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In primary SS (pSS), clinical features in SS can be divided into two facets: the patient perceived manifestations such as dryness, pain and fatigue, and the systemic manifestations. In the past decades, with efforts made by an international collaboration, consensual clinical indexes were developed for assessing both facets: one patient reported outcome, the EULAR SS Patients Reported Index (ESSPRI), and one activity index for systemic manifestations, the EULAR SS Disease Activity Index (ESSDAI). In addition, objective measures were developed to quantify the importance and consequence of ocular and oral dryness, few being specific of pSS. Work is ongoing to develop indexes combining all these approaches. Recent changes in the assessment of pSS patients, and the emergence of new targeted therapies, have put a greater emphasis on the design of clinical trials in pSS, and led for the first time to a positive randomized clinical trial. [ABSTRACT FROM AUTHOR]

Background: Non-infectious scleritis is a potentially sight-threatening condition in which the sclera, the white outer layer of the eye, becomes inflamed. Whilst scleritis can be infective, the majority of cases are due to non-infectious causes, often occurring in association with an underlying systemic autoimmune or auto-inflammatory condition. Thorough systemic work-up is crucial to identify disease aetiology and exclude infection; however, a significant proportion of disease remains idiopathic with the underlying cause unknown. Non-infectious scleritis is normally managed with systemic corticosteroid and immunosuppression, yet there is no widely agreed consensus on the most appropriate therapy, and no national or international guidelines exist for treatment of non-infectious scleritis. Methods: Standard systematic review methodology will be used to identify, select and extract data from comparative studies of pharmacological interventions used to treat patients with non-infectious scleritis. Searches of bibliographic databases (Cochrane Library, MEDLINE, CINAHL and EMBASE) and clinical trial registers will be employed. No restrictions will be placed on language or date of publication. Non-English articles will be translated where necessary. The primary outcome of interest will be disease activity measured by reduction in scleritis grading according to standardised grading systems. Secondary outcomes will include change in best corrected visual acuity, reduction in concurrent dose of systemic corticosteroid, time to treatment failure, adverse events and health-related quality of life. Risk of bias assessment will be conducted appropriate to each study design. Study selection, data extraction and risk of bias assessment will be completed by two reviewers independently. Data will be presented in a table and a narrative synthesis will be undertaken. Meta-analysis will be performed where methodological and clinical homogeneity exists. Subgroup and sensitivity analysis will be undertaken if appropriate. Discussion: Many studies have investigated the effectiveness of pharmacological agents used in the management of non-infectious scleritis. A systematic review is needed to collate and analyse this evidence. Findings of this systematic review will help guide ophthalmologists managing patients with non-infectious scleritis and may form the basis for evidence-based recommendations for future clinical practice and encourage standardisation of treatment protocols. Systematic review registration: PROSPERO CRD42019125198 [ABSTRACT FROM AUTHOR]

The article presents a study conducted to review the treatment of the glandular and systemic features of primary Sjögren's syndrome (pSS). Topics covered include the process of diagnosing pSS, the eligibility and exclusion criteria used in developing the guideline in treating and managing patients with pSS, and the guidelines for treatment of sicca manifestations, management of ocular manifestations of pSS, and miscellaneous treatments for dry eye and ocular complications.

The article presents a pragmatic and practical guideline for treating and managing adults with primary Sjörgen's syndrome (pSS). Topics covered include guidelines relating to the treatment of oral candida, management of salivary gland enlargement, and treatment of systemic disease. It also discusses guidelines relating to the management of pregnancy, and the assessment and management of lymphoma.

Objectives: Mucous membrane pemphigoid with ocular involvement (MMPO) is a sight-threatening autoimmune disease that may lead to severe conjunctival cicatrization and keratopathy. The peak age of onset is in the seventh decade, although the disease may also occur in younger patients (<60 years). This study was designed to evaluate the clinical features of young patients with MMPO and to assess the clinical outcome when compared with patients in the >70 age group. Design: Retrospective, comparative, interventional case series. Participants: Eighteen patients under the age of 60 years and 18 patients above the age of 70. Methods: Patients with documented MMPO were identified from the External Diseases Immunosuppression Database. Main Outcome Measures: Stage of disease (Foster, Mondino), visual acuity, and ocular complications (lid, conjunctival, corneal) were evaluated at presentation, the time when immunosuppression was commenced, and final follow-up. Disease progression, control of ocular inflammation with systemic immunosuppression, the incidence of mucocutaneous lesions, and surgical intervention were also assessed. Results: Patients in the 2 groups (young and classic age groups) were observed for 61 (range, 29–218) and 69 (range, 12–193) months, respectively (P = 0.94). Median ages at the start of immunosuppression were 48.7 (range, 29–60) and 77.6 (range, 71–85) years. Mucocutaneous involvement was more common in the young than in the classic age group (13 [72%], 7 [39%]; P < 0.05). Ocular staging (Mondino, Foster) at presentation, the start of immunosuppression, and final follow-up was more advanced in the younger patients. There was no statistical difference in visual acuity, individual ocular complications, or incidence of surgical intervention between the 2 groups throughout the course of the study. Conclusion: Younger patients with MMPO present with more severe ocular and systemic disease and, despite immunosuppression, progress more rapidly. [Copyright &y& Elsevier]

The sodium transporting capacity of the corneal endothelium is vital for preserving corneal transparency, and has traditionally been attributed to the endothelial pump transporting sodium and bicarbonate across the corneal endothelium, maintaining the cornea in a dehydrated state. Recent studies have shown that the enzyme, serum and glucocorticoid regulated kinase isoform 1 (SGK1), plays a pivotal role in the corticosteroid induction of epithelial sodium transport in tissues such as the distal nephron, through activation of the epithelial sodium channels (ENaC). This study was designed to identify whether these elements were present within the human cornea. In situ hybridisation studies were conducted on paraffin embedded sections from six human eyes, using in-house generated cRNA antisense probes for human SGK1 and ENaC subunits (α, β, γ), and confirmed expression of SGK1 and all ENaC subunits in the corneal endothelial cytoplasm. Although ENaC subunits were not demonstrated in the corneal epithelium, SGK1 mRNA was identified in the nuclear region of central basal cells of the corneal epithelium, and limbal epithelial cells. Minimal chromagen precipitation was seen in the Bowman''s membrane, corneal stroma, or Descemet''s membrane. Control experiments consisted of no antisense probe, competition of the labelled antisense cRNA probe by a 60-fold excess unlabelled antisense cRNA, and use of labelled sense cRNA probes, revealing minimal or no hybridisation signal throughout the corneal layers. These data define components of the mineralocorticoid regulatory pathways of sodium transport in human corneal endothelium, and provide evidence for an additional mechanism contributing to corneal transparency and the ‘metabolic’ sodium pump. [Copyright &y& Elsevier]

