OBJECTIVE: To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients.
METHODS: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively.
RESULTS: From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8 weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk.
CONCLUSIONS: Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients.
UNASSIGNED: CRD42023394226.

The cornea is an avascular tissue in the eye that has multiple functions in the eye to maintain clear vision which can significantly impair one\'s vision when subjected to damage. Peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptor proteins comprising three different peroxisome proliferator-activated receptor (PPAR) isoforms, namely, PPAR alpha (α), PPAR gamma (γ), and PPAR delta (δ), have emerged as potential therapeutic targets for treating corneal diseases. In this review, we summarised the current literature on the therapeutic effects of PPAR agents on corneal diseases. We discussed the role of PPARs in the modulation of corneal wound healing, suppression of corneal inflammation, neovascularisation, fibrosis, stimulation of corneal nerve regeneration, and amelioration of dry eye by inhibiting oxidative stress within the cornea. We also discussed the underlying mechanisms of these therapeutic effects. Future clinical trials are warranted to further attest to the clinical therapeutic efficacy.

BACKGROUND: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Prompt diagnosis and treatment are crucial in ROP management. Thus, the identification of prominent risk factors could facilitate immediate action. Among various risk factors, the effects of mode of delivery on ROP remain unclear. Therefore, this study aims to assess the association between different modes of delivery on ROP incidence.
METHODS: Comprehensive literature search was conducted on PubMed, ProQuest, EBSCOHost and Cochrane databases, to evaluate the association of mode of delivery-vaginal delivery or caesarean section (c-section)-and the incidence of ROP from inception to December 2023. Random-effects meta-analysis was performed to estimate the pooled OR along with their 95% CIs.
RESULTS: This review included 5 cohort studies involving 2048 babies. A higher incidence of ROP was observed in infants born through vaginal delivery compared with caesarean section. Meta-analysis showed that C-section decreased the unadjusted odds of having ROP infants by 46% with low heterogeneity (OR 0.54 (95% CI 0.40 to 0.73); I2=40.73%). However, pooled adjusted effects were statistically insignificant with moderate heterogeneity (adjusted OR 0.59 (95% CI 0.28 to 1.23); I2=70.51%), possibly stemming from multiple variations in the controlled variables of each study.
CONCLUSIONS: Despite varying statistical significance, our findings underscore the crucial need to comprehend the influence of delivery mode on neonatal ophthalmic outcomes. Due to a limited number of existing studies, further research is needed to confirm the association.
UNASSIGNED: CRD42023486278.

Age-related macular degeneration is a major cause of blindness, and the development of anti-vascular endothelial growth factor (VEGF) intravitreal treatments has revolutionised the management of the disease. At the same time, new challenges and unmet needs arose due to the limitations of the current therapeutic options. Neovascularisation development during the course of the disease has a complex pathogenetic mechanism, and several biomarkers and their association with treatment outcomes have been investigated. We reviewed the relevant literature about neovascularisation development and biomarkers related to response to treatment. Improving our knowledge on the field can improve patient outcomes and offer personalised care.

The rising prevalence of myopia is a concern in ophthalmology, with myopic choroidal neovascularisation (m-CNV) significantly affecting vision. However, long-term outcomes of m-CNV management have been unsatisfactory, leading to high recurrence rates. These studies aim to identify risk factors for m-CNV recurrence.
Comprehensive review followed a pre-registered plan in the International Prospective Register of Systematic Reviews (PROSPERO). The search strategy used various databases including PubMed, Cochrane Library, Embase, Scopus and ScienceDirect using the keywords \'Myopic Choroidal Neovascularization\', \'Recurrence\' and \'Risk\'. Eligible studies were identified and analysed based on predetermined criteria. This study was registered on PROSPERO (CRD4202343461).
The systematic review included three retrospective studies investigating risk factors associated with m-CNV recurrence. These factors are: (1) requiring three or more injections for initial disease control, (2) older age, (3) larger myopic macular neovascularisation, (4) juxtafoveal CNV, (5) larger height of hyper-reflective foci (HRF) and (6) destruction or absence of the ellipsoid zone (EZ) and retinal pigment epithelium (RPE).
Risk factors for m-CNV recurrence include a greater number of required injections, older age, large macular CNV, juxtafoveal location, increased HRF height and changes in EZ and RPE structure. Understanding these factors can inform personalised treatment approaches and improve patient outcomes by identifying individuals at higher risk of recurrence and implementing proactive measures to mitigate the impact of m-CNV recurrence and progression. Further investigation is needed to enhance our understanding of the underlying mechanisms and develop innovative therapeutic approaches for effective m-CNV management.
CRD4202343461.

