition of Ishihara? How many plates? "amp" typo "Visual evoked potential testing was done" Details of protocol must be provided It is surprising that all of the patients were 6/6! Was there a 6/5 line on the chart? "To confirm the diagnosis in the three patients with visual symptoms VEP and RNFL OCT was done which showed prolonged P100 latency and thinning of the RNFL layer." what about the patients with abnormal fields but no symptoms? Comment in discussion on blue/yellow deficiency. It is not possible to compare with the other study mentioned as the Ishihara test does not include a tritan plate. The patients in the study may have had blue/yellow dieficiency . Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? No Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Neuro-Ophthalmology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Plant GT. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.177486.r387392 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v3#referee-response-387392 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 11 Sep 2025 Teena Mariet Mendonca , ophthalmology, Kasturba Medical College Hospital Mangalore, Mangalore, India 11 Sep 2025 Author Response 1.Page Para Line 1 4 6 should read: ? should read "whereas bitemporal hemianopic scotomas are more commonly seen with isoniazid toxicity" Response: The correction has ... Continue reading 1.Page Para Line 1 4 6 should read: ? should read "whereas bitemporal hemianopic scotomas are more commonly seen with isoniazid toxicity" Response: The correction has been made. 2. 1 5 "at the earliest" is vague. Is there any evidence regarding the incidence of full recovery related to the time since onset of symptoms? If not it would be helpful to say so here Response: The word ‘earliest is omitted as there is no clear evidence regarding the incidence of full recovery related to the time since onset of the symptoms. 3. 1 7 What was the reason for excluding patients above 50? This should be stated. Also state how many such patients were excluded Response: Individuals over the age of 50 were excluded from the study, as the risk of glaucoma increases with age and may result in alterations to the visual field. 7 such patients were excluded. 4.which edition of Ishihara? How many plates? Response: 38 plates 2021 edition. 5."amp" typo Response: The error is corrected. 5."Visual evoked potential testing was done" Details of protocol must be provided Response: Pattern reversal VEP, black and white checkerboard pattern was done. 6.It is surprising that all of the patients were 6/6! Was there a 6/5 line on the chart? Response: The Snellen visual acuity chart(drum chart) which was used, did not have 6/5 line 7."To confirm the diagnosis in the three patients with visual symptoms VEP and RNFL OCT was done which showed prolonged P100 latency and thinning of the RNFL layer." What about the patients with abnormal fields but no symptoms? Response: RNFL OCT and VEP were not done for the patients who did not have symptoms and had visual field abnormalities because of financial constraints. 8.Comment in the discussion on blue/yellow deficiency. It is not possible to compare with the other study mentioned, as the Ishihara test does not include a tritan plate. The patients in the study may have had blue/yellow deficiency. Response: I agree with the reviewer. The patients in this study may have had blue-yellow abnormalities as Ishihara test doesn’t detect blue-yellow defects. I have omitted the comparison in the discussion. 1.Page Para Line 1 4 6 should read: ? should read "whereas bitemporal hemianopic scotomas are more commonly seen with isoniazid toxicity" Response: The correction has been made. 2. 1 5 "at the earliest" is vague. Is there any evidence regarding the incidence of full recovery related to the time since onset of symptoms? If not it would be helpful to say so here Response: The word ‘earliest is omitted as there is no clear evidence regarding the incidence of full recovery related to the time since onset of the symptoms. 3. 1 7 What was the reason for excluding patients above 50? This should be stated. Also state how many such patients were excluded Response: Individuals over the age of 50 were excluded from the study, as the risk of glaucoma increases with age and may result in alterations to the visual field. 7 such patients were excluded. 4.which edition of Ishihara? How many plates? Response: 38 plates 2021 edition. 5."amp" typo Response: The error is corrected. 5."Visual evoked potential testing was done" Details of protocol must be provided Response: Pattern reversal VEP, black and white checkerboard pattern was done. 6.It is surprising that all of the patients were 6/6! Was there a 6/5 line on the chart? Response: The Snellen visual acuity chart(drum chart) which was used, did not have 6/5 line 7."To confirm the diagnosis in the three patients with visual symptoms VEP and RNFL OCT was done which showed prolonged P100 latency and thinning of the RNFL layer." What about the patients with abnormal fields but no symptoms? Response: RNFL OCT and VEP were not done for the patients who did not have symptoms and had visual field abnormalities because of financial constraints. 8.Comment in the discussion on blue/yellow deficiency. It is not possible to compare with the other study mentioned, as the Ishihara test does not include a tritan plate. The patients in the study may have had blue/yellow deficiency. Response: I agree with the reviewer. The patients in this study may have had blue-yellow abnormalities as Ishihara test doesn’t detect blue-yellow defects. I have omitted the comparison in the discussion. Competing Interests: NIL Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 11 Sep 2025 Teena Mariet Mendonca , ophthalmology, Kasturba Medical College Hospital Mangalore, Mangalore, India 11 Sep 2025 Author Response 1.Page Para Line 1 4 6 should read: ? should read "whereas bitemporal hemianopic scotomas are more commonly seen with isoniazid toxicity" Response: The correction has ... Continue reading 1.Page Para Line 1 4 6 should read: ? should read "whereas bitemporal hemianopic scotomas are more commonly seen with isoniazid toxicity" Response: The correction has been made. 2. 1 5 "at the earliest" is vague. Is there any evidence regarding the incidence of full recovery related to the time since onset of symptoms? If not it would be helpful to say so here Response: The word ‘earliest is omitted as there is no clear evidence regarding the incidence of full recovery related to the time since onset of the symptoms. 3. 1 7 What was the reason for excluding patients above 50? This should be stated. Also state how many such patients were excluded Response: Individuals over the age of 50 were excluded from the study, as the risk of glaucoma increases with age and may result in alterations to the visual field. 