Ophthalmology
Recent Submissions
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Amblyopia, deprivation and health disparities research: challenges in 2020.No abstract available
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Adult presentation of x-linked retinoschisis: patient and physician perspectives.his commentary article is co-authored by an adult patient with X-linked retinoschisis and two ophthalmologists affiliated with the University Hospitals Birmingham NHS Foundation Trust. It describes the patient's experiences of sight loss and the diagnosis and management of X-linked retinoschisis. The treating ophthalmologists then draw upon these experiences and discuss the disease and associated sight loss in a wider context.
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A clinician's guide to artificial intelligence: how to critically appraise machine learning studies.In recent years, there has been considerable interest in the prospect of machine learning models demonstrating expert-level diagnosis in multiple disease contexts. However, there is concern that the excitement around this field may be associated with inadequate scrutiny of methodology and insufficient adoption of scientific good practice in the studies involving artificial intelligence in health care. This article aims to empower clinicians and researchers to critically appraise studies of clinical applications of machine learning, through: (1) introducing basic machine learning concepts and nomenclature; (2) outlining key applicable principles of evidence-based medicine; and (3) highlighting some of the potential pitfalls in the design and reporting of these studies.
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A global review of publicly available datasets for ophthalmological imaging: barriers to access, usability, and generalisability.Health data that are publicly available are valuable resources for digital health research. Several public datasets containing ophthalmological imaging have been frequently used in machine learning research; however, the total number of datasets containing ophthalmological health information and their respective content is unclear. This Review aimed to identify all publicly available ophthalmological imaging datasets, detail their accessibility, describe which diseases and populations are represented, and report on the completeness of the associated metadata. With the use of MEDLINE, Google's search engine, and Google Dataset Search, we identified 94 open access datasets containing 507 724 images and 125 videos from 122 364 patients. Most datasets originated from Asia, North America, and Europe. Disease populations were unevenly represented, with glaucoma, diabetic retinopathy, and age-related macular degeneration disproportionately overrepresented in comparison with other eye diseases. The reporting of basic demographic characteristics such as age, sex, and ethnicity was poor, even at the aggregate level. This Review provides greater visibility for ophthalmological datasets that are publicly available as powerful resources for research. Our paper also exposes an increasing divide in the representation of different population and disease groups in health data repositories. The improved reporting of metadata would enable researchers to access the most appropriate datasets for their needs and maximise the potential of such resources.
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Automated quantification of posterior vitreous inflammation: optical coherence tomography scan number requirements.Quantifying intraocular inflammation is crucial in managing uveitis patients. We assessed the minimum B-scan density for reliable automated vitreous intensity (VI) assessment, using a novel approach based on optical coherence tomography (OCT). OCT volume scans centered on the macula were retrospectively collected in patients with uveitis. Nine B-scans per volume scan at fixed locations were automatically analyzed. The following B-scan selections were compared against the average score of 9 B-scans per volume scan as a reference standard: 1/3/5/7 central scans (1c/3c/5c/7c), 3 widely distributed scans (3w). Image data of 49 patients (31 females) were included. The median VI was 0.029 (IQR: 0.032). The intra-class-correlation coefficient of the VI across the 9 B-scans was 0.923. The median difference from the reference standard ranged between 0.001 (7c) and 0.006 (1c). It was significantly lower for scan selection 3w than 5c, p(adjusted) = 0.022, and lower for selection 7c than 3w, p(adjusted) = 0.003. The scan selections 7c and 3w showed the two highest areas under the receiver operating curve (0.985 and 0.965, respectively). Three widely distributed B-scans are sufficient to quantify VI reliably. Highest reliability was achieved using 7 central B-scans. Automated quantification of VI in uveitis is reliable and requires only few OCT B-scans.
