The authors searched PubMed and other relevant databases for combinations of “human amniotic membrane,” “extracellular vesicles,” “exosomes,” “microvesicles” and “ophthalmology.” Because the number of studies was limited and their methods varied, they did not perform a formal systematic review. Instead, the mini-review critically summarizes key findings, methodological limitations and unresolved translational questions, following the MISEV 2023 guidance for extracellular-vesicle research.

Human amniotic membrane is a layered tissue containing epithelial and mesenchymal stromal cells, and it has long been used in skin and corneal wound repair. Its secretome includes an extracellular-vesicle fraction alongside soluble factors and extracellular-matrix components. Recent studies indicate that vesicles from amniotic epithelial cells and mesenchymal stromal cells carry proteins, microRNAs, lipids and other signaling molecules, but their molecular cargo and functional contributions remain incompletely characterized.

Preclinical evidence links human amniotic membrane-derived vesicles with several potentially relevant biological functions. In mouse and rat models of chronic liver fibrosis, vesicles reduced inflammatory and fibrotic measures, suppressed hepatic stellate-cell activation and migration, and shifted macrophages from a pro-inflammatory toward a pro-regenerative phenotype. In contrast, one study of peripheral blood mononuclear cells found that the EV-free fraction, rather than the EV-enriched fraction, produced the measured immunomodulatory effects. The authors therefore caution that outcomes depend on the cellular source, target cell and biological context, and that soluble mediators may account for some reported effects.

In ocular models, vesicles derived from amniotic mesenchymal stromal cells protected retinal pigment epithelial cells from oxidative stress in vitro and in mice. The reported effects included activation of the PI3K/Akt/FoxO3 pathway, less apoptosis and reactive oxygen species, maintenance of retinal thickness and improved photoreceptor survival in age-related macular degeneration models. In diabetic retinopathy, subconjunctival administration of EV-rich conditioned medium delayed retinal vascular pathology, reduced lens opacity and lessened ocular inflammation in rats.

Other experiments examined the optic nerve, ocular surface and cornea. Intravitreal injection of EV-enriched conditioned medium from amniotic mesenchymal stromal cells or epithelial cells lowered intraocular pressure and preserved retinal ganglion-cell survival in a rat glaucoma model, although the study could not separate vesicle effects from those of soluble factors. Topical epithelial-cell-derived vesicles improved tear-film stability, reduced corneal staining and promoted epithelial regeneration in a mouse dry-eye model. In mouse corneal alkali-burn experiments, the vesicles accelerated re-epithelialization and reduced opacity. Reported molecular and signaling findings included activation of focal adhesion kinase, modulation of extracellular-matrix genes and attenuation of the TGF-beta/SMAD2/3 fibrotic pathway.

These results support further investigation of human amniotic membrane vesicles as cell-free candidates, but they do not establish clinical efficacy. Isolation and enrichment methods used across the literature include ultracentrifugation, affinity purification, size-exclusion chromatography, precipitation kits and filtration or concentration of conditioned media. These approaches can differ substantially in particle recovery, purity and retention of soluble proteins. Studies using EV-enriched conditioned medium are especially difficult to interpret because the specific contribution of vesicles cannot be separated confidently from co-isolated factors.

Translation also faces variability associated with donor, gestational age and anatomical region of the membrane. The review reports that vesicles have been observed at the apical surface of amniotic epithelial cells in the central region, but static microscopy alone cannot establish a specific biogenesis pathway. It also states that no Good Manufacturing Practice manufacturing protocol specific to human amniotic membrane-derived vesicles has yet been reported, although characterization and quality-control work on mesenchymal-cell vesicular fractions provides a starting point. Validated potency assays, reproducible release criteria and larger-animal studies remain necessary.

