RARE DISEASE
Endophthalmitis
Endophthalmitis
Endophthalmitis
Drug discovery
3
drugs
With orphan designations
Overview
Endophthalmitis is a vision-threatening infection involving intraocular fluids (vitreous/aqueous), typically caused by bacteria (e.g., Staphylococcus spp.) or fungi. It manifests as acute-onset pain, vision loss, hypopyon, and vitreous haze, requiring immediate intervention to prevent irreversible damage. Most cases occur postoperatively (e.g., cataract surgery, intravitreal injections) or via trauma, though endogenous spread from systemic infections occurs in high-risk patients [1][3][16].
Population
Most prevalent after cataract surgery (0.08–0.68%) and intravitreal injections (0.008–1.4%) [1][2].
Higher risk in older adults, males, and those with diabetes, renal disease, or immunocompromise [2][4][12].
Endogenous cases often linked to bacteremia/fungemia (e.g., Klebsiella liver abscess, candidemia) [9][12].
Burden
Incidence: 0.09% post-intraocular surgery in Medicare populations [2]; mortality 0.97% in inpatients [4].
Visual outcomes: 53% experience major vision loss despite treatment; worse prognosis with virulent pathogens (e.g., Bacillus) [14][16].
Economic impact: Prolonged hospital stays, repeated procedures, and high costs of intravitreal therapies [3][10].
Prompt diagnosis and aggressive treatment are critical to optimizing outcomes [1][6].
Therapies
Intravitreal antibiotics (vancomycin + ceftazidime) ± corticosteroids; systemic antifungals (echinocandins/fluconazole) for endogenous cases [3][5][8].
Vitrectomy for severe cases (e.g., light perception vision, intraocular foreign bodies) to reduce microbial load [3][13].
Adjunctive topical antibiotics, vigilant monitoring, and early surgical intervention for trauma-related or refractory infections [1][9].
Categories: rare ophthalmic disorders
Research Papers
3,229 drug discovery papers about Endophthalmitis, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
3,229 drug discovery papers about Endophthalmitis, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-13 | Visual Acuity Influences Visual Outcome in Endophthalmitis: A 10-Year Retrospective Observational Cohort Analysis.
Endophthalmitis is a severe, sight-threatening intraocular infection that may follow ophthalmic procedures or arise endogenously. Since the Endophthalmitis Vitrectomy Study (EVS, 1995), surgical and antimicrobial strategies have evolved. This study aimed to evaluate treatment approaches, microbial spectrum, and outcomes of endophthalmitis cases at the University Eye Clinic Innsbruck over the past decade. A retrospective observational cohort analysis of all patients treated for endophthalmitis between January 2013 and December 2023 was conducted. Cases were categorized as exogenous, endogenous, or keratitis-related. Data on etiology, treatment, time to intervention, microbial isolates, and best-corrected visual acuity (BCVA, logMAR) were assessed. Treatment included tap and inject, pars plana vitrectomy (PPV) within 24 h after presentation, or delayed surgery. Regression analyses identified predictors of visual outcome and re-intervention. A total of 118 eyes from 110 patients (median age 72 years) were included. Exogenous cases accounted for 60.2%, endogenous for 28.8%. Median BCVA at diagnosis was 2.3 logMAR, improving to 1.0 logMAR at 6 months. Pathogens were isolated in 58.5% of cases-mainly Staphylococcus epidermidis (57%) in exogenous and Candida albicans (20.6%) in endogenous infections. Median time to intervention in exogenous cases was 3.5 h. BCVA at diagnosis and timepoint were significantly associated with visual outcome over time (p < 0.001, respectively; exogenous cases only). Re-intervention was required in 78 eyes; hazard was significantly higher after delayed surgery in exogenous cases (HR of 5.7, 95% CI [2.9-11.1], p < 0.001 (n = 71, 39 re-interventions). Visual acuity remains the main prognostic factor for visual recovery. In exogenous endophthalmitis, delayed surgery is associated with a high re-intervention rate, which may be reduced by initial tap-and-inject treatment. Prospective studies are needed to establish optimal timing and treatment strategies.
2026-08-06 | An Injectable Dual Bacterial-Trapping Nanozyme Composite Hydrogel for Synergistic Antibacterial/Anti-Inflammatory Therapy of Endophthalmitis.
Bacterial endophthalmitis (BE) is characterized by severe intraocular bacterial infection and sustained inflammation. Current therapeutic efficacy is compromised by the passive diffusion-dominated drug release kinetics of conventional carriers, leading to inadequate bacterial clearance and frequent invasive injections. Herein, an injectable hydrogel is engineered to achieve a synergistic "trap-and-kill" and immunomodulatory therapy. The hydrogel matrix is constructed via dynamic Schiff base crosslinking between quaternized chitosan and oxidized dextran, providing excellent injectability and biocompatibility. The hydrogel integrates boronic acid-decorated cerium metal-organic frameworks (Ce-MOFs) within this dynamic polysaccharide network, possessing dual bacterial-trapping attributed to boronic acid-mediated bacterial surface covalent binding to surface cis-diols and electrostatic attraction. This "bacterial enrichment" effect overcomes the diffusion barrier, markedly enhancing the bactericidal efficiency of the encapsulated vancomycin, resulting in a reduction in the dosage to as low as 14-20% of the clinical amount, yet the effect remains comparable. Furthermore, leveraging the catalase- and superoxide dismutase-mimicking activities of Ce-MOFs, the hydrogel functions as a therapeutic nanozyme to scavenge excessive reactive oxygen species (ROS) and downregulate pro-inflammatory cytokines. Validated by comprehensive in vitro and in vivo models, this integrated platform demonstrates superior bacterial eradication and inflammation resolution, which presents an active, robust therapeutic strategy for those deep-seated implant-associated infections.
2026-07-31 | Outcomes in patients with endophthalmitis and no light perception vision initially treated with intravitreal antibiotics
Abstract Background Management of endophthalmitis presenting with NLP (no light perception) vision remains poorly defined, with limited evidence guiding treatment decisions. We aim to investigate whether treatment with intravitreal antibiotics reduces the rate of enucleation or evisceration of eyes presenting with exogenous or endogenous endophthalmitis and NLP vision. Methods Retrospective chart review of patients who presented with endophthalmitis and NLP vision between 2010 and 2020 at a tertiary referral center. Main outcome measures were the proportion of patients receiving intravitreal antibiotics or enucleation/evisceration (ENEV) as initial treatment and the rate of globe preservation in patients who received intravitreal antibiotics. Results 28 eyes of 26 patients presented with endophthalmitis and NLP vision. The majority of eyes (18/28) were initially treated with intravitreal antibiotics with the aim of globe preservation. Of these 18 eyes, a majority (11/18) achieved globe preservation and the remainder underwent secondary ENEV. Eyes with endogenous and exogenous endophthalmitis that were treated with intravitreal antibiotics achieved similar rates of globe preservation (54% and 57%, respectively). After intravitreal antibiotics, vision in one eye improved to light perception and underwent pars plana vitrectomy to maintain vision. Ultimately, however, the final recorded visual acuity in all eyes was NLP. Additionally, two eyes that received intravitreal antibiotics eventually suffered from phthisical changes, although there was no pain associated with these cases. Conclusion In eyes with NLP vision and endophthalmitis, treatment with intravitreal antibiotics leads to a meaningful rate of globe preservation, however the medical decision making in these cases is complex, requiring consideration of the clinical scenario and the patient’s preferences.
2026-07-30 | Dropless Pars Plana Vitrectomy Using Intravitreal Decanted Triamcinolone and Moxifloxacin: Safety and Efficacy.
To evaluate the safety and efficacy of a dropless regimen using intravitreal decanted triamcinolone acetonide and moxifloxacin at the conclusion of pars plana vitrectomy (PPV), compared with standard postoperative topical therapy. This retrospective study included consecutive patients undergoing PPV at a tertiary retina center. The dropless cohort (May-October 2025) received intravitreal decanted triamcinolone (5 mg) and moxifloxacin (500 μg). The control cohort, operated during the preceding 6 months, received topical moxifloxacin 0.5% and prednisolone acetate 1%. Outcomes included intraocular inflammation, intraocular pressure (IOP), central subfield thickness (CST), cystoid macular edema (CME), and best-corrected visual acuity (BCVA). A prespecified subgroup analysis was performed for epiretinal membrane (ERM). 172 eyes were included (87 dropless, 85 topical). The dropless group demonstrated significantly less anterior chamber inflammation at week 2 (P = 0.0008) and at month 3 (P = 0.0223). Mean CST was lower at week 2 (P = 0.001), month 3 (P = 0.0009), and month 6 (P = 0.012). CME incidence was reduced (P < 0.001). BCVA improvement was greater in the dropless group at week 2 (+15 vs -2.5 ETDRS letters; P = 0.0003), month 3 (+25 vs +9.5 letters; P = 0.002), and month 6 (+20 vs +8 letters; P = 0.01). IOP was similar between groups, and no endophthalmitis occurred. Findings were consistent in the ERM subgroup. A dropless intravitreal regimen at the conclusion of PPV can be a safe and effective alternative to topical therapy, with reduced postoperative inflammation and CME and improved visual outcomes.
2026-07-27 | Current Recommendations, Antibiotic Resistance, and Emerging Treatments for Gram-Positive Ocular Infections in the United States.