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Adherence with medical therapy for primary open-angle glaucoma in Kenya - a pilot study.Background/objectives: Adherence is a major challenge in topical glaucoma therapy, particularly in an African context. We report a pilot study assessing adherence independently for the first time in an African context. Subjects/methods: Participants with newly diagnosed open-angle glaucoma received a weighed bottle of Lumigan 0.01% with counselling on therapy. The bottles were returned monthly for renewal and weighed on return to estimate drops taken during the period. Data collection was for one year with a short compliance questionnaire. Results: 11 patients participated. 5 (45%) failed to complete one full year of topical therapy. The overall mean number of drops per eye per day was 1.74 (SD 0.69) for the 6 with one year of monthly returned bottles and controlled IOPs at each visit. Self-perception of compliance in these patients was good. Conclusion: The signs of poor adherence based on both self-report (previous literature), and in this small-scale study of an objective measure suggest medication may not be the first-line treatment of choice in this environment. Our report does, however, raise the possibility that those patients who return for repeat prescriptions and review are indeed adhering to their treatment regimens.
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A new era for giant cell arteritis.The landscape of the investigation and management of giant cell arteritis (GCA) is advancing. In this review we will outline the recent advances by searching the current English literature for relevant articles using key words of giant cell arteritis, temporal arteritis, Horton's disease, investigation, and treatment. Delay in diagnosis, diagnostic uncertainty and glucocorticoid (GC) morbidity are among the highest concerns of clinicians and patients in this disease area. The positive news is that fast track pathways, imaging techniques and new therapies are emerging for routine management of GCA. Future directions for intervention in the treatment paradigm will be discussed.
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Bilateral autologous penetrating keratoplasty following periorbital necrotising fasciitis.The case report describes a rare instance of a man in his 70s with periorbital necrotising fasciitis (NF) who underwent bilateral autologous penetrating keratoplasty. NF is an acute infection that can lead to severe complications, including vision loss. The patient presented with severe facial swelling and necrosis of the right eyelid, treated with surgical debridement and antibiotics. Post-surgery, he lost vision in the right eye due to compressive optic neuropathy and developed exposure keratopathy, which was managed with tarsorrhaphy. His left eye had poor vision due to herpetic corneal scarring. He met the criteria for a bilateral autologous keratoplasty, transferring his healthy right cornea to his otherwise healthy left eye and the damaged left cornea to the right eye. The surgery was successful, and at 9 months post-operation, the patient achieved improved vision (6/36) and is awaiting contact lens fitting. The report highlights the advantages and considerations of autokeratoplasty over conventional corneal transplants.
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Calculating optic nerve planning organ at risk volume margins for stereotactic radiosurgery using optic nerve motion determined using MRI.Objectives: The combination of sharp dose gradients in stereotactic radiosurgery (SRS) and minute optic nerve motion may significantly increase dose to the optic nerves when treating perioptic lesions. The aim of this study was to calculate optic nerve planning organ at risk volume (PRV) margins for CyberKnife SRS treatment planning. Methods: MRI scans were taken of 10 healthy volunteers looking left, right, up, down, and straight ahead to measure optic nerve motion. The measured optic nerve motion and the uncertainties in the technical accuracy of CyberKnife were used to calculate optic nerve PRV margins. Results: Two optic nerve PRV margins were calculated: a non-isotropic margin of mL/R,PRV=3 mm, mSup/Inf,PRV=2 mm, and mAnt/Post,PRV=1 mm which considers the full range of motion measured in a worst case scenario; and an isotropic margin of mPRV=1 mm which considers a scenario where patients are asked to look neutrally during imaging and treatment. Applying these PRVs to 8 historical sphenoid wing meningioma CyberKnife plans showed tolerance levels may be exceeded due to optic nerve motion. Conclusions: Optic nerve PRV margins may be needed in CyberKnife planning to reduce risk to the optic nerves. The use of a mPRV=1 mm PRV to account for organ motion, along with instructing patients to hold their gaze neutrally during imaging and treatment, may be a suitable organ sparing strategy. Advances in knowledge: Measured optic nerve motion and the technical accuracy of the CyberKnife system have been used to calculate optic nerve PRV margins.
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Early versus delayed timing of vitrectomy after open-globe injuryThis is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of early versus delayed timing of vitrectomy after open-globe injury on visual outcomes.
