The researchers evaluated SAEs from trial results from inherited retinal disease (IRDs), with the prevalence of all IRDs being 1:1380, and with the most common being retinitis pigmentosa (RP, 1:4,000), Stargardt disease (1:10,000), and choroideremia (CHM, 1:50,000). The most commonly utilised viral vector in retinal diseases is adeno-associated virus type 2 (AAV2) across different serotypes, such as AAV2/2 (RPE tropism) and AAV2/8 (cone photoreceptor tropism) and the three main methods of delivery are intravitreal, subretinal, or suprachoroidal injections. Following a systematic review process, the researchers collected 31 clinical trial studies and SAEs were recorded in 51 out of 438 eyes (11.6%) that received subretinal injections and in 11 out of 348 eyes (3.2%) that received intravitreal injections. There were fewer intravitreal-related SAEs and less vision loss compared to subretinal gene therapy.

Figure 1. Serious adverse event breakdown by injection route. For subretinal trials (A) and intravitreal trials (B), the outer wheels show the proportion of SAE type, while the inner wheel shows the proportion of eyes that experienced vision loss due to the associated SAE. For all injected eyes, the number and percentage of eyes that experienced each SAE are included in the provided table (left columns). For any given SAE, the number and percentage of eyes experiencing vision loss are included in the provided tables (right columns).

[The research work is licensed under the terms  of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), cited by Berger et al., entitled by: “Retinal Viral Gene Therapy: Impact of Route of Administration on Serious Adverse Events—A Systematic Review”, Clinical & Experimental Ophthalmology, 2025; 0:1–19 https://doi.org/10.1111/ceo.14593].

Inflammation was the predominant SAE following intravitreal injections, whereas unexplained vision loss was the most common for subretinal injections. Clinical trials utilising subretinal injections met primary or secondary efficacy endpoints more than intravitreal trials. Eighteen studies (429 eyes) of post-approval LUXTURNA (voretigene neparvovec) were reviewed, and SAEs were reported in 24.7% of eyes, retinal degeneration being most common (20.7%). For 58 animal studies, SAEs were recorded in 17.3% of eyes that received subretinal injections and 8.7% of eyes that received intravitreal injections.  In addition, the researchers commented that the purity and quality of drug production is crucial, in particular to the number of capsids loaded with viral genomes. Some capsids may be empty and some may be full.  Without data being made available on the production process, it will be unclear on what the level of dosage of the gene therapy treatment.  In conclusion, the researchers stated that, “we recommend that future viral gene therapy studies evaluate chorioretinal atrophy (CRA) specifically as an adverse event. Studies should follow their subjects for an extended period, preferably at least a year, to assess the development of CRA. For consistency, viral genomes and capsid particles should both be reported. Additionally, when reporting inflammation, quantitative methods should be used such as Standardisation of Uveitis Nomenclature (SUN). For animal studies, visual function assessments should be included in safety assessments. It is also recommended to use animal disease models, when possible, to accurately assess safety.”

Fundus autofluorescence is a non-invasive imaging modality that can map naturally and pathologically occurring fluorophores in the posterior pole, first utilized for in vivo fundus imaging in 1995 characterizing the intrinsic autofluorescent properties of the retina. Technical improvements have developed in the interim utilizing the fluorescent properties of lipofuscin within the retinal pigment epithelium (RPE) to create an image. Lipofuscin, a byproduct of lysosomal breakdown of photoreceptor outer segments, is composed of numerous bisretinoids including A2E, A2PE, isoA2E, and A2-DHP-PE. When subjected to a light source, these bisretinoids absorb blue light with a peak excitation wavelength of 470nm and emit yellow-green light with a peak wavelength of 600nm, depending on the chemical makeup of the lipofuscin. Since many retinal pathologies often lead to RPE dysfunction and an accumulation of lipofuscin, abnormal patterns of autofluorescence (AF) on FAF imaging can act as markers for retinal disease.

Figure 1. Retinoid visual cycle and the origin of fundus autofluorescence signal. An illustration of the retinoid visual cycle that takes place between the retinal pigment epithelium and the outer segments of photoreceptors is shown. Interruption of the visual cycle at any point can lead to the development of inherited retinal degenerations. Accumulation of bisretinoids in retinal pigment epithelium cells as a byproduct of the cycle is the source of fundus autofluorescence signal. [The research work is licensed under the terms  of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), cited by Oh et al., entitled by: “Fundus Autofluorescence in Inherited Retinal Disease: A Review”, Cells 2025, 14, 1092].

