Dry eye syndrome

Summary

Dry eye syndrome (MONDO:0006733) is a disease with 78 GWAS associations across 18 studies and 959 clinical trials. Top therapeutic interventions include cyclosporine, hyaluronate sodium, and lifitegrast. A subtype of lacrimal apparatus disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• GWAS associations: 78
• Clinical trials: 959

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dry eye syndrome
Mondo ID	MONDO:0006733
EFO	EFO:1000906
MeSH	D007638, D015352
DOID	DOID:10140, DOID:12895
ICD-10-CM	H04.12
NCIT	C34553
SNOMED CT	302896008, 46152009
UMLS	C0013238
MedGen	4411
MedDRA	10013777, 100233350
Is cancer (heuristic)	no

Also known as: dry eye · dry eye syndrome · dry eye(s) · eye(s), dry · keratoconjunctivitis sicca · sicca, keratoconjunctivitis

Data availability: 78 GWAS associations (18 studies).

Disease family

This is a subtype of lacrimal apparatus disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye adnexa disorder › lacrimal apparatus disorder › dry eye syndrome

Related subtypes (16): lacrimal passage granuloma, eversion of lacrimal punctum, stenosis of lacrimal punctum, stenosis of lacrimal passage, excessive tearing, primary lacrimal atrophy, secondary lacrimal atrophy, lacrimal system cancer, stenosis of lacrimal sac, acute inflammation of lacrimal passage, chronic inflammation of lacrimal passage, IgG4-related dacryoadenitis and sialadenitis, isolated congenital alacrima, disorder of lacrimal gland, nasolacrimal duct disorder, syndromic lacrimal system disorder

Subtypes (1): xerophthalmia

Genetics & variants

GWAS landscape

78 GWAS associations across 18 studies. Top hits map to 28 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr10:21824727	1e-12		G	0.04
rs10972394	2e-08	UNC13B	?
rs2524181	7e-08	MICC - TMPOP1	A	0.88
rs9692250	9e-08	DNAJB6	T	1.12
rs2734945	1e-07	HLA-H, HLA-H, POLR1HASP, POLR1HASP	G	0.72
rs729999	3e-07	NAV2	A	1.6
rs112017655	4e-07	RNU6-546P - LINC01876	T	0.85
chr4:102275281	7e-07		AAAAAAC	1.76
rs534921742	7e-07	DHFRP3 - LINC01809	C	1.56
rs13111065	8e-07	DCHS2	G	0.71
rs12477826	9e-07	NRXN1-DT, NRXN1	C	1.13
rs62225457	1e-06	EPIC1	A	0.89
rs116890474	1e-06	LINC02055	A	0.64
rs139167636	1e-06	LINC00574 - RPL12P23	G	1.48
rs79256415	2e-06	LINC02817 - DUSP10	T	0.88
chr4:96817054	2e-06		G	1.09
rs812752	2e-06	MAML3	C	1.09
rs7990686	2e-06	RPS10P21 - RPL18AP17	A	1.12
rs2350796	2e-06	RNU6-546P - LINC01876	A	0.87
rs4544377	2e-06	RNU6-546P - LINC01876	G	0.87
rs9677963	2e-06	LINC01937 - TWIST2	T	1.58
rs369757	2e-06	PPP2R2B	C	1.59
chr3:71748207	2e-06		AT	1.45
rs2107195	2e-06	TRIM15	G	0.73
rs6117882	2e-06	MIR8062 - RN7SL547P	A	0.8
rs139976915	2e-06	RPL35AP35 - RNU4-34P	C	0.71
rs77969016	2e-06	CNTN1 - PDZRN4	G	1.43
rs75791291	2e-06	SLIT3	A	1.47
rs1006762	2e-06	PDE1C	C	1.17
rs62532857	3e-06	NFIB-AS1	A	0.87

