Clinical characteristics and aetiology of uveitis in a viral haemorrhagic fever zone.

BACKGROUND/OBJECTIVES: Studies on uveitis in Sierra Leone were conducted prior to the Ebola Virus Disease epidemic of 2013-16, which was associated with uveitis in 20% of survivors. They did not include imaging or investigation of tuberculosis and used laboratory services outside the country. We performed a cross-sectional study on patients presenting with uveitis to establish their clinical characteristics and identify the impact of in-country laboratory diagnoses. METHODS: We invited uveitis cases presenting to Eye Clinics in Sierra Leone from March to September 2022 to participate in the study. They underwent a diagnostic work-up, including fundus and ocular coherence tomography imaging. Active uveitis cases underwent further investigations including serology and immunological tests for syphilis, tuberculosis, herpetic viruses and HIV and chest radiographs. RESULTS: We recruited 128 patients. The median age was 34 (IQR 19) years and there was an equal gender split. Panuveitis was the predominant anatomical uveitis type (n = 51, 40%), followed by posterior uveitis (n = 36, 28%). Bilateral disease affected 40 patients (31%). Active uveitis was identified in 75 (59%) cases. ICD 11 definition of blindness with VA < 3/60 occurred in 55 (33%) uveitis eyes. Aetiology of uveitis from clinical and laboratory assessment demonstrated that most cases were of undifferentiated aetiology (n = 66, 52%), followed by toxoplasmosis (n = 46, 36%). Trauma contributed to eight (6%) cases, syphilis to 5 (4%) cases and Ebola to 2 (2%). CONCLUSIONS: Uveitis was associated with high levels of visual impairment. Posterior and panuveitis contributed to the highest proportion of uveitis cases. Laboratory studies helped differentiate syphilis as a significant aetiology of uveitis.

Clinical Characteristics and Aetiology of Uveitis in a Viral Haemorrhagic Fever Zone.

Background/Objectives: Studies on uveitis in Sierra Leone were conducted prior to the Ebola Virus Disease epidemic of 2013-16, which was associated with uveitis in 20% of survivors. They did not include imaging or investigation of tuberculosis and used laboratory services outside the country. We performed a cross-sectional study on patients presenting with uveitis to establish their clinical characteristics and identify the impact of in-country laboratory diagnoses. Methods: We invited uveitis cases presenting to Eye Clinics in Sierra Leone from March to September 2022 to participate in the study. They underwent a diagnostic work-up, including fundus and ocular coherence tomography imaging. Active uveitis cases underwent further investigations including serology and immunological tests for syphilis, tuberculosis and herpetic viruses and HIV, and chest radiographs. Results: We recruited 128 patients. The mean age was 36 ± 14 years and there was an equal gender split. Panuveitis was the predominant anatomical uveitis type (n=51, 40%), followed by posterior uveitis (n=36, 28%). Bilateral disease affected 40 patients (31%). Active uveitis was identified in 75 (59%) cases. ICD 11 definition of blindness with VA<3/60 occurred in 55 (33%) uveitis eyes. Aetiology of uveitis from clinical and laboratory assessment demonstrated that most cases were of undifferentiated aetiology (n=66, 52%), followed by toxoplasmosis (n=46, 36%). Trauma contributed to eight (6%) cases, syphilis to 5 (4%) cases and Ebola to 2 (2%). Conclusions: Uveitis was associated with high levels of visual impairment. Posterior and panuveitis contributed to the highest proportion of uveitis cases. Laboratory studies helped differentiate syphilis as a significant aetiology of uveitis.

Retinal correlates of neurological disorders.

