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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.

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.

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.

AimsTo investigate and define the nature of big bubbles (BB) formed by injection of viscoelastic in deep anterior lamellar keratoplasty.MethodsIntrastromal injections of 0.1 and 0.3 mL of sodium hyaluronate 1.2% and 0.6% were made into sclera-corneal discs (n = 32) at superficial (anterior-third), midstromal (middle-third) and deep (posterior-third) levels to simulate deep anterior lamellar keratoplasty. Postinjection optical coherence tomograms (OCT) were obtained with the needle in situ. The samples were sectioned and examined histologically. Twelve control samples were injected with air.ResultsWith superficial injections (n=8) only intrastromal accumulation of viscoelastic was noted. With midstromal injections (n=10) intrastromal accumulation of viscoelastic (n=6) and intrastromal big bubbles (IBB) (n=4) with substantial and variable stromal tissue in the walls were noted. No type 1, type 2 or mixed BB were noted. With deep injections (n=14), type 1 BB (n=4), IBB (n=4) and mixed BB (n=6) were obtained.There was no difference in the results with the two different concentrations of viscoelastic used. With air injection (n=12), 10 type 1 and 1 type 2 BB and 1 mixed BB were obtained. No IBB was noted.ConclusionsBB obtained by injection of viscoelastic and air can be different. The former tends to occur at the site of injection, especially with midstromal injections, takes the form of tissue separation by stretch and tearing and does not cleave in a consistent plane like air. Surgeons should be aware of IBB created by viscodissection and not confuse it for a type1 BB. Intraoperative OCT should help identify IBB.

AimNon-traumatic corneal perforations (CPerfs) may present with shallow/flat or formed anterior chamber (AC). This study uses anterior segment optical coherence tomography (ASOCT) to ascertain these differences.MethodThe study included 14 eyes of 13 patients. They underwent high-resolution ASOCT scans at multiple time points, prior to and after cyanoacrylate glueing, between January 2016 and July 2018. A retrospective analysis of over 2500 ASOCT sections and AS photographs was conducted by two independent observers. The findings were correlated with clinical features and diagnoses.ResultAll patients had documented Seidel’s positive sign at the outset. Two groups with distinctive features were identified. In group 1, ‘formed’ AC, there was hydration of the cornea with lamellar separation of the stroma, intrastromal pockets of fluid, epithelial bullae and an indirect communication between AC and the exterior. In group 2, ‘flat’ AC, the corneal hydration was less obvious, there were no pockets of intrastromal fluid, no epithelial bullae and a direct communication of the AC with the exterior. After glueing, the stromal hydration resolved, and healing occurred beneath the glue. The glue and corneal blood vessels consistently cast a dense shadow posteriorly on ASOCT.ConclusionASOCT demonstrates that leaking CPerfs can be indirect or direct. The former is associated with a ‘formed’ AC and the latter with a very shallow/flat AC. The valvular nature of the communication in indirect perforations allows the AC to maintain its volume despite a continuous leak.

To describe in vivo confocal microscopy (IVCM) findings in patients with limbal stem cell deficiency (LSCD).23 eyes of 17 consecutive patients suffering from LSCD were included in this study. A detailed examination by IVCM was performed in addition to a routine slit-lamp biomicroscopy. Size and density of corneal epithelial and conjunctival epithelial cells on cornea were measured and statistically analysed using SPSS version 8.0 software. Results were compared with histology in select cases.Anatomical and morphological differences were observed between normal corneal cells and conjunctival epithelial cells on cornea. Size and density differences reached statistically significant levels between the normal corneal cells and the conjunctival epithelial cells on cornea (p0.01). Goblet cells were visible throughout the conjunctivalised corneal epithelium in eight eyes. Several IVCM features could be correlated with histology in six of our patients.A number of features were demonstrated by laser IVCM in patients presenting clinically with LSCD. Some of these features were corroborated with features observed on histological examination of tissue samples.

