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Self-assessment of driving fitness is mandatory in the United Kingdom. A paucity of data on visual function among drivers exists. We report prevalence of elderly drivers below legal visual acuity (VA) standard from a population study (The Bridlington Eye Assessment Project (BEAP)) conducted from 2002 to 2006. All residents aged ≥65 years were invited, 3459 undergoing structured interviews/ophthalmic examinations. Driving status was recorded, VA measured, and visual field (VF) testing performed. Outcomes were prevalence and characteristics of drivers below VA legal standard and prevalence of bilateral VF defects. Conditions causing reduced VA were explored and those with treatable conditions allowing visual improvement identified. Duration since last optometry review was recorded. Associations were explored using unpaired t-tests for continuous and chi-squared for discrete variables. Logistic regression was used for multivariate analysis and to determine odd ratios in the final adjusted model. Statistical analysis was performed using Stata 14.0 (Stata Corp, Tx). Within this sample, 7.1% (95% CI 6.0–8.3) of drivers fell below the VA legal driving standard (6/12) in their better eye, with 20% not having seen an optometrist for 2 years, including 8.2% who had not attended for over 5 years. The percentage of drivers falling below the VA minimum increases with age reaching 22.8% (95% CI 13.7–35.3) among those aged 85–89 years. 7.2% (95% CI 6.2–8.6) of drivers had bilateral visual field defects. 93% of drivers with reduced VA below legal standard had a cataract, refractive error or both in at least one eye. Significant numbers of elderly drive with VA below legal standard, most having easily correctable causes. Poor attendance with optometrists appears commonplace. Public education raised awareness of legal driving standards and encouraged compliance are required. Regular eye tests, appropriate refractive correction, and cataract surgery when needed should be encouraged.

West African crystalline maculopathy (WACM) is characterized by the presence of macular hyperrefractile crystal-like deposits. Although the underlying pathophysiology has not been elucidated, a few biologic drivers have been proposed. We analyzed a large WACM case series to gain a more robust understanding of its features and etiology.Prospective, cross-sectional cohort study.Participants with WACM were selected from the large cohort recruited in the Ghana Age-Related Macular Degeneration Study.Demographic and detailed medical histories, full ophthalmic examinations, digital color fundus photographs, and OCT images were obtained. All cases with WACM were evaluated by 3 retina experts. Crystal numbers, location, and distribution were determined. Associations between WACM and White age-related macular degeneration (AMD) risk variants were assessed using Firth's bias-reduced logistic regression, including age and sex as covariates.Phenotypic features of, and genetic associations with, WACM.West African crystalline maculopathy was identified in 106 eyes of 53 participants: 22 were bilateral and 24 were unilateral. Grading for AMD was not possible in 1 eye in 7 participants with WACM; therefore, laterality was not assessed in these subjects. Thirty-eight participants were women and were 14 men; sex was unrecorded for 1 participant. The mean age was 68.4 years (range, 45-101 years). Typical WACM crystals were demonstrated on OCT, which were more easily identified at high contrast and predominantly located at the inner limiting membrane. In eyes with copathology, crystals localized deeper in the inner retina, with wider retinal distribution over copathology lesions. There was no association with age or sex. A significant association was observed between the complement factor H (CFH) 402H risk variant and WACM.This study confirms the localization of crystals adjacent to the inner limiting membrane and distribution over lesions in eyes with copathology. The evaluation of OCT images under high contrast allows improved identification. West African crystalline maculopathy may be associated with the CFH-CFHR5 AMD risk locus identified among Whites; however, it is also possible that the combination of crystals and the CFH 402H allele increases the risk for developing late AMD. Further analyses using larger sample sizes are warranted to identify causalities between genotype and WACM phenotype.

Exacerbation of the vascular pathology in radiation retinopathy as a result of pre-existing diabetes has been recognized for many years, as reflected by clinical reports and a few early experimental studies. However, the underlying pathogenetic mechanisms for the synergistic interaction of radiation retinopathy (RR) and diabetic retinopathy (DR) have not been compared and evaluated for insight on this phenomenon. The present work draws attention to the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as common mediators of both conditions and sources of ongoing cellular injury in the radiation-induced bystander effect (RIBE) and the senescence-associated secretory phenotype (SASP). Chronic hyperglycemia-mediated oxidative stress and depleted antioxidant defense in diabetes, together with impaired DNA damage sensing and repair mechanisms, were identified as the primary elements contributing to the increased severity of RR in diabetic patients. We conclude that apart from strategic genetic mutations affecting the DNA damage response (DDR), diabetes represents the most significant common risk factor for vascular injury as a side effect of radiotherapy.

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.

BACKGROUND/OBJECTIVES: Geographic atrophy (GA) is a common cause of visual loss. The UK population prevalence is unknown. We studied GA prevalence, characteristics, and associations in an elderly UK population. METHODS: Masked grading of colour fundus photographs from 3549 participants in the cross-sectional study of Bridlington residents aged ≥65 years. GA size, shape and foveal involvement were correlated with demography and vision. RESULTS: GA was detected in 130 eyes (101 individuals) of 3480 participants with gradable images (prevalence 2.90%; 95% CI 2.39–3.52 either eye), was bilateral in 29/3252 subjects (0.89%, 95% CI 0.62–1.28) with bilateral gradable photos, with mean age of 79.26 years (SD 6.99, range 67–96). Prevalence increased with age, from 1.29% (95% CI 0.69–2.33) at 65–69 to 11.96% (95% CI 7.97–17.50) at 85–90 years. Mean GA area was 4.51 mm(2) (SD 6.48, 95% CI 3.35–5.66); lesions were multifocal in 47/130 eyes (36.2%; 95% CI 28.4–44.7). Foveal involvement occurred in 41/130 eyes (31.5%; 95% CI 24.2–40.0). In eccentric GA, mean distance from circumference to fovea was 671μm (SD 463; 95% CI 570–773). Older age (OR 1.10/year increase; 95% CI 1.06–1.14), RPD (OR 1.87; 95% CI 1.10–3.19) and large drusen/RPD ≥ 125 μm (OR 6.16; 95% CI 3.51–10.75) were significantly associated with GA in multivariate analysis. GA lesions (18/31 eyes; 58%; 95% CI 40.7–73.6) had U-shape configuration more frequently in RPD subjects than those without (9/99 eyes, 9.1%; 95% CI 4.66–16.6) (p = 0.0001). CONCLUSION: GA, commonly solitary and eccentric, occurred in the perifovea. However, one third of GA eyes had foveal and bilateral involvement. Possible association of RPD with GA phenotype exists. Population multimodal imaging studies may improve understanding further.

