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Infectious keratitis (IK) is the 5th leading cause of blindness globally. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though adjuvant treatment or surgeries are often required in refractory cases of IK. This systematic review aimed to examine the effectiveness and safety of adjuvant amniotic membrane transplantation (AMT) for treating IK. Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for relevant articles. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies and case series (n > 5), were included. Primary outcome measure was time to complete corneal healing and secondary outcome measures included corrected-distance-visual-acuity (CDVA), uncorrected-distance-visual-acuity (UDVA), corneal vascularization and adverse events. A total of twenty-eight studies (including four RCTs) with 861 eyes were included. When compared to standard antimicrobial treatment alone, adjuvant AMT resulted in shorter mean time to complete corneal healing (− 4.08 days; 95% CI − 6.27 to − 1.88; p p = 0.04) at 1 month follow-up in moderate-to-severe bacterial and fungal keratitis, with no significant difference in the risk of adverse events (risk ratio 0.80; 0.46–1.38; p = 0.42). One RCT demonstrated that adjuvant AMT resulted in better CDVA and less corneal vascularization at 6 months follow-up (both p

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.

IntroductionInfectious keratitis (IK) represents the 5thleading 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 analysisThis 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. 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 disseminationNo ethical approval is required for this systematic review. We plan to disseminate our findings via presentation/publication in a peer-reviewed journal.Protocol registrationThis systematic review protocol will be registered with the PROSPERO after peer review.STRENGTH AND LIMITATIONS OF THIS STUDY- This study will serve as the most up-to-date systematic review and meta-analysis specifically evaluating the diagnostic performance of deep learning in infectious keratitis.- The quality of the study will depend on the quality of the available published literature related to this topic.- This study will help identify the gaps in the current clinical evidence, which may be related to study design, quality of the research methodologies, setting of reference standard, risk of bias, and outcome reporting.

Corneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for 1.5-2.0 million new cases of monocular blindness per year, highlighting an ongoing uncurbed burden on human health. Among all aetiologies such as infection, trauma, inflammation, degeneration and nutritional deficiency, infectious keratitis (IK) represents the leading cause of corneal blindness in both developed and developing countries, with an estimated incidence ranging from 2.5 to 799 per 100,000 population-year. IK can be caused by a wide range of microorganisms, including bacteria, fungi, virus, parasites and polymicrobial infection. Subject to the geographical and temporal variations, bacteria and fungi have been shown to be the most common causative microorganisms for corneal infection. Although viral and Acanthamoeba keratitis are less common, they represent important causes for corneal blindness in the developed countries. Contact lens wear, trauma, ocular surface diseases, lid diseases, and post-ocular surgery have been shown to be the major risk factors for IK. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though its effectiveness is being challenged by the emergence of antimicrobial resistance, including multidrug resistance, in some parts of the world. In this review, we aim to provide an updated review on IK, encompassing the epidemiology, causative microorganisms, major risk factors and the impact of antimicrobial resistance.摘要: 角膜混浊是全球致盲和视力障碍的第五大原因, 世界范围内大约600万人受其影响。此外, 角膜混浊每年导致的单眼失明约150-200万例, 突显其对人类健康造成的持久性负担。在感染、创伤、炎症、变性和营养缺乏等所有的致病因素中, 感染性角膜炎 (IK) 是发达国家和发展中国家角膜病致盲的主要原因, 大概每100000人口中2.5-799人罹患此病。IK可由多种微生物引起, 包括细菌、真菌、病毒、寄生虫和多重感染。受地理和时间变化的影响, 细菌和真菌已被证明是角膜感染最常见的病原微生物。虽然病毒性角膜炎和棘阿米巴角膜炎并不常见, 但在发达国家, 它们是角膜病致盲的重要原因。接触镜的佩戴、外伤、眼表疾病、眼睑疾病以及眼部手术已证实是IK的主要危险因素。广谱抗生素是目前IK治疗的主要选择, 但是在世界某些地区, 其有效性正在受到抗菌药物耐药性的挑战, 其中包含多重耐药性等。本篇综述旨在提供有关IK的最新进展, 包括流行病学、病原微生物、主要危险因素以及抗生素耐药性对于疗效的影响。.

