DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for keratitis — screening already-approved drugs against its 15-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleKeratitis maps to a 15-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 keratitis 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
neurotrophic receptor tyrosine kinase 3 (NTRK3) — NTRK3 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 4-aminophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6KZD · 1.708 Å · ligand 3-[2-[6-(4-aminophenyl)imidazo[1,2-a]pyrazin-3-yl]ethynyl]-2-methyl-~{N}-[3-(4-methylpiperazin-1-yl)-5-propan-2-yl-phenyl]benzamide (DZ6). Experimental structure, not a prediction.
What the evidence adds up to
In a retrospective series of 198 eyes that underwent therapeutic penetrating keratoplasty for fungal keratitis, 89.9% achieved eradication of infection and anatomical restoration was achieved in 97% of cases. However, 10.1% of eyes developed recurrence, and larger infiltrate size before surgery was associated with a higher risk of recurrence. Median graft survival was only 5.9 months, and grafts smaller than 8 mm survived longer than larger grafts. Twenty-seven eyes required regrafting. The authors concluded that timely surgical intervention should be considered when medical therapy fails, but that alternative strategies for managing postoperative inflammation are needed to prevent graft failure.
A Cochrane review of randomised controlled trials for medical therapy in fungal keratitis, last searched in August 2011, identified nine trials randomising 568 participants, mostly conducted in India. The trials compared various topical and oral antifungals including itraconazole, silver sulphadiazine, miconazole, econazole, natamycin, chlorhexidine, and voriconazole. No statistically significant differences between regimens were found, and the review authors stated that there is no evidence that any particular drug or combination is more effective. The trials were described as small, of variable quality, and generally underpowered.
In vivo confocal microscopy of 183 fungal, 18 Acanthamoeba, and 17 bacterial keratitis cases found that Acanthamoeba appeared as bright spots (89%), double-walled cysts (83%), or signet rings (17%), and clusters were associated with prior topical steroid use. Bacterial keratitis was associated with anterior stromal bullae. A honeycomb distribution of anterior stromal inflammatory cells was associated with fungal keratitis. Aspergillus ulcers were associated with stromal dendritiform cells, while Fusarium ulcers were associated with a stellate appearance of interconnected cell processes with nuclei. These features may help identify the organism but do not constitute treatment evidence.
A prospective study of 120 suspected infectious keratitis cases at a tertiary hospital in 2019 identified an infective aetiology in 51% of cases, with fungal growth in 26% and bacterial growth in 22%. Fusarium was the most common fungal isolate, followed by Aspergillus. Among bacteria, Staphylococcus species predominated. A separate cross-sectional study of 276 patients admitted with presumed microbial keratitis in Israel reported a mean hospital stay of 5.7 days, with 72% still using fortified antibiotics at discharge. Visual acuity improved significantly from admission to first follow-up. Contact lens wear was present in 36.1% but was not significantly related to severity or visual outcome. Hypopyon and anterior chamber cells were associated with longer hospital stay and worse visual outcome. Urgent therapeutic penetrating keratoplasty was required in 2.3% and evisceration in 1% of patients. What remains missing are adequately powered randomised trials comparing antifungal drugs, particularly for fungal keratitis, and studies that stratify patients by organism species, infiltrate size, or prior steroid use to identify which subgroups might benefit from specific medical or surgical strategies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Indian Journal of Ophthalmology · 2019 · 68 citations · open access
Outcomes of therapeutic penetrating keratoplasty in 198 eyes with fungal keratitis
AbstractPurpose: To study the outcomes of therapeutic penetrating keratoplasty in fungal keratitis. Methods: This retrospective, observational, interventional case series involved an audit of 198 consecutive eyes that underwent therapeutic penetrating keratoplasty (ThPK) for fungal keratitis at L V Prasad Eye Institute between January 2008 and December 2010 was performed. The data on demographics, clinical characteristics, intraoperative, and late postoperative complications were noted. The primary outcome measure was eradication of infection and postoperative anatomical success. Secondary outcome measures were graft survival, risk factors, clinical features, and management of recurrent fungal keratitis post ThPK. Results: Mean follow-up after ThPK was 24 ± 17 months. A total of 178 (89.9%) eyes had complete eradication of fungal infection, whereas 20 (10.1%) eyes developed recurrence. Anatomical restoration was achieved in majority of cases (192 eyes; 97%). Larger infiltrate size was associated with a higher risk of recurrence of infection. The median graft survival rate was 5.9 months. The graft survival was better for grafts <8 mm versus those with >8 mm (P = 0.026) and not found significantly related to the species of fungus. Twenty-seven eyes underwent re-grafting: penetrating keratoplasty in 14 eyes, and Descemet's stripping endothelial keratoplasty in 13 eyes. Conclusion: As larger infiltrate prior to therapeutic keratoplasty had much higher risk of recurrences; timely surgical intervention should be considered in cases not responding to medical therapy. Alternative strategies of management of postoperative inflammation need to be considered to prevent graft failures.