The most popular technique for deep anterior lamellar keratoplasty (DALK) is the 'big bubble' (BB) technique wherein air is injected in the cornea to create a bubble that separates Descemet's membrane (DM) from the stroma. An attempt to create a BB often results in the cornea being filled with numerous small bubbles without the formation of a BB. Manual dissection is then required to complete the procedure. The aim of the study is to compare these two groups, successful BB versus failed bubble (FB) dissection to determine whether the clinical outcomes were different.In this retrospective comparative study, 46 patients out of 52 who underwent DALK for various corneal stromal diseases such as keratoconus, stromal dystrophy or corneal scarring (caused by different conditions) were included in the analysis. BB was achieved in 25 patients and in the remaining 21 patients a BB separation of the DM was not possible necessitating manual lamellar dissection of stroma to get as close to the DM as possible.The authors compared best-corrected visual acuity, contrast sensitivity, astigmatism, interface densitometry and Scheimpflug pachymetry in the two groups. Postoperative corneal thickness was higher in the 'small bubbles' group (mean 628.9 vs 564.1 μm; p0.0005), but there was no significant difference in best-corrected visual acuity, astigmatism, contrast sensitivity and densitometry between the groups.In DALK, manual lamellar dissection is a reasonable alternative when BB separation of the DM is not achieved.

Worldwide corneal infections are a major cause of unilateral blindness.1 In some parts of the world, fungal infections are commoner than bacterial infections.2 3 The challenge lies not only in the diagnosis but also in appropriate therapy, once diagnosis is established. It becomes more difficult when laboratory tests are inconclusive or do not support the clinical diagnosis and the challenge is greater when the infection is mixed with bacterial or acanthamoeba co-infections.4 One major reason is the restricted availability of commercially available anti-fungal agents for use in the eye. Although the need is great, it is predominantly in the poorer countries of the world where affordability may not recompense the investment required in developing and licensing a drug. Treatment of fungal keratitis is therefore largely dependent on the use of unlicensed or off-label drugs. Susceptibility of common filamentous and yeast species of pathogenic fungi differs and there is no broad spectrum anti-fungal agent available, even among the off-label and unlicensed preparations, that covers most of this range. Treatment therefore has to be commenced on clinical suspicion supported by preliminary diagnostic examination of smears of corneal samples. The PCR test5 can provide a reliable diagnosis in a few hours but is expensive. Culture can take up to 3 weeks and treatment cannot be deferred that long. A reasonable approach would be to use a combination of Econazole 1% (which is more effective against filamentous fungi such as Aspergillus and Fusarium spp.,) and …

In clinical parlance, the terms ‘corneal angiogenesis’, ‘corneal vascularisation’ and ‘corneal neovascularisation’ are used interchangeably. While the term ‘vasculogenesis’ is used to describe the formation and development of blood vessels in the embryo, angiogenesis refers to blood vessel formation under physiological (endometrium, placenta) or pathological (wound healing, tumours) conditions. The acronym CNV is now established as representing ‘choroidal new vessels’ and should not be used for ‘corneal new vessels’ to avoid confusion in the literature. Hence, it is proposed that the term CVas be used to denote ‘corneal vascularisation’. CVas is a sign of corneal disease processes and not a distinct clinical entity. A wide variety of insults, including infection, inflammation, ischaemia, degeneration, trauma and loss of the limbal stem cell barrier, can cause CVas. The published evidence suggest that although CVas can occasionally serve a beneficial role in the clearing of infections, wound healing and arresting stromal melts,1 its disadvantages are numerous and often lead to tissue scarring, oedema, lipid deposition and persistent inflammation that may significantly alter visual acuity.2 3 CVas may not only reduce visual acuity, but it also results in the loss of the immune privilege of the cornea, thereby worsening the prognosis of subsequent keratoplasty.4 A recent meta-analysis supported multiple previous reports that graft failure …