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Bilateral acute anterior uveitis and iris atrophy caused by moxifloxacinA 56-year-old paramedic was admitted to hospital and treated for severe pneumonia. Shortly after initiating antibiotic treatment (including moxifloxacin), he developed bilaterally painful eyes and was diagnosed with bilateral acute anterior uveitis (AAU). Three years later, he was referred to the ophthalmology clinic with bilateral iris transillumination suggesting iris atrophy and limited pupillary dilation, indicating iris sphincter muscle paralysis. AAU typically presents unilaterally. An onset of bilateral AAU is unusual and warrants investigation for underlying systemic cause. The fluoroquinolone moxifloxacin has been reported in a limited number of cases as a causative agent of bilateral AAU and iris atrophy. This case provides additional supporting evidence that moxifloxacin may cause degradation of collagen and iris muscle in the eye, as well as elsewhere in the body, such as in blood vessels. Additionally, we present novel anterior segment ocular imaging (using optical coherence tomography) demonstrating the ability to detect iris atrophy using non-invasive imaging.
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PHOMS: An apt and accurate acronymNo abstract available
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Pharmacologic treatments for dementia and the risk of developing age-related macular degeneration.Importance: Age-related macular degeneration (AMD) is the leading cause of blindness among people aged 50 years or older worldwide. There is a need for new strategies for the prevention and treatment of AMD. There is some limited evidence to suggest the possibility of a protective association of dementia medications with the development of some types of AMD, but the evidence is weak. Objective: To investigate whether the dementia medications memantine and donepezil are associated with the risk of developing AMD. Design, setting, and participants: Three population-based cohort studies were performed using data from the Clinical Practice Research Datalink GOLD and Aurum databases from May 15, 2002, to June 21, 2022. Participants included individuals with dementia (vascular dementia, nonvascular dementia, or Alzheimer disease) aged 40 years or older. Statistical analysis was carried out between February and November 2023. Exposures: Exposures were dementia medications. Cohort 1 compared patients prescribed donepezil with those prescribed rivastigmine or galantamine using the new-user design. Cohort 2 compared memantine with donepezil, rivastigmine, or galantamine using the prevalent new-user design. In a sensitivity analysis, cohort 3 compared memantine with rivastigmine or galantamine only. Main outcomes and measures: New diagnosis of AMD. Results: There were 132 846 individuals (mean [SD] age, 80.4 [7.6] years; 61.8% women; mean [SD] body mass index [BMI], 25.5 [4.6]) with a diagnosis of dementia included in cohort 1, 159 419 individuals (mean [SD] age, 81.2 [7.6] years; 59.7% women; mean [SD] body mass index [BMI], 25.6 [4.7]) with a diagnosis of dementia included in cohort 2, and 92 328 individuals with a diagnosis of dementia included in cohort 3 (mean [SD] age, 80.9 [7.7] years; 58.5% women; mean [SD] body mass index [BMI], 25.5 [4.7]). The adjusted hazard ratio (HR) for donepezil compared with rivastigmine or galantamine (cohort 1) was 0.95 (95% CI, 0.67-1.35). The adjusted HR for memantine compared with donepezil, rivastigmine, or galantamine (cohort 2) was 1.03 (95% CI, 0.83-1.27). The adjusted HR for memantine vs rivastigmine or galantamine only (cohort 3) was 1.24 (95% CI, 0.83-1.86). Conclusions and relevance: This cohort study of patients with dementia found no significant associations between memantine or donepezil compared with other dementia medications and the risk of development of AMD. Further research is recommended to examine any possible pathophysiological protective action of memantine and other dementia medications against the development of AMD.
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Recent advances in neuro-ophthalmology.This review article represents a collaborative effort across continents, bringing together the latest developments in neuro-ophthalmology with a focus on innovative diagnostic and therapeutic modalities that are shaping the future of the field. Among the most significant advancements is the rise of optical coherence tomography (OCT), now recognized as an indispensable tool in neuro-ophthalmological research, providing unparalleled insights into optic nerve and central nervous system pathologies. Gene therapy, particularly for conditions such as Leber's hereditary optic neuropathy, marks a new frontier in personalized medicine, offering hope for previously untreatable conditions. The article also examines the transformative role of telemedicine and artificial intelligence (AI) in clinical practice, which are revolutionizing patient care and enhancing diagnostic precision. Furthermore, it highlights the impact of novel serological biomarkers on the understanding and management of immune-mediated optic neuritis, and discusses the introduction of new therapeutic agents like Tocilizumab and Teprotumumab, which are redefining treatment paradigms. Collectively, these advancements reflect the profound influence of modern medicine on neuro-ophthalmology, paving the way for improved patient outcomes and fostering new avenues for research and clinical practice.