American Journal of Ophthalmology · 2018 · 60 citations · open access
In Vivo Confocal Microscopy Cellular Features of Host and Organism in Bacterial, Fungal, and Acanthamoeba Keratitis
AbstractPURPOSE: To determine cellular features of fungal (FK), Acanthamoeba (AK), and bacterial keratitis (BK) using HRT3 in vivo confocal microscopy (IVCM). DESIGN: Prospective observational cross-sectional study. METHODS: Eligible participants were adults with microbiologically positive FK, AK, or BK, of size ≥ 3 mm, attending Aravind Eye Hospital from February 2012 to February 2013. Exclusion criteria were descemetocele or perforation. At presentation, IVCM imaging was performed, then corneal scrapes were obtained for culture/light microscopy. An experienced grader (masked to microbiology/clinical features) assessed IVCM images for presence/absence of normal keratocyte-like morphology, stellate interconnected cells with/without visible nuclei, dendritiform cells (DFCs), inflammatory cells in a honeycomb distribution, and organism features. Statistical significance was assessed by logistic regression, adjusted for age, sex, ulcer size, and symptom duration. Main outcome measures were presence/absence of IVCM features in FK, AK, BK. RESULTS: A total of 183 participants had FK, 18 AK, 17 BK. Acanthamoeba appeared as bright spots (16/18, 89%), double-walled cysts (15/18, 83%), or signet rings (3/18, 17%), and often formed clusters after topical steroid use (univariable odds ratio [OR] 9.98, 95% confidence interval [CI] 1.02-97.96, P = .048). BK was associated with bullae in anterior stroma (OR 9.99, 95% CI: 3.11-32.06, P < .001). Honeycomb distribution of anterior stromal inflammatory cells was associated with FK (univariable OR 2.74, 95% CI: 1.01-7.40, P = .047). Aspergillus ulcers were associated with stromal DFCs (OR 11.05, 95% CI: 1.49-82.13, P = .019) and Fusarium ulcers with stellate appearance of interconnected cell processes with nuclei (OR 0.24, 95% CI: 0.09-0.65, P = .005). CONCLUSION: Specific cellular and structural features observed using IVCM in microbial keratitis may be associated with organism.
Cochrane Database of Systematic Reviews · 2012 · 44 citations · open access
Medical interventions for fungal keratitis
AbstractBACKGROUND: Fungal keratitis is a fungal infection of the cornea. It is common in agricultural tropical countries but relatively uncommon in developed countries. Although there are medications available, their effectiveness is unclear. OBJECTIVES: To examine the effect of different antifungal drugs in the management of fungal keratitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 8), MEDLINE (January 1950 to August 2011), EMBASE (January 1980 to August 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 29 August 2011. SELECTION CRITERIA: We included all relevant randomised controlled trials (RCTs) on medical therapy for fungal keratitis. DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion into the review, assessed trials for risk of bias and extracted data. Interventions were compared by the proportions of participants that did not heal after a specific time of therapy. No meta-analysis was performed because the trials studied different medications with different concentrations. MAIN RESULTS: We included nine trials in this review; seven conducted in India, one in Bangladesh and one in Egypt. A total of 568 participants were randomised to the following comparisons: 1% topical itraconazole versus 1% topical itraconazole and oral itraconazole, different concentrations of silver sulphadiazine versus 1% miconazole, 1% silver sulphadiazine ointment versus 1% miconazole ointment, 2% econazole versus 5% natamycin, different concentrations of topical chlorhexidine gluconate versus 5% natamycin, 0.2% chlorhexidine gluconate versus 2.5% natamycin and voriconazole 1% versus natamycin 5%. The included trials were small and of variable quality. Differences between different regimens were not statistically different, which may reflect the low sample sizes. AUTHORS' CONCLUSIONS: Based on the trials included in this review, there is no evidence to date that any particular drug, or combination of drugs, is more effective in the management of fungal keratitis. The trials included in this review were of variable quality and were generally underpowered.