PurposeMethodsResultsConclusionPatients with sight-threatening inflammatory eye disease (IED) are maintained on systemic immunosuppression whilst in long-term clinical remission. There are no clear guidelines on the duration of remission before implementing treatment withdrawal. We present a real-world analysis on the use of immunosuppression in IED in long-term remission and consider strategies for withdrawal.Adult IED patients on systemic immunosuppression were categorised into four disease groups: Corneal Transplant Survival Strategies (CTSS), Ocular Surface Disease (OSD), Non-infectious Uveitis (NIU) and Scleritis. Patients with Behçet’s disease were excluded. Data on systemic immunosuppressants and biologics used; duration of treatment; reasons for drug discontinuation; disease activity/remission status; duration of clinical remission with an emphasis on patients who had been in remission for a minimum of 24 months were captured.Out of a total of 303 IED patients, 128 were on systemic immunosuppression with a clinical remission of their ocular disease for ≥24 months. The median duration of remission was 4–5 years with the longest duration of remission 22 years, and some patients on immunosuppression for up to 23 years. Sixty patients stopped at least one immunosuppressive agent without prior discussion with a health-care practitioner.Progressive conditions, such as cicatrising conjunctivitis may require lifelong immunosuppression, but patients with NIU and Scleritis and those on CTSS, immunosuppression withdrawal should be considered if they remain in remission for 2 years. Any patient stopping a medication should be contacted immediately for counselling. These data will better inform patients, encourage adherence and aide formal guideline development. [ABSTRACT FROM AUTHOR]

The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol [ 1 ]. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence (NICE) accreditation. [ABSTRACT FROM AUTHOR]

DearEditor, Bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV) are autoimmune blistering diseases that present with mucocutaneous blistering and erosions. 10 What is the best way to treat skin wounds in BP, MMP and/or PV, including how should blisters or erosions be best washed and managed and does treatment vary according to body site?. [Extracted from the article]

Worldwide lockdown reduced air pollution during the first phase of the COVID-19 pandemic. The relationship between exposure to ambient air pollution, digital display device use and dry eye symptoms amongst patients with severe ocular surface disease (OSD) were considered. Symptoms and air pollutant concentrations for three different time periods (pre, during and post COVID-19 lockdown) were analysed in 35 OSD patients who achieved an immunosuppression risk-stratification score > 3 fulfilling the UK Government criteria for 12-week shielding. OSDI symptoms questionnaire, residential postcode air pollution data obtained from the Defra Automated Urban and Rural monitoring network for concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter (PM) with diameters below 10 µm and 2.5 µm, and English Indices of Deprivation were analysed. Significant reductions in NO2 and NOx concentrations were observed between pre- and during-lockdown periods, followed by a reversal in the post-lockdown period. Changes were linked to the Living Environment outdoor decile. A 12% increase (p = 0.381) in symptomatology during-lockdown was observed that reversed post-lockdown by 19% (p = 0.144). OSDI scores were significantly correlated with hours spent on digital devices (r2 = 0.243) but not with air pollutant concentrations. Lockdown measures reduced ambient air pollutants whilst OSD symptomatology persisted. Environmental factors such as increased time indoors and use of bluescreen digital devices may have partly played a role. [ABSTRACT FROM AUTHOR]

Purpose: To report the long-term visual outcomes and biocompatibility of a single-piece hydrophilic acrylic intraocular lens (IOL) in patients with uveitis having cataract surgery. Setting: Tertiary referral center, Birmingham, United Kingdom. Design: Retrospective case review. Methods: The review included consecutive uveitis patients in whom phacoemulsification and acrylic IOL implantation was performed by the same surgeon. Outcomes measures are reported as rate/eye-year and included visual acuity and signs of bioincompatibility. Results: The review identified 171 eyes (140 patients; mean age 51 years [range 16 to 85 years]) with uveitis. The mean follow-up was 3.8 years (range 0.9 to 10.3 years). Signs of uveal bioincompatibility were found in 31 eyes, with visually insignificant deposits on the IOL in 17 eyes. The rate of uveal bioincompatibility was 0.06/eye-year. Signs of capsule bioincompatibility were found in 107 (63%) of 171 eyes (0.31/eye-year). Posterior capsule opacification was documented in 102 eyes (0.29/eye-year); neodymium:YAG laser capsulotomy was required in 31 eyes (0.05/eye-year). The rate of failure to maintain a 3 logMAR line improvement in corrected distance visual acuity (CDVA) was 0.08/eye-year; to maintain better than 0.3 logMAR, 0.15/eye-year; and to maintain either, 0.04/eye-year. At 1 year, 85% of eyes had a CDVA of better than 0.3 logMAR or maintained a 3 logMAR–line improvement. Eyes with preexisting macular or optic nerve disease had significantly worse visual outcomes. Conclusions: The long-term safety profile of the hydrophilic acrylic IOL was good in uveitis cases, leading to good visual outcomes and a low rate of vision-impairing uveal and capsule complications. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness and toxicity of a stepladder immunosuppression strategy, including the use of mycophenolate mofetil and combination therapy, in the treatment of ocular mucous membrane pemphigoid. Design: Retrospective, noncomparative, interventional case series. Participants: Two hundred twenty-three eyes of 115 patients. Methods: Patients with a diagnosis of ocular mucous membrane pemphigoid commencing immunosuppression between January 1994 and July 2005 were identified. A treatment episode was defined by the use of a particular therapy or combination of therapies. Main Outcome Measures: For each treatment episode, success of immunosuppressive therapy in controlling ocular inflammation was graded as a success (S), qualified success (QS), or failure (F). Initial and final visual acuities (VAs), stage of cicatrization (Foster, Mondino), grade of conjunctival inflammation, and side effects were recorded. Results: In 70% (80/115) of patients, inflammation was controlled by the end of the study. At least 6 months remission off treatment occurred in 16 patients (14%). Of the 388 treatment episodes, 50% were classified as S; 27%, QS; and 23%, F. The most successful therapies were based on cyclophosphamide (S, 69%; QS, 21%; F, 10%), followed by mycophenolate (S, 59%; QS, 22%; F, 19%), azathioprine (S, 47%; QS, 24%; F, 29%), dapsone (S, 47%; QS, 30%; F, 23%), and sulfapyridine (S, 38%; QS, 27%; F, 35%). Combination sulfa–steroid–myelosuppressive agent therapy increased the response from 73% with single-agent therapy to 87%. Side effects were the reason for 29% of changes in therapy. These were most prominent with azathioprine (40%) and least with mycophenolate (15%). Initial best-corrected VA (BCVA) was 6/60 or less in 17% (37/223) of eyes, pemphigoid being the cause in 13% (29/223). Final BCVA was 6/60 or less in 34% (76/223) of eyes, pemphigoid being the cause in 26% (57/223). By the end of the study, Mondino stage cicatrization had progressed in 41% (92/223) of eyes and 53% (61/115) of patients. Conclusions: Mycophenolate mofetil seems to be an effective and well-tolerated immunosuppressant for moderately active ocular mucous membrane pemphigoid. Combination sulfa–steroid–myelosuppressive agent therapy in a stepladder regimen is a useful strategy to improve disease control. Cicatrization and VA may still progress and worsen despite adequate control of inflammation. [Copyright &y& Elsevier]