Severe bacterial keratitis and endophthalmitis are leading causes of corneal scarring, enucleation, and permanent vision loss, and are increasingly complicated by multidrug-resistant Gram-positive ocular pathogens. In the United States, according to the ARMOR surveillance program (2009-2020), methicillin resistance reached 45.9% of intraocular Staphylococcus aureus and 47.9% of coagulase-negative staphylococci (CoNS), with multidrug resistance exceeding 70% among methicillin-resistant intraocular isolates. While new antibiotics have been approved for systemic infections, vancomycin remains the standard of care for severe Gram-positive ocular infections. However, its ophthalmic use is constrained by limited ocular surface tolerability, physical incompatibility with intravitreal ceftazidime, and an association with hemorrhagic occlusive retinal vasculitis. To address this gap and further stimulate the development of next-generation targeted therapies in ophthalmology, this review focuses on current recommendations and new vancomycin alternative treatments for Gram-positive ocular infections in the antibiotic resistance era. This review details the current antimicrobial recommendations for the most frequent ocular infections, followed by the epidemiology and molecular mechanisms of resistance in S. aureus, CoNS, and S. pneumoniae. Finally, this review discusses new drugs that represent promising alternatives to vancomycin in ophthalmology.
proteins
2026-05-15 | Dual-action antimicrobial peptide therapy: disrupting biofilm formation and targeting bacterial DNA for enhanced treatment of Pseudomonas aeruginosa endophthalmitis.
Intraocular infections caused by Pseudomonas aeruginosa are difficult to treat due to bacterial biofilm-mediated antibiotic resistance. We used cationic polypeptide (XXYY) n to evaluate its effect and mechanism against Pseudomonas aeruginosa biofilm and its efficacy against Pseudomonas aeruginosa intraocular infection. Microbroth dilution showed that the MIC90 of (LLKK)3C against Pseudomonas aeruginosa was 32 μg/mL. After continuous passage for 10 generations, the stability of antibacterial activity of (LLKK)3C against Pseudomonas aeruginosa was better than that of amikacin. TEM, SEM and live/dead staining demonstrated that (LLKK)3C was able to destroy the integrity of bacterial and biofilm and exert antibacterial activity by interacting with phosphatidyl glycerol on the membrane to destroy the bacterial membrane. Electrophoretic gel and Alphafold3 demonstrated that (LLKK)3C binds to bacterial DNA through charge interactions. In the rabbit endophthalmitis model, the intraocular bacterial load decreased after intravitreal injection (LLKK)3C treatment (vs untreated, P < 0.05). Studies have shown that (LLKK)3C has synergistic antibacterial effects through the dual mechanism of targeting membrane destruction and DNA binding, which provides a new treatment strategy for biomembrane-associated intraocular infections. Ocular infections caused by Pseudomonas aeruginosa often lead to severe vision loss due to antibiotic-resistant bacterial biofilms, which shield bacteria from conventional treatments. This study introduces (LLKK)3C, that uniquely attacks biofilms through a dual-action mechanism: physically disrupting bacterial membranes and binding to bacterial DNA. Unlike traditional antibiotics like amikacin, (LLKK)3C maintains robust antibacterial activity even after prolonged exposure, reducing the risk of resistance development. In a rabbit endophthalmitis model, (LLKK)3C significantly reduced intraocular bacterial loads, demonstrating its potential as a targeted therapy for sight-threatening infections. By addressing the dual challenges of biofilm resistance and drug stability, (LLKK)3C offers a promising strategy to improve clinical outcomes for patients with difficult-to-treat eye infections.
2026-03-26 | Resolvin D1 requires TLR2-FPR2 crosstalk for inflammation resolution and protection during ocular bacterial infection.
The eye is highly susceptible to inflammation-induced tissue damage; however, the mechanisms that drive inflammation resolution during ocular infections remain unclear. In this study, we utilize a murine model of intraocular bacterial infection (S. aureus-induced endophthalmitis) and lipidomics analysis to uncover a critical role of pro-resolving lipid mediators, particularly resolvin D1 (RvD1), in resolving inflammation and restoring ocular tissue homeostasis and vision. RvD1 protects mouse eyes from severe endophthalmitis by enhancing bacterial clearance, suppressing intraocular inflammation, and preserving retinal structure and function. Pharmacological inhibition of formyl peptide receptor 2 (FPR2) reveals that RvD1's protective effects mainly rely on FPR2 signaling. Unexpectedly, RvD1 is unable to resolve inflammation or protect the eye in the absence of Toll-like receptor 2 (TLR2), a critical pattern recognition receptor in ocular S. aureus infections. These findings reveal an unrecognized interplay between TLR2 and FPR2 signaling, including their mutual regulation and physical receptor interactions during bacterial infection. Overall, these findings provide new insights into the coordinated roles of TLR2 and FPR2 in resolving inflammation and protecting the eye during bacterial infections.
2025-09-19 | Efficacy and safety of posterior subtenon interferon alfa-2B injection in recurrent inflammatory macular edema.
This study aimed to evaluate the efficacy of posterior subtenon injection of interferon alfa-2B (PSII) as a therapeutic option for managing recurrent inflammatory macular edema (IME). A retrospective study was conducted at a tertiary care eye center in South India. Patients receiving PSII for recurrent infectious or non-infectious IME were included in the study. Recurrent IME was defined as less than 50 µm improvement in central macular thickness (CMT) on spectral-domain optical coherence tomography within 1 month or relapse of IME within 3 months of previous treatment. Patients received a single PSII (1 MIU/mL) under topical anesthesia. Follow-up visits included clinical examinations and CMT measurement, best-corrected visual acuity (BCVA), and intraocular pressure (IOP). The study included 13 patients with a mean age of 46.2 years. Diagnosis varied, including pseudophakic IME, post-endophthalmitis IME, and various forms of uveitis. Mean CMT significantly reduced from 639.0 µm at baseline to 427.45 µm at one week ( P < 0.001). But further increased to 500.62 µm at 1-2 months follow-up ( P < 0.05). Mean BCVA improved from 20/70 (0.57 logMAR) to 20/40 (0.33 logMAR) at 1-month follow-up. No significant adverse effects were observed, although one patient with post-endophthalmitis IME developed granulomatous anterior uveitis 40 days after the injection. The study demonstrates the potential short-term efficacy of PSII in reducing CMT and improving BCVA in patients with recurrent IME. Further research is needed to optimize dosing protocols and explore long-term efficacy.
2025-07-16 | Intraocular tissue plasminogen activator during vitrectomy in the management of acute severe bacterial endophthalmitis.
To describe a novel off-label use of tissue plasminogen activator (tPA) in the setting of severe endophthalmitis for improved surgical outcomes during pars plana vitrectomy. After a limited core vitrectomy is completed, 50mcg/0.1ml tPA is administered intravitreally and allowed to take effect with a 15-minute lights-out period. A fluid-fluid exchange is then carried out to lavage the inflammatory debris and tPA from the posterior segment. This technique allows for significantly improved surgical visualization and complete removal of inflammatory debris in the anterior and posterior segment. Increased clearance of intraocular inflammatory debris may reduce post-infection inflammatory sequalae such as posterior synechiae and preretinal membranes and achieve better surgical outcomes.
2024-05-14 | Recombinant prourokinase in the treatment of postoperative endophthalmitis
Purpose. To determine the effectiveness of prourokinase in the treatment of acute postoperative endophthalmitis. Material and methods. The study included 5 patients with acute endophthalmitis after cataract surgery. Symptoms of endophthalmitis appeared on the 3rd day after surgery in 3 patients, on the 4th in 2 patients. All patients underwent vitrectomy on the day of presentation without inducing posterior detachment of the hyaloid membrane with intravitreal administration of a combination of antibiotic and prourokinase at the end of the operation. Results.On the first day after surgery, all patients had severe inflammatory manifestations, which completely disappeared by day 7. Maximum corrected visual acuity after 1 month was: 0.7 in 1 patient, 0.8 in 1 patient, 1.0 in 3 patients. Conclusion.The use of recombinant prourokinase in combination with intravitreal antibiotics and vitrectomy demonstrated high functional results without complications in the early postoperative period. Keywords: vitreoretinal surgery, vitrectomy, endophthalmitis, fibrinoid syndrome, postoperative inflammation, enzyme therapy, recombinant prourokinase
cell therapies
2026-01-12 | Successful Repair of Glaucoma Drainage Device Tube Exposure With a Corneal Patch Graft and Double-Layer Amniotic Membrane: A Case Report.
Tube exposure is a recognised complication of glaucoma drainage devices (GDD). We report a case of successful repair of GDD tube exposure using a corneal patch graft and double-layer amniotic membrane in a visually precious eye with previous multiple surgeries. A 47-year-old man with juvenile open-angle glaucoma (JOAG) underwent trabeculectomy in both eyes (OU) and two GDD implantations in the right eye (OD). The left eye (OS) trabeculectomy failed, leading to panophthalmitis and evisceration. Six years after the second GDD in the OD, the superonasal tube became exposed (3.8 mm). Initial repair with an amniotic membrane transplant (AMT) failed, leaving the tube partially exposed (3.2 mm) with scarred, stiff conjunctiva but no leakage. Visual acuity (VA) was counting fingers, and intraocular pressure (IOP) was 11 mmHg. Conservative management included autologous serum eye drops, topical antibiotics, oral doxycycline, and a bandage contact lens. After six months, exposure was reduced to 1.0 mm but increased to 2.0 mm by month eight. The patient underwent surgical repair with a corneal patch graft and double-layer AMT. At six months postoperatively, the tube remained fully covered with no conjunctival erosion. Tube exposure is sight-threatening and may lead to endophthalmitis; persistent or recurrent cases can be effectively managed with corneal patch grafting combined with double-layer AMT, providing durable coverage, promoting re-epithelialisation, and allowing assessment of the underlying device.
2025-07-23 | Long-term prognosis of repeat Type I Boston keratoprosthesis.
The Boston Type I keratoprosthesis (B-KPro) is a synthetic corneal implant used to restore vision in cases of corneal blindness. While the B-KPro can achieve a visual acuity of better than 20/200, it is associated with a risk of implant failure. In cases of failure, a repeat B-KPro may offer another opportunity for vision restoration. This study aims to evaluate the long-term outcomes of patients undergoing repeat B-KPro after failure of the initial implant. This is a retrospective cohort study. Eighteen patients who underwent two B-KPro implantations in the same eye, with a mean follow-up period of 8.1 ± 4.6 years. The primary endpoints were the failure rate of the implant and visual acuity at the last follow-up. The failure rate of the repeat B-KPro (11.11% at 5 years) was significantly lower than that of the first B-KPro (88.89% at 5 years) (p < 0.0001) for the repeat cohort. Visual acuity better than 20/200 was achieved in 30.09% and 24.07% of patients at 3 years and 6 years, respectively, following repeat B-KPro, similar to outcomes observed after the first B-KPro. The incidence of phthisis was higher after the repeat B-KPro, but the rates of hypotony, endophthalmitis, corneal melt, and extrusion were lower compared to the first B-KPro. Repeat B-KPro can provide sustained visual acuity better than 20/200 after failure of the initial implant. Further studies with larger cohorts are needed to better understand the risks and benefits associated with repeat B-KPro.
