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.

OBJECTIVE: Choroidal neovascularisation (CNV) in patients with X-linked retinoschisis (XLRS) has been poorly documented. This study aims to investigate the prevalence and clinical characteristics of CNV in patients with XLRS, as well as analyse the preliminary genotype-phenotype correlation.
METHODS: A retrospective case series of patients with genetically confirmed XLRS was included. Demographic, clinical and genetic features were analysed, with a comparison between CNV and non-CNV eyes.
RESULTS: Among 185 eyes of 129 patients with XLRS, the prevalence of CNV was 8.1% (15/185). The mean diagnostic age of all patients with CNV is 5.1±2.56 years. CNV eyes exhibited a mean best-corrected visual acuity (BCVA) (logarithm of the minimal angle of resolution) of 1.37±0.74. All CNVs were classified as subretinal and active. Peripapillary CNVs accounted for 80.0% (12/15), while subfoveal CNVs accounted for 20.0% (3/15). In CNV eyes, the prevalence of macular atrophy (5/15, 33.3%, p=0.013) and bullous peripheral schisis (14/15, 93.3%, p=0.000) was higher compared with non-CNV eyes. Additionally, CNV eyes exhibited poorer integrity of the outer retina and BCVA (p=0.007) compared with non-CNV eyes. All 15 eyes with CNV underwent anti-vascular endothelial growth factor (anti-VEGF) therapy. Genotype analysis revealed that 7 of 10 patients (70.0%, 10 eyes) were predicted to have missense variants, while 3 of 10 patients (30.0%, 5 eyes) exhibited severe variants.
CONCLUSIONS: The prevalence of CNV in XLRS eyes was found to be 8.1%. All CNVs secondary to XLRS were active and classified as type 2. CNV eyes demonstrated poorer visual function and compromised retinal structures. Anti-VEGF therapy demonstrated effectiveness in treating XLRS-CNVs. No significant genotype-phenotype correlation was established.

OBJECTIVE: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD OCT) combined with OCT angiography (OCTA) for myopic myopic macular neovascularisation (MNV) activity.
METHODS: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators.
RESULTS: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01).
CONCLUSIONS: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV.

OBJECTIVE: To develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD).
METHODS: 300 optical coherence tomography volumes from subject eyes with nAMD were collected. Images were manually segmented for the presence of five crucial nAMD features: intraretinal fluid, subretinal fluid, subretinal hyperreflective material, drusen/drusenoid pigment epithelium detachment (PED) and neovascular PED. A deep learning architecture based on a U-Net was trained to perform automatic segmentation of these retinal biomarkers and evaluated on the sequestered data. The main outcome measures were receiver operating characteristic curves for detection, summarised using the area under the curves (AUCs) both on a per slice and per volume basis, correlation score, enface topography overlap (reported as two-dimensional (2D) correlation score) and Dice coefficients.
RESULTS: The model obtained a mean (±SD) AUC of 0.93 (±0.04) per slice and 0.88 (±0.07) per volume for fluid detection. The correlation score (R2) between automatic and manual segmentation obtained by the model resulted in a mean (±SD) of 0.89 (±0.05). The mean (±SD) 2D correlation score was 0.69 (±0.04). The mean (±SD) Dice score resulted in 0.61 (±0.10).
CONCLUSIONS: We present a fully automated segmentation model for five features related to nAMD that performs at the level of experienced graders. The application of this model will open opportunities for the study of morphological changes and treatment efficacy in real-world settings. Furthermore, it can facilitate structured reporting in the clinic and reduce subjectivity in clinicians\' assessments.

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.

