Microbial keratitis in Southern Malawi: a microbiological pilot study.

OBJECTIVE: Microbial keratitis (MK) is a significant cause of blindness in sub-Saharan Africa. We investigated the feasibility of using a novel corneal impression membrane (CIM) for obtaining and processing samples by culture, PCR and whole-genome sequencing (WGS) in patients presenting with suspected MK in Malawi. METHODS AND ANALYSIS: Samples were collected from patients presenting with suspected MK using a 12 mm diameter polytetrafluoroethylene CIM disc. Samples were processed using culture and PCR for Acanthamoeba, herpes simplex virus type 1 (HSV-1) and the bacterial 16S rRNA gene. Minimum inhibitory concentrations of isolates to eight antimicrobials were measured using susceptibility strips. WGS was used to characterise Staphylococcus aureus isolates. RESULTS: 71 eyes of 71 patients were included. The overall CIM isolation rate was 81.7% (58 positive samples from 71 participants). 69 (81.2%) of isolates were Gram-positive cocci. Coagulase-negative Staphylococcus 31.8% and Streptococcus species 14.1% were the most isolated bacteria. Seven (9.9%) participants were positive for HSV-1. Fungi and Acanthamoeba were not detected. Moxifloxacin and chloramphenicol offered the best coverage for both Gram-positive and Gram-negative isolates when susceptibility was determined using known antimicrobial first quartile concentrations and European Committee on Antimicrobial Susceptibility Testing breakpoints, respectively. WGS identified known virulence genes associated with S. aureus keratitis. CONCLUSIONS: In a resource-poor setting, a CIM can be used to safely sample the cornea in patients presenting with suspected MK, enabling identification of causative microorganisms by culture and PCR. Although the microbiological spectrum found was limited to the dry season, these preliminary results could be used to guide empirical treatment.

Small fibre pathology, small fibre symptoms and pain in fibromyalgia syndrome.

A proportion of people with fibromyalgia demonstrate small fibre pathology (SFP). However, it is unclear how SFP directly relates to pain phenomenology. Thirty-three individuals with FMS and ten healthy volunteers underwent assessment of SFP and sensory phenotyping using corneal confocal microscopy, validated questionnaires and quantitative sensory testing (QST). Corneal nerve fibre length was used to stratify participants with fibromyalgia into with SFP [SFP+] and without SFP [SFP-]. SFP was detected in 50% of the fibromyalgia cohort. Current pain score and QST parameters did not differ between SFP+ and SFP-. Mechanical pain sensitivity (MPS) demonstrated a significant gain-of-function in the SFP- cohort compared to healthy-volunteers (p = 0.014, F = 4.806, η2 = 0.22). Further stratification revealed a cohort without structural SFP but with symptoms compatible with small fibre neuropathy symptoms and a significant gain in function in MPS (p = 0.020 Chi-square). Additionally, this cohort reported higher scores for both depression (p = 0.039, H = 8.483, η2 = 0.312) and anxiety (p = 0.022, F = 3.587, η2 = 0.293). This study confirms that SFP is present in a proportion of people with fibromyalgia. We also show that in a proportion of people with fibromyalgia, small fibre neuropathy symptoms are present in the absence of structural SFP. Greater mechanical pain sensitivity, depression and anxiety are seen in these individuals.

Ocular phenotype and therapeutic interventions in keratitis-ichthyosis-deafness (KID) syndrome.

BACKGROUND: To report ocular manifestations, clinical course, and therapeutic management of patients with molecular genetically confirmed keratitis-ichthyosis-deafness syndrome. METHODS: Four patients, aged 19 to 46, with keratitis-ichthyosis-deafness syndrome from across the UK were recruited for a general and ocular examination and GJB2 (Cx26) mutational analysis. The ocular examination included best-corrected visual acuity, slit-lamp bio-microscopy, and ocular surface assessment. Mutational analysis of the coding region of GJB2 (Cx26) was performed by bidirectional Sanger sequencing. RESULTS: All four individuals had the characteristic systemic features of keratitis-ichthyosis-deafness syndrome. Each patient was found to have a missense mutation, resulting in the substitution of aspartic acid with asparagine at codon 50 (p.D50N). Main ophthalmic features were vascularizing keratopathy, ocular surface disease, hyperkeratotic lid lesions, recurrent epithelial defects, and corneal stromal scarring. One patient had multiple surgical procedures, including superficial keratectomies and lamellar keratoplasty, which failed to prevent severe visual loss. In contrast, oral therapy with ketoconazole stabilized the corneal and skin disease in two other patients with keratitis-ichthyosis-deafness syndrome. The patient who underwent intracorneal bevacizumab injection showed a marked reduction in corneal vascularization following a single application. CONCLUSIONS: Keratitis-ichthyosis-deafness syndrome is a rare ectodermal dysplasia caused by heterozygous mutations in GJB2 (Cx26) with a severe, progressive vascularizing keratopathy. Oral ketoconazole therapy may offer benefit in stabilizing the corneal and skin disease.

