無虹彩症

BACKGROUND: To investigate, for the first time, whether an unconjugated VEGF-A antisense oligonucleotide (ASO) can inhibit corneal neovascularisation and improve graft survival in a murine high-risk corneal transplantation model. METHODS: A suture-induced corneal neovascularisation model was established in BALB/c mice, followed by high-risk corneal transplantation using C57BL/6 donor corneas. A VEGF-A RNase H-recruiting ASO (gapmer) was delivered via subconjunctival injection, topical eye drops, or ex vivo preincubation of donor corneas. Blood vessels (BVs) and lymphatic vessels (LVs) were quantified by immunohistochemistry, and Vegfa mRNA expression was measured by qPCR. Immune cell profiles in draining lymph nodes (dLNs), focusing on regulatory T cells (Tregs) and dendritic cells (DCs), were analysed by flow cytometry. Graft survival was monitored for 8 weeks using Kaplan-Meier analysis. RESULTS: Subconjunctival and topical VEGF-A ASO administration significantly suppressed corneal hemangiogenesis and lymphangiogenesis (p < 0.05). Subconjunctival injection also induced regression of established vessels (BVs -21.76%, p = 0.0039; LVs -49.75%, p = 0.0110). Graft survival improved significantly after subconjunctival treatment (p = 0.0438) and donor cornea preincubation (p = 0.0148). Flow cytometry showed increased Treg frequency in dLNs following subconjunctival ASO administration (p = 0.0293). Preincubation of donor corneas markedly reduced Vegfa mRNA levels (p < 0.0001). CONCLUSIONS: VEGF-A-targeting ASO effectively inhibits corneal neovascularisation and improves graft survival in high-risk transplantation. Local and ex vivo VEGF-A inhibition using ASO represents a promising therapeutic strategy for controlling ocular neovascularisation and enhancing corneal transplant outcomes.

BACKGROUND: Congenital aniridia is a rare disorder characterized by partial or complete absence of the iris and is usually associated with other ocular and systemic complications. Its lifelong and multisystem nature creates challenges that extend beyond clinical management and require coordinated, multidisciplinary, and equitable healthcare delivery. METHODS: A scoping review was conducted using the Arksey and O'Malley framework and Joanna Briggs Institute methodology and reported in accordance with PRISMA-ScR. PubMed, Scopus, and Google Scholar were searched for English-language publications from January 2015 to May 2025 addressing organizational models of care, patient-management strategies, and quality-of-life assessment in congenital aniridia. Included sources were descriptively classified by study design and evidence category. Findings were synthesized using a combined deductive and inductive thematic approach. RESULTS: Fourteen sources met the inclusion criteria and represented different geographical and healthcare settings. The evidence was predominantly observational, retrospective, descriptive, or based on expert and organizational recommendations. Across the reviewed literature, recurrent themes included multidisciplinary coordination, access to specialized expertise, structured referral pathways, registries, telemedicine, lifelong monitoring, genetic counseling, rehabilitation, and patient support. However, direct comparative and longitudinal evaluations of organizational models were lacking. Quality-of-life studies used heterogeneous assessment instruments, limiting direct comparison, although poorer visual function, advanced ocular complications, ocular pain, and broader psychological or systemic burden were generally associated with less favorable patient-reported outcomes. CONCLUSION: The available evidence supports the principles of lifelong, multidisciplinary, coordinated, and patient-centered care for congenital aniridia. Future health-system development may benefit from strengthened centers of expertise, standardized referral pathways, registry infrastructure, digital consultation, and improved access to specialized services. Prospective multicentre and longitudinal studies are needed to determine the comparative effectiveness of different organizational models and to standardize patient-reported outcome assessment.

