UNASSIGNED: Most neovascular age-related macular degeneration treatments involve long-term follow-up of disease activity. Home monitoring would reduce the burden on patients and those they depend on for transport, and release clinic appointments for other patients. The study aimed to evaluate three home-monitoring tests for patients to use to detect active neovascular age-related macular degeneration compared with diagnosing active neovascular age-related macular degeneration by hospital follow-up.
UNASSIGNED: There were five objectives: Estimate the accuracy of three home-monitoring tests to detect active neovascular age-related macular degeneration. Determine the acceptability of home monitoring to patients and carers and adherence to home monitoring. Explore whether inequalities exist in recruitment, participants\' ability to self-test and their adherence to weekly testing during follow-up. Provide pilot data about the accuracy of home monitoring to detect conversion to neovascular age-related macular degeneration in fellow eyes of patients with unilateral neovascular age-related macular degeneration. Describe challenges experienced when implementing home-monitoring tests.
UNASSIGNED: Diagnostic test accuracy cohort study, stratified by time since starting treatment.
UNASSIGNED: Six United Kingdom Hospital Eye Service macular clinics (Belfast, Liverpool, Moorfields, James Paget, Southampton, Gloucester).
UNASSIGNED: Patients with at least one study eye being monitored by hospital follow-up.
UNASSIGNED: Detection of active neovascular age-related macular degeneration by an ophthalmologist at hospital follow-up.
UNASSIGNED: KeepSight Journal: paper-based near-vision tests presented as word puzzles. MyVisionTrack®: electronic test, viewed on a tablet device. MultiBit: electronic test, viewed on a tablet device. Participants provided test scores weekly. Raw scores between hospital follow-ups were summarised as averages.
UNASSIGNED: Two hundred and ninety-seven patients (mean age 74.9 years) took part. At least one hospital follow-up was available for 317 study eyes, including 9 second eyes that became eligible during follow-up, in 261 participants (1549 complete visits). Median testing frequency was three times/month. Estimated areas under receiver operating curves were < 0.6 for all index tests, and only KeepSight Journal summary score was significantly associated with the lesion activity (odds ratio = 3.48, 95% confidence interval 1.09 to 11.13, p = 0.036). Older age and worse deprivation for home address were associated with lower participation (χ2 = 50.5 and 24.3, respectively, p < 0.001) but not ability or adherence to self-testing. Areas under receiver operating curves appeared higher for conversion of fellow eyes to neovascular age-related macular degeneration (0.85 for KeepSight Journal) but were estimated with less precision. Almost half of participants called a study helpline, most often due to inability to test electronically.
UNASSIGNED: Pre-specified sample size not met; participants\' difficulties using the devices; electronic tests not always available.
UNASSIGNED: No index test provided adequate test accuracy to identify lesion diagnosed as active in follow-up clinics. If used to detect conversion, patients would still need to be monitored at hospital. Associations of older age and worse deprivation with study participation highlight the potential for inequities with such interventions. Provision of reliable electronic testing was challenging.
UNASSIGNED: Future studies evaluating similar technologies should consider: Independent monitoring with clear stopping rules based on test performance. Deployment of apps on patients\' own devices since providing devices did not reduce inequalities in participation and complicated home testing. Alternative methods to summarise multiple scores over the period preceding a follow-up.
UNASSIGNED: This trial is registered as ISRCTN79058224.
UNASSIGNED: This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/97/02) and is published in full in Health Technology Assessment; Vol. 28, No. 32. See the NIHR Funding and Awards website for further award information.
Treatment for neovascular age-related macular degeneration, the most common cause of sight loss in those over 50 years, involves regular eye injections and frequent follow-up appointments. This is inconvenient for patients and causes capacity issues in the hospital eye service. Finding tests that could be undertaken at home that could detect if a further injection and hospital appointment was required or not would increase capacity to see those at highest risk of sight loss and also reduce the burden on patients and their carers. We investigated three different visual function tests, one paper-based and two applications on an iPod TouchTM tablet (Apple, Cupertino, CA, USA). We wanted to see if they could detect an increase in disease activity that would require treatment, compared to the decision by a retinal specialist at a traditional hospital eye outpatient visit based on clinical examination and retinal imaging. To encourage those without a smartphone or home internet to participate, we provided both an iPod Touch and Mobile Wireless-Fidelity device with a mobile contract. None of the tests performed well enough to safely monitor patients at home. Those who were willing to participate tended to be younger, had previous experience of using smartphones, sending e-mail and internet access and were more well-off than those who chose not to participate. Some participants also experienced difficulties with the devices provided and successfully uploading the data which were not related to the extent of previous information technology experience. There were also significant technical challenges for the research team. The study helpline was used heavily, considerably more than we anticipated. These tests are not ready to be used in this context. Future studies involving mobile health technology need to carefully consider how to reach those unlikely to participate and provide sufficient technical support to support long-term follow-up.

