Patients' Perception of Robot-Driven Technology in the Management of Retinal Diseases.

INTRODUCTION: There is increasing application of robots and other artificial intelligence-driven technologies in the management of retinal disease. These technologies have the potential to meet increasing demands for retinal diseases. However, there is currently a lack of understanding of patients' attitudes towards use of robots in ophthalmology. This study investigates patients' attitudes towards robot-led management of retinal disease. METHODS: Paper questionnaires were distributed to 177 patients attending intravitreal treatment (IVT) at the Princess Alexandra Eye Pavilion between 1 October 2022 and 31 January 2023. The questionnaire collected information on age, sex, diagnosis and postcode. In the questionnaire, patients responded to questions about their attitudes towards robot-led diagnosis, treatment decisions and IVT injections. Responses were collected using a 5-category Likert scale which was analysed using ordinal logistic regression with adjustments for age, sex and deprivation status. RESULTS: Those from affluent socioeconomic backgrounds were significantly (p < 0.001) more accepting of robots diagnosing and deciding on treatment, although the total number of patients who were accepting was only 26 (14.7%). Furthermore, there was an increased proportion of patients who would accept robots if the robot made fewer mistakes than doctors, if the robot reduced waiting or appointment time and if the robot was able to communicate well and have empathy; the same association with socioeconomic background remains (p < 0.001). Lastly, 116 patients (65.5%) would not be happy if IVT injections were performed by a robot; this was more likely the case if the patient was female (p = 0.04) or from a more deprived socioeconomic background (p < 0.001). CONCLUSION: Attitudes towards robot involvement in diagnosis and management of retinal disease are significantly associated with socioeconomic backgrounds and sex. Additional studies are required to further investigate these determinants of robot receptiveness to ensure acceptance and compliance with treatment with these new technologies.

Practical implementation of a q4-q16 aflibercept treat-and-extend pathway for the treatment of neovascular age-related macular degeneration: Updated guidance from a UK expert panel.

OBJECTIVES: This report, based on guidance from a panel of UK retina specialists, introduces a revised intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) pathway for the treatment of neovascular age-related macular degeneration (nAMD). The T&E pathway incorporates the updated IVT-AFL label (April 2021) allowing flexible treatment intervals of 4 weeks to 16 weeks, after three initiation doses and a further dose after 8 weeks. Practical guidance is provided on the clinical implementation of the revised pathway, with the aim of supporting clinical decision-making to benefit patients and addressing capacity issues in nAMD services. METHODS: Three structured round-table meetings of UK retina specialists were held online on 19 May, 16 June and 13 October 2021. These meetings were organised and funded by Bayer. RESULTS: The authors revised the previously published consensus pathway to reflect the changes to the IVT-AFL label and developed guidelines for the implementation of the pathway in UK clinical practice. The guidelines include topics such as recommendations for extending patients with 2- or 4-week adjustments, extending patients to 16-week treatment intervals, managing fellow eye involvement, and reducing treatment intervals for patients with particularly active disease. CONCLUSIONS: The revised IVT-AFL T&E nAMD pathway offers guidance to clinicians seeking to increase the dosing flexibility of IVT-AFL, with 4- to 16-week treatment intervals, in line with the updated IVT-AFL label, to meet the continually evolving demands of nAMD service provision.

Depression secondary to vision loss in old age and an effective rapid screening tool for undiagnosed cases.

BACKGROUND: Zenebe et al. recently stated that despite depression being a common mental health problem in the elderly population, it is underdiagnosed in over half of the cases (Zenebe et al. in Ann Gen Psychiatry, 2021). They described an extensive list of risk factors associated with geriatric depression. However, we noted that they did not include ophthalmic conditions in this list which have previously been identified as an important risk factor for depression in the elderly. MAIN BODY: To determine the extent of undiagnosed anxiety and depression in our elderly population with vision loss, we screened a cohort of our patients, over 60 years with vision loss secondary to macular disease for both conditions. Our cohort included 104 patients with mean best corrected visual acuity 0.58 LogMAR (Snellen equivalent 6/24). In this group, we identified 29.8% (31/104) and 28.8% (30/104) of patients with at least one depression or anxiety-related symptom, respectively, in the past 2 weeks. We identified 7.7% (8/104) and 3.8% (4/104) who had significant symptoms of depression and anxiety, respectively, that warranted further follow-up. Only two of these patients had previously been diagnosed with anxiety or depression with the majority having no previous history of either condition. Patients from our cohort who screened for depression or anxiety often cited frustration completing tasks and loss of independence secondary to declining vision. They also complained that the vision loss resulted in a lack of confidence which in turn resulted in social isolation and loneliness. Most of the patients welcomed referral to their GP for follow-up for input regarding their mental health and they also stated an interest in attending hospital optometry low vision services and counselling support. CONCLUSIONS: With increasing time pressures on healthcare services and the rising use of virtual clinics especially during the COVID-19 pandemic, it is still essential to screen efficiently for depression in those elderly patients who are at significant risk. There is a considerable burden of major depressive disease in the geriatric population, and we would recommend that physicians (Geriatricians, GPs, Ophthalmologists etc.) screen elderly patients with vision loss for depression using the rapid screening tool which we suggest.