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475895	Verma A	2024	84,262	314,374	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477756	Verma A	2024	27,465	78,326	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481119	Verma A	2024	27,465	78,326	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90444399	Hsu CC	2024	14,185	25,927	Predicting Risks of Dry Eye Disease Development Using a Genome-Wide Polygenic Risk Score Model.
GCST90477754	Verma A	2024	11,160	41,110	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651561	Liu TY	2025	10,468	213,222	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90444400	Hsu CC	2024	8,072	25,927	Predicting Risks of Dry Eye Disease Development Using a Genome-Wide Polygenic Risk Score Model.
GCST90444404	Hsu CC	2024	6,703	14,852	Predicting Risks of Dry Eye Disease Development Using a Genome-Wide Polygenic Risk Score Model.
GCST90444401	Hsu CC	2024	6,113	25,927	Predicting Risks of Dry Eye Disease Development Using a Genome-Wide Polygenic Risk Score Model.
GCST90444405	Hsu CC	2024	4,873	14,852	Predicting Risks of Dry Eye Disease Development Using a Genome-Wide Polygenic Risk Score Model.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	50

MAF distribution

Bucket	Variants
common (>=0.05)	38
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	12

Functional consequences

Consequence	Count
intron_variant	28
intergenic_variant	14
unknown	5
non_coding_transcript_exon_variant	3

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr10:21824727				0.362			1e-12	Tier 4: intronic/intergenic
rs10972394	9	35237973	C>T	0.05	intron_variant	UNC13B	2e-08	Tier 4: intronic/intergenic
rs2524181	6	30458326	A>T	0.05	intergenic_variant	MICC - TMPOP1	7e-08	Tier 4: intronic/intergenic
rs9692250	7	157369374	T>C,G	0.05	intron_variant	DNAJB6	9e-08	Tier 4: intronic/intergenic
rs2734945	6	29888168	A>C,G	0.05	non_coding_transcript_exon_variant	HLA-H, HLA-H, POLR1HASP, POLR1HASP	1e-07	Tier 4: intronic/intergenic
rs729999	11	19956172	A>C,G,T	0.314	intron_variant	NAV2	3e-07	Tier 4: intronic/intergenic
rs112017655	2	155557751	C>T	0.05	intron_variant	RNU6-546P - LINC01876	4e-07	Tier 4: intronic/intergenic
chr4:102275281				0.099			7e-07	Tier 4: intronic/intergenic
rs534921742	2	83333307	A>C		intergenic_variant	DHFRP3 - LINC01809	7e-07	Tier 4: intronic/intergenic
rs13111065	4	154317190	A>G	0.491	intron_variant	DCHS2	8e-07	Tier 4: intronic/intergenic
rs12477826	2	51205843	A>C	0.05	intron_variant	NRXN1-DT, NRXN1	9e-07	Tier 4: intronic/intergenic
rs62225457	22	47642882	G>A	0.05	intron_variant	EPIC1	1e-06	Tier 4: intronic/intergenic
rs116890474	8	136134878	G>A,T		intergenic_variant	LINC02055	1e-06	Tier 4: intronic/intergenic
rs139167636	6	170072183	A>G		intergenic_variant	LINC00574 - RPL12P23	1e-06	Tier 4: intronic/intergenic
rs79256415	1	221683759	G>T	0.05	intron_variant	LINC02817 - DUSP10	2e-06	Tier 4: intronic/intergenic
chr4:96817054							2e-06	Tier 4: intronic/intergenic
rs812752	4	139929836	C>T	0.05	intron_variant	MAML3	2e-06	Tier 4: intronic/intergenic
rs7990686	13	72096563	A>G,T	0.05	intergenic_variant	RPS10P21 - RPL18AP17	2e-06	Tier 4: intronic/intergenic
rs2350796	2	155435414	A>G,T	0.05	intron_variant	RNU6-546P - LINC01876	2e-06	Tier 4: intronic/intergenic
rs4544377	2	155400189	G>A,C,T	0.05	intron_variant	RNU6-546P - LINC01876	2e-06	Tier 4: intronic/intergenic
rs9677963	2	238792935	C>G,T	0.279	intergenic_variant	LINC01937 - TWIST2	2e-06	Tier 4: intronic/intergenic
rs369757	5	146637793	A>C	0.227	intron_variant	PPP2R2B	2e-06	Tier 4: intronic/intergenic
chr3:71748207				0.278			2e-06	Tier 4: intronic/intergenic
rs2107195	6	30170089	A>G	0.05	intron_variant	TRIM15	2e-06	Tier 4: intronic/intergenic
rs6117882	20	7608818	G>A	0.05	intergenic_variant	MIR8062 - RN7SL547P	2e-06	Tier 4: intronic/intergenic
rs139976915	17	29379146	G>C	0.05	non_coding_transcript_exon_variant	RPL35AP35 - RNU4-34P	2e-06	Tier 4: intronic/intergenic
rs77969016	12	41184805	A>G		intergenic_variant	CNTN1 - PDZRN4	2e-06	Tier 4: intronic/intergenic
rs75791291	5	168901671	C>A		intron_variant	SLIT3	2e-06	Tier 4: intronic/intergenic
rs1006762	7	32144065	G>A,C,T	0.05	intron_variant	PDE1C	2e-06	Tier 4: intronic/intergenic
rs62532857	9	14432345	G>A,C,T	0.05	intron_variant	NFIB-AS1	3e-06	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated or in trials for this disease

