Vitamin A, systemic T-cells, and the eye: Focus on degenerative retinal disease

The first discovered vitamin, vitamin A, exists in a range of forms, primarily retinoids and provitamin carotenoids. The bioactive forms of vitamin A, retinol and retinoic acid, have many critical functions in body systems including the eye and immune system. Vitamin A deficiency is associated with dysfunctional immunity, and presents clinically as a characteristic ocular syndrome, xerophthalmia. The immune functions of vitamin A extend to the gut, where microbiome interactions and nutritional retinoids and carotenoids contribute to the balance of T cell differentiation, thereby determining immune status and contributing to inflammatory disease around the whole body. In the eye, degenerative conditions affecting the retina and uvea are influenced by vitamin A. Stargardt’s disease (STGD1; MIM 248200) is characterised by bisretinoid deposits such as lipofuscin, produced by retinal photoreceptors as they use and recycle a vitamin A-derived chromophore. Age-related macular degeneration features comparable retinal deposits, such as drusen featuring lipofuscin accumulation; and is characterised by parainflammatory processes. We hypothesise that local parainflammatory processes secondary to lipofuscin deposition in the retina are mediated by T cells interacting with dietary vitamin A derivatives and the gut microbiome, and outline the current evidence for this. No cures exist for Stargardt’s or age-related macular degeneration, but many vitamin A-based therapeutic approaches have been or are being trialled. The relationship between vitamin A’s functions in systemic immunology and the eye could be further exploited, and further research may seek to leverage the interactions of the gut-eye immunological axis

Temporomandibular joint anatomy: Ultrasonographic appearances and sexual dimorphism

Abstract: Introduction: Temporomandibular joint (TMJ) dysfunction is common, with a greater prevalence in females. While magnetic resonance imaging (MRI) is commonly used for clinical investigation, ultrasonography represents a potential alternative in some clinical scenarios. We designed a protocol for ultrasonographic evaluation of the TMJ and assessed its reliability. Presentation was compared between the sexes to establish whether an anatomical dichotomy underlies the female preponderance of TMJ dysfunction. Materials and methods: Ultrasound imaging of the TMJ was carried out in the longitudinal and oblique planes. Standard images were produced using model skulls and healthy volunteers. Measurements were made between the temporal bone, mandibular condyle, joint capsule and overlying skin, as well as of condylar translation during mouth opening. Both joints were scanned in 50 healthy volunteers. Measurements were repeated to evaluate reliability. A novel classification system was used to assess lateral condylar morphology. Results: The protocol facilitated reliable visualization of key anatomical features of the TMJ (average intraclass correlation coefficient = 0.75, p ¯ = 5.4E‐03). Distribution of condylar morphology differed between the sexes. The capsular‐cutaneous distance (‘joint depth’) and condylar‐temporal bone distance (‘interarticular distance’) were significantly greater in males than in females. Conclusions: Ultrasonography provides reliable views of the TMJ in two planes: longitudinal and oblique. Observed sexual dimorphism in TMJ anatomy might be associated with the female preponderance of dysfunction. With a standardized scanning protocol, ultrasound could provide a rapid, cost‐effective alternative to MRI as a point‐of‐care imaging tool in TMJ clinics

Combined Phacoemulsification and Intravitreal Dexamethasone Is an Effective Option for High-Risk Diabetic Macula Oedema Patients.