Novel biallelic USH2A variants in a patient with usher syndrome type IIA- a case report.

BACKGROUND: Usher Syndrome is the commonest cause of inherited blindness and deafness. The condition is clinically and genetically heterogeneous, with no current treatment. We report a case carrying novel biallelic variants in USH2A causing progressive early adolescent onset visual and hearing impairment consistent with Usher Syndrome Type IIA. CASE PRESENTATION: Our patient presented at age 13 with progressive visual field loss and hearing loss, associated with early onset of cataract in her 40s requiring lens extraction. Now 52 years old, latest best corrected visual acuity (BCVA) stands at Logmar Right Eye (RE) 0.8 and Left Eye (LE) 0.2, with significantly constricted visual fields bilaterally. She was registered partially sighted age 46. Clinical and molecular genetic assessment of the proband was consistent with a diagnosis of Usher Syndrome Type IIA. Genetic testing identified two novel USH2A variants, resulting in the premature termination codon p.Leu30Ter and a missense mutation p.Cys3251Tyr. Segregation analysis confirmed that these variants were biallelic in the affected case. Comprehensive in silico analysis confirmed that these mutations are the probable cause of Usher Syndrome Type IIA in this individual. CONCLUSIONS: The identification of novel mutations in USH2A increases the spectrum of genetic variations that lead to Usher Syndrome, aiding genetic diagnosis, assessment of patient prognosis, and emphasising the importance of genetic testing to identify new mutations in patients with undiagnosed progressive visual loss.

Ten-year mortality and long-term visual acuity outcomes in patients with exudative age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections.

PURPOSE: There are limited real-world data on long-term mortality and visual outcomes in patients treated with anti-vascular endothelial growth factor (VEGF) for exudative age-related macular degeneration (exudative AMD). We assessed 10-year mortality and clinical outcomes in exudative AMD patients treated with intravitreal therapy (IVT) anti-VEGF injections on a pro-re-nata (PRN) regime following a standard loading regime. METHODS: Retrospective cohort study of the first 216 exudative AMD patients receiving IVT anti-VEGF for exudative AMD at a public tertiary referral hospital in Scotland. Main outcome measures were mortality, cause of death and best-corrected visual acuity (BCVA). RESULTS: A total of 216 patients were included. Mean age at presentation was 79.1 years [standard deviation (SD) 6.9]. Mean follow-up duration was 6.6 years (SD 3.2) during which there was a mean 24.3 Early Treatment Diabetic Retinopathy Study (ETDRS) letter loss in BCVA (P < 0.0001). Patients received a mean of 2.2 (SD 1.8) injections per year of follow-up. Overall, 52.6% (113/216) died during the period studied. Observed annual mortality incidence risk was 6.5% (SD 3.1) and was found to be significantly lower (P = 0.0064) than the expected annual death incidence risk (9.6%, SD 1.5) based on age and sex standardised Scottish mortality risk. The most common causes of death were malignancies (21.3%) and infection (20.0%). CONCLUSIONS: This study highlights the relatively good long-term prognosis in vision and mortality in exudative AMD treated with a PRN regime in the real world. Although the majority lost vision, the rate of decline was significantly slower than that which would have been experienced in the pre-anti-VEGF era and reassuringly standardised mortality risk was lower than the national average.

The Eye in Forensic Medicine: A Narrative Review.

ABSTRACT: The eye, with its distinctive anatomy, not only reflects a wide variety of diseases in life but also undergoes a myriad of post-mortem changes. Consequently, the eye has long been an area of interest in forensic science, primarily for the estimation of post-mortem interval and therefore the time of death and also for assistance in ascertaining the cause of death. There has been significant progress in the knowledge of ophthalmic forensic science using new technologies which have allowed further possibilities to arise where understanding of this field can assist the forensic pathologist. This review aims to highlight the current knowledge which exists in this field and also to identify important avenues for further investigation. Post-mortem changes of the eye along with its current applications and challenges will be discussed. These include the important areas of post-mortem iris biometrics, pupil size correlation with post-mortem interval, use of point-of-care technology on vitreous humor, and the use of ophthalmic imaging in pediatric abusive head trauma.

Choroidal neovascularisation in a predicted female choroideraemia carrier treated with intravitreal anti-vascular endothelial growth factor.