Background: Giant cell arteritis is an immune-mediated, medium to large vessel vasculopathy affecting individuals over 50 years of age. It can cause sudden, severe and irreversible loss of vision, most commonly from an arteritic posterior ciliary artery occlusion causing anterior ischaemic optic neuropathy. The optic nerve appearance would typically be swollen and chalky white. Visual reduction secondary to choroidal ischaemia is a much less frequent presentation, the signs of which can be more subtle in appearance, making its early recognition potentially more challenging. Case Presentation: A 51-year-old male presented to eye casualty complaining of a one-week history of neck pain, intermittent headaches and jaw claudication, associated with reduced vision in his right eye. Presenting visual acuity was hand movements and 6/5 in the right and left eyes respectively. On examination, he was noted to have a right relative afferent pupillary defect, a pale macular area in the right eye with a possible cherry red spot. There was no optic disc swelling. ESR was 34 and CRP was 46 and he was wrongly diagnosed with a non-arteritic central retinal artery occlusion. He subsequently re-presented 5 weeks later with vision loss in his left eye. Best corrected visual acuity was now 6/60 and 6/12 in the right and left eyes respectively. Dilated fundoscopy showed multiple yellow-white lesions in the posterior pole of the left eye and a retinal cotton wool spot. The right optic nerve was pale, and left was normal. A fundus fluorescein angiogram showed delayed choroidal filling and the temporal artery biopsy was suggestive of GCA. He was started on 110mgs of oral prednisolone. After 4 weeks of steroids his BCVA was 6/36 and 6/6 in the right and left eyes respectively. His neck pain, headaches and jaw claudication had all resolved and his ESR and CRP had returned to normal levels. Conclusion: Our case highlights the need for increased awareness of this uncommon presentation of this potentially blinding disease, to allow prompt and appropriate treatment. Our case is unusual in that despite a delayed diagnosis of 5 weeks, visual acuity initially improved with treatment.

Background: Idiopathic epiretinal membranes (ERM) are common with potential for severe visual loss. Surgical outcomes are excellent but predominantly reported from healthy eye studies rather than those with co-morbidities. We report a series of patients with subretinal drusenoid deposits (SRDD) and comorbid ERM with post-operative complications or poor outcomes, describing potential pitfalls to avoid. Case Presentation: This is a case series illustrating the poor functional and morphological outcomes following ERM surgery in five eyes with SRDD. These eyes appear at risk of geographic atrophy (GA), choroidal neovascular membrane (CNVM) formation (pre-and post-operatively) and outer retinal atrophy (ORA), all of which can limit outcomes. Conclusion: ERM surgery in eyes with SRDD presents specific challenges. Assessment of outer retinal changes can be challenging pre-operatively, particularly with significant oedema. Identification of patients with SRDD in ERM eyes often relies on examination of the contralateral eye. Appropriate listing is paramount, with care taken to rule out pre-existing GA or CNVM through use of fundus fluorescein angiography. Patients should be given a guarded prognosis during the consenting process if the outer retina is poorly visualized.

The management of diabetic retinopathy (DR) has evolved considerably over the past decade, with the availability of new technologies (diagnostic and therapeutic). As such, the existing Royal College of Ophthalmologists DR Guidelines (2013) are outdated, and to the best of our knowledge are not under revision at present. Furthermore, there are no other UK guidelines covering all available treatments, and there seems to be significant variation around the UK in the management of diabetic macular oedema (DMO). This manuscript provides a summary of reviews the pathogenesis of DR and DMO, including role of vascular endothelial growth factor (VEGF) and non-VEGF cytokines, clinical grading/classification of DMO vis a vis current terminology (of centre-involving [CI-DMO], or non-centre involving [nCI-DMO], systemic risks and their management). The excellent UK DR Screening (DRS) service has continued to evolve and remains world-leading. However, challenges remain, as there are significant variations in equipment used, and reproducible standards of DMO screening nationally. The interphase between DRS and the hospital eye service can only be strengthened with further improvements. The role of modern technology including optical coherence tomography (OCT) and wide-field imaging, and working practices including virtual clinics and their potential in increasing clinic capacity and improving patient experiences and outcomes are discussed. Similarly, potential roles of home monitoring in diabetic eyes in the future are explored. The role of pharmacological (intravitreal injections [IVT] of anti-VEGFs and steroids) and laser therapies are summarised. Generally, IVT anti-VEGF are offered as first line pharmacologic therapy. As requirements of diabetic patients in particular patient groups may vary, including pregnant women, children, and persons with learning difficulties, it is important that DR management is personalised in such particular patient groups. First choice therapy needs to be individualised in these cases and may be intravitreal steroids rather than the standard choice of anti-VEGF agents. Some of these, but not all, are discussed in this document.

An aging population leads to increasing demand for medical retina services with chronic diseases being managed in long-term care pathways. Many hospital services struggle to deliver efficient and effective MR care due, at least in part, to infrastructure that does not expand responsively enough to meet the increased demand. A steering committee of retinal specialists from a variety of UK NHS hospital ophthalmology departments with experience of leading and managing NHS retinal services in the intravitreal era came together for the generation of this document to review and compile key aspects that should be considered when optimising intravitreal treatment capacity within MR services. This article aims to provide a useful collation and signposting of key published evidence, consensus and insights on aspects of delivering an intravitreal service, including treatment regimens, virtual clinics, staff training and governance, telemedicine and information technology, and data collection and key performance indicators. The objective is to equip ophthalmologic healthcare professionals with the necessary tools to develop and adapt their local service in the face of current and projected increased demand.

To investigate the use of intravitreal ziv-aflibercept (IVZ) in Ghanaian patients with diabetic macular edema (DME).A retrospective study of patients with DME, who had been treated with IVZ (1.25 mg/0.05 ml), as part of routine clinical practice, on pro re nata basis between 2016 and 2018 who had a minimum follow-up of 6 months was retrieved and analyzed. The primary outcome measure was change in best-corrected visual acuity (BCVA) at 6 months. Secondary outcome measures are change in BCVA at 12 months and at the last follow-up visit, adverse events and change in central macular thickness (CMT).Twenty-five eyes of 17 patients (11 males) were included in this study. Their mean age was 60.82 ± 7.70 years and the mean duration of follow-up was 9.52 ± 3.31 months. The mean baseline BCVA (logMAR) of 0.65 ± 0.3 improved to 0.34 ± 0.16 (p 0.0001) and 0.22 ± 0.15 (p = 0.0004) at 6 and 12 months, respectively. Twelve (48%) eyes had a visual gain of at least three lines at 6 months and 4 of 12 eyes (33.3%) at 1 year. There was a significant reduction in the mean CMT at 6 and 12 months and at the last follow-up visit compared to baseline (p 0.0001). The adverse events recorded were raised intraocular pressure (four eyes) at 3, 6, and 12 months post injection, increased blood pressure in a patient with known systemic hypertension and transient memory loss in one patient.IVZ (1.25 mg) was associated with significant improvement in BCVA and reduction in CMT at 6 and 12 months in eyes with DME. A randomized clinical trial is warranted to assess this potentially cost-effective intervention for DME in low-resource settings.