VERTICAL AND HORIZONTAL METAMORPHOPSIA ONE YEAR AFTER SURGERY FOR MACULAR HOLES ≤ 500 µ m WITH AND WITHOUT INVERTED INTERNAL LIMITING MEMBRANE FLAP.

PURPOSE: To investigate the effect of an inverted internal limiting membrane flap (IF) and other factors on metamorphopsia after macular hole surgery. METHODS: Prospective case series of patients undergoing pars plana vitrectomy with gas tamponade, with either conventional internal limiting membrane peeling (CP) or an IF, for primary idiopathic macular holes ≤ 500 µ m. Vertical and horizontal metamorphopsia were measured as M-scores (degrees) using M-charts preoperatively and at 2, 6, and 12 months postoperatively. RESULTS: Fifty-three eyes of 53 patients were included of whom 27 underwent CP and 26 were treated with an IF. After macular hole surgery, all patients were pseudophakic. Vertical and horizontal metamorphopsia improved from 1.08 (±0.51) and 0.98 (±0.70) preoperatively to 0.58 (±0.37) and 0.45 (±0.36) at 2 months ( P < 0.01), with no further significant improvement at 6 months (0.39 [±0.31], P = 0.07 and 0.31 [±0.28], P = 0.18) or at 12 months (0.37 [±0.30], P = 0.72 and 0.28 [±0.28], P = 0.99). There was no significant difference in the mean vertical and horizontal metamorphopsia between patients with CP and with an IF at 2 months ( P = 0.063, P = 0.10), 6 months ( P = 0.25, P = 0.16), or 12 months ( P = 0.62, P = 0.22). Preoperative vertical M-score improved at 12 months after macular hole surgery by 61% and 64% in the CP and IF groups, respectively ( P = 0.84), and the horizontal M-score by 65% and 71%, respectively ( P = 0.98). CONCLUSION: The use of an IF has no evident bearing on the degree of postoperative metamorphopsia 12 months after surgical repair of macular holes ≤ 500 µ m.

Antimicrobials and antiseptics: Lowering effect on ocular surface bacterial flora - A systematic review.

Topical antimicrobials and antiseptics are used perioperatively to reduce the ocular surface bacteria flora (OSBF) that are involved in the development of post-operative infectious complications. However, their effectiveness is still a controversial topic. This systematic review, performed according to the PRISMA guidelines and registered in PROSPERO, aims to provide an overview of the efficacy of the agents currently used in peri-cataract surgery and -intravitreal injections (IVI) in lowering the OSBF. Although effective in lowering OSBF, perioperative topical antimicrobials are associated with the risk of resistance development, with no obvious additional benefit compared with topical antisepsis. Conversely, the effectiveness of topical antiseptics before cataract surgery and IVI is strongly supported. Based on the available evidence, perioperative antimicrobials are not recommended, whereas the perioperative use of antiseptics is strongly recommended as prophylactic treatment for lowering the infection due to OSBF. Post-operative antimicrobials may be considered in eyes at higher risk for infection.

ROCK Inhibitors in Corneal Diseases and Glaucoma-A Comprehensive Review of These Emerging Drugs.

