Details of Disease

General Information of Disease (ID: DISNOENH)

Disease Name	Keratoconjunctivitis sicca
Synonyms	dry eye; keratoconjunctivitis sicca; dry eye syndrome; sicca, keratoconjunctivitis; KCS; dry eye(s); eye(s), dry; tear film insufficiency
Disease Class	9A79: Keratoconjunctivitis sicca
Definition	A syndrome characterized by dryness of the cornea and conjunctiva. It is usually caused by a deficiency in tear production. Symptoms include a feeling of burning eyes and a possible foreign body presence in the eye.
Disease Hierarchy	DIS6SVEE: Syndromic disease DIS83E37: Lacrimal apparatus disorder DISOYCQC: Keratoconjunctivitis DISNOENH: Keratoconjunctivitis sicca
ICD Code	ICD-11 ICD-11: 9A79
Disease Identifiers	MONDO ID MONDO_0006733 MESH ID D015352 UMLS CUI C0013238 MedGen ID 4411 HPO ID HP:0001097 SNOMED CT ID 302896008

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Drugs in Phase 2 Trial

Drug Name	Drug ID	Highest Status	Drug Type	REF
Piclidenoson	DM2MYNQ	Phase 2 Trial	Small molecular drug	[1]
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This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
CAM-101	DML5JG9	Phase 1/2	Cell therapy	[2]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CHIA	TTJB1O0	Limited	Altered Expression	[3]
KIR2DS2	TTV3CFI	Limited	Biomarker	[4]
LCAT	TTGZ91P	Limited	Biomarker	[5]
MAPKAPK2	TTMUG9D	Limited	Biomarker	[6]
RPS6KA1	TTIXKA4	Limited	Biomarker	[7]
RPS6KA2	TT0ZW9O	Limited	Biomarker	[7]
SPDEF	TT2ZUPY	Limited	Biomarker	[8]
TGM1	TT7A949	moderate	Altered Expression	[9]
TRPM8	TTXDKTO	moderate	Biomarker	[10]
CA6	TTCFSPE	Strong	Biomarker	[11]
DNASE1	TTYWGOJ	Strong	Altered Expression	[12]
MUC5AC	TTEL90S	Strong	Altered Expression	[13]
PRG4	TTSKF4V	Strong	Biomarker	[14]
TMSB4X	TTMVAIU	Strong	Genetic Variation	[15]
TRPV1	TTMI6F5	Strong	Biomarker	[16]
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⏷ Show the Full List of 15 DTT(s)

This Disease Is Related to 31 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AATF	OT1QOKLD	Limited	Biomarker	[17]
BRCC3	OTK0ZN7Y	Limited	Altered Expression	[18]
CD207	OTI9RUDN	Limited	Biomarker	[19]
CNTN3	OTC1274J	Limited	Biomarker	[20]
CREBZF	OTO3TOEU	Limited	Biomarker	[21]
ELOVL1	OTIDTQ8R	Limited	Biomarker	[22]
ELOVL4	OT2M9W26	Limited	Biomarker	[23]
HCFC1	OT0UCK62	Limited	Biomarker	[24]
HTN1	OTH3W1RR	Limited	Biomarker	[25]
LEAP2	OTUOPIS5	Limited	Biomarker	[26]
MPI	OTBH6ZK1	Limited	Genetic Variation	[20]
NFAT5	OTKIE59S	Limited	Altered Expression	[27]
PHETA1	OT4IMC0X	Limited	Biomarker	[28]
PPP1R11	OTSHYPPW	Limited	Biomarker	[29]
PPP1R15A	OTYG179K	Limited	Biomarker	[30]
PRR4	OT26I382	Limited	Biomarker	[31]
RGN	OTD04KB1	Limited	Genetic Variation	[15]
SCRN1	OTELM5C2	Limited	Biomarker	[28]
SPRR1B	OTXNW3P6	Limited	Biomarker	[32]
SPRR2A	OT62ZU6B	Limited	Altered Expression	[33]
TLR10	OTQ1KVJO	Limited	Biomarker	[26]
TMTC3	OTMTTDYG	Limited	Biomarker	[21]
BPIFA2	OTLFSDZD	moderate	Biomarker	[34]
BHLHA15	OTY7IER8	Strong	Biomarker	[35]
HLA-DRA	OT7KZMP2	Strong	Biomarker	[36]
MUC7	OTSTMP0X	Strong	Biomarker	[37]
NLRP6	OTEREN4W	Strong	Biomarker	[38]
RO60	OTLGM5A8	Strong	Biomarker	[39]
SSB	OTCCTPBR	Strong	Biomarker	[39]
TBCE	OTGBSTKS	Strong	Genetic Variation	[40]
TRIM21	OTA4UJCF	Strong	Biomarker	[41]
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⏷ Show the Full List of 31 DOT(s)

