LETTERS TO THE EDITOR
be due to the differences in the geographical REFERENCES
Comment on Microbial
Keratitis After Collagen
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Cross-linking for
Corneal Ectasia
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To the Editor:
W e read with great interest a recently
published article by Khoo et al,1 on
microbial keratitis after collagen cross-
linking for corneal ectasia. We would like
to bring to notice a similar retrospective
observational study published by us.2 Our
study was conducted in a tertiary eye care
center of North India on 532 eyes that
underwent accelerated collagen cross-link-
ing (CXL) for progressive keratoconus
during the study period of 3 years (from
June 2014 to May 2017). All our patients
underwent epi-off CXL at 18 mW/cm2 for
6 minutes followed by the application of a
bandage contact lens (BCL). Out of 532
eyes, 7 developed microbial keratitis.
There are several differences between
our study and the current study which we
would like to highlight here.
In contrast to the study by Khoo et al,
the microbiological profile in our study
indicated 60% of patients with polymicro-
bial infections caused by Staphylococcus
aureus and Mucor sp, coagulase-negative
Staphylococcus aureus (CoNS) and Asper-
gillus fumigatus, Staphylococcus aureus
and Acanthamoeba sp. Besides this, Staph-
ylococcus aureus was found in 2, Alter-
naria sp in 1, and CoNS in 1 patient. BCL
culture was positive in 3 of our cases, sug-
gesting poor postoperative hygiene practi-
ces to be a cause of underlying infection.
This difference in the microbiological
profile in our study and Khoo et al could
Address correspondence and reprint requests to: Pra-
fulla Kumar Maharana, Associate Professor,
Department of Ophthalmology, Room- S1, 1st
floor, Dr. Rajendra Prasad Centre for Ophthalmic
Sciences, All India Institute of Medical Sciences,
New Delhi-110029, India. E-mail: drpraful13@
gmail.com
Copyright ß 2022 Asia-Pacific Academy of Ophthal-
mology. Published by Wolters Kluwer Health, Inc.
on behalf of the Asia-Pacific Academy of Oph-
thalmology. This is an open access article distrib-
uted under the terms of the Creative Commons
Attribution-Non Commercial-No Derivatives
License 4.0 (CCBY-NC-ND), where it is permis-
sible to download and share the work provided it is
properly cited. The work cannot be changed in any
way or used commercially without permission
from the journal.
ISSN: 2162-0989
DOI: 10.1097/APO.0000000000000459
ß 2022 Asia-Pacific Academy of Ophthalmology.
and demographic conditions. In addition,
the long-term use of steroids in the manage-
ment of vernal keratoconjunctivitis (VKC)
could be a risk factor for polymicrobial
infection.
VKC was found to be a predispos-
ing factor for keratoconus in 57.1% of
cases that developed post-CXL keratitis
in our series (n ¼ 4/7), while the present
cohort did not report a single case with
any such association. This could be
related to the geographic variations and
a younger age of cases with keratitis in
our case series.
In addition, resistance to fourth-gen-
eration fluoroquinolones (especially moxi-
floxacin) was found in 83.3% (n ¼ 5/6) of
our cases. Shetty et al also found a high
degree of moxifloxacin resistance in their
cohort.3 This was in oppose to the obser-
vation by Khoo et al,1 in which most of the
organisms were found to be sensitive to
fluoroquinolone. But the sensitivity to
moxifloxacin has been provided by the
authors in only 2 of their cases. It will
be useful for the readers if they elaborate
on this further.
Thus, to conclude, though CXL is a
commonly done procedure that is consid-
ered safe in most settings, it is essential to
explain to the patients the importance of
postoperative care and the slightest risk
of the sight-threatening complication of
microbial keratitis after the procedure.
Following our series, we changed our pro-
tocol of postoperative use of steroids and
now we routinely prescribe steroids only
after the healing of epithelium following
CXL. We also suggest that any association
such as VKC or allergic eye disease must
be controlled, with at least 3 months of
inflammation free period, before proceed-
ing for CXL. The antibiotic sensitivity
must be done in all cases of CXL keratitis
as the sensitivity profile may significantly
vary.
Prafulla K. Maharana, MD, DNB
Gunjan Saluja, MD, DNBy
 uted under the terms of the Creative Commons
Associate Professor Dr Rajendra Prasad
Centre for Ophthalmic Sciences, AIIMS,
New Delhi, India
yBhatia Advanced Eye Care Centre, Bhilai,
Chhattisgarh, India
1. Khoo P, Cabrera-Aguas M, Watson SL.
Microbial keratitis after corneal collagen cross-
linking for corneal ectasia. Asia Pac J
Ophthalmol (Phila). 2021;10:355–359.
2. Maharana PK, Sahay P, Sujeeth M, et al.
Microbial keratitis after accelerated corneal
collagen cross-linking in keratoconus. Cornea.
2018;37:162–167.
3. Shetty R, Kaweri L, Nuijts RM, et al. Profile of
microbial keratitis after corneal collagen cross-
linking. Biomed Res Int. 2014;2014:340509.
Concerning the Paper
‘‘Ocular Surface
Microbiome in Health and
Disease’’
To the Editor:
F irstly, we would like to express our
gratitude toward the authors, Gomes
et al,1 for referring to our paper “Current
Knowledge on the Human Eye Microbiome:
A Systematic Review of Available Amplicon
and Metagenomic Sequencing Data” pub-
lished in Acta Ophthalmologica in 2020.2
We would like to, however, point out
some misleading rephrasing of our system-
atic review’s results, which have led to mis-
interpretation by other authors meanwhile.