Route of administration presents further uncertainty. Topical eye drops may lose vesicles through tear turnover, nasolacrimal drainage and the corneal epithelial barrier, while subconjunctival or intravitreal delivery can improve tissue access but requires injection and may introduce procedure-related risks. Biomaterial depots, ligand targeting and membrane engineering are being investigated to improve retention and delivery, but dosing, biodistribution, clearance, long-term efficacy and reproducibility remain unresolved. The established ophthalmic safety record of amniotic membrane tissue also cannot be directly applied to purified vesicles, particularly for intraocular administration.

Overall, the mini-review describes human amniotic membrane-derived vesicles as a promising experimental platform for regenerative ophthalmology, not as an established treatment. The strongest available evidence comes from cell cultures and small-animal models, with incomplete molecular attribution and substantial technical heterogeneity limiting direct comparisons. Before clinical development can proceed, the field will need standardized preparation and characterization, functional potency testing, rigorous contaminant and immunogenicity screening, delivery optimization, long-term safety evaluation and regulatory oversight under frameworks for complex biological medicinal products.

Subject of Research: Preclinical evidence and translational limitations for human amniotic membrane extracellular vesicles in ophthalmology

Article Title: Activities of human amniotic membrane extracellular vesicles with a focus on ophthalmology

Article References: Lulli, M., Calcagno, S., Peppicelli, S., Isoldi, G., Kaur, I.-P., Papucci, L., Magnelli, L., Mannini, A., & Schiavone, N. (2026). Activities of human amniotic membrane extracellular vesicles with a focus on ophthalmology. Molecular Biology Reports, 53(1), Article 1593. https://doi.org/10.1007/s11033-026-12756-0

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12756-0

Keywords: human amniotic membrane, extracellular vesicles, ophthalmology, regenerative medicine, corneal repair, retinal disease, ocular inflammation, cell-free therapy, extracellular-vesicle manufacturing, Activities, human, amniotic

The macular hole is a full-thickness defect in the macula, the pinprick-sized patch of retinal tissue responsible for sharp central vision. When it forms, patients typically notice distortion, a dark or missing spot in the middle of their visual field, and progressive loss of reading ability. Optical coherence tomography, or OCT, is the diagnostic workhorse: it uses low-coherence light to produce cross-sectional images of the retina with micrometer-scale resolution, letting clinicians see the hole’s edges, the lifted cuff of surrounding tissue, and the state of the underlying choroid. From these scans, ophthalmologists extract a handful of measurements — minimum hole diameter, base diameter, hole height on the left and right sides, and central choroidal thickness — that together inform staging and surgical strategy.

The problem is that these measurements are slow, subjective, and vulnerable to inter-observer variability. Two experienced graders can produce different numbers from the same scan, and in a busy clinic the differences can matter: hole size and configuration influence whether a surgeon expects a high closure rate with a simple gas tamponade or needs more extensive vitreoretinal surgery. Automating the extraction of these parameters has therefore been a long-standing goal, but medical images pose distinctive challenges for deep learning. OCT scans are grayscale, low in contrast compared with natural photographs, and dominated by layered textures that differ radically from the colorful, object-rich images that standard detection networks were designed to handle.

The research team, led by Zhiyuan Zhao, Xinqi Yu, Xiaochun Wang, Bin Wu, and Sheng Zhou from the Institute of Biomedical Engineering of the Chinese Academy of Medical Sciences and Peking Union Medical College together with Tianjin Eye Hospital, tackled these challenges with a fusion architecture. LMMR-YOLO — short for Lightweight Model of Mask R-CNN-YOLO — combines two of the most influential families in computer vision. Mask R-CNN, a two-stage detector prized for its precise instance segmentation, was used to expand the training dataset in a targeted way and to contribute fine-grained localization. YOLOv12-obb, a modern single-stage detector oriented around rotated bounding boxes, supplied the speed and efficiency backbone. The fusion means the system can both delineate the lesion accurately and detect it fast enough for routine use.