This summary explains the findings of the NEW DAY study, which examined two ways of starting treatment for diabetic macular edema (DME). DME is an eye condition that can affect people with diabetes and can cause blurred vision or vision loss if not treated. In the 18-month study, adults with DME who had little or no previous treatment started therapy with either a single fluocinolone acetonide (FAc) implant or a series of aflibercept injections. The FAc implant is a small device placed inside the eye and is designed to slowly release a corticosteroid up to 3 years. Aflibercept is a medicine given as a series of eye injections. After the planned starting treatment, people in both groups could receive extra ("rescue") aflibercept injections if their vision worsened or if eye scans showed worsening DME (retina swelling). After the planned starting treatments, both groups needed a similar number of rescue injections. However, counting the planned starting treatments plus the rescue injections, people who received the FAc implant had fewer total injections and went longer before needing their first rescue injection. Vision and retina swelling improved similarly between groups. Side effects such as cataracts and increases in eye pressure were more common with the FAc implant. Such side effects are expected when steroids are given in the eye and manageable with regular checkups and treatment. Overall, compared with starting DME treatment with aflibercept, starting with the FAc implant reduced the total number of injections while providing similar vision and eye scan improvements. What is this summary about? This is a plain language summary of the results of the NEW DAY study published in Ophthalmology 2026 Jul;133(7):837-851. doi: 10.1016/j.ophtha.2026.03.019. NEW DAY compared ILUVIEN®, a fluocinolone acetonide implant (FAc), with aflibercept in people with diabetic macular edema (DME) who had minimal or no prior treatment for that condition. DME is a complication of diabetes that affects the eye, causing blurred vision and potential vision loss if left untreated. DME happens when small blood vessels are damaged in the retina (an area at the back of the eye where specialized cells sense light and send signals to the brain so that we can see). These damaged blood vessels become leaky and cause swelling (edema) in a central area of the retina called the macula. Current treatments for DME include medicines that reduce inflammation (called corticosteroids) and medicines that block a protein called vascular endothelial growth factor (VEGF) that causes blood vessels to leak (these are called anti-VEGFs). The purpose of the NEW DAY study was to compare the FAc implant (a corticosteroid) with aflibercept (an anti-VEGF) injections as a treatment for people with DME who had either minimal or no prior treatment. Worsening DME may occur in some people despite treatment. During the study, extra aflibercept injections were given when needed after the initial planned treatment. The study compared how many extra, or "rescue", aflibercept injections were needed after the planned treatment. The study also compared the effect of each treatment on vision and swelling of the macula. Side effects of the treatments were also recorded. What were the results? After the planned treatments (either one FAc implant or five aflibercept injections), the average number of extra aflibercept injections was similar between groups. However, when counting the planned treatments, the total number of injections over 18 months was lower in people who received FAc. Rescue injections were needed sooner after the last scheduled aflibercept injection than after receiving a FAc implant. Regardless of initial treatment, improvements in vision and swelling of the retina were similar. Side effects, such as cataracts and increases in eye pressure, were more frequent with FAc than aflibercept. What do the results mean? Starting DME treatment with the FAc implant had similar benefits to vision and swelling as starting with aflibercept. People who started with FAc needed fewer total injections overall than those who started with aflibercept and had a longer time to requiring rescue injections. Side effects of FAc were as expected and were manageable. Knowing the timing of when they happened can help eye-care teams better monitor patients with DME and manage their care.