Purpose: To evaluate adherence to topical medication in patients with inflammatory eye disease.Methods: Questionnaire survey of patients attending inflammatory eye disease clinics. Treatment regimen was validated against hospital-generated clinic letters.Results: There were 86 patients (52 uveitis and 34 ocular surface disease) with 30% (26/86) failing to identify one or more of the medications they were using, and 28% (24/86) unable to offer the correct indication for their treatment. A total of 64% (55/86) failed to use their medication as advised (27% on a daily basis); the commonest reason being forgetfulness. In patients using multiple eye drops, 26% left insufficient time intervals between successive eye drops, and 58% (50/86) reported not being given any instruction on drop instillation.Conclusions: We highlight poor adherence to topical medication in patients with inflammatory eye disease. We recommend a dedicated practitioner providing a proactive approach to patient education to improve adherence. [ABSTRACT FROM AUTHOR]

Background: Microbial keratitis (MK) is the most common non-surgical ophthalmic emergency, and can rapidly progress, causing irreversible sight-loss. This study explored whether the COVID-19 (C19) national lockdown impacted upon the clinical presentation and outcomes of MK at a UK tertiary-care centre. Methods: Medical records were retrospectively reviewed for all patients with presumed MK requiring corneal scrapes, presenting between 23rd March and 30th June in 2020 (Y2020), and the equivalent time windows in 2017, 2018 and 2019 (pre-C19). Results: In total, 181 and 49 patients presented during the pre-C19 and Y2020 periods, respectively. In Y2020, concurrent ocular trauma (16.3% vs. 5.5%, p = 0.030) and immunosuppression use (12.2% vs 1.7%, p = 0.004) were more prevalent. Despite proportionately fewer ward admissions during the pandemic (8.2% vs 32.6%, p<0.001), no differences were observed in baseline demographics; presenting visual acuity (VA; median 0.6 vs 0.6 LogMAR, p = 0.785); ulcer area (4.0 vs 3.0mm2, p = 0.520); or final VA (0.30 vs 0.30 LogMAR, p = 0.990). Whilst the overall rates of culture positivity were similar in Y2020 and pre-C19 (49.0% vs. 54.7%, p = 0.520), there were differences in the cultures isolated, with a lower rate of poly-microbial cultures in Y2020 (8.3% vs. 31.3%, p = 0.022). Conclusions: Patient characteristics, MK severity and final visual outcomes did not appear to be affected in the first UK lockdown, despite fewer patients being admitted for care. Concurrent trauma and systemic immunosuppression use were greater than in previous years. The difference in spectra of isolated organisms may relate to behavioural changes, such as increased hand hygiene. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcome measures (PROMs) can provide valuable insights on the impact of a disease or treatment on a patient's health-related quality of life. In ophthalmology, particularly in dry eye disease (DED) and ocular surface disease (OSD), it is unclear whether the available PROMs were developed using comprehensive guidelines. To address this, we evaluated the methodological quality of studies assessing the psychometric properties of PROMs in DED and OSD [PROSPERO registration number CRD42019142328]. Methods: Four databases were searched; reference list and citation searching of included studies was also conducted. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to appraise the quality of the studies evaluating the psychometric properties of PROMs used in DED and OSD. Results: The search strategy (S3 Table) retrieved 5,761 records, 573 duplicates were removed, 5,188 abstracts were screened and 127 full-text articles were retrieved for further review. Of these, 118 full-text articles did not meet the eligibility criteria and were excluded. Reference list and citation searching, identified an additional 8 articles bringing the total numbers of papers reviewed to 17. In general, psychometric properties such as content validity, measurement error and structural validity were not assessed by the studies included in this review. Studies reviewing The Impact of Dry Eye on Everyday Life (IDEEL) presented with the highest quality scores together with the Ocular Surface Disease Index (OSDI) questionnaire. Conclusions: The quality of studies evaluating PROMs in DED and OSD was considered using the COSMIN standards. The majority of the studies evaluating PROMs included in this review did not meet the recommended COSMIN criteria and the quality of the PROMs evaluated is not assured. Further evaluation of their psychometric properties is required if these are going to be used in clinical practice or research. [ABSTRACT FROM AUTHOR]

In the article, the authors present their study on the association between tonsillectomy (TE) and glandular inflammation in Sjögren's disease, which is characterized by B cell hyperactivity and focal lymphocytic infiltration of salivary glands. Other topics include the association of TE with long-term risk of respiratory, infectious, and allergic diseases, and the history of appendectomy (AE) and TE.