Rho kinase (ROCK) inhibitors have gained significant attention as emerging novel treatment options in the field of ophthalmology in recent years. The evidence supporting their efficacy in glaucoma and corneal pathology includes both in vitro and clinical studies. Among the available options, ripasudil and netarsudil have emerged as the leading ROCK inhibitors, and some countries have approved these therapeutic options as treatments for glaucoma. Various dosing regimens have been studied, including monotherapy and combination therapy, especially for patients with secondary glaucoma who are already on multiple medications. Another rising application of ROCK inhibitors includes their use as an adjunct in surgical procedures such as Descemetorhexis Without Endothelial Keratoplasty (DWEK), Descemet Stripping Only (DSO) to accelerate visual recovery, glaucoma surgeries to reduce scarring process and allow better intraocular pressure (IOP) control, or after complicated anterior segment surgery to treat corneal oedema. This article provides a comprehensive overview of the existing literature in the field, offering recommendations for prescribing ROCK inhibitors and also discussing patient selection, drug efficacy, and possible adverse effects.

Preoperative surgeon evaluation of corneal endothelial status: the Viability Control of Human Endothelial Cells before Keratoplasty (V-CHECK) study protocol.

INTRODUCTION: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability. METHODS AND ANALYSIS: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values. ETHICS AND DISSEMINATION: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05847387.

P27-A149†Liverpool research eye biobank-our exerience of expanding to collect from living donors.

PURPOSE: The Liverpool Research Eye Biobank (LREB) collects tissue for researchers who wish to study a wide range of ophthalmic conditions and develop new and more effective treatments. Historically the LREB has collected whole globes and conjunctiva from cadaveric donors but in 2021 we expanded to start collecting tissues from living donors who were undergoing ophthalmic surgery in the St Paul's Eye Unit in Liverpool. The aim was to provide tissue and fluid samples from patients with specific eye disease to research projects and create a bank of ophthalmic samples that can be provided to future research projects. Here we reflect on our experience after a year of collections. METHODS: The clinical team discuss donation with patients during the pre-op appointment. Consent is taken on the day of surgery using an electronic consent form available on PENS. Samples are taken according to the patient's consent preference and then stored appropriately within a fridge/freezer close to theatre. Samples are then transferred for processing to the University of Liverpool (UoL). Fluids such as aqueous and vitreous are preserved at -80°C. The majority of ocular tissue collected is preserved by fixing in 10% neutral buffered formalin then transferred to 70% ethanol for long term storage. On request samples have been preserved using alternative methods such as snap freezing in liquid nitrogen. All samples are logged using a laboratory information management system. RESULTS: Collections depend on the cooperation of the clinical teams and we have had very good engagement from them. The UoL works closely with St Pauls Eye Unit and the physical proximity between the two has been helpful. The location of the storage fridges close to theatre is important to limit extra effort for busy clinical teams. Regular training of consenters was key to ensure compliance with SOPs. In 11 months, we consented 419 donors and collected 673 samples including corneal tissue, iris, sclera, lens/capsule, retinal membranes, tenons, muscle, aqueous, vitreous, blood. CONCLUSION: After the success of collections from one site we plan to expand to collect from multiple sites including Aintree and Alder Hey Children's Hospital.

INFLUENCE OF PREOPERATIVE POSTURING ON SUBFOVEAL FLUID HEIGHT IN MACULA-OFF RETINAL DETACHMENTS.

PURPOSE: To evaluate the effect of preoperative posturing on subfoveal fluid height (SFFH) in macula-off retinal detachment. METHODS: A prospective study including patients with macula-off retinal detachment with SFFH measurable on optical coherence tomography (OCT) and duration of loss of central vision (LCV) ≤ 7 days. Linear OCT volume scans were performed at baseline, after 1 minute, 1 hour, 4 hours, and on the next morning. For the first hour, all patients remained in an upright position. Patients were then either instructed to posture until the surgery according to the location of the primary retinal break (posturing group) or were not given any instructions (control group). RESULTS: Twenty-four patients were included in the posturing group and 11 patients in the control group. There was no significant change in SFFH between baseline, 1 minute, 1 hour, and 4 hours. The mean SFFH in the control group increased by 243 µ m from 624 (±268) µ m at baseline to 867 (±303) µ m the next morning ( P < 0.01) but decreased in the posturing group by 150 µ m from 728 (±416) to 578 (±445) µ m ( P = 0.03). There was a significant association of the SFFH the next morning with posturing ( P < 0.01) and SFFH at baseline ( P < 0.01), but not with location of primary break ( P = 0.20). The change in SFFH from baseline to the next morning was significantly associated with posturing and primary break location ( P < 0.01), but not with SFFH at baseline ( P = 0.21). CONCLUSION: Preoperative posturing is an effective measure to prevent progression of macular detachment in macula-off retinal detachment.

