Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (830 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A rare degenerative inherited eye disease that appears at birth or in the first few months of life that results in a loss of vision. Not to be confused with leber hereditary optic neuropathy, the disease is thought to be caused by abnormal development of photoreceptor cells in the retina, or by the extremely premature degeneration of retinal cells.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Amauroses, Leber Congenital; Congenital Amauroses, Leber; Congenital Amaurosis, Leber; Leber Congenital Amauroses; Amaurosis, Leber Congenital; Congenital Retinal Blindness; Blindness, Congenital Retinal; Blindnesses, Congenital Retinal.
Where it fits in the MeSH classification
- Broader topics
- Eye Diseases, Hereditary; Retinal Diseases
Related concepts
- Leber Hereditary Optic Neuropathy
- Photoreceptor Cells
- Retina
Research landscape
PubMed indexes 665 records tagged with the MeSH heading “Leber Congenital Amaurosis” (counts retrieved 2026-11-04). 227 of them (34.1%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 425 records.
Reviews account for 109 records (16.4%) and meta-analyses for 2. Randomized controlled trials number 1 (0.2%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 13 |
| 2010-2019 | 425 |
| 2020 onward | 227 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 109 | 16.4% |
| Meta-analyses | 2 | 0.3% |
| Randomized controlled trials | 1 | 0.2% |
Method: PubMed query "Leber Congenital Amaurosis"[MeSH Terms] with publication-type and date filters, retrieved 2026-11-04.
Reading the evidence in eye, ear, nose and throat
Eye, hearing, nose and throat studies rely on specialist tests (visual acuity, eye pressure, audiograms, scopes) and on patient-reported symptoms, which vary between people and with age. Some conditions improve without treatment, so comparison groups matter. Nothing on this page is advice about diagnosis or treatment; sudden loss of sight or hearing needs urgent care from a qualified clinician. Check how the outcome was tested, the age of the people studied and how long they were followed.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions | 2017 | Review article Design not recorded in structured metadata | 260 | cc by PMID 28689169 · DOI · PMC5574398 |
| Basolateral Mg2+ extrusion via CNNM4 mediates transcellular Mg2+ transport across epithelia: a mouse model | 2013 | Research article Design not recorded in structured metadata | 142 | cc by PMID 24339795 · DOI · PMC3854942 |
| Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial | 2022 | Research article Design not recorded in structured metadata | 126 | cc by PMID 35379979 · DOI · PMC9117145 |
| Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids | 2025 | Research article Design not recorded in structured metadata | 9 | cc by PMID 39934925 · DOI · PMC11817871 |
Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms.
- Closing excerpt
- We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (194 words)
Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28689169 · DOI · PMC5574398
Basolateral Mg2+ extrusion via CNNM4 mediates transcellular Mg2+ transport across epithelia: a mouse model [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Transcellular Mg(2+) transport across epithelia, involving both apical entry and basolateral extrusion, is essential for magnesium homeostasis, but molecules involved in basolateral extrusion have not yet been identified.
- Closing excerpt
- These results demonstrate the crucial importance of Mg(2+) extrusion by CNNM4 in organismal and topical regulation of magnesium.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (154 words)
Transcellular Mg(2+) transport across epithelia, involving both apical entry and basolateral extrusion, is essential for magnesium homeostasis, but molecules involved in basolateral extrusion have not yet been identified. Here, we show that CNNM4 is the basolaterally located Mg(2+) extrusion molecule. CNNM4 is strongly expressed in intestinal epithelia and localizes to their basolateral membrane. CNNM4-knockout mice showed hypomagnesemia due to the intestinal malabsorption of magnesium, suggesting its role in Mg(2+) extrusion to the inner parts of body. Imaging analyses revealed that CNNM4 can extrude Mg(2+) by exchanging intracellular Mg(2+) with extracellular Na(+). Furthermore, CNNM4 mutations cause Jalili syndrome, characterized by recessive amelogenesis imperfecta with cone-rod dystrophy. CNNM4-knockout mice showed defective amelogenesis, and CNNM4 again localizes to the basolateral membrane of ameloblasts, the enamel-forming epithelial cells. Missense point mutations associated with the disease abolish the Mg(2+) extrusion activity. These results demonstrate the crucial importance of Mg(2+) extrusion by CNNM4 in organismal and topical regulation of magnesium.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 24339795 · DOI · PMC3854942
Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial [3]
Abstract reading summary — source excerpts
- Opening excerpt
- CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness.
- Closing excerpt
- The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (222 words)
CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 ( NCT03140969 ), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit-risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35379979 · DOI · PMC9117145
Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Bialleleic pathogenic variants in LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment.
