Healthcare experiences of patients with age-related macular degeneration:have things improved? Cross-sectional survey responses of Macular Society members in 2013 compared with 1999

OBJECTIVE: To investigate healthcare experiences of patients with age-related macular degeneration (AMD) and determine whether a previous survey and Royal College of Ophthalmologists (RCOphth) management guidelines brought improvements. DESIGN: Cross-sectional survey of Macular Society members in 2013 compared with previous 1999 survey. SETTING: UK Postal Questionnaires. PARTICIPANTS: 1169 respondents in 2013 (1187 in 1999). INTERVENTION: Publication of 1999 survey results (2002), and RCOphth AMD guidelines (2009). MAIN OUTCOME MEASURES: Respondents answered questions about experiences at diagnosis. Five questions were replicated from the 1999 survey for direct comparison in the 2013 survey which included additional questions based on 2009 RCOphth recommendations for information and support provision for patients with AMD. RESULTS: Most 2013 survey respondents were given the name of their macular condition (91%), felt the healthcare professional was interested in them (71%) and were satisfied overall with the diagnostic consultation (76%). These outcomes show significant improvement since 1999. Within the 2013 sample, multivariable analyses showed gradual trends of improvement over time in: provision of written information, Macular Society information and receiving appropriate help, support and advice at diagnosis. Only overall satisfaction with the diagnostic consultation (but not the other nine areas of information and support provision studied) significantly improved in the time after publication of the RCOphth 2009 guidelines. There were no significant improvements associated with the publication of the 1999 survey results. Low information and support provision remained, for example, 44% of respondents diagnosed after the RCOphth 2009 guidelines reported not receiving information on what to do if vision deteriorated. Lack of such information at diagnosis was significantly associated with registration as sight impaired (p<0.01). Reports of general practitioner (GP) knowledge of AMD remained low: 39% reported their GP was ‘not at all well informed’. The 2013 respondents reported lower levels of help and support from GPs than 1999 respondents (p<0.001). CONCLUSIONS: Patients diagnosed with AMD after 1999 (vs before 1999) reported better experiences at diagnostic consultation. However, information and support provision at diagnosis, and satisfaction with GPs remained low

Patient-reported reasons for delay in diagnosis of age-related macular degeneration: a national survey

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives To investigate whether people with age-related macular degeneration (AMD) are able to self-detect symptoms and, if so, what symptoms they experience, from whom they first seek help, whether help is sought within the 1 week recommended by the Royal College of Ophthalmologists' guidelines and reasons for any delay. Methods and analysis A retrospective, cross-sectional survey design. Postal surveys were sent to 4000 members of the UK Macular Society. Inclusion criteria were participants aged >50 years at diagnosis of AMD with diagnosis after August 2008; criteria were met by 621 respondents. The main outcome was reasons for delays in diagnosis for wet AMD. Data were analysed using χ 2 and conventional content analysis. Results Only one third (n=199; 32%) of respondents were able to self-detect symptoms. In line with national guidance, over half (n=131; 64%) of those self-detecting symptoms sought help promptly. For those whose initial diagnosis was delayed more than 1 week, 27% had potentially treatable wet AMD requiring urgent treatment to prevent vision loss. Reasons for delay reflected individual & service-related issues, including AMD not being detected in the initial consultation, and individuals not perceiving the urgency for symptom investigation. Conclusion In practice most patients sought help within 1 week; however, potentially sight-damaging delays occurred from symptom onset to diagnosis. Suggestions for reducing delay include increasing population awareness of AMD symptoms, the need for urgent detection and close monitoring for AMD and signposting patients to appropriate support services to ensure prompt detection of any future signs of wet AMD

Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells

Retinal diseases are the leading causes of irreversible blindness worldwide. The role of toll-like receptor (TLR) signalling mechanisms (MyD88 and TRIF) in the production of pro-angiogenic growth factors from human microvascular endothelial cells (HMEC-1) under hypoxic stress remains unexplored. HMEC-1 was incubated under normoxic (5% CO2 at 37 °C) and hypoxic (1% O2, 5% CO2, and 94% N2; at 37 °C) conditions for 2, 6, 24, and 48 h, respectively. For TLR pathway analysis, HMEC-1 was pre-treated with pharmacological inhibitors (Pepinh-MyD88 and Pepinh-TRIF) and subjected to normoxia and hypoxia conditions. Gene and protein expressions of vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor (FGF-2), hypoxia inducible factor 1-alpha (HIF1-α) were performed using quantitative polymerase chain reaction (qPCR), ELISA, and Western blot methodologies. Levels of TLR3 and TLR4 were analysed by flow cytometry. Under hypoxia, levels of VEGF-A and FGF-2 were elevated in a time-dependent fashion. Inhibition of MyD88 and TRIF signalling pathways decreased FGF-2 levels but failed to modulate the secretion of VEGF-A from HMEC-1. Blocking a known regulator, endothelin receptor (ETR), also had no effect on VEGF-A secretion from HMEC-1. Overall, this study provides the proof-of-concept to target TLR signalling pathways for the management of blinding retinal diseases

Biofeedback fixation training method for improving eccentric vision in patients with loss of foveal function secondary to different maculopathies

© 2019, The Author(s). Purpose: Fixation stability (FS) of the preferred retinal locus (PRL) may be improved by biofeedback fixation training (BFT) with microperimetry. Such training can be done on the patient’s PRL or in different retinal loci with better functional characteristics. We studied both options and compared the outcomes. Methods: Sixty-seven consecutive patients with bilateral central vision loss, poor FS and visual acuity (VA) lower than 0.3 LogMAR were recruited for BFT with microperimeter. Patients were assigned into 2 groups. In group A, BFT was performed on the patient’s spontaneous PRL. In group B, PRL was located between 2 adjacent loci with the highest light sensitivity and the lowest distance from the fovea. Two sets of 12 weekly BFT sessions were performed. Primary outcomes were: FS, VA and reading speed. Results: Outcomes were statistically significantly better in group B. Mean percentage of FS at therapy end improved from 32 to 35% for group A and from 40 to 55% in group B. Mean VA improved from 1 to 0.86 in group A and from 1 to 0.84 in group B. Reading speed (wpm) improved from 56 to 58 in group A and from 63 to 89 in group B. Conclusions: This study describes a reliable methodology of improving eccentric fixation stability using BFT in microperimetry, when the fixation training locus is individualized as the retinal area with best functional characteristics. Further studies are needed to validate its value in a larger scale of patients, at different stages of the disease, and its persistence over time

Importance of Anatomical Efficacy for Disease Control in Neovascular AMD: An Expert Opinion

BACKGROUND: Neovascular age-related macular degeneration (nAMD) presents a significant treatment burden for patients, carers and medical retina services. However, significant debate remains regarding how best to manage nAMD when assessing disease activity by optical coherence tomography (OCT), and particularly the significance of different types of fluid and how the understanding of anatomical efficacy can influence treatment strategies. This article provides opinion on the practical implications of anatomical efficacy and significance of fluid in the management of nAMD and proposes recommendations for healthcare professionals (HCPs) to improve understanding and promote best practice to achieve disease control. METHODS: An evidence-based review was performed and an expert panel debate from the Retina Outcomes Group (ROG), a forum of retinal specialists, provided insights and recommendations on the definition, role and practical implications of anatomical efficacy and the significance of fluid at the macula in the management of nAMD. RESULTS: The ROG has developed recommendations for achieving disease control through a zero-tolerance approach to the presence of fluid in nAMD as patients who avoid fluctuations in fluid at the macula have better visual outcomes. Recommendations cover five key areas: service protocol, training, regimen, multidisciplinary teams and engagement. This approach facilitates more standardised protocol-based treatment strategies. CONCLUSIONS: Targeting a fluid-free macula and aiming for disease control are essential to improve outcomes. As new therapies and technologies become available, drying the macula and maintaining disease control will become even more achievable. The outlined recommendations aim to promote best practice among HCPs and medical retina services to improve patient outcomes

Safety of intravitreal ziv-aflibercept in choroido-retinal vascular diseases: A randomised double-blind intervention study

