Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy.

Angiogenic VEGF isoforms are upregulated in diabetic retinopathy (DR), driving pathological growth and fluid leakage. Serine-arginine-rich protein kinase-1 (SRPK1) regulates VEGF splicing, and its inhibition blocks angiogenesis. We tested the hypothesis that SRPK1 is activated in diabetes, and an SRPK1 inhibitor (SPHINX31) switches VEGF splicing in DR and prevents increased vascular permeability into the retina. SRPK1 was activated by high glucose (HG), in a PKC-dependent manner, and was blocked by SPHINX31. HG induced release of SRSF1 from the nuclear speckles, which was also SRPK1 dependent, and increased retinal pigment epithelial (RPE) monolayer admittance, which was reversed by SRPK1 inhibition (P < 0.05). Diabetes increased retinal permeability and thickness after 14 days which was blocked by treatment with SPHINX31 eye drops (P < 0.0001). These results show that SRPK1 inhibition, administered as an eye drop, protected the retinal barrier from hyperglycemia-associated loss of integrity in RPE cells in vitro and in diabetic rats in vivo. A clinical trial of another SRPK1 inhibitor has now been initiated in patients with diabetic macular edema.NEW & NOTEWORTHY VEGF-A165b splicing is induced by hyperglycemia through PKC-mediated activation of SRPK1 in RPE cells, increasing their permeability and angiogenic capability. SRPK1 inhibitors can be given as eye drops to reduce retinal permeability and edema in diabetic retinopathy.

Prevalence and phenotype associations of complement factor I mutations in geographic atrophy.

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.

Efficacy of intravitreal ziv-aflibercept in patients with macular edema following retinal vein occlusion in Korle-Bu Teaching Hospital, Ghana: a retrospective case series.

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.

Hypercapnia augments resistive exercise-induced elevations in intraocular pressure in older individuals.

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 < 0.01) elevated IOP in all three phases of the NCAP (rest: 27.0 ± 3.7 mmHg; exercise: 32.2 ± 4.8 mmHg; recovery: 27.4 ± 4.0 mmHg) and HCAP (rest: 27.3 ± 4.3 mmHg; exercise: 34.2 ± 6.0 mmHg; recovery: 29.1 ± 5.8 mmHg) trials, with hypercapnia augmenting the exercise-induced elevation in IOP (P < 0.01). CO, SV, HR and MAP were significantly increased during handgrip dynamometry, but there was no effect of hypercapnia. The observed IOP measured during prone 6° HDT in all phases of the NCAP and HCAP trials exceeded the threshold pressure defining ocular hypertension. The exercise-induced increase in IOP is exacerbated by hypercapnia.

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

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.

Natural course of adult-onset vitelliform lesions in eyes with and without comorbid subretinal drusenoid deposits.

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.

A simulation tool for better management of retinal services.

BACKGROUND: Advances in the management of retinal diseases have been fast-paced as new treatments become available, resulting in increasing numbers of patients receiving treatment in hospital retinal services. These patients require frequent and long-term follow-up and repeated treatments, resulting in increased pressure on clinical workloads. Due to limited clinic capacity, many National Health Service (NHS) clinics are failing to maintain recommended follow-up intervals for patients receiving care. As such, clear and robust, long term retinal service models are required to assess and respond to the needs of local populations, both currently and in the future. METHODS: A discrete event simulation (DES) tool was developed to facilitate the improvement of retinal services by identifying efficiencies and cost savings within the pathway of care. For a mid-size hospital in England serving a population of over 500,000, we used 36 months of patient level data in conjunction with statistical forecasting and simulation to predict the impact of making changes within the service. RESULTS: A simulation of increased demand and a potential solution of the 'Treat and Extend' (T&E) regimen which is reported to result in better outcomes, in combination with virtual clinics which improve quality, effectiveness and productivity and thus increase capacity is presented. Without the virtual clinic, where T&E is implemented along with the current service, we notice a sharp increase in the number of follow-ups, number of Anti-VEGF injections, and utilisation of resources. In the case of combining T&E with virtual clinics, there is a negligible (almost 0%) impact on utilisation of resources. CONCLUSIONS: Expansion of services to accommodate increasing number of patients seen and treated in retinal services is feasible with service re-organisation. It is inevitable that some form of initial investment is required to implement service expansion through T&E and virtual clinics. However, modelling with DES indicates that such investment is outweighed by cost reductions in the long term as more patients receive optimal treatment and retain vision with better outcomes. The model also shows that the service will experience an average of 10% increase in surplus capacity.

