RARE DISEASE
Central retinal vein occlusion
Central retinal vein occlusion
Central retinal vein occlusion
Synonyms: CRVO
Synonyms: CRVO
Synonyms: CRVO
Drug discovery
1
drug
With orphan designation
Overview
Central retinal vein occlusion (CRVO) is a vision-threatening retinal vascular disorder characterized by thrombosis of the central retinal vein, leading to venous stasis, retinal hemorrhage, and macular edema [1][4][9]. Predominantly affecting individuals >50 years, key risk factors include hypertension, diabetes, glaucoma, and atherosclerosis [1][14]. Vision loss stems from ischemic retinal damage or macular edema [4][9]. First-line therapy involves intravitreal anti-VEGF agents (aflibercept, ranibizumab) and corticosteroids, supplemented by laser therapy for neovascular complications [3][7][9].
Population
Primarily occurs in adults >50 years (90% of cases), with hypertension present in 73% of patients [14][10]
Younger patients (<40 years) account for 8-15% of cases, often linked to ocular hypertension, inflammation, or coagulopathies [2][6]
Incidence increases with age, slightly male-predominant (53.8%), and 6-17% risk of bilateral involvement [2][14]
Burden
Affects 4.67 million globally (0.13% prevalence), with 30-50% developing permanent vision impairment [6][10]
Annual healthcare costs exceed $1.5 billion (US) due to frequent monitoring/injections [4][6]
Macular edema occurs in 75% of cases; 50% develop neovascular glaucoma without intervention [9][14]
Therapies
Anti-VEGF therapy: First-line for macular edema (≥3 lines VA improvement in 46-58% with monthly injections) [3][7][9]
Steroids: Dexamethasone implants or triamcinolone for anti-VEGF-resistant cases, despite cataract/glaucoma risks [3][7][12]
Laser photocoagulation: Prevents neovascular glaucoma in ischemic CRVO (50% rubeosis risk without treatment) [9][14]
Categories: rare ophthalmic disorders
Research Papers
2,093 drug discovery papers about Central retinal vein occlusion, with 4 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,093 drug discovery papers about Central retinal vein occlusion, with 4 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-13 | Wnt Pathway Agonism as a Therapeutic Strategy for Retinal Vascular Diseases: A Narrative Review of Evidence to Date.
Breakdown of the blood-retinal barrier (BRB) is implicated in many blinding retinal diseases, including diabetic macular edema, neovascular age-related macular degeneration, and retinal vein occlusion. Anti-vascular endothelial growth factor (anti-VEGF) therapies or laser photocoagulation are currently the standard of care for retinal diseases that are characterized by breakdown of the vascular barrier function and vascular hyperpermeability. However, inadequate response to anti-VEGF therapy is seen in a substantial proportion of patients and laser photocoagulation does not restore vision loss and can lead to collateral damage of the retina. Thus, new therapeutic targets are needed. The β-catenin-dependent wingless-related integration site (Wnt) signaling pathway plays a critical role in inner BRB development and maintenance. There are several potential therapeutics for retinal vascular diseases targeting the Wnt/β-catenin pathway under investigation, including several in preclinical development and one (MK-3000; also known as Restoret and formerly EYE103) with early clinical trial results advancing to late-stage clinical development. In this narrative review we examine the role of Wnt/β-catenin signaling in inner BRB maintenance and in retinal vascular diseases, as well as the potential for Wnt pathway agonism as a therapeutic approach.
2026-07-31 | Cold exposure aggravates vein occlusion through non-shivering thermogenesis-induced thrombocytopoiesis.