Considering the retina as an extension of the brain provides a platform from which to study diseases of the nervous system. Taking advantage of the clear optical media of the eye and ever-increasing resolution of modern imaging techniques, retinal morphology can now be visualized at a cellular level in vivo. This has provided a multitude of possible biomarkers and investigative surrogates that may be used to identify, monitor and study diseases until now limited to the brain. In many neurodegenerative conditions, early diagnosis is often very challenging due to the lack of tests with high sensitivity and specificity, but, once made, opens the door to patients accessing the correct treatment that can potentially improve functional outcomes. Using retinal biomarkers in vivo as an additional diagnostic tool may help overcome the need for invasive tests and histological specimens, and offers the opportunity to longitudinally monitor individuals over time. This review aims to summarise retinal biomarkers associated with a range of neurological conditions including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and prion diseases from a clinical perspective. By comparing their similarities and differences according to primary pathological processes, we hope to show how retinal correlates can aid clinical decisions, and accelerate the study of this rapidly developing area of research.

Topical Curcumin Nanocarriers are Neuroprotective in Eye Disease.

Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione) is a polyphenol extracted from turmeric that has long been advocated for the treatment of a variety of conditions including neurodegenerative and inflammatory disorders. Despite this promise, the clinical use of curcumin has been limited by the poor solubility and low bioavailability of this molecule. In this article, we describe a novel nanocarrier formulation comprising Pluronic-F127 stabilised D-α-Tocopherol polyethene glycol 1000 succinate nanoparticles, which were used to successfully solubilize high concentrations (4.3 mg/mL) of curcumin. Characterisation with x-ray diffraction and in vitro release assays localise curcumin to the nanocarrier interior, with each particle measuring <20 nm diameter. Curcumin-loaded nanocarriers (CN) were found to significantly protect against cobalt chloride induced hypoxia and glutamate induced toxicity in vitro, with CN treatment significantly increasing R28 cell viability. Using established glaucoma-related in vivo models of ocular hypertension (OHT) and partial optic nerve transection (pONT), topical application of CN twice-daily for three weeks significantly reduced retinal ganglion cell loss compared to controls. Collectively, these results suggest that our novel topical CN formulation has potential as an effective neuroprotective therapy in glaucoma and other eye diseases with neuronal pathology.

Glaucoma: Hot Topics in Pharmacology.

BACKGROUND: Glaucoma comprises a group of neurodegenerative diseases resulting in retinal ganglion cell death within the optic nerve head. It is projected to affect almost 80 million people worldwide by 2020. The condition's asymptomatic nature translates to over half of glaucoma sufferers being unaware of their condition. By the time of diagnosis, irreversible blindness is likely to have occurred. Prime areas of glaucoma research therefore include identification and optimization of risk factors for the disease, accurate and early diagnostic tools and novel therapeutic methods. METHODS: The goal of this review was to summarize main areas of latest glaucoma research into risk factors of glaucoma, diagnostic tools and treatments. PubMed was used to search for terms including glaucoma risk factors, glaucoma diagnostics, glaucoma treatment, glaucoma drug delivery and glaucoma IOP. RESULTS: The evidence for risk factors of low CSF pressure, IOP, smoking, vascular risk factors and light toxicity is described. Latest diagnostic and monitoring techniques for glaucoma include SD-OCT, DARC and IOP telemetry. Current and emerging medical and surgical treatments in glaucoma are discussed. Rho kinase inhibitors have the potential to both lower IOP and also provide neuroprotection, several of which are in clinical trials. Several other new medical treatments such as calcium channel blockers and neurotrophic agents also have the capacity to provide neuroprotection. Minimally Invasive Glaucoma Surgery (MIGS) devices provide an improved safety profile compared to traditional trabeculectomy; the latest ab interno and ab externo devices are described. Novel drug delivery methods, including punctual plugs and contact lenses, help overcome the challenges with patient adherence. CONCLUSION: The ultimate goals are to reduce the individual patient risk factors associated with glaucoma, diagnose the condition early and to find treatments that not only reduce IOP but also reverse neurodegeneration of RGCs. The usage of combinations of novel medical and surgical treatments may help maximize IOP reduction and neuroprotection.