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Sophie J Bakri,1 Winfried MK Amoaku,2 Danielle Altman,3 Stéphane Quéré,4 Jaclyn Quilantan,5 Julia Carpenter-Conlin,5 Sujata P Sarda,5 Daniel L Jones,5 Jared S Nielsen6, † 1Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA; 2Faculty of Medicine & Health Sciences, University of Nottingham, Queens Medical Centre, Nottingham, England, UK; 3Modus Outcomes, a THREAD Company, Cary, NC, USA; 4Modus Outcomes, a THREAD Company, Lyon, France; 5Apellis Pharmaceuticals, Inc, Waltham, MA, USA; 6Wolfe Eye Clinic PC, West Des Moines, IA, USA†Dr Jared S Nielsen passed away on June 14, 2024Correspondence: Sophie J Bakri, Department of Ophthalmology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA, Tel +1 507-284-3614, Email bakri.sophie@mayo.eduPurpose: Geographic atrophy (GA) impacts both patients and caregivers, yet little is understood about their respective burdens. The MOSAIC study aimed to identify the clinical, emotional, and financial burden among patients with GA and caregivers.Methods: A total of 28 patients with GA and 17 caregivers from the United States (US), the United Kingdom, and Australia participated in individualized qualitative interviews followed by a cross-sectional quantitative survey of 102 patients and 102 caregivers in the US. Interview transcripts were analyzed to develop conceptual models, which were then used to guide the design of quantitative surveys. Data were described at the item level and score level when appropriate (National Eye Institute Visual Function Questionnaire [NEI VFQ]-39 and Zarit Burden Interview [ZBI]). For the patient/caregiver dyad sample, the association between the NEI VFQ-39 scores and ZBI score was explored through correlation coefficients and scatterplots.Results: GA had a substantial impact on patients’ vision-related quality of life, activities of daily living, and instrumental activities of daily living. There was considerable overlap between perspectives and key concerns identified by patients and caregivers. Eighty-three percent of caregivers reported having to drive patients to appointments due to limited patient mobility, for example, and 41% reported a change in their employment status after becoming a caregiver, with 50% of them unable to work due to caregiving. The burden of patients and caregivers had a correlation ranging from − 0.63 to − 0.21 between NEI VFQ-39 subscale and composite scores and ZBI score.Conclusion: This study confirms the paucity of support for both patients with GA and caregivers. Both groups require expanded access to financial, social, and mental health resources.Plain Language Summary: What is this summary about?People with geographic atrophy, also called GA, can lose their eyesight and have a hard time driving, reading, and recognizing faces. This can worsen their quality of life. Often, people with GA need someone to care for them. The MOSAIC study was done to find out how GA affects health, happiness, and finances of people with GA and their caregivers.What were the results?One hundred and two people with GA and 102 caregivers in the United States were interviewed. The average age of people with GA was 68 years and of caregivers was 46 years. The findings showed that most people with GA did not drive because of their poor eyesight and instead counted on their caregivers to drive them to doctor appointments and other places. They also had a reading and doing things around their home because of their worsened eyesight.Both people with GA and caregivers said they felt stressed. They both worried about spending money on things they need to make living with GA easier. They also felt stressed about their finances because they could not work as much. People with GA worried most about losing their independence and caregivers worried most about the future of their loved one with GA.What do the results mean?This study showed that GA has a serious effect on people’s health and quality of life while also having a major impact on their caregivers.Keywords: age-related macular degeneration, functional vision, geographic atrophy, health-related quality of life, caregiver burden, disease burden

Georgios D Panos,1,2 Arun Lakshmanan,1 Panagiotis Dadoukis,3 Matteo Ripa,4 Lorenzo Motta,4 Winfried M Amoaku1,2 1Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK; 2Division of Ophthalmology and Visual Sciences, Faculty of Medicine & Health Sciences, School of Medicine, University of Nottingham, Nottingham, UK; 3Eye Treatment Centre, Whipps Cross University Hospital, Barts Health NHS Trust, London, UK; 4Department of Ophthalmology, William Harvey Hospital, East Kent Hospitals University NHS Foundation Trust, Kent, UKCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.com Lorenzo Motta, Department of Ophthalmology, William Harvey Hospital, Kennington Road, Willesborough, Ashford, Kent, TN24 0LZ, UK, Tel +44 1233 633331, Email lorenzo.motta@nhs.netAbstract: Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision loss in developed nations. The primary therapeutic approach for managing complications linked to these diseases involves the intravitreal delivery of anti-vascular endothelial growth factor (VEGF) treatments. Faricimab is a novel, humanised, bispecific antibody that simultaneously binds all VEGF-A isoforms and Angiopoietin-2, which has been approved by regulatory agencies, such as the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), for the treatment of neovascular AMD and diabetic macular oedema (DMO). Intravitreal faricimab holds the promise of reducing the treatment burden for patients with these conditions by achieving comparable or superior therapeutic outcomes with fewer clinic visits. The scope of faricimab’s application includes addressing complex macular conditions such as DMO. This review intends to elucidate the distinctive pharmacological characteristics of faricimab and provide an overview of the key clinical trials and real-world studies that assess its effectiveness and safety in treating degenerative macular diseases.Keywords: degenerative macular disorders, faricimab, anti-VEGF, efficacy, safety, intravitreal treatment, age-related macular degeneration, diabetic macular oedema, retinal vein occlusion, diabetic retinopathy

