Topical Glaucoma Therapy Is Associated With Alterations of the Ocular Surface Microbiome

From BugSigDB
Reviewed Marked as Reviewed by KateRasheed on 2025-8-5
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Chang CJ, Somohano K, Zemsky C, Uhlemann AC, Liebmann J, Cioffi GA, Al-Aswad LA, Lynch SV, Winn BJ
Journal
Investigative ophthalmology & visual science
Year
2022
PURPOSE: To investigate the ocular surface microbiome of patients with unilateral or asymmetric glaucoma being treated with topical ophthalmic medications in one eye and to determine whether microbial community changes were related to measures of ocular surface disease. METHODS: V3-V4 16S rRNA sequencing was conducted on ocular surface swabs collected from both eyes of 17 subjects: 10 patients with asymmetric/unilateral glaucoma using topical glaucoma therapy on only one eye and seven age-matched, healthy controls with no history of ocular disease or eyedrop use. Samples were categorized into three groups: patients' glaucomatous eye treated with eyedrops, patients' contralateral eye without eyedrops, and healthy control eyes. Comparisons were made for microbial diversity and composition, with differences in composition tested for association with ocular surface disease measures including tear meniscus height, tear break-up time, and Dry Eye Questionnaire. RESULTS: Samples obtained from the patients' treated and untreated eyes both had significantly greater alpha-diversity and relative abundance of gram-negative organisms compared to healthy controls. The microbial composition of patient eyes was associated with decreased tear meniscus height and tear break-up time, whereas metagenomic predictions, based on 16S rRNA data, suggested increased synthesis of lipopolysaccharide. CONCLUSIONS: The ocular surface microbiome of patients taking unilateral preserved glaucoma drops is characterized by a highly diverse array of gram-negative bacteria that is significantly different from the predominantly gram-positive microbes detected on healthy control eyes. These compositional differences were associated with decreased tear film measures and distinct inferred protein synthesis pathways, suggesting a potential link between microbial alterations and ocular surface inflammation.

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/07/24

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Margin of eyelid , Conjunctiva Free margin of eyelid,Margin of eyelid,margin of eyelid,Conjunctiva,conjunctiva,Conjunctivae,Conjunctivas,Tunica conjunctiva,Wall of conjunctival sac
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Glaucoma glaucoma,glaucoma (disease),Glaucoma (disorder),Glaucoma associated with other ocular disorders,Glaucoma associated with other ocular disorders (disorder),Glaucoma associated with other ocular disorders NOS,Glaucoma associated with other ocular disorders NOS (disorder),GLAUCOMA NEC,Glaucoma NOS,Glaucoma NOS (disorder),Glaucoma, NOS,Glaucomas,Other specified forms of glaucoma,Other specified forms of glaucoma (disorder),Other specified glaucoma,Other specified glaucoma NOS,Other specified glaucoma NOS (disorder),Unspecified glaucoma,Glaucoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control subject samples
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients samples with eyedrops
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Samples from glaucoma patients that were treated with eyedrops
Group 0 sample size Number of subjects in the control (unexposed) group
28
Group 1 sample size Number of subjects in the case (exposed) group
20
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2
Matched on Factors on which subjects have been matched on in a case-control study
age

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/07/24

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 4A, B

Description: Linear discriminant analysis (LDA) effect size (LEfSe) plot of taxonomic biomarkers identified in the ocular surface microbiome of patients and controls

Abundance in Group 1: increased abundance in Patients samples with eyedrops

NCBI Quality ControlLinks
Bacillota
Bacteroides
Candidatus Gastranaerophilales
Intestinimonas
Lawsonella
Oribacterium
Pseudomonadota
Verrucomicrobiota
Lachnospiraceae UCG-003Lachnospiraceae UCG-003
Anaerovoracaceae
Hungatella
Ruminococcaceae CAG-352Ruminococcaceae CAG-352
Lachnospira
Eisenbergiella
Anaerostipes
Monoglobus
[Eubacterium] siraeum
Lachnospira eligens
Flavonifractor
Oscillospiraceae UCG-005Oscillospiraceae UCG-005
Oscillospiraceae NK4A214 groupOscillospiraceae NK4A214 group
Mediterraneibacter gnavus
Lachnoclostridium
Oscillospiraceae
Roseburia
Oscillospiraceae UCG-002Oscillospiraceae UCG-002
[Ruminococcus] torques
Peptoniphilus
Clostridia vadin BB60 groupClostridia vadin BB60 group
Gluconobacter
Lachnospiraceae bacterium NK4A136
Komagataeibacter
Lachnospiraceae
Faecalibacterium
Akkermansia

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/07/24

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 4A, B

Description: Linear discriminant analysis (LDA) effect size (LEfSe) plot of taxonomic biomarkers identified in the ocular surface microbiome of patients and controls

Abundance in Group 1: decreased abundance in Patients samples with eyedrops

NCBI Quality ControlLinks
Actinomycetota
Bradyrhizobium
Deinococcota
Dermacoccaceae
Eubacterium ruminantium
Kocuria
Micrococcus
Novosphingobium
Methylobacterium methylorubrumMethylobacterium methylorubrum
Brevibacterium
Deinococcus
Gordonia
Blautia
Cutibacterium
Corynebacterium