To highlight the potential risk of herpetic eye disease (HED) reactivation following COVID-19 vaccine.Retrospective analysis of all patients who presented with HED within 28 days post-first dose COVID-19 vaccination.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).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.

Purpose: The purpose of this study is to examine the seasonal patterns of incidence, demographic factors and microbiological profiles of infectious keratitis (IK) in Nottingham, UK. Methods: A retrospective study of all patients who were diagnosed with IK and underwent corneal scraping during 2008–2019 at a UK tertiary referral centre. Seasonal patterns of incidence (in per 100,000 population-year), demographic factors, culture positivity rate and microbiological profiles of IK were analysed. Results: A total of 1272 IK cases were included. The overall incidence of IK was highest during summer (37.7, 95% confidence interval (CI): 31.3–44.1), followed by autumn (36.7, 95% CI: 31.0–42.4), winter (36.4, 95% CI: 32.1–40.8) and spring (30.6, 95% CI: 26.8–34.3), though not statistically significant (p = 0.14). The incidence of IK during summer increased significantly over the 12 years of study (r = 0.58, p = 0.049), but the incidence of IK in other seasons remained relatively stable throughout the study period. Significant seasonal variations were observed in patients’ age (younger age in summer) and causative organisms, including Pseudomonas aeruginosa (32.9% in summer vs. 14.8% in winter; p < 0.001) and gram-positive bacilli (16.1% in summer vs. 4.7% in winter; p = 0.014). Conclusion: The incidence of IK in Nottingham was similar among four seasons. No temporal trend in the annual incidence of IK was observed, as reported previously, but there was a significant yearly increase in the incidence of IK during summer in Nottingham over the past decade. The association of younger age, P. aeruginosa and gram-positive bacilli infection with summer was likely attributed to contact lens wear, increased outdoor/water activity and warmer temperature conducive for microbial growth.

To evaluate the renewal of corneal nerve structure and function in patients with neurotrophic keratopathy (NK) treated with recombinant human nerve growth factor (rhNGF) eye drops.Prospective, interventional, before-and-after case series.This study included 18 patients with NK with a persistent epithelial defect or corneal ulcer, treated with topical rhNGF, and age-matched healthy controls. Patients underwent clinical examination with corneal fluorescein staining, Schirmer 1 tear test, assessment of corneal sensitivity with the Cochet-Bonnet esthesiometer, and morphologic examination of the nerves by in vivo confocal microscopy (IVCM) at baseline and at 4 and 8 weeks of treatment. IVCM analysis was used to assess corneal sub-basal nerve density, number of nerve branches, and the diameter of nerve fibers.A complete resolution of the epithelial defect was observed in all patients within 8 weeks. Schirmer 1 test showed a significant improvement of tear film secretion. Change from baseline in corneal sensation was significant (P.001) but did not approach that of healthy controls. After 8 weeks of treatment, there was a significant increase in the mean nerve density in affected eyes as compared to baseline (P = .007) as well as in the number of nerve branches (P = .008) and nerve fiber diameter (P = .007).Topical treatment with rhNGF was effective in promoting complete corneal healing of persistent epithelial defects and corneal ulcers in patients with NK. This was associated with an improvement of corneal sensitivity and an increase of sub-basal nerve density, diameter, and number of nerve branches, indicating improvement in structure and function of corneal nerves.