Current Opinion in Ophthalmology · 2016 · 34 citations
Use of adjunctive topical corticosteroids in bacterial keratitis
AbstractPURPOSE OF REVIEW: Topical corticosteroid use in the setting of infectious keratitis has been a controversial issue. The aim of this review is to provide an update on the evidence for use of topical corticosteroids in addition to antibiotics in bacterial keratitis. RECENT FINDINGS: Judicious use of steroids is postulated to limit the inflammatory component of bacterial keratitis, but can theoretically retard healing. Three small randomized controlled trials and one large-scale trial, the Steroids for Corneal Ulcers Trial, have provided the most recent evidence to address this debate. Adjunctive topical corticosteroids initiated after at least 48 h of antibiotic usage in cases of culture-proven bacterial keratitis appear generally safe in the treatment of bacterial keratitis. They may be beneficial in cases of severe ulcers especially when initiated early in the course of the infection, in non-Nocardia ulcers, and in certain Pseudomonas ulcers. SUMMARY: Several randomized controlled trials have greatly contributed to our understanding of the controversy over steroid use in the management of bacterial keratitis. Future studies are needed to confirm subgroup analysis findings and define optimal timing, dosage, and the most appropriate treatment populations.
Cochrane Database of Systematic Reviews · 2003 · 25 citations
Interventions for herpes simplex virus epithelial keratitis
AbstractBACKGROUND: Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus eye disease have evaluated different interventions, but a systematic review of all comparative clinical studies has not previously been undertaken. OBJECTIVES: The objective of this review is to compare the effects of various treatments for dendritic or geographic herpes simplex virus epithelial keratitis. SEARCH STRATEGY: Sources searched for relevant studies were the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group trials register), (Issue 3 2002), MEDLINE (1966 to August 2002), EMBASE (1980 to August 2002), LILACS (up to 2002), Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960 to 1973), reference lists of primary reports and review articles, and conference proceedings pertaining to ocular virology. SELECTION CRITERIA: This review includes comparative clinical trials that assessed one-week and/or two-week healing rates of topical ophthalmic or oral antiviral agents and/or physical or chemical debridement in people with active epithelial keratitis. DATA COLLECTION AND ANALYSIS: The reviewer extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrollment. MAIN RESULTS: This review includes data from 97 trials that randomised a total of 5102 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir generally resulted in a significantly greater proportion of participants healing within one week of treatment. Among these three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical or physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis, but not better than other antiviral agents, although interferon was very useful combined with debridement or with another antiviral agent such as trifluridine. REVIEWER'S CONCLUSIONS: Currently available antiviral agents are effective and nearly equivalent. The combination of a nucleoside antiviral with either debridement or with interferon seems to speed healing. Future trials of the acute treatment of herpes simplex virus epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome of epithelial healing and should consider the effect of lesion size and other characteristics on treatment response.
Journal of Family Medicine and Primary Care · 2020 · 18 citations · open access
Etiological spectrum of infectious keratitis in the era of MALDI-TOF-MS at a tertiary care hospital
AbstractBackground: Infectious Keratitis (Ik) Is A Potential Vision-Threatening Ocular Infection Caused By A Variety Of Microorganisms. Aim: To Explore Risk Factors And Etiological Agents Associated With Ik. Design: A Prospective Cross-Sectional Study In Which Corneal Scrapings From 120 Suspected Cases Were Evaluated At A Tertiary Health Care Institute From January To December 2019. Methods: Scrapings Were Subjected To Direct Microscopy, Culture, And Identification By Both Conventional Methods And Maldi-Tof-Ms. The Patient's Demographic Data And Predisposing Factors, If Any Were Recorded. Results: The Mean Age Of Patients Was 48.9 Years And Predisposing Factors Were Documented In 46% (55/120) Of Cases. Overall, Infective Etiology Could Be Established In 51% ( N = 61/120) Of Cases. Fungal Growth In 26% ( N = 31/120) Of Cases And Bacterial Growth In 22% ( N = 27/120) Of Cases Was Obtained. Growth Of More Than One Species Of Fungi Or Growth Of Bacteria Along With Fungus Were Observed In 2% ( N = 3/120) Of Cases. Of All The Fungal Isolates Obtained ( N = 34), The Most Common Isolate Was Fusarium (18/34) Followed By Aspergillus (8/34), Curvularia (4/34), Pseudallescheria Boydii (3/34), And Geotrichum (1/34). Among The Gram-Positive Bacterial Isolates ( N = 16), Staphyloccus Species (15/16) Were Isolated In Maximum Number Followed By Streptococcus Pneumoniae (1/16). Among The Gram-Negative Isolates ( N = 13), Pseudomonas Species (8/13) Were Isolated In Maximum Number Of Cases, Followed By Acinetobacter (3/13), Klebsiella Pneumoniae (1/13), And Escherichia Coli (1/13). Conclusion: For Initiating Appropriate Empirical Therapy, The Knowledge Of The Epidemiological Pattern Of Infectious Keratitis Of A Particular Geographical Region Is Crucial.