To analyse long-term outcomes of antivascular endothelial growth factor (anti-VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD) using pro re nata (PRN) regimen in a single-centre clinical practice.
All patients receiving intravitreal injection (IVI) for nAMD between 1 January 2008 and 31 December 2020 were searched from electronic medical records. All 3844 treatment-naïve eyes of 3008 patients were included with a total of 50 146 IVIs (87% bevacizumab) administered. Main outcome measures were mean change in visual acuity (VA) from baseline, proportion of eyes within 15 letters of baseline, proportion of eyes with VA ≥20/40 Snellen and ≤20/200 Snellen, number of annual visits and number of annual IVIs.
The mean baseline VA was 55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and the mean change in VA from baseline was +2, +2, ±0, -2, -2 and -4 ETDRS letters at year 1, 2, 3, 5, 7 and 10, respectively. Proportions of eyes within 15 letters of baseline were 88%, 87%, 82%, 80%, 76% and 72% at the end of years 1, 2, 3, 5, 7 and 10, respectively. The median number of annual IVI was 6 at years 1-7 and 5 at year 10. The median number of annual total visits was 10 at year 1, 9 at years 2-7 and 8 at year 10, respectively.
VA was maintained short-term and long-term with anti-VEGF therapy using PRN treatment regimen.

Myocardial infarction, caused by a thrombus or coronary vascular occlusion, leads to irreversible ischaemic injury. Advances in early reperfusion strategies have significantly reduced short-term mortality after myocardial infarction. However, survivors have an increased risk of developing heart failure, which confers a high risk of death at 1 year. The capacity of the injured neonatal mammalian heart to regenerate has stimulated extensive research into whether recapitulation of developmental regeneration programmes may be beneficial in adult cardiovascular disease. Restoration of functional blood and lymphatic vascular networks in the infarct and border regions via neovascularisation and lymphangiogenesis, respectively, is a key requirement to facilitate myocardial regeneration. An improved understanding of the endogenous mechanisms regulating coronary vascular and lymphatic expansion and function in development and in adult patients after myocardial infarction may inform future therapeutic strategies and improve translation from pre-clinical studies. In this review, we explore the underpinning research and key findings in the field of cardiovascular regeneration, with a focus on neovascularisation and lymphangiogenesis, and discuss the outcomes of therapeutic strategies employed to date. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness in adults worldwide. Artificial intelligence (AI) with autonomous deep learning algorithms has been increasingly used in retinal image analysis, particularly for the screening of referrable DR. An established treatment for proliferative DR is panretinal or focal laser photocoagulation. Training autonomous models to discern laser patterns can be important in disease management and follow-up.
METHODS: A deep learning model was trained for laser treatment detection using the EyePACs dataset. Data was randomly assigned, by participant, into development (n=18 945) and validation (n=2105) sets. Analysis was conducted at the single image, eye, and patient levels. The model was then used to filter input for three independent AI models for retinal indications; changes in model efficacy were measured using area under the receiver operating characteristic curve (AUC) and mean absolute error (MAE).
RESULTS: On the task of laser photocoagulation detection: AUCs of 0.981, 0.95, and 0.979 were achieved at the patient, image, and eye levels, respectively. When analysing independent models, efficacy was shown to improve across the board after filtering. Diabetic macular oedema detection on images with artefacts was AUC 0.932 vs AUC 0.955 on those without. Participant sex detection on images with artefacts was AUC 0.872 vs AUC 0.922 on those without. Participant age detection on images with artefacts was MAE 5.33 vs MAE 3.81 on those without.
CONCLUSIONS: The proposed model for laser treatment detection achieved high performance on all analysis metrics and has been demonstrated to positively affect the efficacy of different AI models, suggesting that laser detection can generally improve AI-powered applications for fundus images.

