Choroidal neovascularization

Summary

Choroidal neovascularization (MONDO:0810000) is a disease with 2 cohort genes and 104 clinical trials. Top therapeutic interventions include ranibizumab, verteporfin, and bevacizumab.

At a glance

• Cohort genes: 2
• ClinVar variants: 4
• Clinical trials: 104

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	choroidal neovascularization
Mondo ID	MONDO:0810000
MeSH	D020256
UMLS	C0600518
MedGen	154726
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › choroidal neovascularization

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity; other, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3807	NM_000372.5(TYR):c.1A>G (p.Met1Val)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99562	NM_000372.5(TYR):c.325G>A (p.Gly109Arg)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3779	NM_000372.5(TYR):c.1205G>A (p.Arg402Gln)	TYR	Conflicting classifications of pathogenicity; other	criteria provided, conflicting classifications
523490	NM_001354768.3(NRL):c.448_466dup (p.Glu156fs)	NRL	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TYR	Orphanet:352734	Minimal pigment oculocutaneous albinism type 1
TYR	Orphanet:352737	Temperature-sensitive oculocutaneous albinism type 1
TYR	Orphanet:79431	Oculocutaneous albinism type 1A
TYR	Orphanet:79434	Oculocutaneous albinism type 1B
TYR	Orphanet:895	Waardenburg syndrome type 2
NRL	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	clinvar
NRL	HGNC:8002	ENSG00000129535	P54845	Neural retina-specific leucine zipper protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TYR	Tyrosinase	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.
NRL	Neural retina-specific leucine zipper protein	Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.228
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TYR	Enzyme (other)	yes	1.14.18.1	Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
NRL	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf

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
male germ line stem cell (sensu Vertebrata) in testis	2
pigmented layer of retina	1
upper leg skin	1
cortical plate	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TYR	59	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin
NRL	129	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYR	3,663
NRL	937

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TYR	P14679	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NRL	P54845	72.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Melanin biosynthesis	1	2284.0×	9e-04	TYR
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.004	TYR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
eye pigment biosynthetic process	1	4213.0×	0.002	TYR
visual perception	2	79.5×	0.002	TYR, NRL
melanin biosynthetic process from tyrosine	1	2106.5×	0.002	TYR
response to blue light	1	1685.2×	0.002	TYR
retinal rod cell development	1	842.6×	0.004	NRL
melanin biosynthetic process	1	648.1×	0.004	TYR
response to vitamin D	1	401.2×	0.005	TYR
pigmentation	1	351.1×	0.005	TYR
response to cAMP	1	255.3×	0.007	TYR
response to UV	1	183.2×	0.008	TYR
thymus development	1	168.5×	0.008	TYR
cell population proliferation	1	51.4×	0.024	TYR
positive regulation of gene expression	1	19.4×	0.059	NRL
positive regulation of transcription by RNA polymerase II	1	7.4×	0.139	NRL
regulation of transcription by RNA polymerase II	1	5.8×	0.164	NRL

Therapeutics

Drugs indicated for this disease

1 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ranibizumab	Approved (phase 4)
Aflibercept	Phase 3 (in late-stage trials)
Bevacizumab	Phase 3 (in late-stage trials)
Brolucizumab	Phase 3 (in late-stage trials)
Pegaptanib Octasodium	Phase 3 (in late-stage trials)
Triamcinolone Acetonide	Phase 3 (in late-stage trials)
Verteporfin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Adalimumab, Daclizumab, Dexamethasone, Faricimab, Infliximab, Pegaptanib Sodium, Sirolimus.

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TYR	ASCORBIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYR	10	4
NRL	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ASCORBIC ACID	4	TYR
HEXYLRESORCINOL	4	TYR
HYDROQUINONE	4	TYR
CURCUMIN	3	TYR
RESVERATROL	3	TYR
QUERCETIN	3	TYR
BUTYLATED HYDROXYTOLUENE	2	TYR
LUTEOLIN	2	TYR
ARBUTIN	2	TYR
KAEMPFEROL	1	TYR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TYR	211	Binding:209, ADMET:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TYR	1.14.18.1	tyrosinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TYR	211

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

10 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.

