DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for open-angle glaucoma — screening already-approved drugs against its 40-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleOpen-angle glaucoma maps to a 40-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
No approved-drug candidate for open-angle glaucoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
carbonic anhydrase 2 (CA2) — CA2 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet hydroxymercurydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3K34 · 0.9 Å · ligand 4-(HYDROXYMERCURY)BENZOIC ACID (HGB). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 systematic review for the U.S. Preventive Services Task Force found high-level evidence that medical treatment and trabeculectomy reduce the risk for optic nerve damage and visual field loss compared with no treatment in open-angle glaucoma. The same review concluded that the direct effect of treatments on visual impairment and the comparative efficacy of different treatments are not clear. Harms of medical treatment were primarily local (ocular redness, irritation), while surgical treatment carried a small risk for more serious complications. The review noted heterogeneous outcome definitions and the exclusion of many treatment studies that did not stratify results by glaucoma type.
A 2010 study of CO2 laser-assisted sclerectomy surgery (CLASS) in 37 patients with primary or pseudoexfoliative open-angle glaucoma reported that mean baseline intraocular pressure (IOP) of 26.3±7.8 mm Hg dropped to 14.4±3.4 mm Hg at 6 months and 14.3±3.1 mm Hg at 12 months, representing reductions of 42.4% and 40.7% respectively. Complete success (IOP 5–18 mm Hg with 20% reduction and no medication) was achieved by 76.7% at 6 months and 60% at 12 months; qualified success (same IOP range with or without medication) was achieved by 83.3% and 86.6% at those time points. Mitomycin C was used in 83.3% of procedures. Complications were described as mild and transitory with no sequela.
A 2019 retrospective cohort study of 37 eyes from 31 primary open-angle glaucoma (POAG) patients who underwent phacoemulsification with pupillary expansion found that mean IOP in the POAG group increased from 15.0±4.6 mm Hg to 15.9±3.5 mm Hg after one year, while a control group of 29 eyes from 28 patients without POAG decreased from 14.1±3.6 mm Hg to 11.9±3.9 mm Hg. Multivariate analysis showed glaucoma was associated with a 5.56 mm Hg increase in IOP at 12 months postoperatively. The average number of glaucoma medications decreased significantly from 1.7±1.4 at baseline to 1.3±1.3 after one year. The authors concluded that no significant drop in mean IOP was noted after complex cataract surgery for this cohort, although medication burden decreased.
A 2017 analysis of the drug development pipeline from 1995 to 2015 identified 158 registered clinical trials for open-angle glaucoma with a drug-based intervention. Pharmaceutical companies sponsored 95.3% of trials. Prostaglandin analogues were involved in 62.7% of trials. Other drug classes tested included Rho-kinase inhibitors (15 trials), carbonic anhydrase inhibitors (14), beta-blockers (7), angiostatic steroids (6), alpha2-adrenergic agonists (4), 5-HT2A receptor agonists (4), and NMDA receptor antagonists (2). A 1998 review noted that the pathogenesis of open-angle glaucoma remains elusive and that the greatest risk factors remain IOP, age, race and refractive error, with an unfolding association with vascular disease. A 2011 commentary stated that known disease-causing genes are difficult to explain some glaucomatous cases and that study on susceptibility genes had not achieved new breakthroughs. What remains missing is a clear understanding of which treatments best prevent visual disability and improve patient-reported outcomes, as well as stratification of patients by pathogenic subtype so that therapy can be targeted at mechanisms rather than risk factors.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Internal Medicine · 2013 · 301 citations
Comparative Effectiveness of Treatments for Open-Angle Glaucoma: A Systematic Review for the U.S. Preventive Services Task Force
AbstractBACKGROUND: Glaucoma is an acquired degeneration of the optic nerve and a leading cause of blindness worldwide. Medical and surgical treatments that decrease intraocular pressure may prevent visual impairment and blindness. PURPOSE: To compare the effectiveness of medical, laser, and surgical treatments in adults with open-angle glaucoma with regard to decreasing intraocular pressure and preventing optic nerve damage, vision loss, and visual impairment. DATA SOURCES: MEDLINE, CENTRAL, and an existing database for systematic reviews (through 2 March 2011); MEDLINE, EMBASE, LILACS, and CENTRAL for primary studies (through 30 July 2012). STUDY SELECTION: English-language systematic reviews; randomized, controlled trials; and quasi-randomized, controlled trials for most outcomes and observational studies for quality of life and harms. DATA EXTRACTION: Two investigators abstracted or checked information about study design, participants, and outcomes and assessed risk of bias and strength of evidence. DATA SYNTHESIS: High-level evidence suggests that medical, laser, and surgical treatments decrease intraocular pressure and that medical treatment and trabeculectomy reduce the risk for optic nerve damage and visual field loss compared with no treatment. The direct effect of treatments on visual impairment and the comparative efficacy of different treatments are not clear. Harms of medical treatment are primarily local (ocular redness, irritation); surgical treatment carries a small risk for more serious complications. LIMITATION: Heterogeneous outcome definitions and measurements among the included studies; exclusion of many treatment studies that did not stratify results by glaucoma type. CONCLUSION: Medical and surgical treatments for open-angle glaucoma lower intraocular pressure and reduce the risk for optic nerve damage over the short to medium term. Which treatments best prevent visual disability and improve patient-reported outcomes is unclear.
