DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for angle-closure glaucoma — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAngle-closure glaucoma maps to a 5-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
approvedChlorthalidoneThiazide-sensitive sodium-chloride cotransporter inhibitorapprovedBrinzolamideApproved drug
Structures already discussed alongside angle-closure glaucoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Genetically engineered Carbonic Anhydrase IX — Brinzolamide has a real, experimentally solved structure in complex with this target (PDB 4M2V, 1.718 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 bz1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4M2V · 1.718 Å · ligand Brinzolamide (BZ1). Experimental structure, not a prediction.
What the evidence adds up to
A 2019 review of drug-induced acute angle-closure glaucoma (AACG) describes it as an ophthalmological emergency with potentially blinding consequences. Anatomical risk factors include shallow anterior chamber depth, short axial length, plateau iris configuration, thick lens, anteriorly positioned lens, and rarely intraocular tumour. Demographic risk factors are female sex, Asian ethnicity, family history, and advanced age. In predisposed patients, AACG can be triggered by adrenergic agonists, anticholinergics, cholinergics, sulfonamides, supplements, and serotonergic medications. Two main mechanisms are identified: pupillary block with mydriasis, and anterior displacement of the lens-iris diaphragm due to mass effect, uveal effusion, or weakened zonules. A 2021 case report describes bilateral choroidal effusions leading to angle closure without pupillary block in a patient on topical latanoprost, brimonidine 0.2%, and brinzolamide 0.1%; symptoms resolved after cessation of drops and initiation of steroids and cycloplegics.
A 2002 review states that medical management of angle closure glaucoma aims to eliminate pupillary block, re-open the angle, and lower intraocular pressure. Commonly used pharmacologic agents include topical carbonic anhydrase inhibitors, prostaglandin analogues, and selective alpha2-adrenergic agonists. A 2017 review notes that surgical management of angle-closure glaucoma remains integral but that the distinctive anatomy of angle-closure eyes and few objective lines of evidence supporting the effectiveness of different surgical options present a challenge. A 2022 review of minimally invasive glaucoma surgery (MIGS) in primary angle-closure glaucoma (PACG) reports that MIGS may become one of the preferred surgical treatments for PACG in future clinical management.
A 2010 study of CO2 laser-assisted sclerectomy surgery (CLASS) in open-angle glaucoma (not angle-closure) enrolled 37 patients, with 30 completing 12 months. Mean baseline 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 (42.4% and 40.7% reduction, P<0.001). Complete success (IOP 5–18 mm Hg and ≥20% reduction without medication) was achieved by 76.7% at 6 months and 60% at 12 months; qualified success (same IOP range with or without medication) by 83.3% and 86.6% respectively. Mitomycin C was used in 83.3% of procedures. Complications were mild and transitory.
What is still missing are prospective, controlled trials directly comparing medical, laser, and surgical interventions specifically for angle-closure glaucoma, with adequate sample sizes and long-term follow-up. The evidence base for surgical options in angle-closure eyes remains thin, and patient stratification by underlying mechanism (pupillary block, uveal effusion, plateau iris) is rarely performed in trials. Funding for such stratified trials is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JOURNAL OF CURRENT GLAUCOMA PRACTICE · 2019 · 92 citations · open access
Drug-induced Acute Angle-closure Glaucoma: A Review
AbstractAIM: Our goal is to review current literature regarding drug-induced acute angle-closure glaucoma (AACG) and provide ophthalmologists and general practitioners with a thorough understanding of inciting medications and treatment pitfalls to be avoided. BACKGROUND: Drug-induced AACG is an ophthalmological emergency that ophthalmologists and general practitioners should be familiar with, given its potentially blinding consequences. Common anatomical risk factors for AACG include a shallow anterior chamber depth, short axial length, plateau iris configuration, thick lens, anteriorly positioned lens, and rarely, intraocular tumor. Demographic risk factors include female sex, Asian ethnicity, family history, and advanced age. In patients with predisposing factors, acute angle closure can be triggered by various classes of medications including adrenergic agonists, anticholinergics, cholinergics, sulfonamides, supplements, and serotonergic medications. Physicians prescribing such inciting medications should be aware of their potentially sight-threatening adverse effects and to inform patients of the warning symptoms. Patients typically present with elevated intraocular pressure (IOP), headache, nausea, blurry vision, and halos around lights. REVIEW RESULTS: There are two main mechanisms of drug-induced AACG, both with different treatment strategies. The first mechanism of drug-induced AACG is pupillary block and iridocorneal angle closure secondary to thickening of iris base with mydriasis. The second mechanism of drug-induced AACG is anterior displacement of the lens-iris diaphragm due to mass effect (e.g., blood, misdirected aqueous humor, and tumors), uveal effusion, or weakened zonules. CONCLUSION: This paper reviews drug-induced AACG, high-risk anatomical features, underlying mechanisms, inciting medications, and options for treatment and prevention. CLINICAL SIGNIFICANCE: With proper understanding of the underlying mechanism of drug-induced AACG, physicians can respond promptly to save their patients' vision by employing the correct treatment strategy. HOW TO CITE THIS ARTICLE: Yang MC, Lin KY. Drug-induced Acute Angle-closure Glaucoma: A Review. J Curr Glaucoma Pract 2019;13(3):104-109.
