Challenges in the diagnosis and management of atypical fungal keratitis during the COVID-19 pandemic: a case series
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Fungal keratitis is a time-sensitive ocular infection that often requires a high index of suspicion followed by intensive medical/surgical interventions to achieve a successful clinical outcome. COVID-19 pandemic-related restrictions, necessitated the modification of conventional protocols and guidelines associated with the treatment of keratomycosis. We report four cases of atypical fungal keratitis with poorly differentiated clinical characteristics. The challenges faced during their management were (1) the dilemma of clinically differentiating fungal ( Scedosporium and Purpureocillium lilacinum ) and bacterial keratitis; (2) treatment of Scedosporium and Trichosporon keratitis with natamycin monotherapy; (3) mixed infection of Candida albicans and Aureobasidium pullulans and continuing medications before rescraping the corneal ulcer against the recommended treatment guidelines; (4) phenotypic identification and differentiation among morphologically resembling fungi; and (5) decision making arising out of disparities between KOH and fungal culture results. Three patients responded well to conservative treatments. The fourth patient underwent therapeutic keratoplasty but was lost to follow-up due to travel - related pandemic restrictions. This case series seeks to broaden the clinician’s knowledge of rare and emerging moulds as presumptive aetiologies of keratomycosis. It also intends to emphasize the significance of early microbiological investigations, (direct microscopy and culture), in resource-limited settings, for initiating empirical treatment for a better visual prognosis.
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This is a study that would be of interest to the field and community.
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Comments to Author
No further comment. All comments have been answered by the author(s).
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
The authors present 4 compelling case studies detailing the difficulties of identifying fungal pathogens implicated in fungal keratitis in developing countries. The author addresses the reviewers comments to a sufficient level.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied …
Comments to Author
The authors present 4 compelling case studies detailing the difficulties of identifying fungal pathogens implicated in fungal keratitis in developing countries. The author addresses the reviewers comments to a sufficient level.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
-
Comments to Author
Authors have fulfilled all minor suggestions I have indicated (reviewer 7). In this version, Line 269, consider «Case 1» instead of «For Case 1».
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments.
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Comments to Author
The authors address the atypical fungal keratitis, reporting an interesting set of cases. This is a hard-to-treat clinical entity, whose interest is emphasized by Covid-19 pandemic background in which the cases appeared. In addition, the unusual incidence of the involved fungi and the implicit clinic/laboratory strong interaction are additional interesting points of the manuscript. Moreover, the whole manuscript is well-structured and generally well-written; the good quality of the photographs is noteworthy. There are a few points that I wish to take to the attention of the authors: 1. Lines 219-221: the authors refer that when improvement was lacking, the patient's treatment was suspended for 24h to obtain another sample. Thus, the benefit compensated the risk. Can the authors argument a little more …
Comments to Author
The authors address the atypical fungal keratitis, reporting an interesting set of cases. This is a hard-to-treat clinical entity, whose interest is emphasized by Covid-19 pandemic background in which the cases appeared. In addition, the unusual incidence of the involved fungi and the implicit clinic/laboratory strong interaction are additional interesting points of the manuscript. Moreover, the whole manuscript is well-structured and generally well-written; the good quality of the photographs is noteworthy. There are a few points that I wish to take to the attention of the authors: 1. Lines 219-221: the authors refer that when improvement was lacking, the patient's treatment was suspended for 24h to obtain another sample. Thus, the benefit compensated the risk. Can the authors argument a little more about this issue? 2. Several phrasing or wording shortcomings were noticed: - some full stops are inserted before references or before «Table» or «Figure»; some other are located after those items. Now and then, there are commas that seem to be missing or are misplaced. In addition, spacings and unnecessary capitals (e.g., Potassium, Day, Tab, Itraconazole, Posaconazole, Amphotericin) indicate that an additional review of the English will standardize the manuscript. - Lines 89 & 113: man and woman would be preferred to gentleman and lady - Lines 95-96: regarding moxifloxacin and amikacin administration «two hourly», do the authors mean every 2 hours? - Lines 104 & 249: please verify whether the limitation was of the eye or the eyelid - Line 105: «…any other cranial nerve…», instead of «…any cranial nerve…». - Lines 142-143: The text related to the consent appear to be repeated (in Lines 352-354). I suggest to remove the first appearance. - Line 224: «microbial keratitis»; do the authors mean «fungal keratitis»?