The researchers explained that FAF is “an indispensable tool in the diagnosis and monitoring of numerous retinal diseases. Across the spectrum of IRDs, including Stargardt disease and pattern dystrophies, RP, choroideremia, and mitochondrial retinopathies, FAF has demonstrated consistent utility in disease diagnosis, monitoring of progression, and guiding prognostication. Several biomarkers for potential clinical trials, such as changes in hyperautofluorescent ring size or area of hypoautofluorescent atrophy, are increasingly being considered as potential outcome measurements in clinical trials. As our understanding of IRDs deepens, FAF will likely remain a mainstay of both clinical care and research.”

Figure 2. Hyperautofluorescent rings in retinitis pigmentosa seen on fundus autofluorescence compared to color fundus photography. (A) Montage color fundus photographs of a 36-year-old patient with autosomal dominant retinitis pigmentosa due to mutations in RHO demonstrate waxy pallor of the optic nerve, vascular attenuation and nasal and inferior bone spicules. (B) 55◦ field fundus autofluorescence demonstrates a central hyperautofluorescent ring, smaller in the right eye than the left, which is not seen on color fundus photographs (green arrows). Areas of both definitely decreased autofluorescence (red arrows) and questionably decreased autofluorescence can be seen (pink arrows). [The research work is licensed under the terms  of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), cited by Oh et al., entitled by: “Fundus Autofluorescence in Inherited Retinal Disease: A Review”, Cells 2025, 14, 1092].

In addition, fundus autofluorescence provides a quantitative outcome measure for natural history studies, valuable for subsequently supporting clinical trials from new experimental treatments. The recent US researchers have commented that “such studies have become increasingly common, particularly for genetically defined forms of RP, with many incorporating FAF to monitor disease progression. In the past two years alone, multiple natural history studies for various forms of RP have been described”.  According to the researchers, FAF enables objective quantitative assessment of retinal atrophy to evaluate whether treatment slows disease progression compared to untreated eyes”.

The AI algorithm (termed “AIRDetect”) automatically identified segment relevant features from SD-OCT images, providing a more detailed and comprehensive direct view of the 3D structure of the retina, compared to 2D FAF images. The basic results of the study showed that automatic segmentation was applied to 272,168 b-scans across 7,405 SD-OCT volumes encompassing 176 unique genes. Accounting for age, male patients exhibited significantly more EZ-loss (19.6mm² vs 17.9mm², p<2.8×10⁻⁴) and RPE-loss (7.79mm² vs 6.15mm², p<3.2×10⁻⁶) than females. RPE-loss was significantly higher in Asian patients than other ethnicities (9.37mm² vs 7.29mm², p<0.03). ICS average total volume was largest in RS1 (0.47mm³) and NR2E3 (0.25mm³), SRF in BEST1 (0.21mm³) and PED in EFEMP1 (0.34mm³). BEST1 and PROM1 showed significantly different patterns of EZ-loss (p<10⁻⁴) and RPE-loss (p<0.02) comparing the dominant to the recessive forms. Sectoral analysis revealed significantly increased EZ-loss in the inferior quadrant compared to superior quadrant for RHO (Δ=−0.414 mm², p=0.036) and EYS (Δ=−0.908 mm², p=1.5×10⁻⁴).

The researchers analysed the phenotypes of genes associated with both recessive and dominant inheritance patterns. In summary, in BEST1,  there was higher ICS and SRF in the recessive forms of the condition which resulted in higher retina thickness. In PROM1 there was higher EZ- and RPE-loss overall in the recessive form, whereas in the dominant form EZ- and RPE-loss were limited to the centre.  In RP1, the recessive form had higher EZ- and RPE-loss and a decreased retina thickness and, in GUCY2D, the dominant form had increased central EZ- and RPE-loss, compared to the recessive form observing a milder pathology and a thicker retina. Finally, in NR2E3, the dominant form had widespread EZ-loss and increased inferior RPE-loss, whereas the recessive form was milder (Figure 1 below):

Figure 1: EDTRS region plots highlighting different phenotypes between dominant and recessive forms of disease for a.) BEST1, b.) PROM1, c.) RP1, d.) GUCY2D and e.) NR2E3. The recessive forms of disease are more severe for BEST1, PROM1 and RP1 and less severe for GUCY2D and NR2E3. [Open access content is authored by Woof et al., entitled, “Quantification of Optical Coherence Tomography Features in >3500 Patients with Inherited Retinal Disease Reveals Novel Genotype-Phenotype Associations”, as a medRxiv preprint doi: https://doi.org/10.1101/2025.07.03.25330767; this version posted July 3, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license].