7 such patients were excluded. 4.which edition of Ishihara? How many plates? Response: 38 plates 2021 edition. 5."amp" typo Response: The error is corrected. 5."Visual evoked potential testing was done" Details of protocol must be provided Response: Pattern reversal VEP, black and white checkerboard pattern was done. 6.It is surprising that all of the patients were 6/6! Was there a 6/5 line on the chart? Response: The Snellen visual acuity chart(drum chart) which was used, did not have 6/5 line 7."To confirm the diagnosis in the three patients with visual symptoms VEP and RNFL OCT was done which showed prolonged P100 latency and thinning of the RNFL layer." What about the patients with abnormal fields but no symptoms? Response: RNFL OCT and VEP were not done for the patients who did not have symptoms and had visual field abnormalities because of financial constraints. 8.Comment in the discussion on blue/yellow deficiency. It is not possible to compare with the other study mentioned, as the Ishihara test does not include a tritan plate. The patients in the study may have had blue/yellow deficiency. Response: I agree with the reviewer. The patients in this study may have had blue-yellow abnormalities as Ishihara test doesn’t detect blue-yellow defects. I have omitted the comparison in the discussion. 1.Page Para Line 1 4 6 should read: ? should read "whereas bitemporal hemianopic scotomas are more commonly seen with isoniazid toxicity" Response: The correction has been made. 2. 1 5 "at the earliest" is vague. Is there any evidence regarding the incidence of full recovery related to the time since onset of symptoms? If not it would be helpful to say so here Response: The word ‘earliest is omitted as there is no clear evidence regarding the incidence of full recovery related to the time since onset of the symptoms. 3. 1 7 What was the reason for excluding patients above 50? This should be stated. Also state how many such patients were excluded Response: Individuals over the age of 50 were excluded from the study, as the risk of glaucoma increases with age and may result in alterations to the visual field. 7 such patients were excluded. 4.which edition of Ishihara? How many plates? Response: 38 plates 2021 edition. 5."amp" typo Response: The error is corrected. 5."Visual evoked potential testing was done" Details of protocol must be provided Response: Pattern reversal VEP, black and white checkerboard pattern was done. 6.It is surprising that all of the patients were 6/6! Was there a 6/5 line on the chart? Response: The Snellen visual acuity chart(drum chart) which was used, did not have 6/5 line 7."To confirm the diagnosis in the three patients with visual symptoms VEP and RNFL OCT was done which showed prolonged P100 latency and thinning of the RNFL layer." What about the patients with abnormal fields but no symptoms? Response: RNFL OCT and VEP were not done for the patients who did not have symptoms and had visual field abnormalities because of financial constraints. 8.Comment in the discussion on blue/yellow deficiency. It is not possible to compare with the other study mentioned, as the Ishihara test does not include a tritan plate. The patients in the study may have had blue/yellow deficiency. Response: I agree with the reviewer. The patients in this study may have had blue-yellow abnormalities as Ishihara test doesn’t detect blue-yellow defects. I have omitted the comparison in the discussion. Competing Interests: NIL Close Report a concern COMMENT ON THIS REPORT Version 2 VERSION 2 PUBLISHED 01 Aug 2024 Revised Views 0 Cite How to cite this report: Sitaula S. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.169511.r343804 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v2#referee-response-343804 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 27 Dec 2024 Sanjeeta Sitaula , Department of Ophthalmology, Tribhuvan University, Kirtipur, Central Development Region, Nepal Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.169511.r343804 The authors have highlighted an important topic of ATT induced visual field changes. However, there are a few comments. 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR ... Continue reading READ ALL The authors have highlighted an important topic of ATT induced visual field changes. However, there are a few comments. 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR TB. TB induced optic neuropathy are reported by ethambutol, isoniazid and linezolid. It is not clear in the study what was the average dose and duration of each of the drugs, whether more than one of the drugs were being used, and which drug was suspected to cause toxicity in the study. 2. How was toxic optic neuropathy defined in the study? 3. Were changes in Mean Deviation / Pattern Standard Deviation noted in Humphrey visual field 30-2 in patients before and after ATT? 4. What was the cause for changes in visual field of 4 other patients with no visual complaints? Was further testing like VEP or OCT done? Was ATT stopped? Did the changes improve? Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sitaula S. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.169511.r343804 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v2#referee-response-343804 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 26 Feb 2025 Teena Mariet Mendonca , ophthalmology, Kasturba Medical College Hospital Mangalore, Mangalore, India 26 Feb 2025 Author Response Reviewer Comments: 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR TB. TB induced optic neuropathy are reported by ethambutol, isoniazid ... Continue reading Reviewer Comments: 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR TB. TB induced optic neuropathy are reported by ethambutol, isoniazid and linezolid. It is not clear in the study what was the average dose and duration of each of the drugs, whether more than one of the drugs were being used, and which drug was suspected to cause toxicity in the study. Response: We agree that the study population is heterogeneous since we included all the newly diagnosed patients in the study during the study time period. The dosage of each drug was based on their weight. The average dosage of INH was 5mg/KG once daily, Ethambutol was 20mg/kg once daily and Linezolid was 600 mg once daily. The standard TB regimen was followed. Whenever toxicity was suspected ethambutol and INH was stopped. In addition to these drugs Linezolid was stopped in MDR cases. Reviewer Comments: 2. How was toxic optic neuropathy defined in the study? Response: The occurrence of any visual disturbances supported by diminished visual acuity or color vision