Background: The main objective of the study was to determine the prevalence of diabetic retinopathy (DR), other diabetes-related ocular changes (e.g., cataracts, corneal ulceration), and non-diabetic ocular disease in Ghanaian children and adolescents. The second objective was to evaluate the relationship between these conditions and age at diagnosis, current age, diabetes mellitus (DM) duration, and participant’s sex. Methods: A cross-sectional study, undertaken by a multidisciplinary team, included a cohort of children and adolescents (4–19 years) with DM recruited from selected health facilities in Ghana, from March 2016 to September 2019, after written informed consent or assent. The cohort will be followed up for 3 years to determine the natural course of the ocular changes, reported later. Participants were examined for all microvascular and macrovascular complications, non-diabetic ocular disease, anthropometric measurements, laboratory characteristics and quality of life issues. Full ocular examination was also undertaken. Statistical Package for Social Sciences (SPSS Version 25.0) was used for the data analysis. Continuous and categorical variables were presented as mean and standard deviation (SD), median (interquartile range) and as percentages (%), respectively. T-test and Mann–Whitney U test were used in establishing associations. Results: A total of 58 participants were recruited. DR was detected in only 1 out of 58 (1.7%) participants at baseline. Cataracts were the most common ocular finding, detected in 42 (72%) at baseline. Other anterior segment changes observed included blepharitis 46 (79.3%) and tear film instability 38 (65.5%). There was a significant positive association between duration of the DM and the risk of cataract (p = 0.027). Participants’ age at diagnosis was significantly associated with the presence of prominent corneal nerves (p = 0.004). Conclusions: DR was uncommon in this cohort of young persons with DM in Ghana. Cataracts, blepharitis and refractive errors were ocular changes commonly observed. All young persons with diabetes should undergo regular eye examination in all clinics where follow-up care is provided.

There is growing evidence that the pathogenesis of retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) have a significant chronic inflammatory component. A vital part of the inflammatory cascade is through the activation of pattern recognition receptors (PRR) such as toll-like receptors (TLR). Here, we reviewed the past and current literature to ascertain the cumulative knowledge regarding the effect of TLRs on the development and progression of retinal diseases. There is burgeoning research demonstrating the relationship between TLRs and risk of developing retinal diseases, utilising a range of relevant disease models and a few large clinical investigations. The literature confirms that TLRs are involved in the development and progression of retinal diseases such as DR, AMD, and ischaemic retinopathy. Genetic polymorphisms in TLRs appear to contribute to the risk of developing AMD and DR. However, there are some inconsistencies in the published reports which require further elucidation. The evidence regarding TLR associations in retinal dystrophies including retinitis pigmentosa is limited. Based on the current evidence relating to the role of TLRs, combining anti-VEGF therapies with TLR inhibition may provide a longer-lasting treatment in some retinal vascular diseases.

Quite often patients present at the clinic or surgery complaining of watering eyes. It may be the golfer whose glasses keep misting up on the fairways or the housewife who is embarrassed by tears dropping onto the food when cooking, or it may be the 6-month-old baby whose eyes have watered and discharged since birth. Sometimes an elderly patient may complain of watering eyes when on examination there is no evidence of tear overflow but the vision has been made blurred by cataracts. Some degree of tear overflow is quite normal in windy weather, and the anxious patient may over-emphasise this; it is important to assess the actual amount of overflow by asking the patient whether it occurs all the time both in and out of doors.

Diabetes mellitus is an important cause of blindness: about 1000 people are registered blind from diabetes per year in the United Kingdom. Most of these patients are elderly, but diabetes is the commonest cause of blindness in young people in this country. The management of diabetic eye disease has improved greatly over the past 10 years so that much of this blindness can now be prevented. In spite of this, most general practitioners are aware of tragic cases of rapidly progressive blindness in young diabetics. The more serious manifestations of diabetes in the eye tend to affect patients in the prime of life. The tragedy is even greater when one considers that this blindness is largely avoidable.

This chapter describes the anatomy of the eyeball, the visual pathway, and the ocular adnexae. It also provides a basic introduction to the physiology and functioning of the eye.

This is common and tends to occur spontaneously or sometimes after straining or, especially, vomiting. The eye becomes suddenly red and although the patient may experience a slight pricking, the condition is usually first noticed in the mirror or by a friend. The haemorrhage gradually absorbs in about ten days and investigations usually fail to reveal any underlying cause. Very rarely, it is necessary to cauterise the site of bleeding if the haemorrhage is repeated so often that it becomes a nuisance to the patient (Fig. 5.1).

Significantly reduced levels of the anti-inflammatory gaseous transmitter hydrogen sulfide (H2S) are observed in diabetic patients and correlate with microvascular dysfunction. H2S may protect the microvasculature by preventing loss of the endothelial glycocalyx. We tested the hypothesis that H2S could prevent or treat retinal microvascular endothelial dysfunction in diabetes. Bovine retinal endothelial cells (BRECs) were exposed to normal (NG, 5.5 mmol/L) or high glucose (HG, 25 mmol/L) ± the slow-release H2S donor NaGYY4137 in vitro. Glycocalyx coverage (stained with WGA-FITC) and calcein-labeled monocyte adherence were measured. In vivo, fundus fluorescein angiography (FFA) was performed in normal and streptozotocin-induced (STZ) diabetic rats. Animals received intraocular injection of NaGYY4137 (1 μM) or the mitochondrial-targeted H2S donor AP39 (100 nM) simultaneously with STZ (prevention) or on day 6 after STZ (treatment), and the ratio of interstitial to vascular fluorescence was used to estimate apparent permeability. NaGYY4137 prevented HG-induced loss of BREC glycocalyx, increased monocyte binding to BRECs (p ≤ 0.001), and increased overall glycocalyx coverage (p ≤ 0.001). In rats, the STZ-induced increase in apparent retinal vascular permeability (p ≤ 0.01) was significantly prevented by pre-treatment with NaGYY4137 and AP39 (p < 0.05) and stabilized by their post-STZ administration. NaGYY4137 also reduced the number of acellular capillaries (collagen IV + /IB4-) in the diabetic retina in both groups (p ≤ 0.05). We conclude that NaGYY4137 and AP39 protected the retinal glycocalyx and endothelial permeability barrier from diabetes-associated loss of integrity and reduced the progression of diabetic retinopathy (DR). Hydrogen sulfide donors that target the glycocalyx may therefore be a therapeutic candidate for DR.

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.

Choroidal diseases including inflammation and neovascularization seem to have predilection for different vascular beds. In order to improve our understanding of human macular choroidal angiogenic diseases, we investigate the differences in gene expression between matched human macular and peripheral inner choroidal endothelial cells (CEC) and matched human macular inner and outer CEC. The gene expression profiles of matched, unpassaged human macular and peripheral inner CEC and matched human unpassaged macular inner and outer CEC were conducted using Affymetrix GeneChip arrays. Selected differences in gene expression were validated by real-time-PCR and immunohistochemistry. No differences in probeset expression were demonstrated between inner CECs compared with peripheral inner CECs. In comparison, there was a difference of 1.6% of probesets when matched, unpassaged proliferating human macular inner CEC and macular outer CEC from the same donors were compared. Macular inner CECs demonstrated up-regulation of probesets involved in nervous system development, growth factors, PLVAP, and collagen XVI, while macular outer CECs demonstrated up-regulation of probesets involved in immune function and intracellular signalling. There was a marked homogeneity of human macular and peripheral inner CECs. This suggests that gene expression differences in inner CECs are not responsible for the site specific selectivity of choroidal neovascularisation. Variability was noted, however, in the gene expression of matched macular inner and outer CECs. This could be explained by the differences in the roles and microenvironments of the inner and outer choroid.