Vein occlusion (VO), including deep venous thrombosis (DVT) and retinal vein occlusion (RVO), is a common cause of multiple diseases that severely compromise the quality of life of affected individuals. Epidemiological evidence indicates that VO prevalence increases in cold seasons, yet the underlying mechanism remains unknown. Here, we show that cold exposure markedly elevates peripheral platelet counts, thereby aggravating VO in mouse models. Cold-augmented thrombocytopoiesis depends on the activation of adipose thermogenesis and subsequent increase in circulating free fatty acid (FFA) levels. Mechanistically, FFA-β-oxidation promotes acetyl-CoA production, which upregulates and stabilizes C/EBPα by shifting the balance between p300 acetyltransferase and SIRT1 deacetylase. Acetyl-C/EBPα transcriptionally upregulates GATA-1 and NF-E2 for megakaryocyte maturation and platelet production. Depletion of adipose triglyceride lipase PNPLA2, megakaryocyte-specific knockout of key β-oxidation enzyme CPT1α, or pharmacological inhibition of CPT1α and p300 abolishes cold-augmented thrombocytopoiesis and alleviates DVT and RVO in mouse models. In healthy volunteers, tolerable cold exposure activates adipose thermogenesis, increases circulating FFA levels, and increases platelet counts. Moreover, a retrospective cohort study of 425 patients reveals elevated platelet counts and higher DVT incidence during cold seasons. Similarly, increased platelet counts are observed in 448 patients with RVO at the time of diagnosis in cold seasons. Our study provides novel mechanistic insights into the increased VO risk induced by cold exposure and proposes a new therapeutic paradigm for VO by targeting megakaryocyte metabolism.
2026-07-31 | Direct randomized evidence comparing ranibizumab and bevacizumab for macular edema secondary to retinal vein occlusion: a systematic review and meta-analysis.
Intravitreal anti-vascular endothelial growth factor therapy is the first-line treatment for macular edema secondary to retinal vein occlusion. However, direct comparative evidence between ranibizumab and bevacizumab from randomized controlled trials remains limited. This study aimed to compare the efficacy and safety of these two agents using evidence from randomized controlled trials. We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science from database inception to February 11, 2026. Eligible studies were published randomized controlled trials directly comparing intravitreal ranibizumab and bevacizumab monotherapy in adults with RVO-ME. Nonrandomized and noncomparative studies were excluded. Four randomized controlled trials involving 759 participants were included. At 6 months, no significant difference was observed in mean best-corrected visual acuity (BCVA) change (MD 0.61 letters, 95% CI -1.95 to 3.18). The pooled mean difference in central macular thickness (CMT) change was 1.52 μm (95% CI -237.41 to 240.46). The proportion of eyes gaining ≥ 15 ETDRS letters was comparable (RR 0.97, 95% CI 0.82 to 1.14). Safety profiles were broadly similar. Rare systemic events were infrequent and associated with considerable statistical uncertainty. Certainty of evidence was moderate for visual outcomes and low to very low for rare adverse events. Ranibizumab and bevacizumab show comparable short-term efficacy and safety for macular edema secondary to retinal vein occlusion, although evidence for rare systemic events remains uncertain. Not applicable. PROSPERO CRD420251172336.
2026-07-28 | Early Real-World Experience of Switching to Faricimab for Macular Oedema Secondary to Vein Occlusion.
