DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for macular retinal edema — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMacular retinal edema maps to a 6-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedBromfenacApproved drug
Structures already discussed alongside macular retinal edema in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
E. coli sliding clamp — Bromfenac has a real, experimentally solved structure in complex with this target (PDB 4MJQ, 1.73 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 27rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4MJQ · 1.73 Å · ligand Bromfenac (27R). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 Cochrane systematic review and meta-analysis found that the only intervention for uveitic macular edema with sufficiently robust randomised controlled trials was acetazolamide, which was shown to be ineffective in improving vision and is now rarely used. The same review noted that dexamethasone implants, immunomodulatory drugs, and anti-vascular endothelial growth factor agents showed promise, but that more randomised trials with long follow-up were needed. The pathophysiology of macular edema was described in a 2010 chapter as a common final pathway involving breakdown of the blood-ocular barrier, cytokine release, and inflammation, sometimes complicated by ischaemia.
A 2007 prospective study of 81 eyes from 58 uveitis patients treated medically found complete resolution of macular edema in 38 eyes (47%). Mean visual acuity improved from 20/34 to 20/27 (p = 0.04), and mean central foveal thickness fell from 319 micrometres to 241 micrometres (p < 0.001). However, the correlation between thickness reduction and visual improvement was weak (r = 0.3). The presence of an epiretinal membrane and a diffuse edema pattern on optical coherence tomography were significant predictors of treatment failure. In 30 patients with central retinal vein occlusion and macular edema, vitreous fluid levels of VEGF, soluble VEGF receptor 2, soluble intercellular adhesion molecule 1, interleukin 6, monocyte chemotactic protein 1, and pentraxin 3 were all significantly higher than in controls, and most correlated with retinal thickness.
A 2013 genetic study of 263 non-anterior uveitis patients and 724 controls found that two functional variants of the IRF5 gene (rs2004640 and rs10954213) were associated with the absence of macular edema. The odds ratios for protection were 1.48 and 1.54 in case-control analysis, and the association held in subphenotype analysis comparing patients with and without edema. A 2020 review noted that anti-VEGF proteins and glucocorticoids, given as repeated intraocular injections over years, limit visual symptoms but do not prevent the condition, and called for better understanding of why edema forms.
What is still missing are adequately powered randomised trials with long follow-up for most interventions, a clearer grasp of the underlying mechanisms that could allow prevention rather than repeated treatment, and patient stratification by genetic markers such as IRF5 variants or by the presence of epiretinal membranes, which predict treatment failure.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical ophthalmology · 2013 · 65 citations · open access
Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis
AbstractBACKGROUND: Uveitic macular edema is the major cause of reduced vision in eyes with uveitis. OBJECTIVES: To assess the effectiveness of interventions in the treatment of uveitic macular edema. SEARCH STRATEGY: Cochrane Central Register of Controlled Trials, Medline, and Embase. There were no language or data restrictions in the search for trials. The databases were last searched on December 1, 2011. Reference lists of included trials were searched. Archives of Ophthalmology, Ophthalmology, Retina, the British Journal of Ophthalmology, and the New England Journal of Medicine were searched for clinical trials and reviews. SELECTION CRITERIA: Participants of any age and sex with any type of uveitic macular edema were included. Early, chronic, refractory, or secondary uveitic macular edema were included. We included trials that compared any interventions of any dose and duration, including comparison with another treatment, sham treatment, or no treatment. DATA COLLECTION AND ANALYSIS: Best-corrected visual acuity and central macular thickness were the primary outcome measures. Secondary outcome data including adverse effects were collected. CONCLUSION: More results from randomized controlled trials with long follow-up periods are needed for interventions for uveitic macular edema to assist in determining the overall long-term benefit of different treatments. The only intervention with sufficiently robust randomized controlled trials for a meta-analysis was acetazolamide, which was shown to be ineffective in improving vision in eyes with uveitic macular edema, and is clinically now rarely used. Interventions showing promise in this disease include dexamethasone implants, immunomodulatory drugs and anti-vascular endothelial growth-factor agents. When macular edema has become refractory after multiple interventions, pars plana vitrectomy could be considered. The disease pathophysiology is uncertain and the course of disease unpredictable. As there are no clear guidelines from the literature, interventions should be tailored to the individual patient.
Developments in ophthalmology · 2010 · 63 citations
General Pathophysiology
AbstractMacular edema represents a common final pathway for many disease processes. Related ocular disorders include diabetic retinopathy, vascular occlusions, post surgical situations and inherited disorders. The pathophysiology includes breakdown of the blood ocular barrier, release of various cytokines and significant inflammations. These mechanisms may be complicated by ischemic processes. The various pathogenetic mechanisms and their contribution to the edema process are described in detail in this chapter.