Hemal Mehta,1,2 Leah N Kim,2 Thibaud Mathis,3,4 Pardis Zalmay,1 Faruque Ghanchi,5 Winfried M Amoaku,6 Laurent Kodjikian3,4 1Ophthalmology, Royal Free London NHS Foundation Trust, London, UK; 2Macular Research Group, Save Sight Institute, Sydney University, Sydney, Australia; 3Service d’ophtalmologie, Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital de la Croix-Rousse, Lyon, France; 4Laboratoire UMR-CNRS 5510 Matéis, Université Lyon 1, Villeurbanne, Lyon, France; 5Ophthalmology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK; 6Academic Ophthalmology and Vision Sciences, Division of Clinical Neurosciences, Eye and ENT Centre, Queen’s Medical Centre, University of Nottingham, Nottingham, UKCorrespondence: Hemal MehtaRoyal Free London NHS Foundation Trust, Pond Street, Hampstead, London, UKEmail HM@cantab.netPurpose: 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.Keywords: anti-vascular endothelial growth factor, anti-VEGF, macular degeneration, treatment, systematic review, aflibercept, ranibizumab, intravitreal therapy

Introduction: Neovascular age-related macular degeneration is a global public-health concern, associated with a considerable burden to individuals, healthcare systems, and society. The objective of this study was to understand different perspectives on the challenges associated with the clinical management of neovascular age-related macular degeneration, which could elucidate measures to comprehensively improve clinical care and outcomes., Methods: A survey was carried out of patients with neovascular age-related macular degeneration, their providers, and clinic staff in 77 clinics across 24 countries on six continents, from a diverse range of healthcare systems, settings, and reimbursement models. Surveys comprised a series of single/multiple-response questions completed anonymously. Data gathered included patient personal characteristics, appointment attendance challenges, treatment experiences, and opportunities to improve support. Provider and clinic staff surveys asked similar questions about their perspectives; clinic characteristics were also captured., Results: There were 6425 responses; 4558 patients with neovascular age-related macular degeneration, 659 providers, and 1208 clinic staff. Challenges identified included concern about patient burden to family/friends, high frequency of treatment, difficulties in traveling to appointments, long waiting times, and insufficient comprehension of neovascular age-related macular degeneration. Participants identified logistical (improved financial assistance with treatment and out-of-pocket costs, and appointment reminders), operational (addressing clinic set up to reduce waiting times and improving the amount of time providers spend with patients), and educational (improving quality and provision of patient information and expectation-setting) opportunities to improve care., Conclusions: The wealth of data generated by this global survey highlights the breadth of challenges associated with clinical management of patients with neovascular age-related macular degeneration. Addressing the opportunities raised could improve patient adherence to treatment and potentially outcomes, reduce appointment burden, and increase clinic capacity., Competing Interests: Declarations. Conflict of Interest: Anat Loewenstein: Consultant: 4DMT, AbbVie, Alkeus, Annexon, Apellis, Astellas, Bayer Health Care, Beyeonics, Eyepoint, Johnson & Johnson, NotalVision, Novartis, Ocular Therapeutics, Oculis, Ocuphire Pharma, Ocuterra, Opthea, Oxurion, Roche, Syneos; Michelle Sylvanowicz: Employee: Bayer; Winfried M. Amoaku: Advisory board