To evaluate the real-world effectiveness, durability, and safety of faricimab 6 mg in eyes with treatment-refractory retinal vein occlusion (RVO)-associated macular oedema (MO) in the United Kingdom (UK). This was a retrospective, single-centre observational study of eyes with RVO that were switched to faricimab after prior treatment with previous anti-vascular endothelial growth factor (anti-VEGF) agents. Baseline demographics, treatment history, pinhole visual acuity (VA), optical coherence tomography (OCT) biomarkers, and injection intervals were recorded. Eyes were treated using a treat-and-extend regimen without a loading phase. Functional, anatomical, durability, and safety outcomes were assessed over follow-up. A total of 22 eyes from 22 patients were included, with a mean (SD) age of 67.9 (11.9) years and a mean (SD) RVO duration of 201.4 (153.1) weeks. Eyes had received a mean (SD) of 20.8 (16.9) prior anti-VEGF injections. The mean (SD) follow-up was 45.7 (15.8) weeks, with a mean (SD) of 5.9 (2.3) faricimab injections. There was no significant change in pinhole VA (53.5 (18.5) vs. 55.0 (18.8) letters, p = 0.08). The central subfield thickness (CST) reduced from 407.6 (102.1) to 377.0 (186.5) µm, and the maximum central retinal thickness from 483.6 (103.1) to 442.2 (187.2) µm, although these changes were not statistically significant (p > 0.05). The proportion of eyes with subretinal fluid (SRF) decreased from 18.2% to 4.5%, and intraretinal fluid (IRF) from 100% to 81.8%. Injection intervals between the first and second faricimab injections increased significantly from 4.9 (1.4) to 7.7 (3.4) weeks (final injection interval, p = 0.004). Six eyes (27.3%) discontinued faricimab, with three (13.6%) requiring an intravitreal dexamethasone implant following a suboptimal response. One eye (4.5%) developed transient intraocular pressure elevation; no cases of intraocular inflammation or endophthalmitis were observed. In this heavily pre-treated, chronic RVO cohort, switching to faricimab without a loading phase resulted in stable visual acuity, modest but non-significant anatomical improvements, and a significant extension in treatment intervals. These findings suggest that faricimab may provide durability benefits and disease stabilisation in treatment-refractory RVO, although functional gains may be limited in chronic disease. Further prospective studies are required to define optimal switching strategies.
2026-07-28 | AI-assisted OCT biomarker quantification reveals distinct retinal fluid trajectories in central retinal vein occlusion.
To characterize longitudinal patterns of intraretinal (IRF) and subretinal fluid (SRF) dynamics using AI-assisted optical coherence tomography (OCT) biomarker quantification and to evaluate their association with long-term visual outcomes in eyes with central retinal vein occlusion (CRVO). Patients with previously treatment-naïve CRVO and a documented 24-month follow-up were retrospectively included. All eyes received intravitreal aflibercept administered according to a treat-and-extend protocol. Spectral-domain OCT scans were analyzed at baseline, and after 3 and 24 months. IRF and SRF volumes were quantified using RetinAI Discovery OCT Biomarker Detector (Ikerian AG). Linear regression models were used to assess the association between fluid volumes and 24-month corrected distance visual acuity (CDVA). Patients were clustered according to their IRF trajectories over time to identify distinct fluid-response phenotypes. Out of 173 patients, 64 eyes (64 patients) were included. Baseline IRF and SRF volumes showed no significant association with 24-month CDVA. Cluster analysis of longitudinal IRF trajectories identified four distinct fluid-response patterns. Eyes with low or rapidly resolving IRF achieved the best long-term visual outcomes (median CDVA 73 letters), whereas those with persistent or recurrent IRF showed poorer outcomes (median 53 letters; p=0.008). Early IRF resolution tended to predict superior visual recovery at 24 months. AI-based volumetric OCT analysis suggests that distinct retinal fluid trajectories in CRVO may have prognostic implications for long-term visual acuity, though these findings are preliminary and require validation. Dynamic IRF resolution patterns are more informative than static fluid volumes for predicting functional outcomes following anti-VEGF therapy.
2026-08-13 | Wnt Pathway Agonism as a Therapeutic Strategy for Retinal Vascular Diseases: A Narrative Review of Evidence to Date.
Breakdown of the blood-retinal barrier (BRB) is implicated in many blinding retinal diseases, including diabetic macular edema, neovascular age-related macular degeneration, and retinal vein occlusion. Anti-vascular endothelial growth factor (anti-VEGF) therapies or laser photocoagulation are currently the standard of care for retinal diseases that are characterized by breakdown of the vascular barrier function and vascular hyperpermeability. However, inadequate response to anti-VEGF therapy is seen in a substantial proportion of patients and laser photocoagulation does not restore vision loss and can lead to collateral damage of the retina. Thus, new therapeutic targets are needed. The β-catenin-dependent wingless-related integration site (Wnt) signaling pathway plays a critical role in inner BRB development and maintenance. There are several potential therapeutics for retinal vascular diseases targeting the Wnt/β-catenin pathway under investigation, including several in preclinical development and one (MK-3000; also known as Restoret and formerly EYE103) with early clinical trial results advancing to late-stage clinical development. In this narrative review we examine the role of Wnt/β-catenin signaling in inner BRB maintenance and in retinal vascular diseases, as well as the potential for Wnt pathway agonism as a therapeutic approach.