Compound	Max phase	Cohort target (bioactivity)
ASCORBIC ACID	4	TYR
HEXYLRESORCINOL	4	TYR
HYDROQUINONE	4	TYR
CURCUMIN	3	TYR
RESVERATROL	3	TYR
QUERCETIN	3	TYR
BUTYLATED HYDROXYTOLUENE	2	TYR
LUTEOLIN	2	TYR
ARBUTIN	2	TYR
KAEMPFEROL	1	TYR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TYR
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	1	NRL

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NRL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 104.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	34
PHASE2	20
PHASE3	16
PHASE1	11
PHASE4	9
PHASE2/PHASE3	8
PHASE1/PHASE2	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07187804	PHASE4	NOT_YET_RECRUITING	Long Term Efficacy of Faricimab Using a Treat and Extend Regimen for Type 3 Macular Neovascularization
NCT00327470	PHASE4	TERMINATED	An Open Label Trial to Investigate Macugen for the Preservation of Visual Function in Subjects With Neovascular AMD
NCT00473642	PHASE4	COMPLETED	Reduced Fluence Photodynamic Therapy (PDT) With Visudyne in Combination With Lucentis for Age-Related Macular Degeneration
NCT00533520	PHASE4	COMPLETED	Evaluation of Dosing Interval of Higher Doses of Ranibizumab
NCT01628354	PHASE4	COMPLETED	Study to Investigate the Safety and Efficacy of Ranibizumab in Patients With Choroidal Neovascularisation Due to Causes Other Than Age Related Macular Degeneration
NCT01666236	PHASE4	WITHDRAWN	Triple Treatment for Detachment of Retinal Pigment Epithelium Secondary to Polypoidal Choroidal Vasculopathy
NCT03042871	PHASE4	COMPLETED	Dosing Strategy of Intravitreal Ranibizumab for Pathological Myopia Choroidal Neovascularization
NCT03393767	PHASE4	COMPLETED	Time Course of Activity Signs at SD-OCT High Frequency Intravitreal Ranibizumab Treatment in CNV Due to AMD
NCT03409250	PHASE4	COMPLETED	SD-OCT-guided Intravitreal Ranibizumab Treatment in Choroidal Neovascularization Due to Myopia
NCT04704921	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Pivotal 1 Study of ABBV-RGX-314 (Also Known as RGX-314) Gene Therapy Administered Via Subretinal Delivery One Time in Participants With nAMD
NCT07440225	PHASE2/PHASE3	RECRUITING	A Clinical Trial of EYE201/MK-8748 in People With Macular Degeneration (MK-8748-002)
NCT07496567	PHASE2/PHASE3	RECRUITING	A Clinical Trial of EYE201/MK-8748 in People With Macular Degeneration (MK-8748-003)
NCT00000158	PHASE3	UNKNOWN	Macular Photocoagulation Study (MPS)
NCT00021736	PHASE2/PHASE3	COMPLETED	Phase II/III Study of Anti-VEGF in Neovascular AMD
NCT00242580	PHASE3	COMPLETED	A Safety and Efficacy Study Comparing the Combination Treatments of Verteporfin Therapy Plus One of Two Different Doses of Intravitreal Triamcinolone Acetonide and the Verteporfin Therapy Plus Intravitreal Pegaptanib
NCT00251459	PHASE3	COMPLETED	A Study to Evaluate Ranibizumab in Subjects With Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD)
NCT00260403	PHASE2/PHASE3	UNKNOWN	TTT Versus PDT for Treatment of Choroidal Neovascularization in Age-Related Macular Degeneration
NCT00305630	PHASE2/PHASE3	COMPLETED	Neovascular Age Related Macular Degeneration (AMD), Periocular Corticosteroids, and Photodynamic Therapy (PDT)
NCT00331864	PHASE3	COMPLETED	SUSTAIN - Study of Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration
NCT00370786	PHASE3	COMPLETED	Effect of Intravitreal Bevacizumab on Non -Age-Related Macular Degeneration (AMD) Related Choroidal Neovascularization (CNV)
NCT00406744	PHASE3	TERMINATED	Efficacy of Retreatments With Intravitreal Bevacizumab
NCT00417833	PHASE2/PHASE3	TERMINATED	Multifocal Electrophysiologic Findings After Intravitreal Bevacizumab(Avastin)Treatment
NCT00429962	PHASE3	COMPLETED	Study Comparing Ranibizumab Monotherapy With Combined Verteporfin Therapy in Subfoveal CNV
NCT00433017	PHASE2/PHASE3	TERMINATED	Verteporfin Photodynamic Therapy Administered in Conjunction With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration (AMD)
NCT00436553	PHASE3	COMPLETED	Efficacy/Safety of Verteporfin Photodynamic Therapy and Ranibizumab Compared With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization
NCT00470678	PHASE3	COMPLETED	EXTEND III - Efficacy and Safety of Ranibizumab in Patients With Subfoveal Choroidal Neovascularization (CNV) Secondary to Age-related Macular Degeneration (AMD)
NCT00599820	PHASE3	TERMINATED	Use of Intravitreal Bevacizumab in Eyes With Choroidal Neovascularization Secondary to Angioid Streaks
NCT00967850	PHASE3	COMPLETED	Efficacy and Safety of Intravitreal Bevacizumab in the Treatment of Choroidal Neovascular Membranes Associated to High Myopia
NCT01840410	PHASE3	COMPLETED	Assess the Efficacy/Safety of Intravitreal Ranibizumab in Patients With Vision Loss Due to Choroidal Neovascularization.
NCT01908816	PHASE3	COMPLETED	An Open-label Extended Clinical Protocol of Ranibizumab to Evaluate Safety and Efficacy in Rare VEGF Driven Ocular Diseases.
NCT01948830	PHASE3	COMPLETED	Randomized Study for Efficacy and Safety of Ranibizumab 0.5mg in Treat-extend and Monthly Regimens in Patients With nAMD
NCT02307682	PHASE3	COMPLETED	Efficacy and Safety of RTH258 Versus Aflibercept - Study 1
NCT02434328	PHASE3	COMPLETED	Efficacy and Safety of RTH258 Versus Aflibercept - Study 2
NCT00100087	PHASE1/PHASE2	UNKNOWN	Safety Study for Treatment of Wet Macular Degeneration Using the TheraSight(TM) Ocular Brachytherapy System
NCT00304954	PHASE2	COMPLETED	Infliximab, Sirolimus and Daclizumab to Treat Age-Related Macular Degeneration
NCT00363714	PHASE1/PHASE2	COMPLETED	A Dose Escalation Trial of an Intravitreal Injection of Sirna-027 in Patients With Subfoveal Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD)
NCT00426998	PHASE2	COMPLETED	Combination Bevacizumab and Verteporfin (Two Different Sequences of Treatment)in Neovascular AMD
NCT00492284	PHASE2	COMPLETED	Reduced Fluence Visudyne-Anti-VEGF-Dexamethasone In Combination for AMD Lesions (RADICAL)
NCT00509548	PHASE2	TERMINATED	Open-Label, Pilot Study of TG100801 in Patients With Choroidal Neovascularization Due to AMD
NCT00510965	PHASE2	COMPLETED	Ranibizumab to Treat Choroidal Neovascularization (CNV) in Patients With Pseudoxanthoma Elasticum (PXE)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RANIBIZUMAB	4	28
VERTEPORFIN	4	5
BEVACIZUMAB	4	1
DACLIZUMAB	4	1
FARICIMAB	4	1
FLUOCINOLONE ACETONIDE	4	1
PADELIPORFIN POTASSIUM	4	1
PEGAPTANIB SODIUM	4	1
TALAPORFIN	4	1
TRIAMCINOLONE ACETONIDE	4	1
FOSBRETABULIN	3	4
CONBERCEPT	3	2
FLUOCINOLONE	1	1
CHEMBL6134069	0	5
S-ROLIPRAM	0	1