2024-10-14 | Unveiling the Innate and Adaptive Immunity Interplay: Global Transcriptomic Profiling of the Host Immune Response in Candida albicans Endophthalmitis in a Murine Model.
Intraocular fungal infection poses a significant clinical challenge characterized by chronic inflammation along with vision impairment. Understanding the host defense pathways involved in fungal endophthalmitis will play a pivotal role in identifying adjuvant immunotherapy. Clinical isolates of Candida albicans (15,000 CFU/μL) were intravitreally injected in C57BL/6 mice followed by enucleation at 24 and 72 h postinfection. Histopathological analysis was performed to evaluate the retinal changes and the disease severity. RNA-seq analysis was conducted on homogenized eyeballs to assess the relevant gene profiles and their differentially expressed genes (DEGs). Pathway enrichment analysis was performed to further annotate the functions of the DEGs. Histopathological analysis demonstrated a higher disease severity with increased inflammatory cells at 72 hpi and transcriptome analysis revealed 27,717 DEGs, of which 1493 were significant (adj p value ≤0.05, FC ≥ 1.5). Among these, 924 were upregulated, and 569 were downregulated. Majority of the upregulated genes were associated with the inflammatory/host immune response and signal transduction and enriched in the T-cell signaling pathway, natural killer cell-mediated cytotoxicity, C-type receptor signaling pathway, and NOD-like receptor signaling pathway. Furthermore, inflammation-associated genes such as T-cell surface glycoprotein CD3, cathelicidin antimicrobial peptide, and lymphocyte cell-specific protein tyrosine kinase were enriched, while pathways such as MAPK, cAMP, and metabolic pathways were downregulated. Regulating the T-cell influx could be a potential strategy to modulate excessive inflammation in the retina and could potentially aid in better vision recovery in fungal endophthalmitis.
2024-04-30 | Global Transcriptomic Profiling of Innate and Adaptive Immunity During Aspergillus flavus Endophthalmitis in a Murine Model.
Fungal endophthalmitis is characterized by chronic inflammation leading to the partial or complete vision loss. Herein, we analyzed the transcriptomic landscape of Aspergillus flavus (A. flavus) endophthalmitis in C57BL/6 mice to understand the host-pathogen interactions. Endophthalmitis was induced by intravitreal injection of A. flavus spores in C57BL/6 mice and monitored for disease progression up to 72 hours. The enucleated eyeballs were subjected to histopathological analysis and mRNA sequencing using the Illumina Nextseq 2000. Pathway enrichment analysis was performed to further annotate the functions of differentially expressed genes (DEGs) and validation of cytokines was performed in vitreous of patients with fungal endophthalmitis using multiplex ELISA. Transcriptomic landscape of A. flavus endophthalmitis revealed upregulated T-cell receptor signaling, PI3K-AKT, MAPK, NF-κB, JAK-STAT, and NOD like receptor signaling pathways. We observed significant increase in the T-cells during infection especially at 72 hours infection along with elevated expression levels of IL-6, IL-10, IL-12, IL-18, IL-19, IL-23, CCR3, and CCR7. Furthermore, host-immune response associated genes, such as T-cell interacting activating receptor, TNF receptor-associated factor 1, TLR1, TLR9, and bradykinin receptor beta 1, were enriched. Histopathological assessment validated the significant increase in inflammatory cells, especially T-cells at 72 hours post-infection along with increased disruption in the retinal architecture. Additionally, IL-6, IL-8, IL-17, TNF-α, and IL-1β were also significantly elevated, whereas IL-10 was downregulated in vitreous of patients with Aspergillus endophthalmitis. Regulating T-cell influx could be a potential strategy to modulate the excessive inflammation in the retina and potentially aid in better vision recovery in fungal endophthalmitis.
2023-04-26 | The art of fixing a ticking time bomb: Combined phacoemulsification and amniotic membrane transplantation.
Bleb leakage is a notorious complication of glaucoma filtration surgery which increases the risk of sight-threatening conditions. A 25-year-old female with severe bilateral juvenile open-angle glaucoma was treated for blebitis and exogenous endophthalmitis secondary to chronic bleb leak after undergoing XEN implantation, followed by multiple rounds of bleb needling, and augmented trabeculectomy. In the right eye, visual acuity was hand movement with cataract, intraocular pressure was 6 mmHg and the bleb was large, highly elevated from 10 to 1 o'clock, avascular, thin wall, and cystic with leaking points. Combined surgery of low-setting phacoemulsification and amniotic membrane transplantation without excising and manipulating the bleb was performed in the same setting. At postoperative 1 month, 6 months, and 1 year, her right vision had improved to 6/24, and the intraocular pressure was 12-14 mmHg, and the bleb leakage had resolved. This successful treatment was accomplished by maintaining the bleb's viability, preventing additional injury, and promoting wound healing.
antibodies
2026-08-02 | Twelve-month functional and structural outcomes of Candida endogenous endophthalmitis in immunocompetent patients: a longitudinal cohort study of an outbreak.
To characterize twelve-month visual outcomes, structural complications, and retinal pigment epithelium (RPE) dynamics stratified by initial lesion morphology in an iatrogenic, single-center outbreak of Candida endogenous endophthalmitis (EFE) among immunocompetent patients. This retrospective longitudinal cohort study included patients from a single-source outbreak. Of 26 eyes in the original cohort, 18 were classified with chorioretinal involvement and 8 with intraretinal or preretinal involvement. After excluding eyes with severe baseline destruction or loss to follow-up, 13 chorioretinal eyes and 8 intraretinal or preretinal eyes completed the twelve-month follow-up. Main outcome measures included best-corrected visual acuity (BCVA), complication rates, the incidence of secondary macular neovascularization (MNV) using optical coherence tomography angiography (OCTA), and longitudinal RPE lesion area changes quantified via optical coherence tomography (OCT). Although both groups experienced functional improvement after treatment, the chorioretinal group had significantly worse final BCVA at twelve months (median 0.80 versus 0.20 LogMAR; P = 0.005) and a higher overall complication burden (92.3% versus 25.0%; P < 0.001) than the intraretinal or preretinal group. Secondary MNV developed in 100.0% of evaluable eyes in the chorioretinal group (10/10; 95% CI, 69.2%-100.0%), whereas no MNV occurred in the intraretinal/preretinal group (0/8; 95% CI, 0.0%-36.9%; P < 0.001). In the chorioretinal group, the RPE lesion area increased during the first three months and subsequently decreased by month twelve, occurring concurrently with sustained BCVA improvement. Initial chorioretinal involvement was associated with poorer visual recovery and a markedly higher incidence of secondary MNV. The early expansion of RPE lesions alongside visual improvement likely reflects tissue remodeling and may be less suggestive of ongoing infection. These findings support routine OCT and OCTA surveillance and timely anti-vascular endothelial growth factor therapy for eyes with chorioretinal involvement.
2026-05-29 | Endophthalmitis rates following intravitreal injection of aflibercept using a prefilled syringe - a multicenter study.
To evaluate endophthalmitis rates following intravitreal injection of aflibercept, comparing between vial preparation and prefilled syringe use. We retrospectively collected data from ten ophthalmology departments in Israel. The number of intravitreal anti-VEGF injections administered in years 2022 and 2023 was recorded. Endophthalmitis rates in 2022 (vial use) and in 2023 (prefilled syringe use) were compared. Clinical details of endophthalmitis cases were reviewed. In 2022, out of 119,904 intravitreal injections, 31,991 (27%) were aflibercept injections prepared from vials. In 2023, out of 128,306 intravitreal injections, 35,589 (28%) were aflibercept injections from prefilled syringes. Endophthalmitis rates were similar between vial preparation (1:1991) and prefilled syringe (1:2372) (p = 0.63). Notably, aflibercept injections exhibited significantly higher endophthalmitis rates compared to bevacizumab and ranibizumab combined, in both years (1:1999 vs. 1:5494 in 2022, and 1:2373 vs. 1:7132 in 2023, respectively; p < 0.01 for both). Despite the transit to prefilled aflibercept syringes, endophthalmitis rates following aflibercept injection did not decrease. Post-injection endophthalmitis rates were significantly higher with aflibercept compared to bevacizumab and ranibizumab, with both vial and prefilled syringe.
2026-05-19 | A Humanized Anti-gD Broadly Neutralizing Antibody Confers Complete Post-Exposure Protection against Pseudorabies Virus.
Pseudorabies virus (PRV), an α‑herpesvirus, has recently been recognized as a potentially significant zoonotic pathogen, causing severe encephalitis and endophthalmitis in humans with high mortality and disability rates. Despite its growing public‑health threat, no effective therapeutics are available for human PRV infection. Here, we isolated a broadly neutralizing monoclonal antibody, designated 6F7, which targets the PRV glycoprotein D (gD) and neutralizes all tested PRV lineages. Mechanistic studies reveal that 6F7 does not impede viral attachment or internalization; instead, it specifically blocks the fusion of the viral envelope with cellular membranes, thereby preventing viral replication. Moreover, the antibody also potently suppresses cell‑to‑cell spread of PRV. We demonstrate that the interaction between gD and the PRV receptor Nectin‑1 is blocked by 6F7. Last, a humanized version of 6F7 confers complete protection in mice challenged with a lethal PRV variant and blocks the establishment of latency at a dose of 15 mg/kg per mouse. Overall, the humanized broadly neutralizing antibody represents a promising therapeutic candidate for human PRV infection.