AbstractPURPOSE: To evaluate the efficacy of CO2 laser-assisted sclerectomy surgery (CLASS) in primary and pseudoexfoliative open-angle glaucoma. MATERIALS AND METHODS: Patients for primary filtration surgery underwent CLASS with a CO2 laser system (OT-134-IOPtiMate, IOPtima Ltd., Ramat Gan, Israel). This self-controlled system gradually ablates and removes scleral layers until percolating fluid absorbs the energy, attenuating further tissue ablation. Intraocular pressure (IOP) was measured at baseline, 1, 2, 4, and 6 weeks, and 3, 6, and 12 months, respectively. Complete success was defined as 5≤IOP≤18 mm Hg and 20% IOP reduction with no medication at a 12-month endpoint visit, and qualified success as the same IOP range with or without medication. RESULTS: Thirty of 37 patients completed 12 months of follow-up. Mitomycin C was used in 25 procedures (83.3%). The mean baseline IOP of 26.3±7.8 mm Hg (mean±SD) dropped to 14.4±3.4 and 14.3±3.1 mm Hg at 6 and 12 months, respectively, with 42.4% and 40.7% IOP reduction at 6 and 12 months, respectively (P<0.001). Complete success was achieved by 76.7% and 60% of the patients at 6 and 12 months, respectively, whereas qualified success was achieved by 83.3% and 86.6% of the patients at 6 and 12 months, respectively. Complications were mild and transitory with no sequela. CONCLUSIONS: Short-term and intermediate results suggest that CLASS may become a simple, safe, and effective means of choice for the treatment of open-angle glaucoma.
Ophthalmic Research · 2017 · 16 citations · open access
Open-Angle Glaucoma: Drug Development Pipeline during the Last 20 Years (1995-2015)
Abstract<b><i>Objectives:</i></b> To analyse drug development for open-angle glaucoma during the last 20 years. <b><i>Methods:</i></b> Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition “open-angle glaucoma” with the intervention “drug” was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered. <b><i>Results:</i></b> We recorded 158 studies for the condition of open-angle glaucoma with a drug-based intervention; 65 of the studies reported phase 2 trials and 74 reported phase 3 trials. Pharmaceutical companies were the primary sponsors of 95.3% of the trials. Most of the studies (66.5%, <i>n</i> = 105) involved a new drug, and the remainder (33.5%, <i>n</i> = 53) tested fixed drug associations. The bulk of the trials (<i>n</i> = 99, 62.7%) involved the use of prostaglandin analogues, either as a comparator or a study drug. In descending order of frequency, the studies conducted involved Rho-kinase inhibitors (<i>n</i> = 15), carbonic anhydrase inhibitors (<i>n</i> = 14), β-blockers (<i>n</i> = 7), angiostatic steroids (<i>n</i> = 6), α<sub>2</sub>-adrenergic agonists (<i>n</i> = 4), 5-HT<sub>2A</sub> receptor agonists (<i>n</i> = 4), and NMDA receptor antagonists (<i>n</i> = 2). A cyclin-dependent kinase inhibitor, an LIM-domain kinase 2 inhibitor, an A1 adenosine receptor agonist, catechin, macrolide, saffron, and seawater were each tested in 1 clinical trial. <b><i>Conclusion:</i></b> Research into the medical treatment of glaucoma indicates the use of prostaglandin analogues. However, there are a significant number of trials testing other drug classes, particularly Rho-kinase inhibitors. This new focus could lead to a potential increase in the number of therapeutical options for the management of glaucoma in the future.