- Closing excerpt
- In summary, iPSC-derived retinal organoids are a powerful model for investigating the molecular and cellular changes associated with loss of LCA5 function and highlight the therapeutic potential of small molecules to treat retinal ciliopathies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (260 words)
Bialleleic pathogenic variants in LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. Here, we report the use of gene editing to generate isogenic LCA5 knock-out (LCA5 KO) induced pluripotent stem cells (iPSC) and their differentiation to retinal organoids. The molecular and cellular phenotype of the LCA5 KO retinal organoids was studied in detail and compared to isogenic controls as well as patient-derived retinal organoids. The absence of LCA5 was confirmed in retinal organoids by immunohistochemistry and western blotting. There were no major changes in retinal organoid differentiation or ciliation, however, the localisation of CEP290 and IFT88 was significantly altered in LCA5 KO and patient photoreceptor cilia with extension along the axoneme. The LCA5-deficient organoids also had shorter outer segments and rhodopsin was mislocalised to the outer nuclear layer. We also identified transcriptomic and proteomic changes associated with the loss of LCA5. Importantly, treatment with the small molecules eupatilin, fasudil or a combination of both drugs reduced CEP290 and IFT88 accumulation along the cilia. The treatments also improved rhodopsin traffic to the outer segment and reduced mislocalisation of rhodopsin in the outer nuclear layer (ONL). The improvements in cilia-associated protein localisation and traffic were accompanied by significant changes in the transcriptome towards control gene expression levels in many of the differentially expressed genes. In summary, iPSC-derived retinal organoids are a powerful model for investigating the molecular and cellular changes associated with loss of LCA5 function and highlight the therapeutic potential of small molecules to treat retinal ciliopathies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39934925 · DOI · PMC11817871
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy [5]
- Research article Inherited retinal diseases: Therapeutics, clinical trials and end points-A review [6]
- Research article The Status of RPE65 Gene Therapy Trials: Safety and Efficacy [7]
- Research article Let There Be Light: Gene and Cell Therapy for Blindness [8]
- Research article Gene therapy for RPE65-related retinal disease [9]
- Research article Gene therapy for inherited retinal diseases: progress and possibilities [10]
Full-text reviews on EvidenceLib
Open-access review articles about this topic, reproduced in full with authors, licence and references.
A Systematic Review and Meta-Analyses of Interventional Clinical Trial Studies for Gene Therapies for the Inherited Retinal Degenerations (IRDs)
Gearóid P. Tuohy, Roly Megaw · Biomolecules 2021 · CC BY 4.0
References
- Kumaran N, Moore AT, Weleber RG, Michaelides M. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions. . 2017. PMID 28689169 · DOI · PMC5574398
- Yamazaki D, Funato Y, Miura J, Sato S, Toyosawa S, Furutani K, et al.. Basolateral Mg2+ extrusion via CNNM4 mediates transcellular Mg2+ transport across epithelia: a mouse model. . 2013. PMID 24339795 · DOI · PMC3854942
- Russell SR, Drack AV, Cideciyan AV, Jacobson SG, Leroy BP, Van Cauwenbergh C, et al.. Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial. . 2022. PMID 35379979 · DOI · PMC9117145
- Athanasiou D, Afanasyeva TAV, Chai N, Ziaka K, Jovanovic K, Guarascio R, et al.. Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids. . 2025. PMID 39934925 · DOI · PMC11817871
- Cideciyan AV. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res. 2010. PMID 20399883 · DOI · PMC2903652
- Georgiou M, Fujinami K, Michaelides M. Inherited retinal diseases: Therapeutics, clinical trials and end points-A review. Clin Exp Ophthalmol. 2021. PMID 33686777 · DOI
- Pierce EA, Bennett J. The Status of RPE65 Gene Therapy Trials: Safety and Efficacy. Cold Spring Harb Perspect Med. 2015. PMID 25635059 · DOI · PMC4561397
- Dalkara D, Goureau O, Marazova K, Sahel JA. Let There Be Light: Gene and Cell Therapy for Blindness. Hum Gene Ther. 2016. PMID 26751519 · DOI · PMC4779297
- Miraldi Utz V, Coussa RG, Antaki F, Traboulsi EI. Gene therapy for RPE65-related retinal disease. Ophthalmic Genet. 2018. PMID 30335549 · DOI
- Hu ML, Edwards TL, O'Hare F, Hickey DG, Wang JH, Liu Z, et al.. Gene therapy for inherited retinal diseases: progress and possibilities. Clin Exp Optom. 2021. PMID 33689657 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.