Diabetic macular edema

Summary

Diabetic macular edema (MONDO:0004728) is a disease with 2 cohort genes (4 GWAS associations across 2 studies) and 525 clinical trials. Top therapeutic interventions include bevacizumab, aflibercept, and faricimab.

At a glance

• Cohort genes: 2
• GWAS associations: 4
• Clinical trials: 525

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	diabetic macular edema
Mondo ID	MONDO:0004728
EFO	EFO:0009321
DOID	DOID:9191
SNOMED CT	312912001
UMLS	C0730285
MedGen	676494
Is cancer (heuristic)	no

Data availability: 4 GWAS associations (2 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal vascular disorder › diabetic retinopathy › diabetic macular edema

Related subtypes (2): proliferative diabetic retinopathy, background diabetic retinopathy

Genetics & variants

GWAS landscape

4 GWAS associations across 2 studies. Top hits map to 4 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2239785	2e-24	APOL1	?	1.65
rs10402468	1e-13	BABAM1, USHBP1	?	1.5
rs1990145	4e-06	MRPL19	A	2.02
rs4771506	7e-06	LINC00343 - RNA5SP38	C	1.97

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST006282	Graham PS	2018	270	0	Genome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy.
GCST90383918	Stockwell AD	2023	99	0	Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	4
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	2
missense_variant	1
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2239785	22	36265284	G>A,C	0.05	missense_variant	APOL1	2e-24	Tier 1: coding
rs10402468	19	17273194	C>A	0.05	intron_variant	BABAM1, USHBP1	1e-13	Tier 4: intronic/intergenic
rs1990145	2	75650524	G>A,T	0.268	intron_variant	MRPL19	4e-06	Tier 4: intronic/intergenic
rs4771506	13	105843651	T>C	0.263	intergenic_variant	LINC00343 - RNA5SP38	7e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MRPL19	HGNC:14052	ENSG00000115364	P49406	Large ribosomal subunit protein bL19m	gwas
LINC00343	HGNC:42500	ENSG00000226620		long intergenic non-protein coding RNA 343	gwas

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MRPL19	Scaffold/PPI	no		Ribosomal_bL19, Translation_prot_SH3-like_sf, Ribosomal_bL19_sf
LINC00343	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
gastrocnemius	1
muscle of leg	1
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MRPL19	285	ubiquitous	marker	adrenal tissue, gastrocnemius, muscle of leg
LINC00343	85	tissue_specific	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MRPL19	3,672
LINC00343	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MRPL19	P49406	87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial translation	1	137.6×	0.013	MRPL19
Mitochondrial translation initiation	1	126.9×	0.013	MRPL19
Mitochondrial translation elongation	1	126.9×	0.013	MRPL19
Mitochondrial ribosome-associated quality control	1	122.8×	0.013	MRPL19
Mitochondrial translation termination	1	109.8×	0.013	MRPL19
Translation	1	62.1×	0.019	MRPL19
Metabolism of proteins	1	12.4×	0.081	MRPL19

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitochondrial translation	1	173.7×	0.006	MRPL19

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MRPL19	0	0
LINC00343	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MRPL19	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	MRPL19, LINC00343