AIM:To evaluate the safety of 1.25mg and 2mg intravitreal ziv-aflibercept (IVZ) in Ghanaian eyes with choroido-retinal vascular diseases. DESIGN:Prospective, randomised, double blind, interventional study. METHODS:Twenty patients with centre involving macular oedema in diabetic retinopathy, retinal vein occlusion, and neovascular age-related macular degeneration were assigned to 2 groups receiving 3 doses of 1.25mg/0.05ml (group 1) and 2mg/0.08ml IVZ (Group 2) at 4 weekly intervals. Safety data was collected after 30 minutes, 1 and 7 days, and 4, 8 and 12 weeks after injection. Changes in continuous variables were compared using paired t-test and categorical variables were compared using chi-square test of proportions. Repeated-Measures ANOVA with nesting test was used to compare variations in continuous variables by IVZ dose over time. Primary outcome measures were ocular and systemic adverse events at 4 weeks. RESULTS:Eleven females and nine males, with mean age of 63.2± 7.3 years were included. Ocular adverse events included subconjunctival haemorrhage in 1 eye, intraocular pressure (IOP) >21mmHg at 30 minutes in 6 eyes and mild pain in 3 eyes at 1-day. There was no significant difference in IOP rise between the 2 groups at 30 minutes (p = 0.21). No other ocular or systemic adverse events were observed. There was significant improvement in the best corrected visual acuity (LogMAR) from 0.95±0.6 to 0.6±0.4 (p<0.01) and 0.47±0.3 (p<0.01), reduction in central subfield foveal thickness from 405.9±140 um at baseline to 255.6±75 um (p<0.01) and 238±88 um (p<0.01) at 4 and 12 weeks respectively, although no difference was observed between the 2 groups (p = 0.34). CONCLUSION:IVZ at 1.25mg and 2mg had similar safety profiles, and did not have any major unexpected adverse events. Further studies with larger cohorts are required to confirm efficacy

In vivo confocal microscopy features and clinicohistological correlation of limbal nerve corpuscles

Aims To describe the in vivo confocal microscopy (IVCM) features of human limbal nerve corpuscles (LNCs) and correlate these with the histological features.Methods We examined 40 eyes of 29 healthy living subjects (17 female, 12 male; mean age=47.6) by IVCM. Four limbal quadrants were scanned through all epithelial layers and stroma to identify the LNCs and associated nerves. Ten fresh normal human corneoscleral discs from five deceased patients with a mean age of 67 years and 17 eye-bank corneoscleral rims with a mean age of 57.6 years were stained as whole mounts by the acetylcholinesterase (AChE) method to demonstrate LNCs and corneal nerves. Stained tissue was scanned in multiple layers with the NanoZoomer digital pathology microscope. The in vivo results were correlated to the histological findings.Results On IVCM, LNCs were identified in 65% of the eyes studied and were mainly (84%) located in the inferior or superior limbal regions. They appeared either as bright (hyper-reflective) round or oval single structures within the hyporeflective, relatively acellular fibrous core of the palisades or were clustered in groups, often located anterior to the palisades of Vogt. They measured 36 µm in largest diameter (range 20–56 µm). The in vivo features were consistent with the histology, which showed LNCs as strongly AChE positive round or oval structures.Conclusion The strong correlation with histology will enable use of IVCM to study LNCs in normal and disease conditions

Assessing the ex vivo permeation behaviour of functionalised contact lens coatings engineered using an electrohydrodynamic technique

In vitro testing alone is no longer considered sufficient evidence presented solely with respect to drug release and permeation testing. These studies are thought to be more reliable and representative when using tissue or animal models; as opposed to synthetic membranes. The release of anti-glaucoma drug timolol maleate from electrically atomised coatings was assessed here using freshly excised bovine corneal tissue. Electrohydrodynamic processing was utilised to engineer functionalised fibrous polyvinylpyrrolidone-Poly (N-isopropylacrylamide) coatings on the outer side of commercial silicone contact lenses. Benzalkonium chloride, ethylenediaminetetraacetic acid, Brij® 78 and borneol were employed as permeation enhancers to see their effect on ex vivo permeation of timolol maleate through the cornea. Formulations containing permeation enhancers showed a vast improvement with respect to cumulative amount of drug permeating through the cornea as shown by a six fold decrease in lag time compared to enhancer-free formulations. Most drug delivery systems require the drug to pass or permeate through a tissue or biological membrane. This study has shown that to fully appreciate and understand how a novel drug delivery system will behave not only within the device but with the external environment or tissue, it is imperative to have in vitro and ex vivo data in conjunction