Several technical innovations underpin the model’s performance on grayscale medical data. The researchers integrated a grayscale image adaptation module with Efficient Channel Attention, a mechanism that lets the network learn which feature channels carry the most diagnostic information — essentially teaching it where to look in the layered structure of a retinal scan. They replaced heavy backbone components with C2f_Ghost and A2C2f_Lite modules, lightweight building blocks that preserve feature extraction power while slashing computational cost. An Oriented Bounding Box detection head allows the model to fit tightly around lesions that appear at arbitrary angles in the scan, and an Image Enhancement Algorithm sharpens contrast before detection, with a Fusion Detection Algorithm merging the outputs of the enhanced pipeline and the Mask R-CNN branch into a single verdict.

The study was retrospective, drawing on 606 OCT images from 61 patients, with ethics approval from Tianjin Eye Hospital and a waiver of individual informed consent because the data were anonymized. Performance was evaluated with the standard battery of detection metrics: precision, recall, mean average precision at an intersection-over-union threshold of 0.5, F1-score, and accuracy. On the internal test set, LMMR-YOLO achieved an mAP@0.5 of 92.69 percent and an overall accuracy of 94.78 percent for key-point detection of macular hole parameters. Precision reached 97.14 percent, meaning that when the model flags a measurement point, it is almost always correct, while recall of 87.88 percent indicates it catches the large majority of true points. The harmonic F1-score of 92.28 percent balances those two figures and sits comfortably in the range clinicians would expect from careful human graders.

Two secondary results are particularly telling about the model’s reliability. Normalized classification accuracy for central choroidal thickness — a parameter that reflects the health of the vascular layer beneath the retina and is increasingly used in staging — came out at 0.97. And the mirror misidentification rate between left hole height and right hole height, an error mode in which a system confuses the two sides of an asymmetric hole, was just 0.03. Those numbers matter because staging systems for macular holes depend on exactly such lateral distinctions; a model that routinely swapped left and right would be clinically useless no matter how impressive its headline accuracy.

Equally important is what the model does not cost. LMMR-YOLO carries only 3.34 million trainable parameters and requires 11.10 gigafloating-point operations per inference — figures that place it firmly in the lightweight category, small enough to contemplate running on standard clinic hardware or even portable devices rather than server farms. Inference speed measured 9.44 frames per second, approaching real-time performance, and the training time was short. In medical AI, where many celebrated models demand billions of parameters and hours of GPU time per scan batch, a system that balances accuracy against efficiency is arguably more valuable than a marginally more accurate but computationally prohibitive alternative. The authors frame this balance as a new paradigm for medical grayscale image analysis and model training.

The clinical implications extend beyond the numbers. Accurate, automated extraction of minimum hole diameter, base diameter, hole height, and choroidal thickness could standardize staging of full-thickness and lamellar macular holes, reduce grading variability between centers, and support personalized surgical planning — for example, helping surgeons anticipate closure likelihood and choose among operative techniques. Because the pipeline is fast and light, it could also be embedded in screening workflows, flagging urgent cases in high-volume imaging services where specialist reading time is scarce. The researchers suggest the approach supports ophthalmic diagnosis, staging, and personalized care, and its architecture — grayscale adaptation, channel attention, oriented detection, and fusion of segmentation and detection branches — is general enough to be adapted to other retinal and medical imaging tasks.

Caveats remain, as they do for any retrospective single-center study. The dataset of 606 images from 61 patients, while substantial for a rare lesion, will need validation on larger and more diverse cohorts before the model can be trusted across different scanner manufacturers, image qualities, and patient populations. The published version is an early-release, peer-reviewed accepted manuscript that will undergo further editorial refinement. Still, the trajectory is clear: the fusion of segmentation precision with detection speed, tuned specifically for the grayscale, low-contrast world of OCT, has produced a system that measures the anatomy of a sight-threatening lesion nearly as well as experts do — and does it in milliseconds. For the millions of people at risk of macular holes worldwide, that speed and consistency could eventually translate into earlier detection, better-planned surgery, and more preserved vision.