3 approved drugs — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Lifitegrast	Approved (phase 4)
Loteprednol Etabonate	Approved (phase 4)
Perfluorohexyloctane	Approved (phase 4)

54 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
BRM-421	Phase 3
Bromfenac	Phase 3
Carboxymethylcellulose Sodium	Phase 3
Cenegermin	Phase 3
Cinhyaluronate Sodium	Phase 3
Cyclosporine	Phase 3
Dexamethasone Phosphoric Acid	Phase 3
Fluorometholone	Phase 3
Fonadelpar	Phase 3
Hypromellose	Phase 3
Isunakinra	Phase 3
OMEGA-3 FATTY ACIDS	Phase 3
OMEGA-3-ACID ETHYL ESTERS	Phase 3
Ozagrel	Phase 3
POLYETHYLENE GLYCOL 4000	Phase 3
Piclidenoson	Phase 3
Propylene Glycol	Phase 3
Rebamipide	Phase 3
Reproxalap	Phase 3
Rimexolone	Phase 3
Sodium Chloride	Phase 3
Sodium Citrate	Phase 3
Tanfanercept	Phase 3
Tavilermide	Phase 3
Timbetasin Acetate	Phase 3
Tivanisiran	Phase 3
Varenicline	Phase 3
Acetylcysteine	Phase 2
Betamethasone	Phase 2
Brimonidine	Phase 2
Canakinumab	Phase 2
Dexamethasone	Phase 2
Difluprednate	Phase 2
Ecabet	Phase 2
Estradiol	Phase 2
Glycerin	Phase 2
Human Immunoglobulin G	Phase 2
Mapracorat	Phase 2
Mycophenolic Acid	Phase 2
Naltrexone	Phase 2
Olive Oil	Phase 2
Pilocarpine	Phase 2
Pimecrolimus	Phase 2
Polyethylene Glycol	Phase 2
Pregabalin	Phase 2
Recoflavone	Phase 2
Rivoglitazone	Phase 2
Secukinumab	Phase 2
Sirolimus	Phase 2
Sodium Phosphate, Dibasic, Anhydrous	Phase 2
Thymosin	Phase 2
Tofacitinib	Phase 2
Voclosporin	Phase 2
Zucapsaicin	Phase 2

Clinical trials & evidence

Clinical trials

Clinical trials: 959.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	509
PHASE4	157
PHASE2	114
PHASE3	97
PHASE1	33
PHASE1/PHASE2	21
PHASE2/PHASE3	18
EARLY_PHASE1	10

