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Gene therapy for neovascular age-related macular degeneration: rationale, clinical trials and future directions

2020· review· en· W3015569704 on OpenAlexfundno aff
Thales A. C. de Guimarães, Michalis Georgiou, James Bainbridge, Michel Michaelides

Bibliographic record

VenueBritish Journal of Ophthalmology · 2020
Typereview
Languageen
FieldMedicine
TopicRetinal Diseases and Treatments
Canadian institutionsnot available
FundersNational Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyMoorfields Eye Hospital NHS Foundation TrustRetina UKNational Institute for Health and Care ResearchNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchMoorfields Eye CharityWellcome TrustWellcomeFight for SightFoundation Fighting Blindness
KeywordsMacular degenerationMedicineClinical trialBlindnessGenetic enhancementBevacizumabIntensive care medicineOphthalmologyOptometrySurgeryPathologyGeneChemotherapy

Abstract

fetched live from OpenAlex

Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the developed world. Antivascular endothelial growth factor therapy has transformed the management and outcome of neovascular AMD (nAMD), although the need for repeated intravitreal injections-even lifelong-and the related complications, high drug costs, frequent clinic visits and repeated imaging have resulted in an enormous burden both to healthcare systems and patients. The application of gene therapy approaches for sustained delivery of a range of antiangiogenic proteins has the promise of helping to address these aforementioned challenges. A number of early phase clinical trials of gene therapy in nAMD have provided encouraging results, with many more ongoing or anticipated. There remain significant areas of controversy, including regarding the optimal treatment targets, routes of administration and potential safety concerns. In this review we aim to provide an update of the current status of gene therapy for nAMD and briefly discuss future prospects.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0020.002
Science and technology studies0.0000.001
Scholarly communication0.0010.002
Open science0.0010.001
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0050.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.171
GPT teacher head0.457
Teacher spread0.287 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations90
Published2020
Admission routes1
Has abstractyes

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