Epithelium-on versus epithelium-off corneal collagen crosslinking for keratoconus: a systematic review and meta-analysis.

PURPOSE: Corneal collagen crosslinking (CXL) is the primary treatment for progressive keratoconus which has a significant impact on vision and quality of life. Our study aimed to compare the efficacy and safety of epithelium-on versus epithelium-off CXL to treat keratoconus. METHODS: We searched PubMed, Medline, Embase, Web of Science, and Scopus databases. We included studies that compared standard epithelium-off with epithelium-on CXL. The primary outcome measures were changes in corrected distance visual acuity (CDVA) and maximum keratometry (Kmax), and the secondary outcomes were uncorrected distance visual acuity (UDVA), central corneal thickness (CCT), and adverse events. A meta-analysis was performed on the primary and secondary outcomes based on the weighted mean differences between baseline to 12-month follow-up. RESULTS: The search retrieved 887 publications with 27 included in the systematic review. A total of 1622 eyes (1399 patients; age 25.51 ± 4.02 years) were included in comparisons of epithelium-off to epithelium-on CXL in keratoconus. Epithelium-off CXL treated 800 eyes and epithelium-on CXL for 822 eyes. At 12-month follow-up, CDVA and Kmax showed no significant difference between the epithelium-off and epithelium-on CXL. The secondary outcomes showed that UDVA was better in epithelium-off CXL (- 0.11D, 95% CI - 0.12, - 0.1; p < 0.001) and there was more thinning in CCT in epithelium-off CXL (- 3.23 µm, 95% CI - 4.64, - 1.81; p <0.001). CONCLUSION: Epithelium-off and epithelium-on CXL were both effective to treat progressive keratoconus. Further research is needed to compare the long-term outcomes and safety of both CXL protocols for adaptation into clinical practice.

Spontaneous Extrusion of a Conjunctivolith Containing Herpes Virus Confirmed by Electron Microscopy and Energy Dispersive Spectroscopy.

: This report describes the spontaneous extrusion from between the eyelids of a presumed conjunctivolith in a patient with resolving severe herpes zoster ophthalmicus. A 57-year-old man presented for ophthalmologic assessment and management due to severe left herpes zoster ophthalmicus. At one subsequent ophthalmologic assessment, a conjunctivolith spontaneously egressed the lateral commissure of the OS when the lateral fornix was inspected. The conjunctivolith was retrieved from the floor of the consulting room. Electron microscopic analysis and energy dispersive spectroscopy was undertaken to determine its composition. Scanning electron microscopy showed that the conjunctivolith was composed of carbon, calcium, and oxygen. Transmission electron microscopy diagnosed Herpes virus within the conjunctivolith. Conjunctivoliths, or possible lacrimal gland stones, are a very rare phenomenon, and their etiology is currently unclear. In this case, there was likely to have been an association between herpes zoster ophthalmicus and the conjunctivolith.

Deep neural network-estimated age using optical coherence tomography predicts mortality.

The concept of biological age has emerged as a measurement that reflects physiological and functional decline with ageing. Here we aimed to develop a deep neural network (DNN) model that predicts biological age from optical coherence tomography (OCT). A total of 84,753 high-quality OCT images from 53,159 individuals in the UK Biobank were included, among which 12,631 3D-OCT images from 8,541 participants without any reported medical conditions at baseline were used to develop an age prediction model. For the remaining 44,618 participants, OCT age gap, the difference between the OCT-predicted age and chronological age, was calculated for each participant. Cox regression models assessed the association between OCT age gap and mortality. The DNN model predicted age with a mean absolute error of 3.27 years and showed a strong correlation of 0.85 with chronological age. After a median follow-up of 11.0 years (IQR 10.9-11.1 years), 2,429 deaths (5.44%) were recorded. For each 5-year increase in OCT age gap, there was an 8% increased mortality risk (hazard ratio [HR] = 1.08, CI:1.02-1.13, P = 0.004). Compared with an OCT age gap within ± 4 years, OCT age gap less than minus 4 years was associated with a 16% decreased mortality risk (HR = 0.84, CI: 0.75-0.94, P = 0.002) and OCT age gap more than 4 years showed an 18% increased risk of death incidence (HR = 1.18, CI: 1.02-1.37, P = 0.026). OCT imaging could serve as an ageing biomarker to predict biological age with high accuracy and the OCT age gap, defined as the difference between the OCT-predicted age and chronological age, can be used as a marker of the risk of mortality.

The Role of Inflammation in Age-Related Macular Degeneration-Therapeutic Landscapes in Geographic Atrophy.