Subject of Research: Deep learning-based automatic detection and measurement of macular hole parameters in optical coherence tomography images

Article Title: A deep learning-based study on automatic extraction and measurement of macular hole parameters

Article References: Zhao, Z., Yu, X., Wang, X., Lu, K., Wu, B., & Zhou, S. (2026). A deep learning-based study on automatic extraction and measurement of macular hole parameters. BMC Medical Imaging. https://doi.org/10.1186/s12880-026-02899-8

Image Credits: AI Generated

DOI: 10.1186/s12880-026-02899-8

Keywords: macular hole, deep learning, optical coherence tomography, LMMR-YOLO, Mask R-CNN, YOLOv12, medical imaging, ophthalmology, retinal disease, image segmentation, lightweight neural network, computer-aided diagnosis

The prize itself carries a layered history. Known previously as the Yergin-New International Prize for Biomedical Research, it was renamed this year in recognition of the Yergin family’s longstanding support of the program. It commemorates Maria I. New, MD, the groundbreaking Mount Sinai pediatric endocrinologist who passed away in 2024 and whose six-decade career transformed the understanding and treatment of adrenal steroid disorders. The prize, now in its fifth year, is awarded annually to a distinguished physician-scientist whose lifetime achievements have led, or may lead, to new ways to prevent and treat human disease, and it has quickly become regarded as one of the foremost international honors in medical research.

Ferrara will receive a $50,000 award and deliver the Yergin Family Distinguished Lecture during a ceremony at Mount Sinai in New York City on Wednesday, November 18. The recognition caps a career that has already earned election to both the National Academy of Sciences and the National Academy of Medicine, along with the 2010 Lasker-DeBakey Clinical Medical Research Award, the 2013 Breakthrough Prize in Life Sciences, and the 2014 Canada Gairdner International Award. Together, these honors trace an unusually complete arc from basic discovery to clinical revolution.

The scientific story began in earnest in 1989, when Ferrara and his colleagues isolated and cloned VEGF, finally pinning down the biological signal responsible for angiogenesis, the formation of new blood vessels. The problem they tackled had puzzled vascular biologists for decades. Tumors, embryonic tissues, and healing wounds all emit some diffusible factor that coaxes nearby capillaries to extend toward them, but the identity of that factor remained elusive. By purifying and cloning the molecule, Ferrara’s team gave the field both a concrete target and a powerful set of experimental tools, including antibodies and genetic models that could test what VEGF actually does in living organisms.

Subsequent work revealed a biology of elegant duality. VEGF is indispensable for normal blood-vessel development, guiding the vascular system as it wires the embryo and maintains tissue health in adulthood. Yet the same signaling pathway, when overactive, becomes an engine of disease. Ferrara’s laboratory demonstrated that tumors exploit VEGF to sustain angiogenesis, supplying themselves with the oxygen and nutrients needed to grow beyond a few millimeters. In the eye, excessive VEGF drives the abnormal, leaky vessel growth that destroys vision in neovascular age-related macular degeneration, diabetic retinopathy, and other retinal diseases. The insight that a single pathway could be both essential and pathological set the stage for a new therapeutic strategy: block the signal, and starve the disease.

That strategy bore fruit in oncology first. Ferrara’s group showed that neutralizing VEGF could slow tumor growth in preclinical models, an achievement that led directly to bevacizumab, a monoclonal antibody designed to bind VEGF and prevent it from activating its receptors on blood-vessel cells. In 2004, the U.S. Food and Drug Administration approved bevacizumab for metastatic colorectal cancer, making it the first anti-angiogenic cancer therapy ever approved. Anti-VEGF approaches have since become part of standard treatment for several malignancies, including colorectal, kidney, lung, cervical, and ovarian cancers. In hepatocellular carcinoma, combinations of anti-VEGF drugs with immunotherapy are now standard of care, reflecting a growing understanding that pruning a tumor’s vasculature can also reshape the immune environment around it.