Optical coherence tomography for the monitoring of neovascular age-related macular degeneration: a systematic review.

TOPIC: To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition. CLINICAL RELEVANCE: Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests. METHODS: Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias. RESULTS: We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%-93%) and 48% (95% CI, 30%-67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias. CONCLUSIONS: There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

Expression of Toll-like receptors in human retinal and choroidal vascular endothelial cells.

Toll-like receptors (TLRs) are a family of proteins that initiate the innate immune response in reaction to invading microbes. Studies confirm the expression of TLRs in a variety of ocular tissues and cells, and it has also been suggested that selected TLRs may be associated with geographic atrophy and neovascularisation in age-related macular degeneration, diabetic retinopathy and other vascular and inflammatory diseases of the ocular posterior segment. However, TLR expression and localisation in the retinal and choroidal vasculature has not been defined. A better understanding of differential TLR expression in the choroid and retina, particularly in endothelial cells would improve our knowledge of vascular and inflammatory diseases in the posterior segment of the eye. In this study the gene (mRNA) expression of TLRs 1-10 was investigated using RT-PCR and comparative qPCR and the protein expression and localisation of selected TLRs (3, 4, 6 and 9) were examined using western blotting, flow cytometry and immunofluorescent staining. PCR showed gene expression of TLR1-6 and 9 in human choroidal endothelial cells (hCEC) and TLR2-6, 9 and 10 in human retinal endothelial cells (hREC). Western blotting detected TLR3, 4 and 9 proteins in both hCEC and hREC with higher levels in hCEC, whilst TLR6 protein was not detectable in either endothelial cell type. Flow cytometry detected all four TLRs (3, 4, 6 and 9) on the cell surface and intracellularly, TLR6 expression was detectable but low. The expression and localisation of TLR3, 4 and 9 were confirmed by immunofluorescent staining in endothelial cells and whole tissue sections and their functionality tested by expression of IL-6 (ELISA) in response to stimulation with specific TLR ligands. This study has, for the first time, identified the differential expression and localisation of TLRs in intraocular endothelial cells. This profiling will help inform our understanding of different retinal and choroidal vascular diseases, as well as the development of future treatments for intraocular vascular diseases.

Electrophysiological and microperimetry changes in vitamin A deficiency retinopathy.

PURPOSE: To describe a follow-up case of vitamin A deficiency (VAD)-related retinopathy with macular involvement monitored with electroretinography and microperimetry. METHODS: Flash (ERG), pattern (PERG), and multifocal (mfERG) electroretinography were recorded in parallel with microperimetry before and during 7-month follow-up of vitamin A treatment on a 65-year-old man presented with a 1-year history of night blindness. The patient had undergone ileostomy procedure for Crohn's disease 14 years ago. His best corrected visual acuity was 6/6 in each eye. Fundus examination revealed macular and mid-peripheral yellow-white lesions compatible with drusen. RESULTS: Before treatment, PERG was reduced, and mfERG was reduced and delayed, worse in responses from the central rings. These results revealed evidence of bilateral macular and central cone dysfunction. The flash ERG showed reduced dark-adapted 0.01 ERG (rod response); a-wave of dark-adapted 3.0 and 10.0 ERG was normal but b-wave was reduced (negative configuration); light-adapted 3.0 ERG was slightly reduced. The flash ERG revealed evidence of bilateral generalised retinal dysfunction affecting the rod more than cone system. Microperimetry showed deep reduction in retinal sensitivity. Fixation stability was unstable with eccentric locus. During treatment, ERG and microperimetry demonstrated significant improvements. Fixation stability reached normal values after the third treatment week. CONCLUSIONS: This case illustrates the importance of electrophysiological investigation in early VAD-related retinopathy detection correlated with microperimetry. Our findings indicate a more delayed central cone function recovery than that of generalised rod and cone function. There was a marked correlation between ERG and microperimetric changes.