Despite worldwide awareness of Acanthamoeba as a cause of corneal infection, Acanthamoeba keratitis continues to be misdiagnosed or inadequately treated. The clinical presentation can range from the non-specific (corneal epithelial irregularities and microerosions with some pain and irritation), to the classic (radial keratoneuritis and ring or double ring infiltrates).1 Early lesions presenting as coarse punctuate keratitis are often attributed to dryness or contact-lens-related corneal epitheliopathy that has been treated with artificial tears and some antibiotic drops. When the infection manifests as (pseudo)dentritiform epithelial lesions, it is often mistaken for herpes simplex keratitis and treated with antiviral medication. On several occasions, an associated anterior chamber reaction has directed the observer to a diagnosis of iritis with use of steroid drops as part of the treatment plan. Delay allows the organism, which may primarily be in the epithelium at the onset of disease, to make its way into the stroma feeding on keratocytes and along stromal nerves, entrenching itself and resulting in an indolent recalcitrant keratitis. The emphasis on “pain out of proportion to signs” is not always borne …

The World Health Organization (WHO) defines blindness as a visual acuity of less than 3/60, or corresponding visual-field loss to less than 10°, in the better eye with best possible correction. In 2002, according to WHO estimates, there were 161 million visually impaired people living on this planet. Of these, 124 million had low vision, and 37 million were blind. Blindness can be broadly divided into “incurable” and “curable” or treatable. Age-related cataract is responsible for 48% of world blindness amounting to around 18 million people,1 who in theory should be cured by appropriate intervention. No one can argue that this is a compelling reason for increasing the number of cataract operations performed. The number of cataract operations performed per 100 000 population per year, known as the cataract surgery rate (CSR), serves as an indicator of the efforts made by any community towards alleviating cataract blindness. Except for the most developed countries, cataract remains the leading cause of blindness in all regions of the world. Associated with ageing, it is even more significant as a cause of low vision. Across the world, as a proportion of the total blind, the distribution is uneven. In the (WHO) Regions of the Americas and the European region,2 the percentage of total world blindness is only 7% for each. In the South-East Asia region it is 32%, in the Western pacific region it is 25%, and in the African region it is 18%.3 Almost half of these figures are accounted for by cataract alone. More than 90% of the world’s visually impaired live in developing countries. This contrasts …

Lamellar corneal grafts, both anterior and posterior, are rapidly taking over as procedures of choice for several indications requiring corneal transplantation. Despite the promised advantages of lamellar procedures, worldwide, penetrating keratoplasty (PK) remains the predominant procedure. In the future, even when the practice of PK diminishes, its consequences among those who have had the procedure will continue to be encountered for quite a while thereafter. Discounting primary graft failure, there are three main issues that have dogged PK ever since its inception. These are immune-mediated rejection, spherical and astigmatic refractive errors and a weak wound for the rest of the patient’s life. These are intricately inter-related, as interventions to deal with any one can affect the other(s). In this issue, Jeganathan et al report on a retrospective review of 947 consecutive patients who had received a PK. Of these, 5.4% required re-suturing. Individuals who required PK for microbial keratitis had a higher incidence of re-suturing (12%) compared with those with keratoconus (10%) and endothelial decompensation (2.5%). The commonest cause for re-suturing was wound dehiscence (43%) either traumatic or spontaneous. Spontaneous wound dehiscence occurred at a mean of 18.8 months post-PK (following suture removal), highlighting the perpetual weakness of the wound (see page 893) .1 Various strategies have been adopted to combat rejection, of which topical steroid medication remains the mainstay. This must be an important factor that affects the strength of the wound at the graft host junction, as it is often administered for a year or more.2 Much attention has focused on suture material and suturing techniques to control postgraft astigmatism and influence wound quality. Suture materials act as “foreign bodies” capable of inciting inflammation, attracting new vessels, acting as a nidus for infection and consequently affecting the wound-healing response, often adversely.3 Biodegradable material such …

A 65-year-old Caucasian male was referred for suspected keratoconus with Fleischer ring in both eyes. He had worn hard contact lenses since 1975 and recently changed to rigid gas permeable lens due to intolerance towards hard lens. His family history revealed that his son was diagnosed as having keratoconus. His best contact lens corrected visual acuity was 6/9 and 6/6 in the right and left eye, respectively. Slit-lamp examination revealed paracentral thinning, Vogt striae …