2026-02-11 | Non-physician delivered intravitreal injection service: A systematic review of safety, implementation, training and patient experience.
The global demand for intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy continues to rise, straining ophthalmic capacity worldwide. Task shifting from physicians to trained non-physician healthcare professionals has emerged as a potential strategy to expand service delivery. This systematic review summarizes current evidence on the safety, implementation, training and patient experiences associated with non-physician-delivered intravitreal injection services. We systematically searched 13 scientific literature databases for studies of anti-VEGF injections performed by non-physicians. Data were extracted on safety outcomes, implementation, training, supervision and patient-reported experience. Results from individual studies were qualitatively reviewed according to these four organizational themes. Sixteen studies comprising 100 150 injections were included, primarily from the United Kingdom and Scandinavia. All injectors completed structured training under an ophthalmologist's supervision. Complication rates were very low, including 0.015%-0.07% for endophthalmitis which were comparable to physician-led benchmarks. Implementation of non-physician-delivered intravitreal injection services increased clinical capacity by 25%-85%, reduced waiting times and costs, and maintained safety and efficiency. Patients reported high satisfaction, confidence and acceptance of non-physician-delivered injections. Non-physician-delivered intravitreal injection services are safe, feasible and well accepted when supported by structured training and robust governance frameworks. This task-shifting model offers a scalable solution to meet growing global demand for anti-VEGF therapy. Standardized international training and certification frameworks may further enhance safety and sustainability.
2025-11-24 | Novel Needle for Intravitreal Injections Does Not Affect Biological Activity of Anti-VEGF Drugs.
In this in vitro study, we investigated if the biological activity of commonly used VEGF antagonists might be affected by their passage through a newly designed 30 G needle (NDN) for intravitreal injection (IVI). To reduce the risk of intraocular inflammation compared to conventional injection with a standard hypodermic 30 G needle (SHN), the NDN contains an occluded front orifice and a side port for drug delivery, resulting in an altered direction of the injection stream. Anti-VEGF drugs, such as ranibizumab, faricimab, and aflibercept, were passed twice through one of the two needle types to imitate IVI. To evaluate the VEGF-A-binding capacity of the un- or pretreated antagonists, VEGF-A165 was incubated with a 1-10fold molar excess of them for 15 min at 37°C, and unbound VEGF-A was determined by ELISA. As the capture antibody and antagonists bind to the same region of the growth factor, only the non-complexed VEGF-A was measured. Biological activity of pretreated antagonists was studied by assessing their capacity to prevent VEGF-A165-induced impairment of the barrier formed by retinal endothelial cells: VEGF-A165 plus antagonists were added to the cells and, as a measure of permeability, the cell index was continuously monitored by electric cell-substrate impedance measurements for three days. Only a marginal amount of free VEGF-A, if any, was detected after incubation of the growth factor with a fourfold molar excess of any of the antagonists, independent of the drugs' pretreatment. VEGF-A165-induced low cell index values, indicative of a dysfunctional barrier, were similarly prevented by different pretreated antagonists. The passage of the proteins through NDN or SHN did neither affect efficient binding to their target, nor their capacity to prevent VEGF-A165-induced barrier dysfunction. Overall, regarding the stability of therapeutic proteins, the NDN was not inferior to the SHN, and can now be considered for evaluation in clinical studies.
other
2025-02-06 | Utilizing the subtractive proteomics approach to design ensemble vaccine against Candida lusitaniae for immune response stimulation; a bioinformatics study.
Vaccines have always been one of the promising therapeutic sources against many pathogens including infectious fungi. Candida lusitaniae is also one of those fungi which is responsible for different infections in human beings including vaginitis, endocarditis, endophthalmitis and blood stream infections. There is thus, a need to adopt effective therapeutic strategies to tackle such infections. Vaccine is one of those efficient therapeutic agents which stimulates immune response and prevents a certain infection to get hazardous. Keeping in view this very important concept, we have designed in-silico vaccine against C. lusitaniae by following the subtractive proteomics approach. Initially, the screening of therapeutic targets was performed to identify potent vaccine candidates from the whole proteome of C. lusitaniae. Several significant factors were taken into account in this context, such as stability index, IFN status, allergenicity, and antigenicity. As a result, four distinct proteins that were both antigenic and non-allergenic, were selected from the whole proteome. Furthermore, physiochemical investigation revealed that these vaccine candidates were stable and that their IFN status was positive. Notably, each of these proteins was non-homologous to human beings. This particular attribute of the selected proteins i.e., to be non-homologous, was made in order to possess the ability to trigger an immunological response in host (humans). Furthermore, the whole proteome (WP) vaccine was constructed accordingly. The structural modelling of all the selected vaccine candidates was then performed to proceed them further for docking with the human toll-like receptor 2 (TLR2). Afterwards, the codon optimization was executed, followed by in-silico cloning of the final vaccine construct. The pet28A plasmid was incorporated for this purpose while, the SnapGene tool was utilized for this particular analysis. Ultimately, the immune simulations were executed to assess the immune response of the designed vaccine (WP). Upon final results, it was found that highest count of IgG and IgM was achieved i.e., up to 700000 between the days 8 to 13 and then slowly neutralized till the day 30. These results signified that the designed vaccine possessed the potential to stimulate the required immune response.
2024-08-21 | miR-27a-3p promotes inflammatory response in infectious endophthalmitis via targeting TSC1.
Infectious endophthalmitis (IE) poses a significant threat to vision. This study aimed to explore the impact of microRNA (miR)-27a-3p on inflammation in IE. A rat model was developed through intravitreal injection of lipopolysaccharide. Clinical and demographic data were collected for 54 participants: 31 diagnosed with IE and 23 non-infectious patients with idiopathic macular holes. Expression levels of miR-27a-3p and inflammatory genes were quantified via reverse transcription quantitative polymerase chain reaction. Concentrations of inflammatory cytokines in human vitreous samples were measured using enzyme-linked immunosorbent assay. In vitro studies were conducted to explore the target gene of miR-27a-3p. The final animal experiments further verified the role of miR-27a-3p and tuberous sclerosis complex (TSC)1 in inflammatory responses. Results showed that miR-27a-3p was elevated in LPS-treated rats and IE patients. Thirty-one IE patients were divided into the High (n = 15) and Low (n = 16) groups according to the expression of miR-27a-3p. No significant differences were observed in baseline clinical and demographic characteristics between the control and IE patient groups. Pro-inflammatory cytokine mRNA levels and concentrations were notably increased in both LPS-treated rats and the High group of patients. Besides, results showed that TSC1 is a target gene of miR-27a-3p. Moreover, TSC1 inhibition promoted inflammation in rat vitreous samples. In summary, our findings suggested that miR-27a-3p exacerbated inflammatory responses in IE though targeting TSC1, offering novel insights for potential therapeutic strategies targeting miR-27a-3p in the clinical management of IE.
2024-07-17 | Feasibility of Direct Vitrectomy-Sparing Subretinal Injection for Gene Delivery in Large Animals.
To assess the safety and feasibility of direct vitrectomy-sparing subretinal injection for gene delivery in a large animal model. The experimental Liběchov minipigs were used for subretinal delivery of a plasmid DNA vector (pS/MAR-CMV-copGFP) with cytomegalovirus (CMV) promoter, green fluorescent protein (GFP) reporter (copGFP) and a scaffold/matrix attachment region (S/MAR) sequence. The eyes were randomized to subretinal injection of the vector following pars plana vitrectomy (control group) or a direct injection without prior vitrectomy surgery (experimental group). Intra- and post-operative observations up to 30 days after surgery were compared. Six eyes of three mini-pigs underwent surgery for delivery into the subretinal space. Two eyes in the control group were operated with a classical approach (lens-sparing vitrectomy and posterior hyaloid detachment). The other four eyes in the experimental group were injected directly with a subretinal cannula without vitrectomy surgery. No adverse events, such as endophthalmitis, retinal detachment and intraocular pressure elevation were observed post-operatively. The eyes in the experimental group had both shorter surgical time and recovery while achieving the same surgical goal. This pilot study demonstrates that successful subretinal delivery of gene therapy vectors is achievable using a direct injection without prior vitrectomy surgery.
2024-05-26 | The association between endophthalmitis risk following a variety of intra-ocular procedures and defensin gene profile
Endophthalmitis is a sight threatening complication of intra-ocular procedures. It has been suggested that a predisposition to endophthalmitis is linked to a specific genotype in the human beta-defensin 1 (HBD-1) gene when previously analysed in a small UK cohort undergoing cataract surgery. We sought to test out this hypothesis in a larger international case: control study (centres in UK, Netherlands and Canada) following a variety of intraocular procedures. International case: control study 660 individuals undergoing an intraocular procedure were recruited (165 cases of endophthalmitis and 495 controls). DNA was extracted. Single nucleotide polymorphisms, SNPs, rs11362, rs1800972 and rs2702877 in the HBD-1 gene were analysed (both individual genotypes and haplotypes were obtained). No associations were found when individual SNPs were analysed across the combined international cohort. However, analysis of the Toronto sub-cohort, showed a statistically significant association between the endophthalmitis cohort and the rs1800972 C allele (OR: 3.18, CI: 1.32 - 7.68, p = 0.01) and rs2702877 G allele (OR: 3.06, CI: 1.35 - 6.95, p = 0.017). No haplotype association was identified with endophthalmitis compared to control in both institution sub-cohorts and combined cohort analysis. A strong trend associating the rs1800972, rs11362 GG mini-haplotype with culture positive endophthalmitis groups across all groups was noted, but this did not reach statistical significance. This is the first study to demonstrate a genetic link between a certain genetic profile (HBD-1 gene SNP variation) and endophthalmitis. Future pre-operative genetic testing could help identify patients at risk of endophthalmitis to guide invasive treatment options.
2023-07-17 | Antisense Oligonucleotides Selectively Enter Human-Derived Antibiotic-Resistant Bacteria through Bacterial-Specific ATP-Binding Cassette Sugar Transporter.
