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Background/aims: This systematic review critically evaluated peer-reviewed publications describing morphological features consistent with, or using terms related to, a 'neuroma' or 'microneuroma' in the human cornea using laser-scanning in vivo confocal microscopy (IVCM)., Methods: The review was prospectively registered on PROSPERO (CRD42020160038). Comprehensive literature searches were performed in Ovid MEDLINE, Ovid Embase and the Cochrane Library in November 2019. The review included primary research studies and reviews that described laser-scanning IVCM for examining human corneal nerves. Papers had to include at least one of a pre-specified set of keyword stems, broadly related to neuromas and microneuromas, to describe a corneal nerve feature., Results: Twenty-five papers (20 original studies; 5 reviews) were eligible. Three original studies evaluated corneal nerve features in healthy eyes. Most papers assessed corneal nerves in ocular and systemic conditions; seven studies did not include a control/comparator group. There was overlap in terminology used to describe nerve features in healthy and diseased corneas (eg, bulb-like/bulbous, penetration, end/s/ing). Inspection of IVCM images within the papers revealed that features termed 'neuromas' and 'microneuromas' could potentially be physiological corneal stromal-epithelial nerve penetration sites. We identified inconsistent definitions for terms, and limitations in IVCM image acquisition, sampling and/or reporting that may introduce bias and lead to inaccurate representation of physiological nerve characteristics as pathological., Conclusion: These findings identify a need for consistent nomenclature and definitions, and rigorous IVCM scanning and analysis protocols to clarify the prevalence of physiological, as opposed to pathological, corneal nerve features., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: The limbus is a remarkable anatomical site endowed with specialised functions to ensure corneal health and transparency, which is essential for exquisite vision. Cell types that contribute to homeostasis and the disease-free state of the cornea include epithelial and stromal stem cells, and antigen-presenting dendritic cells (DCs). DCs are found throughout the corneal epithelium and stroma, but the protein markers that discriminate between cells in different locations have not been properly identified. S100 proteins are expressed in normal and diseased ocular surfaces and are implicated in DC differentiation., Methods: This study used transplant quality human cadaveric donor corneas (n=6) and immunofluorescence to determine the spatial distributions of S100A8 (A8) and S100A9 (A9), and to characterise the cell types expressing these proteins., Results: A8-expressing and A9-expressing cells were predominantly confined to the limbal stroma and represented 0.25%±0.1% and 0.39%±0.1%, respectively, of the total stromal cell population. They were phenotyped as CD45(+)/HLA-DR(+)/CD11c(+), markers characteristic of DCs. Interestingly, A8 and A9 immunoreactivity was only associated with stromal DCs, but not those entrenched in the epithelium., Conclusions: A8 and A9 expression may distinguish between subpopulations of DC that reside in different regions of the human cornea and may influence their maturation status., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Pterygium is a common, benign fibrovascular disease of the human ocular surface that can impair vision and restrict ocular mobility if not removed. Surgical excision is the most common form of treatment; however, non-surgical therapeutics are being developed, which target the angiogenic component of this disease. Nestin is a class VI intermediate filament protein expressed in neuroepithelium with an emerging role in angiogenesis and tumourigenesis. Given the tumour-like and angiogenic features of pterygia, we postulated that nestin partakes in its development., Methods and Results: Formalin-fixed, paraffin-embedded pterygia and donor-matched conjunctiva (n=22) were obtained, sectioned and stained for nestin by immunohistochemistry and immunofluorescence. Immunoreactivity for nestin was semi-quantified and microvessel density counted. Significantly, higher nestin expression was identified in pterygium epithelial cells and blood vessels compared with matched normal conjunctiva. Interestingly, a high proportion of the pterygium specimens displayed nuclear staining for nestin within the basal and suprabasal epithelium. Immunofluorescence was used to simultaneously detect nestin in CD31(+) blood vessels; however, this protein was absent from Lyve-1(+) lymphatic vessels. In addition, blood and lymphatic vessel density was significantly higher in pterygia compared with corresponding control conjunctiva., Conclusions: These results demonstrate for the first time the expression of nestin in the pterygium vasculature and indicate that this protein may play a central role in the angiogenic response, which characterises this disease. Targeting nestin pharmacologically could be considered as an alternative or adjuvant therapeutic strategy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The pathogenesis of acute and recurrent anterior uveitis is poorly understood. Here, recent evidence is presented for the hypothesis that this disease may be associated with activation of receptors of the innate immune system, such as Toll-like receptors, by pathogen associated molecule patterns, such as lipopolysaccharide, derived from triggering gram negative bacteria. Acute anterior uveitis results in ocular tissue damage and the release of endogenous molecules (damage associated molecular patterns), such as heat shock proteins and S100 proteins that can also activate Toll-like receptors and thus perpetuate or reactivate intraocular inflammation.

Background: This study was initiated after observation of some intriguing epithelial growth properties of contact lenses used as a bandage for patients after pterygium surgery., Aim: To determine the efficacy of culturing human ocular surface epithelial cells on therapeutic contact lenses in autologous serum with a view of using this system to transfer epithelial cells to patients with persistent corneal or limbal defects., Methods: Excess graft tissue resected from patients undergoing pterygium surgery (n = 3) consisting of limbal epithelium was placed on siloxane-hydrogel contact lenses (lotrafilcon A and balafilcon A). Limbal explants were cultured in media with 10% autologous serum. Morphology, proliferative capacity and cytokeratin profile were determined by phase contrast, light and electron microscopy, and immunohistochemical analysis., Results: Lotrafilcon A contact lenses sustained proliferation and migration from limbal tissue. Cells became confluent after 10-14 days and consisted of 2-3 layers with a corneal phenotype (CK3(+)/CK12(+)/CK19(-)) and a propensity to proliferate (p63(+)). Electron microscopy showed microvilli on the apical surface with adhesive projections, indicating that these cells were stable and likely to survive for a long term. Growth was not observed from limbal explants cultured on balafilcon A contact lenses., Conclusion: A method for culturing human ocular surface epithelium on contact lenses that may facilitate expansion and transfer of autologous limbal epithelial cells while avoiding the risks associated with transplanting allogeneic tissue has been developed. This technique may be potentially useful for the treatment of patients with limbal stem cell deficiency.