disturbances with or without visual field defects was considered toxic optic neuropathy. Since the objective of the study was to study the visual field defects associated with ATT, patients were followed up only at 6 months post-ATT unless visual complaints were reported by the patient. The patients who had visual symptoms were further subjected to VEP to prove the diagnosis. Reviewer Comments: 3. Were changes in mean deviation / Pattern Standard Deviation noted in Humphrey visual field 30-2 in patients before and after ATT? Response: We did not do the comparison of MD/PSD. This is one of the limitations of the study. Thank you for bringing out the flaw, we have included it in limitations of the study. Reviewer Comments: 4. What was the cause for changes in the visual field of 4 other patients with no visual complaints? Was further testing like VEP or OCT done? Was ATT stopped? Did the changes improve? Response: The changes in visual field of 4 patients who had no visual symptoms could be because of subclinical visual field defects associated with ATT. Since the patients take fixed drug combinations, it is not possible to pinpoint the offending drug. VEP showed a normal response in those patients. Since we diagnosed subclinical visual field defects only after completion of ATT (according to the study design), patients had already stopped the drugs. Reviewer Comments: 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR TB. TB induced optic neuropathy are reported by ethambutol, isoniazid and linezolid. It is not clear in the study what was the average dose and duration of each of the drugs, whether more than one of the drugs were being used, and which drug was suspected to cause toxicity in the study. Response: We agree that the study population is heterogeneous since we included all the newly diagnosed patients in the study during the study time period. The dosage of each drug was based on their weight. The average dosage of INH was 5mg/KG once daily, Ethambutol was 20mg/kg once daily and Linezolid was 600 mg once daily. The standard TB regimen was followed. Whenever toxicity was suspected ethambutol and INH was stopped. In addition to these drugs Linezolid was stopped in MDR cases. Reviewer Comments: 2. How was toxic optic neuropathy defined in the study? Response: The occurrence of any visual disturbances supported by diminished visual acuity or color vision disturbances with or without visual field defects was considered toxic optic neuropathy. Since the objective of the study was to study the visual field defects associated with ATT, patients were followed up only at 6 months post-ATT unless visual complaints were reported by the patient. The patients who had visual symptoms were further subjected to VEP to prove the diagnosis. Reviewer Comments: 3. Were changes in mean deviation / Pattern Standard Deviation noted in Humphrey visual field 30-2 in patients before and after ATT? Response: We did not do the comparison of MD/PSD. This is one of the limitations of the study. Thank you for bringing out the flaw, we have included it in limitations of the study. Reviewer Comments: 4. What was the cause for changes in the visual field of 4 other patients with no visual complaints? Was further testing like VEP or OCT done? Was ATT stopped? Did the changes improve? Response: The changes in visual field of 4 patients who had no visual symptoms could be because of subclinical visual field defects associated with ATT. Since the patients take fixed drug combinations, it is not possible to pinpoint the offending drug. VEP showed a normal response in those patients. Since we diagnosed subclinical visual field defects only after completion of ATT (according to the study design), patients had already stopped the drugs. Competing Interests: NIL Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 26 Feb 2025 Teena Mariet Mendonca , ophthalmology, Kasturba Medical College Hospital Mangalore, Mangalore, India 26 Feb 2025 Author Response Reviewer Comments: 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR TB. TB induced optic neuropathy are reported by ethambutol, isoniazid ... Continue reading Reviewer Comments: 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR TB. TB induced optic neuropathy are reported by ethambutol, isoniazid and linezolid. It is not clear in the study what was the average dose and duration of each of the drugs, whether more than one of the drugs were being used, and which drug was suspected to cause toxicity in the study. Response: We agree that the study population is heterogeneous since we included all the newly diagnosed patients in the study during the study time period. The dosage of each drug was based on their weight. The average dosage of INH was 5mg/KG once daily, Ethambutol was 20mg/kg once daily and Linezolid was 600 mg once daily. The standard TB regimen was followed. Whenever toxicity was suspected ethambutol and INH was stopped. In addition to these drugs Linezolid was stopped in MDR cases. Reviewer Comments: 2. How was toxic optic neuropathy defined in the study? Response: The occurrence of any visual disturbances supported by diminished visual acuity or color vision disturbances with or without visual field defects was considered toxic optic neuropathy. Since the objective of the study was to study the visual field defects associated with ATT, patients were followed up only at 6 months post-ATT unless visual complaints were reported by the patient. The patients who had visual symptoms were further subjected to VEP to prove the diagnosis. Reviewer Comments: 3. Were changes in mean deviation / Pattern Standard Deviation noted in Humphrey visual field 30-2 in patients before and after ATT? Response: We did not do the comparison of MD/PSD. This is one of the limitations of the study. Thank you for bringing out the flaw, we have included it in limitations of the study. Reviewer Comments: 4. What was the cause for changes in the visual field of 4 other patients with no visual complaints? Was further testing like VEP or OCT done? Was ATT stopped? Did the changes improve? Response: The changes in visual field of 4 patients who had no visual symptoms could be because of subclinical visual field defects associated with ATT. Since the patients take fixed drug combinations, it is not possible to pinpoint the offending drug. VEP showed a normal response in those patients. Since we diagnosed subclinical visual field defects only after completion of ATT (according to the study design), patients had already stopped the drugs. Reviewer Comments: 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR TB. TB induced optic neuropathy are reported by ethambutol, isoniazid and linezolid. It is not clear in the study what was the average dose