RSS 1.0Ophthalmology
Recent Submissions
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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.
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Temporary keratoprosthesis and primary corneal graft for ocular trauma: A systematic review and meta-analysis.Purpose: When severe retinal and corneal injury occur together, a temporary keratoprosthesis (TKP) is often a last resort to allow posterior segment visualization to enable vitreoretinal surgery, followed by a penetrating keratoplasty (PKP) which can restore corneal clarity in a single operation. We aimed to assess visual outcomes following combined PKP and vitreoretinal surgery with the use of a TKP for cases of ocular trauma. Design: A systematic literature review was performed following PRISMA guidelines (PROSPERO registration number: CRD42023423518). Methods: CENTRAL, MEDLINE, Embase, ISRCTN registry, and ClinicalTrials.gov were searched from inception to 27 April 2023. Randomized and nonrandomized studies assessing visual outcomes after combined vitreoretinal surgery and PKP with the use of a TKP after ocular trauma were eligible for inclusion. Outcomes included change in best corrected visual acuity, corneal graft survival and retinal reattachment at final follow up. Proportional meta-analysis was used to estimate the overall rate of the primary outcomes. Risk of bias for nonrandomized studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist for case series. Results: A total of 19 studies met inclusion criteria reporting a total of 352 eyes. All studies were retrospective and nonrandomized with follow up times ranging from 6 to 91 months, with at least 79% of outcomes reported after 6 months. After combined surgery the rate of corneal graft survival was 52% (95% CI 0.41-0.62; I2 60%) successful retinal attachment was 79% (95% CI 0.73-0.84; I2 0%). and improved visual acuity, when compared to no change or decrease in visual acuity, was 45% (95% CI 0.32-0.59; I2 66%). Conclusion: Patients with severe injury affecting the anterior and posterior segments have very limited treatment options. This systematic review found that when combined vitreoretinal surgery and PKP with a TKP are performed, approximately half of corneal grafts survive, anatomically successful retinal reattachment is likely, and a similar proportion of patients benefit in terms of improved visual acuity, compared to their preoperative function. This systematic review of the available literature may help inform surgeons of the benefits of using a TKP for cases of ocular trauma.
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Myeloproliferative neoplasia masquerading as idiopathic intracranial hypertension: a case reportAbstract P113 of the European Neuro-Ophthalmological Society (EUNOS) 15th Meeting, Birmingham, 20-23 June 2022.
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Diagnostic performance of deep learning for infectious keratitis: a systematic review and meta-analysisBackground: Infectious keratitis (IK) is the leading cause of corneal blindness globally. Deep learning (DL) is an emerging tool for medical diagnosis, though its value in IK is unclear. We aimed to assess the diagnostic accuracy of DL for IK and its comparative accuracy with ophthalmologists. Methods: In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, and clinical registries for studies related to DL for IK published between 1974 and July 16, 2024. We performed meta-analyses using bivariate models to estimate summary sensitivities and specificities. This systematic review was registered with PROSPERO (CRD42022348596). Findings: Of 963 studies identified, 35 studies (136,401 corneal images from >56,011 patients) were included. Most studies had low risk of bias (68.6%) and low applicability concern (91.4%) in all domains of QUADAS-2, except the index test domain. Against the reference standard of expert consensus and/or microbiological results (seven external validation studies; 10,675 images), the summary estimates (95% CI) for sensitivity and specificity of DL for IK were 86.2% (71.6-93.9) and 96.3% (91.5-98.5). From 28 internal validation studies (16,059 images), summary estimates for sensitivity and specificity were 91.6% (86.8-94.8) and 90.7% (84.8-94.5). Based on seven studies (4007 images), DL and ophthalmologists had comparable summary sensitivity [89.2% (82.2-93.6) versus 82.2% (71.5-89.5); P = 0.20] and specificity [(93.2% (85.5-97.0) versus 89.6% (78.8-95.2); P = 0.45]. Interpretation: DL models may have good diagnostic accuracy for IK and comparable performance to ophthalmologists. These findings should be interpreted with caution due to the image-based analysis that did not account for potential correlation within individuals, relatively homogeneous population studies, lack of pre-specification of DL thresholds, and limited external validation. Future studies should improve their reporting, data diversity, external validation, transparency, and explainability to increase the reliability and generalisability of DL models for clinical deployment.