Primary SS (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands leading to glandular dysfunction, resulting in dryness of the eyes, mouth and other mucosal surfaces. Systemic manifestations also occur in the majority of patients. There has been increasing interest in recent years, with a number of publications regarding the classification criteria, diagnostic tools, disease activity, damage, impact and potential treatments. This article reviews recent advances in the diagnosis and treatment of ocular and oral involvement in pSS. Recent stand-out developments include measurement of tear osmolarity as a marker in dry eye disease diagnosis, new devices measuring tear constituents and meibomian gland structure and treatment of its dysfunction. Lip biopsy is still valuable despite emerging evidence of non-invasive diagnostic techniques, notably salivary gland ultrasound. [ABSTRACT FROM AUTHOR]

Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are part of a disease continuum of vesiculobullous mucocutaneous reactions affecting the skin and mucous membranes including the ocular surface. Manifestations of disease range from mild dry eye to progressive conjunctival cicatrisation, limbal epithelial stem cell failure and corneal blindness. In Far Eastern and South East Asian populations where SJS/TEN is prevalent, numerous human leukocyte antigen (HLA) gene variants at the A, B and C loci have been identified as risk factors for developing SJS/TEN with severe ocular complications (SOC). By contrast, the incidence of SJS/TEN with SOC in European countries is relatively low. To date, ocular SJS/TEN risk altering alleles have not been widely investigated in European populations. In this study, we analysed the association of HLA -A, -B and -C alleles with SJS/TEN in 33 patients residing in the UK with age matched controls. The data showed statistically significant novel negative allele association with HLA-B*0702 and a trend with HLA-C*0702 in the patient group, indicating these alleles are protective. Further characterisation of protective and risk alleles in other ethnic groups is required to fully elucidate the putative role of these alleles in the susceptibility of SJS/TEN with or without severe ocular complications in patients in the UK. [ABSTRACT FROM AUTHOR]

Aims/Purpose: We hypothesize that exacerbated mitochondrial fusion abrogates mitophagy in diabetic retinopathy [DR]. Our aim was to rescue this process pharmacologically to prevent vision loss in a mouse model of type‐1 diabetes. Methods: We generated a drug screening platform mimicking mitochondrial hyperfusion in DR. To this end, retinal Müller cells (mouse primary and MIO‐M1 cell line) were antagonized for mitochondrial fission using a Drp1 inhibitor peptide under elevated glucose (30.5 mM) conditions. Pharmacological 'hits' rescuing mitophagy in conditions of diabetes‐induced hyperfusion were assessed for their capability to improve mitochondrial health (membrane potential [ΔΨm]) and bioenergetics (Seahorse). The bio‐activity of lead compounds were corroborated in vivo using diabetic mitophagy reporter mice (Mito‐QC Ins2Akita), while effectiveness to alleviate retinal degeneration was evaluated via electroretinography (ERG), retinal thickness (SD‐OCT) and morphometric analysis of retinal neurons. Results: Among all drugs screened, we identified PA‐01 (a PINK1‐mitophagy activator) as capable of safely rescuing mitophagy under conditions of diabetes‐induced mitochondrial hyperfusion. Accordingly, PA‐01 rescued mitochondrial health (ΔΨm) and bioenergetics in Müller glia cultures, by optimizing metabolic flux (basal‐ and ATP‐linked respiration). The bio‐activity of PA‐01 was demonstrated in vivo, where long‐term oral administration rescued mitochondrial hyperfusion and mitophagy in the diabetic retina, while further preventing neurodegeneration. This was reflected in i) improved scotopic ERG responses (increased a‐wave and b‐wave amplitudes), ii) improved SD‐OCT retinal thickness and iii) neuroprotection to photoreceptors, synaptic terminals and amacrine cells. Conclusions: Exacerbated mitochondrial fusion contributes to DR pathology by inhibiting mitophagy in Müller glia. Rescuing this process pharmacologically holds promising therapeutic potential to alleviate vision loss in DR. [ABSTRACT FROM AUTHOR]

Aims/Purpose: The accumulation of dysfunctional mitochondria has been implicated in the pathogenesis of diabetic eye disease through the impairment of mitochondrial quality control (MQC). This study aimed to investigate whether mitophagy‐activating drugs can alleviate pathology in the anterior and posterior ocular tissues of type‐1 diabetic mice. Methods: Mitophagy was evaluated in corneal and retinal tissues from diabetic mitophagy reporter mice (mitoQC‐Ins2Akita). The therapeutic potential of targeting mitophagy was evaluated by treating diabetic Ins2Akita mice with PIA‐01 (a PINK1‐independent mitophagy activator). Treatment was delivered orally between 4 and 8 months of diabetes. Ocular degenerative changes were evaluated by scotopic electroretinography (ERG), along with immunohistochemical analysis of retinal neurons and corneal cytoarchitecture. Results: Indicative of deteriorated MQC, mitophagy and mitochondrial transcription factor A (TFAM) positive mitochondrial nucleoids (which contain mtDNA) significantly decreased in the cornea and retina by 8 months of diabetes. Oral delivery of PIA‐01 restored TFAM+ mitochondrial nucleoids, leading to improved visual outcomes in Ins2Akita mice. In the retina, this was reflected by improved ERG responses (e.g. increased scotopic a‐wave and b‐wave amplitudes), while also protecting retinal neurons, including cone‐photoreceptors, synaptic structures, amacrine cells and retinal ganglion cells. This protection extended to the anterior segment, where PIA‐01 rescued corneal cytoarchitecture (basal epithelium and stroma) in diabetic mice. Conclusions: Diabetes progresses with deterioration of MQC in anterior and posterior ocular tissues. Rescuing MQC via mitophagy‐activating drugs may allow for multisystem therapies to control diabetic eye disease. [ABSTRACT FROM AUTHOR]

Drug delivery by topical application has higher patient acceptance and lower morbidity than intraocular injection, but many ophthalmic treatments are unable to enter the eye or reach the posterior segment after topical application. The first stage towards posterior segment delivery after topical application is ocular surface penetration and existing models are in vivo or use large quantities of tissue. We therefore developed a novel ex vivo model using discs of porcine and human cornea and sclera (5 mm diameter) to assess penetration of a candidate neuroprotective siRNA. siRNA against caspase 2 or control solutions of known penetrance were applied to the corneal epithelial surface and trans-corneal penetration and corneal adsorbance measured at fixed time points. To demonstrate that leakage did not occur, we applied dextran blue, which should not penetrate the intact cornea and did not do so in our model. Fluorescein penetration (0.09%) was less than rhodamine B (6.98%) at 60 min. siCASP2 penetration was 0.01% by 60 min. When the applied siCASP2 was washed off after 2 min, (representing lacrimal drainage) 0.071% penetrated porcine cornea by 60 min and 0.0002% penetrated human cornea and 0.001% penetrated human sclera. Our ex vivo model rapidly and cost-effectively assesses transcorneal penetration of candidate topical therapies, allowing rates of trans-corneal penetration for potential therapies such as siRNA to be evaluated with small quantities of human or animal tissue. [ABSTRACT FROM AUTHOR]

Background: The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury.Methods: Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea.Results: At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1gfp/gfp mice treated with decorin.Conclusions: Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury. [ABSTRACT FROM AUTHOR]