Managing Post-Keratoplasty Astigmatism: High-Tech vs. Low-Tech Imaging Techniques for Guiding Suture Manipulation.

Astigmatism is a visually significant condition that can develop after keratoplasty. The management of post-keratoplasty astigmatism can be performed both when transplant sutures are in place and when they have been removed. Fundamental for astigmatism management is its identification and characterization in terms of type, amount, and direction. Commonly, post-keratoplasty astigmatism is evaluated through corneal tomography or topo-aberrometry; however, many other techniques can be used in case these instruments are not readily available. Here, we describe several low-tech and high-tech techniques used for post-keratoplasty astigmatism detection in order to quickly understand if it contributes to low vision quality and to determine its characteristics. The management of post-keratoplasty astigmatism through suture manipulation is also described.

Average paraxial power of a lens and visual acuity.

To provide a solution for average paraxial lens power (ApP) of a lens. Orthogonal and oblique sections through a lens of power [Formula: see text] were reduced to a paraxial representation of lens power followed by integration. Visual acuity was measured using lenses of different powers (cylinders of - 1.0 and - 2.0D) and axes, mean spherical equivalent (MSE) of S + C/2, ApP and a toric correction, with the order of correction randomised. A digital screen at 6 m was used on which a Landolt C with crowding bars was displayed for 0.3 s before vanishing. The general equation for a symmetrical lens of refractive index (n), radius of curvature R, in medium of refractive index n1, through orthogonal ([Formula: see text]) and oblique meridians ([Formula: see text]) as a function of the angle of incidence ([Formula: see text]) reduces for paraxial rays ([Formula: see text]) to [Formula: see text]. The average of this function is [Formula: see text] providing a solution of [Formula: see text] for ApP.For central (p = 0.04), but not peripheral (p = 0.17) viewing, correction with ApP was associated with better visual acuity than a MSE across all tested refractive errors (p = 0.04). These findings suggest that [Formula: see text] may be a more inclusive representation of the average paraxial power of a cylindrical lens than the MSE.

Deep Learning Using Preoperative AS-OCT Predicts Graft Detachment in DMEK.

Purpose: To evaluate a novel deep learning algorithm to distinguish between eyes that may or may not have a graft detachment based on pre-Descemet membrane endothelial keratoplasty (DMEK) anterior segment optical coherence tomography (AS-OCT) images. Methods: Retrospective cohort study. A multiple-instance learning artificial intelligence (MIL-AI) model using a ResNet-101 backbone was designed. AS-OCT images were split into training and testing sets. The MIL-AI model was trained and validated on the training set. Model performance and heatmaps were calculated from the testing set. Classification performance metrics included F1 score (harmonic mean of recall and precision), specificity, sensitivity, and area under curve (AUC). Finally, MIL-AI performance was compared to manual classification by an experienced ophthalmologist. Results: In total, 9466 images of 74 eyes (128 images per eye) were included in the study. Images from 50 eyes were used to train and validate the MIL-AI system, while the remaining 24 eyes were used as the test set to determine its performance and generate heatmaps for visualization. The performance metrics on the test set (95% confidence interval) were as follows: F1 score, 0.77 (0.57-0.91); precision, 0.67 (0.44-0.88); specificity, 0.45 (0.15-0.75); sensitivity, 0.92 (0.73-1.00); and AUC, 0.63 (0.52-0.86). MIL-AI performance was more sensitive (92% vs. 31%) but less specific (45% vs. 64%) than the ophthalmologist's performance. Conclusions: The MIL-AI predicts with high sensitivity the eyes that may have post-DMEK graft detachment requiring rebubbling. Larger-scale clinical trials are warranted to validate the model. Translational Relevance: MIL-AI models represent an opportunity for implementation in routine DMEK suitability screening.

Low-Dose Propofol with Peribulbar Anaesthesia for Cataract Surgery.