PURPOSE: To report a case of choroidal neovascularisation and leakage in a myopic female predicted to be a choroideraemia carrier treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: Case report. RESULTS: A female magazine editor presented with sudden decrease in vision in her right eye, with Snellen visual acuities (VAs) of 1/60 and 3/60 in the right and left eyes respectively. She was diagnosed with choroidal neovascularisation (CNV) formation and subretinal haemorrhage in her right eye. This is on a background of previous presentations, the first of which was 20 years ago for declining left eye vision. She was subsequently found to be a predicted choroideraemia carrier. However, she also has high myopia, and it is unclear whether the predicted choroideraemia carrier status or high myopia is the main underlying cause of her CNV, although we believe that the former is more likely. The first episode of CNV in her right eye was treated successfully with intravitreal anti-VEGF. However, she experienced four further CNV reactivations in her right eye, all of which were treated successfully with anti-VEGF. At her last follow-up visit to date, Snellen VAs were 6/9 and 3/60 in her right and left eye respectively. CONCLUSION: This is a unique case of CNV formation in a predicted choroideraemia carrier who also has co-existent high myopia. Prompt treatment of CNV activity with anti-VEGF has been efficacious in prevention of subretinal fibrosis and irreversible vision loss and allowed the patient to continue working in her chosen career.

Unilateral retinitis pigmentosa occurring in an individual with a mutation in the CLRN1 gene.

This case report depicts the clinical course of a female patient with unilateral retinitis pigmentosa, who first presented at the age of 12 years. Fundus photography at the time revealed unilateral pigmentary retinopathy, which was associated with extinguished electroretinogram (ERG) signal. At 35 years of age, fundus examination revealed deterioration of pre-existing unilateral pigmentary retinopathy with progressive visual field defect detected on Goldmann visual field testing. ERG findings remained unchanged and multifocal ERG showed unilateral decrease in amplitude in the affected eye. The patient was referred for genetic counselling. Next-generation sequencing identified a deleterious heterozygous c.118T>G (p.Cys40Gly) mutation in the CLRN1 gene.

Clinical outcomes of switching to aflibercept using a pro re nata treatment regimen in patients with neovascular age-related macular degeneration who incompletely responded to ranibizumab.

BACKGROUND: To assess the effect of switching patients previously incompletely treated with ranibizumab (RBZ) to aflibercept (AFL) using a pro re nata (PRN) treatment strategy in neovascular age-related macular degeneration (nvAMD). METHODS: A retrospective case series was conducted on patients who had persistent or recurrent intra- and/or sub-retinal fluid treated initially with RBZ and subsequently switched to AFL. The main outcome measures were best corrected visual acuity (BCVA) and central retinal thickness (CRT) measured at different stages of the study. Friedman analysis of variance and Wilcoxon test were used to examine differences in BCVA and CRT. RESULTS: Two hundred and seven eyes from 182 patients were included. BCVA and CRT improved significantly initially following 3 RBZ injections with a mean gain of 3.7 letters (p < 0.001) and a mean loss of 69 µm (p < 0.001) respectively. Following PRN RBZ therapy and immediately prior to switching to AFL (mean 129 weeks), there was a mean loss of 6.7 letters (p < 0.001) BCVA and a mean gain of 24 µm (p < 0.001) CRT. AFL loading resulted in a mean improvement of 0.7 letters (p = 0.28) BCVA and 55 µm (p < 0.001) CRT. At final follow-up following AFL PRN therapy (mean 85 weeks), there was a mean loss of 8.9 letters (p < 0.001) BCVA and a mean gain of 12 µm (p < 0.05) CRT. CONCLUSION: AFL loading resulted in a significant anatomical improvement but no significant change in visual acuity. However, the benefits of switching were gradually lost over time with AFL PRN dosing despite an increased injection rate when compared with RBZ PRN treatment. TRIAL REGISTRATION: Not applicable.

A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy (PCV), a subtype of 'wet' age-related macular degeneration (AMD), constitutes up to 55% of cases of wet AMD in Asian patients. In contrast to the choroidal neovascularization (CNV) subtype, the genetic risk factors for PCV are relatively unknown. Exome sequencing analysis of a Han Chinese cohort followed by replication in four independent cohorts identified a rare c.986A>G (p.Lys329Arg) variant in the FGD6 gene as significantly associated with PCV (P = 2.19 × 10(-16), odds ratio (OR) = 2.12) but not with CNV (P = 0.26, OR = 1.13). The intracellular localization of FGD6-Arg329 is distinct from that of FGD6-Lys329. In vitro, FGD6 could regulate proangiogenic activity, and oxidized phospholipids increased expression of FGD6. FGD6-Arg329 promoted more abnormal vessel development in the mouse retina than FGD6-Lys329. Collectively, our data suggest that oxidized phospholipids and FGD6-Arg329 might act synergistically to increase susceptibility to PCV.

New loci and coding variants confer risk for age-related macular degeneration in East Asians.

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10(-22)). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l(-1) (P=5.82 × 10(-21)) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10(-18)), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10(-11)) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10(-8)). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.