Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID

Background/AimsLong COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID.MethodsForty subjects who had recovered from COVID-19 and 30 control participants were included in this cross-sectional comparative study undertaken at a university hospital. All patients underwent assessment with the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia questionnaires, and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), and total, mature and immature DC density.ResultsThe mean time after the diagnosis of COVID-19 was 3.7±1.5 months. Patients with neurological symptoms 4 weeks after acute COVID-19 had a lower CNFD (p=0.032), CNBD (p=0.020), and CNFL (p=0.012), and increased DC density (p=0.046) compared with controls, while patients without neurological symptoms had comparable corneal nerve parameters, but increased DC density (p=0.003). There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD (ρ=−0.436; p=0.005, ρ=−0.387; p=0.038, respectively) and CNFL (ρ=−0.404; p=0.010, ρ=−0.412; p=0.026, respectively).ConclusionCorneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.

Clinicopathological correlations of sural nerve biopsies in TTR Val30Met familial amyloid polyneuropathy

Familial amyloid polyneuropathy with the substitution of methionine for valine at position 30 in the TTR gene is the most common type of hereditary transthyretin amyloidosis. Although several authors have previously reported a size-dependent fibre loss, predominantly involving unmyelinated and small-diameter myelinated fibres, the mechanisms of nerve fibre loss have not been fully understood. In this study, we establish the morphometric pattern of peripheral neuropathy in patients with familial amyloid polyneuropathy and asymptomatic mutation carriers in the biopsies from our archive and correlated the pathological findings with clinical features. A total of 98 patients with familial amyloid polyneuropathy and 37 asymptomatic mutation carriers (TTR Val30Met mutation), aged between 17 and 84 years, who underwent sural nerve biopsy between 1981 and 2017 at Centro Hospitalar Universitário do Porto were studied. Thirty-one controls were included for comparison. The median age at nerve biopsy was 26.0 [interquartile range = 23.5–39.5] years for asymptomatic mutation carriers, 45.0 [35.0–60.0] years for patients with familial amyloid polyneuropathy and 44.0 [30.0–63.0] years for controls. The median duration between nerve biopsy and symptoms’ onset was 7.0 [3.3–11.8] years (range: 1–27 years) in the asymptomatic carriers. Most patients were in an earlier disease stage (93% with a polyneuropathy disability scale ≤2). Patients had loss of small and myelinated fibres compared with both asymptomatic carriers and controls (P < 0.001), whereas asymptomatic carriers showed loss of small myelinated fibres when compared with controls (P < 0.05). The loss of myelinated fibres increased with disease progression (P < 0.001), and patients in more advanced clinical stage showed more frequent amyloid deposition in the nerve (P = 0.001). There was a positive correlation between large myelinated fibre density and time to symptoms’ onset in the asymptomatic carriers that developed early-onset form of the disease (r = 0.52, P < 0.01). In addition, asymptomatic carriers with amyloid deposition already present in sural nerve biopsies developed symptoms earlier than those with no amyloid (P < 0.01). In conclusion, this study confirms that the loss of small fibre size is an initial event in familial amyloid polyneuropathy, already present in asymptomatic gene carriers, starting several years before the onset of symptoms. We show for the first time that large myelinated fibres’ loss and amyloid deposition are pathological features that correlate independently with short period to the onset of symptoms for asymptomatic carriers that developed early-onset form of the disease. These findings are therapeutically relevant, as it would allow for a better interpretation of the role of disease-modifying agents in transthyretin familial amyloid polyneuropathy.

New optical fibres for high-capacity optical communications

Researchers are within a factor of 2 or so from realizing the maximum practical transmission capacity of conventional single-mode fibre transmission technology. It is therefore timely to consider new technological approaches offering the potential for more cost-effective scaling of network capacity than simply installing more and more conventional single-mode systems in parallel. In this paper, I review physical layer options that can be considered to address this requirement including the potential for reduction in both fibre loss and nonlinearity for single-mode fibres, the development of ultra-broadband fibre amplifiers and finally the use of space division multiplexing.