Relationship of posterior peripheral corneal layers and the trabecular meshwork: an immunohistological and anatomical study.

BACKGROUND/AIM: With the popularity of endothelial keratoplasty (EK) procedures, Descemet membrane (DM) EK and pre-Descemet EK, considerable work has been done on understanding the posterior corneal anatomy. Most of the information available relates to the central cornea. We evaluated the peripheral cornea to explore the immunohistological and anatomical relationship between the pre-Descemet layer (PDL), DM and trabecular meshwork (TM). METHODS: Six donor human sclerocorneal discs were studied. PDL, DM and TM were examined by light microscopy, transmission electron microscopy (TEM) and immunohistology. The DM was peeled from the centre to the limit of its peripheral attachment, to reach the transition zone (TZ) between TM and peripheral cornea. Ten-micron sections were stained with antibodies against collagens 1, 2, 3, 4, 5, 6, 12, elastin, myocilin, wnt-1, aquaporin, tenascin C, laminin and integrin alpha 3. RESULTS: Collagens 2, 3, 4, laminin and myocilin were predominantly seen in the TZ between TM and peripheral cornea. Wnt-1, integrin alpha 3 and tenascin C were highly concentrated in TM. Collagen 1 was present predominantly in the corneal stroma. On TEM; DM was thinner with a denser banded structure spread throughout its thickness in the periphery compared with the central cornea where it presents as the distinct anterior banded layer. CONCLUSION: The TZ between DM, PDL and TM shows a unique histological structure at the periphery. The collagen and elastin fibres of the TM are continuous with the PDL. The structures are firmly attached to each other. These findings provide structural information that is relevant to the preparation of DMEK donor tissue.

A 7-year review of clinical characteristics, predisposing factors and outcomes of post-keratoplasty infectious keratitis: the Nottingham infectious keratitis study.

Background/objectives: Post-keratoplasty infectious keratitis (PKIK) is a unique sight-threatening clinical entity which often poses significant therapeutic challenges. This study aimed to examine the clinical presentation, risk factors, management, and clinical outcomes of PKIK. Methods: This was a retrospective study of all patients who presented to the Queen's Medical Centre, Nottingham, with PKIK between September 2015 and August 2022 (a 7-year period). Relevant data on types of keratoplasty, clinical presentations, causative microorganisms, management, and outcome were analyzed. Results: Forty-nine PKIK cases, including four cases of interface infectious keratitis, were identified during the study period. The most common graft indications for PKP, DALK and EK were failed grafts (9, 37.5%), keratoconus (6, 54.5%) and Fuchs endothelial corneal dystrophy (FECD; 8, 57.1%), respectively. Staphylococcus spp. were the most commonly identified organisms (15, 50.0%). Bullous keratopathy (18, 36.7%), ocular surface disease (18, 36.7%), and broken/loose sutures (15, 30.6%) were the most common risk factors. Concurrent use of topical steroids was identified in 25 (51.0%) cases. Of 31 functioning grafts at presentation, 12 (38.7%) grafts failed at final follow-up with 15 (48.4%) patients retaining a CDVA of ≥1.0 logMAR. The overall estimated 5-year survival rate post-PKIK was 55.9% (95% CI, 35.9%-75.9%), with DALK having the highest survival rate [63.6% (95% CI, 28.9%-98.3%)], followed by EK [57.1% (95% CI, 20.4%-93.8%)] and PKP [52.7% (95% CI, 25.1%-80.3%)], though no statistical difference was observed (p=0.48). Conclusions: PKIK represents an important cause of IK and graft failure. Bullous keratopathy, OSD and suture-related complications are the commonest risk factors, highlighting the potential benefit of prophylactic topical antibiotics (for unhealthy ocular surface) and early suture removal (where possible) in reducing the risk of PKIK. Graft survival may be higher in lamellar keratoplasty following PKIK but larger studies are required to elucidate this observation.