Intraocular neovascularisation is associated with common blinding conditions including neovascular age-related macular degeneration (nAMD). Vascular endothelial growth factor (VEGF) is central in driving choroidal neovascularisation in this disease. Many clinical therapies target VEGF-A with intravitreal anti-VEGF drugs, which, however, have limited efficacy and require repeated, prolonged treatment. Other cytokines are known to be involved, including hepatocyte growth factor (HGF), which is shown to have a role in the early stages of nAMD. We investigated the effect of HGF and its co-operation with VEGF-A on human choroidal endothelial cells (CEC). The expression of HGF and related molecules in CEC was investigated using immunofluorescence, Western blotting and flow cytometry. In vitro assays for proliferation, tubule formation and migration were used to assess the potential role of HGF in neovascularisation. Primary human CEC expressed HGF, VEGF-A and their receptors MET and VEGF receptor 2 (VEGFR2). HGF increased CEC proliferation, tubule formation and migration, the increased proliferation and migration appeared to be additive with that achieved with VEGF-A. This study provides insight into growth factor co-operation in CEC signalling and indicates that simultaneous blockage of multiple growth factors or common downstream signalling pathways may provide a more sustained treatment response, enhancing treatments in nAMD.

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.

Rare variants in the complement factor I (CFI) gene, associated with low serum factor I (FI) levels, are strong risk factors for developing the advanced stages of age-related macular degeneration (AMD). No studies have been undertaken on the prevalence of disease-causing CFI mutations in patients with geographic atrophy (GA) secondary to AMD. A multicenter, cross-sectional, noninterventional study was undertaken to identify the prevalence of pathogenic rare CFI gene variants in an unselected cohort of patients with GA and low FI levels. A genotype-phenotype study was performed. Four hundred and sixty-eight patients with GA secondary to AMD were recruited to the study, and 19.4% (n = 91) demonstrated a low serum FI concentration (below 15.6 μg/ml). CFI gene sequencing on these patients resulted in the detection of rare CFI variants in 4.7% (n = 22) of recruited patients. The prevalence of CFI variants in patients with low serum FI levels and GA was 25%. Of the total patients recruited, 3.2% (n = 15) expressed a CFI variant classified as pathogenic or likely pathogenic. The presence of reticular pseudodrusen was detected in all patients with pathogenic CFI gene variants. Patients with pathogenic CFI gene variants and low serum FI levels might be suitable for FI supplementation in therapeutic trials.

Background/Objectives. Currently, in England, antivascular endothelial growth factor (anti-VEGF) is the first-line treatment for diabetic macular oedema (DMO) where central macular thickness (CMT) is ≥400 microns. In pseudophakic eyes with suboptimal response to first-line therapy, intravitreal corticosteroids may also be used. In practice, despite rigorous anti-VEGF therapy, suboptimal response occurs in nearly half of all eyes with DMO. The objective of this study was to investigate structural and functional outcomes and examine anti-VEGF treatment delivery in pseudophakic eyes receiving anti-VEGF injections for DMO. Methods. We performed a retrospective review of outcomes in 81 pseudophakic eyes with DMO that received at least 6 anti-VEGF injections. We reviewed baseline and posttreatment optical coherence tomography images, visual acuity, prescribing patterns, time taken to deliver anti-VEGF injections, and structural and functional outcomes. Results. It took an average of 913 ± 454.1 days to deliver a mean of 11.1 ± 4.7 anti-VEGF injections. Time from baseline to receiving the first 6 anti-VEGF injections was longer than 9 months in 74.7% (n = 59/79) of eyes. There was a mean gain of 1.6 letters (−0.03 logMAR) from baseline to the end point. After 5 anti-VEGF intravitreal injections, the mean CMT was 391.9 μm from 474.4 μm at baseline ( p < 0.0001 ). In 52 of 79 eyes (65.8%), more than one type of anti-VEGF agent was used. Conclusions. The anti-VEGF treatment used to treat these eyes with DMO was suboptimal, a finding consistent with recently published “real-world” data. There was a strong tendency for patients to be switched within the class to a second anti-VEGF agent.

Purpose: The principal aim of this pilot study was to investigate the concordance between the different stages of Age-Related Macular Degeneration (AMD), as determined by the simplified classification of the Age Related Eye Disease Study Group (AREDS), and new evaluation criteria using a microperimetry system. Methods: A complete eye examination and a microperimetry MAIATM (Macular Integrity Assessment, CenterVue, Padova, Italy) examination was performed on 59 eyes with early, intermediate or advanced AMD. We analysed 19 evaluation criteria for every clinical group category. Results: There were 20 female and 12 male participants included with a median age of 74 years (min: 54, max: 87). Thirteen eyes (22%) were classified as category 1, 11 eyes (18.6%) as category 2, 17 eyes (28.8%) as category 3 and 18 eyes (30.6%) as category 4 AMD. All evaluated microperimetry criteria related to retinal sensitivity were found to have a statistically significant difference among the stages ( p Conclusions: The mean sensitivity and the categorized sensitivity (set to 25, 15 and 5 dB), the five higher and lower stimuli sensitivity appeared to be the most sensitive criteria to differentiate the four AMD categories. Microperimetry provides a new reproducible method of anatomical-functional macular analysis.

Background Diabetes is associated with premature morbidity and mortality from its many complications. There are limited data on the chronic complications of diabetes in children and adolescents in sub-Saharan Africa. Objective The study aims to determine the (1) burden and related factors of chronic systemic complications of diabetes, including diabetic and nondiabetic ocular conditions in children and adolescents, and (2) quality of life (QoL) of participants compared to healthy controls. This manuscript describes the study methodology. Methods Demographic information, medical history, anthropometric measurements, and laboratory characteristics were collected, and the participants were screened for microvascular and macrovascular complications as well as nondiabetic ocular disease. QoL questionnaires were administered to participants, their caregivers, and controls. Participants were followed up annually up to 3 years to determine the natural history of and trends in these conditions. SPSS Version 25.0 will be used for data analysis. Continuous and categorical data will be presented as mean (SD) and as percentages (%), respectively. t tests and analysis of variance will be used to compare means, and chi-square tests will be used to compare categorical data. Correlation, regression, and logistic regression analyses will be employed to establish linear associations and causal associations as appropriate. Relative risk and odds ratios will be used to estimate risk. QoL outcomes in Ghanaian children and adolescents with diabetes mellitus compared with caregivers and healthy controls will be assessed using the Pediatric Quality of Life inventory. Significance will be set at α=.05. Results Institutional approval from the Ethical and Protocol Review Committee of the University of Ghana Medical School was received on August 22, 2014 (Protocol Identification Number: MS-Et/M.12-P4.5/2013-2014). Funding for the project was received from the University of Ghana Research Fund (#UGRF/9/LMG-013/2015-2016) in March 2016. Patient recruitment, clinical examination, and data collection commenced in August 2016 and was completed in September 2019. A total of 58 children and adolescents with diabetes mellitus have been recruited. Blood samples were stored at –80 °C for analysis, which was completed at the end of July 2020. Data analysis is ongoing and will be completed by the end of December 2020. Investigators plan to submit the results for publication by the end of February 2021. Conclusions The prevalence, natural history, trends in diabetic complications and nondiabetic ocular disease, and QoL will be provided. Our data may inform policies and interventions to improve care given to children and adolescents with diabetes. International Registered Report Identifier (IRRID) DERR1-10.2196/21440