OBJECTIVE: To explore prognostic multimarker models for progression to macular fibrosis (MF) over 24 months specific to type 3 macular neovascularisation (T3 MNV).
METHODS: This retrospective, exploratory, single-centre, cohort study comprised 65 eyes of 43 Caucasian patients with treatment naive T3 MNV, all with a 24-month follow-up post anti-VEGF therapy using a strict pro-re-nata (PRN) regimen. Data on demographic features, clinical findings, frequency of intravitreal treatments and optical coherence tomography biomarkers were collected at baseline and after 12 and 24 months of follow-up. Logistic regression models (LRM) and receiver-operating curve (C-index) analyses were performed to evaluate the prognostic ability of the studied biomarkers in discriminating between MF affected and unaffected patients.
RESULTS: At final follow-up, MF was present in 46.2% of eyes. Subretinal hyper-reflective material (SHRM) and subretinal pigment epithelium multilaminar hyper-reflectivity (multilaminae) emerged as significant predictors for MF, with adjusted odds ratios (OR) of 18.0 (95% CL 13.4 to 24.1) and 11.8 (95% CL 8.66 to 16.0), respectively. Additionally, the presence of multifocal lesions (OR 0.04, 95% CL 0.01 to 0.30) appeared to decrease the likelihood of MF. C-indexes for the selected LRMs ranged between 0.92 and 0.88, indicating a comparably high discriminant ability. Despite consistent treatment schedules between the two groups (MF: median intravitreal treatment (IVT) number=10.5, IQR=7; non-MF: median IVT=10, IQR=6), a decline in best-corrected visual acuity was noted in the group with MF onset over the 24-month follow-up (-13.0 ETDRS letters; 95% CL -22.1 to -3.9; p=0.006).
CONCLUSIONS: Our study identifies SHRM and multilaminae as relevant predictors of 24-month onset of MF in patients with T3 MNV. These findings enrich our understanding of the development of MF in T3 MNV and can guide improved risk prognostication. Future research should consider larger samples and prospective designs to validate these predictors.

To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD).
Prospective, double-masked, randomised, phase 3 trial.
Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch\'s membrane). Additional endpoints included safety, PK and immunogenicity.
Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 µm and -132.4 µm for SB15/SB15 and -126.6 µm and -136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups.
Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.

OBJECTIVE: This study aimed to investigate the effect of human adipose tissue derived stromal vascular fraction (AD-SVF) and mesenchymal stem cells (AD-MSCs) on blood flow recovery and neovascularisation in a rat hindlimb ischaemia model.
METHODS: SVF was isolated using an automated centrifugal system, and AD-MSCs were obtained from adherent cultures of SVF cells. Rats were divided into four groups of six rats each: non-ischaemia (Group 1); saline treated ischaemia (Group 2); SVF treated ischaemia (Group 3); and AD-MSC treated ischaemia (Group 4). Unilateral hindlimb ischaemia was induced in Sprague-Dawley rats via femoral artery ligation. Saline, SVF, or AD-MSCs were injected intramuscularly into the adductor muscle intra-operatively. Cell viability was calculated as the percentage of live cells relative to total cell number. Blood flow improvement, muscle fibre injury, and angiogenic properties were validated using thermal imaging and histological assessment.
RESULTS: The viabilities of SVF and AD-MSCs were 83.3% and 96.7%, respectively. Group 1 exhibited no significant temperature difference between hindlimbs, indicating a lack of blood flow changes. The temperature gradient gradually decreased in SVF and AD-MSC treated rats compared with saline treated rats. In addition, only normal muscle fibres with peripherally located nuclei were observed in Group 1. Groups 3 and 4 exhibited significantly fewer centrally located nuclei, indicating less muscle damage compared with Group 2. Regarding angiogenic properties, CD31 staining of endothelial cells showed similar patterns among all groups, whereas expression of vascular endothelial growth factor, as a crucial angiogenesis factor, was enhanced in the SVF and AD-MSC treated groups.
CONCLUSIONS: SVF and AD-MSCs improved blood flow and neovascularisation in a rat hindlimb ischaemia model, suggesting their potential ability to promote angiogenesis. Further extensive research is warranted to explore their potential applications in the treatment of severe lower extremity arterial disease.

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.