Current Opinion in Ophthalmology · 1998 · 15 citations
Pathogenetic mechanisms of glaucoma not related to intraocular pressure
AbstractThe pathogenesis of the diseases termed open-angle glaucoma remains elusive but progress is being made in understanding more clearly the optic nerve head, vascular, and cellular mechanisms that are associated with them. Even though the greatest risk factors remain intraocular pressure, age, race and refractive error, the association with vascular disease continues to unfold in the literature. Clinical and laboratory studies, although not addressing mechanisms directly as far as we know, continue to probe potential pathways that will ultimately lead to subsets of open-angle glaucoma. Only when this is accomplished will we be able to focus therapy at pathogenesis rather than at risks.
JOURNAL OF CURRENT GLAUCOMA PRACTICE · 2019 · 1 citations · open access
Outcomes of Complex Cataract Surgery in Patients with Primary Open-angle Glaucoma
AbstractAIM: Whether pupillary expansion during phacoemulsification causes a change in postoperative intraocular pressure (IOP) is currently unknown. However, a growing proportion of patients can present with concurrent glaucoma and cataracts, which poses an increased risk of having small pupils and makes finding the answer to this question imperative for treating physicians. MATERIALS AND METHODS: This was a retrospective, observational cohort study which utilized data from 2008 to 2016 from the University Hospital, Newark, New Jersey, USA. All patients with primary open-angle glaucoma (POAG) who underwent phacoemulsification with pupillary expansion were considered for inclusion. Cases were subsequently excluded if they had prior incisional glaucoma surgery, if phacoemulsification was combined with another surgery, or if they had any incisional surgery in the eye 1 year preoperatively or postoperatively. The control group was made up of patients without POAG. The primary outcome was IOP. RESULTS: Thirty-seven eyes from 31 glaucoma patients and 29 eyes from 28 control patients met inclusion criteria. The mean IOP in the POAG group increased from 15.0 ± 4.6 mm Hg to 15.9 ± 3.5 mm Hg after 1 year, whereas the control group decreased from 14.1 ± 3.6 mm Hg to 11.9 ± 3.9 mm Hg. Multivariate analysis showed that glaucoma was associated with a 5.56 mm Hg increase in IOP at 12 months postoperatively. The average number of glaucoma medications decreased significantly from 1.7 ± 1.4 at the baseline to 1.3 ± 1.3 after 1 year. CONCLUSION: In contrast with non-POAG patients, no significant drop in the mean IOP was noted after complex cataract surgery for this cohort of glaucoma patients, although medication burden significantly decreased and VA improved significantly. CLINICAL SIGNIFICANCE: Phacoemulsification with intraoperative pupillary expansion in POAG patients may not decrease IOP after 12 months but it can decrease the number of anti-glaucoma medications they take. HOW TO CITE THIS ARTICLE: Outcomes of Complex Cataract Surgery in Patients with Primary Open-angle Glaucoma. J Curr Glaucoma Pract 2019;13(2):62-67.
A expectation for breakthrough of glaucoma-related genetic study
AbstractGlaucoma,especially common primary open-angle glaucoma and primary angle-closure glaucoma,shows high genetic heterogeneity. The causing-disease genes known are difficult to explain some glaucomatous cases,and the study on the susceptibial gene of glaucoma do not achieve new breakthroughs. Combined with the newest progression in genetic study of glaucoma,some views were proposed in this paper in order to better understand the updating study of the pathogenesis mechanism.
Key words:
Glaucoma; Genetics; Gene; Genome wide association study
Acute angle closure triggered by oral benzodiazepines
AbstractABSTRACT Benzodiazepines are psychoactive drugs that are prescribed worldwide with limited information on their ocular side effects. Acute angle closure glaucoma is an adverse event with a high risk of blinding, especially in the elderly. We report two patients under 45 years old who presented with bilateral acute angle closure secondary to use of two long half-life benzodiazepines (clonazepam and alprazolam). In addition to suspending the use of these medications and administering ocular hypotensive drugs, both patients were successfully treated with bilateral peripheral laser iridotomy. To the best of our knowledge, this is the first report of bilateral acute angle closure secondary to the use of clonazepam and alprazolam.
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.