Scarring/Opacity on the surface of the eye and vascularisation following infectious diseases, inflammation and corneal trauma are often a leading cause of blindness. The 'gold standard' treatment to prevent corneal scarring is the application of amniotic membrane (AM) to the ocular surface in the acute stage of injury. Although clinically effective, the use of the AM is associated with biological variability and unpredictable responses. Potential health risks including disease transmission, significant ethical issues surrounding the tissue donation process and stringent regulations/storage conditions, preclude widespread use. Consequently, there is a demand for the development of a new, synthetic alternative, that is stable at room temperature, capable of protecting the wound and has the capacity to deliver anti-scarring and anti-inflammatory mediators. Here we have developed a micro-structured fluid gel eye drop, to deliver a potent anti-scarring molecule, decorin. We have compared the release of decorin from the formulated dressing to a typical gel film, demonstrating enhanced release for the fluid gel eye-drops. Therefore, we have investigated the effect of the fluid gel system in 2D human corneal fibroblast culture models, as well as shown the retention of the gellan fluid gel in an in vivo rat model. At the same time the efficacy of the fluid gel eye drop was studied in an organ culture model, whereby the fluid gel containing decorin, significantly (P < 0.05) increased re-epithelialisation within 4 days of treatment. Image 1 [ABSTRACT FROM AUTHOR]

Neurotrophic Keratopathy (NK) refers to a condition where corneal epitheliopathy leading to frank epithelial defect with or without stromal ulceration (melting) is associated with reduced or absent corneal sensations. Sensory nerves serve nociceptor and trophic functions, which can be affected independently or simultaneously. Loss of trophic function and consequent epithelial breakdown exposes the stroma making it susceptible to enzymatic degradation. Nerve pathology can range from attrition to aberrant re-generation with corresponding symptoms from anaesthesia to hyperaesthesia/allodynia. Many systemic and ocular conditions, including surgery and preserved medications can lead to NK. NK can be mild (epithelium and tear film changes), moderate (non-healing epithelial defect) or severe (stromal melting and perforation). Moderate and severe NK can profoundly affect vision and adversely impact on the quality of life. Medical management with lubricating agents from artificial tears to serum/plasma drops, anti-inflammatory agents, antibiotics and anti-proteases all provide non-specific relief, which may be temporary. Contact lenses, punctal plugs, lid closure with botulinum toxin and surgical interventions like tarsorrhaphy, conjunctival flaps and amniotic membrane provide greater success but often at the cost of obscuring sight. Corneal surgery in a dry ocular surface with reduced sensation is at high risk of failure. The recent advent of biologicals such as biopolymers mimicking heparan sulfate; coenzyme Q10 and antisense oligonucleotide that suppress connexin 43 expression, all offer promise. Recombinant nerve growth factor (cenegermin), recently approved for human use targets the nerve pathology and has the potential of addressing the underlying deficit and becoming a specific therapy for NK. [ABSTRACT FROM AUTHOR]

Introduction: Primary Sjögren’s Syndrome (pSS) affects exocrine glands such as those producing the tear film, leading to dry and painful eyes, but is also associated with fatigue. The experience of fatigue in pSS, and its relationship with sicca symptoms, is poorly understood. Methods: Twenty people diagnosed with pSS were recruited to participate in a semi-structured qualitative interview about their symptoms experience. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Results: People with pSS described physical tiredness, mental fatigue and ocular fatigue. Mental fatigue was characterised by difficulties in attention, particularly, the ability to follow conversations and short-term memory problems. Participants linked their experience of fatigue to feeling of depression, frustration, irritation and anxiety, and therefore, fatigue was suggested to have had a large impact on their psychological well-being. People with pSS also described a range of ocular symptoms including pain, dryness, and itching, which were compounded by fatigue. For some, eye fatigue was pervasive, and daily activities involving the eyes such as reading, using the computer and driving were impaired. In some cases, the level of ocular discomfort was so severe it prevented sleep, which in turn impacted on general fatigue levels. Conclusions: People with pSS experience fatigue in a range of ways; physical, mental and ocular fatigue were described. Fatigue was suggested to exacerbate other ocular symptoms, posed serious physical limitations and caused psychological distress. Further research into the nature of fatigue and ocular symptoms in pSS is required. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye and ocular surface disease (OSD) are the most common causes of eye discomfort with up to 50%1 of the global population affected. Anterior segment optical coherence tomography (AS‐OCT) is essential to diagnose and track ocular surface changes. This study aims at assessing the precision of a modern swept source AS‐OCT in OSD vs healthy control. Methods: Five clinical groups were included: G1 = Sjögren's syndrome (n = 46); G2 = Ocular Mucous Membrane Pemphigoid, Graft‐versus‐Host Disease, etc. (n = 58); G3 = Meibomian Gland Disease (n = 47); G4 = Miscellaneous (Neurotrophic, Exposure, Transplant, etc.) (n = 36); G5 healthy controls (n = 41). Three consecutive measurements using a radial scan mode were collected using the AS‐OCT Casia2 (Tomey, Japan) and the repeatability limits (RLs) were calculated. The following parameters were obtained: anterior chamber depth (ACD), AC width (ACW), angle opening distance (AOD) and angle recess area (ARA) both at 250, 500 and 750 μm, angle to angle (ATA), central thickness apex (CTapex), lens vault (LV), trabecular iris angle (TIA) and trabecular iris‐space area (TISA) both at 250, 500 and 750 μm. Dry eye metrics such as OSDI® questionnaire, fluorescein break‐up time (FBUT), tear meniscus height (TMH), conjunctival inflammation (INFLCONJ) and ocular surface staining (OSS) were considered. Results: The higher RLs values were observed within the G4 cohort considering AOD (0.28, 0.29, 0.36, 0.35, 0.43 vs G5 0.18, 0.21, 0.18, 0.20, 0.26 mm),ARA (0.08, 0.10, 0.16, 0.18, 0.25, 0.27 vs. G5 0.06, 0.06, 0.09, 0.10, 0.14, 0.15 mm2), CTapex (66.12 vs. G5 13.55 μm), TIA (33.90, 22.57, 14.55, 20.02 vs. G5 30.94, 18.31, 9.44, 14.76 degrees) and TISA (0.06, 0.07, 0.14, 0.15, 0.23, 0.24 vs. G5 0.04, 0.05, 0.08, 0.09, 0.12, 0.14 mm2). G1 cohort reported the worst dry eye metrics (OSDI 52.90 ± 20.58 score, FBUT 3.51 ± 2.36 s, TMH 0.10 ± 0.07 mm, INFLCONJ 1.07 ± 1.78 score, OSS 4.27 ± 2.35 score). Conclusions: This is the first study to consider anterior segment analysis repeatability limits in OSD vs healthy cohorts with the AS‐OCT Casia2. Despite G1 cohort reported the worse dry eye metrics, the higher repeatability limits were observed in the G4 Miscellaneous group. Reference 1. Stapleton, F. et al. TFOS DEWS II Epidemiology Report. Ocular Surface 15, 334–365, doi:10.1016/j.jtos.2017.05.003 (2017). [ABSTRACT FROM AUTHOR]