Clinical trials use multiple metrics for psychophysical tests, electrophysiological tests, multimodal imaging and adaptive optics however, analysis of choroidal structure, with genetically characterized RP (autosomal dominant (AD), autosomal recessive (AR), and X-linked (XL) subgroups), could also provide other valuable metrics. In their current study in Vancouver, researchers used choroidal parameters (thickness, area, volume, and choroidal vascularity index (CVI)) to assess for functional relationships and predictors of degenerative pathologies. A normal central thickness of the choroid are approximately 225 to 300 μm, supporting the metabolic demands of the outer retina (see Table 1 below). Choroidal blood flow is dynamic in health and disease and these changes are quantifiable – choroidal thickness [CT], choroidal vascularity index [CVI] – as markers of disease activity. Consequently, researchers propose that choroidal anatomy may be warranted in patients with RP and other IRDs.

Figure 1. Technique for measuring choroidal parameters. (a) Choroidal thickness (CT), (b) choroidal area (CA), (c) choroidal volume (CV). [The research work is licensed under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 International License, cited by Stephenson, et al., entitled by: “Quantitative Choroidal Analysis of Molecularly Characterized Retinitis Pigmentosa”, Investigative Ophthalmology & Visual Science, July 2025, Vol. 66, 11, 2025; doi.org/10.1167/iovs.66.9.11].

Table 1: Choroidal and Retinal Parameters for Genotype and Inheritance Groups [Stephenson, et al., entitled by: “Quantitative Choroidal Analysis of Molecularly Characterized Retinitis Pigmentosa”, Investigative Ophthalmology & Visual Science, July 2025, Vol. 66, 11, 2025; doi.org/10.1167/iovs.66.9.11].

In their analysis, a cohort of sixty-five patients (mean age, 47.3 ± 19.5 years; 52.3% female) showed that CT was thinner in RP patients than controls (P = 0.003). The proportions from each genotype group were USH2A (n = 23 [35.4%]), RPGR (n = 20 [30.8%]), RHO (n = 14 [21.5%]), and PRPF31 (n = 8 [12.3%], Table 1), providing inheritance groups of similar size. A thinner choroid was associated with older age (r = −0.512; P < 0.001) and worse BCVA (r = 0.298, P = 0.002) but not SE (P = 0.194). Although variable, no statistically significant differences were found for choroidal measures between groups. Leptochoroid (≤100 µm) was associated with advanced age (P < 0.001) and worse BCVA (P = 0.032), but not greater myopia (P = 0. 533). Greater CVI was only associated with better BCVA (P < 0.001) and no other parameters. The researchers commented that, “to our knowledge, this is the first quantitative report of choroidal features in RP which compares large groups with known genotypes. We present the study in the context of retinal structure and function.”

Epidemiological studies suggest that AMD affects nearly 200 million people worldwide, with the number expected to reach 290 million by 2040.  While genetic and environmental factors that have shown major roles in AMD, several disease mechanisms and complexities of treatment are required to conduct current research.  In their research at the Hubei University of Medicine, Shiyan, the study evaluated linkage disequilibrium score regressions (LDSC) using GWAS summary statistics, a method typically unaffected by sample overlap  In particular, mendelian randomization (MR) using a method that quantitates summary data from GWAS outcomes to assess the causal effects of diseases, diet, and other factors on disease. MR controls for potential confounding factors using instrumental variables (IVs) and not affected by environmental confounding and reverse causation.

Table 1: The result of MR analysis. [The research work is licensed under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 International License, cited by Jia, Q.,, et al., entitled by: “Genetic Correlation and Mendelian Randomization Analyses Support Causal Relationships Between Instant Coffee and Age-Related Macular Degeneration”, Food Science & Nutrition, 2025; 13:e70439, https://doi.org/10.1002/fsn3.70439].