Purpose To evaluate the safety and efficacy of corneal collagen cross-linking (CXL) performed on overlaying a corneal lenticule to thin recipient corneas of progressive keratoconus (KC) patients. Methods In this study were enrolled eyes of patients affected by progressive KC with a minimum corneal thickness less than 400 µm, after overlaying a lenticule of human corneal stroma prepared with the femtosecond laser. The lenticules used were 100 µm thick and of 8.5 mm diameter in all the cases. Both the host cornea and the lenticules were subjected to epithelial debridement. CXL was carried out according to the standard protocol. Visual acuity, refraction, slit-lamp examination, endothelial cell density, pachymetry and keratometry, anterior segment tomography (AS-OCT) and confocal microscopy were evaluated preoperatively and at 1, 3, 6 and 12 months postoperatively. Results CXL was performed in 10 eyes of 8 patients (main age 23), corneal thickness range 379–414 µm, mean 387.6 µm. One patient was lost at follow-up. In all other cases, visual acuity and the endothelial cell density remained stable over a 12-month follow-up. Preoperative mean K1 and mean K2 were 46.91 ± 1.9 and 50.75 ± 2.93, respectively, and at 12 months mean K1 was 47.36 ± 2.66 and mean K2 50.53 ± 3.35. The AS-OCT clearly showed a demarcation line in all patients at 1, 3 (mean depth 283 µm and 267 µm, respectively) and in some cases at 6 months. Reduced keratocyte density and stromal oedema were observed immediately up to 1 month after treatment, while a slight subepithelial haze was present at 1-month and completely disappeared by 6 months. Conclusion This new technique seems to offer a therapeutic opportunity for young patients suffering from progressive KC with very thin corneas, in which the standard treatment is not indicate, and delay or avoid the need for a corneal transplant.

Background/aimsTo examine the incidence, causative microorganisms and in vitro antimicrobial susceptibility and resistance profiles of infectious keratitis (IK) in Nottingham, UK.MethodsA retrospective study of all patients who were diagnosed with IK and underwent corneal scraping between July 2007 and October 2019 (a 12-year period) at a UK tertiary referral centre. Relevant data, including demographic factors, microbiological profiles and in vitro antibiotic susceptibility of IK, were analysed.ResultsThe estimated incidence of IK was 34.7 per 100 000 people/year. Of the 1333 corneal scrapes, 502 (37.7%) were culture-positive and 572 causative microorganisms were identified. Sixty (4.5%) cases were of polymicrobial origin (caused by ≥2 different microorganisms). Gram-positive bacteria (308, 53.8%) were most commonly isolated, followed by Gram-negative bacteria (223, 39.0%), acanthamoeba (24, 4.2%) and fungi (17, 3.0%). Pseudomonas aeruginosa (135, 23.6%) was the single most common organism isolated. There was a significant increase in Moraxella spp (pKlebsiella spp (p=0.004) over time. The in vitro susceptibilities of Gram-positive and Gram-negative bacteria to cephalosporin, fluoroquinolone and aminoglycoside were 100.0% and 81.3%, 91.9% and 98.1%, and 95.2% and 98.3%, respectively. An increase in resistance against penicillin was observed in Gram-positive (from 3.5% to 12.7%; p=0.005) and Gram-negative bacteria (from 52.6% to 65.4%; p=0.22).ConclusionIK represents a relatively common and persistent burden in the UK and the reported incidence is likely underestimated. Current broad-spectrum antimicrobial treatment provides a good coverage for IK, although challenged by some level of antimicrobial resistance and polymicrobial infection.