Purpose: To determine how the dysregulated interplay between mitochondrial dynamics and mitophagy contribute to the progression of diabetic retinopathy [DR]. Methods: 3‐months and 9‐month‐old diabetic mitophagy reporter (MitoQC‐Ins2Akita) mice and their non‐diabetic siblings, were used to evaluate the interplay between mitochondrial dynamics and mitophagy by confocal morphometry. To model the dysregulation of mitochondrial quality control processes in vitro, mitochondrial fission was antagonized in retinal Müller cells (mouse primary and MIO‐M1 cell‐line) using a Drp1 inhibitor peptide (P110), under physiological (5.5 mM) and elevated glucose (30.5 mM) conditions. Mitochondrial fitness was assessed via metabolic flux (Seahorse) along with mitochondrial membrane potential (JC‐1), while the Müller glia inflammatory secretome was determined using Luminex. Results: In contrast to younger ages, 9‐month‐old diabetic mice displayed exacerbated mitochondrial fusion at the outer retina (e.g., increased interconnectivity and mitochondrial aspect ratios), which was strongly associated with impaired mitophagy levels (r2 = 0.7, p < 0.001). P110 peptide inhibited mitochondrial fission/exacerbated fusion in retinal Müller cells, and abrogated mitophagy similarly to that found at advanced DR stages. Importantly, exacerbated mitochondrial fusion under hyperglycaemia (but not normoglycaemia) disrupted mitochondrial membrane potential (p < 0.05) in Müller cell cultures, further compromising mitochondrial fitness, as shown by decreased spare respiratory capacity and bioenergetic health index (p < 0.001 both). This was accompanied by significantly elevated secretion of key DR pro‐inflammatory factors, particularly CCL2 and VEGF‐A (p < 0.05 both). Conclusions: Exacerbated mitochondrial fusion contributes to DR pathology by inhibiting mitophagy in Müller glia. Therapies aimed at facilitating mitochondrial fission/mitophagy in a controlled fashion may hold therapeutic potential for managing DR. [ABSTRACT FROM AUTHOR]

Aims The aims of this study were as follows: (i) To assess the prevalence of periodontitis among patients with primary Sjögren's syndrome ( pSS) and comparator groups of patients with rheumatoid arthritis ( RA) and osteoarthritis ( OA). (ii) To perform a pilot study to compare serum antibody responses to 10 oral/periodontal bacteria in these patient groups and a historical comparator group of patients with periodontitis. Materials and Methods Standard clinical periodontal assessments were performed on 39 pSS, 36 RA and 23 OA patients and 'In-house' antibody ELISAs for serum antibodies against 10 oral/periodontal bacteria were performed in these groups. Results Forty-six percent of the pSS group, 64% of the RA group and 48% of the OA group had moderate/severe periodontitis. These frequencies did not reach statistical significance between groups. Raised antibody levels to Prevotella denticola were found in the pSS, RA and periodontitis groups compared to the OA group. Significant between group differences were seen for Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Campylobacter showae. None of these differences were specifically associated with pSS. Conclusion This study showed no increase in periodontitis in pSS patients. Although the P. denticola data are of interest, identifying bacterial triggering factors for pSS will likely require alternative strategies including modern techniques such as microbiome analysis. [ABSTRACT FROM AUTHOR]

Innate immune responses have a critical role in regulating sight-threatening ocular surface (OcS) inflammation. While glucocorticoids (GCs) are frequently used to limit tissue damage, the role of intracrine GC (cortisol) bioavailability via 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in OcS defense, remains unresolved. We found that primary human corneal epithelial cells (PHCEC), fibroblasts (PHKF) and allogeneic macrophages (M1, GM-CSF; M2, M-CSF) were capable of generating cortisol (M1>PHKF>M2>PHCEC) but in corneal cells, this was independent of Toll-like receptor (TLR) activation. While PolyI∶C induced maximal cytokine and chemokine production from both PHCEC (IFNγ, CCL2, CCL3, and (CCL4), IL6, CXCL10, CCL5, TNFα) and PHKF (CCL2, IL-6, CXCL10, CCL5), only PHKF cytokines were inhibited by GCs. Both Poly I∶C and LPS challenged-corneal cells induced M1 chemotaxis (greatest LPS-PHKF (250%), but down-regulated M1 11β-HSD1 activity (30 and 40% respectively). These data were supported by clinical studies demonstrating reduced human tear film cortisol∶cortisone ratios (a biomarker of local 11β-HSD1 activity) in pseudomonas keratitis (1∶2.9) versus healthy controls (1∶1.3; p<0.05). This contrasted with putative TLR3-mediated OcS disease (Stevens-Johnson Syndrome, Mucous membrane pemphigoid) where an increase in cortisol∶cortisone ratio was observed (113.8∶1; p<0.05). In summary, cortisol biosynthesis in human corneal cells is independent of TLR activation and is likely to afford immunoprotection under physiological conditions. Contribution to ocular mucosal innate responses is dependent on the aetiology of immunological challenge. [ABSTRACT FROM AUTHOR]

