Herpes simplex keratitis (HSK) is a common, potentially blinding condition characterised by recurrent infections of the cornea, seen by both general ophthalmologists and corneal specialists. ...Successful treatment of recurrences reduces disease duration, prevents progressive corneal scaring leading to vision loss and reduces risk of further recurrences. In this review we discuss the relative advantages of the diagnostic laboratory investigations including polymerase chain reaction, viral culture and fluorescence-based immunohistochemistry. We review treatment strategies in selected aspects of HSK and discuss the management options in cases not responding to treatment.
We report two cases of endothelial corneal allograft rejection following immunisation with SARS-CoV-2 messenger RNA (mRNA) vaccine BNT162b2 and describe the implications for management of transplant ...recipients postvaccination for COVID-19.
A 66-year-old woman with Fuchs endothelial corneal dystrophy (FECD) and a unilateral Descemet's membrane endothelial keratoplasty (DMEK) transplant received COVID-19 mRNA vaccine BNT162b2 14 days post-transplant. Seven days later, she presented with symptoms and signs of endothelial graft rejection. An 83-year-old woman with bilateral DMEK transplants for FECD 3 and 6 years earlier developed simultaneous acute endothelial rejection in both eyes, 3 weeks post second dose of COVID-19 mRNA vaccine BNT162b2. Rejection in both cases was treated successfully with topical corticosteroids.
We believe this is the first report of temporal association between corneal transplant rejection following immunisation against COVID-19 and the first report of DMEK rejection following any immunisation. We hypothesise that the allogeneic response may have been initiated by the host antibody response following vaccination. Clinicians and patients should be aware of the potential of corneal graft rejection associated with vaccine administration and may wish to consider vaccination in advance of planned non-urgent keratoplasties. Patients should be counselled on the symptoms and signs that require urgent review to allow early treatment of any confirmed rejection episode.
Cognitive faculties such as imagination, planning, and decision-making entail the ability to represent hypothetical experience. Crucially, animal behavior in natural settings implies that the brain ...can represent hypothetical future experience not only quickly but also constantly over time, as external events continually unfold. To determine how this is possible, we recorded neural activity in the hippocampus of rats navigating a maze with multiple spatial paths. We found neural activity encoding two possible future scenarios (two upcoming maze paths) in constant alternation at 8 Hz: one scenario per ∼125-ms cycle. Further, we found that the underlying dynamics of cycling (both inter- and intra-cycle dynamics) generalized across qualitatively different representational correlates (location and direction). Notably, cycling occurred across moving behaviors, including during running. These findings identify a general dynamic process capable of quickly and continually representing hypothetical experience, including that of multiple possible futures.
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•Firing across hippocampal neurons can regularly “take turns” (cycle) every ∼125 ms•Cycle firing is seen at single-cell, cell-pair, and population levels•Cycle firing encodes hypothetical experience, including multiple possible futures•Cycle coding generalizes across representational correlates, implying common process
Imagination, planning, and decision-making require the ability to generate representations of hypothetical experience. Kay et. al. find that neurons in the rat hippocampus can represent alternative hypothetical scenarios both regularly and quickly (every ∼125 ms). Further, the underlying activity has a temporal structure that is equivalent across different representational correlates (location and direction), implying a common process.
The diagnosis and management of keratoconus in the paediatric age group presents additional challenges to those encountered in adults. The most significant of these, encountered in some young ...patients, are delayed presentation of unilateral disease, more advanced disease at diagnosis, difficulty in obtaining reliable corneal imaging, faster rates of disease progression and challenges in contact lens management. The stabilisation effect of corneal cross-linking (CXL), more extensively studied in adults with randomised trials and long-term follow-up, has been much less rigorously examined in children and adolescents. The high heterogeneity of published studies in younger patients, particularly in the choice of tomography parameters designated as primary outcome measures and the definitions of progression, indicates that improved standardisation for future studies on CXL will be necessary. There is no evidence that corneal transplant outcomes in young patients are poorer than those in adults. This review provides a current perspective on the optimal diagnosis and treatment of keratoconus in children and adolescents.
To compare Kaplan-Meier survival curves and funnel plots for the audit of surgeon-specific corneal transplantation outcomes.
We obtained data on all patients with Fuchs endothelial dystrophy (FED) ...receiving a first corneal transplant in one eye between January 2012 and December 2017. We produced 2-year Kaplan-Meier graft survival curves to compare a simulated individual surgeon's graft survival rate to national pooled data. We used funnel plots to compare all surgeon outcomes to the national graft survival rate with superimposed 95 and 99.8% confidence limits. We defined an outlier as a surgeon who performed ≥10 transplants and had graft survival below the 99.8% national lower limit. To assess the effect of the surgeon case mix, we also compared unadjusted and risk-adjusted graft survival rates.
There were 3616 first corneal transplants for FED patients with complete data, performed or overseen by 196 surgeons. The 2-year national graft survival rate was 88%. The median change from the unadjusted to the risk-adjusted graft survival rate for individual surgeons was 0% (IQR: 0%- -2%). Of the 108 surgeons who had performed ≥10 transplants, we identified two outliers based on the unadjusted graft survival funnel plot, compared to four outliers based on the risk-adjusted graft survival funnel plot.
