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Harminder S Dua,1 Tarek Katamish,2 Dalia G Said,1 Lana A Faraj1 1Section of Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK; 2Department of Ophthalmology, Cairo University, Cairo, EgyptWe read with interest the paper by Anwar et al.1 The authors have described a technique to bare Descemet’s membrane (DM) by multiple lamellar dissection of the deep corneal stroma when stromal injection of air fails to achieve a big bubble (BB) in deep anterior lamellar keratoplasty (DALK).Read the original article

Background/objectives: To examine the clinical characteristics, risk factors and outcomes of contact lens-related bacterial keratitis (CLBK) in a large UK tertiary referral centre., Subjects/methods: A retrospective analysis of all patients who presented to the Queen's Medical Centre, Nottingham, UK, with suspected CLBK between October 2015 to September 2022 (a 7-year period) was performed. Relevant data on demographic factors, CL wear behaviour, causes, clinical characteristics, and outcomes were analysed., Results: We included 138 patients with CLBK; the mean age was 42.0 ± 17.8 years and 74 (53.6%) patients were male. Most CLBK were related to soft CL wear (94.5%), particularly monthly disposable (42.5%) and daily disposable (24.4%) CLs. Poor CL wear behaviour/hygiene was documented in 57.1% cases. Among the 64 (46.4%) microbiological-positive cases (n = 73 organisms), Pseudomonas aeruginosa (36, 49.3%) and Staphylococcus spp. (16, 21.9%) were most commonly identified. Six (4.3%) cases were polymicrobial. Most (97.0%) patients were successfully treated with topical antibiotics alone, with 80.6% achieving good final corrected-distance-visual-acuity (CDVA) of ≥ 0.30 logMAR. Poor visual outcome (final CDVA < 0.30 logMAR) was significantly associated with presenting CDVA < 0.6 logMAR (p = 0.002) and central ulcer (p = 0.004). Poor corneal healing (complete healing of > 30 days from initial presentation) was significantly associated with age > 50 years (p = 0.028), female gender (p = 0.020), and infiltrate size >3 mm (p = 0.031)., Conclusions: Poor CL wear behaviour/hygiene is commonly observed in CLBK, highlighting the importance of improved counselling and awareness regarding CL use and hygiene. When presented early and managed appropriately, most patients are able to achieve good clinical outcomes with medical treatment alone., Competing Interests: Competing interests: DGS serves as a member of the Eye editorial board. All other authors have competing interests to declare., (© 2024. Crown.)

Background: Infectious keratitis (IK) is the leading cause of corneal blindness globally. Deep learning (DL) is an emerging tool for medical diagnosis, though its value in IK is unclear. We aimed to assess the diagnostic accuracy of DL for IK and its comparative accuracy with ophthalmologists., Methods: In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, and clinical registries for studies related to DL for IK published between 1974 and July 16, 2024. We performed meta-analyses using bivariate models to estimate summary sensitivities and specificities. This systematic review was registered with PROSPERO (CRD42022348596)., Findings: Of 963 studies identified, 35 studies (136,401 corneal images from >56,011 patients) were included. Most studies had low risk of bias (68.6%) and low applicability concern (91.4%) in all domains of QUADAS-2, except the index test domain. Against the reference standard of expert consensus and/or microbiological results (seven external validation studies; 10,675 images), the summary estimates (95% CI) for sensitivity and specificity of DL for IK were 86.2% (71.6-93.9) and 96.3% (91.5-98.5). From 28 internal validation studies (16,059 images), summary estimates for sensitivity and specificity were 91.6% (86.8-94.8) and 90.7% (84.8-94.5). Based on seven studies (4007 images), DL and ophthalmologists had comparable summary sensitivity [89.2% (82.2-93.6) versus 82.2% (71.5-89.5); P = 0.20] and specificity [(93.2% (85.5-97.0) versus 89.6% (78.8-95.2); P = 0.45]., Interpretation: DL models may have good diagnostic accuracy for IK and comparable performance to ophthalmologists. These findings should be interpreted with caution due to the image-based analysis that did not account for potential correlation within individuals, relatively homogeneous population studies, lack of pre-specification of DL thresholds, and limited external validation. Future studies should improve their reporting, data diversity, external validation, transparency, and explainability to increase the reliability and generalisability of DL models for clinical deployment., Funding: NIH, Wellcome Trust, MRC, Fight for Sight, BHP, and ESCRS., Competing Interests: HA is the Chief Scientific Officer of Preemptive Medicine and Health, Flagship Pioneering., (© 2024 The Author(s).)