An approach to reduce Descemet's membrane scrolling: Relevance to Descemet's membrane endothelial keratoplasty (DMEK).

Purpose: We aimed to determine whether Descemet's membrane (DM) scrolling occurs primarily along the vertical or horizontal axis and establish whether oval trephination along the axis of least scrolling can reduce the grade of the scroll. Methods: The longest limbus-to-limbus axis on 28 sclerocorneal discs was taken as the horizontal axis. The horizontal (n = 7) or (right angles to it) vertical (n = 6) axis was marked on DM before peeling it off. The direction and grade of scrolling was observed. Narrow strips (3-4 mm wide) were then cut along the two axes (n = 4 each) and the scrolling pattern was observed. Ellipses (7 × 9 mm) of DM were punched along the two axes (n = 6 each) and the scrolls graded. Immunofluorescent staining for elastin on horizontal and vertical tissue sections from three DM samples was performed. The intensity and thickness of elastin staining were measured. Results: Twenty-four (85.72%) DM samples showed scrolling along the horizontal axis, none showed scrolling along the vertical axis, and four (14.28%) samples showed a spiral scroll, regardless of which axis was marked (grade 3.7 and 3.6). Vertically oval discs showed significantly reduced scrolling (grade 1.2) compared to horizontally oval discs (grade 3.5). Narrow strips of DM showed a similar scrolling pattern. Immunohistology showed no difference in any of the parameters examined along the two axes or from the center to the periphery. Conclusion: DM scrolls primarily along the horizontal axis. Vertically oval DM samples show minimal scrolling, which can be an advantage in DMEK. Differential scrolling is not determined by the distribution of elastin.

Management of keratoconus: an updated review.

Keratoconus is the most common corneal ectatic disorder. It is characterized by progressive corneal thinning with resultant irregular astigmatism and myopia. Its prevalence has been estimated at 1:375 to 1:2,000 people globally, with a considerably higher rate in the younger populations. Over the past two decades, there was a paradigm shift in the management of keratoconus. The treatment has expanded significantly from conservative management (e.g., spectacles and contact lenses wear) and penetrating keratoplasty to many other therapeutic and refractive modalities, including corneal cross-linking (with various protocols/techniques), combined CXL-keratorefractive surgeries, intracorneal ring segments, anterior lamellar keratoplasty, and more recently, Bowman's layer transplantation, stromal keratophakia, and stromal regeneration. Several recent large genome-wide association studies (GWAS) have identified important genetic mutations relevant to keratoconus, facilitating the development of potential gene therapy targeting keratoconus and halting the disease progression. In addition, attempts have been made to leverage the power of artificial intelligence-assisted algorithms in enabling earlier detection and progression prediction in keratoconus. In this review, we provide a comprehensive overview of the current and emerging treatment of keratoconus and propose a treatment algorithm for systematically guiding the management of this common clinical entity.

Diagnostic performance of deep learning in infectious keratitis: a systematic review and meta-analysis protocol.

INTRODUCTION: Infectious keratitis (IK) represents the fifth-leading cause of blindness worldwide. A delay in diagnosis is often a major factor in progression to irreversible visual impairment and/or blindness from IK. The diagnostic challenge is further compounded by low microbiological culture yield, long turnaround time, poorly differentiated clinical features and polymicrobial infections. In recent years, deep learning (DL), a subfield of artificial intelligence, has rapidly emerged as a promising tool in assisting automated medical diagnosis, clinical triage and decision-making, and improving workflow efficiency in healthcare services. Recent studies have demonstrated the potential of using DL in assisting the diagnosis of IK, though the accuracy remains to be elucidated. This systematic review and meta-analysis aims to critically examine and compare the performance of various DL models with clinical experts and/or microbiological results (the current 'gold standard') in diagnosing IK, with an aim to inform practice on the clinical applicability and deployment of DL-assisted diagnostic models. METHODS AND ANALYSIS: This review will consider studies that included application of any DL models to diagnose patients with suspected IK, encompassing bacterial, fungal, protozoal and/or viral origins. We will search various electronic databases, including EMBASE and MEDLINE, and trial registries. There will be no restriction to the language and publication date. Two independent reviewers will assess the titles, abstracts and full-text articles. Extracted data will include details of each primary studies, including title, year of publication, authors, types of DL models used, populations, sample size, decision threshold and diagnostic performance. We will perform meta-analyses for the included primary studies when there are sufficient similarities in outcome reporting. ETHICS AND DISSEMINATION: No ethical approval is required for this systematic review. We plan to disseminate our findings via presentation/publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022348596.