Age-related macular degeneration (AMD) is the leading cause of vision loss and visual impairment in people over 50 years of age. In the current therapeutic landscape, intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies have been central to the management of neovascular AMD (also known as wet AMD), whereas treatments for geographic atrophy have lagged behind. Several therapeutic approaches are being developed for geographic atrophy with the goal of either slowing down disease progression or reversing sight loss. Such strategies target the inflammatory pathways, complement cascade, visual cycle or neuroprotective mechanisms to slow down the degeneration. In addition, retinal implants have been tried for vision restoration and stem cell therapies for potentially a dual purpose of slowing down the degeneration and restoring visual function. In particular, therapies focusing on the complement pathway have shown promising results with the FDA approved pegcetacoplan, a complement C3 inhibitor, and avacincaptad pegol, a complement C5 inhibitor. In this review, we discuss the mechanisms of inflammation in AMD and outline the therapeutic landscapes of atrophy AMD. Improved understanding of the various pathway components and their interplay in this complex neuroinflammatory degeneration will guide the development of current and future therapeutic options, such as optogenetic therapy.

The association between retinal microvasculature derived from optical coherence tomography angiography and systemic factors in type 2 diabetics.

Aims: To investigate the correlation between the retinal microvasculature using optical coherence tomography angiography (OCTA) and systemic factors in type 2 diabetes mellitus (T2DM) patients. Methods: This cross-sectional study obtained OCTA data from patients with T2DM administered at hospital and referred to ophthalmic services. Patient data about demographics, comorbid conditions, and blood biomarkers were extracted from electronic medical records. Data from OCTA scans obtained by CIRRUS HD-OCT Model 5,000 were obtained. Vessel density (VD) and perfusion density (PD) within the superficial capillary plexus, and foveal avascular zone (FAZ) area were automatically segmented. These parameters were tested for their correlations with systemic factors by univariate and multivariable linear regression analyses. Results: A total of 144 T2DM patients (236 eyes) were available for analysis, with mean age of 53.6 (SD = 10.34) and 56.9% were male. Chronic kidney disease, cardiovascular disease, increased serum creatinine (Scr), red blood cell count (RBC), platelets (PLT), apolipoprotein B (APOB), and decreased urine albumin to creatinine ratio (UACR) were significantly associated with lower VD and PD (all p < 0.013). UACR and triglyceride (TRIG) were significantly correlated with FAZ area (all p < 0.017). In multivariate analyses, PLT, eGFR, and APOB were independent risk factors for retinal rarefaction, and UACR was a significant predictor of FAZ area. Conclusion: We found several systemic risk factors, such as PLT, renal function and lipid profiles were associated with PD, VD, and FAZ area among Chinese T2DM patients.

Myopic maculopathy among Chinese children with high myopia and its association with choroidal and retinal changes: the SCALE-HM study.

AIMS: To investigate myopic maculopathy in Chinese children with high myopia and its association with choroidal and retinal changes. METHODS: This cross-sectional study included Chinese children aged 4-18 years with high myopia. Myopic maculopathy was classified by fundus photography and retinal thickness (RT) and choroidal thickness (ChT) in the posterior pole were measured by swept-source optical coherence tomography. A receiver operation curve was used to determine the efficacy of fundus factors in classifying myopic maculopathy. RESULTS: In total, 579 children aged 12.8±3.2 years with a mean spherical equivalent of -8.44±2.20 D were included. The proportions of tessellated fundus and diffuse chorioretinal atrophy were 43.52% (N=252) and 8.64% (N=50), respectively. Tessellated fundus was associated with a thinner macular ChT (OR=0.968, 95% CI: 0.961 to 0.975, p<0.001) and RT (OR=0.977, 95% CI: 0.959 to 0.996, p=0.016), longer axial length (OR=1.545, 95% CI: 1.198 to 1.991, p=0.001) and older age (OR=1.134, 95% CI: 1.047 to 1.228, p=0.002) and less associated with male children (OR=0.564, 95% CI: 0.348 to 0.914, p=0.020). Only a thinner macular ChT (OR=0.942, 95% CI: 0.926 to 0.959, p<0.001) was independently associated with diffuse chorioretinal atrophy. When using nasal macular ChT for classifying myopic maculopathy, the optimal cut-off value was 129.00 µm (area under the curve (AUC)=0.801) and 83.85 µm (AUC=0.910) for tessellated fundus and diffuse chorioretinal atrophy, respectively. CONCLUSION: A large proportion of highly myopic Chinese children suffer from myopic maculopathy. Nasal macular ChT may serve as a useful index for classifying and assessing paediatric myopic maculopathy. TRIAL REGISTRATION NUMBER: NCT03666052.

Oxygen in Corneal Collagen Crosslinking to Treat Keratoconus: A Systematic Review and Meta-Analysis.