membership: AbbVie, Alcon, Alimera, Allergan, Apellis, Bayer, Bausch + Lomb, Bioeq, Novartis, Pfizer; Speaker fees: Alimera, Allergan, Bayer, Novartis, Pfizer; Support for travel: Alimera, Allergan, Bayer, Novartis, Pfizer; Research sponsorship and funding: Allergan, Bayer, Boehringer Ingelheim, CenterVue, Gyroscope, Novartis, Optos; Tariq Aslam: Tariq Aslam is an Editor in Chief of Ophthalmology and Therapy, and was not involved in the selection of peer reviewers for the manuscript nor any subsequent editorial decisions. Consultant: Novartis, Bayer, Laboratoires, Théa Pharmaceuticals, Bausch & Lomb, Oraya; Chui Ming Gemmy Cheung: Financial support (to institution): Allergan, Bayer, Boehringer Ingelheim, Novartis, Roche, Topcon, Zeiss; Stock: Avirmax; Bora Eldem: Consultant: Allergan, Bayer, Novartis, Roche; Robert P. Finger: Research grant: CentreVue, Heidelberg Engineering, Novartis, Zeiss; Consultant: Alimera, Allergan, Bayer, Ellex, Inositec, Novartis, Opthea, Roche/Genentech, Santhera; Support for travel: Novartis; Richard P. Gale: Consultant/advisory boards: Allergan, Alimera, Bayer, Novartis, Santen; Educational travel grants: Allergan, Bayer, Heidelberg, Novartis; Research grants: Allergan, Bayer, Novartis, Roche; Laurent Kodjikian: Consultant: AbbVie, Alcon, Allergan, Bayer, Krystal Biotech, Novartis, Regeneron, Théa; Adrian Koh: Consultant: Allergan, Bayer, Carl Zeiss, Heidelberg, Novartis, Topcon; Jean-François Korobelnik: Consultant: AbbVie, Apellis, Bayer, Eyepoint Pharma, Ocuphire, Roche, Thea, Carl Zeiss Meditec; Member of DSMB for Alexion, Novo Nordisk, Opthea; Xiaofeng Lin: Consultant: Bayer; Paul Mitchell: Consultant: Allergan, Bayer, Novartis; Steering Committee member: Bayer; Moira Murphy: Employee: Exploristics, Ltd.; Mali Okada: Non-financial support and personal fees: Bayer; Ian Pearce: Lecture fees: Allergan, Bayer, Heidelberg, Novartis; Consultant: Allergan, Alimera, Bayer, Novartis; Support for travel: Allergan, Bayer, Novartis; Francisco J. Rodriguez: Consultant: Bayer, Novartis, Roche; Speaker: Bayer, Novartis, Roche; Research funding: Novartis; Jude Stern: Employee: The International Agency for the Prevention of Blindness; S. James Talks: Advisory board member, speaker fees, and research support: Bayer, Novartis; research grants: Boehringer Ingelheim, Roche; Consultant: Bayer; David T. Wong: Grants/research support: Bayer, Novartis, Roche; Consultant: Alcon, Allergan, Bausch Health, Bayer, Novartis, Topcon, Zeiss; Equity: Arctic DX; Tien Yin Wong: Clinical trial grants: Allergan, Bayer, Boehringer Ingelheim, Genentech, Merck, Novartis, Oxurion (formerly ThromboGenics), Roche, Samsung Bioepis, NMRC Singapore, Novartis Singapore; Consulting fees/travel support/review fees: Allergan, Bayer, Boehringer Ingelheim, Genentech, Merck, Novartis, Oxurion (formerly ThromboGenics), Roche, Samsung Bioepis; Stock: EyRIS, Plano; Focke Ziemssen: Travel grants and personal fees: Allergan, Alimera, Bayer Healthcare, Biogen, Boehringer Ingelheim, Clearside, Novartis, Novo Nordisk, MSD Sharp & Dohme, Roche, Optos; Jane Barratt: Consultant: Bayer. Ethical Approval: The survey was designed and developed according to the Declaration of Helsinki and the World Health Organization’s International Ethical Guidelines for Biomedical Research. While the survey is a Primary Market Research Survey (which does not require ethics committee approval), individual institutions and countries assessed local requirements. Furthermore, informed consent was acquired, no personally identifiable information was collected, and treatment decisions were not informed by response to the survey., (© 2024. The Author(s).)