Proliferative diabetic retinopathy (PDR) the sequel of diabetic retinopathy (DR), a frequent complication of diabetes mellitus (DM), is the leading cause of blindness in the working-age population. The current screening process for the DR risk is not sufficiently effective such that often the disease is undetected until irreversible damage occurs. Diabetes-associated small vessel disease and neuroretinal changes create a vicious cycle resulting in the conversion of DR into PDR with characteristic ocular attributes including excessive mitochondrial and retinal cell damage, chronic inflammation, neovascularisation, and reduced visual field. PDR is considered an independent predictor of other severe diabetic complications such as ischemic stroke. A \"domino effect\" is highly characteristic for the cascading DM complications in which DR is an early indicator of impaired molecular and visual signaling. Mitochondrial health control is clinically relevant in DR management, and multi-omic tear fluid analysis can be instrumental for DR prognosis and PDR prediction. Altered metabolic pathways and bioenergetics, microvascular deficits and small vessel disease, chronic inflammation, and excessive tissue remodelling are in focus of this article as evidence-based targets for a predictive approach to develop diagnosis and treatment algorithms tailored to the individual for a cost-effective early prevention by implementing the paradigm shift from reactive medicine to predictive, preventive, and personalized medicine (PPPM) in primary and secondary DR care management.

Type 2 diabetes (T2DM) defined as the adult-onset type that is primarily not insulin-dependent, comprises over 95% of all diabetes mellitus (DM) cases. According to global records, 537 million adults aged 20-79 years are affected by DM that means at least 1 out of 15 persons. This number is projected to grow by 51% by the year 2045. One of the most common complications of T2DM is diabetic retinopathy (DR) with an overall prevalence over 30%. The total number of the DR-related visual impairments is on the rise, due to the growing T2DM population. Proliferative diabetic retinopathy (PDR) is the progressing DR and leading cause of preventable blindness in working-age adults. Moreover, PDR with characteristic systemic attributes including mitochondrial impairment, increased cell death and chronic inflammation, is an independent predictor of the cascading DM-complications such as ischemic stroke. Therefore, early DR is a reliable predictor appearing upstream of this \"domino effect\". Global screening, leading to timely identification of DM-related complications, is insufficiently implemented by currently applied reactive medicine. A personalised predictive approach and cost-effective targeted prevention shortly - predictive, preventive and personalised medicine (PPPM / 3PM) could make a good use of the accumulated knowledge, preventing blindness and other severe DM complications. In order to reach this goal, reliable stage- and disease-specific biomarker panels are needed characterised by an easy way of the sample collection, high sensitivity and specificity of analyses. In the current study, we tested the hypothesis that non-invasively collected tear fluid is a robust source for the analysis of ocular and systemic (DM-related complications) biomarker patterns suitable for differential diagnosis of stable DR versus PDR. Here, we report the first results of the comprehensive ongoing study, in which we correlate individualised patient profiles (healthy controls versus patients with stable D as well as patients with PDR with and without co-morbidities) with their metabolic profiles in the tear fluid. Comparative mass spectrometric analysis performed has identified following metabolic clusters which are differentially expressed in the groups of comparison: acylcarnitines, amino acid & related compounds, bile acids, ceramides, lysophosphatidyl-choline, nucleobases & related compounds, phosphatidyl-cholines, triglycerides, cholesterol esters, and fatty acids. Our preliminary data strongly support potential clinical utility of metabolic patterns in the tear fluid indicating a unique metabolic signature characteristic for the DR stages and PDR progression. This pilot study creates a platform for validating the tear fluid biomarker patterns to stratify T2DM-patients predisposed to the PDR. Moreover, since PDR is an independent predictor of severe T2DM-related complications such as ischemic stroke, our international project aims to create an analytical prototype for the \"diagnostic tree\" (yes/no) applicable to healthrisk assessment in diabetes care.