and duration of each of the drugs, whether more than one of the drugs were being used, and which drug was suspected to cause toxicity in the study. Response: We agree that the study population is heterogeneous since we included all the newly diagnosed patients in the study during the study time period. The dosage of each drug was based on their weight. The average dosage of INH was 5mg/KG once daily, Ethambutol was 20mg/kg once daily and Linezolid was 600 mg once daily. The standard TB regimen was followed. Whenever toxicity was suspected ethambutol and INH was stopped. In addition to these drugs Linezolid was stopped in MDR cases. Reviewer Comments: 2. How was toxic optic neuropathy defined in the study? Response: The occurrence of any visual disturbances supported by diminished visual acuity or color vision disturbances with or without visual field defects was considered toxic optic neuropathy. Since the objective of the study was to study the visual field defects associated with ATT, patients were followed up only at 6 months post-ATT unless visual complaints were reported by the patient. The patients who had visual symptoms were further subjected to VEP to prove the diagnosis. Reviewer Comments: 3. Were changes in mean deviation / Pattern Standard Deviation noted in Humphrey visual field 30-2 in patients before and after ATT? Response: We did not do the comparison of MD/PSD. This is one of the limitations of the study. Thank you for bringing out the flaw, we have included it in limitations of the study. Reviewer Comments: 4. What was the cause for changes in the visual field of 4 other patients with no visual complaints? Was further testing like VEP or OCT done? Was ATT stopped? Did the changes improve? Response: The changes in visual field of 4 patients who had no visual symptoms could be because of subclinical visual field defects associated with ATT. Since the patients take fixed drug combinations, it is not possible to pinpoint the offending drug. VEP showed a normal response in those patients. Since we diagnosed subclinical visual field defects only after completion of ATT (according to the study design), patients had already stopped the drugs. Competing Interests: NIL Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 01 Jul 2024 Views 0 Cite How to cite this report: Mahesh KV. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.164337.r298163 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v1#referee-response-298163 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 Jul 2024 Karthik Vinay Mahesh , Department of Neurology, PGIMER, Chandigarh, Chandigarh, India Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.164337.r298163 The authors look into an important field of drug induced optic neuropathy in patients of tuberculosis, which is a public health concern. However, there are several shortcomings in the methodology 1.) The most important factor is the offending ... Continue reading READ ALL The authors look into an important field of drug induced optic neuropathy in patients of tuberculosis, which is a public health concern. However, there are several shortcomings in the methodology 1.) The most important factor is the offending drug, Ethambutol being the most common needs special mention regarding its dosage / Kg body weight and duration of intake before visual symptoms 2) The incidence of visual field defects should be treated as signs of optic neuropathy not just decrease in visual acuity as its based on central field of vision which is the last to go. 3)The other important comorbidities like diabetes/ old age/ renal dysfunction/ Vit- B12 deficiency and tb arachnoiditis with optic neuropathy should be ruled out 4) the inclusion criteria of the study is not mentioned, the study has very high no. of patients taking MDR regimen/ Bedaquiline. which is very high for the population. 5) The citations are incorrect. " TB affects 1/3rd of world population " source has been mentioned by an article on Ocular TB by V Gupta et al. The references need to substantiate the content which the authors are quoting. 6) The study needs major revisions with manuscript writing methodology. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? No Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Areas of intrest is Neurology. Neuro-ophthalmology and neuroinfections I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Mahesh KV. Reviewer Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.164337.r298163 ) The direct URL for this report is: https://f1000research.com/articles/13-719/v1#referee-response-298163 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 01 Aug 2024 Teena Mariet Mendonca , ophthalmology, Kasturba Medical College Hospital Mangalore, Mangalore, India 01 Aug 2024 Author Response Reviewer Comment: The authors look into an important field of drug-induced optic neuropathy in patients of tuberculosis, which is a public health concern. 1.) The most important factor is ... Continue reading Reviewer Comment: The authors look into an important field of drug-induced optic neuropathy in patients of tuberculosis, which is a public health concern. 1.) The most important factor is the offending drug, Ethambutol being the most common needs special mention regarding its dosage / Kg body weight and duration of intake before visual symptoms Author Response: The average dosage of ethambutol received by the patients in our study was 20mg/kg body weight for 6 months. However, all oral longer MDR TB regimen patients received Linezolid 600 mg for 6 months. Since all the patients were assessed at 6 months, the duration of drug intake in the study cohort was 6 months. 45 out of 48 patients had no visual symptoms during treatment. 3 patients presented with blurred vision at the end of 6 months. Reviewer Comment: 2) The incidence of visual field defects should be treated as signs of optic neuropathy not just decrease in visual acuity as its based on central field of vision which is the last to go. Author Response: We agree with the reviewer. The message we want to convey to the reader is subclinical visual field defects could be the first sign of impending optic neuropathy in patients receiving ATT. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where visual evoked potential testing and RNFL-OCT are not available. Reviewer Comment: 3)The other important comorbidities like diabetes/ old age/ renal dysfunction/ Vit- B12 deficiency and tb arachnoiditis with optic neuropathy should be ruled out Author Response: We have excluded patients under the age of 15 and above 50 years of age. All the conditions causing retinal pathology/optic neuropathy such as diabetics, patients with renal dysfunction, those with previously documented visual field defects, patients with nutrional optic neuropathy including vitamin B12 deficiency and patients with TB arachnoiditis and patients with previously treated TB. The suggested changes have been made in the article. Reviewer Comment: 4) the inclusion criteria of the study is not mentioned, the study has very high no. of patients taking MDR regimen/ Bedaquiline. which is very high for the population. Author Response: Inclusion criteria has been mentioned in the article. Our center is district TB center which is a nodal center for TB control and referral center for drug resistant TB. Hence probably the the number of MDR cases are high. Reviewer Comment: 5) The citations are incorrect. " TB affects 1/3rd of world population " source has been mentioned by an article on Ocular TB by V Gupta et al. The references need to substantiate the content which the authors are quoting. Author Response: As per the reviewer’s suggestion I have made correction in the text as well as the reference. Reviewer Comment: 6) The study needs major revisions with manuscript writing methodology. Author Response: Our best attempt to revise the manuscript has been made Reviewer Comment: The authors look into an important field of drug-induced optic neuropathy in patients of tuberculosis, which is a public health concern. 1.) The most important factor is the offending drug, Ethambutol being the most common needs special mention regarding its dosage / Kg body weight and duration of intake before visual symptoms Author Response: The average dosage of ethambutol received by the patients in our study was 20mg/kg body weight for 6 months. However, all oral longer MDR TB regimen patients received Linezolid 600 mg for 6 months. Since all the patients were assessed at 6 months, the duration of drug intake in the study cohort was 6 months. 45 out of 48 patients had no visual symptoms during treatment. 3 patients presented with blurred vision at the end of 6 months. Reviewer Comment: 2) The incidence of visual field defects should be treated as signs of optic neuropathy not just decrease in visual acuity as its based on central field of vision which is the last to go. Author Response: We agree with the reviewer. The message we want to convey to the reader is subclinical visual field defects could be the first sign of impending optic neuropathy in patients receiving ATT. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where visual evoked potential testing and RNFL-OCT are not available. Reviewer Comment: 3)The other important comorbidities like diabetes/ old age/ renal dysfunction/ Vit- B12 deficiency and tb arachnoiditis with optic neuropathy should be ruled out Author Response: We have excluded patients under the age of 15 and above 50 years of age. All the conditions causing retinal pathology/optic neuropathy such as diabetics, patients with renal dysfunction, those with previously documented visual field defects, patients with nutrional optic neuropathy including vitamin B12 deficiency and patients with TB arachnoiditis and patients with previously treated TB. The suggested changes have been made in the article. Reviewer Comment: 4) the inclusion criteria of the study is not mentioned, the study has very high no. of patients taking MDR regimen/ Bedaquiline. which is very high for the population. Author Response: Inclusion criteria has been mentioned in the article. Our center is district TB center which is a nodal center for TB control and referral center for drug resistant TB. Hence probably the the number of MDR cases are high. Reviewer Comment: 5) The citations are incorrect. " TB affects 1/3rd of world population " source has been mentioned by an article on Ocular TB by V Gupta et al. The references need to substantiate the content which the authors are quoting. Author Response: As per the reviewer’s suggestion I have made correction in the text as well as the reference. Reviewer Comment: 6) The study needs major revisions with manuscript writing methodology. Author Response: Our best attempt to revise the manuscript has been made Competing Interests: NIL Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 01 Aug 2024 Teena Mariet Mendonca , ophthalmology, Kasturba Medical College Hospital Mangalore, Mangalore, India 01 Aug 2024 Author Response Reviewer Comment: The authors look into an important field of drug-induced optic neuropathy in patients of tuberculosis, which is a public health concern. 1.) The most important factor is ... Continue reading Reviewer Comment: The authors look into an important field of drug-induced optic neuropathy in patients of tuberculosis, which is a public health concern. 1.) The most important factor is the offending drug, Ethambutol being the most common needs special mention regarding its dosage / Kg body weight and duration of intake before visual symptoms Author Response: The average dosage of ethambutol received by the patients in our study was 20mg/kg body weight for 6 months. However, all oral longer MDR TB regimen patients received Linezolid 600 mg for 6 months. Since all the patients were assessed at 6 months, the duration of drug intake in the study cohort was 6 months. 45 out of 48 patients had no visual symptoms during treatment. 3 patients presented with blurred vision at the end of 6 months. Reviewer Comment: 2) The incidence of visual field defects should be treated as signs of optic neuropathy not just decrease in visual acuity as its based on central field of vision which is the last to go. Author Response: We agree with the reviewer. The message we want to convey to the reader is subclinical visual field defects could be the first sign of impending optic neuropathy in patients receiving ATT. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where visual evoked potential testing and RNFL-OCT are not available. Reviewer Comment: 3)The other important comorbidities like diabetes/ old age/ renal dysfunction/ Vit- B12 deficiency and tb arachnoiditis with optic neuropathy should be ruled out Author Response: We have excluded patients under the age of 15 and above 50 years of age. All the conditions causing retinal pathology/optic neuropathy such as diabetics, patients with renal dysfunction, those with previously documented visual field defects, patients with nutrional optic neuropathy including vitamin B12 deficiency and patients with TB arachnoiditis and patients with previously treated TB. The suggested changes have been made in the article. Reviewer Comment: 4) the inclusion criteria of the study is not mentioned, the study has very high no. of patients taking MDR regimen/ Bedaquiline. which is very high for the population. Author Response: Inclusion criteria has been mentioned in the article. Our center is district TB center which is a nodal center for TB control and referral center for drug resistant TB. Hence probably the the number of MDR cases are high. Reviewer Comment: 5) The citations are incorrect. " TB affects 1/3rd of world population " source has been mentioned by an article on Ocular TB by V Gupta et al. The references need to substantiate the content which the authors are quoting. Author Response: As per the reviewer’s suggestion I have made correction in the text as well as the reference. Reviewer Comment: 6) The study needs major revisions with manuscript writing methodology. Author Response: Our best attempt to revise the manuscript has been made Reviewer Comment: The authors look into an important field of drug-induced optic neuropathy in patients of tuberculosis, which is a public health concern. 