Introduction: In contrast with patients receiving therapy for retinal disease during clinical trials, those treated in routine clinical practice experience various challenges (including administrative, clinic, social, and patient-related factors) that can often result in high patient and clinic burden, and contribute to suboptimal visual outcomes. The objective of this study was to understand the challenges associated with clinical management of diabetic macular edema from the perspectives of patients, healthcare providers, and clinic staff, and identify opportunities to improve eye care for people with diabetes., Methods: We conducted a survey of patients with diabetic macular edema, providers, and clinic staff in 78 clinics across 24 countries on six continents, representing a diverse range of individuals, healthcare systems, settings, and reimbursement models. Surveys comprised a series of single- and multiple-response questions completed anonymously. Data gathered included patient personal characteristics, challenges with appointment attendance, treatment experiences, and opportunities to improve support. Provider and clinic staff surveys asked similar questions about their perspectives; and clinic characteristics were also captured., Results: Overall, 5681 surveys were gathered: 3752 from patients with diabetic macular edema, 680 from providers, and 1249 from clinic staff. Too many appointments, too short treatment intervals, difficulties in traveling to the clinic or arranging adequate support to travel, out-of-pocket costs, office/parking fees, and long waiting times were noted by all as contributing to increase the burden on the patient and caregiver. Patients generally desired more in-depth discussions with their provider, which would help with information exchange and better expectation-setting., Conclusions: The wealth of systematic data generated by this global survey highlights the breadth and scale of challenges associated with the clinical management of patients with diabetic macular edema. Addressing the opportunities for improvement raised by patients, providers, and clinic staff could increase patient adherence to treatment, reduce appointment burden, and improve clinic capacity., Competing Interests: Declarations. Conflict of Interest: Focke Ziemssen: Travel grants and personal fees: Allergan/AbbVie, Alimera, Bayer Healthcare, Biogen, Boehringer Ingelheim, Clearside, Janssen, Novartis, Novo Nordisk, Merck, Sharp & Dohme, Regeneron, Roche/Genentech, Sanofi, Sandoz, and Stada. Michelle Sylvanowicz: Employee: Bayer; Winfried M. Amoaku: Advisory board membership: AbbVie, Alcon, Alimera, Allergan, Apellis, Bayer, Bausch + Lomb, Bioeq, Novartis, and Pfizer; Speaker fees: Alimera, Allergan, Bayer, Novartis, and Pfizer; Support for travel: Alimera, Allergan, Bayer, Novartis, and Pfizer; Research sponsorship and funding: Allergan, Bayer, Boehringer Ingelheim, CenterVue, Gyroscope, Novartis, and Optos; Tariq Aslam: Tariq Aslam is an Editor in Chief of Ophthalmology and Therapy, and was not involved in the selection of peer reviewers for the manuscript nor any subsequent editorial decisions. Consultant: Bausch & Lomb, Bayer, Laboratoires Théa Pharmaceuticals, Novartis, Oraya, and Roche; Bora Eldem: Consultant: Allergan, Bayer, Novartis, and Roche; Robert P. Finger: Research grant: CentreVue, Heidelberg Engineering, Novartis, and Zeiss; Consultant: Alimera, Allergan, Bayer, Ellex, Inositec, Novartis, Opthea, Roche/Genentech, and Santhera; Support for travel: Novartis; Richard P. Gale: Consultant/advisory boards: Allergan, Alimera, Bayer, Novartis, and Santen; Educational travel grants: Allergan, Bayer, Heidelberg, and Novartis; Research grants: Allergan, Bayer, Novartis, and Roche; Laurent Kodjikian: Consultant: AbbVie, Alcon, Allergan, Bayer, Krystal Biotech, Novartis, Regeneron, and Théa; Jean-François Korobelnik: Consultant: AbbVie, Apellis, Bayer, Eyepoint Pharma, Ocuphire, Roche, Thea, Carl Zeiss Meditec; Member of DSMB for Alexion, Novo Nordisk, Opthea; Xiaofeng Lin: Consultant: Bayer; Anat Loewenstein: Consultant: 4DMT, AbbVie, Alkeus, Annexon, Apellis, Astellas, Bayer Health Care, Beyeonics, Eyepoint, Johnson & Johnson, NotalVision, Novartis, Ocular Therapeutics, Oculis, Ocuphire Pharma, Ocuterra, Opthea, Oxurion, Roche, Syneos; Paul Mitchell: Consultant: Allergan, Bayer, and Novartis; Steering Committee member: Bayer; Moira Murphy: Employee: Exploristics, Ltd.; David R. Owens: Consultant: Bayer; Nick Parker: Employee: The International Agency for the Prevention of Blindness; Ian Pearce: Lecture fees: Allergan, Bayer, Heidelberg Pharma, and Novartis; Consultant: Allergan, Alimera, Bayer, and Novartis, Support for travel: Allergan, Bayer, and Novartis; Francisco J. Rodríguez: Consultant: Bayer, Novartis, and Roche; Speaker: Bayer, Novartis, and Roche; Research funding: Novartis; Jude Stern: Employee: The International Agency for the Prevention of Blindness; S. James Talks: Advisory board member, speaker fees, and research support: Bayer and Novartis; Research grants: Boehringer Ingelheim and Roche; Consultant: Bayer; David T. Wong: Grants/research support: Bayer, Novartis, and Roche; Consultant: Alcon, Allergan, Apellis, Bausch Health, Bayer, Novartis, Roche, Topcon, and Zeiss; Equity: Arctic DX; Tien Yin Wong: Consulting fees/travel support/review fees: Aldropika Therapeutics, Bayer, Boehringer Ingelheim, Genentech, Iveric Bio, Novartis, Oxurion, Plano, Roche, Sanofi, Shanghai Henlius; Stock: EyRIS; Jane Barratt: Consultant: Bayer. Ethical Approval: The survey was developed according to guidelines from the Declaration of Helsinki and the World Health Organization’s International Ethical Guidelines for Biomedical Research. As a Primary Market Research Survey, ethics committee approvals are not required; however, local requirements were assessed by individual institutions and countries. Informed consent was acquired, no personally identifiable information was collected, and the survey did not inform treatment decisions., (© 2024. The Author(s).)