Blindness in the elderly is often caused by age-related macular degeneration (AMD). The advanced type of AMD known as neovascular AMD (nAMD) has been linked to being the predominant cause of visual impairment in these people. Multiple neovascular structures including choroidal neovascular (CNV) membranes, fluid exudation, hemorrhages, and subretinal fibrosis, are diagnostic of nAMD. These pathological alterations ultimately lead to anatomical and visual loss. It is known that vascular endothelial growth factor (VEGF), a type of proangiogenic factor, mediates the pathological process underlying nAMD. Therefore, various therapies have evolved to directly target the disease. In this review article, an attempt has been made to discuss general explanations about this disease, all common treatment methods based on anti-VEGF drugs, and the use of drug delivery systems in the treatment of AMD. Initially, the pathophysiology, angiogenesis, and different types of AMD were described. Then we described current treatments and future treatment prospects for AMD and outlined the advantages and disadvantages of each. In this context, we first examined the types of therapeutic biomolecules and anti-VEGF drugs that are used in the treatment of AMD. These biomolecules include aptamers, monoclonal antibodies, small interfering RNAs, microRNAs, peptides, fusion proteins, nanobodies, and other therapeutic biomolecules. Finally, we described drug delivery systems based on liposomes, nanomicelles, nanoemulsions, nanoparticles, cyclodextrin, dendrimers, and composite vehicles that are used in AMD therapy.

Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO3-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO3-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans.

Wet age-related macular degeneration (wet AMD) is the most common cause of blindness, and chronic intravitreal injection of anti-vascular endothelial growth factor (VEGF) proteins has been the dominant therapeutic approach. Less intravitreal injection and a prolonged inter-injection interval are the main drivers behind new wet AMD drug innovations. By rationally engineering the surface residues of a model anti-VEGF nanobody, we obtained a series of anti-VEGF nanobodies with identical protein structures and VEGF binding affinities, while drastically different crystallization propensities and crystal lattice structures. Among these nanobody crystals, the P212121 lattice appeared to be denser and released protein slower than the P1 lattice, while nanobody crystals embedding zinc coordination further slowed the protein release rate. The polymorphic protein crystals could be a potentially breakthrough strategy for chronic intravitreal administration of anti-VEGF proteins.

Introduction: To evaluate the effect of antivascular endothelial growth factor (anti-VEGF)-related endophthalmitis on intravitreal injection (IVI) frequency in patients with neovascular age-related macular degeneration (nAMD). Methods: A retrospective chart review was performed of all cases of post IVI endophthalmitis that occurred in Edmonton, Alberta, Canada, between 2012 and 2019. Contralateral eyes affected by nAMD but without endophthalmitis served as a control group. The main outcome measures were the frequency of anti-VEGF injections, visual acuity, and activity of choroidal neovascularization before and after endophthalmitis. Results: Seventeen eyes met the inclusion criteria, 2 (12%) of which never resumed IVI after endophthalmitis because of the quiescence of disease. Post-endophthalmitis eyes received IVI less frequently in the 1 year after endophthalmitis (mean 0.52 ± 0.42 IVI/month) than those that received IVI 1 year before endophthalmitis (1.09 ± 0.36 IVI/month) (P = .001). The 17 contralateral eyes also received anti-VEGF injections less frequently after endophthalmitis than before (P = .001). There was no significant change in optical coherence tomography markers of disease activity in cases or controls. Conclusions: In patients with nAMD, endophthalmitis resolution is associated with a decrease in anti-VEGF injection frequency. The same decrease in anti-VEGF injection frequency is also seen in contralateral eyes unaffected by endophthalmitis. Markers of disease activity remain unchanged in both eyes, suggesting disease quiescence despite reduced IVI frequency.

In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this connection, illuminating the hidden influence of APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN\'s multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on choroidal neovascularization (CNV). The elucidation of these relationships fosters a deeper understanding of adipose tissue\'s profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD, although the possibility to treat human AMD is in the early stage and more clinical research is needed. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging.