AimTo evaluate the efficacy of ziv-aflibercept in Ghanaian patients with macular edema (ME) secondary to retinal vein occlusion (RVO).MethodologyIn this retrospective study, the medical records of patients with ME secondary to RVO who had been treated with intravitreal ziv-aflibercept (IVZ) (1.25 mg/0.05 ml), as part of routine clinical practice, on pro re nata basis with a minimum follow-up of 6 months were retrieved and analyzed. The main outcome measures are mean change in best-corrected visual acuity (BCVA) and central subfield foveal thickness (CSFT) measured on optical coherence tomography from baseline to 12 months post-IVZ, and ocular and systemic safety.ResultsForty-three eyes were included in this study. Their mean age was 62.8 ± 11.9 years, 67.4% had at least 12-month duration of follow-up, 50% had primary open-angle glaucoma and 38 (88.4%) eyes were treatment naive. There was significant improvement in mean BCVA in LogMAR at 1 month post-initiation of IVZ (0.8 ± 0.5 vs. 1.1 ± 0.6), and visual improvement was maintained up to 12 months (p p = 0.01). There was significant reduction in mean CSFT up to 12 months post-IVZ injection compared to baseline (p ConclusionWe have observed significant improvement in functional and anatomic outcomes 12 months post-initiation of IVZ. There is the need to confirm long-term efficacy and safety of IVZ in a large prospective study.

Purpose To report trends in real-world outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) over the last decade. Design Systematic review. Methods Medline, PubMed, and Embase databases were searched from 9 April 2010 to 8 April 2020 for publications that met the inclusion criteria: treatment-naïve eyes, UK-only data and ≥1 year of follow-up. ICHOM (International Consortium for Health Outcome Measures) outcomes and study quality were assessed. Visual acuity (VA) trends were assessed in studies with ≥100 eyes at baseline. Results Twenty-six studies (n=25,761 eyes) were included, meeting 14–17 out of 20 Institute of Health Economics Quality Appraisal of Case Series checklist domains. Only ranibizumab and aflibercept outcome data were available. The mean injection number in the first year of treatment was 5.9 in publications from 2010 to 2015 and 7.1 from 2015 to 2020. Average baseline VA and mean one-year, two-year and three-year VA gains gradually improved over the last decade. Longer-term studies reported that the visual gains achieved in the first year of treatment were rarely maintained, with under-treatment a likely contributing factor. Conclusion UK real-world outcomes have improved over the last decade with improved service delivery and the adoption of more proactive treatment regimens but are still not always as impressive as registration clinical trial results. Access to longer-acting anti-VEGF therapies would reduce the treatment burden for patients, carers, and the healthcare system, potentially making replication of clinical trial results possible in the NHS.

Objective: To report fixation stability changes in patients with different forms of infantile nystagmus syndrome (INS), who have undergone a visual rehabilitation through biofeedback fixation training (BFT) with microperimetry (MP). Design: Retrospective study. Methods: Patients 6 to 12 years-old with INS who performed BFT with MP. Initially 10 once-weekly followed by eight twice-weekly sessions of BFT during a minimum of 6 months period were performed. Visual acuity (VA) and MP fixation stability indices were analyzed, including displacement from fixation point (P1, P2) and percentage of retinal loci used during fixation attempt (BCEA 63% and 95%). Statistical analysis was conducted at baseline (BL), 10 weeks (W10) and 6 months (M6). Results: Twelve patients (mean age 8.9 years.) with INS completed the whole training session. All patients showed significant improvement in the mean BCEA fixation area (deg2): For BCEA@95% BL was 78.0, 46.1 at W10, and 27.4 at M6 ( p-value = 0.004). For BCEA@63% BL was 27.3, 15.4 in W10, and 9.17 at M6 ( p = 0.01). The ANOVA test for the FS indices of P1 and P2, as well as for BCVA showed no significant difference when compared at the same intervals. Conclusion: Fixation stability (FS) indices of BCEAs (63% and 95%) improved at W10 and M6, while P1 and P2 showed significant improvement at W10 but not at M6, probably because BCEA involves a much larger area than P1 and P2. VA did not show significant improvement at any time point.

Digital retinal imaging is at the core of a revolution that is continually improving the screening, diagnosis, documentation, monitoring, and treatment of infant retinal diseases. Historically, imaging the retina of infants had been limited and difficult to obtain. Recent advances in photographic instrumentation have significantly improved the ability to obtain high quality multimodal images of the infant retina. These include color fundus photography with different camera angles, ultrasonography, fundus fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. We provide a summary of the current literature on retinal imaging in infants and highlight areas where further research is required.

BACKGROUND Diabetes is associated with premature morbidity and mortality from its many complications. There are limited data on the chronic complications of diabetes in children and adolescents in sub-Saharan Africa. OBJECTIVE The study aims to determine the (1) burden and related factors of chronic systemic complications of diabetes, including diabetic and nondiabetic ocular conditions in children and adolescents, and (2) quality of life (QoL) of participants compared to healthy controls. This manuscript describes the study methodology. METHODS Demographic information, medical history, anthropometric measurements, and laboratory characteristics were collected, and the participants were screened for microvascular and macrovascular complications as well as nondiabetic ocular disease. QoL questionnaires were administered to participants, their caregivers, and controls. Participants were followed up annually up to 3 years to determine the natural history of and trends in these conditions. SPSS Version 25.0 will be used for data analysis. Continuous and categorical data will be presented as mean (SD) and as percentages (%), respectively. t tests and analysis of variance will be used to compare means, and chi-square tests will be used to compare categorical data. Correlation, regression, and logistic regression analyses will be employed to establish linear associations and causal associations as appropriate. Relative risk and odds ratios will be used to estimate risk. QoL outcomes in Ghanaian children and adolescents with diabetes mellitus compared with caregivers and healthy controls will be assessed using the Pediatric Quality of Life inventory. Significance will be set at α=.05. RESULTS Institutional approval from the Ethical and Protocol Review Committee of the University of Ghana Medical School was received on August 22, 2014 (Protocol Identification Number: MS-Et/M.12-P4.5/2013-2014). Funding for the project was received from the University of Ghana Research Fund (#UGRF/9/LMG-013/2015-2016) in March 2016. Patient recruitment, clinical examination, and data collection commenced in August 2016 and was completed in September 2019. A total of 58 children and adolescents with diabetes mellitus have been recruited. Blood samples were stored at –80 °C for analysis, which was completed at the end of July 2020. Data analysis is ongoing and will be completed by the end of December 2020. Investigators plan to submit the results for publication by the end of February 2021. CONCLUSIONS The prevalence, natural history, trends in diabetic complications and nondiabetic ocular disease, and QoL will be provided. Our data may inform policies and interventions to improve care given to children and adolescents with diabetes. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/21440