Objective Cataract surgery in diabetic patients carries an increased risk of post-operative macula oedema, particularly in those with a history of diabetic macula oedema (DMO) treatment or DMO at the time of surgery. We investigated whether simultaneous phacoemulsification with intravitreal Ozurdex® reduces the risk of developing new, or deteriorating current, DMO. Methods We conducted a retrospective review of 79 consecutive 'high-risk' diabetic patients who underwent phacoemulsification with intraocular lens insertion and intravitreal Ozurdex® implantation immediately subsequently. 'High risk' was defined as diabetic patients with prior treatment history for DMO or current DMO. Central macula thickness (CMT), best-corrected visual acuity and intraocular pressure were recorded pre-operatively, at two to four weeks and at three months post-operatively. A significant change in CMT was defined as a change of ≥0.1 LogOCT units. Results The mean age was 72.6 years; 52% were males. The mean pre-operative CMT was 365um. Thirty-seven per cent (37%) patients had prior DMO history that had resolved; 63% had confirmed DMO in surgery. Two to four weeks post-operatively, 82% of patients had stable CMT and 18% showed improvement. No patients deteriorated. Three months post-operatively, 48% of patients had stable CMT relative to pre-operative measurements, 38% improved, and 14% deteriorated. Analysis of variance (ANOVA) indicated no significant differences in response with demographical or pathological factors, including diabetic retinopathy grade and treatment history. Conclusion Phacoemulsification surgery combined with Ozurdex® insertion at the end of the procedure is a highly effective strategy for protecting against the formation of new, or the deterioration of current DMO, in the highest risk diabetic patients undergoing cataract surgery

Vitamin A, systemic T-cells, and the eye: Focus on degenerative retinal disease.

The first discovered vitamin, vitamin A, exists in a range of forms, primarily retinoids and provitamin carotenoids. The bioactive forms of vitamin A, retinol and retinoic acid, have many critical functions in body systems including the eye and immune system. Vitamin A deficiency is associated with dysfunctional immunity, and presents clinically as a characteristic ocular syndrome, xerophthalmia. The immune functions of vitamin A extend to the gut, where microbiome interactions and nutritional retinoids and carotenoids contribute to the balance of T cell differentiation, thereby determining immune status and contributing to inflammatory disease around the whole body. In the eye, degenerative conditions affecting the retina and uvea are influenced by vitamin A. Stargardt's disease (STGD1; MIM 248200) is characterised by bisretinoid deposits such as lipofuscin, produced by retinal photoreceptors as they use and recycle a vitamin A-derived chromophore. Age-related macular degeneration features comparable retinal deposits, such as drusen featuring lipofuscin accumulation; and is characterised by parainflammatory processes. We hypothesise that local parainflammatory processes secondary to lipofuscin deposition in the retina are mediated by T cells interacting with dietary vitamin A derivatives and the gut microbiome, and outline the current evidence for this. No cures exist for Stargardt's or age-related macular degeneration, but many vitamin A-based therapeutic approaches have been or are being trialled. The relationship between vitamin A's functions in systemic immunology and the eye could be further exploited, and further research may seek to leverage the interactions of the gut-eye immunological axis

Analgesia for retinopathy of prematurity screening: A systematic review.

BACKGROUND AND AIMS: Premature neonates require regular ophthalmological examination, generally indirect ophthalmoscopy, to screen for retinopathy of prematurity (ROP). Conventional analgesia is provided with topical anesthetic eyedrops and oral sugar solution, but neonates still experience significant pain. Here, the literature base was examined to evaluate the usefulness of other pharmacological analgesics. MATERIALS AND METHODS: A systematic review was undertaken, adhering to a PROSPERO preregistered protocol in accordance with PRISMA guidelines (identifier CRD42022302459). Electronic databases were searched for primary research articles on pharmacological pain interventions used for ROP screening in neonates. The primary outcome measure was pain scores recorded using validated pain scoring tools, with and without pharmacological interventions in neonates during eye examination. For analysis, studies were separated into two categories: topical anesthesia and alternative pharmacological treatments. RESULTS: Eleven studies met the inclusion criteria. Topical analgesia, oral paracetamol, and intranasal fentanyl were found to be effective in reducing the pain of eye examination. Oral morphine and inhaled nitrous oxide had no significant effect on premature infant pain profile (PIPP) scores during indirect ophthalmoscopy. DISCUSSION: In addition to topical anesthesia, premedication with oral paracetamol is recommended during screening examination for ROP. The routine use of fentanyl is not recommended due to the risk of potential side effects. Non-pharmacological measures, such as sweet oral solutions and comfort techniques should also be employed. Further research is required to determine whether the use of nitrous oxide has a role, and to develop a safe and effective analgesic strategy to fully ameliorate the pain of ROP screening