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MRPL19	2	—
LINC00343	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 525.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	177
PHASE2	94
PHASE4	78
PHASE3	70
PHASE1	47
PHASE1/PHASE2	34
PHASE2/PHASE3	21
EARLY_PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04469595	PHASE4	ACTIVE_NOT_RECRUITING	A Study of Intravitreal ILUVIEN® Implant as Baseline Therapy in Patients With Early Diabetic Macular Edema (DME)
NCT04910503	PHASE4	RECRUITING	Medico Economic Evaluation of Fluocinolone Acetonide Implant Versus Dexametheasone Implant in Resistant Diabetic Macular Oedema
NCT05224102	PHASE4	ACTIVE_NOT_RECRUITING	A Study to Investigate Faricimab Treatment Response in Treatment-Naive, Underrepresented Patients With Diabetic Macular Edema
NCT05610319	PHASE4	ACTIVE_NOT_RECRUITING	Treat & Extend Versus Fixed Dosing With Faricimab for Management of Diabetic Macular Edema: A Pragmatic, Multi-center, Open-label, Randomized, Controlled Trial
NCT06305143	PHASE4	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Conbercept for Diabetic Macular Edema Combined With Severe Non-proliferative Diabetic Retinopathy
NCT06498050	PHASE4	ACTIVE_NOT_RECRUITING	Brolucizumab Efficacy and Safety Single-Arm Descriptive Trial in Patients With Persistent Diabetic Macular Edema
NCT06662994	PHASE4	RECRUITING	High Dose Aflibercept in Diabetic Macular Edema in Patients With Previous Vitrectomy
NCT07301775	PHASE4	NOT_YET_RECRUITING	Comparing Single Versus Multiple Anti-VEGF Injections in Diabetic Patients Undergoing Cataract Surgery
NCT07438119	PHASE4	NOT_YET_RECRUITING	Efficacy Comparison of DExamethasone Intravitreal Implant Combined With Aflibercept Versus Aflibercept Monotherapy in Treatment-naïve Inflammatory Diabetic Macular Edema Patients
NCT07456826	PHASE4	ENROLLING_BY_INVITATION	Study Evaluating the Efficacy and Safety of Chloroprocaine HCl Ophthalmic Gel 3% vs Proparacaine Ophthalmic Solution 0.5% Plus Subconjunctival Lidocaine in Patients Undergoing Intravitreal Injections
NCT07612904	PHASE4	NOT_YET_RECRUITING	Zhuochuming®-3T&E-DME Study (Treatment-naïve Patients)
NCT00496405	PHASE4	WITHDRAWN	Unilateral Bevacizumab for Bilateral Diabetic Macular Edema
NCT00682539	PHASE4	COMPLETED	Intraocular Anti-VEGF Compared With Intraocular Triamcinolone in Patients With Diabetic Macular Edema
NCT00737971	PHASE4	COMPLETED	Efficacy Study of Triamcinolone and Bevacizumab Intravitreal for Treatment of Diabetic Macular Edema
NCT00758628	PHASE4	COMPLETED	Randomized, Double Blind Trial of Bromfenac BID (0.09%) as an Adjunct to Argon Laser Therapy in the Treatment of Diabetic Macular Edema.
NCT01297569	PHASE4	COMPLETED	Ranibizumab Treat and Extend in Diabetic Macular Edma
NCT01309451	PHASE4	COMPLETED	Ozurdex as Adjunct to Avastin Compared to Avastin Alone in Treatment of Patients With Diabetic Macular Edema
NCT01486238	PHASE4	COMPLETED	Pegaptanib for Retinal Edema Secondary to Diabetic Vascular Disease(Preserve) Study
NCT01546402	PHASE4	COMPLETED	Intraoperative Dexamethasone Implant Improves Outcome of Cataract Surgery With Diabetic Macular Edema
NCT01573572	PHASE4	COMPLETED	Extension Study to Gather Data on Effect of Macugen on the Corneal Endothelium