Current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic-resistant bacteria. Herein, bacteria-specific ATP-binding cassette (ABC) sugar transporters are leveraged to selectively internalize ASOs by hitchhiking them on α (1-4)-glucosidically linked glucose polymers. Compared with their cell-penetrating peptide counterparts, which are non-specifically engulfed by mammalian and bacterial cells, the presented therapeutics consisting of glucose polymer and antisense peptide nucleic-acid-modified nanoparticles are selectively internalized into the human-derived multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e., 51.6%). The developed strategy allows specific and efficient killing of nearly 100% of the antibiotic-resistant bacteria. Its significant curative efficacy against bacterial keratitis and endophthalmitis is also shown. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.
small molecules
2026-08-13 | Visual Acuity Influences Visual Outcome in Endophthalmitis: A 10-Year Retrospective Observational Cohort Analysis.
Endophthalmitis is a severe, sight-threatening intraocular infection that may follow ophthalmic procedures or arise endogenously. Since the Endophthalmitis Vitrectomy Study (EVS, 1995), surgical and antimicrobial strategies have evolved. This study aimed to evaluate treatment approaches, microbial spectrum, and outcomes of endophthalmitis cases at the University Eye Clinic Innsbruck over the past decade. A retrospective observational cohort analysis of all patients treated for endophthalmitis between January 2013 and December 2023 was conducted. Cases were categorized as exogenous, endogenous, or keratitis-related. Data on etiology, treatment, time to intervention, microbial isolates, and best-corrected visual acuity (BCVA, logMAR) were assessed. Treatment included tap and inject, pars plana vitrectomy (PPV) within 24 h after presentation, or delayed surgery. Regression analyses identified predictors of visual outcome and re-intervention. A total of 118 eyes from 110 patients (median age 72 years) were included. Exogenous cases accounted for 60.2%, endogenous for 28.8%. Median BCVA at diagnosis was 2.3 logMAR, improving to 1.0 logMAR at 6 months. Pathogens were isolated in 58.5% of cases-mainly Staphylococcus epidermidis (57%) in exogenous and Candida albicans (20.6%) in endogenous infections. Median time to intervention in exogenous cases was 3.5 h. BCVA at diagnosis and timepoint were significantly associated with visual outcome over time (p < 0.001, respectively; exogenous cases only). Re-intervention was required in 78 eyes; hazard was significantly higher after delayed surgery in exogenous cases (HR of 5.7, 95% CI [2.9-11.1], p < 0.001 (n = 71, 39 re-interventions). Visual acuity remains the main prognostic factor for visual recovery. In exogenous endophthalmitis, delayed surgery is associated with a high re-intervention rate, which may be reduced by initial tap-and-inject treatment. Prospective studies are needed to establish optimal timing and treatment strategies.
2026-08-06 | An Injectable Dual Bacterial-Trapping Nanozyme Composite Hydrogel for Synergistic Antibacterial/Anti-Inflammatory Therapy of Endophthalmitis.
Bacterial endophthalmitis (BE) is characterized by severe intraocular bacterial infection and sustained inflammation. Current therapeutic efficacy is compromised by the passive diffusion-dominated drug release kinetics of conventional carriers, leading to inadequate bacterial clearance and frequent invasive injections. Herein, an injectable hydrogel is engineered to achieve a synergistic "trap-and-kill" and immunomodulatory therapy. The hydrogel matrix is constructed via dynamic Schiff base crosslinking between quaternized chitosan and oxidized dextran, providing excellent injectability and biocompatibility. The hydrogel integrates boronic acid-decorated cerium metal-organic frameworks (Ce-MOFs) within this dynamic polysaccharide network, possessing dual bacterial-trapping attributed to boronic acid-mediated bacterial surface covalent binding to surface cis-diols and electrostatic attraction. This "bacterial enrichment" effect overcomes the diffusion barrier, markedly enhancing the bactericidal efficiency of the encapsulated vancomycin, resulting in a reduction in the dosage to as low as 14-20% of the clinical amount, yet the effect remains comparable. Furthermore, leveraging the catalase- and superoxide dismutase-mimicking activities of Ce-MOFs, the hydrogel functions as a therapeutic nanozyme to scavenge excessive reactive oxygen species (ROS) and downregulate pro-inflammatory cytokines. Validated by comprehensive in vitro and in vivo models, this integrated platform demonstrates superior bacterial eradication and inflammation resolution, which presents an active, robust therapeutic strategy for those deep-seated implant-associated infections.
2026-07-31 | Outcomes in patients with endophthalmitis and no light perception vision initially treated with intravitreal antibiotics
Abstract Background Management of endophthalmitis presenting with NLP (no light perception) vision remains poorly defined, with limited evidence guiding treatment decisions. We aim to investigate whether treatment with intravitreal antibiotics reduces the rate of enucleation or evisceration of eyes presenting with exogenous or endogenous endophthalmitis and NLP vision. Methods Retrospective chart review of patients who presented with endophthalmitis and NLP vision between 2010 and 2020 at a tertiary referral center. Main outcome measures were the proportion of patients receiving intravitreal antibiotics or enucleation/evisceration (ENEV) as initial treatment and the rate of globe preservation in patients who received intravitreal antibiotics. Results 28 eyes of 26 patients presented with endophthalmitis and NLP vision. The majority of eyes (18/28) were initially treated with intravitreal antibiotics with the aim of globe preservation. Of these 18 eyes, a majority (11/18) achieved globe preservation and the remainder underwent secondary ENEV. Eyes with endogenous and exogenous endophthalmitis that were treated with intravitreal antibiotics achieved similar rates of globe preservation (54% and 57%, respectively). After intravitreal antibiotics, vision in one eye improved to light perception and underwent pars plana vitrectomy to maintain vision. Ultimately, however, the final recorded visual acuity in all eyes was NLP. Additionally, two eyes that received intravitreal antibiotics eventually suffered from phthisical changes, although there was no pain associated with these cases. Conclusion In eyes with NLP vision and endophthalmitis, treatment with intravitreal antibiotics leads to a meaningful rate of globe preservation, however the medical decision making in these cases is complex, requiring consideration of the clinical scenario and the patient’s preferences.
2026-07-30 | Dropless Pars Plana Vitrectomy Using Intravitreal Decanted Triamcinolone and Moxifloxacin: Safety and Efficacy.
To evaluate the safety and efficacy of a dropless regimen using intravitreal decanted triamcinolone acetonide and moxifloxacin at the conclusion of pars plana vitrectomy (PPV), compared with standard postoperative topical therapy. This retrospective study included consecutive patients undergoing PPV at a tertiary retina center. The dropless cohort (May-October 2025) received intravitreal decanted triamcinolone (5 mg) and moxifloxacin (500 μg). The control cohort, operated during the preceding 6 months, received topical moxifloxacin 0.5% and prednisolone acetate 1%. Outcomes included intraocular inflammation, intraocular pressure (IOP), central subfield thickness (CST), cystoid macular edema (CME), and best-corrected visual acuity (BCVA). A prespecified subgroup analysis was performed for epiretinal membrane (ERM). 172 eyes were included (87 dropless, 85 topical). The dropless group demonstrated significantly less anterior chamber inflammation at week 2 (P = 0.0008) and at month 3 (P = 0.0223). Mean CST was lower at week 2 (P = 0.001), month 3 (P = 0.0009), and month 6 (P = 0.012). CME incidence was reduced (P < 0.001). BCVA improvement was greater in the dropless group at week 2 (+15 vs -2.5 ETDRS letters; P = 0.0003), month 3 (+25 vs +9.5 letters; P = 0.002), and month 6 (+20 vs +8 letters; P = 0.01). IOP was similar between groups, and no endophthalmitis occurred. Findings were consistent in the ERM subgroup. A dropless intravitreal regimen at the conclusion of PPV can be a safe and effective alternative to topical therapy, with reduced postoperative inflammation and CME and improved visual outcomes.
2026-07-27 | Current Recommendations, Antibiotic Resistance, and Emerging Treatments for Gram-Positive Ocular Infections in the United States.
Severe bacterial keratitis and endophthalmitis are leading causes of corneal scarring, enucleation, and permanent vision loss, and are increasingly complicated by multidrug-resistant Gram-positive ocular pathogens. In the United States, according to the ARMOR surveillance program (2009-2020), methicillin resistance reached 45.9% of intraocular Staphylococcus aureus and 47.9% of coagulase-negative staphylococci (CoNS), with multidrug resistance exceeding 70% among methicillin-resistant intraocular isolates. While new antibiotics have been approved for systemic infections, vancomycin remains the standard of care for severe Gram-positive ocular infections. However, its ophthalmic use is constrained by limited ocular surface tolerability, physical incompatibility with intravitreal ceftazidime, and an association with hemorrhagic occlusive retinal vasculitis. To address this gap and further stimulate the development of next-generation targeted therapies in ophthalmology, this review focuses on current recommendations and new vancomycin alternative treatments for Gram-positive ocular infections in the antibiotic resistance era. This review details the current antimicrobial recommendations for the most frequent ocular infections, followed by the epidemiology and molecular mechanisms of resistance in S. aureus, CoNS, and S. pneumoniae. Finally, this review discusses new drugs that represent promising alternatives to vancomycin in ophthalmology.
proteins
2026-05-15 | Dual-action antimicrobial peptide therapy: disrupting biofilm formation and targeting bacterial DNA for enhanced treatment of Pseudomonas aeruginosa endophthalmitis.