PURPOSE: Corneal crosslinking (CXL) using riboflavin and ultraviolet A (UV-A) illumination is widely used to stabilize progressive ectatic corneal disorders such as keratoconus. However, the photochemical reaction generates oxidative stress and may induce apoptosis, while potential differences between healthy human corneal fibroblasts (HCF) and human corneal fibroblasts derived from keratoconus corneas (KC-HCF) remain insufficiently understood. This study examined in-vitro changes in pro- and anti-apoptotic markers in HCF and KC-HCF following riboflavin-UV-A illumination. METHODS: Cell cultures of HCFs (n = 5) and KC-HCFs (n = 5) were incubated with 0.01% or 0.1% riboflavin-dextran solutions (RF) for subsequent crosslinking and either placed in a dark chamber or illuminated with UV-A light (250 s, 375 nm, 2 J/cm2). The expression profiles of pro-apoptotic markers (BCL-2 homologous antagonist/killer (BAK), BCL-2 associated agonist of cell death protein (BAD), caspase-9 (CASP9) and cytochrome c (CYCS)) and the anti-apoptotic marker Baculoviral IAP Repeat Containing 5 (BIRC5) were analyzed using quantitative reverse transcription polymerase chain reaction (RT-PCR) (0.01%/0.1% RF; n = 5; for 2 h (h), 4 h, n = 3; for 24 h) and Western blot (0.1% RF; n = 4 for 24 h). Cell proliferation was assessed after 2 h, and ultrastructural changes were examined by transmission electron microscopy (TEM) after 24 h (0.1% RF; n = 1). RESULTS: Cell proliferation was significantly reduced in HCFs and KC-HCFs after 2 h in both treatment groups (0.01%/0.1% RF). Gene expression analysis showed a significant increase in BAK and BAD expression in KC-HCFs after 24 h with 0.01% RF, but not after 0.1% riboflavin-UV-A illumination. For CYCS and CASP9 gene expression levels remained unchanged for HCFs and KC-HCFs in both treatment groups. BIRC5 was significantly reduced in HCFs (0.01%/0.1% RF) and in KC-HCFs (0.1% RF). Protein expression analysis revealed a significant increase in BAK and CYCS after 24 h in HCFs and KC-HCFs, while CASP9 expression was significantly decreased. TEM showed some ultrastructural features of apoptosis after 24 h (0.1% RF). CONCLUSION: Riboflavin-UV-A illumination induced a time- and dose-dependent cellular response in both HCFs and KC-HCFs with KC-HCFs showing an increased sensitivity to photochemical stress.

OBJECTIVE: To clarify the molecular and clinical characteristics of anterior-segment dysgenesis (ASD)/aniridia and microphthalmia/anophthalmia caused by monogenic variants. DESIGN: Clinical and genetic analyses of a large cohort of patients with bilateral ocular lesions. PARTICIPANTS: A total of 111 patients and their family members were recruited through a multicenter collaborative study in Japan. METHODS: Next-generation sequencing using custom-designed panels for 11 and 12 major causative genes for ASD/aniridia and microphthalmia/anophthalmia, respectively. We analyzed the clinical information of patients with pathogenic or likely pathogenic variants. MAIN OUTCOME MEASURES: Collated genetic results and clinical data. RESULTS: We achieved genetic diagnosis rates of 50.0% for ASD/aniridia and 37.5% for microphthalmia/anophthalmia. We identified 11 previously unreported variants. De novo variants in the PAX6, PITX2, or GJA8 genes and parentally derived variants in the FOXC1 and CYP1B1 genes were the major causes of ASD/aniridia. Microphthalmia/anophthalmia‑associated variants in the ABCB6, BMP4, and OTX2 genes were predominantly inherited from parents with no or different ocular phenotypes. We observed phenotypic diversity and variable ocular and systemic complications in variant-positive patients. Most importantly, this study showed a high incidence of glaucoma in patients with CYP1B1 and FOXC1 variants and frequent systemic abnormalities in patients with FOXC1 and PITX2 variants. In addition, BMP4 and RARB variants were associated with neurologic abnormalities. CONCLUSIONS: This study provides evidence that targeted gene panel approaches are useful for the clinical diagnosis of ASD/aniridia and microphthalmia/anophthalmia. Our data clarified the mutation spectrum and phenotypic characteristics of these disorders caused by monogenic variants. This study confirmed that various phenotypes classified as ASD, such as Peters anomaly and Axenfeld anomaly, constitute a group of disorders on the same spectrum, may overlap with aniridia, and exhibit genetic heterogeneity. The findings, which demonstrate an association between genotypes and complications, are expected to contribute to better management and care for children with these rare intractable eye diseases. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.