The ophthalmic branch of the story proved equally transformative. Ferrara and his collaborators established that VEGF is a key driver of neovascular age-related macular degeneration, in which rogue vessels invade the retina and leak fluid into tissue that must remain dry and precisely layered to support sight. Their work led to ranibizumab, an antibody fragment engineered for intraocular use, and helped establish anti-VEGF injection therapy as the standard of care for several serious eye disorders. For patients who once faced inevitable central vision loss, the ability to preserve or even improve sight through regular treatment has been one of the most consequential clinical advances of the past two decades.

Leaders at Mount Sinai framed the award as a case study in the value of fundamental research. “Dr. Ferrara’s work is a remarkable example of how a fundamental discovery in biology can change the course of medicine,” said Mone Zaidi, MD, PhD, MACP, Director of Mount Sinai’s Institute for Translational Medicine and Pharmacology and Mount Sinai Professor of Clinical Medicine. “By identifying VEGF and demonstrating its role in blood-vessel growth, he opened the door to treatments that have changed outcomes for patients with cancer and serious eye diseases around the world.” Daniel Yergin, PhD, the Pulitzer Prize-winning author and economic historian who endowed the prize along with his wife, foreign policy expert Angela Stent, PhD, echoed that theme: “Napoleone Ferrara’s discovery demonstrates the extraordinary impact that fundamental biomedical research can have on human health. His work has transformed the treatment of cancer and blinding eye diseases and continues to influence the development of new therapies.”

Ferrara’s laboratory has not rested on its accomplishments. His current research continues to probe VEGF and other pathways governing blood-vessel growth, with two clinical problems in sharp focus. The first is treatment burden: patients with retinal disease typically require frequent intraocular injections, and his team is developing longer-acting therapies that could extend the interval between treatments. The second is geographic atrophy, the advanced, dry form of age-related macular degeneration, for which treatment options remain limited and which represents one of the largest unmet needs in ophthalmology. Both efforts extend the same logic that produced the original breakthrough, namely that understanding the molecular machinery of the vasculature reveals new points of therapeutic intervention.

The selection process behind the award reflects its international ambitions. Winners are chosen by a jury of distinguished physician-scientists chaired by Dr. Zaidi. The 2026 jury included Nobel laureate Aaron Ciechanover of the Technion in Haifa; Nancy Andrews of Boston Children’s Hospital; Michael J. Welsh of the University of Iowa; Jeffrey Friedman of The Rockefeller University and the Howard Hughes Medical Institute; and Anna Wedell of the Karolinska Institutet in Stockholm. “We are grateful to the distinguished members of the international jury for dedicating their time and expertise to reviewing this year’s exceptional group of nominees and selecting Dr. Ferrara as the recipient,” Dr. Zaidi said. Eric J. Nestler, MD, PhD, Dean of the Icahn School of Medicine at Mount Sinai and Chief Scientific Officer of the Mount Sinai Health System, noted that the award was first established in honor of Dr. New and her extraordinary legacy, and expressed gratitude for the vision of Daniel Yergin and Angela Stent in endowing the program to live in perpetuity. “Dr. Ferrara’s achievements reflect the lasting impact of research that begins with fundamental questions and ultimately changes the way diseases are treated,” Nestler said. Administered by Mount Sinai’s Institute for Translational Medicine and Pharmacology, the prize stands as both a tribute to Maria New’s legacy and a reminder that the path from a cloned molecule to medicines used around the world often begins with a single, persistent question about how life works.