2026-07-31 | Cold exposure aggravates vein occlusion through non-shivering thermogenesis-induced thrombocytopoiesis.
Vein occlusion (VO), including deep venous thrombosis (DVT) and retinal vein occlusion (RVO), is a common cause of multiple diseases that severely compromise the quality of life of affected individuals. Epidemiological evidence indicates that VO prevalence increases in cold seasons, yet the underlying mechanism remains unknown. Here, we show that cold exposure markedly elevates peripheral platelet counts, thereby aggravating VO in mouse models. Cold-augmented thrombocytopoiesis depends on the activation of adipose thermogenesis and subsequent increase in circulating free fatty acid (FFA) levels. Mechanistically, FFA-β-oxidation promotes acetyl-CoA production, which upregulates and stabilizes C/EBPα by shifting the balance between p300 acetyltransferase and SIRT1 deacetylase. Acetyl-C/EBPα transcriptionally upregulates GATA-1 and NF-E2 for megakaryocyte maturation and platelet production. Depletion of adipose triglyceride lipase PNPLA2, megakaryocyte-specific knockout of key β-oxidation enzyme CPT1α, or pharmacological inhibition of CPT1α and p300 abolishes cold-augmented thrombocytopoiesis and alleviates DVT and RVO in mouse models. In healthy volunteers, tolerable cold exposure activates adipose thermogenesis, increases circulating FFA levels, and increases platelet counts. Moreover, a retrospective cohort study of 425 patients reveals elevated platelet counts and higher DVT incidence during cold seasons. Similarly, increased platelet counts are observed in 448 patients with RVO at the time of diagnosis in cold seasons. Our study provides novel mechanistic insights into the increased VO risk induced by cold exposure and proposes a new therapeutic paradigm for VO by targeting megakaryocyte metabolism.
2026-07-31 | Direct randomized evidence comparing ranibizumab and bevacizumab for macular edema secondary to retinal vein occlusion: a systematic review and meta-analysis.
Intravitreal anti-vascular endothelial growth factor therapy is the first-line treatment for macular edema secondary to retinal vein occlusion. However, direct comparative evidence between ranibizumab and bevacizumab from randomized controlled trials remains limited. This study aimed to compare the efficacy and safety of these two agents using evidence from randomized controlled trials. We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science from database inception to February 11, 2026. Eligible studies were published randomized controlled trials directly comparing intravitreal ranibizumab and bevacizumab monotherapy in adults with RVO-ME. Nonrandomized and noncomparative studies were excluded. Four randomized controlled trials involving 759 participants were included. At 6 months, no significant difference was observed in mean best-corrected visual acuity (BCVA) change (MD 0.61 letters, 95% CI -1.95 to 3.18). The pooled mean difference in central macular thickness (CMT) change was 1.52 μm (95% CI -237.41 to 240.46). The proportion of eyes gaining ≥ 15 ETDRS letters was comparable (RR 0.97, 95% CI 0.82 to 1.14). Safety profiles were broadly similar. Rare systemic events were infrequent and associated with considerable statistical uncertainty. Certainty of evidence was moderate for visual outcomes and low to very low for rare adverse events. Ranibizumab and bevacizumab show comparable short-term efficacy and safety for macular edema secondary to retinal vein occlusion, although evidence for rare systemic events remains uncertain. Not applicable. PROSPERO CRD420251172336.
2026-07-28 | Early Real-World Experience of Switching to Faricimab for Macular Oedema Secondary to Vein Occlusion.