Intraocular infections caused by Pseudomonas aeruginosa are difficult to treat due to bacterial biofilm-mediated antibiotic resistance. We used cationic polypeptide (XXYY) n to evaluate its effect and mechanism against Pseudomonas aeruginosa biofilm and its efficacy against Pseudomonas aeruginosa intraocular infection. Microbroth dilution showed that the MIC90 of (LLKK)3C against Pseudomonas aeruginosa was 32 μg/mL. After continuous passage for 10 generations, the stability of antibacterial activity of (LLKK)3C against Pseudomonas aeruginosa was better than that of amikacin. TEM, SEM and live/dead staining demonstrated that (LLKK)3C was able to destroy the integrity of bacterial and biofilm and exert antibacterial activity by interacting with phosphatidyl glycerol on the membrane to destroy the bacterial membrane. Electrophoretic gel and Alphafold3 demonstrated that (LLKK)3C binds to bacterial DNA through charge interactions. In the rabbit endophthalmitis model, the intraocular bacterial load decreased after intravitreal injection (LLKK)3C treatment (vs untreated, P < 0.05). Studies have shown that (LLKK)3C has synergistic antibacterial effects through the dual mechanism of targeting membrane destruction and DNA binding, which provides a new treatment strategy for biomembrane-associated intraocular infections. Ocular infections caused by Pseudomonas aeruginosa often lead to severe vision loss due to antibiotic-resistant bacterial biofilms, which shield bacteria from conventional treatments. This study introduces (LLKK)3C, that uniquely attacks biofilms through a dual-action mechanism: physically disrupting bacterial membranes and binding to bacterial DNA. Unlike traditional antibiotics like amikacin, (LLKK)3C maintains robust antibacterial activity even after prolonged exposure, reducing the risk of resistance development. In a rabbit endophthalmitis model, (LLKK)3C significantly reduced intraocular bacterial loads, demonstrating its potential as a targeted therapy for sight-threatening infections. By addressing the dual challenges of biofilm resistance and drug stability, (LLKK)3C offers a promising strategy to improve clinical outcomes for patients with difficult-to-treat eye infections.
2026-03-26 | Resolvin D1 requires TLR2-FPR2 crosstalk for inflammation resolution and protection during ocular bacterial infection.
The eye is highly susceptible to inflammation-induced tissue damage; however, the mechanisms that drive inflammation resolution during ocular infections remain unclear. In this study, we utilize a murine model of intraocular bacterial infection (S. aureus-induced endophthalmitis) and lipidomics analysis to uncover a critical role of pro-resolving lipid mediators, particularly resolvin D1 (RvD1), in resolving inflammation and restoring ocular tissue homeostasis and vision. RvD1 protects mouse eyes from severe endophthalmitis by enhancing bacterial clearance, suppressing intraocular inflammation, and preserving retinal structure and function. Pharmacological inhibition of formyl peptide receptor 2 (FPR2) reveals that RvD1's protective effects mainly rely on FPR2 signaling. Unexpectedly, RvD1 is unable to resolve inflammation or protect the eye in the absence of Toll-like receptor 2 (TLR2), a critical pattern recognition receptor in ocular S. aureus infections. These findings reveal an unrecognized interplay between TLR2 and FPR2 signaling, including their mutual regulation and physical receptor interactions during bacterial infection. Overall, these findings provide new insights into the coordinated roles of TLR2 and FPR2 in resolving inflammation and protecting the eye during bacterial infections.
2025-09-19 | Efficacy and safety of posterior subtenon interferon alfa-2B injection in recurrent inflammatory macular edema.
This study aimed to evaluate the efficacy of posterior subtenon injection of interferon alfa-2B (PSII) as a therapeutic option for managing recurrent inflammatory macular edema (IME). A retrospective study was conducted at a tertiary care eye center in South India. Patients receiving PSII for recurrent infectious or non-infectious IME were included in the study. Recurrent IME was defined as less than 50 µm improvement in central macular thickness (CMT) on spectral-domain optical coherence tomography within 1 month or relapse of IME within 3 months of previous treatment. Patients received a single PSII (1 MIU/mL) under topical anesthesia. Follow-up visits included clinical examinations and CMT measurement, best-corrected visual acuity (BCVA), and intraocular pressure (IOP). The study included 13 patients with a mean age of 46.2 years. Diagnosis varied, including pseudophakic IME, post-endophthalmitis IME, and various forms of uveitis. Mean CMT significantly reduced from 639.0 µm at baseline to 427.45 µm at one week ( P < 0.001). But further increased to 500.62 µm at 1-2 months follow-up ( P < 0.05). Mean BCVA improved from 20/70 (0.57 logMAR) to 20/40 (0.33 logMAR) at 1-month follow-up. No significant adverse effects were observed, although one patient with post-endophthalmitis IME developed granulomatous anterior uveitis 40 days after the injection. The study demonstrates the potential short-term efficacy of PSII in reducing CMT and improving BCVA in patients with recurrent IME. Further research is needed to optimize dosing protocols and explore long-term efficacy.
2025-07-16 | Intraocular tissue plasminogen activator during vitrectomy in the management of acute severe bacterial endophthalmitis.
To describe a novel off-label use of tissue plasminogen activator (tPA) in the setting of severe endophthalmitis for improved surgical outcomes during pars plana vitrectomy. After a limited core vitrectomy is completed, 50mcg/0.1ml tPA is administered intravitreally and allowed to take effect with a 15-minute lights-out period. A fluid-fluid exchange is then carried out to lavage the inflammatory debris and tPA from the posterior segment. This technique allows for significantly improved surgical visualization and complete removal of inflammatory debris in the anterior and posterior segment. Increased clearance of intraocular inflammatory debris may reduce post-infection inflammatory sequalae such as posterior synechiae and preretinal membranes and achieve better surgical outcomes.
2024-05-14 | Recombinant prourokinase in the treatment of postoperative endophthalmitis
Purpose. To determine the effectiveness of prourokinase in the treatment of acute postoperative endophthalmitis. Material and methods. The study included 5 patients with acute endophthalmitis after cataract surgery. Symptoms of endophthalmitis appeared on the 3rd day after surgery in 3 patients, on the 4th in 2 patients. All patients underwent vitrectomy on the day of presentation without inducing posterior detachment of the hyaloid membrane with intravitreal administration of a combination of antibiotic and prourokinase at the end of the operation. Results.On the first day after surgery, all patients had severe inflammatory manifestations, which completely disappeared by day 7. Maximum corrected visual acuity after 1 month was: 0.7 in 1 patient, 0.8 in 1 patient, 1.0 in 3 patients. Conclusion.The use of recombinant prourokinase in combination with intravitreal antibiotics and vitrectomy demonstrated high functional results without complications in the early postoperative period. Keywords: vitreoretinal surgery, vitrectomy, endophthalmitis, fibrinoid syndrome, postoperative inflammation, enzyme therapy, recombinant prourokinase
cell therapies
2026-01-12 | Successful Repair of Glaucoma Drainage Device Tube Exposure With a Corneal Patch Graft and Double-Layer Amniotic Membrane: A Case Report.
Tube exposure is a recognised complication of glaucoma drainage devices (GDD). We report a case of successful repair of GDD tube exposure using a corneal patch graft and double-layer amniotic membrane in a visually precious eye with previous multiple surgeries. A 47-year-old man with juvenile open-angle glaucoma (JOAG) underwent trabeculectomy in both eyes (OU) and two GDD implantations in the right eye (OD). The left eye (OS) trabeculectomy failed, leading to panophthalmitis and evisceration. Six years after the second GDD in the OD, the superonasal tube became exposed (3.8 mm). Initial repair with an amniotic membrane transplant (AMT) failed, leaving the tube partially exposed (3.2 mm) with scarred, stiff conjunctiva but no leakage. Visual acuity (VA) was counting fingers, and intraocular pressure (IOP) was 11 mmHg. Conservative management included autologous serum eye drops, topical antibiotics, oral doxycycline, and a bandage contact lens. After six months, exposure was reduced to 1.0 mm but increased to 2.0 mm by month eight. The patient underwent surgical repair with a corneal patch graft and double-layer AMT. At six months postoperatively, the tube remained fully covered with no conjunctival erosion. Tube exposure is sight-threatening and may lead to endophthalmitis; persistent or recurrent cases can be effectively managed with corneal patch grafting combined with double-layer AMT, providing durable coverage, promoting re-epithelialisation, and allowing assessment of the underlying device.
2025-07-23 | Long-term prognosis of repeat Type I Boston keratoprosthesis.
The Boston Type I keratoprosthesis (B-KPro) is a synthetic corneal implant used to restore vision in cases of corneal blindness. While the B-KPro can achieve a visual acuity of better than 20/200, it is associated with a risk of implant failure. In cases of failure, a repeat B-KPro may offer another opportunity for vision restoration. This study aims to evaluate the long-term outcomes of patients undergoing repeat B-KPro after failure of the initial implant. This is a retrospective cohort study. Eighteen patients who underwent two B-KPro implantations in the same eye, with a mean follow-up period of 8.1 ± 4.6 years. The primary endpoints were the failure rate of the implant and visual acuity at the last follow-up. The failure rate of the repeat B-KPro (11.11% at 5 years) was significantly lower than that of the first B-KPro (88.89% at 5 years) (p < 0.0001) for the repeat cohort. Visual acuity better than 20/200 was achieved in 30.09% and 24.07% of patients at 3 years and 6 years, respectively, following repeat B-KPro, similar to outcomes observed after the first B-KPro. The incidence of phthisis was higher after the repeat B-KPro, but the rates of hypotony, endophthalmitis, corneal melt, and extrusion were lower compared to the first B-KPro. Repeat B-KPro can provide sustained visual acuity better than 20/200 after failure of the initial implant. Further studies with larger cohorts are needed to better understand the risks and benefits associated with repeat B-KPro.
2024-10-14 | Unveiling the Innate and Adaptive Immunity Interplay: Global Transcriptomic Profiling of the Host Immune Response in Candida albicans Endophthalmitis in a Murine Model.