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06017362	PHASE4	RECRUITING	Clinical Trial to Determine the Efficacy and Safety of Insulin Eye Drops in Dry Eye in Patients with Topical Hypotensors
NCT06404541	PHASE4	ACTIVE_NOT_RECRUITING	A Comparative Study Between Preservative With Benzalkonium Chloride vs Preservative Free Eye Drops on the Ocular Surface
NCT06525961	PHASE4	NOT_YET_RECRUITING	iTear Single-center, Open-label, Single-arm Study
NCT06565650	PHASE4	ACTIVE_NOT_RECRUITING	A Study to Evaluate Corneal Endothelial Cell Density (ECD) in Subjects With Dry Eye Disease (DED) Administering Miebo® (Perfluorohexyloctane Ophthalmic Solution) for 12 Months.
NCT06860659	PHASE4	ENROLLING_BY_INVITATION	Efficacy of 0.28% Sodium Hyaluronate Eye Drops in Patient With Moderate to Severe Dry Eye
NCT06939959	PHASE4	RECRUITING	Evaluating the Efficacy of Topical Insulin for the Restoration of Ocular Surface Interface in Dry Eye Disease.
NCT06947850	PHASE4	ACTIVE_NOT_RECRUITING	DOMPE -MT Neurotrophic Keratitis
NCT06964269	PHASE4	RECRUITING	Use of Acthar Gel Single-Dose Pre-Filled SelfJectTM Injector in Patients With Moderate-Severe Keratitis and Autoimmune Disease
NCT07113210	PHASE4	RECRUITING	Quality of Life in Presbyopic Patients Who Are Treated With Qlosi
NCT07155070	PHASE4	RECRUITING	Efficacy of Kera Sol Tears on Signs and Symptoms of Surgical Temporary Ocular Discomfort Syndrome (STODS) in Subjects Following LASIK
NCT07191847	PHASE4	RECRUITING	Assessment of CataClear, Tear Film Stability, Tear Volume, and Dry Eye Symptoms Using Stem Cells Fortified Eye Drops
NCT07266948	PHASE4	RECRUITING	Impact of TRYPTYR on a Patient’s Quality of Life and Ability to Perform Work
NCT07267299	PHASE4	NOT_YET_RECRUITING	Switching From Restasis to TRYPTYR
NCT07267481	PHASE4	NOT_YET_RECRUITING	Switching From Xiidra to TRYPTYR
NCT07490535	PHASE4	NOT_YET_RECRUITING	This is a Single Center, Open-label Prospective Study to Evaluate the Effect of Xiidra® (Lifitegrast Ophthalmic Solution 5.0%) on Tear Film Biomarkers in Dry Eye
NCT07510620	PHASE4	RECRUITING	Single-Arm Study of a Treatment for Dry Eye in People Who Struggle to Wear Contact Lenses
NCT07553455	PHASE4	ENROLLING_BY_INVITATION	Vevye + Flarex Combination Therapy for Dry Eye
NCT07560735	PHASE4	NOT_YET_RECRUITING	Clinical Evaluation of Lifitegrast Ophthalmic Solution 5.0% in Dry Eye Disease Using In Vivo Confocal Microscopy
NCT07606625	PHASE4	RECRUITING	Ocular Surface Health and Tear Film Stability With a Nasal Spray Dry Eye Treatment
NCT00284999	PHASE4	COMPLETED	Soothe Versus Refresh
NCT00349440	PHASE4	COMPLETED	Efficacy of Cyclosporine for the Prevention and Treatment of Dry Eye Symptoms Following LASIK or Photorefractive Keratectomy
NCT00349583	PHASE4	COMPLETED	Efficacy of Topical Cyclosporine Versus Tears for Improving Visual Outcomes Following Multifocal IOL Implantation