Retinal and Choroidal Thickness in an Indigenous Population from Ghana: Comparison with Individuals with European or African Ancestry.

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.

The MOSAIC Study: A Mixed-Methods Study of the Clinical, Emotional, and Financial Burden of Geographic Atrophy Among Patients and Caregivers in the US.

Purpose: 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.

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.

Prevalence and Associations of Epiretinal Membranes in an Elderly English Population: The Bridlington Eye Assessment Project.

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.

Vitreomacular interface abnormalities in the Ghanaian African.

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.

Defining an Ageing-Related Pathology, Disease or Syndrome: International Consensus Statement.

Background: Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased healthspan. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity, and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand, and meet the healthcare, workforce, wellbeing, and socioeconomic needs of ageing populations, while supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. Methods: The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19 th , 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥70% for approval. Results: The accepted criteria for an ageing-related pathology, disease or syndrome were: Develops and/or progresses with increasing chronological age.Should be associated with, or contribute to, functional decline, or an increased susceptibility to functional decline.Evidenced by studies in humans. Conclusions: Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.

Faricimab: Transforming the Future of Macular Diseases Treatment - A Comprehensive Review of Clinical Studies.

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.

Diagnosis and Management of Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Delphi Consensus Exercise.

Geographic atrophy (GA) is a progressive and irreversible retinal disease with no comprehensive recommendations for diagnosis or monitoring. We used a Delphi approach to determine consensus in key areas around diagnosis and management of GA. A steering committee of eight retina specialists developed two sequential online surveys administered to eye care professionals (ECPs). Consensus was defined as agreement by ≥ 75% of respondents. Up to 177 ECPs from eight countries completed one or both surveys. Consensus was achieved in several topics related to diagnostic imaging, including the use of optical coherence tomography, and the urgent need for treatments and beneficial interventions to reduce the associated burden. Currently, low-vision aids and smoking cessation are considered the most beneficial interventions. We demonstrate consensus for diagnosis and management of patients with GA including best practices in patient identification and monitoring, and unmet needs. [Ophthalmic Surg Lasers Imaging Retina 2023;54:589-598.].

A multi-centre investigation of macrovascular and non-ocular microvascular complications in children and adolescents with diabetes mellitus in southern Ghana.

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.

Visual evoked potential (VEP) and multifocal electroretinogram (mfERG) in ocular syphilitic posterior segment inflammation.

The aim of this study is to correlate multifocal electroretinogram (mfERG) and visual evoked potential (VEP) changes with visual acuity and clinical features in patients with posterior segment inflammation secondary to syphilis. A retrospective interventional case series of 4 patients with visual loss secondary to syphilitic uveitis is reported. The mfERG (P1) showed diminished amplitudes and prolonged latency in 7 affected eyes. Visual acuity rapidly improved 2 weeks after initiation of therapy. OCT demonstrated anatomical recovery at 1 month. In three patients, visual acuity was restored to 6/6 at 6-9 months but mfERG responses remained significantly reduced and delayed for 12-15 months before recovery to normal levels. One patient developed a retinal detachment, but achieved 6/9 vision at 30 months. VEP changes, interpreted in combination with mfERG responses, showed evidence of optic nerve involvement in 6 eyes. Ocular findings, including posterior placoid chorioretinitis, are important diagnostic features of secondary and tertiary syphilis. Visual acuity and clinical recovery occur early with appropriate diagnosis and treatment, and precede full electrophysiological recovery of the outer retina-RPE complex. Ophthalmologists have the opportunity to play a key role in undetected or missed diagnoses of syphilis, and with appropriate treatment the visual prognosis is excellent.