Objective The objective of this review is to systematically examine the effectiveness of early adjuvant amniotic membrane transplant versus standard antimicrobial therapy for infectious keratitis. Introduction Infectious keratitis is a major cause of corneal blindness worldwide. Broad-spectrum topical antimicrobial therapy is currently the gold standard for treatment. Amniotic membrane transplant has been employed as an adjuvant therapy to promote corneal healing; however, high-quality evidence is limited. Inclusion criteria This review will consider studies that include patients of all ages with all types of infectious keratitis, including bacterial, fungal, viral, acanthamoeba, mixed, and culture-negative presumed infectious keratitis. The authors will exclude patients who have undergone other types of primary surgery other than amniotic membrane transplant during the initial management and those who had less than seven days' follow-up from the commencement of the treatment. Methods Electronic databases, including MEDLINE, Embase, Cochrane CENTRAL, and relevant registries, will be searched for pertinent studies. Titles, abstract, and full text of the relevant studies will be independently assessed by two reviewers. Extracted data will include authors, year of publication, sample size, types of amniotic membrane transplant techniques, types of causative microorganisms, main outcomes, visual acuity, and adverse events. No restriction will be applied to the date or language. Bibliographies of the included articles will be independently and manually screened by two authors to identify further relevant studies. Eligible studies will be critically appraised by two independent reviewers for methodological quality. A meta-analysis will be performed for the included randomized controlled trials when there are sufficient similarities. Systematic review registration number This systematic review has been registered with PROSPERO (CRD42020175593).

Pre-Descemet endothelial keratoplasty (PDEK) is an alternative technique to Descemet membrane endothelial keratoplasty (DMEK). The preparation of PDEK tissue by pneumatic dissection is simple and reproducible. The PDEK clamp helps to consistently obtain a type 1 big bubble. The mean size of type 1 big bubble is 7.255 ± 0.535 × 6.745 ± 0.668 mm. The volume of air required to obtain type 1 big bubble is 0.14 to 0.37 mL. Dissection of PDEK tissue can be achieved by trephination or manual excision. Insertion of tissue into the recipient eye can be by injection or pulling. Unfolding techniques used for PDEK are similar to those used in DMEK. Unlike DMEK, PDEK tissue is easier to handle and unscroll and allows use of younger donors. It could help surgeons converting to endothelial keratoplasty, with significant advantages in preparation, handling, and unscrolling in the eye.

Corneal opacity represents the fifth leading cause of blindness and visual impairment globally, affecting around 6 million of the population.1 Corneal transplantation serves as the mainstay of treatment in restoring vision in patients affected by corneal opacity.2 It is the most commonly performed transplantation worldwide, though the success has been persistently challenged by the global shortage of donor cornea.2 To date, a wide range of initiatives and advancement, including public campaigns to increase awareness, introduction of telephone consent, refinement in the donation–transplantation pathway and improvement in surgical techniques,3–6 have been implemented to improve corneal donation and utility of donor corneal tissues. On 20 May 2020, England has implemented an opt-out system, also known as the Max and Keira’s Law, with an aim to improve the rate of organ/tissue donation, joining countries such as Spain, France and Italy and many others. Under the new, soft opt-out system, all adults in England are assumed to be willing organ/tissue donors unless they have registered their intent otherwise. However, the process of eye donation remains largely unchanged as consent from the family members is still required before retrieval can proceed. Junior doctors at frontline services, particularly those who work in intensive care, oncology and palliative care units may serve as valuable members to the multidisciplinary team in contributing to the process of organ/tissue donations. Nonetheless, the knowledge of corneal donation and the new opt-out system among junior doctors in the UK has not been explored. Our study aimed to evaluate the knowledge of corneal donation and the opt-out system among the junior doctors in East Midlands, UK. This was a cross-sectional study performed between 28 June 2020 and 29 September 2020. A 26-item questionnaire-based online survey was distributed to the junior doctors/house officers (

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.

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 (&gt, 3 mm), and poor presenting CDVA (&lt, 1.0 logMAR) as significant negative predictive factors for poor visual outcome (CDVA of &lt, 1.0 logMAR) and poor corneal healing (&gt, 60 days of healing time or occurrence of corneal perforation requiring emergency keratoplasty, all p &lt, 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.

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.

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 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.