The results of the GWAS found that instant coffee appears to significantly increase the risk of AMD, with each standard deviation (SD) increases in instant coffee consumption, corresponding to an odds ratio of approximately 6.92 for dry AMD, indicating a 6.92-fold increased risk.  According to the results, the authors of their paper stated that, “the current study showed that co-localization analyses did not identify shared genetic regions or variants between coffee intake and AMD, suggesting that the causal effect of instant coffee on the risk of dry AMD may not be driven by a single genetic variant, but rather involves a variety of complex biological mechanisms, including polygenic regulatory effects, gene–environment interactions, and epigenetic modifications.”

According to the researchers, Riksstroke had 409,546 stroke patients, while SMR had 33,585 nAMD patients who have received intravitreal anti-VEGF injections over a 12-year period. Of the total number of injections, 26,263 were unilateral and 6,555 were bilateral treatment.   The cross-linking of the two databases showed that 1,693 patients had a stroke, and among those patients, 1,330 received ranibizumab, 503 received aflibercept and 314 received bevacizumab. Of all stroke incidents, 936 occurred within 90 days of the last treatment, 527 within 30 days, 295 within 31–60 days and 114 within 61–90 days.

Table 1*. Incidence of stroke within 30, 31–60 and 61–90 days of last Anti-VEGF treatment in SMR with Ranibizumab, Aflibercept and Bevacizumab.(RR, risk ratio; CI, confidence interval).

Table 2*: RR for a stroke within 90 days for stroke patients on anti-VEGF treatment and Non anti-VEGF treatment. (RR, risk ratio; CI, confidence interval; p, probability).

*The research work is licensed under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 International License, cited by Falemban, A.H., et al, (2025), entitled: “Intravitreal anti-vascular endothelial growth factor injections and risks of stroke in patients with neovascular age-related macular degeneration—A registry-based cohort study. Acta Ophthalmologica, available from: https://doi.org/10.1111/aos.17534.

The study results showed that, compared with non-use, intravitreal anti-VEGF agent was associated with an increased risk of stroke within 90 days of anti-VEGF treatment in 2.9% of the nAMD-patients [Risk Ratio (RR) 1.27, 95% confidence interval (CI) 1.22; 1.33], compared to non-users. The RR within 30, 31–60 and 61–90 days were 1.36 (1.15; 1.66), 1.40 (1.09; 1.79) and 0.58 (0.52; 0.65), respectively.  The researchers commented that, “even though the risk is small, intravitreal injections with anti-VEGF agents for the treatment of nAMD are associated with an increased risk of stroke/TIA. The risk seems to be higher within 60 days of last injection. An assessment of high-risk populations and risk-benefit weighting is necessary before intravitreal anti-VEGF injections are considered.”  In addition, the authors commented that, “these variations in stroke risk between the agents in our study need to be interpreted with caution as our data were not able to determine whether they were caused by confounding by indication or by an actual risk difference. The majority of our study cases (78.5%) were treated with ranibizumab, which could be partially explained by the fact that ranibizumab was the only anti-VEGF agent used in Sweden between 2006 and 2011.”

LUGANO dosed the first patient in October 2024, while LUCIA dosed the first patient in December 2024 (the LUGANO identifier at clinicaltrials.gov is NCT06668064 and LUCIA identifier is NCT06683742).  The primary endpoint of the Phase 3 pivotal trials is the average change in BCVA at weeks 52 and 56 versus baseline and secondary endpoints including safety, reduction in treatment burden, and the “percentage of eyes free of supplemental aflibercept injections and anatomical results as measured by optical coherence tomography (OCT)”, as reported by the sponsor.  Vorolanib was developed as a potential sustained-delivery maintenance treatment for patients from chronic VEGF-mediated retinal disease. Previous Phase 1 and 2 results reported clinically meaningful efficacy with stable visual acuity and CST presenting an ”impressive treatment burden reduction of approximately 88% six months after treatment” and with “>80% of patients supplement-free or receiving only one supplemental anti-VEGF injection.”