Background: To compare the diagnostic performance of microbiological culture and 16S/18S rRNA gene polymerase chain reaction (PCR)-Sanger sequencing for infectious keratitis (IK) and to analyse the effect of clinical disease severity on test performance and inter-test concordance., Methods: This was a three-arm, diagnostic cross-sectional study. We included all eligible patients who presented with presumed bacterial/fungal keratitis to the Queen's Medical Centre, Nottingham, UK, between June 2021 and September 2022. All patients underwent simultaneous culture (either direct or indirect culture, or both) and 16S (pan-bacterial)/18S (pan-fungal) ribosomal RNA (rRNA) PCR-Sanger sequencing. The bacterial/fungal genus and species identified on culture were confirmed using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Relevant clinical data were also collected to analyze for any potential clinico-microbiological correlation. Main outcome measures included the diagnostic yield, test accuracy (including sensitivity and specificity), and inter-test agreement [including percent agreement and Cohen's kappa ( k )]., Results: A total of 81 patients (86 episodes of IK) were included in this study. All organisms identified were of bacterial origin. Diagnostic yields were similar among direct culture (52.3%), indirect culture (50.8%), and PCR (43.1%; p = 0.13). The addition of PCR enabled a positive diagnostic yield in 3 (9.7%) direct culture-negative cases. Based on composite reference standard, direct culture had the highest sensitivity (87.5%; 95% CI, 72.4-95.3%), followed by indirect culture (85.4%; 95% CI, 71.6-93.5%) and PCR (73.5%; 95% CI, 59.0-84.6%), with 100% specificity noted in all tests. Pairwise comparisons showed substantial agreement among the three tests (percent agreement = 81.8-86.2%, Cohen's k = 0.67-0.72). Clinico-microbiological correlation demonstrated higher culture-PCR concordance in cases with greater infection severity., Conclusions: This study highlights a similar diagnostic performance of direct culture, indirect culture and 16S rRNA PCR for bacterial keratitis, with substantial inter-test concordance. PCR serves as a useful diagnostic adjuvant to culture, particularly in culture-negative cases or those with lesser disease severity (where culture-PCR concordance is lower)., Competing Interests: DJIT, JC, and JH are employees of Micropathology Ltd, UK, but the company has no role in the design of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hammoudeh, Suresh, Ong, Lister, Mohammed, Thomas, Cottell, Holden, Said, Dua and Ting.)

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., Competing Interests: Competing interests: HSD: Artic Vision and Thea Pharmaceuticals. Shares in NuVision biotherapies and GlaxoSmithKline., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of competing interest Harminder S Dua: Consultant and travel support from Allergan, Bausch & Lomb, Dompe, Santen, Thea and VisuFarma. Shares in NuVision biothereapies and Glaxosmithkline. Rui Freitas: None. Imran Mohammed: None. Darren SJ Ting: None. Dalia G Said: UK advisory board member of Dompe., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: None

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ong, Wong, Suresh, Hammoudeh, Lister, Said, Dua and Ting.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Deshmukh, Ong, Rampat, Alió del Barrio, Barua, Ang, Mehta, Said, Dua, Ambrósio and Ting.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2023. Crown.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier Inc.)