Ex vivo demonstration of canine corneal pre-Descemet's anatomy using pneumodissection as for the big bubble technique for deep anterior lamellar keratoplasty.

The recent discovery and characterization of pre-Descemet's layer (PDL; also termed the Dua's layer or the Dua-Fine layer) has advanced the understanding of various posterior corneal pathologies and surgeries in human. This study aimed to characterize the ultrastructure of the posterior stroma and interfacial zone of Descemet's membrane (DM) in canine eyes. Eighteen canine corneo-scleral discs were included. Intrastromal air injection resulted in the formation of type 1 big bubble (BB) in 73% (n = 11/15) of corneas, with a mean diameter of 11.0 ± 1.3 mm. No type 2 BB was created. Anterior segment optical coherence tomography, histology and transmission electron microscopy confirmed that the wall of BB was composed of DM, in contact with remaining stroma (canine PDL; cPDL). The cPDL was populated with keratocytes, of varying thickness of 16.2 ± 4.2 µm in close apposition to the DM, and composed of collagen bundles arranged in transverse, longitudinal and oblique directions. The interfacial zone, between DM and cPDL, showed fibril extension in all three directions, predominantly longitudinal. Irregular extensions of DM material into cPDL stroma were observed. No long-spaced collagen was detected. In conclusion, there exists a well-defined cleavage plane between the posterior stroma and cPDL, with similar but not identical characteristics as in humans, that is revealed by pneumodissection. This adds to our understanding of the anatomy of the posterior most canine cornea, which will have significant clinical impact on posterior corneal surgery and understanding of corneal pathology in dogs.

The pre-Descemet's layer (Dua's layer, also known as the Dua-Fine layer and the pre-posterior limiting lamina layer): Discovery, characterisation, clinical and surgical applications, and the controversy.

The pre-Descemet's layer/Dua's layer, also termed the Dua-Fine layer and the pre-posterior limiting lamina layer, lies anterior to the Descemet's membrane in the cornea, is 10 µm (range 6-16) thick, made predominantly of type I and some type VI collagen with abundant elastin, more than any other layer of the cornea. It has high tensile strength (bursting pressure up to 700 mm of Hg), is impervious to air and almost acellular. At the periphery it demonstrates fenestrations and ramifies to become the core of the trabecular meshwork, with implications for intraocular pressure and glaucoma. It has been demonstrated in some species of animals. The layer has assumed considerable importance in anterior and posterior lamellar corneal transplant surgery by improving our understanding of the behaviour of corneal tissue during these procedures, improved techniques and made the surgery safer with better outcomes. It has led to the innovation of new surgical procedures namely, pre-Descemet's endothelial keratoplasty, suture management of acute hydrops, DALK-triple and Fogla's mini DALK. The discovery and knowledge of the layer has introduced paradigm shifts in our age old concepts of Descemet's membrane detachment, acute corneal hydrops in keratoconus and Descemetoceles, with impact on management approaches. It has been shown to contribute to the pathology and clinical signs observed in corneal infections and some corneal dystrophies. Early evidence suggests that it may have a role in the pathogenesis of keratoconus in relation to its elastin content. Its contribution to corneal biomechanics and glaucoma are subjects of current investigations.

Surgical management of infectious keratitis.