1.) The most important factor is the offending drug, Ethambutol being the most common needs special mention regarding its dosage / Kg body weight and duration of intake before visual symptoms Author Response: The average dosage of ethambutol received by the patients in our study was 20mg/kg body weight for 6 months. However, all oral longer MDR TB regimen patients received Linezolid 600 mg for 6 months. Since all the patients were assessed at 6 months, the duration of drug intake in the study cohort was 6 months. 45 out of 48 patients had no visual symptoms during treatment. 3 patients presented with blurred vision at the end of 6 months. Reviewer Comment: 2) The incidence of visual field defects should be treated as signs of optic neuropathy not just decrease in visual acuity as its based on central field of vision which is the last to go. Author Response: We agree with the reviewer. The message we want to convey to the reader is subclinical visual field defects could be the first sign of impending optic neuropathy in patients receiving ATT. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where visual evoked potential testing and RNFL-OCT are not available. Reviewer Comment: 3)The other important comorbidities like diabetes/ old age/ renal dysfunction/ Vit- B12 deficiency and tb arachnoiditis with optic neuropathy should be ruled out Author Response: We have excluded patients under the age of 15 and above 50 years of age. All the conditions causing retinal pathology/optic neuropathy such as diabetics, patients with renal dysfunction, those with previously documented visual field defects, patients with nutrional optic neuropathy including vitamin B12 deficiency and patients with TB arachnoiditis and patients with previously treated TB. The suggested changes have been made in the article. Reviewer Comment: 4) the inclusion criteria of the study is not mentioned, the study has very high no. of patients taking MDR regimen/ Bedaquiline. which is very high for the population. Author Response: Inclusion criteria has been mentioned in the article. Our center is district TB center which is a nodal center for TB control and referral center for drug resistant TB. Hence probably the the number of MDR cases are high. Reviewer Comment: 5) The citations are incorrect. " TB affects 1/3rd of world population " source has been mentioned by an article on Ocular TB by V Gupta et al. The references need to substantiate the content which the authors are quoting. Author Response: As per the reviewer’s suggestion I have made correction in the text as well as the reference. Reviewer Comment: 6) The study needs major revisions with manuscript writing methodology. Author Response: Our best attempt to revise the manuscript has been made Competing Interests: NIL Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 4 VERSION 4 PUBLISHED 01 Jul 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 4 (revision) 30 Jul 25 read read Version 3 (revision) 26 Feb 25 read Version 2 (revision) 01 Aug 24 read Version 1 01 Jul 24 read Karthik Vinay Mahesh , PGIMER, Chandigarh, India Sanjeeta Sitaula , Tribhuvan University, Kirtipur, Nepal Gordon T Plant , University College London, London, UK Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Plant G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 25 Oct 2025 | for Version 4 Gordon T Plant , University College London, London, UK 0 Views copyright © 2025 Plant G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors have responded to my comments and corrections in a satifactory manner Competing Interests No competing interests were disclosed. Reviewer Expertise Neuro-Ophthalmology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Plant GT. Peer Review Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.184006.r401598) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-719/v4#referee-response-401598 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Sitaula S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 23 Aug 2025 | for Version 4 Sanjeeta Sitaula , Department of Ophthalmology, Tribhuvan University, Kirtipur, Central Development Region, Nepal 0 Views copyright © 2025 Sitaula S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Thank you for the authors responses. There are still a number of concerns in the study. 1. TB regimen- In MDR TB the authors have stated "27 with drug resistance, 25 patients were initiated on a shorter bedaquiline regimen and 3 on all oral longer MDR TB regimens" the total adds upto 28! The table 1 however shows 3 groups of MDR treatment- 1. MDR TB Rifampicin resistant 2. Shorter bedaquiline 3.Longer MDR TB regimen. The authors have stated that " longer MDR TB regimen patients received Linezolid 600 mg for 6 months." Did the other groups of MDR TB not receive Linezolid? Did any groups of treatment contain both ethambutol and linezolid? Please elaborate on the drugs used for different regimens of ATT. 2. Among the 3 patients with visual impairment, what was the average duration of ethambutol and or linezolid? Were the patients on only linezolid or both linezolid and ethambutol? Did none of the patient present prior to 6 month follow up for visual symptoms? 3. In the findings of RNFL OCT among the 3 patients with visual impairment- 2 cases had hyperemic discs where we would expect increase in RNFL thickness, rather that thinning. Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Sitaula S. Peer Review Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.184006.r401599) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-719/v4#referee-response-401599 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Plant G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 03 Jun 2025 | for Version 3 Gordon T Plant , University College London, London, UK 0 Views copyright © 2025 Plant G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The study is addressing an important issue. Traditionally we have relied upon patients reporting visual symptoms as the trigger for taking action to avoid optic neuropathy. However if perimetry can be utilised to detect "preclinical" optic nerve damage this will prevent permanent damage as it is clear that it is delay in management that gives rise to permanent damage Detailed comments: Page Para Line 1 4 6 should read: ? should read "whereas bitemporal hemianopic scotomas are more commonly seen with izoniazid toxicity" 1 5 "at the earliest" is vague. Is there any evidence regarding the incidence of full recovery related to the time since onset of symptoms? If not it would be helpful to say so here 1 7 What was the reason for excluding patients above 50? This should be stated. Also state how many such patients were excluded which edition of Ishihara? How many plates? "amp" typo "Visual evoked potential testing was done" Details of protocol must be provided It is surprising that all of the patients were 6/6! Was there a 6/5 line on the chart? "To confirm the diagnosis in the three patients with visual symptoms VEP and RNFL OCT was done which showed prolonged P100 latency and thinning of the RNFL layer." what about the patients with abnormal fields but no symptoms? Comment in discussion on blue/yellow deficiency. It is not possible to compare with the other study mentioned as the Ishihara test does not include a tritan plate. The patients in the study may have had blue/yellow dieficiency . Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? No Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Neuro-Ophthalmology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 11 Sep 2025 Teena Mariet Mendonca, ophthalmology, Kasturba Medical College Hospital Mangalore, Mangalore, India 1.Page Para Line 1 4 6 should read: ? should read "whereas bitemporal hemianopic scotomas are more commonly seen with isoniazid toxicity" Response: The correction has been made. 2. 1 5 "at the earliest" is vague. Is there any evidence regarding the incidence of full recovery related to the time since onset of symptoms? If not it would be helpful to say so here Response: The word ‘earliest is omitted as there is no clear evidence regarding the incidence of full recovery related to the time since onset of the symptoms. 3. 1 7 What was the reason for excluding patients above 50? This should be stated. Also state how many such patients were excluded Response: Individuals over the age of 50 were excluded from the study, as the risk of glaucoma increases with age and may result in alterations to the visual field. 7 such patients were excluded. 4.which edition of Ishihara? How many plates? Response: 38 plates 2021 edition. 5."amp" typo Response: The error is corrected. 5."Visual evoked potential testing was done" Details of protocol must be provided Response: Pattern reversal VEP, black and white checkerboard pattern was done. 6.It is surprising that all of the patients were 6/6! Was there a 6/5 line on the chart? Response: The Snellen visual acuity chart(drum chart) which was used, did not have 6/5 line 7."To confirm the diagnosis in the three patients with visual symptoms VEP and RNFL OCT was done which showed prolonged P100 latency and thinning of the RNFL layer." What about the patients with abnormal fields but no symptoms? Response: RNFL OCT and VEP were not done for the patients who did not have symptoms and had visual field abnormalities because of financial constraints. 8.Comment in the discussion on blue/yellow deficiency. It is not possible to compare with the other study mentioned, as the Ishihara test does not include a tritan plate. The patients in the study may have had blue/yellow deficiency. Response: I agree with the reviewer. The patients in this study may have had blue-yellow abnormalities as Ishihara test doesn’t detect blue-yellow defects. I have omitted the comparison in the discussion. View more View less Competing Interests NIL reply Respond Report a concern Plant GT. Peer Review Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.177486.r387392) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-719/v3#referee-response-387392 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Sitaula S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 27 Dec 2024 | for Version 2 Sanjeeta Sitaula , Department of Ophthalmology, Tribhuvan University, Kirtipur, Central Development Region, Nepal 0 Views copyright © 2024 Sitaula S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors have highlighted an important topic of ATT induced visual field changes. However, there are a few comments. 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR TB. TB induced optic neuropathy are reported by ethambutol, isoniazid and linezolid. It is not clear in the study what was the average dose and duration of each of the drugs, whether more than one of the drugs were being used, and which drug was suspected to cause toxicity in the study. 2. How was toxic optic neuropathy defined in the study? 3. Were changes in Mean Deviation / Pattern Standard Deviation noted in Humphrey visual field 30-2 in patients before and after ATT? 4. What was the cause for changes in visual field of 4 other patients with no visual complaints? Was further testing like VEP or OCT done? Was ATT stopped? Did the changes improve? Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 26 Feb 2025 Teena Mariet Mendonca, ophthalmology, Kasturba Medical College Hospital Mangalore, Mangalore, India Reviewer Comments: 1. The study population is heterogenous with some patients receiving ATT for drug sensitive TB and some MDR TB. TB induced optic neuropathy are reported by ethambutol, isoniazid and linezolid. It is not clear in the study what was the average dose and duration of each of the drugs, whether more than one of the drugs were being used, and which drug was suspected to cause toxicity in the study. Response: We agree that the study population is heterogeneous since we included all the newly diagnosed patients in the study during the study time period. The dosage of each drug was based on their weight. The average dosage of INH was 5mg/KG once daily, Ethambutol was 20mg/kg once daily and Linezolid was 600 mg once daily. The standard TB regimen was followed. Whenever toxicity was suspected ethambutol and INH was stopped. In addition to these drugs Linezolid was stopped in MDR cases. Reviewer Comments: 2. How was toxic optic neuropathy defined in the study? Response: The occurrence of any visual disturbances supported by diminished visual acuity or color vision disturbances with or without visual field defects was considered toxic optic neuropathy. Since the objective of the study was to study the visual field defects associated with ATT, patients were followed up only at 6 months post-ATT unless visual complaints were