Subject of Research: Award of the 2026 Yergin Family International Prize for Biomedical Research to VEGF discoverer Napoleone Ferrara

Article Title: Napoleone Ferrara, MD, receives 2026 Yergin Family International Prize for Biomedical Research

Article References: Napoleone Ferrara, MD, receives 2026 Yergin Family International Prize for Biomedical Research. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: Napoleone Ferrara, VEGF, angiogenesis, Yergin Family Prize, Mount Sinai, bevacizumab, ranibizumab, age-related macular degeneration, cancer therapy, anti-angiogenic treatment, retinal disease, biomedical research award

The new analysis, led by Kai-Yang Chen of Chang Gung Memorial Hospital in Taiwan, together with Hoi-Chun Chan of China Medical University and Chi-Ming Chan of Cardinal Tien Hospital and Fu Jen Catholic University, was prospectively registered with PROSPERO and conducted according to the PRISMA 2020 reporting guidelines. The team searched PubMed, Scopus, Web of Science, ScienceDirect, and the Cochrane Library from inception through April 21, 2026, screening more than 1,200 records to identify 25 eligible studies spanning in vitro experiments, animal models, and early- to late-phase human trials.

The biological rationale is compelling. Diabetic retinopathy alone affects approximately 22 percent of people with diabetes, roughly 103 million adults as of 2020, and is projected to reach 160 million by 2045. Neovascular age-related macular degeneration shares a common final pathway: VEGF-driven pathological angiogenesis and breakdown of the blood-retinal barrier, producing macular edema, capillary nonperfusion, and progressive retinal damage. Current anti-VEGF injections suppress these processes only transiently, requiring repeated administration and carrying procedural risks including endophthalmitis, elevated intraocular pressure, and cataract. Gene therapy, typically delivered via adeno-associated viral (AAV) vectors, aims to turn the eye itself into a factory for therapeutic proteins, achieving sustained pathway-level disease control after a single procedure.

The preclinical results are striking. Across eight animal and in vitro studies, gene therapy significantly reduced pathological neovascularization, with a pooled standardized mean difference of −1.16 (95 percent confidence interval, −1.48 to −0.84; p < 0.001), meaning the reduction exceeded one full standard deviation compared with controls. Remarkably, heterogeneity was negligible, with an I² of 0 percent, indicating extraordinary consistency despite differences in vector platforms, transgenes, and disease models. Within the oxygen-induced retinopathy subgroup, the effect was even larger, with a standardized mean difference of approximately −1.29, reflecting robust suppression of ischemia-driven retinal angiogenesis by constructs including soluble VEGF receptor sFLT-1, pigment epithelium-derived factor (PEDF), angiostatin, and the antioxidant enzyme MnSOD.

Vascular leakage, the other hallmark of these diseases, was also significantly reduced. Three preclinical experimental studies using AAV- and adenovirus-mediated gene transfer showed a pooled mean difference of 0.215 on a directionally harmonized scale (95 percent CI, 0.178 to 0.251; p < 0.001), again with zero heterogeneity. Complementary mechanistic work showed that sFLT-1 expression reduced VEGF-induced endothelial permeability by roughly 40 to 60 percent while preserving tight junction proteins, and antioxidant gene transfer reduced oxidative stress-driven barrier breakdown. In vivo, fluorescein leakage scores fell by 30 to 70 percent following anti-VEGF or PEDF gene delivery, while antioxidant therapy reduced acellular capillaries by approximately 40 to 60 percent, indicating preservation of the retinal microvasculature beyond angiogenesis alone.

The clinical evidence, though still early-stage, points in the same direction. Across eight clinical cohorts, ocular gene therapy produced a statistically significant reduction in central subfield thickness of −55.30 micrometers (95 percent CI, −72.58 to −38.03; p < 0.001), a meaningful anatomical improvement reflecting reduced macular edema and fluid accumulation. In the phase 1 trial of intravitreal AAV2-sFLT01 reported by Heier and colleagues, individual eyes showed central thickness reductions of up to roughly 600 micrometers at week 18 and 860 micrometers by week 52, while the phase 2a trial of subretinal rAAV.sFLT-1 by Constable and colleagues demonstrated stabilization of retinal thickness over 52 weeks.

