Congenital aniridia is a rare bilateral ocular malformation characterized by the partial or complete absence of the iris and is frequently associated with various anomalies, including keratopathy, cataract, glaucoma, and foveal and optic nerve hypoplasia. Additionally, nearly 50% of individuals with congenital aniridia experience symptoms of ocular dryness. Traditional treatment encompasses artificial tears and autologous serum. This study aimed to assess the effectiveness and safety of using platelet rich in growth factors (PRGF) plasma in patients with congenital aniridia and ocular dryness symptoms.
METHODS: The included patients underwent two cycles of a 3-month PRGF treatment. At 6 months, symptomatology was evaluated using the OSDI and SANDE questionnaires, and ocular surface parameters were analyzed.
RESULTS: The OSDI and SANDE values for frequency and severity demonstrated statistically significant improvements (p < 0.05). Ocular redness, corneal damage (corneal staining), and tear volume (Schirmer test) also exhibited statistically significant improvements (p < 0.05). No significant changes were observed in visual acuity or in the grade of meibomian gland loss.
CONCLUSIONS: The use of PRGF in patients with congenital aniridia and ocular dryness symptoms led to significant improvements in symptomatology, ocular redness, and ocular damage. No adverse effects were observed during the use of PRGF.

Congenital aniridia is a rare genetic eye disorder characterized by the complete or partial absence of the iris from birth. Various theories and animal models have been proposed to understand and explain the pathogenesis of aniridia. In the majority of cases, aniridia is caused by a mutation in the PAX6 gene, which affects multiple structures within the eye. Treating these ocular complications is challenging and carries a high risk of side effects. However, emerging approaches for the treatment of aniridia-associated keratopathy, iris abnormalities, cataract abnormalities, and foveal hypoplasia show promise for improved outcomes. Genetic counseling plays a very important role to make informed choices. We also provide an overview of the newer diagnostic and therapeutic approaches such as next generation sequencing, gene therapy, in vivo silencing, and miRNA modulation.

Three years ago, our patient, at that time a 16-month-old boy, was discovered to have bilateral kidney lesions with a giant tumor in the right kidney. Chemotherapy and bilateral nephron-sparing surgery (NSS) for Wilms tumor with nephroblastomatosis was carried out. The patient also had eye affection, including glaucoma, eye enlargement, megalocornea, severe corneal swelling and opacity, complete aniridia, and nystagmus. The diagnosis of WAGR syndrome was suspected. De novo complex chromosomal rearrangement with balanced translocation t(10,11)(p15;p13) and a pericentric inversion inv(11)(p13q12), accompanied by two adjacent 11p14.1p13 and 11p13p12 deletions, were identified. Deletions are raised through the complex molecular mechanism of two subsequent rearrangements affecting chromosomes 11 and 10. WAGR syndrome diagnosis was clinically and molecularly confirmed, highlighting the necessity of comprehensive genetic testing in patients with congenital aniridia and/or WAGR syndrome.

This study investigates the distribution of PAX6-associated congenital aniridia (AN) and WAGR syndrome across Russian Federation (RF) districts while characterizing PAX6 gene variants. We contribute novel PAX6 pathogenic variants and 11p13 chromosome region rearrangements to international databases based on a cohort of 379 AN patients (295 families, 295 probands) in Russia. We detail 100 newly characterized families (129 patients) recruited from clinical practice and specialized screening studies. Our methodology involves multiplex ligase-dependent probe amplification (MLPA) analysis of the 11p13 chromosome, PAX6 gene Sanger sequencing, and karyotype analysis. We report novel findings on PAX6 gene variations, including 67 intragenic PAX6 variants and 33 chromosome deletions in the 100 newly characterized families. Our expanded sample of 295 AN families with 379 patients reveals a consistent global PAX6 variant spectrum, including CNVs (copy number variants) of the 11p13 chromosome (31%), complex rearrangements (1.4%), nonsense (25%), frameshift (18%), and splicing variants (15%). No genetic cause of AN is defined in 10 patients. The distribution of patients across the Russian Federation varies, likely due to sample completeness. This study offers the first AN epidemiological data for the RF, providing a comprehensive PAX6 variants spectrum. Based on earlier assessment of AN prevalence in the RF (1:98,943) we have revealed unexamined patients ranging from 55% to 87%, that emphases the need for increased awareness and comprehensive diagnostics in AN patient care in Russia.

This study aims to present a clinical case involving the unique co-occurrence of congenital aniridia and Down syndrome in a young girl and to analyze the combined impact of these conditions on the patient\'s phenotype. The investigation involved comprehensive pediatric and ophthalmological examinations alongside karyotyping and Sanger sequencing of the PAX6 gene. The patient exhibited distinctive features associated with both congenital aniridia and Down syndrome, suggesting a potential exacerbation of their effects. Cytogenetic and molecular genetic analysis revealed the presence of trisomy 21 and a known pathogenic nonsense variant in exon 6 of the PAX6 gene (c.282C>A, p.(Cys94*)) corresponding to the paired domain of the protein. The observation of these two hereditary anomalies offers valuable insights into the molecular pathogenetic mechanisms underlying each condition. Additionally, it provides a basis for a more nuanced prognosis of the complex disease course in this patient. This case underscores the importance of considering interactions between different genetic disorders in clinical assessments and treatment planning.