Purpose To evaluate outcomes of epiretinal membrane (ERM) surgery in eyes with subretinal drusenoid deposits (SRDDs) and to compare them with those with isolated ERM. Design Retrospective case-control study of consecutive patients who underwent pars plana vitrectomy (PPV) with ERM peeling. Participants Twenty-five patients with SRDDs on spectral-domain (SD)-OCT who underwent surgery for ERM were included in the study. From the same cohort, for each case, we selected 2 age-matched control participants (50 eyes with isolated ERM). Preoperative best-corrected visual acuity (BCVA) also was matched as closely as possible. Methods All participants underwent PPV and ERM peel for primary ERM. Main Outcome Measures Postoperative BCVA, improvement in BCVA, preoperative and postoperative central macular thickness, surgical complications, and development of age-related macular degeneration (AMD) were recorded. Results At final examination, mean postoperative BCVA was significantly less for eyes with SRDDs (0.51 logarithm of the minimal angle of resolution [logMAR] vs. 0.21 logMAR; P = 0.0001). Eyes with SRDDs demonstrated less improvement in BCVA after ERM surgery (0.13 logMAR vs. 0.30 logMAR; P = 0.0032). Eyes with SRDDs were significantly less likely to gain 2 or more Snellen lines of BCVA after ERM surgery (28% vs. 56%; P = 0.028). Three of 25 patients (12%) undergoing ERM surgery showed worsening of Snellen BCVA by 2 lines or more. Three of 25 eyes (12%) with SRDDs demonstrated advanced AMD after surgery, compared with 0 participants in the control group (P = 0.034). Conclusions Epiretinal membrane surgery in eyes with SRDDs is associated with less favorable visual outcomes. Fewer patients demonstrate gain in BCVA, whereas a significant number show a deleterious decline. After surgery, AMD incidence seems high and patients may have an increased risk of raised intraocular pressure. These findings require further study to establish whether this represents a causal relationship. Surgeons should be vigilant for these complications. Appropriate patient counseling during the consenting process must be made.

AIMS: To determine disc haemorrhage (DH) prevalence in an elderly UK population—the Bridlington Eye Assessment Project (BEAP). METHODS: Thirty-degree 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: In all, 3548 participants with photographs in at least one eye. DHs were present in 53 subjects (1.49%), increasing from 1.17% (65- to 69-year age group) to 2.19% (80- to 84-year age 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 eyes had NTG, two 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 Age-related Macular Degeneration (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.

Background Amniotic membrane (AM) has been used as a biological substrate in ophthalmology and other fields for several years. It has a valuable role in ocular surface burns and non-healing ulcers. It is known that AM is non-immunogenic and has anti-inflammatory and anti-fibrotic properties and supports epithelial cell proliferation and migration. These are supposedly mediated through a host of growth factors and cytokines. Despite its clinically accepted role in reducing corneal vascularisation when applied on the eye, there have been contradicting reports on the effect of AM on angiogenesis. Methods The effect of soluble factors released from clinically prepared cryo-preserved AM on cultured human umbilical vein endothelial cell (HUVEC) proliferation was quantified and angiogenesis assessed on matrigel. Antibody blockage of soluble tissue inhibitors of metalloproteinase (TIMP)2 and Thrombospondin, identified on Searchlight protein arrays, was used to evaluate their role in the effect of cryo-preserved AM. Results AM conditioned medium (AMCM) was found to reduce HUVEC proliferation and angiogenesis. Angiogenesis was reduced by direct application of AM, a gradient effect was observed, where HUVEC closer to the AM failed completely in forming any tubules. In addition, HUVEC failed to survive directly on the AM. Analysis of the soluble factors released by the amnion included high levels of anti-angiogenic factors, thrombospondin and TIMP 1 and 2. Antibody blockage of TIMP2 and thrombospondin prevented the anti-angiogenic effect of AMCM and AM. Conclusion AM in vitro has potent anti-angiogenic properties dependent on secreted TIMP2 and thrombospondin, validating some of the effects observed clinically.

The aim of this systematic literature review was to evaluate the efficacy and safety of interventions for the treatment of choroidal neovascularization (CNV) secondary to etiologies other than age-related macular degeneration and pathologic myopia. Relevant randomized controlled trials (RCTs) and prospective observational studies were identified by searching MEDLINE, MEDLINE In-Process, EMBASE, and CENTRAL. The search identified 5 RCTs; no relevant observational studies were identified. The studies differed in terms of underlying cause of CNV, patient numbers (n = 9–178), follow-up time (2–36 months) and quality assessment. In the largest RCT (n = 178 across a range of rare CNV etiologies), intravitreal ranibizumab showed superior efficacy versus sham from baseline to month 2 [mean best-corrected visual acuity (BCVA): + 9.5 vs. − 0.4 letters; p

India is considered the diabetes capital of the world, and a significant proportion of patients undergoing cataract surgery are diabetic. Considering this, we reviewed the principles and guidelines of managing cataract in patients with diabetes. The preoperative, intraoperative, and postoperative factors are of paramount importance in the management of diabetic cataract patients. Particularly, the early recognition and treatment of diabetic retinopathy or maculopathy before cataract surgery influence the final visual outcome and play a major role in perioperative decision-making. Better understanding of various factors responsible for favorable outcome of cataract surgery in diabetic patients may guide us in better overalll management of these patients and optimizing the results.