Intraocular fungal infection poses a significant clinical challenge characterized by chronic inflammation along with vision impairment. Understanding the host defense pathways involved in fungal endophthalmitis will play a pivotal role in identifying adjuvant immunotherapy. Clinical isolates of Candida albicans (15,000 CFU/μL) were intravitreally injected in C57BL/6 mice followed by enucleation at 24 and 72 h postinfection. Histopathological analysis was performed to evaluate the retinal changes and the disease severity. RNA-seq analysis was conducted on homogenized eyeballs to assess the relevant gene profiles and their differentially expressed genes (DEGs). Pathway enrichment analysis was performed to further annotate the functions of the DEGs. Histopathological analysis demonstrated a higher disease severity with increased inflammatory cells at 72 hpi and transcriptome analysis revealed 27,717 DEGs, of which 1493 were significant (adj p value ≤0.05, FC ≥ 1.5). Among these, 924 were upregulated, and 569 were downregulated. Majority of the upregulated genes were associated with the inflammatory/host immune response and signal transduction and enriched in the T-cell signaling pathway, natural killer cell-mediated cytotoxicity, C-type receptor signaling pathway, and NOD-like receptor signaling pathway. Furthermore, inflammation-associated genes such as T-cell surface glycoprotein CD3, cathelicidin antimicrobial peptide, and lymphocyte cell-specific protein tyrosine kinase were enriched, while pathways such as MAPK, cAMP, and metabolic pathways were downregulated. Regulating the T-cell influx could be a potential strategy to modulate excessive inflammation in the retina and could potentially aid in better vision recovery in fungal endophthalmitis.
2024-04-30 | Global Transcriptomic Profiling of Innate and Adaptive Immunity During Aspergillus flavus Endophthalmitis in a Murine Model.
Fungal endophthalmitis is characterized by chronic inflammation leading to the partial or complete vision loss. Herein, we analyzed the transcriptomic landscape of Aspergillus flavus (A. flavus) endophthalmitis in C57BL/6 mice to understand the host-pathogen interactions. Endophthalmitis was induced by intravitreal injection of A. flavus spores in C57BL/6 mice and monitored for disease progression up to 72 hours. The enucleated eyeballs were subjected to histopathological analysis and mRNA sequencing using the Illumina Nextseq 2000. Pathway enrichment analysis was performed to further annotate the functions of differentially expressed genes (DEGs) and validation of cytokines was performed in vitreous of patients with fungal endophthalmitis using multiplex ELISA. Transcriptomic landscape of A. flavus endophthalmitis revealed upregulated T-cell receptor signaling, PI3K-AKT, MAPK, NF-κB, JAK-STAT, and NOD like receptor signaling pathways. We observed significant increase in the T-cells during infection especially at 72 hours infection along with elevated expression levels of IL-6, IL-10, IL-12, IL-18, IL-19, IL-23, CCR3, and CCR7. Furthermore, host-immune response associated genes, such as T-cell interacting activating receptor, TNF receptor-associated factor 1, TLR1, TLR9, and bradykinin receptor beta 1, were enriched. Histopathological assessment validated the significant increase in inflammatory cells, especially T-cells at 72 hours post-infection along with increased disruption in the retinal architecture. Additionally, IL-6, IL-8, IL-17, TNF-α, and IL-1β were also significantly elevated, whereas IL-10 was downregulated in vitreous of patients with Aspergillus endophthalmitis. Regulating T-cell influx could be a potential strategy to modulate the excessive inflammation in the retina and potentially aid in better vision recovery in fungal endophthalmitis.
2023-04-26 | The art of fixing a ticking time bomb: Combined phacoemulsification and amniotic membrane transplantation.
Bleb leakage is a notorious complication of glaucoma filtration surgery which increases the risk of sight-threatening conditions. A 25-year-old female with severe bilateral juvenile open-angle glaucoma was treated for blebitis and exogenous endophthalmitis secondary to chronic bleb leak after undergoing XEN implantation, followed by multiple rounds of bleb needling, and augmented trabeculectomy. In the right eye, visual acuity was hand movement with cataract, intraocular pressure was 6 mmHg and the bleb was large, highly elevated from 10 to 1 o'clock, avascular, thin wall, and cystic with leaking points. Combined surgery of low-setting phacoemulsification and amniotic membrane transplantation without excising and manipulating the bleb was performed in the same setting. At postoperative 1 month, 6 months, and 1 year, her right vision had improved to 6/24, and the intraocular pressure was 12-14 mmHg, and the bleb leakage had resolved. This successful treatment was accomplished by maintaining the bleb's viability, preventing additional injury, and promoting wound healing.
antibodies
2026-08-02 | Twelve-month functional and structural outcomes of Candida endogenous endophthalmitis in immunocompetent patients: a longitudinal cohort study of an outbreak.
To characterize twelve-month visual outcomes, structural complications, and retinal pigment epithelium (RPE) dynamics stratified by initial lesion morphology in an iatrogenic, single-center outbreak of Candida endogenous endophthalmitis (EFE) among immunocompetent patients. This retrospective longitudinal cohort study included patients from a single-source outbreak. Of 26 eyes in the original cohort, 18 were classified with chorioretinal involvement and 8 with intraretinal or preretinal involvement. After excluding eyes with severe baseline destruction or loss to follow-up, 13 chorioretinal eyes and 8 intraretinal or preretinal eyes completed the twelve-month follow-up. Main outcome measures included best-corrected visual acuity (BCVA), complication rates, the incidence of secondary macular neovascularization (MNV) using optical coherence tomography angiography (OCTA), and longitudinal RPE lesion area changes quantified via optical coherence tomography (OCT). Although both groups experienced functional improvement after treatment, the chorioretinal group had significantly worse final BCVA at twelve months (median 0.80 versus 0.20 LogMAR; P = 0.005) and a higher overall complication burden (92.3% versus 25.0%; P < 0.001) than the intraretinal or preretinal group. Secondary MNV developed in 100.0% of evaluable eyes in the chorioretinal group (10/10; 95% CI, 69.2%-100.0%), whereas no MNV occurred in the intraretinal/preretinal group (0/8; 95% CI, 0.0%-36.9%; P < 0.001). In the chorioretinal group, the RPE lesion area increased during the first three months and subsequently decreased by month twelve, occurring concurrently with sustained BCVA improvement. Initial chorioretinal involvement was associated with poorer visual recovery and a markedly higher incidence of secondary MNV. The early expansion of RPE lesions alongside visual improvement likely reflects tissue remodeling and may be less suggestive of ongoing infection. These findings support routine OCT and OCTA surveillance and timely anti-vascular endothelial growth factor therapy for eyes with chorioretinal involvement.
2026-05-29 | Endophthalmitis rates following intravitreal injection of aflibercept using a prefilled syringe - a multicenter study.
To evaluate endophthalmitis rates following intravitreal injection of aflibercept, comparing between vial preparation and prefilled syringe use. We retrospectively collected data from ten ophthalmology departments in Israel. The number of intravitreal anti-VEGF injections administered in years 2022 and 2023 was recorded. Endophthalmitis rates in 2022 (vial use) and in 2023 (prefilled syringe use) were compared. Clinical details of endophthalmitis cases were reviewed. In 2022, out of 119,904 intravitreal injections, 31,991 (27%) were aflibercept injections prepared from vials. In 2023, out of 128,306 intravitreal injections, 35,589 (28%) were aflibercept injections from prefilled syringes. Endophthalmitis rates were similar between vial preparation (1:1991) and prefilled syringe (1:2372) (p = 0.63). Notably, aflibercept injections exhibited significantly higher endophthalmitis rates compared to bevacizumab and ranibizumab combined, in both years (1:1999 vs. 1:5494 in 2022, and 1:2373 vs. 1:7132 in 2023, respectively; p < 0.01 for both). Despite the transit to prefilled aflibercept syringes, endophthalmitis rates following aflibercept injection did not decrease. Post-injection endophthalmitis rates were significantly higher with aflibercept compared to bevacizumab and ranibizumab, with both vial and prefilled syringe.
2026-05-19 | A Humanized Anti-gD Broadly Neutralizing Antibody Confers Complete Post-Exposure Protection against Pseudorabies Virus.
Pseudorabies virus (PRV), an α‑herpesvirus, has recently been recognized as a potentially significant zoonotic pathogen, causing severe encephalitis and endophthalmitis in humans with high mortality and disability rates. Despite its growing public‑health threat, no effective therapeutics are available for human PRV infection. Here, we isolated a broadly neutralizing monoclonal antibody, designated 6F7, which targets the PRV glycoprotein D (gD) and neutralizes all tested PRV lineages. Mechanistic studies reveal that 6F7 does not impede viral attachment or internalization; instead, it specifically blocks the fusion of the viral envelope with cellular membranes, thereby preventing viral replication. Moreover, the antibody also potently suppresses cell‑to‑cell spread of PRV. We demonstrate that the interaction between gD and the PRV receptor Nectin‑1 is blocked by 6F7. Last, a humanized version of 6F7 confers complete protection in mice challenged with a lethal PRV variant and blocks the establishment of latency at a dose of 15 mg/kg per mouse. Overall, the humanized broadly neutralizing antibody represents a promising therapeutic candidate for human PRV infection.
2026-02-11 | Non-physician delivered intravitreal injection service: A systematic review of safety, implementation, training and patient experience.
The global demand for intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy continues to rise, straining ophthalmic capacity worldwide. Task shifting from physicians to trained non-physician healthcare professionals has emerged as a potential strategy to expand service delivery. This systematic review summarizes current evidence on the safety, implementation, training and patient experiences associated with non-physician-delivered intravitreal injection services. We systematically searched 13 scientific literature databases for studies of anti-VEGF injections performed by non-physicians. Data were extracted on safety outcomes, implementation, training, supervision and patient-reported experience. Results from individual studies were qualitatively reviewed according to these four organizational themes. Sixteen studies comprising 100 150 injections were included, primarily from the United Kingdom and Scandinavia. All injectors completed structured training under an ophthalmologist's supervision. Complication rates were very low, including 0.015%-0.07% for endophthalmitis which were comparable to physician-led benchmarks. Implementation of non-physician-delivered intravitreal injection services increased clinical capacity by 25%-85%, reduced waiting times and costs, and maintained safety and efficiency. Patients reported high satisfaction, confidence and acceptance of non-physician-delivered injections. Non-physician-delivered intravitreal injection services are safe, feasible and well accepted when supported by structured training and robust governance frameworks. This task-shifting model offers a scalable solution to meet growing global demand for anti-VEGF therapy. Standardized international training and certification frameworks may further enhance safety and sustainability.