The successful management of infectious keratitis is usually achieved with a combination of tools for accurate diagnosis and targeted timely antimicrobial therapy. An armamentarium of surgical interventions is available in the acute stage which can be resorted to in a step wise manner or in combination guided by the response to treatment. Simple surgical modalities can facilitate accurate diagnosis e.g. corneal biopsy and alcohol delamination. Surgery to promote epithelial healing can vary from tarsorrhaphy, amniotic membrane transplantation or conjunctival flaps depending on the extent of infection, visual prognosis, availability of tissue and surgeon's experience. Collagen crosslinking has been increasingly utilized with successful results to strengthen the cornea and reduce the infective load consequently the need for further elaborate surgical interventions. It has shown encouraging results specially in superficial bacterial and fungal keratitis but for deeper infections, viral and acanthamoeba keratitis, its use remains questionable. When globe integrity is compromised, corneal gluing is the most commonly used procedure to seal small perforations. In larger perforations/fulminant infections a tectonic/therapeutic graft is advisable. Partial thickness grafts are increasingly popular to treat superficial infection or internally tamponade perforations. Peripheral therapeutic grafts face challenges with potential requirement for a manually fashioned graft, and increased risk of rejection due to proximity to the limbal vessels. Late stage visual rehabilitation is likely to require further surgical interventions after complete resolution of infection and inflammation. A preliminary assessment of corneal sensation and integrity of the ocular surface are key for any successful surgical intervention to restore vision.

Management of limbal stem cell deficiency by amnion-assisted conjunctival epithelial redirection using vacuum-dried amniotic membrane and fibrin glue.

PURPOSE: To study the outcome of a modified amnion-assisted conjunctival epithelial redirection (ACER) technique using vacuum-dried amnion (Omnigen) and fibrin glue for managing total limbal stem cell deficiency (LSCD). METHOD: A retrospective, interventional case series of all patients with total LSCD who underwent limbal stem cell transplant (LSCT) using the modified ACER procedure between 2016 and 2019. The outcome was defined as: (1) success: complete corneal re-epithelialisation without conjunctivalisation; (2) partial success: sub-total corneal re-epithelialisation with partial non-progressive conjunctivalisation sparing the visual axis and (3) failure: conjunctivalisation affecting the visual axis. RESULTS: Ten patients (six men), with a mean age of 46.2±18.4 years, were included. The mean follow-up was 23.0±13.9 months. Causes of LSCD were chemical eye injury (30%), congenital aniridia-related keratopathy (30%), ocular surface malignancy (20%), Steven-Johnson syndrome (10%) and contact lens overuse (10%). 50% were bilateral. The time from diagnosis to ACER (for acquired causes) was 45.6±44.4 months. 80% of patients achieved a complete/partial success following ACER and 20% of patients required repeat LSCT. Auto-LSCT was associated with a significantly higher chance of success than allo-LSCT (p=0.048). The mean best-corrected-visual-acuity (logMAR) improved significantly from 1.76±0.64 preoperatively to 0.94±0.94 at final follow-up (p=0.009). Omnigen was available off-the-shelf stored at room temperature and its transparency enabled visualisation of the healing epithelium beneath. CONCLUSION: LSCT using the modified ACER serves as an effective ocular surface reconstruction technique in managing total LSCD and improving vision. Vacuum-dried amnion provides advantages of easy handling, transparency and storage at room temperature.

Manifestation of Herpetic Eye Disease after COVID-19 Vaccine: A UK Case Series.

PURPOSE: To highlight the potential risk of herpetic eye disease (HED) reactivation following COVID-19 vaccine. METHODS: Retrospective analysis of all patients who presented with HED within 28 days post-first dose COVID-19 vaccination. RESULTS: Eleven eyes (n = 10 patients) were included. The mean interval between COVID-19 vaccination and ocular symptoms/signs was 12.3 ± 10.3 days. Four (40%) patients presented with HSV keratitis, and six (60%) patients presented with VZV keratitis (five had concurrent other signs of herpes zoster ophthalmicus). Common ocular signs included multiple scattered dendritic/pseudodendritic corneal epitheliopathy (90.9%), anterior uveitis (63.6%), and endothelitis (27.3%). All cases were successfully treated with topical and systemic antiviral treatment and/or topical corticosteroids (mean healing time = 3.9 ± 1.6 weeks). CONCLUSIONS: Our case series highlights the potential temporal association between HED and COVID-19 vaccine. Prophylactic antiviral treatment is recommended in patients with a history of HED prior to COVID-19 vaccination.