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
-
Comments to Author
The authors present a thorough and well written case study series demonstrating the use of laboratory culture techniques to identify microbial species associated with fungal keratitis in a resource limited setting. I commend the authors for highlighting limitations of these techniques and improvements required for effective diagnostic testing. I have a handful of minor comments. Line 58 - 59: Remove, not required Line 72 - 76: Be consistent with nomenclature, include spp. after every genus described Line 153 - 156: Please provide references to protocols for species identification used in this study, or alternatively provide additional brief detail. Figures: Please add scale bars to acquired microscopy images. Figures 1 - 4 could be presented as a single figure in A4 format.
Please rate …
Comments to Author
The authors present a thorough and well written case study series demonstrating the use of laboratory culture techniques to identify microbial species associated with fungal keratitis in a resource limited setting. I commend the authors for highlighting limitations of these techniques and improvements required for effective diagnostic testing. I have a handful of minor comments. Line 58 - 59: Remove, not required Line 72 - 76: Be consistent with nomenclature, include spp. after every genus described Line 153 - 156: Please provide references to protocols for species identification used in this study, or alternatively provide additional brief detail. Figures: Please add scale bars to acquired microscopy images. Figures 1 - 4 could be presented as a single figure in A4 format.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
-
Comments to Author
The manuscript describes the challenges in diagnosing and managing atypical fungal keratitis during the COVID-19 pandemic, intending to broaden the clinician's knowledge of rare but emerging moulds as presumptive aetiologies of keratomycosis. It also intends to reinforce the significance of early microbiological investigations (direct microscopy and culture) in resource-limited settings for initiating empirical treatment towards a better visual prognosis. Overall, the case report is interesting. However, improvements are needed for clarity. Page 4 line 72 and line 76 - spp. should be written if full when first mentioned. Page 5 line 91 - 3 days should be written as 'three'. All numbers from 1 to 10 should be written in full. Page 5 line 97 - potassium should be small letter. Page 5 line 105 - 3 weeks …
Comments to Author
The manuscript describes the challenges in diagnosing and managing atypical fungal keratitis during the COVID-19 pandemic, intending to broaden the clinician's knowledge of rare but emerging moulds as presumptive aetiologies of keratomycosis. It also intends to reinforce the significance of early microbiological investigations (direct microscopy and culture) in resource-limited settings for initiating empirical treatment towards a better visual prognosis. Overall, the case report is interesting. However, improvements are needed for clarity. Page 4 line 72 and line 76 - spp. should be written if full when first mentioned. Page 5 line 91 - 3 days should be written as 'three'. All numbers from 1 to 10 should be written in full. Page 5 line 97 - potassium should be small letter. Page 5 line 105 - 3 weeks should be written as 'three'. Page 5 line 113 - suggest to replace lady with female. Page 5 line 114 - 3 days should be written as 'three'. Page 5 line 96 and 118- What do you mean by two hourly? Is it twice or two times? Page 6 line 123, Page 12 line 255, Page 12 line 274, Page 13 line 294 - itraconazole should be written in small letter. Please check other names of antifungal used as well in the whole manuscript. Better to standardised in to use capital letter. Page 6 line 131 - What is Tab.fluconazole? Page 6 line 138 - What do you mean by 'two hourly'? Page 6 line 138 - 6 should be written in full. Page 6 line 139 - 3 days should be written in full. Page 6 line 149 - Why the culture plates were incubated at two different temperatures? Please justify. Page 6 line 149 - 4 weeks should be written in full. Page 7 line 153 - Why Gram stain was conducted to test fungi? Gram stain is to differentiate between Gram positive and Gram negative bacteria. All fungi should give dark blue colour since the eukaryotic microorganism generally will have cell wall. Please justify the purpose of Gram stain in the study. Similar comment to Table 1 on Candida albicans isolates. Page 10 line 204 - ..negative smears. Page 10 line 206 - 4 should be written in full. Page 11 line 243 - Scedosporium keratitis should be written as S. keratitis when mentioned for the second time. Page 11 line 245 - 5 and 8 cases should be written in full. Page 12 line 259, 263 - Candida albicans should be written as C. albicans.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Partially support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
-