The management of diabetic retinopathy (DR) has evolved considerably over the past decade, with the availability of new technologies (diagnostic and therapeutic). As such, the existing Royal College of Ophthalmologists DR Guidelines (2013) are outdated, and to the best of our knowledge are not under revision at present. Furthermore, there are no other UK guidelines covering all available treatments, and there seems to be significant variation around the UK in the management of diabetic macular oedema (DMO). This manuscript provides a summary of reviews the pathogenesis of DR and DMO, including role of vascular endothelial growth factor (VEGF) and non-VEGF cytokines, clinical grading/classification of DMO vis a vis current terminology (of centre-involving [CI-DMO], or non-centre involving [nCI-DMO], systemic risks and their management). The excellent UK DR Screening (DRS) service has continued to evolve and remains world-leading. However, challenges remain, as there are significant variations in equipment used, and reproducible standards of DMO screening nationally. The interphase between DRS and the hospital eye service can only be strengthened with further improvements. The role of modern technology including optical coherence tomography (OCT) and wide-field imaging, and working practices including virtual clinics and their potential in increasing clinic capacity and improving patient experiences and outcomes are discussed. Similarly, potential roles of home monitoring in diabetic eyes in the future are explored. The role of pharmacological (intravitreal injections [IVT] of anti-VEGFs and steroids) and laser therapies are summarised. Generally, IVT anti-VEGF are offered as first line pharmacologic therapy. As requirements of diabetic patients in particular patient groups may vary, including pregnant women, children, and persons with learning difficulties, it is important that DR management is personalised in such particular patient groups. First choice therapy needs to be individualised in these cases and may be intravitreal steroids rather than the standard choice of anti-VEGF agents. Some of these, but not all, are discussed in this document.

While intraocular pressure (IOP) is a well-known risk factor for glaucoma, intracranial pressure (ICP) is attracting heightened interest because of its influence on optic nerve head biomechanics. Studies have shown that ICP can have marked impact on posterior eye health by modifying the translaminar pressure gradient across the optic nerve. There is also growing evidence that IOP and ICP may be interconnected, though the mechanism of their putative interaction is unknown. We sought to test the hypothesis that ICP modulates IOP by altering aqueous humor dynamics. The anterior chamber and lateral ventricle of anesthetized Brown-Norway rats were cannulated with fine-gauge needles connected to a programmable pump and saline reservoir, respectively. ICP was manipulated by varying reservoir height, and eye outflow facility (C) was determined from the pump flowrate required to hold IOP at different levels. C was 22 ± 4 nl/min/mmHg at resting ICP and 13 ± 3 nl/min/mmHg when ICP was raised 15 mmHg, a reduction of 41 ± 13% (n=18). The decrease in outflow facility was independent of blood pressure, reversible, scaled with ICP elevation, and correlated with increases in resting IOP. It was physiological in origin because C returned to baseline values after euthanasia and corneal application of tetrodotoxin though ICP remained elevated. These results indicate that a neural feedback mechanism driven by ICP regulates conventional outflow facility in rats. The mechanism may protect the eye from translaminar pressure swings and may offer a new target for glaucoma treatment.

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Purpose Adult vitelliform lesions (AVL) are associated with age related macular degeneration (AMD) and subretinal drusenoid deposits (SRDD). We evaluated the natural course of AVL, assessing the influence of SRDD on disease progression, visual function and incidence of macular atrophy (MA) and choroidal neovascular membranes (CNVM). Methods A retrospective cohort study was conducted between January 2011 and March 2016. Demographic, clinical and imaging data from 26 consecutive AVL patients were analysed following case note review. Optical coherence tomography images were graded for SRDD and patients divided into those with/without SRDD. Outcomes included presenting/changes in best corrected visual acuity (BCVA) and incidence of MA/CNVM. Results Mean age was 78.6 ± 7.6 years. Mean follow-up was 51.5 ± 25.6 months. Twelve patients (46.2%) had SRDD at presentation with 3 more (11.5%) developing them. Subjects with SRDD were older (mean 81.7 ± 6.1 years vs 74.3 ± 7.6 years, p = 0.010). Mean presenting BCVA was worse in SRDD eyes (0.39 ± 0.31 logMAR vs 0.19 ± 0.18 logMAR, p = 0.017). Eight of 15 patients with SRDD (53.3%) developed incident MA or CNVM; higher than those with no SRDD (1/11, 9.1%; p = 0.036). Two patients (7.7%) developed full thickness macular holes. Conclusions Patients with AVL and SRDD likely represent an advanced pathological stage or phenotype with worse visual outcome and higher risk of MA/CNVM. Possible overlap with AMD exists. Follow-up, counselling and provisions for early detection/treatment of complications should be made. Better classification including improved understanding of phenotypic and genetic variations with reference to comorbid diseases including AMD is required. Presence of SRDD in AVL offers a dichotomous classification, indicating risk of future MA/CNVM formation.

NEW FINDINGS What is the central question of this study? Astronauts on-board the International Space Station (ISS) perform daily exercises designed to prevent muscle atrophy and bone demineralization: what is the effect of resistive exercise performed by subjects while exposed to the same level of hypercapnia as on the ISS on intraocular pressure (IOP)? What is the main finding and its importance? The static exercise-induced elevation in IOP during 6° prone head-down tilt (simulating the headward shift of body fluids in microgravity) is augmented by hypercapnia and exceeds the ocular hypertension threshold. ABSTRACT The present study assessed the effect of 6° head-down (establishing the cephalad fluid displacement noted in astronauts in microgravity) prone (simulating the effect on the eye) tilt during rest and exercise (simulating exercise performed by astronauts to mitigate the sarcopenia induced by unloading of weight-bearing limbs), in normocapnic and hypercapnic conditions (the latter simulating conditions on the International Space Station) on intraocular pressure (IOP). Volunteers (mean age = 57.8 ± 6 years, n = 10) participated in two experimental sessions, each comprising: (i) 10 min rest, (ii) 3 min static handgrip exercise (30% max), and (iii) 2 min recovery, inspiring either room air (NCAP) or a hypercapnic mixture (1% CO2 , HCAP). We measured IOP in the right eye, cardiac output (CO), stroke volume (SV), heart rate (HR) and mean arterial pressure (MAP) at regular intervals. Baseline IOP in the upright seated position while breathing room air was 14.1 ± 2.9 mmHg. Prone 6° head-down tilt significantly (P

ObjectivesTo 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 analysisA 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 χ2 and conventional content analysis.ResultsOnly 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.ConclusionIn 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.

Purpose: The purpose of this study was to characterize foveal pit morphology in an African (Ghanaian) population, to compare it to that of a Caucasian group and to determine if it varied with age in the two populations. Methods: The depth, diameter, slope, and volume of the foveal pit were interpolated from optical coherence tomography volume scans recorded in 84 Ghanaian and 37 Caucasian individuals. Their association with age, sex, and ethnicity was investigated using multilevel regression models. Results: The foveal pit differed significantly in width, slope, and volume between Ghanaian men and women (P < 0.001), but only in width and volume between Caucasian men and women (P < 0.01). In Ghanaians, age was associated with a narrowing of the foveal depression and a reduction of its volume. Overall, these changes were more pronounced in women as compared to men and were largely absent from the Caucasian group. When controlled for age, the foveal pit of Ghanaians was significantly wider and larger in volume as compared to the Caucasian group (P < 0.001). Conclusions: The morphology of the foveal pit differs between African and Caucasian individuals. These anatomic differences should be considered when examining differences in prevalence and clinical features of vitreoretinal disorders involving the fovea between the two populations. Translational Relevance: Differences in retinal anatomy may partly explain variations in the prevalence and clinical features of retinal diseases between African and Caucasian. Such differences should be adequately considered in diagnoses and monitoring of ocular diseases in patients with African ancestry.