Real-world experience of using ciclosporin-A 0.1% in the management of ocular surface inflammatory diseases.

PURPOSE: To report the real-world experience of using topical ciclosporin, Ikervis, in the management of ocular surface inflammatory diseases (OSIDs). METHODS: This was a retrospective study of patients treated with Ikervis for OSIDs at the Queen's Medical Centre, Nottingham, between 2016 and 2019. Relevant data, including demographics, indications, clinical parameters, outcomes and adverse events, were collected and analysed for patients who had completed at least 6 months follow-up. For analytic purpose, clinical outcome was categorised as 'successful' (resolved or stable disease), 'active disease' and 'drug intolerance'. RESULTS: 463 patients were included; mean age was 51.1±21.6 years, with a 59.0% female predominance. Mean follow-up was 14.6±9.2 months. The most common diagnosis was dry eye disease (DED; 322, 69.5%), followed by allergic eye disease (AED; 53, 11.4%) and ocular mucous membrane pemphigoid/Steven-Johnson syndrome (OMMP/SJS; 38, 8.2%). Successful treatment was achieved in 343 (74.1%) patients, with 44 (9.5%) requiring additional treatment and 76 (16.4%) reporting drug intolerance. The efficacy of Ikervis was highest in DED (264, 82.0%), followed by OMMP/SJS (25, 65.8%) and post-keratoplasty (7, 50.0%; p<0.001). Logistic regression analysis demonstrated age <70 years (p=0.007), AED (p=0.002) and OMMP/SJS (p=0.001) as significant predictive factors for Ikervis intolerance. AED and post-keratoplasty were 8.16 times (95% CI, 2.78 to 23.99) and 13.98 times (95% CI, 4.22 to 46.28), respectively, more likely to require additional treatment compared with DED. CONCLUSIONS: Ikervis is a useful steroid-sparing topical treatment for managing OSIDs in the real-world setting. Preparations with improved tolerability are needed to benefit a larger number of patients.

Diagnostic armamentarium of infectious keratitis: A comprehensive review.

Infectious keratitis (IK) represents the leading cause of corneal blindness worldwide, particularly in developing countries. A good outcome of IK is contingent upon timely and accurate diagnosis followed by appropriate interventions. Currently, IK is primarily diagnosed on clinical grounds supplemented by microbiological investigations such as microscopic examination with stains, and culture and sensitivity testing. Although this is the most widely accepted practice adopted in most regions, such an approach is challenged by several factors, including indistinguishable clinical features shared among different causative organisms, polymicrobial infection, long diagnostic turnaround time, and variably low culture positivity rate. In this review, we aim to provide a comprehensive overview of the current diagnostic armamentarium of IK, encompassing conventional microbiological investigations, molecular diagnostics (including polymerase chain reaction and mass spectrometry), and imaging modalities (including anterior segment optical coherence tomography and in vivo confocal microscopy). We also highlight the potential roles of emerging technologies such as next-generation sequencing, artificial intelligence-assisted platforms. and tele-medicine in shaping the future diagnostic landscape of IK.

Clinical Characteristics and Outcomes of Fungal Keratitis in the United Kingdom 2011-2020: A 10-Year Study.