Prevalence of peripapillary choroidal neovascular membranes (PPCNV) in an elderly UK population—the Bridlington eye assessment project (BEAP): a cross-sectional study (2002–2006)

© 2018, The Royal College of Ophthalmologists. Purpose: There is paucity of data on the epidemiology of peripapillary choroidal neovascularisartion (PPCNV). Our aim was to determine prevalence of PPCNV in the elderly UK population of Bridlington residents aged ≥65 years. Methods: Eyes with PPCNV in the Bridlington eye assessment project (BEAP) database of 3475 participants were analysed. PPCNV outline was drawn, its area measured, and clock-hour involvement of disc circumference recorded. Location and shortest distance from the lesion edge to fovea were recorded. Masked grading for age-related maculopathy (ARM)/reticular pseudodrusen (RPD) within the ETDRS grid was assigned for each eye using a modified Rotterdam scale. Peripapillary retinal pigment epithelial (RPE) changes/drusen were recorded. Visual acuity (VA) and demographic details analysed separately were merged with grading data. Results: PPCNV were identified in ten subjects, and were bilateral in two (20%), a population prevalence of 0.29%, and 0.06% bilaterality. Gender-specific prevalence were 0.36% and 0.19% for females and males, respectively. Age ranged from 66 to 85 years [mean 76.3 (SD 6.4)]. PPCNV were located nasal to disc in 41.7%, measuring 0.46–7.93 mm 2 [mean 2.81 mm 2 (SD 2.82)]. All PPCNV eyes had peripapillary RPE changes. One subject had no ARM, 1 angioid streaks, and 30% RPD. No direct foveal involvement, or reduced VA attributable to PPCNV was observed. Conclusion: PPCNV were infrequent in this population, more common in females, and often located nasal to the disc, without foveal extension. Peripapillary degenerative changes were universal, and strong association with ARM was observed in eyes with PPCNV. Typically, PPCNV were asymptomatic with VA preservation

Prevalence of optic disc haemorrhages in an elderly UK Caucasian population and possible association with reticular pseudodrusen—the Bridlington Eye Assessment Project (BEAP): a cross-sectional study (2002–2006)

Aims: To determine disc haemorrhages (DH) prevalence in an elderly UK population-the Bridlington Eye Assessment Project (BEAP).Methods: Thirty-degree (30°) fundus photographs (3549 participants ≥65 years) were graded for DH/macula changes. Glaucoma evaluation included Goldmann tonometry, 26-point suprathreshold visual-fields and mydriatic slit-lamp assessment for glaucomatous optic neuropathy.Results: 3548 participants with photographs in at least one eye. DH were present in 53 subjects (1.49%), increasing from 1.17% (65-69-year age-group) to 2.19% (80-84-year age53 group), p=0.06. DH was found in 9/96 (9.38%) right eyes (RE) with open angle glaucoma (OAG). Two of twelve RE (16.67%) with normal tension glaucoma (NTG) had DH. Prevalence in eyes without glaucoma was lower (32/3452, [0.93%]). Reticular pseudodrusen (RPD) occurred in 170/3212 (5.29%) subjects without DH, and 8/131 subjects (6.11%) with OAG. Twenty (20) eyes had normal tension glaucoma (NTG), 2 of whom had RPD (10%) (p=0.264). Within a logistic regression model, DH was associated with glaucoma (OR 10.2, 95% CI 5.32 - 19.72) and increasing age (OR 1.05, 95% CI 1.00-1.10, p=0.03). DH was associated with RPD (p=0.05) with univariate analysis but this was not statistically significant in the final adjusted model. There was no significant association with gender, diabetes mellitus (DM), hypertension treatment or AMD grade.Conclusion: DH prevalence is 1.5% in those over 65 years old and significantly associated with glaucoma and increasing age. There appears to be increased RPD prevalence in eyes with DH and NTG with age acting as a confounding factor. Larger studies are required to fully assess the relationship and investigate a possible shared aetiology of choroidal ischaemia