NCT00386646	PHASE4	COMPLETED	Comparative Study of 0.5% Carboxymethylcellulose With 0.005% Stabilized Oxychlorocomplex (PURITE™) Versus 0.5% Carboxymethylcellulose in the Treatment of Dry Eye
NCT00388791	PHASE4	COMPLETED	Comparison of Systane Free vs. Saline in the Treatment of Dry Eye
NCT00399061	PHASE4	COMPLETED	Efficacy of Optive Versus Systane Concomitant With Restasis (Cyclosporine A) for the Treatment of Dry Eye Symptoms
NCT00399230	PHASE4	COMPLETED	A Comparison of Optive in Patients Previously Using Systane for the Treatment of Dry Eye
NCT00405457	PHASE4	COMPLETED	Efficacy and Safety of a New Multi-dose Lubricant Eye Drop Concomitant With Restasis® (Cyclosporine A) for the Treatment of Dry Eye Symptoms
NCT00406510	PHASE4	COMPLETED	Comparison of Frequency of Use of Optive and Systane
NCT00407043	PHASE4	COMPLETED	Multicenter, Randomized, Controlled Study of the Effect of Lotemax on Initiation of Dry Eye Treatment With Restasis
NCT00469157	PHASE4	COMPLETED	Refractive Surgery and Optive Compatibility Study
NCT00469573	PHASE4	COMPLETED	Safety and Efficacy of Optive in Contact Lens Wearers With Dry Eyes
NCT00477763	PHASE4	COMPLETED	Oasys vs. Extreme H20 Xtra 59
NCT00493662	PHASE4	COMPLETED	Cross-Over Evaluation of Two Lubricating Eye Drops
NCT00553735	PHASE4	TERMINATED	The Prophylactic Use of Topical Cyclosporine A 0.05% to Prevent Graft Versus Host Disease Related Dry Eye
NCT00620893	PHASE4	COMPLETED	Bilateral, Masked Comparison of PEG-400 Based Artificial Tear vs. Systane for Dry Eye Signs, Symptoms & Refractive Regression Associated With Myopic Laser in Situ Keratomilieusis (LASIK).
NCT00622037	PHASE4	COMPLETED	Bilateral, Masked Comparison of PEG-400 Based Artificial Tear and Systane for the Treatment of Dry Eye Signs, Symptoms and Visual Quality
NCT00704275	PHASE4	UNKNOWN	Comparison of Efficacy, Safety and Anti-Inflammatory Effect Between Topical 0.05%Cyclosporine A Emulsion and REFRESH® in Patients With Moderate to Severe Dry Eyes
NCT00724412	PHASE4	COMPLETED	Evaluate Artificial Tear Efficacy in Moderate to Severe Dry Eye
NCT00756678	PHASE4	COMPLETED	Efficacy and Acceptability of Two Lubricant Eye Drops
NCT00761202	PHASE4	COMPLETED	Performance and Acceptance of Optive Versus Hylocomod Eyedrops in Patients With Dry Eye Symptoms

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOSPORINE	4	38
HYALURONATE SODIUM	4	15
LIFITEGRAST	4	15
DIQUAFOSOL	4	11
BRIMONIDINE	4	9
LOTEPREDNOL ETABONATE	4	9
HYPROMELLOSE	4	4
PERFLUOROHEXYLOCTANE	4	4
CENEGERMIN	4	3
DOXYCYCLINE ANHYDROUS	4	3
FLUOROMETHOLONE	4	3
GLYCERIN	4	3
OLIVE OIL	4	3
OZAGREL	4	3
TOBRAMYCIN	4	3
TOFACITINIB	4	3
AZITHROMYCIN	4	2
LEVOFLOXACIN ANHYDROUS	4	2
PILOCARPINE	4	2
PREDNISOLONE	4	2
RETINOL	4	2
TETRAHYDROZOLINE	4	2
BETAMETHASONE	4	1
CANAKINUMAB	4	1
CORTICOTROPIN	4	1
DEXAMETHASONE	4	1
DIPYRIDAMOLE	4	1
ESOMEPRAZOLE	4	1
FLUOROMETHOLONE ACETATE	4	1
HYDROCORTISONE	4	1