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Assessment of necroptosis in the retina in a repeated primary ocular blast injury mouse model.Primary blast injury (caused by the initial rapid increase in pressure following an explosive blast) to the retina and optic nerve (ON) causes progressive visual loss and neurodegeneration. Military personnel are exposed to multiple low-overpressure blast waves, which may be in quick succession, such as during breacher training or in combat. We investigated the necroptotic cell death pathway in the retina in a mouse repeated primary ocular blast injury (rPBI) model using immunohistochemistry. We further evaluated whether intravitreal injections of a potent necroptosis inhibitor, Necrostatin-1s (Nec-1s), protects the retina and ON axons by retinal ganglion cells (RGC) counts, ON axonal counting and optical coherence tomography (OCT) analysis of vitreous haze. Receptor interacting protein kinase (RIPK) 3, increased in the inner plexiform layer 2 days post injury (dpi) and persisted until 14 dpi, whilst RIPK1 protein expression did not change after injury. The number of degenerating ON axons was increased at 28 dpi but there was no evidence of a reduction in the number of intact ON axons or RNA-binding protein with multiple splicing (RBPMS)+ RGC in the retina by 28 dpi in animals not receiving any intravitreal injections. But, when intravitreal injections (vehicle or Nec-1s) were given there was a significant reduction in RBPMS+ RGC numbers, suggesting that rPBI with intraocular injections is damaging to RGC. There were fewer RGC lost after Nec-1s than vehicle injection, but there was no effect of Nec-1s or vehicle treatment on the number of degenerating axons. OCT analysis demonstrated no effect of rPBI on vitreous haze, but intravitreal injection combined with rPBI increased vitreous haze (P = 0.004). Whilst necroptosis may be an active cell death signalling pathway after rPBI, its inhibition did not prevent cell death, and intravitreal injections in combination with rPBI increased vitreous inflammation and reduced RBPMS+
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The medical algorithmic audit.Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.
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Total anterior staphyloma secondary to acanthamoeba keratitis.There are very few published cases of total anterior staphyloma, all of which have been reported as secondary to fungal keratitis. This study reports the clinical and histopathological findings and subsequent management of a 27-year-old healthy female patient who developed total anterior staphyloma after poor compliance with treatment for clinically diagnosed acanthamoeba keratitis. She underwent a successful evisceration with good long-term results. This case highlights that total anterior staphyloma may also result from untreated keratitis which is not fungal in origin. In cases of fungal and acanthamoeba keratitis, patient compliance with both treatment and follow-up is paramount to avoid vision-threatening sequelae that present significant challenges in their management.
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WFS1 protein expression correlates with clinical progression of optic atrophy in patients with Wolfram syndromeBackground: Wolfram syndrome (WFS) is a rare disorder characterised by childhood-onset diabetes mellitus and progressive optic atrophy. Most patients have variants in the WFS1 gene. We undertook functional studies of WFS1 variants and correlated these with WFS1 protein expression and phenotype. Methods: 9 patients with a clinical diagnosis of WFS were studied with quantitative PCR for markers of endoplasmic reticulum (ER) stress and immunoblotting of fibroblast protein extracts for WFS1 protein expression. Luciferase reporter assay was used to assess ATF-6 dependent unfolded protein response (UPR) activation. Results: 6 patients with compound heterozygous nonsense mutations in WFS1 had no detectable WFS1 protein expression; 3 patients with missense variants had 4%, 45% and 48% WFS1 protein expression. One of these also had an OPA1 mutation and was reclassified as autosomal dominant optic atrophy-plus syndrome. There were no correlations between ER stress marker mRNA and WFS1 protein expression. ERSE-luciferase reporter indicated activation of the ATF6 branch of UPR in two patients tested. Patients with partial WFS1 expression showed milder visual acuity impairment (asymptomatic or colour blind only), compared with those with absent expression (registered severe vision impaired) (p=0.04). These differences remained after adjusting for duration of optic atrophy. Conclusions: Patients with WFS who have partial WFS1 protein expression present with milder visual impairment. This suggests a protective effect of partial WFS1 protein expression on the severity and perhaps progression of vision impairment and that therapies to increase residual WFS1 protein expression may be beneficial.