BackgroundFungal keratitis (FK) is the leading cause of unilateral blindness in the developing world. Antimicrobial peptides (AMPs) have been shown to play an important role on human ocular surface (OS) during bacterial, viral and protozoan infections. In this study, our aim was to profile a spectrum of AMPs in corneal tissue from patients with FK during the active pase of infection and after healing.MethodsOS samples were collected from patients at presentation by impression cytology and scraping. Corneal button specimens were collected from patients undergoing therapeutic penetrating keratoplasty for management of severe FK or healed keratitis. Gene expression of human beta-defensin (HBD)-1, -2, -3 and -9, S100A7, and LL-37 was determined by quantitative real-time PCR.ResultsMessenger RNA expression (mRNA) for all AMPs was shown to be significantly upregulated in FK samples. The levels of HBD-1 and -2 mRNA were found to be elevated in 18/20 FK samples. Whereas mRNA for HBD-3 and S100A7 was upregulated in 11/20 and HBD9 was increased in 15/20 FK samples. LL-37 mRNA showed moderate upregulation in 7/20 FK samples compared with controls. In healed scar samples, mRNA of all AMPs was found to be low and matching the levels in controls.ConclusionAMP expression is a consistent feature of FK, but not all AMPs are equally expressed. HBD-1 and -2 are most consistently expressed and LL-37 the least, suggesting some specificity of AMP expression related to FK. These results will help to identify HBD sequence templates for designing FK-specific peptides to test for therapeutic potential.

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.

Purpose To examine the efficacy of adjuvant photoactivated chromophore for infectious keratitis–corneal cross-linking (PACK-CXL) for the treatment of infectious keratitis (IK). Methods Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for articles related to PACK-CXL. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies, case series and case reports, were included. A meta-analysis was further performed when there were sufficient similarities in the included RCTs. Primary outcome measure was time to complete corneal healing and secondary outcome measures included size of epithelial defect and infiltrate, corrected-distance-visual-acuity (CDVA), and adverse events. Results Forty-six eligible studies (including four RCTs) with 435 patients were included. When compared to standard antimicrobial treatment (SAT) alone, adjuvant PACK-CXL resulted in shorter mean time to complete corneal healing (−7.44 days; 95% CI, −10.71 to −4.16) and quicker resolution of the infiltrate at 7 days (−5.49 mm2; 95% CI, −7.44 to −3.54) and at 14–30 days (−5.27 mm2; 95% CI, −9.12 to −1.41). There was no significant difference in the size of epithelial defect, CDVA and risk of adverse events. Evidence on the use of PACK-CXL in acanthamoeba and mixed IK was insufficient. Conclusions Our study demonstrates that adjuvant PACK-CXL expedites the healing of IK when compared to SAT alone (low-quality evidence). Further adequately powered, high-quality RCTs are required to fully ascertain the therapeutic effect of PACK-CXL.

AimsTo describe clinical and in vivo confocal microscopy (IVCM) features of neuropathic corneal pain (NCP) without clinically visible signs.MethodsProspective, observational study of 27 eyes of 14 patients who had continuous severe ocular pain for one or more years, with minimal or no ocular surface signs and were non-responsive to topical lubricants, steroids and/or ciclosporin. All patients were evaluated using Ocular Surface Disease Index, Oxford grading scale, Schirmer test 1, Cochet Bonnet esthesiometry and response to topical anaesthesia. Central and paracentral regions of the cornea of patients and seven healthy controls were studied by IVCM. Corneal epithelial thickness and sub-basal nerve density were measured in patients and controls.ResultsFour patients responded to topical anaesthesia (responsive group (RG)), indicating peripheral NCP while 10 patients did not show any improvement (non-responsive group (NRG)), indicating central NCP. Schirmer-1 test was within normal limits in the RG but significantly greater in the NRG (pConclusionNCP without visible clinical signs does not represent typical dry eye disease. Distinct signs demonstrated on IVCM suggest that peripheral NCP, which responds to topical anaesthesia, and central NCP, which does not, are separate entities.