Funnel plots provide a visually accessible method for comparing individual graft survival rates to the national rate. Risk-adjustment accounts for clinical factors, and this has advantages for audit and clinical governance.
Congenital corneal anaesthesia (CCA) is an uncommon cause of corneal ulceration in young patients, with a reported poor visual prognosis. We correlated clinical findings in patients with CCA with ...corneal sub-basal nerve plexus (SBNP) morphology and dendritiform cell density (DCD) on confocal microscopy.
A prospective, case-control study was conducted at a referral clinic. History includied presenting features in patients with CCA, clinical course and examination findings. Differences in SBNP morphology and DCD on
confocal microscopy (IVCM) were compared in cases and control subjects with healthy corneas.
Eight patients with CCA were examined, of which three had a diagnosis of familial dysautonomia. Age at initial diagnosis of corneal disease ranged from infancy to 22 years, the most common presentation being corneal ulceration. All patients with CCA except one with optic neuropathy had corrected visual acuity 6/18 (logMAR 0.35) or better in at least one eye. Measured corneal sensation was minimal in all patients. Major abnormalities were found on confocal microscopy in all patients with CCA, whether or not inherited, including statistically significant reduction in SBNP nerve fibre density, fibre length and branch density. Increased DCD in superficial cornea was found in all patients with CCA.
Good visual acuity can be maintained in eyes with corneal anaesthesia present from birth. IVCM provides direct evidence of a morphological correlate for measured corneal anaesthesia. Increased DCD may indicate an enhanced role for innate immune cells in superficial cornea in protection of the anaesthetic ocular surface.
Purpose To compare national outcomes of endothelial keratoplasty (EK) and penetrating keratoplasty (PK) during comparable 6-year periods. Design Prospective cohort study of national registry data. ...Methods setting : United Kingdom National Transplant Registry, 2000 through 2011, inclusive. patient population : All United Kingdom patients undergoing first EK (n = 2074) for Fuchs endothelial dystrophy or pseudophakic bullous keratopathy from January 2006 through December 2011. Comparison cohort of patients undergoing first PK (n = 2622, same indications, January 2000 through December 2005). observation procedure : Year of surgery, surgeon and center experience, corneal diagnosis, donor factors, patient factors, and surgical risk factors were analyzed against graft survival and visual outcomes. Results For both Fuchs endothelial dystrophy and pseudophakic bullous keratopathy, EK achieved better average best-corrected acuity and lower refractive error. For both groups, graft failure was significantly higher for EK than PK. EK failure in Fuchs endothelial dystrophy was associated with center experience (hazard ratio HR, 2.3; P < .0001), donor endothelial density (HR, 1.8; P = .01), glaucoma at time of surgery (HR, 2.1; P = .003), and donor age older than 75 years (HR, 1.3; P = .05). EK failure in pseudophakic bullous keratopathy was associated with center experience of fewer than 15 cases (HR, 2.0; P < .0001) and glaucoma at time of surgery (HR, 1.7; P = .002). Conclusions Prospective national registry data for EK showed higher graft failure than is seen in PK or in retrospective case series of EK. Higher failure rates may be acceptable given established benefits of the procedure, including lower refractive error, structural globe integrity, and faster visual recovery. Center experience influenced EK survival more than surgeon experience, and overall surgical outcomes may be improved by standardized techniques and support within experienced units.
To investigate the attitudes and practice of corneal specialists if patients with keratoplasty sought advice regarding common vaccinations and risk for potential graft rejection.
An online ...questionnaire was posted on the Kera-net listserv and the EuCornea Web site in early 2020. Attitudes toward vaccinations and keratoplasty were obtained. Decision making for common keratoplasty (endothelial keratoplasty, deep anterior lamellar keratoplasty, and penetrating keratoplasty) scenarios at early and late time points was explored regarding the herpes zoster and influenza vaccines.
There were 142 respondents: 51.1% (70/137) specifically advise their patients with keratoplasty to get all vaccinations; 19.7% (27/137) stated clinical experience of a vaccine-associated rejection episode; 42.2% (57/135) were unaware of any such cases; and 64% (27/42) of those concerned would recommend delay if within 3 months of transplant surgery, recent corneal infection, or a recent rejection episode. The 2245 total responses to 18 clinical scenarios demonstrated wide variability in management of grafts in the setting of vaccination. Generally, 45.9% would not alter management, 26.2% would increase frequency of topical steroids, and 22.2% would recommend delay to vaccinations. Increased concern was expressed with recent surgery, live zoster vaccine and higher-risk penetrating keratoplasty scenarios.
Nearly half of the respondents do not alter management in the setting of keratoplasty and zoster and/or influenza vaccinations. Anecdotal rejection episodes possibly associated with vaccinations were reported by some. Vaccine-related rejection has not been shown in higher-level research, but that has not eliminated clinical concerns. Prospective research into the true vaccine-related risks in keratoplasty is necessary if evidence-based management guidelines are to be developed or definitive reassurance provided.
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