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., Competing Interests: Competing interests: HSD is consultant to Artic Vision, Electrospinning, Santen, Thea and has shares in Glaxosmithkline and NuVision biotherapies (manufacturers of Omnigen) and is joint patent holder for the vacuum drying method for preparing Omnigen). None of the other authors have any conflict of interest to declare. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. HSD has received an unconditional educational grant from Santen, which is not related to the content of this paper., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: HSD is consultant to Artic Vision, Electrospinning, Santen, Thea and has shares in Glaxosmithkline and NuVision biotherapies. HSD has received an unconditional educational grant from Santen. The opinions expressed in this paper are entirely those of the authors., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with several of the authors (DSJT, MN)., (Copyright © 2021 Ting, Li, Verma, Goh, Nubile, Mastropasqua, Said, Beuerman, Lakshminarayanan, Mohammed and Dua.)

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 log 10 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., (© 2021. The Author(s).)

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., (© 2020. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ting, Cairns, Gopal, Ho, Krstic, Elsahn, Lister, Said and Dua.)

Background: Fungal 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., Methods: OS 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., Results: Messenger 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., Conclusion: AMP 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., Competing Interests: Competing interests: HSD: Honoraria and Travel expenses from Allergan, Arctic Vision, Croma, Dompe, Santen, Thea. Shares in NuVision Biotherapies and GlaxoSmithKline., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Song, Deshmukh, Lin, Ang, Mehta, Chodosh, Said, Dua and Ting.)

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., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 < 0.001) and better UDVA (- 0.26 logMAR; - 0.50 to - 0.02; 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 < 0.001). None of the RCTs examined the use of adjuvant AMT in herpetic or Acanthamoeba keratitis, though the benefit was supported by a number of case series. In conclusion, AMT serves as a useful adjuvant therapy in improving corneal healing and visual outcome in bacterial and fungal keratitis (low-quality evidence). Further adequately powered, high-quality RCTs are required to ascertain its therapeutic potential, particularly for herpetic and Acanthamoeba keratitis. Future standardization of the core outcome set in IK-related trials would be invaluable.

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.

Background/aims: To examine the incidence, causative microorganisms and in vitro antimicrobial susceptibility and resistance profiles of infectious keratitis (IK) in Nottingham, UK., Methods: A 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., Results: The 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 (p<0.001) and significant decrease in Klebsiella 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)., Conclusion: IK 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

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.

Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To examine the optical coherence tomography (OCT) and histologic features of Descemet membrane detachment (DMD) to ascertain the involvement of the pre-Descemet layer (PDL)., Design: Retrospective, observational case series., Methods: Clinical, histopathologic, and OCT features of a cohort of 41 cases with diagnosis of DMD from 4 centers were studied. OCT images were evaluated independently by 3 observers for number of detached layers (1 or 2), reflectivity, configuration (straight line or wavy), distance from posterior stroma, and presence or absence of a tear with any scrolling of the torn edges. Five had a histology specimen. The main outcome measure was the involvement of the PDL in DMD and its confirmation by histology., Results: Three types of DMD were identified: type 1, where the PDL and DM were detached together; type 2, where only the DM was detached; and mixed, where the PDL and DM were detached but also separated from each other. These were further found to be rhegmatogenous or nonrhegmatogenous depending on the presence of absence of a tear in DM or both layers. Histology confirmed involvement of PDL in all 5 cases and showed it to be infiltrated by cells in 3 of 5 cases., Conclusions: The PDL is involved in DMD. This fact significantly changes our understanding of DMD and could have implications for management. The detached PDL can be infiltrated with cells. A prospective study in relation to etiology and types of DMD is needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: 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., Design: Prospective, interventional, before-and-after case series., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: Non-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., Method: The 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., Result: All 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., Conclusion: ASOCT 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., Competing Interests: Competing interests: HSSD: Honoraria and travel expenses from Dompe, Croma, Santen, Allergan and Thea, and shares in NuVision and GlaxoSmithKline., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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).