Perhaps the most clinically consequential finding concerns treatment burden. Across seven clinical cohorts, the pooled logit event rate of 0.62 (95 percent CI, 0.20 to 1.04; p = 0.0039) corresponds to approximately 65 percent of participants meeting study-specific criteria for reduced supplemental anti-VEGF injections after gene therapy. Heterogeneity was low, at roughly 11 percent, despite differences between AAV and lentiviral platforms, delivery routes, and dosing regimens. This outcome directly addresses the central weakness of current standard care: the cumulative burden and adherence challenges of repeated intravitreal injections.

The analysis also situates these findings within a rapidly advancing clinical pipeline. Next-generation programs including ABBV-RGX-314, ADVM-022 (ixo-vec), and 4D-150 have progressed into phase II/III trials for neovascular retinal diseases, with early data showing reductions in anti-VEGF injection burden of up to 80 to 97 percent alongside stable visual and anatomical outcomes. Notably, 4D-150 employs dual inhibition of VEGF-A and VEGF-C, an evolution beyond earlier single-target constructs, while ADVM-022 offers intravitreal delivery that avoids surgery, and RGX-314 has shown durability across both subretinal and suprachoroidal routes. The concordance between these emerging results and the meta-analysis findings reinforces the biological validity of sustained intraocular VEGF suppression.

The authors are careful to acknowledge limitations. Some functional outcomes were drawn from trials of non-angiogenic inherited retinal disorders, including Leber hereditary optic neuropathy, RPE65-associated Leber congenital amaurosis, and X-linked retinitis pigmentosa, and were interpreted as proof of concept for gene delivery and durability rather than anti-angiogenic efficacy. The XIRIUS phase 2/3 trial of cotoretigene toliparvovec in X-linked retinitis pigmentosa, for example, missed its primary endpoint, underscoring the importance of disease context, dose selection, and intervention timing. Animal models, meanwhile, do not fully reproduce the chronic metabolic milieu of human diabetic retinopathy. Publication bias analyses were largely reassuring, though small-study effects were flagged for central subfield thickness and injection burden outcomes, and trim-and-fill sensitivity analyses supported the robustness of the primary estimates.

Safety data across translational stages suggest an acceptable early profile, with adverse events largely procedure-related or reflecting transient ocular inflammation. However, the authors caution that limited sample sizes, heterogeneous reporting, and incomplete long-term follow-up constrain safety conclusions, particularly given the potential irreversibility of ocular gene transfer. The path forward, they argue, requires adequately powered, disease-specific randomized trials, standardized outcome definitions, harmonized optical coherence tomography metrics, and long-term surveillance of transgene durability and immunogenicity. If those trials confirm the signals synthesized here, ocular gene therapy could shift the treatment of neovascular retinal disease from a lifetime of monthly injections toward long-acting or single-administration therapy, fundamentally changing the outlook for the hundreds of millions at risk of preventable vision loss worldwide.

Subject of Research: Ocular gene therapy targeting retinal angiogenesis and vascular leakage in neovascular retinal diseases

Article Title: Ocular gene therapy targeting retinal angiogenesis and vascular leakage: translational and clinical evidence from a systematic review and meta-analysis

Article References: Chen, K.-Y., Chan, H.-C., & Chan, C.-M. (2026). Ocular gene therapy targeting retinal angiogenesis and vascular leakage: translational and clinical evidence from a systematic review and meta-analysis. Angiogenesis, 29(4), Article 66. https://doi.org/10.1007/s10456-026-10050-y

Image Credits: AI Generated

DOI: 10.1007/s10456-026-10050-y

Keywords: ocular gene therapy, retinal angiogenesis, vascular leakage, anti-VEGF, adeno-associated virus, neovascular age-related macular degeneration, diabetic retinopathy, systematic review, meta-analysis, sFLT-1, central subfield thickness, retinal disease