2025-11-24 | Novel Needle for Intravitreal Injections Does Not Affect Biological Activity of Anti-VEGF Drugs.
In this in vitro study, we investigated if the biological activity of commonly used VEGF antagonists might be affected by their passage through a newly designed 30 G needle (NDN) for intravitreal injection (IVI). To reduce the risk of intraocular inflammation compared to conventional injection with a standard hypodermic 30 G needle (SHN), the NDN contains an occluded front orifice and a side port for drug delivery, resulting in an altered direction of the injection stream. Anti-VEGF drugs, such as ranibizumab, faricimab, and aflibercept, were passed twice through one of the two needle types to imitate IVI. To evaluate the VEGF-A-binding capacity of the un- or pretreated antagonists, VEGF-A165 was incubated with a 1-10fold molar excess of them for 15 min at 37°C, and unbound VEGF-A was determined by ELISA. As the capture antibody and antagonists bind to the same region of the growth factor, only the non-complexed VEGF-A was measured. Biological activity of pretreated antagonists was studied by assessing their capacity to prevent VEGF-A165-induced impairment of the barrier formed by retinal endothelial cells: VEGF-A165 plus antagonists were added to the cells and, as a measure of permeability, the cell index was continuously monitored by electric cell-substrate impedance measurements for three days. Only a marginal amount of free VEGF-A, if any, was detected after incubation of the growth factor with a fourfold molar excess of any of the antagonists, independent of the drugs' pretreatment. VEGF-A165-induced low cell index values, indicative of a dysfunctional barrier, were similarly prevented by different pretreated antagonists. The passage of the proteins through NDN or SHN did neither affect efficient binding to their target, nor their capacity to prevent VEGF-A165-induced barrier dysfunction. Overall, regarding the stability of therapeutic proteins, the NDN was not inferior to the SHN, and can now be considered for evaluation in clinical studies.
other
2025-02-06 | Utilizing the subtractive proteomics approach to design ensemble vaccine against Candida lusitaniae for immune response stimulation; a bioinformatics study.
Vaccines have always been one of the promising therapeutic sources against many pathogens including infectious fungi. Candida lusitaniae is also one of those fungi which is responsible for different infections in human beings including vaginitis, endocarditis, endophthalmitis and blood stream infections. There is thus, a need to adopt effective therapeutic strategies to tackle such infections. Vaccine is one of those efficient therapeutic agents which stimulates immune response and prevents a certain infection to get hazardous. Keeping in view this very important concept, we have designed in-silico vaccine against C. lusitaniae by following the subtractive proteomics approach. Initially, the screening of therapeutic targets was performed to identify potent vaccine candidates from the whole proteome of C. lusitaniae. Several significant factors were taken into account in this context, such as stability index, IFN status, allergenicity, and antigenicity. As a result, four distinct proteins that were both antigenic and non-allergenic, were selected from the whole proteome. Furthermore, physiochemical investigation revealed that these vaccine candidates were stable and that their IFN status was positive. Notably, each of these proteins was non-homologous to human beings. This particular attribute of the selected proteins i.e., to be non-homologous, was made in order to possess the ability to trigger an immunological response in host (humans). Furthermore, the whole proteome (WP) vaccine was constructed accordingly. The structural modelling of all the selected vaccine candidates was then performed to proceed them further for docking with the human toll-like receptor 2 (TLR2). Afterwards, the codon optimization was executed, followed by in-silico cloning of the final vaccine construct. The pet28A plasmid was incorporated for this purpose while, the SnapGene tool was utilized for this particular analysis. Ultimately, the immune simulations were executed to assess the immune response of the designed vaccine (WP). Upon final results, it was found that highest count of IgG and IgM was achieved i.e., up to 700000 between the days 8 to 13 and then slowly neutralized till the day 30. These results signified that the designed vaccine possessed the potential to stimulate the required immune response.
2024-08-21 | miR-27a-3p promotes inflammatory response in infectious endophthalmitis via targeting TSC1.
Infectious endophthalmitis (IE) poses a significant threat to vision. This study aimed to explore the impact of microRNA (miR)-27a-3p on inflammation in IE. A rat model was developed through intravitreal injection of lipopolysaccharide. Clinical and demographic data were collected for 54 participants: 31 diagnosed with IE and 23 non-infectious patients with idiopathic macular holes. Expression levels of miR-27a-3p and inflammatory genes were quantified via reverse transcription quantitative polymerase chain reaction. Concentrations of inflammatory cytokines in human vitreous samples were measured using enzyme-linked immunosorbent assay. In vitro studies were conducted to explore the target gene of miR-27a-3p. The final animal experiments further verified the role of miR-27a-3p and tuberous sclerosis complex (TSC)1 in inflammatory responses. Results showed that miR-27a-3p was elevated in LPS-treated rats and IE patients. Thirty-one IE patients were divided into the High (n = 15) and Low (n = 16) groups according to the expression of miR-27a-3p. No significant differences were observed in baseline clinical and demographic characteristics between the control and IE patient groups. Pro-inflammatory cytokine mRNA levels and concentrations were notably increased in both LPS-treated rats and the High group of patients. Besides, results showed that TSC1 is a target gene of miR-27a-3p. Moreover, TSC1 inhibition promoted inflammation in rat vitreous samples. In summary, our findings suggested that miR-27a-3p exacerbated inflammatory responses in IE though targeting TSC1, offering novel insights for potential therapeutic strategies targeting miR-27a-3p in the clinical management of IE.
2024-07-17 | Feasibility of Direct Vitrectomy-Sparing Subretinal Injection for Gene Delivery in Large Animals.
To assess the safety and feasibility of direct vitrectomy-sparing subretinal injection for gene delivery in a large animal model. The experimental Liběchov minipigs were used for subretinal delivery of a plasmid DNA vector (pS/MAR-CMV-copGFP) with cytomegalovirus (CMV) promoter, green fluorescent protein (GFP) reporter (copGFP) and a scaffold/matrix attachment region (S/MAR) sequence. The eyes were randomized to subretinal injection of the vector following pars plana vitrectomy (control group) or a direct injection without prior vitrectomy surgery (experimental group). Intra- and post-operative observations up to 30 days after surgery were compared. Six eyes of three mini-pigs underwent surgery for delivery into the subretinal space. Two eyes in the control group were operated with a classical approach (lens-sparing vitrectomy and posterior hyaloid detachment). The other four eyes in the experimental group were injected directly with a subretinal cannula without vitrectomy surgery. No adverse events, such as endophthalmitis, retinal detachment and intraocular pressure elevation were observed post-operatively. The eyes in the experimental group had both shorter surgical time and recovery while achieving the same surgical goal. This pilot study demonstrates that successful subretinal delivery of gene therapy vectors is achievable using a direct injection without prior vitrectomy surgery.
2024-05-26 | The association between endophthalmitis risk following a variety of intra-ocular procedures and defensin gene profile
Endophthalmitis is a sight threatening complication of intra-ocular procedures. It has been suggested that a predisposition to endophthalmitis is linked to a specific genotype in the human beta-defensin 1 (HBD-1) gene when previously analysed in a small UK cohort undergoing cataract surgery. We sought to test out this hypothesis in a larger international case: control study (centres in UK, Netherlands and Canada) following a variety of intraocular procedures. International case: control study 660 individuals undergoing an intraocular procedure were recruited (165 cases of endophthalmitis and 495 controls). DNA was extracted. Single nucleotide polymorphisms, SNPs, rs11362, rs1800972 and rs2702877 in the HBD-1 gene were analysed (both individual genotypes and haplotypes were obtained). No associations were found when individual SNPs were analysed across the combined international cohort. However, analysis of the Toronto sub-cohort, showed a statistically significant association between the endophthalmitis cohort and the rs1800972 C allele (OR: 3.18, CI: 1.32 - 7.68, p = 0.01) and rs2702877 G allele (OR: 3.06, CI: 1.35 - 6.95, p = 0.017). No haplotype association was identified with endophthalmitis compared to control in both institution sub-cohorts and combined cohort analysis. A strong trend associating the rs1800972, rs11362 GG mini-haplotype with culture positive endophthalmitis groups across all groups was noted, but this did not reach statistical significance. This is the first study to demonstrate a genetic link between a certain genetic profile (HBD-1 gene SNP variation) and endophthalmitis. Future pre-operative genetic testing could help identify patients at risk of endophthalmitis to guide invasive treatment options.
2023-07-17 | Antisense Oligonucleotides Selectively Enter Human-Derived Antibiotic-Resistant Bacteria through Bacterial-Specific ATP-Binding Cassette Sugar Transporter.
Current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic-resistant bacteria. Herein, bacteria-specific ATP-binding cassette (ABC) sugar transporters are leveraged to selectively internalize ASOs by hitchhiking them on α (1-4)-glucosidically linked glucose polymers. Compared with their cell-penetrating peptide counterparts, which are non-specifically engulfed by mammalian and bacterial cells, the presented therapeutics consisting of glucose polymer and antisense peptide nucleic-acid-modified nanoparticles are selectively internalized into the human-derived multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e., 51.6%). The developed strategy allows specific and efficient killing of nearly 100% of the antibiotic-resistant bacteria. Its significant curative efficacy against bacterial keratitis and endophthalmitis is also shown. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.
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Drug Discovery Landscape
3 orphan drug designations for Endophthalmitis.
3 orphan drug designations for Endophthalmitis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
povidone iodine | small molecules | FDA | 2018-11-30 | — | Cumulus Pharmaceutical LLC |
povidone iodine | small molecules | FDA | 2017-11-27 | — | Veloce BioPharma LLC |
vancomycin | small molecules | FDA | 2012-12-27 | — | Fera Pharmaceuticals, LLC |
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