Figure 1. Vorolanib is a selective and patent protected tyrosine kinase inhibitor that provides a new mechanism of action and treatment paradigm for retinal diseases beyond existing anti-VEGF large molecule ligand blocking therapies. The technology, termed “DURAVYU™” is an investigational product utilizes a bio-erodible insert technology licensed to EyePoint Pharmaceuticals, exclusively by Equinox Sciences, a Betta Pharmaceuticals affiliate for the localized treatment of all ophthalmic diseases outside of China, Macao, Hong Kong and Taiwan(https://eyepointpharma.com/science-and-technology/).

According to the sponsor, both Phase 3 studies enroll >400 patients each, for LUGANO and LUCIA, randomly assigned into two groups and receive either vorolanib 2.7 mg, or an on-label aflibercept control. Patients in the treatment arm will receive a 2.7-mg intravitreal injection every 6 months beginning at month 2 of the trial.  Commenting on the announcement, Brittney Statler, M.D., Principal Investigator in the LUGANO clinical trial and Medical Retina Specialist at Panorama Eyecare, Fort Collins, Colorado, stated that “the pace of enrollment in the LUGANO trial highlights EyePoint’s engagement with the retinal community and underscores the enthusiasm for this patient-centric pivotal program for DURAVYU.  One of the many compelling elements of this program is the fact that all patients receive active treatment with either aflibercept or DURAVYU, enabling us to effectively evaluate this potential next generation treatment for wet AMD in a real-world clinical practice setting. We are honoured to be part of this innovative clinical research for a treatment that has the potential to change the current treatment paradigm and revolutionize clinical outcomes for patients suffering from serious retinal diseases.”  The completion of enrollment for LUGANO’s topline data is anticipated in mid-2026.

Infantile nystagmus syndrome (INS) is an ocular motor disorder characterized by involuntary, rhythmic oscillation of the eyes, often manifesting within the first six months and is the most common form of nystagmus in infancy and childhood. The researchers showed that ninety per cent of INS cases are associated with inherited ocular disorders with distinct inheritance patterns, including autosomal recessive, autosomal dominant, X-linked, and mitochondrial modes.   Obtaining of a genetic diagnosis for INS patients is critical for several aspects including genetic counselling, support of family members,  and importantly, for defining eligibility for up-coming gene-based therapies.

Following their study, clinical researchers enrolled 205 unrelated pediatric patients who underwent genetic testing, 117 males (57%) and 88 females (43%). Ages at genetic testing ranged from 0.3 to 40 years, with a mean of 8.54 ± 7.91 years and the most frequently mutated genes included TYR (n = 17 [20%]) and OCA2 (n = 4 [4.7%]) for oculocutaneous albinism, CNGB3 (n = 8 [9.4%]) for achromatopsia, GPR143 (n = 6 [7%]) for X-linked ocular albinism, RPGR (n = 6 [7%]) for X-linked retinitis pigmentosa, ABCA4 (n = 5 [5.9%]) for Stargardt disease, and FRMD7 (n = 3 [3.5%]) for idiopathic INS. Their study found that eight LCA-associated genes (AIPL1, CABP4, GUCY2D, IMPDH1, NMNAT1, RDH12, PRPH2 and RPGRIP1) accounted for 15% of genetically diagnosed cases, with other genes having lower prevalence.

Figure 1. Types of gene variants and prevalence of disease-associated causative genes identified in the genetically solved INS cohort. (A) Pie chart showing the distribution of all the gene variants underlying INS or its associated conditions according to their types. (B) Prevalence of disease-associated genes harboring causative variants in patients with INS. [This graphic and work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, authored Gong, X.,  et al. Clinical spectrum and molecular characteristics of inherited ocular diseases in a cohort of pediatric patients with infantile nystagmus syndrome. Invest Ophthalmol Vis Sci. 2025;66(4):39. https://doi.org/10.1167/iovs.66.4.39.]