Background/objective: Describe vitreomacular interface abnormalities (VMIA) using spectral-domain optical coherence tomography (SD-OCT), and correlations with age-related macular degeneration (AMD) grade in Ghanaian Africans., Subjects/methods: Prospective, cross-sectional study of adults aged ≥50 years recruited in Ghana AMD Study. Participant demographics, medical histories, ophthalmic examination, digital colour fundus photography (CFP) were obtained. High-resolution five-line raster OCT, Macular Cube 512 × 128 scans, and additional line scans in areas of clinical abnormality, were acquired. SD-OCT VMI features classified by International Vitreomacular Traction Study Group system and relationships to AMD grade were evaluated., Outcomes: VMIA prevalence, posterior vitreous detachment (PVD), vitreomacular adhesions (VMA), vitreomacular traction (VMT), epiretinal membranes (ERM), correlations with AMD grade., Results: The full Ghana AMD cohort included 718 participants; 624 participants (1248 eyes) aged ≥50 years (range = 50-101, mean = 68.8), 68.9% female were included in this analysis. CFP with OCT scans were available for 776 eyes (397 participants); 707 (91.1%) had gradable CFP and OCT scans for both AMD and VMI grading forming the dataset for this report. PVD was absent in 504 (71.3%); partial and complete PVD occurred in 16.7% and 12.0% respectively. PVD did not increase with age (p = 0.720). VMIA without traction and macular holes were observed in 12.2% of eyes; 87.8% had no abnormalities. VMIA was not significantly correlated with AMD grade (p = 0.819)., Conclusions: This provides the first assessment of VMIA in Ghanaian Africans. VMIA are common in Africans; PVD may be less common than in Caucasians. There was no significant association of AMD grade with VMIA., (© 2023. The Author(s).)

Purpose: To determine the prevalence and risk factors of epiretinal membranes (ERMs) in an adult English population. Methods: The Bridlington Eye Assessment Project is a population-based study of eye disease among residents aged 65 years or older. Comprehensive interviews and ophthalmic examinations were conducted to assess potential risk factors. Digital mydriatic nonstereoscopic 30° colour fundus photography (CFP) was performed. ERMs were classified as primary/idiopathic or secondary on the basis of findings from the ocular examination and the structured questionnaire. Logistic regression models were used to determine the independence of potential risk factors for idiopathic ERMs. Results: In a comprehensive screening of 3588 patients aged over 65, we identified an eye-based prevalence of ERMs of 4.26% and a subject-based prevalence of ERMs of 6.88%. The majority of these cases were idiopathic in nature (90.7%), while 9.3% were secondary ERMs; predominantly, there was a history of cataract surgery (43.5%). No significant correlation between idiopathic ERMs and factors such as age, gender, diabetes, hypertension, a history of stroke, or the presence of AMD was found. Conclusions: The prevalence of ERMs in an elderly English population and the proportion of idiopathic and secondary ERMs are similar to previous reports. However, in elderly patients aged over 65 years, age is not a risk factor for the presence of idiopathic ERMs. The presence of diabetes, hypertension, a history of stroke, and AMD of any grade was not associated with ERMs.

Purpose: To evaluate the thickness of the macular retina and central choroid in an indigenous population from Ghana, Africa and to compare them with those measured among individuals with European or African ancestry., Design: Cross-sectional study, systematic review, and meta-analyses., Participants: Forty-two healthy Ghanaians, 37 healthy individuals with European ancestry, and an additional 1427 healthy subjects with African ancestry from previously published studies., Methods: Macular retinal thickness in the fovea, parafovea, and perifovea and central choroidal thickness were extracted from OCT volume scans. Associations with ethnicity, age, and sex were assessed using mixed-effect regression models. Monte Carlo simulations were performed to determine the sensitivity of significant associations to additional potential confounders. Pooled estimates of retinal thickness among other groups with African ancestry were generated through systematic review and meta-analyses., Main Outcome Measures: Macular retinal thickness and central choroidal thickness and their association with ethnicity, age, and sex., Results: When adjusted for age and sex, the macular retina and central choroid of Ghanaians are significantly thinner as compared with subjects with European ancestry ( P < 0.001). A reduction in retinal and choroidal thickness is observed with age, although this effect is independent of ethnicity. Meta-analyses indicate that retinal thickness among Ghanaians differs markedly from that of African Americans and other previously reported indigenous African populations., Conclusions: The thickness of the retina among Ghanaians differs not only from those measured among individuals with European ancestry, but also from those obtained from African Americans. Normative retinal and choroidal parameters determined among individuals with African or European ancestry may not be sufficient to describe indigenous African populations., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)