Background/Purpose Stem cells of the corneal epithelium reside in the limbal palisades and associated limbal epithelial crypts. The limbus constitutes a barrier between the conjunctival and corneal phenotype of cells. When the limbal barrier is breached, stem cell deficiency (LSCD) results with conjunctivalisation of the cornea. The purpose of this study was to document an early manifestation of LSCD which is consistent and distinct across several causes of LSCD. # Methods Seventeen eyes of 11 consecutive patients with diverse known causes of LSCD were included. Patients were examined clinically with the slit lamp and fluorescein staining, and by in vivo confocal microscopy. All corneas were photographed with a slit lamp camera. Seven patients underwent in vivo confocal microscopy examination. # Results There were 6 males and 5 females. Six cases had bilateral involvement and the other 5 were unilateral. All patients showed predominantly superior loss of limbal anatomy with effacement of the palisades of Vogt, superficial vascularization encroaching on the peripheral cornea and alternating columns, 6–20 in number, of late fluorescein staining conjunctivalised and normal epithelium extending for a variable distance towards the corneal centre. These were related to prolonged contact lens wear, atopic keratoconjunctivitis, superficial ocular surface burns, ocular cicatricial pemphigoid, rosacea keratoconjunctivitis, old trachoma and neurotrophic keratopathy. In vivo confocal microscopy confirmed features of LSCD. # Conclusion Alternating columns of conjunctivalized and normal epithelia encroaching on the cornea from the superior limbus is a distinct manifestation of early LSCD across a diverse range of causes. The reason for this manifestation is unclear but could be related to the random dysfunction or loss of the palisade architecture.

Egypt is a middle-income country, belonging to the Eastern Mediterranean Region (EMR). Egypt used to be the worst performing EMR country, with over 45 fatalities per 100,000 population. It is considered an example case of many EMR countries in the region where there is a need for quantitative assessment of safety on its roads. The Highway Safety Manual (HSM) offers several functions to calculate safety performance (SPFs), which can estimate crash frequency on a highway network according to its geometric and traffic characteristics. The HSM was developed in the United States using road and crash data specific to its environment. Jurisdictions and other non-U.S. regions were encouraged to develop locally derived models suitable for the local characteristics of roads and crashes. The objective of this paper is to assess the suitability of using the HSM models on rural multi-lane divided highways in Egypt. The calibrated SPFs considering Egyptian road factors were compared with the actual crash events. The results showed that there was a need to develop locally derived SFPs using negative binomial models. The modeling approach and a validation procedure were presented and are applicable when developing local SPFs to compare how well the model performs to the actual data, and to HSM calibrated models. The models were created using 90% of the data and tested on the remaining 10% of the data. The study found that the results relating to driver behavior would help designers in regions other than the United States to benefit from the HSM.

Extensive research efforts have been devoted to identify and improve roadway features that impact safety. Maintaining roadway safety features relies on costly manual operations of regular road surveying and data analysis. This paper introduces an automatic roadway safety features detection approach, which harnesses the potential of artificial intelligence (AI) computer vision to make the process more efficient and less costly. Given a front-facing camera and a global positioning system (GPS) sensor, the proposed system automatically evaluates ten roadway safety features. The system is composed of an oriented (or rotated) object detection model, which solves an orientation encoding discontinuity problem to improve detection accuracy, and a rule-based roadway safety evaluation module. To train and validate the proposed model, a fully-annotated dataset for roadway safety features extraction was collected covering 473 km of roads. The proposed method baseline results are found encouraging when compared to the state-of-the-art models. Different oriented object detection strategies are presented and discussed, and the developed model resulted in improving the mean average precision (mAP) by 16.9% when compared with the literature. The roadway safety feature average prediction accuracy is 84.39% and ranges between 91.11% and 63.12%. The introduced model can pervasively enable/disable autonomous driving (AD) based on safety features of the road, and empower connected vehicles (CV) to send and receive estimated safety features, alerting drivers about black spots or relatively less-safe segments or roads.