Accurate interpretation of genetic variants is crucial for precise diagnosis, clinical management, genetic counselling, and potential access to gene-based therapies due to the prevalence of nystagmus across several ocular disorders.  INS-associated IODs exhibit phenotypic heterogeneity due to diverse genotypes. Clinically, they can be classified into two main categories: non-syndromic and syndromic. Non-syndromic IODs primarily result from mutations in retina-specific genes, including those associated with achromatopsia, LCA, X-linked RP, blue cone monochromatism and congenital stationary night blindness (CSNB). Syndromic IODs involve multiple organs beyond the eyes, such as albinism. In concluding their results, the researchers commented that the molecular diagnosis in 41.5% of pediatric INS cases, using targeted NGS, had “actionable findings for gene-based therapies in 35% of solved cases. The remaining unresolved cases highlight the need for more comprehensive genetic testing, including WGS, and further research into non-coding regions and CNVs. A multidisciplinary approach, integrating clinical, genetic, and imaging data, is essential for managing INS and its associated conditions.”

Researchers have outlined that the photoreceptor cilium actin regulator (PCARE) gene was first identified as a cause of non-syndromic autosomal recessive retinitis pigmentosa (RP54) in 2010.  The disorder is characterized by typical signs of RP, including poor night vision and peripheral field loss, retinal bone spicule-type pigment deposits, pale optic discs, and markedly reduced or extinguished responses on electroretinography.  The gene encodes a 1,289-amino acid protein predominantly expressed in the primary cilium of retinal photoreceptors, regulating outer segment disk formation and renewal. In their current research, a retrospective cohort study evaluated 28 patients (56 eyes) with main outcome measures of best-corrected visual acuity (BCVA) and degree of vision impairment, kinetic visual field (KVF), area of macular atrophy (MA) with definitely decreased autofluorescence (DDAF) on short-wavelength autofluorescence, total macular volume (TMV) and foveal sparing (FS) on optical coherence tomography.

Figure 1. Time-to-event curves for development of foveal atrophy, low vision, and blindness in PCARE-associated retinopathy. The median age for the loss of foveal sparing is 45 years, while the median ages for the development of low vision (best corrected visual acuity in the better-seeing eye worse than 0.5 [logMAR] or 20/70 [Snellen]) and blindness (best-corrected visual acuity in the better-seeing eye worse than 1.3 [logMAR] or 20/400 [Snellen]) are 50 and 57 years, respectively. [This figure is provided from an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license: http://creativecommons.org/licenses/by/4.0/, authored by Bianco, L et al., entitled, “PCARE-Associated Retinopathy – Genetics, Clinical Characteristics, and Natural History”, published in Invest Ophthalmol Vis Sci. 2025;66(4):61. https://doi.org/10.1167/iovs.66.4.61].

The results of the natural history of the PCARE-associated retinopathy showed a phenotype consistent with a severe generalized photoreceptor dystrophy, with macular atrophy and with DDAF observed in 85% of the eyes the study population. Loss of foveal sparing (FS) (occurring at a median age of 45 years) was associated with a mean BCVA (logMAR) worsening by 1.1 (95% confidence interval [CI] = 0.6 to 1.5, P < 0.001) and low vision and blindness in the better-seeing eye occurred at median ages of 50 and 57 years, respectively.  The comprehensive natural history is key to support subsequent experimental treatments in the coming years.  The recent study results, collected longitudinal data over an average follow-up of almost 7 years, will likely capable for exploring potential functional and structural outcome measures for upcoming clinical trials.  In concluding their work, the clinicians commented that, “none of the patients experienced blindness in both eyes before the age of 40 years. These findings suggest that the optimal therapeutic window for future gene augmentation approaches might be before the fifth decade of life.”

The Consolidated Standards of Reporting Trials (CONSORT) are a set of guidelines adopted by various journals regarding the content of published reports  of randomised trials.  The guidelines arose from researchers in the 1990s to ensure that improvements and consistency applied for randomized trials were to be used across all researchers internationally and these initiatives were originally published in 1996 and then revised in 2001 and 2010.  The new revision is now published in 2025, issued at https://www.consort-spirit.org, and simultaneously published in BMJ, JAMA, The Lancet, Nature Medicine and PLoS Medicine(see BMJ. 2025; 388:e081123. https://dx.doi.org/10.1136/bmj-2024-081123).

The summary points for the new CONSORT 2025 statement were outlined in the consortium’s work including:

• To interpret a randomised trial accurately, readers need complete and transparent information on its methods and findings.
• The CONSORT 2025 statement provides updated guidance for reporting the results of randomised trials, that reflects methodological advancements and feedback from end users.
• The CONSORT 2025 statement consists of a 30-item checklist of essential items, a diagram for documenting the flow of participants through the trial, and an expanded checklist that details the critical elements of each checklist item.
• Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.