To evaluate the real-world effectiveness, durability, and safety of faricimab 6 mg in eyes with treatment-refractory retinal vein occlusion (RVO)-associated macular oedema (MO) in the United Kingdom (UK). This was a retrospective, single-centre observational study of eyes with RVO that were switched to faricimab after prior treatment with previous anti-vascular endothelial growth factor (anti-VEGF) agents. Baseline demographics, treatment history, pinhole visual acuity (VA), optical coherence tomography (OCT) biomarkers, and injection intervals were recorded. Eyes were treated using a treat-and-extend regimen without a loading phase. Functional, anatomical, durability, and safety outcomes were assessed over follow-up. A total of 22 eyes from 22 patients were included, with a mean (SD) age of 67.9 (11.9) years and a mean (SD) RVO duration of 201.4 (153.1) weeks. Eyes had received a mean (SD) of 20.8 (16.9) prior anti-VEGF injections. The mean (SD) follow-up was 45.7 (15.8) weeks, with a mean (SD) of 5.9 (2.3) faricimab injections. There was no significant change in pinhole VA (53.5 (18.5) vs. 55.0 (18.8) letters, p = 0.08). The central subfield thickness (CST) reduced from 407.6 (102.1) to 377.0 (186.5) µm, and the maximum central retinal thickness from 483.6 (103.1) to 442.2 (187.2) µm, although these changes were not statistically significant (p > 0.05). The proportion of eyes with subretinal fluid (SRF) decreased from 18.2% to 4.5%, and intraretinal fluid (IRF) from 100% to 81.8%. Injection intervals between the first and second faricimab injections increased significantly from 4.9 (1.4) to 7.7 (3.4) weeks (final injection interval, p = 0.004). Six eyes (27.3%) discontinued faricimab, with three (13.6%) requiring an intravitreal dexamethasone implant following a suboptimal response. One eye (4.5%) developed transient intraocular pressure elevation; no cases of intraocular inflammation or endophthalmitis were observed. In this heavily pre-treated, chronic RVO cohort, switching to faricimab without a loading phase resulted in stable visual acuity, modest but non-significant anatomical improvements, and a significant extension in treatment intervals. These findings suggest that faricimab may provide durability benefits and disease stabilisation in treatment-refractory RVO, although functional gains may be limited in chronic disease. Further prospective studies are required to define optimal switching strategies.
2026-07-28 | AI-assisted OCT biomarker quantification reveals distinct retinal fluid trajectories in central retinal vein occlusion.
To characterize longitudinal patterns of intraretinal (IRF) and subretinal fluid (SRF) dynamics using AI-assisted optical coherence tomography (OCT) biomarker quantification and to evaluate their association with long-term visual outcomes in eyes with central retinal vein occlusion (CRVO). Patients with previously treatment-naïve CRVO and a documented 24-month follow-up were retrospectively included. All eyes received intravitreal aflibercept administered according to a treat-and-extend protocol. Spectral-domain OCT scans were analyzed at baseline, and after 3 and 24 months. IRF and SRF volumes were quantified using RetinAI Discovery OCT Biomarker Detector (Ikerian AG). Linear regression models were used to assess the association between fluid volumes and 24-month corrected distance visual acuity (CDVA). Patients were clustered according to their IRF trajectories over time to identify distinct fluid-response phenotypes. Out of 173 patients, 64 eyes (64 patients) were included. Baseline IRF and SRF volumes showed no significant association with 24-month CDVA. Cluster analysis of longitudinal IRF trajectories identified four distinct fluid-response patterns. Eyes with low or rapidly resolving IRF achieved the best long-term visual outcomes (median CDVA 73 letters), whereas those with persistent or recurrent IRF showed poorer outcomes (median 53 letters; p=0.008). Early IRF resolution tended to predict superior visual recovery at 24 months. AI-based volumetric OCT analysis suggests that distinct retinal fluid trajectories in CRVO may have prognostic implications for long-term visual acuity, though these findings are preliminary and require validation. Dynamic IRF resolution patterns are more informative than static fluid volumes for predicting functional outcomes following anti-VEGF therapy.
Access all drug discovery papers and probability of success in trials forecasts:
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Drug Discovery Landscape
1 orphan drug designation for Central retinal vein occlusion.
1 orphan drug designation for Central retinal vein occlusion.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Aganirsen | oligonucleotides | EMA | 2014-06-10 | — | Gene Signal SAS |
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