NCT01613716	PHASE4	COMPLETED	Ozurdex for Diabetic Macular Edema Treated With Pars Plana vitrEctomy and Membrane RemovAl (OPERA Study)
NCT02036424	PHASE4	COMPLETED	Anti-Vascular Endothelial Growth Factor (Anti-VEGF) Alone Versus Ozurdex Given Every 3 Months for Treatment of Persistent Diabetic Macular Edema
NCT02055911	PHASE4	WITHDRAWN	Retinal Ganglion Cell Function After Intravitreous Ranibizumab in Patients With Diabetic Macular Edema
NCT02059772	PHASE4	UNKNOWN	Combination of Standard Lucentis Therapy With Micropulse Diode Laser for the Treatment of Diabetic Macular Edema
NCT02096874	PHASE4	COMPLETED	Bevacizumab and Peripheral Retinal Changes on Wide Field Angiography in Diabetic Macular Edema
NCT02107131	PHASE4	COMPLETED	Performance Assessment Tests in Working Individuals With DME Following Treatment With Ranibizumab
NCT02297204	PHASE4	COMPLETED	The Endurance 1 Trial
NCT02299336	PHASE4	COMPLETED	Long-Term Efficacy & Safety of Aflibercept IVT for the Treatment of DME in Subjects Who Completed the VISTA-DME Trial
NCT02359526	PHASE4	COMPLETED	A Pilot Study on the Effect and Safety of Iluvien® in Chronic Diabetic Macular Edema Patients
NCT02392364	PHASE4	COMPLETED	Variable Interval Versus Set Interval Aflibercept for DME
NCT02424019	PHASE4	COMPLETED	Phase 4 IOP Signals Associated With ILUVIEN®
NCT02441907	PHASE4	COMPLETED	Predictors of Treatment Response to Aflibercept and Aqueous Cytokine Levels in Diabetic Macular Edema
NCT02443012	PHASE4	COMPLETED	Topical Nepafenac as Supplement for Diabetic Macular Edema
NCT02471651	PHASE4	COMPLETED	Dexamethasone Intravitreal Implant for the Treatment of Persistent Diabetic Macular Edema
NCT02472366	PHASE4	COMPLETED	A Non-Randomized, Open-Label, Single Center Phase 4 Study of the Effect and Safety of ILUVIEN® in Chronic Diabetic Macular Edema Patients Considered Insufficiently Responsive to Available Therapies (Laser, Anti-VEGF) With or Without Intravitreal Corticosteroid Therapy
NCT02503540	PHASE4	COMPLETED	Peripheral and Macular Retinal Vascular Perfusion and Leakage in DME and RVO
NCT02633852	PHASE4	COMPLETED	Multicenter Study to Evaluate the Efficacy of Treat and Extend Regimen of Aflibercept (EYLEA) as a Second Line Treatment for Diabetic Macular Edema
NCT02651168	PHASE4	UNKNOWN	Predictors of Treatment Response to Aflibercept and Aqueous Cytokine Levels in Patients With Persistent Diabetic Macular Edema Following Treatment With Ranibizumab: An Interventional Prospective Study
NCT02684084	PHASE4	TERMINATED	Combination OZURDEX® & LUCENTIS® vs. OZURDEX® Monotherapy in Incomplete-Responders With Diabetic Macular Edema
NCT02902744	PHASE4	WITHDRAWN	Fluocinolone Acetonide Insert (ILUVIEN®) for Diabetic Macular Edema (FAD) Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BEVACIZUMAB	4	38
AFLIBERCEPT	4	25
FARICIMAB	4	15
RANIBIZUMAB	4	13
BROLUCIZUMAB	4	7
FLUOCINOLONE ACETONIDE	4	7
TRIAMCINOLONE ACETONIDE	4	7
TRIAMCINOLONE	4	6
BROMOCRIPTINE	4	3
DEXTROMETHORPHAN	4	3
MECAMYLAMINE	4	3
NEPAFENAC	4	3
PROPARACAINE	4	3
DANAZOL	4	2
DEXAMETHASONE	4	2
DORZOLAMIDE	4	2
METOPROLOL	4	2
PEGAPTANIB SODIUM	4	2
POVIDONE-IODINE	4	2
TAMSULOSIN	4	2
CHOLINE FENOFIBRATE	4	1
DICLOFENAC	4	1
EFALIZUMAB	4	1
FLUORESCEIN	4	1
HYPOCHLOROUS ACID	4	1
LIDOCAINE HYDROCHLORIDE	4	1
LOTEPREDNOL ETABONATE	4	1
MINOCYCLINE	4	1
OCRIPLASMIN	4	1
OCTREOTIDE	4	1