Objectives: To investigate the prevalence of macrovascular and non-ocular microvascular complications and the associated factors among children and adolescents with diabetes mellitus in selected hospitals in southern Ghana., Design: A cross-sectional study., Setting: The out-patient clinics of the Departments of Child Health, Medicine and Therapeutics, Family Medicine, Ophthalmology, and the National Diabetes Management and Research Centre, all at the Korle Bu Teaching Hospital, Accra, as well as from Cape-Coast Teaching Hospital in the Central Region of Ghana., Participants: Fifty-eight children and adolescents aged 4-19 years who had been diagnosed with diabetes mellitus., Main Outcome Measures: Macrovascular (peripheral artery disease and coronary heart disease) and non-ocular microvascular complications (neuropathy and nephropathy)., Results: Data from 58 children and adolescents with diabetes were analysed. The mean age of participants was 14.6±2.6 years, and a female preponderance was observed (45, 77.6%). The prevalence of macrovascular and non-ocular microvascular complications was 27.6% and 8.6%, respectively. Long duration of diabetes diagnosis (p=0.044) and low triglycerides (p=0.009) were associated with microvascular complications, while high triglycerides (p=0.032), lower HDL cholesterol (p=0.046), and abnormal body mass index (p=0.020) were associated with macrovascular complications., Conclusions: Macrovascular and non-ocular microvascular complications are common among children and adolescents with diabetes in southern Ghana and are associated with a long duration of diabetes diagnosis, abnormal body mass index, low HDL cholesterol, and triglyceride levels. Therefore, the early institution of regular screening for diabetes-related complications to allow early detection and appropriate management is recommended., Funding: University of Ghana Research Fund., Competing Interests: Conflict of interest: None declared, (Copyright © The Author(s).)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Craig Wilde et al.)

Objective: 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., Design: Prospective, cross-sectional cohort study., Subjects: Participants with WACM were selected from the large cohort recruited in the Ghana Age-Related Macular Degeneration Study., Methods: 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., Main Outcome Measures: Phenotypic features of, and genetic associations with, WACM., Results: 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., Conclusions: 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., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the use of intravitreal ziv-aflibercept (IVZ) in Ghanaian patients with diabetic macular edema (DME)., Methods: 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)., Results: 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., Conclusion: 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., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Titi-Lartey, Mohammed and Amoaku.)

Diabetic retinopathy is a microangiopathy resulting from the chronic effects of diabetes mellitus. Healthcare professionals often work in isolation to deliver highly specialised care efficiently and effectively for people living with diabetes. It is not uncommon for people with diabetes to be making frequent visits to community and hospital clinics to see a variety of specialists and healthcare professionals, with seemingly little opportunity for coordination of this complex health management programme between the wider team. In a field that is so diverse and rapidly changing, healthcare professionals of all specialties need to be aware of developments across all aspects of diabetes management. In this article, we discuss the epidemiology and natural history of diabetic retinopathy and describe an approach to its assessment and diagnosis. We provide an overview of the principles of diabetic retinopathy management and outline possible future treatments for diabetic retinopathy., (© Royal College of Physicians 2022. All rights reserved.)

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  μ m from 474.4  μ m 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., Competing Interests: DZ has no conflicts of interest. IJ has received honoraria for speaker fees from Novartis and Thea Pharmaceuticals. WMA has received honoraria for advisory board memberships from AbbVie, Alcon, Alimera, Allergan, Bayer, Bausch and Lomb, Novartis, Pfizer, and Roche, speaker fees from Alimera, Allergan, Bayer, Novartis, and Pfizer, and educational travel grants from Alimera, Allergan, Bayer, Novartis, Pfizer, and Roche. He has undertaken clinical research sponsored by Allergan, Bayer, Gyroscope, and Novartis. His institution has received research funding from Allergan, Bayer, Boehringer Ingelheim, CenterVue, Novartis, and Optos Plc., (Copyright © 2021 Di Zou et al.)

Aim: To evaluate the efficacy of ziv-aflibercept in Ghanaian patients with macular edema (ME) secondary to retinal vein occlusion (RVO)., Methodology: In 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., Results: Forty-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 < 0.001). Eyes with ME following BRVO had better mean BCVA at baseline and on subsequent visits compared to eyes with CRVO/HRVO (p = 0.01). There was significant reduction in mean CSFT up to 12 months post-IVZ injection compared to baseline (p < 0.001). Ocular complications observed were consistent with complications associated with RVO., Conclusion: We 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.

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 (deg 2 ): 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.

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.

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., Competing Interests: Competing interests: HSSD: Honoraria and Travel expenses from Dompe, Croma, Santen, Allergan, Thea, Shares in NuVision and Glaxosmithkline., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (©Vera Adobea Essuman, Naa Naamuah Tagoe, Josephine Akpalu, Akye Essuman, Adziri H Sackey, CF Hayfron-Benjamin, George Asare, Benjamin Abaidoo, AGB Amoah, Thomas Ndanu, IDB Ofori-Adjei, NA Barnes, BL Appiah-Thompson, Winfried M Amoaku. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 06.01.2021.)