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.
Case Reports in Ophthalmological Medicine · 2016 · 9 citations · open access
Bilateral, Simultaneous, Acute Angle Closure Glaucoma in Pseudophakia Induced by Chlorthalidone
AbstractUNLABELLED: Purpose. To report two persons with acute, bilateral, and simultaneous angle closure glaucoma in pseudophakia secondary to uveal effusions induced by administration of chlorthalidone. Methods. CASE REPORTS: Results. Bilateral shallow anterior chambers and high intraocular pressure with decline in visual acuity were reported in two patients within days of intake of chlorthalidone for systemic hypertension. Gonioscopy confirmed appositional angle closure while choroidal detachment and ciliochoroidal detachment were revealed on ultrasonographic studies. Discontinuing chlorthalidone and institution of aqueous suppressants to reduce IOP and cycloplegics reversed angle closure and glaucoma. Conclusions. Reports of angle closure glaucoma in pseudophakic eyes induced by idiosyncratic reaction to chlorthalidone confirms that osmotic changes in the crystalline lens has no role in the pathogenesis of drug induced glaucoma and reaffirms that glaucoma is secondary to ciliochoroidal detachment and ciliary body rotation and edema.
Developments in ophthalmology · 2017 · 8 citations
Surgical Treatment of Angle-Closure Glaucoma
AbstractAdvances in anterior segment imaging modalities have contributed new insights towards a better understanding of the various mechanisms of angle-closure glaucoma (ACG). This development is key to good decision making when confronted with angle-closure patients needing appropriate therapy. Surgical management of ACG remains an integral part of glaucoma patient care. The distinctive anatomy of angle-closure eyes and the few objective lines of evidence to support the effectiveness of the different surgical treatment options present a challenge to glaucoma surgeons.
AbstractManagement of angle closure glaucoma requires an understanding of the underlying pathophysiologic mechanisms. Treatment is aimed at eliminating pupillary block and other causes of angle closure, re-opening the angle, and preventing further damage to the optic nerve by lowering intraocular pressure. Medical therapy plays an important role in the successful management of this condition. This article describes commonly used pharmacologic agents, as well as newer classes of drugs such as topical carbonic anhydrase inhibitors, prostaglandin analogues and selective alpha2- adrenergic agonists. Use of these drugs in several clinically distinct angle closure syndromes and modes of presentation are discussed.
American Journal of Ophthalmology Case Reports · 2021 · 6 citations · open access
Multimodal etiology of drug induced angle closure with topical glaucoma therapy
AbstractPURPOSE: We present a case of acute onset of bilateral choroidal effusions leading to angle closure glaucoma attributed to multiple mechanism of actions causing ciliary body and aqueous flow disruption in the setting of topical glaucoma therapy with latanoprost, brimonidine 0.2%, and Brinzolamide 0.1%. OBSERVATION: The patient presented with ocular hypertension in the setting of bilateral choroidal effusions, leading to angle closure without pupillary block. After cessation of the glaucoma drops and starting steroids and cycloplegics, the patient's symptoms resolved. CONCLUSIONS AND IMPORTANCE: This case report highlights the various physiological mechanisms of action that can induce angle closure glaucoma from commonly used topical medications for glaucoma treatment. Thus, a keen awareness is warranted of this idiosyncratic reaction in order to avoid morbidity and long term vision loss.
[Advances of minimally invasive glaucoma surgery in the combined treatment of primary angle-closure glaucoma].
AbstractGlaucoma is the leading irreversible blinding eye disease worldwide, and China has the largest amount of primary angle-closure glaucoma (PACG). To reduce blindness, the therapeutic evolution can play a role. With the technical development of minimally invasive glaucoma surgery (MIGS), the treatment of angle-closure glaucoma has been in a transformation. This article reviews the literatures related to the advances of MIGS in the combined treatment of PACG. The research findings show that MIGS may become one of the preferred surgical treatments for PACG in the future clinical management of glaucoma.
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.