Age-related macular degeneration (AMD), particularly wet AMD characterised by choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. The hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway contributes to CNV pathogenesis. Previous gene editing research indicated that disrupting these genes in retinal pigment epithelial cells could have a preventive effect on CNV progression. However, no studies have yet been conducted using gene editing to disrupt VEGF signalling after CNV induction for therapeutic validation, which is critical to the clinical application of wet AMD gene editing therapies.
Here, we employed the single-adeno-associated virus-mediated Nme2 Cas9 to disrupt key molecules in VEGF signalling, Hif1α, Vegfa and Vegfr2 after inducing CNV and estimated their therapeutic effects.
We found that Nme2 Cas9 made efficient editing in target genes up to 71.8% post 11 days in vivo. And only Nme2 Cas9-Vegfa treatment during the early stage of CNV development reduced the CNV lesion area by 49.5%, compared to the negative control, while Nme2 Cas9-Hif1α or Nme2 Cas9-Vegfr2 treatment did not show therapeutic effect. Besides, no off-target effects were observed in Nme2 Cas9-mediated gene editing in vivo.
This study provides proof-of-concept possibility of employing Nme2 Cas9 for potential anti-angiogenesis therapy in wet AMD.

OBJECTIVE: To investigate whether a seasonal distribution of the frequency of exudative age-related macular degeneration (wet AMD) recurrences exists.
METHODS: In total, 129 eyes with 171 recurrences in patients suffering from wet AMD were included in the study. All the patients had been treated with intravitreal anti-VEGF injections according to Pro Re Nata treatment regimen. Recurrence was defined as the re-detection of sub-retinal fluid, intraretinal fluid, and/or sub-macular hemorrhage in optical coherence tomography scans, after at least two consecutive monthly examinations with a \"dry\" macula. The year was divided in three 4-month periods (zone A: June-September, zone B: October-January, and zone C: February-May) based on the weather conditions prevailing in each period. Mean temperature and hours of sunlight exposure were the main weather markers recorded.
RESULTS: Eighty-two recurrences (48%) occurred during the period June-September, 50 (29.2%) during the period October-January, and 39 (22.8%) during the period February-May (Chi-square = 17.5, p < 0.001). Among the groups, neither patients\' age (78 ± 8 years A, 76 ± 7 years B, and 79 ± 8 years C, p = 0.15) nor gender status (40% men A, 36% men B, and 51% men C, p = 0.35) differed significantly. Mean temperature was 27.6 ± 1.8 °C, 15.1 ± 4.6 °C, and 16.5 ± 4.4 °C in zones A, B, and C, respectively. Hours (h) of sunlight exposure (average hours/month) were 344 ± 34 h, 188 ± 42 h, and 223 ± 57 h in zones A, B, and C.
CONCLUSIONS: We demonstrated that the frequency of wet AMD recurrences is significantly elevated during the warmer months, possibly due to the higher levels of UV radiation and mean temperature. Further research is necessary to validate our findings.

Background and Objectives: The purpose was to provide the patients\' perspective on the monitoring of their wet age-related macular degeneration (wet AMD) during coronavirus disease 2019 (COVID-19) and the importance of telemedicine. Materials and Methods: Wet AMD patients that underwent intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in two Swiss ophthalmology clinics, completed two questionnaires after the first confinement due to COVID-19 in Switzerland. The first evaluated their views concerning their adherence to scheduled injections during the confinement, and the application of telemedicine in the future. The second, adapted from the National Eye Institute Visual Function Questionnaire-25, assessed their opinions on visual function change during confinement. Results: From a total of 130 patients, 8.5% responded they did not respect their assigned schedule (group 1) while 91.5% responded they did (group 2). A total of 78.7% of group 2 considered treatment reception as more relevant compared to the risk of COVID-19 contraction. During the pre-lockdown period, group 2 patients required more help from others than group 1 patients (p = 0.02). In the possibility of another lockdown, 36.3% of group 1 and 8.7% of group 2 would choose telemedicine to monitor their wet AMD (p = 0.02), 54.5% and 86.9% would rather visit the clinic (p = 0.02), while 9.0% and 4.3% would cancel their appointment, respectively. It was found that 70% of group 1 and 33.6% of group 2 would prefer to use the telemedicine services than visiting a telemedicine centre (p = 0.04). Conclusions: During circumstances similar to the COVID-19 confinement, most patients would prefer to visit the clinic. Group 1 would prefer wet AMD monitoring via telemedicine at a higher rate than group 2.

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the retina which ultimately results in the irreversible loss of central vision. AMD is one of the foremost causes of blindness in people over the age of 50. Although the precise pathogenesis of AMD has not yet been elucidated, AMD results from a complex interaction between genetic predisposition and environmental provoking factors. These factors might lead to ocular homeostasis dysfunction resulting in inflammation, oxidative stress, and in some cases neovascularization. MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNAs and are approximately 22 nucleotides long. miRNAs play a central role in several pathophysiological processes such as immune and inflammatory responses, pathological angiogenesis, and the response to oxidative stress, all of which have been suggested to be associated with AMD pathogenesis and progression. Here we discuss methods to isolate miRNAs using serum specimens from AMD patients and miRNA profiling for the better understanding of the pathogenesis and progression of AMD.