For our review, we obtained access to
raw data from 11 studies. This allowed us
to reanalyze them and define the com-
monly found microbiota or “core” ocular
surface microbiota. In the conclusion sec-
tion (page 510) of the paper published in
your journal, this core bacteria have been
described as “40% of the total ocular
surface”. Due to the sentence structure,
Address correspondence and reprint Requests to:
Heleen Delbeke, Department of Ophthalmology,
University Hospitals Leuven, Belgium. E-mail:
heleen.delbeke@uzleuven.be
Copyright ß 2022 Asia-Pacific Academy of Ophthal-
mology. Published by Wolters Kluwer Health, Inc.
on behalf of the Asia-Pacific Academy of Oph-
thalmology. This is an open access article distrib-
Attribution-Non Commercial-No Derivatives
License 4.0 (CCBY-NC-ND), where it is permis-
sible to download and share the work provided it is
properly cited. The work cannot be changed in any
way or used commercially without permission
from the journal.
ISSN: 2162-0989
DOI: 10.1097/APO.0000000000000463
https://journals.lww.com/apjoo | 89
 Letters to the Editor
this leads to confusion with area measures.
It would be accurate to rephrase to “40% of
the total ocular surface microbiome” when
referring to our results as we did not ana-
lyze surface dimensions.
Furthermore, several imprecisions
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lead to incorrect reports of our publication,
we listed the main below.
Page 507: “A recent systematic review
of 11 published controlled cohorts used
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16S rRNA sequencing to define, at a phy-
lum level, the most commonly present bac-
teria or the core genera.”
We reviewed more than 11 cohorts,
the 11 cohorts (page 507) mentioned in our
review are the once we had access to raw
data, making it possible to reanalyze the
data. Furthermore, the last part of the sen-
tence implies that we only defined the core
microbiome at the phylum level, which
is incorrect.
Page 507: “A publication using 16S
rRNA sequencing described the phyla levels
of the microbiome core at a pediatric level
(younger than 18 years old). The 3 main
phyla were Actinobacteria, which repre-
sented 53% of bacteria, Proteobacteria,
which represented 39%, and Firmicutes,
which represented 8%. No core genera
belong to the phylum Bacteroidetes.”
In terms of the pediatric core ocular
surface microbiome, we only had raw data
of 2 publications3,4 at pediatric level
(<18 years old) and our criteria for “core”
90 | https://journals.lww.com/apjoo
Asia-Pacific Journal of Ophthalmology  Volume 11, Number 1, January/February 2022
were met only by the genus Corynebacte-
rium as it had a relative abundance >1% and
was found in both publications.
Page 510: “The core bacteria, including
Actinobacteria (Corynebacterium and Pro-
pionibacterium), represent precisely 53% of
the ocular surface microbiome, followed by
Proteobacteria (Pseudomonas and Acineto-
bacter) accounting for 39%, and Firmicutes
(Staphylococcus and Streptococcus) for 8%.”
Bacteria belonging to the phylum Acti-
nobacteria represent 53% of the core ocular
surface microbiome but not the ocular sur-
face microbiome in general. The relative
abundances of the general ocular surface
are for Proteobacteria 41%  0.16 for Acti-
nobacteria 27%  0.19 and for Firmicutes
and Bacteroides 17%  0.08 and 7%  0.06
respectively. In our paper, we defined the
healthy core microbiome as genera present in
a minimum of 5 out of the 11 published
control cohorts with available raw data
(retrieved from publications or provided by
the corresponding author) with a relative
abundance of at least 1%. This definition is
based on earlier work in the gut but is never-
theless arbitrary. The proportion of bacteria
in the “core” should therefore not be con-
fused with actual abundances.
Heleen Delbeke, MDy
Ingele Casteels, MDy
Marie Joossens, MD, PhDz

Department of Ophthalmology,
University Hospitals Leuven,
Leuven, Belgium
yKU Leuven, Biomedical Sciences Group,
Department of Neurosciences, Research
Group Ophthalmology, Leuven, Belgium
zDepartment of Molecular Bacteriology,
REGA Institute, Catholic University
Leuven, Leuven, Belgium
REFERENCES
1. Gomes JAP, Frizon L, Demeda VF. Ocular
surface microbiome in health and disease. Asia
Pac J Ophthalmol (Phila). 2020;9:505–511. doi:
10.1097/APO.0000000000000330
2. Delbeke H, Younas S, Casteels I, Joossens M.
Current knowledge on the human eye
microbiome: a systematic review of available
amplicon and metagenomic sequencing data.
Acta Ophthalmol. 2020. Published online
June 29, 2020. doi:10.1111/aos.14508
3. Butcher RMR, Sokana O, Jack K, et al. Active
trachoma cases in the Solomon Islands have
varied polymicrobial community structures but
do not associate with individual non-chlamydial
pathogens of the eye. Front Med (Lausanne).
2017;4:251. Epub in 2017.
4. Yau JWK, Hou J, Tsui SKW, et al.
Characterization of ocular and nasopharyngeal
microbiome in allergic rhinoconjunctivitis.
Pediatr Allergy Immunol. 2019;30:624–631.
ß 2022 Asia-Pacific Academy of Ophthalmology.