References

1	ClinicalTrials.gov (NCT01235234) Trial of CF101 to Treat Patients With Dry Eye Disease. U.S. National Institutes of Health.
2	ClinicalTrials.gov (NCT03414645) Randomized Multicenter Double-Masked Placebo-Controlled Parallel Phase I/II Study to Determine the Safety and Exploratory Efficacy of Topical Fibrinogen Depleted Human Platelet Lysate in Patients With Dry Eye Secondary to Graft vs Host Disease. U.S.National Institutes of Health.
3	Acidic mammalian chitinase in dry eye conditions.Cornea. 2009 Jul;28(6):667-72. doi: 10.1097/ICO.0b013e31819bc308.
4	Association of killer cell immunoglobulin-like receptor and human leukocyte antigen-C genotype with dry eye disease in a Chinese Han population.Genet Test Mol Biomarkers. 2012 Aug;16(8):910-4. doi: 10.1089/gtmb.2011.0355. Epub 2012 Apr 17.
5	Ocular and Genetic Characteristics Observed in Two Cases of Fish-Eye Disease.Cornea. 2019 Mar;38(3):379-383. doi: 10.1097/ICO.0000000000001804.
6	Therapeutic Effect of MK2 Inhibitor on Experimental Murine Dry Eye.Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4898-4907. doi: 10.1167/iovs.17-22240.
7	Diquafosol Sodium Inhibits Apoptosis and Inflammation of Corneal Epithelial Cells Via Activation of Erk1/2 and RSK: In Vitro and In Vivo Dry Eye Model.Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):5108-5115. doi: 10.1167/iovs.17-22925.
8	Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease.Int J Mol Sci. 2017 May 5;18(5):978. doi: 10.3390/ijms18050978.
9	Spdef null mice lack conjunctival goblet cells and provide a model of dry eye.Am J Pathol. 2013 Jul;183(1):35-48. doi: 10.1016/j.ajpath.2013.03.017. Epub 2013 May 10.
10	The Immunosuppressant Macrolide Tacrolimus Activates Cold-Sensing TRPM8 Channels.J Neurosci. 2019 Feb 6;39(6):949-969. doi: 10.1523/JNEUROSCI.1726-18.2018. Epub 2018 Dec 13.
11	Utility of Novel Autoantibodies in the Diagnosis of Sjgren's Syndrome Among Patients With Dry Eye.Cornea. 2018 Apr;37(4):405-411. doi: 10.1097/ICO.0000000000001471.
12	Anti-DNase I Antibody: A New Serological Reactivity in Primary Sjgren Syndrome.J Clin Rheumatol. 2020 Jan;26(1):19-23. doi: 10.1097/RHU.0000000000000905.
13	Secreted Mucins on the Ocular Surface.Invest Ophthalmol Vis Sci. 2018 Nov 1;59(14):DES151-DES156. doi: 10.1167/iovs.17-23623.
14	A Two-Week, Randomized, Double-masked Study to Evaluate Safety and Efficacy of Lubricin (150g/mL) Eye Drops Versus Sodium Hyaluronate (HA) 0.18% Eye Drops (Vismed) in Patients with Moderate Dry Eye Disease.Ocul Surf. 2017 Jan;15(1):77-87. doi: 10.1016/j.jtos.2016.08.004. Epub 2016 Sep 8.
15	RGN-259 (thymosin 4) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model.Sci Rep. 2018 Jul 12;8(1):10500. doi: 10.1038/s41598-018-28861-5.
16	Dry eye sensitizes cool cells to capsaicin-induced changes in activity via TRPV1.J Neurophysiol. 2019 Jun 1;121(6):2191-2201. doi: 10.1152/jn.00126.2018. Epub 2019 Apr 10.
17	A clinical utility assessment of the automatic measurement method of the quality of Meibomian glands.Biomed Eng Online. 2017 Jun 24;16(1):82. doi: 10.1186/s12938-017-0373-4.
18	Mitochondrial DNA oxidation induces imbalanced activity of NLRP3/NLRP6 inflammasomes by activation of caspase-8 and BRCC36 in dry eye.J Autoimmun. 2017 Jun;80:65-76. doi: 10.1016/j.jaut.2017.02.006. Epub 2017 Feb 24.
19	Langerhans cells prevent subbasal nerve damage and upregulate neurotrophic factors in dry eye disease.PLoS One. 2017 Apr 25;12(4):e0176153. doi: 10.1371/journal.pone.0176153. eCollection 2017.
20	Dysfunctional Coping Mechanisms Contribute to Dry Eye Symptoms.J Clin Med. 2019 Jun 24;8(6):901. doi: 10.3390/jcm8060901.