Fungal keratitis (FK) is a serious ocular infection that often poses significant diagnostic and therapeutic dilemmas. This study aimed to examine the causes, clinical characteristics, outcomes, and prognostic factors of FK in the UK. All culture-positive and culture-negative presumed FK (with complete data) that presented to Queen's Medical Centre, Nottingham, and the Queen Victoria Hospital, East Grinstead, between 2011 and 2020 were included. We included 117 patients (n = 117 eyes) with FK in this study. The mean age was 59.0 ± 19.6 years (range, 4-92 years) and 51.3% of patients were female. Fifty-three fungal isolates were identified from 52 (44.4%) culture-positive cases, with Candida spp. (33, 62.3%), Fusarium spp. (9, 17.0%), and Aspergillus spp. (5, 9.4%) being the most common organisms. Ocular surface disease (60, 51.3%), prior corneal surgery (44, 37.6%), and systemic immunosuppression (42, 35.9%) were the three most common risk factors. Hospitalisation for intensive treatment was required for 95 (81.2%) patients, with a duration of 18.9 ± 16.3 days. Sixty-six (56.4%) patients required additional surgical interventions for eradicating the infection. Emergency therapeutic/tectonic keratoplasty was performed in 29 (24.8%) cases, though 13 (44.8%) of them failed at final follow-up. The final corrected-distance-visual-acuity (CDVA) was 1.67 ± 1.08 logMAR. Multivariable logistic regression analyses demonstrated increased age, large infiltrate size (>3 mm), and poor presenting CDVA (<1.0 logMAR) as significant negative predictive factors for poor visual outcome (CDVA of <1.0 logMAR) and poor corneal healing (>60 days of healing time or occurrence of corneal perforation requiring emergency keratoplasty; all p < 0.05). In conclusion, FK represents a difficult-to-treat ocular infection that often results in poor visual outcomes, with a high need for surgical interventions. Innovative treatment strategies are urgently required to tackle this unmet need.

Evaluation of Host Defense Peptide (CaD23)-Antibiotic Interaction and Mechanism of Action: Insights From Experimental and Molecular Dynamics Simulations Studies.

Background/Aim: Host defense peptides (HDPs) have the potential to provide a novel solution to antimicrobial resistance (AMR) in view of their unique and broad-spectrum antimicrobial activities. We had recently developed a novel hybrid HDP based on LL-37 and human beta-defensin-2, named CaD23, which was shown to exhibit good in vivo antimicrobial efficacy against Staphylococcus aureus in a bacterial keratitis murine model. This study aimed to examine the potential CaD23-antibiotic synergism and the secondary structure and underlying mechanism of action of CaD23. Methods: Peptide-antibiotic interaction was evaluated against S. aureus, methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa using established checkerboard and time-kill assays. Fractional inhibitory concentration index (FICI) was calculated and interpreted as synergistic (FIC<0.5), additive (FIC between 0.5-1.0), indifferent (FIC between >1.0 and ≤4), or antagonistic (FIC>4). SYTOX green uptake assay was performed to determine the membrane-permeabilising action of CaD23. Molecular dynamics (MD) simulations were performed to evaluate the interaction of CaD23 with bacterial and mammalian mimetic membranes. Circular dichroism (CD) spectroscopy was also performed to examine the secondary structures of CaD23. Results: CaD23-amikacin and CaD23-levofloxacin combination treatment exhibited a strong additive effect against S. aureus SH1000 (FICI = 0.60-0.69) and MRSA43300 (FICI = 0.56-0.60) but an indifferent effect against P. aeruginosa (FIC = 1.03-1.15). CaD23 (at 25 µg/ml; 2xMIC) completely killed S. aureus within 30 min. When used at sub-MIC concentration (3.1 µg/ml; 0.25xMIC), it was able to expedite the antimicrobial action of amikacin against S. aureus by 50%. The rapid antimicrobial action of CaD23 was attributed to the underlying membrane-permeabilising mechanism of action, evidenced by the SYTOX green uptake assay and MD simulations studies. MD simulations revealed that cationicity, alpha-helicity, amphiphilicity and hydrophobicity (related to the Trp residue at C-terminal) play important roles in the antimicrobial action of CaD23. The secondary structures of CaD23 observed in MD simulations were validated by CD spectroscopy. Conclusion: CaD23 is a novel alpha-helical, membrane-active synthetic HDP that can enhance and expedite the antimicrobial action of antibiotics against Gram-positive bacteria when used in combination. MD simulations serves as a powerful tool in revealing the peptide secondary structure, dissecting the mechanism of action, and guiding the design and optimisation of HDPs.