The new CONSORT 2025 statement has updated the checklist, up from 25 items in 2010, now providing 30 items on the list, including “seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions (Harms, Outcomes and Non-Pharmacological Treatment). The CONSORT 2025 statement supersedes the CONSORT 2010 statement, which should no longer be used. Journal editors and publishers should update their instructions to authors to refer to CONSORT 2025.”

Figure 1. CONSORT 2025 flow diagram. Flow diagram of the progress through the phases of a randomised trial of two groups (ie, enrolment, intervention allocation, follow-up, and data analysis). CONSORT=Consolidated Standards of Reporting Trials. [This figure is provided from an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license: http://creativecommons.org/licenses/by/4.0/, authored by Hopewell, S et al., entitled, “CONSORT 2025 statement: updated guideline for reporting randomised trials”, published in BMJ 2025; 389 doi: https://doi.org/10.1136/bmj-2024-081123].

According to the researchers in their publication the authors commented that: “Extensions to CONSORT have been developed to tackle the methodological issues associated with reporting different types of trial designs, data and interventions. Examples of extensions for trial designs include recommendations for adaptive designs, cluster trials, crossover trials, early phase trials, factorial trials, non-inferiority and equivalence trials, pragmatic trials, multi-arm trials, n-of-1 trials, pilot and feasibility trials, and within-person trials.”  In summary, the authors concluded that, “we also strongly recommend the submission of a completed CONSORT 2025 checklist as part of the manuscript submission process, detailing where in the manuscript checklist items are reported, and uploaded as part of the supplementary materials. An explicit description of what was done and what was found, without ambiguity or omission, best serves the interests of all readers.”

*

• Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, University of Oxford, UK.
• Department of Medicine, Women’s College Research Institute, University of Toronto, Toronto, Ontario, Canada.
• UK EQUATOR Centre, Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
• Centre for Evidence-Based Medicine Odense and Cochrane Denmark, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
• Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark.
• Centre for Journalology, Clinical Epidemiology Programme, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
• Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
• Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
• Office of Science Dissemination, Centers for Disease Control and Prevention, Atlanta, GA, USA.
• Department of Biostatistics and Epidemiology, School of Public Health, Center for Pharmacoepidemiology and Treatment Science, Rutgers University, New Brunswick, NJ, USA.
• JAMA Network Open, Chicago, IL, USA.
• Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
• Child Health Evaluation Services, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
• Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
• Aberdeen Centre for Evaluation, University of Aberdeen, Aberdeen, UK.
• Project PINK BLUE – Health & Psychological Trust Centre, Utako, Abuja, Nigeria.
• Department of Sociology and Gerontology, Miami University, Oxford, OH, USA.
• Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
• Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
• Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
• Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
• Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA.
• Institute for Evidence-Based Healthcare, Faculty of Health Sciences and Medicine, Bond University, Robina, Queensland, Australia.
• Departments of Medicine, of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA.
• MRC Clinical Trials Unit at University College London, London, UK.
• University College London, UCL Great Ormond Street Institute of Child Health, London, UK.
• NIHR Exeter Biomedical Research Centre, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
• Edinburgh Clinical Trials Unit, Usher Institute-University of Edinburgh, Edinburgh BioQuarter, Edinburgh, UK.
• The BMJ, BMA House, London, UK.
• Harvard Medical School, Boston, MA, USA.
• Université Paris Cité, Inserm, INRAE, Centre de Recherche Epidémiologie et Statistiques, Université Paris Cité, Paris, France.
• Clinical Trials Ontario, MaRS Centre, Toronto, Ontario, Canada.
• Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
• Department of Emergency Medicine, University of California, Los Angeles, CA, USA.
• South African Medical Research Council, Cape Town, South Africa.
• Warwick Applied Health, Warwick Medical School, University of Warwick, Coventry, UK.
• MRC/CSO Social and Public Health Sciences Unit & Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
• Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
• St Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada.
• York Trials Unit, Department of Health Sciences, University of York, York, UK.
• Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
• Université Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Centre for Research in Epidemiology and Statistics (CRESS), Paris, France.
• Centre d’Epidémiologie Clinique, Hôpital Hôtel Dieu,AP-HP, Paris, France.