Robot-Assisted Eye Surgery: A Systematic Review of Effectiveness, Safety, and Practicality in Clinical Settings.

Purpose: Surgical innovation in ophthalmology is impeded by the physiological limits of human motion, and robotic assistance may facilitate an expansion of the surgical repertoire. We conducted a systematic review to identify ophthalmic procedures in which robotic systems have been trialled, evaluate their performance, and explore future directions for research and development of robotic techniques. Methods: The Cochrane Library, Embase, MEDLINE, Scopus, and Web of Science were searched. Screening adhered to five criteria: (1) English language; (2) primary research article; (3) human patients; (4) ophthalmological surgery; and (5) robot-assisted surgery. Quality assessment was conducted with Joanna Briggs Institute Tools for Critical Appraisal. The study protocol was registered prospectively (PROSPERO ID CRD42023449793). Results: Twelve studies were included. In comparative studies, there was no difference in the occurrence of ocular harms in robot-assisted procedures and conventional surgery. However, robotic assistance did not demonstrate consistent benefits over manual surgery in terms of effectiveness or practicality, likely reflecting the learning curve associated with these systems. Single studies indicated the potential of robotic assistance to improve the consistency of subretinal drug infusion and efficiency of instrument manipulation in vitreoretinal surgery. Conclusions: Proof-of-concept studies have demonstrated the potential of robotic assistance to facilitate procedures otherwise infeasible or impractical, and may broaden access to surgery. However, robot-assisted surgery has not yet demonstrated any significant benefits over standard surgical practice. Improving the speed and reducing perioperative requirements of robot-assisted surgery are particular priorities for research and innovation to improve the practicality of these novel techniques. Translational Relevance: This systematic review summarizes the potential and limitations of robotic systems for assisting eye surgery and outlines what is required for these systems to benefit patients and surgeons.

Nanohydroxyapatite Coating Attenuates Fibrotic and Immune Responses to Promote Keratoprosthesis Biointegration in Advanced Ocular Surface Disorders.

Keratoprosthesis (KPro) implantation is frequently the only recourse for patients with severe corneal disease. However, problems arise due to inadequate biointegration of the KPro, particularly the PMMA optical cylinder, such as tissue detachment, tissue melting, or eye-threatening infection in the interface. Here, using the AuroKPro as a model prosthesis, a surface functionalization approach─coating the optical cylinder with nanohydroxyapatite (nHAp)─was trialed in rabbit eyes with and without a proceeding chemical injury. In chemically injured eyes, which simulated total limbal epithelial stem cell deficiency, clear benefits were conferred by the coating. The total modified Hackett-McDonald score and area of tissue apposition differences 12 weeks after implantation were 5.0 and 22.5%, respectively. Mechanical push-in tests revealed that 31.8% greater work was required to detach the tissues. These differences were less marked in uninjured eyes, which showed total score and tissue apposition differences of 2.5 and 11.5%, respectively, and a work difference of 23.5%. The improved biointegration could be contributed by the attenuated expression of fibronectin (p = 0.036), collagen 3A1 (p = 0.033), and α-smooth muscle actin (p = 0.045)─proteins typically upregulated during nonadherent fibrous capsule envelopment of bioinert material─adjacent to the optical cylinders. The coating also appeared to induce a less immunogenic milieu in the ocular surface tissue, evidenced by the markedly lower expression of tear proteins associated with immune and stimulus responses. Collectively, the level of these tear proteins in eyes with coated prostheses was 1.1 ± 13.0% of naïve eyes: substantially lower than with noncoated KPros (246.5 ± 79.3% of naïve, p = 0.038). Together, our results indicated that nHAp coating may reduce the risk of prosthesis failure in severely injured eyes, which are representative of the cohort of KPro patients.

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. In summary, 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. STATEMENT OF SIGNIFICANCE: Corneal blindness affects over six million patients worldwide. For patients requiring corneal transplantation, current cadaver-based procedures are limited by the short shelf-life of donor tissue. Electron-beam (E-beam) sterilisation extends this shelf-life from weeks to years but there are few published studies of its use. We demonstrated that E-beam-irradiated corneas are a viable source of lenticules for implantation. We conducted in vitro, in vivo, and ex vivo comparisons of E-beam and fresh corneal lenticules. The only differences exhibited by E-beam-treated lenticules were reduced expression of glycosaminoglycans, resulting in greater tissue compression and lower refraction suggesting that a thicker cut is required to achieve the same optical and refractive outcome; and lower Young's modulus indicating extra care with handling.

Artificial intelligence and digital health in global eye health: opportunities and challenges.

Global eye health is defined as the degree to which vision, ocular health, and function are maximised worldwide, thereby optimising overall wellbeing and quality of life. Improving eye health is a global priority as a key to unlocking human potential by reducing the morbidity burden of disease, increasing productivity, and supporting access to education. Although extraordinary progress fuelled by global eye health initiatives has been made over the last decade, there remain substantial challenges impeding further progress. The accelerated development of digital health and artificial intelligence (AI) applications provides an opportunity to transform eye health, from facilitating and increasing access to eye care to supporting clinical decision making with an objective, data-driven approach. Here, we explore the opportunities and challenges presented by digital health and AI in global eye health and describe how these technologies could be leveraged to improve global eye health. AI, telehealth, and emerging technologies have great potential, but require specific work to overcome barriers to implementation. We suggest that a global digital eye health task force could facilitate coordination of funding, infrastructural development, and democratisation of AI and digital health to drive progress forwards in this domain.

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.

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.

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.

Temporomandibular joint anatomy: Ultrasonographic appearances and sexual dimorphism.

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.