Hybrid derivative of cathelicidin and human beta defensin-2 against Gram-positive bacteria: A novel approach for the treatment of bacterial keratitis.

Bacterial keratitis (BK) is a major cause of corneal blindness globally. This study aimed to develop a novel class of antimicrobial therapy, based on human-derived hybrid host defense peptides (HyHDPs), for treating BK. HyHDPs were rationally designed through combination of functional amino acids in parent HDPs, including LL-37 and human beta-defensin (HBD)-1 to -3. Minimal inhibitory concentrations (MICs) and time-kill kinetics assay were performed to determine the concentration- and time-dependent antimicrobial activity and cytotoxicity was evaluated against human corneal epithelial cells and erythrocytes. In vivo safety and efficacy of the most promising peptide was examined in the corneal wound healing and Staphylococcus aureus (ATCC SA29213) keratitis murine models, respectively. A second-generation HyHDP (CaD23), based on rational hybridization of the middle residues of LL-37 and C-terminal of HBD-2, was developed and was shown to demonstrate good efficacy against methicillin-sensitive and methicillin-resistant S. aureus [MIC = 12.5-25.0 µg/ml (5.2-10.4 µM)] and S. epidermidis [MIC = 12.5 µg/ml (5.2 µM)], and moderate efficacy against P. aeruginosa [MIC = 25-50 µg/ml (10.4-20.8 µM)]. CaD23 (at 25 µg/ml or 2× MIC) killed all the bacteria within 30 min, which was 8 times faster than amikacin (25 µg/ml or 20× MIC). After 10 consecutive passages, S. aureus (ATCC SA29213) did not develop any antimicrobial resistance (AMR) against CaD23 whereas it developed significant AMR (i.e. a 32-fold increase in MIC) against amikacin, a commonly used treatment for BK. Pre-clinical murine studies showed that CaD23 (0.5 mg/ml) achieved a median reduction of S. aureus bioburden by 94% (or 1.2 log10 CFU/ml) while not impeding corneal epithelial wound healing. In conclusion, rational hybridization of human-derived HDPs has led to generation of a potentially efficacious and safe topical antimicrobial agent for treating Gram-positive BK, with no/minimal risk of developing AMR.

Risk Factors, Clinical Outcomes, and Prognostic Factors of Bacterial Keratitis: The Nottingham Infectious Keratitis Study.

Background/Aim: To examine the risk factors, clinical characteristics, outcomes, and prognostic factors of bacterial keratitis (BK) in Nottingham, UK. Methods: This was a retrospective study of patients who presented to the Queen's Medical Centre, Nottingham, with suspected BK during 2015-2019. Relevant data, including the demographic factors, risk factors, clinical outcomes, and potential prognostic factors, were analysed. Results: A total of 283 patients (n = 283 eyes) were included; mean age was 54.4 ± 21.0 years and 50.9% were male. Of 283 cases, 128 (45.2%) cases were culture-positive. Relevant risk factors were identified in 96.5% patients, with ocular surface diseases (47.3%), contact lens wear (35.3%) and systemic immunosuppression (18.4%) being the most common factors. Contact lens wear was most commonly associated with P. aeruginosa whereas Staphylococci spp. were most commonly implicated in non-contact lens-related BK cases (p = 0.017). At presentation, culture-positive cases were associated with older age, worse presenting corrected-distance-visual-acuity (CDVA), use of topical corticosteroids, larger epithelial defect and infiltrate, central location and hypopyon (all p < 0.01), when compared to culture-negative cases. Hospitalisation was required in 57.2% patients, with a mean length of stay of 8.0 ± 8.3 days. Surgical intervention was required in 16.3% patients. Significant complications such as threatened/actual corneal perforation (8.8%), loss of perception of light vision (3.9%), and evisceration/enucleation (1.4%) were noted. Poor visual outcome (final corrected-distance-visual-acuity of <0.6 logMAR) and delayed corneal healing (>30 days from initial presentation) were significantly affected by age >50 years, infiltrate size >3 mm, and reduced presenting vision (all p < 0.05). Conclusion: BK represents a significant ocular morbidity in the UK, with ocular surface diseases, contact lens wear, and systemic immunosuppression being the main risk factors. Older age, large infiltrate, and poor presenting vision were predictive of poor visual outcome and delayed corneal healing, highlighting the importance of prevention and early intervention for BK.