PURPOSE: Keratoconus is a disorder that results in visual loss from increased corneal high-order aberrations and irregular astigmatism and reduces quality of life. The primary treatment for progressive keratoconus is crosslinking (CXL). Recently, it has been suggested that oxygen enhances the type II photodynamic reaction of CXL that is oxygen dependent. Our study investigated the effect of increased oxygen availability in epithelium-on CXL on visual acuity and corneal curvature. METHODS: We searched PubMed, EMBASE, Medline, Web of Science, and Scopus databases on November 3, 2021. We included studies that reported increased oxygen availability during CXL in patients with keratoconus published within the last 10 years. A meta-analysis on the primary outcomes, maximum keratometry, and corrected distance visual acuity, was conducted. RESULTS: The search yielded 108 publications which were screened and assessed for eligibility. Six studies were included in the systematic review and 5 studies were included in our meta-analysis of the outcomes of increased oxygen availability in accelerated CXL. The meta-analysis on data after 6 months of follow-up found a significant decrease in mean maximum keratometry of 1.2 diopter (95% confidence interval: 0.2-2.3; P =0.02) and an improvement in mean corrected distance visual acuity by 0.08 logMAR (95% confidence interval, 0.02-0.13; P =0.01). There were no serious adverse events reported. CONCLUSIONS: Increasing oxygen during epithelium-on CXL improved visual acuity and produced corneal flattening without any serious adverse events in patients with keratoconus. The demarcation line depth was significantly higher with oxygen compared to the control group. Further data are required with a control group and long-term follow-up across a range of CXL protocols for implementation into standard clinical practice.

Daily Patterns of Accelerometer-Measured Movement Behaviors in Glaucoma Patients: Insights From UK Biobank Participants.

PURPOSE: The purpose of this study is to compare daily patterns of accelerometer-measured movement behaviors between glaucoma patients and those without glaucoma. METHODS: From 2013 to 2015, 106,053 UK Biobank participants took part in a 7-day accelerometer test. Based on established algorithms, continuous accelerometer data were classified into 4 movement behaviors: moderate to vigorous physical activity (MVPA), light physical activity, sedentary behaviors, and sleep. Glaucoma and other covariates were defined according to baseline assessments and inpatient diagnosis records. Negative binomial regression models were used to compare daily patterns of movement behaviors between glaucoma patients and those without glaucoma. RESULTS: Accelerometer data from 1262 glaucoma patients and 81,551 participants without glaucoma were included. Compared with participants without glaucoma, glaucoma patients spent 4.7% less time on MVPA in multivariable models [mean=28.3 vs 31.4 min/d; incidence-rate ratio (IRR) 0.953, 95% confidence interval (CI): 0.910-0.998; P=0.044], which was mainly attributed to the decreased MVPA time during 18:00-23:59 (IRR=0.863, Bonferroni-corrected 95% CI: 0.768-0.970; P=0.002). Subgroup analyses indicated that compared with those with normal body mass index, the decreased MVPA time was more pronounced in participants with overweight and obesity (IRR=0.912, Bonferroni-corrected 95% CI: 0.851-0.978; P for interaction=0.007). No significant association was found between glaucoma and time spent on other movement behaviors including light physical activity, sedentary behaviors, and sleep. CONCLUSIONS: Daily patterns of movement behaviors were significantly changed in glaucoma patients. Compared with those without glaucoma, glaucoma patients spent less time on MVPA, especially in the evening.

Flucloxacillin and paracetamol induced pyroglutamic acidosis.

A 75-year-old woman was admitted to a regional hospital with an acute kidney injury (AKI) and nausea on a background of recent treatment for Staphylococcus aureus bacteraemia secondary to pneumonia. The treatment thereof resulted in a high anion gap metabolic acidosis (HAGMA). The pneumonia was initially treated with intravenous piperacillin and tazobactam and the patient transferred to a tertiary hospital. There, the diagnosis of S. aureus bacteraemia secondary to a pulmonary source was confirmed and treatment was changed to intravenous flucloxacillin and the patient was discharged to hospital in the home (HITH is a service that allows short-term healthcare at home to be provided to people who would otherwise need to be in hospital) to complete the antibiotic course. Five weeks after commencing flucloxacillin, the patient was referred back to hospital with nausea and worsening kidney function with an associated significant HAGMA. The patient has a background of chronic kidney disease and chronic back pain for which she was taking long-term paracetamol. The HAGMA was determined to be due to a pyroglutamic acidosis (PGA), deemed secondary to the combined use of paracetamol and flucloxacillin. This was subsequently confirmed with a plasma pyroglutamic acid concentration level of 7467 µmol/L (reference range 20-50 µmol/L) and a urinary level of 1700 mmol/mol creatinine (<110 mmol/mol creatinine). To our knowledge, this is the highest plasma and urinary levels published to date. Furthermore, considering the common use of paracetamol and penicillins, it is important to recognise HAGMA as a potential complication of co-administration of paracetamol and iso-oxylopenicillin. The HAGMA resolved after cessation of flucloxacillin despite the continuation of paracetamol and without administration of N-acetylcysteine. PGA-related HAGMA appears to be a unique potential side effect of iso-oxylopenicillin rather than other beta-lactams.