Electron beam-irradiated donor cornea for on-demand lenticule implantation to treat corneal diseases and refractive error

The cornea is the major contributor to the refractive power of the eye, and corneal diseases are a leading cause of reversible blindness. The main treatment for advanced corneal disease is keratoplasty: allograft transplantation of the cornea. Examples include lenticule implantation to treat corneal disorders (e.g. keratoconus) or correct refractive errors. These procedures are limited by the shelf-life of the corneal tissue, which must be discarded within 2-4 weeks. Electron-beam irradiation is an emerging sterilisation technique, which extends this shelf life to 2 years. Here, we produced lenticules from fresh and electron-beam (E-beam) irradiated corneas to establish a new source of tissue for lenticule implantation. In vitro, in vivo, and ex vivo experiments were conducted to compare fresh and E-beam-irradiated lenticules. Results were similar in terms of cutting accuracy, ultrastructure, optical transparency, ease of extraction and transplantation, resilience to mechanical handling, biocompatibility, and post-transplant wound healing process. Two main differences were noted. First, ~59% reduction of glycosaminoglycans resulted in greater compression of E-beam-irradiated lenticules post-transplant, likely due to reduced corneal hydration—this appeared to affect keratometry after implantation. Cutting a thicker lenticule would be required to ameliorate the difference in refraction. Second, E-beam-sterilised lenticules exhibited lower Young’s modulus which may indicate greater care with handling, although no damage or perforation was caused in our procedures. E-beam-irradiated corneas are a viable source of tissue for stromal lenticules, and may facilitate on-demand lenticule implantation to treat a wide range of corneal diseases. Our study suggested that its applications in human patients are warranted

Human spinal cord tissue is an underutilised resource in degenerative cervical myelopathy: findings from a systematic review of human autopsies.

STUDY DESIGN: Systematic review. BACKGROUND: Although degenerative cervical myelopathy (DCM) is the most prevalent spinal cord condition worldwide, the pathophysiology remains poorly understood. Our objective was to evaluate existing histological findings of DCM on cadaveric human spinal cord tissue and explore their consistency with animal models. METHODS: MEDLINE and Embase were systematically searched (CRD42021281462) for primary research reporting on histological findings of DCM in human cadaveric spinal cord tissue. Data was extracted using a piloted proforma. Risk of bias was assessed using Joanna Briggs Institute critical appraisal tools. Findings were compared to a systematic review of animal models (Ahkter et al. 2020 Front Neurosci 14). RESULTS: The search yielded 4127 unique records. After abstract and full-text screening, 19 were included in the final analysis, reporting on 150 autopsies (71% male) with an average age at death of 67.3 years. All findings were based on haematoxylin and eosin (H&E) staining. The most commonly reported grey matter findings included neuronal loss and cavity formation. The most commonly reported white matter finding was demyelination. Axon loss, gliosis, necrosis and Schwann cell proliferation were also reported. Findings were consistent amongst cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Cavitation was notably more prevalent in human autopsies compared to animal models. CONCLUSION: Few human spinal cord tissue studies have been performed. Neuronal loss, demyelination and cavitation were common findings. Investigating the biological basis of DCM is a critical research priority. Human spinal cord specimen may be an underutilised but complimentary approach

Generative Artificial Intelligence Through ChatGPT and Other Large Language Models in Ophthalmology

The rapid progress of large language models (LLMs) driving generative artificial intelligence applications heralds the potential of opportunities in health care. We conducted a review up to April 2023 on Google Scholar, Embase, MEDLINE, and Scopus using the following terms: “large language models,” “generative artificial intelligence,” “ophthalmology,” “ChatGPT,” and “eye,” based on relevance to this review. From a clinical viewpoint specific to ophthalmologists, we explore from the different stakeholders’ perspectives—including patients, physicians, and policymakers—the potential LLM applications in education, research, and clinical domains specific to ophthalmology. We also highlight the foreseeable challenges of LLM implementation into clinical practice, including the concerns of accuracy, interpretability, perpetuating bias, and data security. As LLMs continue to mature, it is essential for stakeholders to jointly establish standards for best practices to safeguard patient safety. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article