Artificial Intelligence in Cornea, Refractive Surgery, and Cataract: Basic Principles, Clinical Applications, and Future Directions.

ABSTRACT: Corneal diseases, uncorrected refractive errors, and cataract represent the major causes of blindness globally. The number of refractive surgeries, either cornea- or lens-based, is also on the rise as the demand for perfect vision continues to increase. With the recent advancement and potential promises of artificial intelligence (AI) technologies demonstrated in the realm of ophthalmology, particularly retinal diseases and glaucoma, AI researchers and clinicians are now channeling their focus toward the less explored ophthalmic areas related to the anterior segment of the eye. Conditions that rely on anterior segment imaging modalities, including slit-lamp photography, anterior segment optical coherence tomography, corneal tomography, in vivo confocal microscopy and/or optical biometers, are the most commonly explored areas. These include infectious keratitis, keratoconus, corneal grafts, ocular surface pathologies, preoperative screening before refractive surgery, intraocular lens calculation, and automated refraction, among others. In this review, we aimed to provide a comprehensive update on the utilization of AI in anterior segment diseases, with particular emphasis on the recent advancement in the past few years. In addition, we demystify some of the basic principles and terminologies related to AI, particularly machine learning and deep learning, to help improve the understanding, research and clinical implementation of these AI technologies among the ophthalmologists and vision scientists. As we march toward the era of digital health, guidelines such as CONSORT-AI, SPIRIT-AI, and STARD-AI will play crucial roles in guiding and standardizing the conduct and reporting of AI-related trials, ultimately promoting their potential for clinical translation.

Post-keratoplasty Infectious Keratitis: Epidemiology, Risk Factors, Management, and Outcomes.

Post-keratoplasty infectious keratitis (PKIK) represents a unique clinical entity that often poses significant diagnostic and therapeutic challenges. It carries a high risk of serious complications such as graft rejection and failure, and less commonly endophthalmitis. Topical corticosteroids are often required to reduce the risk of graft rejection but their use in PKIK may act as a double-edged sword, particularly in fungal infection. The increased uptake in lamellar keratoplasty in the recent years has also led to complications such as graft-host interface infectious keratitis (IIK), which is particularly difficult to manage. The reported incidence of PKIK differs considerably across different countries, with a higher incidence observed in developing countries (9.2-11.9%) than developed countries (0.02-7.9%). Common risk factors for PKIK include the use of topical corticosteroids, suture-related problems, ocular surface diseases and previous corneal infection. PKIK after penetrating keratoplasty or (deep) anterior lamellar keratoplasty is most commonly caused by ocular surface commensals, particularly Gramme-positive bacteria, whereas PKIK after endothelial keratoplasty is usually caused by Candida spp. Empirical broad-spectrum antimicrobial treatment is the mainstay of treatment for both PKIK, though surgical interventions are required in medically refractory cases (during the acute phase) and those affected by visually significant scarring (during the late phase). In this paper, we aim to provide a comprehensive overview on PKIK, encompassing the epidemiology, risk factors, causes, management and outcomes, and to propose a treatment algorithm for systematically managing this challenging condition.