Brief Background: Retinal vascular diseases are a significant cause of visual loss world-wide, including Ghana. Anti-vascular endothelial growth factor (anti-VEGF) such as aflibercept, ranibizumab and bevacizumab have become the standard of care for diabetic macular edema (DME), macular edema (ME) following retinal vein occlusions (RVO), and neovascular age related macular degeneration(nvAMD). Aflibercept has been approved by the United States of America (USA) Food and Drug Administration (FDA) for the treatment of DME, nvAMD, and ME following RVO. The recommended dose of intravitreal aflibercept is 2mg in 0.05ml administered monthly or initial monthly injections for the first 3 months followed by 2 monthly injections. Aflibercept is highly expensive (USD1850 per dose) and not available in many developing countries including Ghana. Ziv-aflibercept, a molecule structurally identical to aflibercept but differs due to its formulation with hyper-osmolality has been approved by the USA FDA for the treatment of metastatic colorectal cancers. Ziv-aflibercept, used off-label, has been found to be safe in patients with DME and nvAMD in phase 1 trials at a dose of 1.25mg in 0.05ml. The cost of compounded ziv-aflibercept is much reduced to USD 67 per dose. The 1.25mg dose of ziv-aflibercept is below that recommended for intravitreal injections of aflibercept. However, to the best of our knowledge, there are no data available on the safety of 2mg of ziv-aflibercept, although in vitro studies indicate that it is safe. Furthermore, there is no data on the intravitreal administration of ziv-aflibercept in the Ghanaian population to date. Aim: To evaluate the safety of 1.25mg and 2mg ziv-aflibercept in Ghanaian population with retinal vascular diseases. Methodology: This is a prospective, randomised, double masked, phase 1, interventional study. Twenty (20) patients with centre involving DME, ME following RVO, and nvAMD will be assigned to 2 groups: 1.25mg/0.05ml (control) and 2mg/0.08ml ziv- aflibercept and will receive 3 doses of ziv-aflibercept at 4 weekly intervals. Intraocular pressure will be determined 30 minutes following injection and in subsequent visits. Safety data will be collected at days 1and 7 after initiation of treatment, and at 4, 8 and 12 weeks. Primary outcome measures are ocular safety parameters- including the incidence of pain, blurred vision, raised intraocular pressure, intraocular inflammation and endophthalmitis(eye infection), as well as systemic safety at 4 weeks. Secondary outcome measures are ocular and systemic safety parameters at 12 weeks, change in BCVA (ETDRS letters), central subfield foveal thickness (CSFT) and central retinal thickness (CRT) as measured on optical coherent tomography (OCT) at 4 and 12 weeks. Expected Outcome: We seek to evaluate the safety of 2 different doses of ziv-aflibercept in patients with DME, ME following RVO and nvAMD in a Ghanaian population. We expect that there will be no differences in safety between the 2 doses of ziv-aflibercept.

Aim To report the natural history of subretinal fluid (SRF) causing foveal detachment in macular telangiectasia type 2 (MacTel) and our experience of therapeutic intervention with intravitreal steroids or antivascular endothelial growth factor inhibitor (anti-VEGF) agents in some cases. Methods Retrospective case series. Three of the MacTel study9s largest registries were searched to identify eyes with foveal detachment. Results We identified 7 eyes from 6 exclusively female patients. The prevalence of foveal detachment was low, present in 1.4% of the assessed MacTel population. Age at presentation ranged from 50 to 66 years. Follow-up ranged from 2 to 8 years. There was late-phase leakage on fluorescein angiography from what was presumed to be ectatic capillaries. The SRF fluctuated without a rapid decline in visual acuity in cases that were not treated. When they were, intravitreal anti-VEGF and steroid therapy in general reduced SRF, at least temporarily, but did not halt the gradual long-term decrease in visual acuity. In one case, optical coherence tomography angiography showed significant reduction in the extent of the predominantly deep intraretinal vascular complex 1 month after anti-VEGF therapy. Discussion and conclusions As the natural history of this unusual MacTel phenotype is not characterised by rapid visual decline, intervention with intravitreal anti-VEGF or steroid therapy may not be necessary.

Diabetic macular oedema (DMO), a leading cause of preventable visual loss in the working population, is caused by an increase in microvascular endothelial cell permeability, and its prevalence is on the increase in parallel with the rising worldwide prevalence of diabetes. It is known that retinal vascular leakage in DMO is contributed to by VEGF upregulation as well as non-VEGF dependent inflammatory pathways, and the potential use of anti-inflammatory agents such as the glucocorticoids, including dexamethasone are being extensively studied. However, the mechanisms of action of dexamethasone in DMO reduction are not fully understood. Using human primary retinal endothelial cells (REC) the in vitro effect of dexamethasone in modulating the proliferation, permeability and gene expression of key tight and adheren junction components, and the expression of angiopoietins (Ang) 1 and 2 in high (25 mM) glucose conditions were investigated. High glucose decreased REC proliferation, an effect that was reversed by dexamethasone. High glucose conditions significantly increased REC permeability and decreased claudin-5, occludin and JAM-A gene expression; dexamethasone was effective in partially reversing these changes, restoring EC permeability to the normal or near normal state. High glucose levels resulted in reduction of Ang1 secretion, although Ang2 levels were consistently high. DEX increased Ang1 and decreased Ang2, indicating that the balance of Ang1/Ang2 may be important in determining functional changes in REC under high glucose conditions.

PurposeTo report the association and prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting adult onset foveomacular vitelliform dystrophy (AFVD). To compare the strength of association with other pathologies resulting from dysfunction of the choroid-Bruch's membrane-retinal pigment epithelium (RPE) complex, including eyes with geographic atrophy (GA) and angioid streaks.MethodsRetrospective single-centre review of all consecutive newly presenting AFVD. Multimodal imaging with spectral domain optical coherence tomography, fundus photographs, red-free/blue light images, and fundus fluorescein angiograms were graded for the presence of RPD. For comparison, all consecutive newly presenting cases of GA and eyes with angioid streaks were studied.ResultsFifteen (15) patients were identified with AFVD (mean age of 77.3 years; 73.3% female). Mean age of patients with AFVD and RPD was 80.5 years (SD 3.7), whereas that of patients with AFVD without RPD was 75.1 years (SD 7.0). This age difference did not reach statistical significance, P=0.1. Six (40%) had identifiable RPD; being a bilateral finding in 100% of patients. No males with AFVD and RPD were identified. A total of 92 eyes presented with GA. Twenty-three (23) of these (25.0%) had RPD. Twelve (12) patients presented with identifiable angioid streaks, with 4 (36.4%) having RPD.ConclusionRPD are a frequent finding in eyes with newly presenting AFVD; not being restricted to AMD, but a finding common among diseases where pathophysiological mechanisms involve damage to Bruch's membrane and the RPE, whether genetic or degenerative. Our study supports the concept that they occur with high but variable frequencies in eyes with various pathologies.

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