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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.

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 Africans and Caucasians. Such differences should be adequately considered in diagnoses and monitoring of ocular diseases in patients with African ancestry., Competing Interests: Disclosure: M.A. Zouache, None; G. Silvestri, None; W.M. Amoaku, None; V. Silvestri, None; W.C. Hubbard, None; C. Pappas, None; S. Akafo, None; S. Lartey, None; R.R. Mastey, None; J. Carroll, None; G.S. Hageman, Voyant Biotherapeutics, LLC (C, I), (Copyright 2020 The Authors.)

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.

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., (© 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.)

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., Competing Interests: The authors have declared that no competing interests exist.

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.

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.

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., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Aims: To determine prevalence, associations, and risk factors for reticular pseudodrusen (RPD) in a UK population., Methods: Cross-sectional study of Bridlington residents aged ≥65 years. Masked grading of colour fundus photographs from 3549 participants. RPD presence, phenotype, and topography were recorded, demographic details were analysed, and prevalence was calculated., Results: RPD was detected in 281 eyes (176 individuals) of 3476 participants (5.06%) with gradable images, and bilateral in 76.6%. Digital enhancement increased detection by 15.7%. Prevalence increased significantly with age from 1.18% (65-69 years) to 27.27% (≥90 years) (mean age 81.1, SD 6.01; OR 1.18, 95% CI 1.15-1.21, p value <0.001), was higher in females (5.9% vs 4.0%; OR 1.52, 95% CI 1.09-2.13, p = 0.014), and associated with diabetes (OR 1.97, CI 1.20-3.17, p = 0.005). History of antihypertension treatment appeared protective (OR 0.64, 95% CI 0.46-0.90, p = 0.009). RPD subtypes were dot in 18.5%, ribbon in 36.7%, and mixed in 36.3%. RPD were located outside the ETDRS grid in 88%, and most commonly in the outer superior subfield. Central grid involvement occurred in 12.1% of right and 14.3% of left eyes. RPD occurred in 25.9% of participants with grade 4 AMD in at least one eye. RPD was associated with visual dissatisfaction after controlling for age (OR 0.63, 95% CI 0.45-0.88, p = 0.007)., Conclusion: RPD occur more commonly than previously reported, most frequently in the upper-outer macular subfield, but also within the central subfield, albeit with reduced frequency and altered morphology. RPD may be associated with visual dissatisfaction and diabetes, but are less frequent in persons receiving antihypertension therapy.

Introduction: 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., Methods: Relevant randomized controlled trials (RCTs) and prospective observational studies were identified by searching MEDLINE, MEDLINE In-Process, EMBASE, and CENTRAL., Results: 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 < 0.001]; the gain was maintained up to month 12. In the treatment of CNV secondary to presumed ocular histoplasmosis syndrome (POHS), both intravitreal ranibizumab and photodynamic therapy (PDT) showed significant improvement from baseline BCVA over the 12-month period (n = 9); however, all patients in the PDT group required rescue ranibizumab therapy. Unlicensed intravitreal bevacizumab was associated with a statistically significant improvement in BCVA compared to PDT at 12 months (p < 0.001) in patients with CNV secondary to multifocal choroiditis (n = 27). The use of steroids before PDT showed better BCVA outcomes than PDT alone (p < 0.05) in patients with idiopathic CNV (n = 20). Argon green laser therapy showed limited efficacy in patients with CNV secondary to OHS (n = 134)., Conclusion: There is evidence from a relatively large, good-quality study to support the use of intravitreal ranibizumab for the treatment of CNV secondary to rare diseases. However, the limited number of RCTs for this indication and differences in study characteristics between RCTs mean that there is uncertainty regarding comparative clinical effectiveness of interventions. RCTs with an active comparator are required to fully establish the comparative effectiveness of treatments for CNV secondary to rare diseases., Funding: Novartis Pharmaceuticals UK Ltd, Surrey, UK.

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 study's 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., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