21	Dry Eye After LASIK.Invest Ophthalmol Vis Sci. 2018 Nov 1;59(14):DES109-DES115. doi: 10.1167/iovs.17-23538.
22	Very long-chain tear film lipids produced by fatty acid elongase ELOVL1 prevent dry eye disease in mice.FASEB J. 2018 Jun;32(6):2966-2978. doi: 10.1096/fj.201700947R. Epub 2018 Jan 17.
23	A role for ELOVL4 in the mouse meibomian gland and sebocyte cell biology.Invest Ophthalmol Vis Sci. 2014 May 1;55(5):2832-40. doi: 10.1167/iovs.13-13335.
24	Relation of accommodative microfluctuation with dry eye symptoms in short tear break-up time dry eye.PLoS One. 2017 Sep 8;12(9):e0184296. doi: 10.1371/journal.pone.0184296. eCollection 2017.
25	Presence of Histatin-1 in Human Tears and Association with Aqueous Deficient Dry Eye Diagnosis: A Preliminary Study.Sci Rep. 2019 Jul 16;9(1):10304. doi: 10.1038/s41598-019-46623-9.
26	Increased expression of hepcidin and toll-like receptors 8 and 10 in viral keratitis.Cornea. 2011 Aug;30(8):899-904. doi: 10.1097/ICO.0b013e31820126e5.
27	Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling.Int J Mol Sci. 2019 Nov 13;20(22):5691. doi: 10.3390/ijms20225691.
28	Incidence and Risk Factors of Dry Eye in a Spanish Adult Population: 11-Year Follow-Up From the Salns Eye Study.Cornea. 2018 Dec;37(12):1527-1534. doi: 10.1097/ICO.0000000000001713.
29	Corneal autophagy and ocular surface inflammation: A new perspective in dry eye.Exp Eye Res. 2019 Jul;184:126-134. doi: 10.1016/j.exer.2019.04.023. Epub 2019 Apr 21.
30	GADD34 Function in Protein Trafficking Promotes Adaptation to Hyperosmotic Stress in Human Corneal Cells.Cell Rep. 2017 Dec 5;21(10):2895-2910. doi: 10.1016/j.celrep.2017.11.027.
31	Lacrimal proline rich 4 (LPRR4) protein in the tear fluid is a potential biomarker of dry eye syndrome.PLoS One. 2012;7(12):e51979. doi: 10.1371/journal.pone.0051979. Epub 2012 Dec 18.
32	Small proline-rich protein 1B (SPRR1B) is a biomarker for squamous metaplasia in dry eye disease.Invest Ophthalmol Vis Sci. 2008 Jan;49(1):34-41. doi: 10.1167/iovs.07-0685.
33	Elevation of autophagy markers in Sjgren syndrome dry eye.Sci Rep. 2017 Dec 8;7(1):17280. doi: 10.1038/s41598-017-17128-0.
34	Prevalence of Novel Candidate Sjgren Syndrome Autoantibodies in the Penn Sjgren's International Collaborative Clinical Alliance Cohort.Cornea. 2019 Dec;38(12):1500-1505. doi: 10.1097/ICO.0000000000002147.
35	Aire-deficient mice provide a model of corneal and lacrimal gland neuropathy in Sjgren's syndrome.PLoS One. 2017 Sep 19;12(9):e0184916. doi: 10.1371/journal.pone.0184916. eCollection 2017.
36	Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1.Front Immunol. 2018 Oct 15;9:2271. doi: 10.3389/fimmu.2018.02271. eCollection 2018.
37	Ocular mucin gene expression levels as biomarkers for the diagnosis of dry eye syndrome.Invest Ophthalmol Vis Sci. 2011 Oct 28;52(11):8363-9. doi: 10.1167/iovs.11-7655.
38	TLR4-MyD88 pathway promotes the imbalanced activation of NLRP3/NLRP6 via caspase-8 stimulation after alkali burn injury.Exp Eye Res. 2018 Nov;176:59-68. doi: 10.1016/j.exer.2018.07.001. Epub 2018 Jul 2.
39	Clinical and immunological parameters of Sjgren's syndrome.Autoimmun Rev. 2018 Oct;17(10):1053-1064. doi: 10.1016/j.autrev.2018.05.005. Epub 2018 Aug 10.
40	Scleral lenses for severe chronic GvHD-related keratoconjunctivitis sicca: a retrospective study by the SFGM-TC.Bone Marrow Transplant. 2017 Jun;52(6):878-882. doi: 10.1038/bmt.2017.9. Epub 2017 Feb 20.
41	Immune Response Targeting Sjgren's Syndrome Antigen Ro52 Suppresses Tear Production in Female Mice.Int J Mol Sci. 2018 Sep 27;19(10):2935. doi: 10.3390/ijms19102935.