In this paper, we investigate the effect of sedation using low-dose propofol on patient reported outcome measures (PROMS) in patients undergoing cataract surgery. This is a randomised, single-blinded observational prospective study. Patients undergoing elective cataract surgery using peribulbar anaesthesia over consecutive cataract lists were selected for this trial. Patients were randomised to receive either no sedation or low-dose propofol (20 to 30 mg followed by 10 mg increments until the patient developed slurred speech alone) prior to the administration of local anaesthesia. Pain, satisfaction, anxiety, needle recall, pulse, and blood pressure (BP) were measured. A total of 97 patients were included, 50 of whom received propofol. There were 4 senior surgeons and anaesthetists. There were no ocular or systemic complications and all patients had uncomplicated surgery. Anxiety (p = 0.026), needle recall (p < 0.001), difference in systolic BP (p = 0.043), and pulse (p = 0.046) were dependent on patient age (p < 0.001) and the use of propofol (p = 0.007). Lower pain was associated with propofol (p = 0.008), as well as lower anxiety (p = 0.002), and increased patient age (p = 0.014). The administration of propofol was significantly associated with lower needle recall (p < 0.001), pre- to post-operative difference in systolic BP (p = 0.029), and mean BP (p = 0.044). Low-dose propofol given immediately prior to administration of local anaesthesia was associated with reduced pain and needle recall, as well as lower BP.

Antimicrobial resistance in topical treatments for microbial keratitis: protocol for a systematic review and meta-analysis.

INTRODUCTION: There is evidence for increased resistance against the antimicrobials used to treat keratitis. This review aims to provide global and regional prevalence estimates of antimicrobial resistance in corneal isolates and the range of minimum inhibitory concentrations (MIC) with their associated resistance breakpoints. METHODS AND ANALYSIS: We report this protocol following Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols guidelines. We will conduct an electronic bibliographic search in MEDLINE, EMBASE, Web of Science and the Cochrane Library. Eligible studies will report in any language data for the resistance or MIC for antimicrobials against bacterial, fungal or amoebic organisms isolated from suspected microbial keratitis. Studies that only report on viral keratitis will not be included. There will be no time restrictions on the date of publication. Screening for eligible studies, assessment of risk of bias and data extraction will be conducted by two reviewers independently, using predefined inclusion criteria and prepiloted data extraction forms. We will resolve disagreements between the reviewers by discussion and, if required, a third (senior) reviewer will arbitrate. We will assess the risk of bias using a tool validated in prevalence studies. The certainty of the evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. Pooled proportion estimates will be calculated using a random-effects model. Heterogeneity will be assessed using the I2 statistic. We will explore differences between Global Burden of Disease regions and temporal trends. ETHICS APPROVAL AND DISSEMINATION: Ethics approval is not required as this is a protocol for a systematic review of published data. The findings of this review will be published in an open-access, peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023331126.

Artificial Intelligence Based Analysis of Corneal Confocal Microscopy Images for Diagnosing Peripheral Neuropathy: A Binary Classification Model.

Diabetic peripheral neuropathy (DPN) is the leading cause of neuropathy worldwide resulting in excess morbidity and mortality. We aimed to develop an artificial intelligence deep learning algorithm to classify the presence or absence of peripheral neuropathy (PN) in participants with diabetes or pre-diabetes using corneal confocal microscopy (CCM) images of the sub-basal nerve plexus. A modified ResNet-50 model was trained to perform the binary classification of PN (PN+) versus no PN (PN-) based on the Toronto consensus criteria. A dataset of 279 participants (149 PN-, 130 PN+) was used to train (n = 200), validate (n = 18), and test (n = 61) the algorithm, utilizing one image per participant. The dataset consisted of participants with type 1 diabetes (n = 88), type 2 diabetes (n = 141), and pre-diabetes (n = 50). The algorithm was evaluated using diagnostic performance metrics and attribution-based methods (gradient-weighted class activation mapping (Grad-CAM) and Guided Grad-CAM). In detecting PN+, the AI-based DLA achieved a sensitivity of 0.91 (95%CI: 0.79-1.0), a specificity of 0.93 (95%CI: 0.83-1.0), and an area under the curve (AUC) of 0.95 (95%CI: 0.83-0.99). Our deep learning algorithm demonstrates excellent results for the diagnosis of PN using CCM. A large-scale prospective real-world study is required to validate its diagnostic efficacy prior to implementation in screening and diagnostic programmes.