ImportanceThere is paucity of data on prevalence and disease asymmetry of age-related macular degeneration (AMD), particularly the earlier stages, in the UK population.Objective and PurposeTo determine the prevalence of age-related macular degeneration in an elderly Caucasian UK population.DesignCross-sectional population study, 2002-2006.ParticipantsResidents in the study area of Bridlington aged 65 years and older.MethodsFull-ophthalmic examination was undertaken in 3549 participants, of eligible 6319 Caucasian population (response rate of 56%). Non-stereoscopic Colour fundus photographs (30°) were graded masked using a modified Rotterdam Classification for 3475 (98%) participants with gradable images. Prevalence for different AMD grades were calculated. Demographic details were analysed then integrated with the AMD gradings for full analysis. Prevalence rates for the different AMD Grades were calculated, as well as the age-specific prevalences.ResultsAMD prevalence in the worst eye were 38.5% grade 0, 41.4% grade 1, 12.8% grade 2, 2.8% grade 3, and 4.6% grade 4. Geographic atrophy (grade 4a) occurred in 2.5%, and neovascular AMD (grade 4b) in 1.8%. Prevalence increased with age such that grade 4 (advanced) AMD was 2.2% in the 65-69 years group, 15.8% for the 85-90, and 21.2% for over 90 years. There was significant asymmetry between the two eyes of individuals with advanced AMD (P<0.001), such that vision loss was unilateral. Persons with more advanced AMD grades were more likely to be dissatisfied with their vision.ConclusionsAdvanced AMD occurs more commonly in the UK Caucasian population than previously reported. Significant asymmetry between the two eyes occurs in individuals with unilateral advanced AMD so that visual impairment statistics do not represent true prevalence of advanced AMD. Persons with more advanced AMD were more likely to be dissatisfied with their vision.

Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group, a subgroup of phylogenetically related members of the nuclear receptor (NR) superfamily of transcription factors. We assessed the ability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLX ligand-binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD was able to form homodimers, but also exhibited robust interactions with the LBDs of peroxisome proliferator-activated receptor-γ (PPARγ)/NR1C3 and thyroid hormone receptor b (TRb) TRβ/NR1A2. The binding of PNR to PPARγ was specific for this paralog, as no interaction was observed with the LBDs of PPARα/NR1C1 or PPARδ/NR1C2. In support of these findings, PPARγ and PNR were found to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARγ LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARγ complex formation. Wild-type PNR, but not a PNR309G mutant, was able to repress PPARγ-mediated transcription in reporter assays. In summary, our results reveal novel heterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPARγ and TRβ that have potential importance in retinal development and disease.

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: The purpose of this study was to establish a normal reference database for fixation stability measured with the bivariate contour ellipse area (BCEA) in the Macular Integrity Assessment (MAIA) microperimeter., Methods: Subjects were 358 healthy volunteers who had the MAIA examination. Fixation stability was assessed using two BCEA fixation indices (63% and 95% proportional values) and the percentage of fixation points within 1° and 2° from the fovea (P1 and P2). Statistical analysis was performed with linear regression and Pearson's product moment correlation coefficient., Results: Average areas of 0.80 deg 2 (min = 0.03, max = 3.90, SD = 0.68) for the index BCEA@63% and 2.40 deg 2 (min = 0.20, max = 11.70, SD = 2.04) for the index BCEA@95% were found. The average values of P1 and P2 were 95% (min = 76, max = 100, SD = 5.31) and 99% (min = 91, max = 100, SD = 1.42), respectively. The Pearson's product moment test showed an almost perfect correlation index, r = 0.999, between BCEA@63% and BCEA@95%. Index P1 showed a very strong correlation with BCEA@63%, r = -0.924, as well as with BCEA@95%, r = -0.925. Index P2 demonstrated a slightly lower correlation with both BCEA@63% and BCEA@95%, r = -0.874 and -0.875, respectively., Conclusions: The single parameter of the BCEA@95% may be taken as accurately reporting fixation stability and serves as a reference database of normal subjects with a cutoff area of 2.40 ± 2.04 deg 2 in MAIA microperimeter., Translational Relevance: Fixation stability can be measured with different indices. This study originates reference fixation values for the MAIA using a single fixation index.

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

Purpose: To use multimodal imaging to evaluate the prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting neovascular age-related macular degeneration (nAMD) in a UK population and explore associations with RPD and angiographic subtypes of nAMD., Methods: A retrospective review of all spectral-domain optical coherence tomography, color fundus photographs, red-free and blue channel images, and fundus fluorescein angiograms of 202 consecutive patients who presented to a rapid access macular clinic over a 4-year period was performed. All images were graded by at least 2 ophthalmologists for the presence of RPD and choroidal neovascular membrane (CNV) subtypes., Results: A total of 231 consecutive eyes were studied, of which 131 (56.7%) were in women. Of these, 51 eyes with CNV (22.1%) had identifiable RPD, with one or more imaging methods in that eye. A total of 30.3% of patients with newly presenting CNV in either or both eyes had identifiable RPD. The RPD were bilateral in 85.4% of patients and were identified more commonly in women than men (72.5% vs 27.5%), a difference that reached statistical significance (p = 0.011). No association between RPD and any particular CNV subtype was demonstrated, including for retinal angiomatous proliferations (RAP)., Conclusions: Reticular pseudodrusen have a high prevalence in eyes presenting with nAMD (22.1%), although at rates much lower than that of conventional drusen. They are largely a bilateral finding, occurring more frequently in women. Unlike other previous reports, we found no difference in their occurrence between the different subtypes of CNV including RAPs.