Revision editor(s): Anne-mariesharp

Experiment 2


Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/07/24

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients samples with no eyedrops
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Samples from glaucoma patients that were not treated with eyedrops

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/07/24

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 4C, D

Description: Linear discriminant analysis (LDA) effect size (LEfSe) plot of taxonomic biomarkers identified in the ocular surface microbiome of patients and controls

Abundance in Group 1: increased abundance in Patients samples with no eyedrops

NCBI Quality ControlLinks
Actinomyces
Akkermansia
Anaerostipes
Bacillota
Candidatus Neoarthromitus
Candidatus Gastranaerophilales
Colidextribacter
Eubacterium xylanophilum
Faecalibacterium
Gluconobacter
Hungatella
Intestinimonas
Komagataeibacter
Lachnoclostridium
Lachnospira
Lachnospira eligens
Lachnospiraceae bacterium NK4A136
Lactobacillus
Monoglobus
Oscillibacter
Oscillospiraceae
Pseudomonadota
Romboutsia
Verrucomicrobiota
[Ruminococcus] torques
Clostridia UCG 014Clostridia UCG 014
Oscillospiraceae UCG 002Oscillospiraceae UCG 002
Ruminococcaceae A2Ruminococcaceae A2
Ruminococcaceae CAG 352Ruminococcaceae CAG 352
Bacteria incertae sedis

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/07/24

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 4C, D

Description: Linear discriminant analysis (LDA) effect size (LEfSe) plot of taxonomic biomarkers identified in the ocular surface microbiome of patients and controls

Abundance in Group 1: decreased abundance in Patients samples with no eyedrops

NCBI Quality ControlLinks
Actinomycetota
Deinococcota
Lawsonella
Bradyrhizobium
Kocuria
Deinococcus
Eubacterium ruminantium
Novosphingobium
Dermacoccus
Methylobacterium
Micrococcus
Blautia
Cutibacterium
Brevibacterium
Gordonia
Corynebacterium

Revision editor(s): Anne-mariesharp

Experiment 3


Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/08/04

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients samples with eyedrops
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Samples from glaucoma patients that were treated with eyedrops

Lab analysis

Statistical Analysis

Statistical test
Wald Test
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/08/04

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Table 4, Supplemental Table 1

Description: Significant differentially abundant taxa between patient samples with eyedrops and control subject samples

Abundance in Group 1: increased abundance in Patients samples with eyedrops

NCBI Quality ControlLinks
Aedoeadaptatus coxii
Akkermansia muciniphila
Anaerobutyricum hallii
Anaerococcus vaginalis
Anaerostipes
Anaerostipes hadrus
Bifidobacterium bifidum
Bifidobacterium longum
Blautia
Butyricicoccus
Enterorhabdus
Eubacterium coprostanoligenes
Ezakiella
Faecalibacterium prausnitzii
Flavonifractor plautii
Gluconobacter oxydans
Intestinibacter bartlettii
Lachnoclostridium
Lachnospira
Lachnospira eligens
Lachnospiraceae
Lachnospiraceae bacterium NK4A136
Mediterraneibacter gnavus
Monoglobus
Negativibacillus
Oscillibacter
Oscillospiraceae
Roseburia
Roseburia intestinalis
Roseburia inulinivorans
Rothia mucilaginosa
Ruminococcus bromii
Ruminococcus callidus
[Eubacterium] siraeum
[Ruminococcus] torques
Komagataeibacter rhaeticus/xylinusKomagataeibacter rhaeticus/xylinus
Ruminococcaceae CAG-352Ruminococcaceae CAG-352
Oscillospiraceae NK4A214 groupOscillospiraceae NK4A214 group
Oscillospiraceae UCG-002Oscillospiraceae UCG-002
Clostridia vadin BB60 groupClostridia vadin BB60 group
Blautia obeum/wexleraeBlautia obeum/wexlerae

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/08/04

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Table 4, Supplemental Table 1

Description: Significant differentially abundant taxa between patient samples with eyedrops and control subject samples

Abundance in Group 1: decreased abundance in Patients samples with eyedrops

NCBI Quality ControlLinks
Corynebacterium bovis
Corynebacterium kroppenstedtii
Corynebacterium macginleyi
Corynebacterium aurimucosum/pseudogenitalium/tuberculostearicumCorynebacterium aurimucosum/pseudogenitalium/tuberculostearicum
Cutibacterium acnes/avidumCutibacterium acnes/avidum
Bradyrhizobium
Rothia dentocariosa
Blautia coccoides/hansenii/marasmi/productaBlautia coccoides/hansenii/marasmi/producta
Sphingobium yanoikuyae
Lachnospiraceae
Lachnospiraceae A2 groupLachnospiraceae A2 group
Clostridium sensu stricto 1 perfringens/thermophilusClostridium sensu stricto 1 perfringens/thermophilus
Micrococcus aloeverae/luteus/lylae/yunnanensisMicrococcus aloeverae/luteus/lylae/yunnanensis
Lawsonella
Corynebacterium fournieri/mucifaciens/ureicelerivoransCorynebacterium fournieri/mucifaciens/ureicelerivorans
Novosphingobium
Eubacterium ruminantium
Anaerococcus
Bifidobacterium adolescentis/faecale/stercorisBifidobacterium adolescentis/faecale/stercoris
Cutibacterium granulosum
Cutibacterium