Purpose: Quantifying the extent of conjunctival fibrosis for documentation of progression in conjunctival scarring disease is a clinical challenge. Measurement of forniceal foreshortening facilitates monitoring of these disorders. This study aims (1) to define the limits of the normal human conjunctival fornices and how these alter with age and (2) to provide normative data for upper and lower fornix depths (FDs) and fornix intercanthal distance (FICD) within a healthy South Asian, racially distinct population. Design: Epidemiologic, cross-sectional study. Participants: A total of 240 subjects with national origins from South Asia, with no known ocular history and normal adnexal and conjunctival examination, aged 20 to 80 years. Methods: An FICD modification of a custom-designed fornix depth measurer (FDM) was validated and used for measurement of both lower and upper FDs together with FICDs in 480 healthy eyes with no ocular comorbidities. Data were analyzed using repeated-measures analysis of variance and presented as means with 95% confidence intervals (CIs). Main Outcome Measures: Mean lower and upper FDs and FICD for the entire cohort, stratified according to age decade and sex. Results: For this South Asian population, the overall upper and lower FDs were 15.3 mm (95% CI, 14.9–15.6) and 10.9 mm (95% CI, 10.7–11.1), respectively, with FICD defined as 32.9 mm (95% CI, 32.5–33.4) (upper) and 31.7 mm (95% CI, 31.3–32.1) (lower). With increasing age, a progressive reduction of all measured parameters (P < 0.001) was noted, with female subjects having significantly shallower fornices (upper FD, P < 0.001; lower FD, P < 0.001; upper FICD, P = 0.081; and lower FICD, P = 0.015). Conclusions: This is the first study to define the limits of normal upper FD and FICDs in any population group. Our study demonstrates sex variations and progressive conjunctival shrinkage with age. Although it provides important, objective data for normal forniceal anatomy, further study is recommended in other populations to confirm the generalizability of these data or to enable normal comparative datasets for the assessment of conjunctival scarring disorders among all anthropological groups. [Copyright &y& Elsevier]

Aims Severe ocular inflammation is a blinding ophthalmological emergency. This study evaluates the efficacy and patient tolerance of a validated regime of pulsed intravenous cyclophosphamide and methylprednisolone ('PICM protocol') for these patients. Methods 26 patients with severe inflammatory eye disease (43 eyes: 22 uveitis, 21 scleritis/sclerokeratitis; median age 52 years (IQR 40.25-62.25)) presenting to a regional tertiary referral centre were recruited over a 10-year period (January 2002-December 2011) into the PICM protocol, comprising intravenous cyclophosphamide 15 mg/kg, intravenous methylprednisolone 10 mg/kg, maximum nine pulses over 20 weeks supplemented with low-dose continuous oral prednisolone. Data were captured pretreatment and at 6 and 12 months follow-up. Primary outcome measures were control of inflammation according to standard criteria and reduction in systemic glucocorticoid to ≤10 mg prednisolone/day. Results A median of six pulses (IQR 5-6) were administered over a median of 3 months (IQR 2.25-4). In the scleritis/sclerokeratitis group, 15/21(71%) achieved success or partial success at 6 and 12 months versus 9/22 (41%) for the same time points in the uveitis group (χ²=4.058, p=0.044). Two patients had adverse events requiring treatment withdrawal. Conclusions This PICM protocol is a well-tolerated regimen for managing severe ocular inflammation and appears particularly useful in patients with scleritis/ sclerokeratitis. [ABSTRACT FROM AUTHOR]

The conjunctiva is a highly specialized ocular mucosal surface that, like other mucosa, houses a number of leukocyte populations. These leukocytes have been implicated in age-related inflammatory diseases such as dry-eye, but their phenotypic characteristics remain largely undetermined. Existing literature provides rudimentary data from predominantly immunohistochemical analyses of tissue sections, prohibiting detailed and longitudinal examination of these cells in health and disease. Using recovered cells from ocular surface impression cytology and flow cytometry, we examined the frequency of leukocyte subsets in human conjunctival epithelium and how this alters with age. Of the total CD45+ leukocyte population within the conjunctival epithelium, 87% [32-99] (median) [range] comprised lymphocytes, with 69% [47-90] identified as CD3 + CD56- T cells. In contrast to peripheral blood, the dominant conjunctival epithelial population was TCRαβ + CD8αβ + (80% [37-100]) with only 10% [0-56%] CD4+ cells. Whilst a significant increase in the CD4+ population was seen with age (r = 0.5; p < 0.01) the CD8+ population remained unchanged, resulting in an increase in the CD4:CD8 ratio (r = 0.5;p < 0.01). IFNγ expression was detectable in 18% [14-48] of conjunctival CD4+ T cells and this was significantly higher among older individuals (<35 years, 7[4-39] vs. >65 years, 43[20-145]; p < 0.05). The elevation of CD4+ cells highlights a potentially important age-related alteration in the conjunctival intra-epithelial leukocyte population, which may account for the vulnerability of the aging ocular surface to disease. [ABSTRACT FROM AUTHOR]

The appearance of the optic disc is a key measure of disease status in idiopathic intracranial hypertension (IIH). The Frisén classification describes stages of optic disc swelling (grades 0-5). It is the only classification of papilloedema, and is used internationally in clinical and research practice. Despite this, there has been very limited evaluation of the scale. We assessed the inter-rater reproducibility and ability to discriminate optic disc changes over time using the Frisén classification compared with a system of ranking papilloedema severity in patients with IIH. Paired disc photographs (before and after treatment) were obtained from 47 patients with IIH (25 acute and 22 chronic). Six neuro-ophthalmologists blinded to patient identity, clinical information and chronology of the photographs reviewed the discs and allocated a Frisén grade and ranked the paired discs in order of papilloedema severity (disc ranking). A total of 188 optic disc photographs were reviewed. All six reviewers agreed in only three comparisons (1.6%) when using the Frisén classification, compared with 42 comparisons (45.2%) when using disc ranking. The probability of agreement between any two reviewers was 36.1% for Frisén grade and 70.0% for disc ranking. Disc ranking had significantly greater sensitivity for finding differences in degree of disc oedema, identifying a difference in 75.3% of paired photographs compared to 53.2% detected using the Frisén classification ( p < 0.001). This study demonstrated the limited reproducibility and discriminative ability of the Frisén classification in identifying changes in serial optic disc photographs in IIH. Simple optic disc ranking appears to be a more sensitive and reliable tool to monitor changes in optic disc appearance. The use of disc ranking in clinical practice and research studies is recommended to monitor alterations in optic disc appearance until alternative schemes, specific to IIH, have been developed. [ABSTRACT FROM AUTHOR]