reported by the patient. The patients who had visual symptoms were further subjected to VEP to prove the diagnosis. Reviewer Comments: 3. Were changes in mean deviation / Pattern Standard Deviation noted in Humphrey visual field 30-2 in patients before and after ATT? Response: We did not do the comparison of MD/PSD. This is one of the limitations of the study. Thank you for bringing out the flaw, we have included it in limitations of the study. Reviewer Comments: 4. What was the cause for changes in the visual field of 4 other patients with no visual complaints? Was further testing like VEP or OCT done? Was ATT stopped? Did the changes improve? Response: The changes in visual field of 4 patients who had no visual symptoms could be because of subclinical visual field defects associated with ATT. Since the patients take fixed drug combinations, it is not possible to pinpoint the offending drug. VEP showed a normal response in those patients. Since we diagnosed subclinical visual field defects only after completion of ATT (according to the study design), patients had already stopped the drugs. View more View less Competing Interests NIL reply Respond Report a concern Sitaula S. Peer Review Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.169511.r343804) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-719/v2#referee-response-343804 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Mahesh K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 12 Jul 2024 | for Version 1 Karthik Vinay Mahesh , Department of Neurology, PGIMER, Chandigarh, Chandigarh, India 0 Views copyright © 2024 Mahesh K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors look into an important field of drug induced optic neuropathy in patients of tuberculosis, which is a public health concern. However, there are several shortcomings in the methodology 1.) The most important factor is the offending drug, Ethambutol being the most common needs special mention regarding its dosage / Kg body weight and duration of intake before visual symptoms 2) The incidence of visual field defects should be treated as signs of optic neuropathy not just decrease in visual acuity as its based on central field of vision which is the last to go. 3)The other important comorbidities like diabetes/ old age/ renal dysfunction/ Vit- B12 deficiency and tb arachnoiditis with optic neuropathy should be ruled out 4) the inclusion criteria of the study is not mentioned, the study has very high no. of patients taking MDR regimen/ Bedaquiline. which is very high for the population. 5) The citations are incorrect. " TB affects 1/3rd of world population " source has been mentioned by an article on Ocular TB by V Gupta et al. The references need to substantiate the content which the authors are quoting. 6) The study needs major revisions with manuscript writing methodology. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? No Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Areas of intrest is Neurology. Neuro-ophthalmology and neuroinfections I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 01 Aug 2024 Teena Mariet Mendonca, ophthalmology, Kasturba Medical College Hospital Mangalore, Mangalore, India Reviewer Comment: The authors look into an important field of drug-induced optic neuropathy in patients of tuberculosis, which is a public health concern. 1.) The most important factor is the offending drug, Ethambutol being the most common needs special mention regarding its dosage / Kg body weight and duration of intake before visual symptoms Author Response: The average dosage of ethambutol received by the patients in our study was 20mg/kg body weight for 6 months. However, all oral longer MDR TB regimen patients received Linezolid 600 mg for 6 months. Since all the patients were assessed at 6 months, the duration of drug intake in the study cohort was 6 months. 45 out of 48 patients had no visual symptoms during treatment. 3 patients presented with blurred vision at the end of 6 months. Reviewer Comment: 2) The incidence of visual field defects should be treated as signs of optic neuropathy not just decrease in visual acuity as its based on central field of vision which is the last to go. Author Response: We agree with the reviewer. The message we want to convey to the reader is subclinical visual field defects could be the first sign of impending optic neuropathy in patients receiving ATT. Visual field evaluation can be an important tool for the early detection of optic neuropathy in patients receiving ATT in clinical settings where visual evoked potential testing and RNFL-OCT are not available. Reviewer Comment: 3)The other important comorbidities like diabetes/ old age/ renal dysfunction/ Vit- B12 deficiency and tb arachnoiditis with optic neuropathy should be ruled out Author Response: We have excluded patients under the age of 15 and above 50 years of age. All the conditions causing retinal pathology/optic neuropathy such as diabetics, patients with renal dysfunction, those with previously documented visual field defects, patients with nutrional optic neuropathy including vitamin B12 deficiency and patients with TB arachnoiditis and patients with previously treated TB. The suggested changes have been made in the article. Reviewer Comment: 4) the inclusion criteria of the study is not mentioned, the study has very high no. of patients taking MDR regimen/ Bedaquiline. which is very high for the population. Author Response: Inclusion criteria has been mentioned in the article. Our center is district TB center which is a nodal center for TB control and referral center for drug resistant TB. Hence probably the the number of MDR cases are high. Reviewer Comment: 5) The citations are incorrect. " TB affects 1/3rd of world population " source has been mentioned by an article on Ocular TB by V Gupta et al. The references need to substantiate the content which the authors are quoting. Author Response: As per the reviewer’s suggestion I have made correction in the text as well as the reference. Reviewer Comment: 6) The study needs major revisions with manuscript writing methodology. Author Response: Our best attempt to revise the manuscript has been made View more View less Competing Interests NIL reply Respond Report a concern Mahesh KV. Peer Review Report For: Visual field changes in patients receiving antitubercular therapy: A prospective cross-sectional study from South India [version 4; peer review: 1 approved, 2 not approved] . F1000Research 2025, 13 :719 ( https://doi.org/10.5256/f1000research.164337.r298163) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-719/v1#referee-response-298163 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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