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Quantitative and qualitative assessment of anterior segment optical coherence tomography capture of disease state in childhood anterior uveitisBackground/aims: Anterior segment optical coherence tomography (AS-OCT) assessment of anterior chamber inflammation is an emerging tool. We describe the performance of AS-OCT in a paediatric population. Methods: A mixed-methods prospective study, using routine clinical assessment as reference standard, and AS-OCT, with Tomey CASIA2 or Heidelberg Spectralis HS1, as index test, with data collected on patient perceptions of imaging. Repeatability, diagnostic indices, responsiveness to clinical change and clinical correlations of imaging-based metrics (image cell count, size, density and brightness) were assessed, with construction of receiver operated characteristic curves. Exploratory thematic analysis of responses from families was undertaken. Results: A total of 90 children (180 eyes) underwent imaging. Bland Altman limits of agreement for CASIA2 repeatability ranged from +17 cells (95% CI 13.6 to 21.1) to -19 cells (95% CI -15.6 to -23.2) and HS1 from +1 (95% CI 0.9 to 1.2) to -1.0 (-1.2 to -0.8) cells. CASIA2 imaging had higher sensitivity of 0.92 (95% CI 0.78 to 0.97) vs HS1 imaging 0.17 (95% CI 0.07 to 0.34), with positive correlation between clinical grade and CASIA2 cell count (coefficient 12.8, p=0.02, 95% CI 2.2 to 23.4). Change in clinical grade at follow-up examinations correlated with change in image based 'cell' count (r2=0.79, p<0.001). Patients reported a potential positive impact of seeing their disease activity. Conclusion: Our findings suggest that OCT-based imaging holds the promise of deeper understanding of disease, improved patient experience and more granular monitoring of activity with resultant improved outcomes, but further work is needed to refine acquisition and analysis protocols.
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Stability of OCT and OCTA in the intensive therapy unit setting.To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24-48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 µm, p = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients.
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Selective laser trabeculoplasty versus 0·5% timolol eye drops for the treatment of glaucoma in Tanzania: a randomised controlled trial.Background: Glaucoma is a major cause of sight loss worldwide, with the highest regional prevalence and incidence reported in Africa. The most common low-cost treatment used to control glaucoma is long-term timolol eye drops. However, low adherence is a major challenge. We aimed to investigate whether selective laser trabeculoplasty (SLT) was superior to timolol eye drops for controlling intraocular pressure (IOP) in patients with open-angle glaucoma. Methods: We did a two-arm, parallel-group, single-masked randomised controlled trial at the Eye Department of Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Eligible participants (aged ≥18 years) had open-angle glaucoma and an IOP above 21 mm Hg, and did not have asthma or a history of glaucoma surgery or laser. Participants were randomly assigned (1:1) to receive 0·5% timolol eye drops to administer twice daily or to receive SLT. The primary outcome was the proportion of eyes from both groups with treatment success, defined as an IOP below or equal to target pressure according to glaucoma severity, at 12 months following randomisation. Re-explanation of eye drop application or a repeat SLT was permitted once. The primary analysis was by modified intention-to-treat, excluding participants lost to follow-up, using logistic regression; generalised estimating equations were used to adjust for the correlation between eyes. This trial was registered with the Pan African Clinical Trials Registry, number PACTR201508001235339. Findings: 840 patients were screened for eligibility, of whom 201 (24%) participants (382 eligible eyes) were enrolled between Aug 31, 2015, and May 12, 2017. 100 (50%) participants (191 eyes) were randomly assigned to the timolol group and 101 (50%; 191 eyes) to the SLT group. After 1 year, 339 (89%) of 382 eyes were analysed. Treatment was successful in 55 (31%) of 176 eyes in the timolol group (16 [29%] of 55 eyes required repeat administration counselling) and in 99 (61%) of 163 eyes in the SLT group (33 [33%] of 99 eyes required repeat SLT; odds ratio 3·37 [95% CI 1·96-5·80]; p<0·0001). Adverse events (mostly unrelated to ocular events) occurred in ten (10%) participants in the timolol group and in eight (8%) participants in the SLT group (p=0·61). Interpretation: SLT was superior to timolol eye drops for managing patients with open-angle high-pressure glaucoma for 1 year in Tanzania. SLT has the potential to transform the management of glaucoma in sub-Saharan Africa, even where the prevalence of advanced glaucoma is high. Funding: Christian Blind Mission, Seeing is Believing Innovation Fund, and the Wellcome Trust.
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Public perceptions of eye symptoms and hospital services during the first UK lockdown of the COVID-19 pandemic: a web survey study.Objective: This study aimed to explore the British public's healthcare-seeking beliefs concerning eye symptoms, and assess how the first COVID-19 lockdown influenced these. Methods and analysis: An anonymous web-based survey was disseminated through mailing lists and social media between June and August 2020. The survey sought participants' views on the severity and urgency of the need for medical review for four ophthalmic and two general medical scenarios on a five-point scale. Participants were asked to answer questions twice: once ignoring the COVID-19 pandemic, and once taking this into account, with additional questions asked to identify factors influencing the decision to seek medical attention and ward admission. Results: A total of 402 participants completed the survey (mean age 61.6 years, 63.1% female and 87.7% of white ethnicity). Scores for symptom severity and urgency of medical review increased significantly with the severity of the clinical scenario (both p<0.001). However, participants gave significantly lower scores for the urgency of medical attention when accounting for the COVID-19 pandemic (compared with no pandemic) for all scenarios (all p<0.001). Younger age, greater deprivation and non-white ethnicity were correlated with a lower perception of seriousness and urgency of medical attention. Conclusions: During the first UK lockdown of the COVID-19 pandemic, reduced urgency of medical review for ocular and systemic pathologies was reported in response to the pandemic, which represents a barrier to healthcare-seeking behaviour. This has the potential to critically delay medical review and timely management, negatively impacting patient outcomes.