Arquivos Brasileiros de Oftalmologia · 2013 · 6 citations · open access
Clinical characteristics and outcomes of patients admitted with presumed microbial keratitis to a tertiary medical center in Israel
AbstractPURPOSES: Microbial keratitis is commonly diagnosed worldwide, and continues to cause significant ocular morbidity, requiring prompt and appropriate treatment. The objective of this study is to describe the clinical characteristics and outcomes of patients with presumed microbial keratitis admitted to The Goldschleger Eye Institute, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel. METHODS: A cross-sectional study was conducted, in which the medical records of patients with presumed microbial keratitis admitted during a period of 3 years were reviewed. RESULTS: Keratitis was diagnosed in 276 patients (51% males and 48.9% females). The mean age was 39.29 ± 22.30 years. The hospital length of stay ranged from 1 to 65 days (mean 5.69 ± 5.508). Fortified antibiotics were still used at discharge in 72% of the cases. Overall visual acuity improved significantly from the time of admission to the 1st-week follow up visit showing a p<0.001 on the Wilcoxon signed ranks test. Contact lens wearing was present in 36.1% of the patients, although there was no significant relation with severity of the presentation and visual outcome (p>0.05). The degree of hypopyon and cells in the anterior chamber was significantly related to the hospital length of stay (r Spearman=0.31; p<0.001 and r Spearman=0.21; p<.001, respectively) as well as to a worse visual outcome (r Spearman=0.32; p<0.01 and r Spearman=0.18; p=0.01, respectively). Of all patients, 2.3% required an urgent therapeutic penetrating keratoplasty, and 1% underwent evisceration. There was no enucleation. CONCLUSION: Treating keratitis aggressively and assuring patient compliance is imperative for a good final visual outcome. Inpatient treatment may have a positive impact on this outcome.
Randomized Double-Masked Placebo-Controlled Trial for the Management of Pythium Keratitis: Combination of Antibiotics Versus Monotherapy
AbstractPURPOSE: The aim of this study was to compare the efficacy of monotherapy (topical linezolid 0.2%) versus a combination of antibiotics (topical linezolid 0.2% and topical azithromycin 1%) for the treatment of Pythium insidiosum keratitis. METHODS: Cases of P. insidiosum keratitis were prospectively randomized into group A on topical 0.2% linezolid along with topical placebo (sodium carboxymethyl cellulose [CMC] 0.5%) and group B on a combination of topical 0.2% linezolid and topical 1% azithromycin. Both groups were compared by proportion of both clinical resolution and worsening of keratitis along with the number of therapeutic penetrating keratoplasty (TPK) performed at 3 months. RESULTS: We initially planned N = 66 patients but later limited to 20 (N = 10 in each group) patients owing to one interim analysis. The average size of the infiltrate in group A and B was 5.6 ± 1.5 mm and 4.8 ± 2.0 mm, respectively, with a mean Logarithm of the Minimum Angle of Resolution (logMAR) visual acuity of 2.74 ± 0.55 and 1.79 ± 1.19. At 3 months, from group A, 7 (70%) patients needed TPK and 2 patients had signs of resolution, whereas from group B, 6 (60%) patients achieved complete resolution ( P = 0.0003) and 2 were improving while only 1 needed TPK ( P = 0.02). The median duration of treatment in group A and B, with the study drugs, was 31 days (17.8-47.8) and 101.5 days (80-123.3), P value = 0.003, respectively. Final visual acuity at 3 months was 2.50 ± 0.81 and 0.75 ± 0.87, P = 0.02, respectively. CONCLUSIONS: A combination of topical linezolid and topical azithromycin was found to have superior efficacy than the monotherapy with topical linezolid for the management of Pythium keratitis.
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.
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