Ocular Immunology and Inflammation · 2007 · 53 citations
Course of Macular Edema in Uveitis under Medical Treatment
AbstractOBJECTIVE: To describe the response of uveitic macular edema to various treatment methods using optical coherence tomography (OCT). METHODS: This is a prospective study of consecutive uveitis patients with macular edema in at least one eye. The patients received medical treatment. Best corrected Snellen Visual Acuity (BCVA) and tomographic features of the macula, including macular thickness measurement, were obtained at one, three, six, and 12 months after commencing treatment. RESULTS: Eighty-one eyes of 58 patients were analyzed. Complete resolution of macular edema occurred in 38 eyes (47%). The average BCVA was 20/34 logarithm of minimum angle of resolution (-logMAR, 0.2 +/- 0.3) upon study entry and 20/27 (-logMAR, 0.13 +/- 0.29) upon study completion. The difference was statistically significant (p = 0.04). The corresponding mean retinal thickness at the central fovea was 319 +/- 150 microm at the beginning of the study compared to 241 +/- 125 microm at 12 months (p < 0.001). A weak but statistically significant correlation between the reduction of macular thickness and the improvement of BCVA (r = 0.3, p = 0.01) was found. Thirteen of the 43 eyes (30%) with persistent macular edema had a more than 15% reduction of macular thickness compared to baseline, whereas 10 eyes (23, 3%) had a more than 15% increase in macular thickness. Statistical analysis indicated that the presence of an epiretinal membrane and an OCT pattern of diffuse macular edema was a significant factor associated with medical treatment failure. CONCLUSION: This study demonstrates the overall favorable visual prognosis of uveitic macular edema under medical treatment. The presence of an epiretinal membrane is an important factor associated with medical treatment failure.
PENTRAXIN 3 AND OTHER INFLAMMATORY FACTORS IN CENTRAL RETINAL VEIN OCCLUSION AND MACULAR EDEMA
AbstractPURPOSE: To evaluate the association between vitreous fluid levels of inflammatory factors and macular edema in patients with central retinal vein occlusion (CRVO). METHODS: In 30 CRVO patients with macular edema and 29 controls with idiopathic macular hole, vitreous fluid samples were obtained during vitreoretinal surgery. Retinal ischemia was evaluated from capillary nonperfusion on fluorescein angiography. Macular edema was examined by optical coherence tomography. RESULTS: Vitreous fluid levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor 2 (sVEGFR-2), soluble intercellular adhesion molecule 1 (sICAM-1), interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and pentraxin 3 (PTX3) were significantly higher in CRVO patients than in macular hole patients. Vitreous fluid levels of VEGF, sICAM-1, IL-6, MCP-1, and PTX3 were significantly correlated with the retinal thickness at the central fovea. There were significant correlations between the vitreous fluid level of VEGF and the levels of sICAM-1, IL-6, and MCP-1 in the CRVO patients. There was also a significant correlation between sVEGFR-2 and PTX3 but not between VEGF and PTX3. CONCLUSION: These findings suggest the importance of VEGF, its signal transduction pathways, and the cytokine network and may be useful for understanding the mechanism of macular edema in CRVO and developing new treatments.
Asia-Pacific Journal of Ophthalmology · 2014 · 10 citations
Treatment Paradigm After Uncomplicated Cataract Surgery
AbstractPURPOSE: To compare 3 clinical variables, namely, visual recovery, anterior chamber inflammation, and macular edema, between 2 different regimens after uncomplicated cataract surgery. DESIGN: Prospective, randomized, single-blind study at a single center, private, teaching practice in Las Vegas, NV. METHODS: Patients randomized to group I (nonsteroidal anti-inflammatory drugs, n = 113) received besifloxacin ophthalmic suspension 0.6% and bromfenac 0.09%, whereas those randomized to group II (steroid, n = 109) received besifloxacin ophthalmic suspension 0.6% and prednisolone acetate 1%.Preoperative evaluation included a baseline macular optical coherence tomography. Postoperative data collected included visual acuity, direct visual anterior segment cell and flare counts, and macular optical coherence tomographies. Foveal thickness and total macular volume were used to assess the presence of cystoid macular edema. RESULTS: Visual recovery was statistically insignificant with P values at 0.7, 0.10, 0.2, and 0.7 at 1 day, 1 week, 1 month, and 2 months, respectively.The degree of anterior segment inflammation was not statistically significant (P = 0.8) between the studied populations.The foveal thickness (1 week, P = 0.8; 1 month, P = 0.2; 2 months, P = 0.2) and total macular volume (1 week, P = 0.7; 1 month, P = 0.1; 2 months, P = 0.2) were not statistically significant between the groups, and the observed power were 0.902 and 0.666, respectively. CONCLUSIONS: This study demonstrated that bromfenac was equally efficacious when compared with a potent topical steroid in restoring visual function, decreasing and resolving anterior chamber inflammation, and preventing the development of macular edema.
Two Functional Variants of IRF5 Influence the Development of Macular Edema in Patients with Non-Anterior Uveitis
AbstractOBJECTIVE: Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. METHODS: Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. RESULTS: A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. CONCLUSION: Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.
[Macular edema: Understand mechanisms to develop treatments].
AbstractMacular edema is an increase in volume of the central area of the retina, responsible for visual acuity. Visual symptoms handicap the lives of millions of patients with macular edema secondary to chronic and sometimes acute retinal disease. Proteins that neutralize the vascular endothelial growth factor (VEGF) pathway or glucocorticoids, at the cost of repeated intraocular injections over years, limit visual symptoms. A better understanding of why and how edema forms and how therapeutic molecules exert an anti-edematous effect will help prevent this disabling and blinding retinal complication from occurring.
AbstractAbstract Macular edema (ME) is a leading cause of vision loss in retinal disease including retinal vein occlusion. The development of macular edema is mediated by angiogenic as well as Inflammatory processes. There is increasing evidence that management of the inflammatory part is important in the treatment of the edema. Therefore, theoretically steroid therapy has a good potential in the treatment of macular edema. Regarding retinal vein occlusion specifically treatment by Ozurdex implant, containing dexamethasoe provides visual recovery with excellent safety outcomes.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