ObjectivesTo evaluate the knowledge of corneal donation and the new opt-out system among junior doctors in the East Midlands, UK.MethodsThis was a cross-sectional study performed during June-September 2020. A 26-item questionnaire-based survey was disseminated to all 340 junior doctors working in the East Midlands, UK. Relevant data, including participants background, knowledge of corneal donation and the new opt-out system introduced in England, were analysed.ResultsA total of 143 responses were received (response rate=42.1%). Nineteen (13.3%) junior doctors had previously discussed about corneal donation. The majority (100, 69.9%) of them perceived the importance of obtaining consent for corneal donation as junior doctors, but only 24 (16.8%) felt comfortable in discussing corneal donation. The knowledge of corneal donation was low, with a mean correct response rate of 33.3+/-20.8%. Only 28 (19.6%) doctors were aware of the 24-hour death-to-enucleation time limit. The majority (116, 81.1%) of doctors would consider certifying a death on the ward quicker if they knew it could potentially compromise the quality of corneas. Most (103, 72%) doctors were aware of the new opt-out system but only 56 (39.2%) doctors correctly stated that donation can only proceed with family consent.ConclusionJunior doctors working at the frontline services serve as valuable members in contributing to the process of obtaining consent for organ/tissue donation. Our study highlights the lack of knowledge of corneal donation and the opt-out system amongst junior doctors in the UK. Targeted postgraduate training during the induction process may potentially enhance the donation rate.

PurposeTo 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).MethodA 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.ResultsTen 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.ConclusionLSCT 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.

Alcohol (ethanol) has been used in medicine since time immemorial. In ophthalmic practice, besides as an antiseptic, it was given as retrobulbar injections to relieve severe ocular pain. Alcohol can be applied topically to the surface of neoplastic or suspicious lesions to kill cells that might desquamate and seed during surgical excision, to treat epithelial ingrowth that can occur following corneal surgeries, particularly laser in situ keratomileusis (LASIK), and to treat superficial infectious keratitis. In view of its ability to achieve a smooth cleavage plane between the epithelium and the Bowman's layer, alcohol-assisted delamination (ALD) of the corneal epithelium has been used widely and effectively for a variety of diagnostic and therapeutic indications, at times delivering both outcomes. Diagnostically, ALD yields an intact epithelial sheet which can be fixed flat to provide excellent orientation for histopathological evaluation. Therapeutically, it is most commonly used to treat recurrent corneal erosion syndrome, where its efficacy is comparable to that of phototherapeutic keratectomy but with several advantages. It has also been used to treat various forms of epithelial/anterior stromal dystrophies, which can obviate or delay the need for corneal transplantation for several years. In addition, ALD is performed in corneal collagen cross-linking and corneal refractive surgery for relatively atraumatic removal of the epithelium. In this review, we aimed to provide a comprehensive overview of the diagnostic and therapeutic use of topical alcohol in ophthalmology, to describe the surgical and fixation techniques of ALD, and to highlight our experience in ALD over the past decade.

PurposeTo report the real-world experience of using topical ciclosporin, Ikervis, in the management of ocular surface inflammatory diseases (OSIDs).MethodsThis 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’.Results463 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%; pConclusionsIkervis 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.