Background The syndrome of childhood blepharokeratoconjunctivitis (BKC) is frequently underestimated. While prevalent and aggressive among Indo-Pakistani/Middle-Eastern populations, we observe a recalcitrant destructive phenotype in white children/ adolescents that persists into early adulthood and may require systemic immunosuppression. Methods A cohort of 10 white patients (20 eyes), median age 15.2 (range 6-27) years were identified among 62 patients with BKC attending a tertiary referral centre. Clinical features were graded and lid/conjunctiva swabs were performed, before instituting a hierarchical therapeutic protocol comprising lid hygiene, topical/ systemic antibiotics, intensive topical glucocorticoids and systemic immunosuppression. Results The median duration of symptoms prior to presentation was 4.3 (range 1.2-16.3) years, with 14 eyes (nine patients) demonstrating 3608 peripheral corneal vascularisation associated with encroachment/ involvement of the visual axis in 10 eyes (six patients). Corneal perforation(s) occurred in three eyes (two patients). Intensive topical glucocorticoids enabled disease control in 10 eyes (seven patients). In six eyes (three patients), persistent active disease necessitated systemic immunosuppression (azathioprine (2), mycophenolate mofetil (1), prednisolone (1)) achieving disease remission within three months with no adverse events reported. Conclusions Suboptimal treatment of BKC in white children may permit a progressively destructive sightthreatening phenotype, which may last into adulthood and require immunosuppression. Appropriate aggressive steroid-based and steroid-sparing strategies are vital for disease remission. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 68-year-old British-Chinese patient diagnosed with post-phacoemulsification cytomegalovirus (CMV) corneal endotheliitis and treated with endothelial surgery and anti-virals. It states that quantitative polymerase chain reaction (qPCR) is important in monitoring and diagnosing CMV endotheliitis. It mentions that CMV endotheliitis is often caused by intraocular surgery.

Aqueous humor (AqH) has been shown to have significant immunosuppressive effects on APCs in animal models. We wanted to establish whether, in humans, AqH can regulate dendritic cell (DC) function and to identify the dominant mechanism involved. Human AqH inhibited the capacity of human peripheral blood monocyte-derived DC to induce naive CD4+ T cell proliferation and cytokine production in vitro, associated with a reduction in DC expression of the costimulatory molecule CD86. This was seen both for DC cultured under noninflammatory conditions (immature DC) and for DC stimulated by proinflammatory cytokines (mature DC). DC expression of MHC classes I/II and CD83 was reduced (mature DC only). Myeloid DC from peripheral blood were similarly sensitive to the effects of human AqH, but only under inflammatory conditions. The addition of a-melanocyte stimulating hormone and vasoactive intestinal peptide did not cause significant inhibition at physiological levels. However, the addition of exogenous cortisol at physiological levels recapitulated the AqH-induced reduction in CD86 and inhibition of DC-induced T cell proliferation, and blockade of cortisol in AqH partially reversed its suppressive effects. TGF-β2 had an additional effect with cortisol, and although simultaneous blockade of cortisol and TGF-β2 in AqH reduced its effectiveness, there was still a cortisol- and TGF-β-independent component. In humans, AqH regulates DC maturation and function by the combined actions of cortisol and TGF-β2, a pathway that is likely to contribute to the maintenance of immune privilege in the eye. [ABSTRACT FROM AUTHOR]

Abstract: The effect of different collagen and cell concentrations on the mechanical and remodeling behaviors of corneal stroma wound healing models consisting of collagen hydrogels seeded with human corneal fibroblasts during a 25 day culture period were examined. Human corneal fibroblasts were seeded at 1 × 105, 3 × 105 or 5 × 105 cells per hydrogel, and collagen concentrations of 2.5 mg/ml, 3.5 mg/ml or 4.5 mg/ml were examined. Two non-destructive techniques, spherical indentation and optical coherence tomography, were used to measure the elastic modulus and dimensional changes respectively at several time-points over the culture period. The elastic modulus of the hydrogels increased continuously over 25 days. Hydrogels with higher initial cell seeding densities and lower initial collagen concentrations were found to increase in elastic modulus faster and possessed a higher elastic modulus by the end of the culture period when compared to the other hydrogels. A mathematical equation was applied to accurately fit the change in elastic modulus over time. This study demonstrates a robust in vitro technique able to monitor the effect of different parameters on the cell–matrix mechanical relationship in a corneal stroma model during prolonged culture periods and enhances our understanding on corneal wound healing processes. [ABSTRACT FROM AUTHOR]

Abstract: Idiopathic intracranial hypertension (IIH) is a common blinding condition amongst the young obese female population (20 per 100,000) characterised by elevated intracranial pressure (ICP). The aetiology of IIH is not known. In this review we explore the literature investigating the pathogenesis of IIH and suggest additional hypotheses. Chronic inflammation is emerging as an aetiological factor in the pathogenesis of obesity and we propose that this may be a feature of IIH. Obesity is also related to dysregulation of cortisol production by the pre-receptor enzyme, 11β-hydroxysteroid dehydrogenase, and we speculate that this may have a role in the pathogenesis of obesity and raised ICP seen in IIH. [Copyright &y& Elsevier]

• cTA-NLC got access into HCF cells in 2 h and retain there for 24 h. • cTA-NLC showed ∼2-fold increase in corneal permeation than drug suspension. • cTA-NLC has higher anti-inflammatory activity than blank-NLC, and drug suspension. • cTA-NLC is efficacious in uveitis treatment at much lower conc. (0.1 %) of drug. Topical administration of corticosteroids is the cornerstone treatment of anterior uveitis, but poor corneal penetration and retention cause hindrance in their therapeutic utility. The conventional eye drops are less valuable in conditions where inflammation reaches deeper regions of the eye. Therefore, there is a clear need for an effective drug delivery system, which can increase corticosteroid penetration after topical application. To address this, cationic nanostructured lipid carriers of the drug triamcinolone acetonide (cTA-NLC) were prepared. The cTA-NLC were prepared by a hot microemulsion method and evaluated for drug release, permeation, cell uptake, cytotoxicity, anti-inflammatory activity and ocular irritancy. The cTA-NLC are nanometric in size (< 200 nm), with a zeta potential of about +35 mv and % drug EE of 88 %. The nanocarriers exhibited slow and sustained release of around 84 % in 24 h and transcorneal drug permeation of 51 % in 8 h. The nanocarriers exhibited no cytotoxicity (% cell viability of>90 %). The cell uptake study showed that nanocarriers could retain inside the cells for 24 h. The developed formulation could significantly reduce the TNF-α level in LPS induced inflamed cells. The studies indicated that cTA-NLC could be a promising option for the topical treatment of uveitis. [ABSTRACT FROM AUTHOR]

The article offers information on a study which investigated the efficacy of weight loss in reducing intracranial pressure and treating patients with idiopathic intracranial hypertension. The study subjects, who were recruited in two hospitals in Great Britain, were 25 women with chronic active idiopathic and intracranial pressure. Outcome measures studied were reduction in intracranial pressure after the diet and papilloedema as measured by ultrasonography of the optic disc elevation and nerve sheath diameter. The research findings are presented.