Revision editor(s): Anne-mariesharp

Experiment 4


Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/08/04

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients samples without eyedrops
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Samples from glaucoma patients that were not treated with eyedrops

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/08/04

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Table 4, Supplemental Table 2

Description: Significant differentially abundant taxa between patient samples without eyedrops and control subject samples

Abundance in Group 1: increased abundance in Patients samples without eyedrops

NCBI Quality ControlLinks
Agathobacter
Akkermansia muciniphila
Anaerostipes hadrus
Bacteria incertae sedis
Bifidobacterium bifidum
Bifidobacterium longum
Blautia
Candidatus Neoarthromitus
Colidextribacter
Eubacterium coprostanoligenes
Eubacterium xylanophilum
Faecalibacterium prausnitzii
Gluconobacter
Intestinimonas
Lachnospira
Lachnospira eligens
Lachnospiraceae
Lachnospiraceae bacterium NK4A136
Lactobacillus
Methanobrevibacter
Monoglobus
Oscillospiraceae
Roseburia intestinalis
Roseburia inulinivorans
Ruminococcus bicirculans (ex Liu et al. 2021)
Subdoligranulum
[Eubacterium] siraeum
[Ruminococcus] torques
Oscillospiraceae UCG-002Oscillospiraceae UCG-002
Oscillospiraceae NKA214 groupOscillospiraceae NKA214 group
Komagataeibacter rhaeticus/xylinusKomagataeibacter rhaeticus/xylinus
Blautia Obeum/wexleraeBlautia Obeum/wexlerae
Ruminococcaceae CAG-352Ruminococcaceae CAG-352
Clostridia UCG-014Clostridia UCG-014
Christensenellaceae R-7 groupChristensenellaceae R-7 group
Anaerovoracaceae Family XIII AD3011 groupAnaerovoracaceae Family XIII AD3011 group
Clostridia vadin BB60 groupClostridia vadin BB60 group
Bifidobacterium
Candidatus Saccharimonas
Ruminococcus callidus
Ruminococcus
Negativibacillus
Oscillospiraceae UCG -003Oscillospiraceae UCG -003
Romboutsia ilealis/timonensisRomboutsia ilealis/timonensis
Cloacibacillus
Clostridia UCG -014Clostridia UCG -014
Lachnoclostridium
Lachnospira pectinoschiza
Enterorhabdus
Anaerostipes
Lachnospiraceae A2Lachnospiraceae A2
Oscillibacter
Peptoniphilus
Selenomonadales
[Eubacterium] nodatum
Akkermansia
Roseburia
Muribaculaceae
Christensenellaceae

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-5

Curated date: 2025/08/04

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Table 4, Supplemental Table 2

Description: Significant differentially abundant taxa between patient samples without eyedrops and control subject samples

Abundance in Group 1: decreased abundance in Patients samples without eyedrops

NCBI Quality ControlLinks
Agathobacter
Blautia
Corynebacterium bovis
Corynebacterium kroppenstedtii
Corynebacterium macginleyi
Eggerthella lenta
Endobacter medicaginis
Enterorhabdus
Eubacterium coprostanoligenes
Lachnospiraceae bacterium NK4A136
Lancefieldella parvula
Methylobacterium jeotgali
Muribaculaceae
Peptoniphilus
Roseburia
Roseburia hominis
Rothia
Slackia isoflavoniconvertens
Tyzzerella
Corynebacterium aurimucosum/pseudogenitalium/tuberculostearicumCorynebacterium aurimucosum/pseudogenitalium/tuberculostearicum
Cutibacterium acnes/avidumCutibacterium acnes/avidum
Anaerovoracaceae Family XIII AD3011 groupAnaerovoracaceae Family XIII AD3011 group
Corynebacterium afermentans/coyleaeCorynebacterium afermentans/coyleae
Oscillospiraceae UCG-002Oscillospiraceae UCG-002
Lawsonella
Rothia dentocariosa
Sphingobium yanoikuyae
Micrococcus aloeverae/luteus/lylae/yunnanensisMicrococcus aloeverae/luteus/lylae/yunnanensis
Lachnospiraceae A2Lachnospiraceae A2
Corynebacterium fournieri/mucifaciens/ureicelerivoransCorynebacterium fournieri/mucifaciens/ureicelerivorans
Fusobacterium periodonticum
Novosphingobium
Eubacterium ruminantium
Ruminococcus bromii
Anaerococcus
Bifidobacterium adolescentis/faecale/stercorisBifidobacterium adolescentis/faecale/stercoris
Cutibacterium granulosum
Bradyrhizobium
Corynebacterium amycolatum/jeikeium/lactis/urealyticum/vitaeruminisCorynebacterium amycolatum/jeikeium/lactis/urealyticum/vitaeruminis
Cutibacterium

Revision editor(s): Anne-mariesharp