Chemical eye injury (CEI) is an acute emergency which can threaten sight and life. These commonly occur at home or the workplace with the former being generally mild and the latter more severe and bilateral. Major workplace accidents involve other parts of the body and can be associated with inhalation or ingestion of the chemical. Alkali injuries cause damage by saponification of tissue and deeper penetration as a consequence. Acid injuries cause rapid coagulation of tissue, which impedes penetration and limits damage. Irritants such as alcohols, cause superficial epithelial denudation. Severe chemical insult can affect all anterior segment structures causing iris, pupil and lens abnormalities. Eye pressure is variably affected and can be low or high or start as one and rapidly change to the other. Chorioretinal changes in the form of vasculopathy are seen and ascribed to be secondary to anterior segment inflammation rather than due to the direct effect of CEI. Final outcome related to structure and function is determined by the injurious agent, duration of exposure, nature of treatment and the rapidity with which it is instituted. Prevention of further damage by profuse and prolonged eye wash, after ascertaining pH of both eyes, together with exploration and removal of all particulate matter, is the key. Other management principles include a complete and thorough assessment, control of inflammation, facilitation of healing and prevention and management of sequelae and complications. Intraocular pressure is often forgotten and must be assessed and managed. Management often requires a multidisciplinary approach.摘要: 本文曾在2019年剑桥眼科专题研讨会进行讲演。 HS Dua从Dompe、Croma、Santen、Allergan和Thea获得酬金和差旅费, 并拥有NuVision biotherapies和GlaxoSmithKline的股份。NuVision Biotherapies是文中提到的Omnigen的制造商。 化学性眼损伤 (Chemical eye injury, CEI) 是严重威胁视力和生命的急症, 通常发生在家里或工作场所, 前者一般较轻, 而后者较重, 并且双眼受累。严重的工作意外伤害还涉及其他身体部位的损伤, 可能与吸入或吞入化学物质有关。碱烧伤导致组织皂化反应并且渗透组织的程度深。酸损伤会导致组织快速凝固, 阻止渗透并使损伤局限。刺激性物质——如酒精可造成表层上皮剥脱。严重的化学损伤会影响整个眼前节结构, 造成虹膜、瞳孔及晶状体异常。眼压受到的影响不一, 可能会降低或升高, 或从一开始的眼压情况迅速转变为另一种。脉络膜视网膜血管病变被认为继发于眼前节炎症, 而不是因为CEI的直接作用。与结构及功能相关的最终结果取决于致伤物、暴露时间、治疗手段及其干预的速度。在确定双眼PH值后, 通过大量和持久的眼部冲洗以防止进一步损伤, 以及寻找和清除所有微粒物质是关键。其他治疗原则包括对眼部的全面评估、控制炎症、促进愈合以及后遗症和并发症的预防及管理。眼内压易被忽视, 但必须对其进行评估和管理。管理通常需要多学科的合作。.

Neurotrophic Keratopathy (NK) refers to a condition where corneal epitheliopathy leading to frank epithelial defect with or without stromal ulceration (melting) is associated with reduced or absent corneal sensations. Sensory nerves serve nociceptor and trophic functions, which can be affected independently or simultaneously. Loss of trophic function and consequent epithelial breakdown exposes the stroma making it susceptible to enzymatic degradation. Nerve pathology can range from attrition to aberrant re-generation with corresponding symptoms from anaesthesia to hyperaesthesia/allodynia. Many systemic and ocular conditions, including surgery and preserved medications can lead to NK. NK can be mild (epithelium and tear film changes), moderate (non-healing epithelial defect) or severe (stromal melting and perforation). Moderate and severe NK can profoundly affect vision and adversely impact on the quality of life. Medical management with lubricating agents from artificial tears to serum/plasma drops, anti-inflammatory agents, antibiotics and anti-proteases all provide non-specific relief, which may be temporary. Contact lenses, punctal plugs, lid closure with botulinum toxin and surgical interventions like tarsorrhaphy, conjunctival flaps and amniotic membrane provide greater success but often at the cost of obscuring sight. Corneal surgery in a dry ocular surface with reduced sensation is at high risk of failure. The recent advent of biologicals such as biopolymers mimicking heparan sulfate; coenzyme Q10 and antisense oligonucleotide that suppress connexin 43 expression, all offer promise. Recombinant nerve growth factor (cenegermin), recently approved for human use targets the nerve pathology and has the potential of addressing the underlying deficit and becoming a specific therapy for NK.