Anterior Segment Dysgenesis (ASD) represents a spectrum of rare, congenital disorders that pose significant challenges to ophthalmological management due to their complex and heterogeneous nature. The management of ASD becomes particularly complex when associated with other serious ocular conditions. This report discusses the case of a 4-year-old girl diagnosed with ASD exhibiting a combination of sclerocornea, aphakia, aniridia, and secondary glaucoma. Owing to the complexity of such condition, a multi-disciplinary approach is required. Despite successful initial surgical interventions on the left eye, eye was lost due to subsequent endophthalmitis and retinal detachment, resulting in a decision to adopt a conservative, non-surgical approach for the right eye. Although a series of therapeutic interventions have been performed, the final visual outcome was poor, demonstrating the complexity and seriousness of such cases. This case serves as a reminder of the need for regular follow-up, prompt recognition, and management of potential complications. Further research is necessary to optimize the outcomes in patients with similar presentations.

Congenital PAX6-aniridia, initially characterized by the absence of the iris, has progressively been shown to be associated with other developmental ocular abnormalities and systemic features making congenital aniridia a complex syndromic disorder rather than a simple isolated disease of the iris. Moreover, foveal hypoplasia is now recognized as a more frequent feature than complete iris hypoplasia and a major visual prognosis determinant, reversing the classical clinical picture of this disease. Conversely, iris malformation is also a feature of various anterior segment dysgenesis disorders caused by PAX6-related developmental genes, adding a level of genetic complexity for accurate molecular diagnosis of aniridia. Therefore, the clinical recognition and differential genetic diagnosis of PAX6-related aniridia has been revealed to be much more challenging than initially thought, and still remains under-investigated. Here, we update specific clinical features of aniridia, with emphasis on their genotype correlations, as well as provide new knowledge regarding the PAX6 gene and its mutational spectrum, and highlight the beneficial utility of clinically implementing targeted Next-Generation Sequencing combined with Whole-Genome Sequencing to increase the genetic diagnostic yield of aniridia. We also present new molecular mechanisms underlying aniridia and aniridia-like phenotypes. Finally, we discuss the appropriate medical and surgical management of aniridic eyes, as well as innovative therapeutic options. Altogether, these combined clinical-genetic approaches will help to accelerate time to diagnosis, provide better determination of the disease prognosis and management, and confirm eligibility for future clinical trials or genetic-specific therapies.

BACKGROUND: The aim of the study was to evaluate the impact of simultaneous amniotic membrane transplantation (AMT), status of the cornea (own cornea vs. graft) and underlying disease on the success and recurrence rates of autologous serum (AS) in therapy-resistant epithelial defects.
METHODS: Between 2007 and 2019, 990 treatments with AS in 703 eyes of 645 patients were retrospectively examined. The presence of erosion or ulcer, use of AMT, status of the cornea and the underlying disease were recorded. Epithelial closure rate within 4 weeks and the recurrence rate after epithelial closure were main outcome measures. The median observation period was 50 months.
RESULTS: Epithelial closure was seen in 73.6% and recurrence in 27.4%. AMT was used significantly more often for ulcers (p < 0.001) and recurrences (p = 0.048). Without AMT, there was a significantly higher epithelial closure rate (p < 0.001) and faster healing tendency (p < 0.001). There was no difference between own corneas and grafts with respect to epithelial closure rate (p = 0.47). On the grafts there was a significantly higher recurrence rate (p = 0.004) and faster recurrence (p = 0.03), especially ≤6 months after epithelial closure. The underlying diseases showed a significant difference in epithelial closure rate (p = 0.02) and recurrence rate (p < 0.001) with highest success in corneal dystrophies and lowest in congenital aniridia.
CONCLUSIONS: AS is an effective therapeutic option for therapy-resistant epithelial defects. There was a high success rate for the grafts but with a higher tendency to develop recurrences. In cases of simultaneous AMT, a reduced success rate can be expected, due to the higher complexity of the given situation. AS can be used successfully in various underlying diseases, with limitations in case of congenital aniridia.
UNASSIGNED: HINTERGRUND: Ziel der Studie war es, den Einfluss einer simultanen Amnionmembrantransplantation (AMT), des Hornhaut(HH)-Status (eigene HH vs. Transplantat [TPL]) und der Grunderkrankung auf die Erfolgs- und Rezidivraten des autologen Serums (AS) bei therapieresistenten Epitheldefekten zu evaluieren.
UNASSIGNED: Von 2007 bis 2019 wurden 990 Therapien mit AS an 703 Augen von 645 Patienten retrospektiv untersucht. Erfasst wurden das Vorliegen einer Erosio oder Ulkus, die Anwendung einer AMT, der HH-Status und die Grunderkrankung. Zielgrößen waren die Epithelschlussrate innerhalb 4 Wochen und die Rezidivrate nach Epithelschluss. Die mediane Beobachtungszeit betrug 50 Monate.
UNASSIGNED: Ein Epithelschluss zeigte sich bei 73,6 % und ein Rezidiv bei 27,4 %. Eine AMT wurde signifikant häufiger bei Ulzera (p < 0,001) und Rezidiven (p = 0,048) angewandt. Ohne AMT ergab sich eine signifikant höhere Epithelschlussrate (p < 0,001) und schnellere Heilungstendenz (p < 0,001). Es bestand kein Unterschied zwischen der eigenen HH und dem TPL in der Epithelschlussrate (p = 0,47). Auf dem TPL zeigte sich eine signifikant höhere Rezidivrate (p = 0,004) und ein schnelleres Rezidivauftreten (p = 0,03), v. a. ≤6 Monate nach Epithelschluss. Die Grunderkrankungen zeigten einen signifikanten Unterschied in der Epithelschluss- (p = 0,02) und Rezidivrate (p < 0,001) mit höchstem Erfolg bei HH-Dystrophien und geringstem bei kongenitaler Aniridie.
UNASSIGNED: Das AS stellt eine effektive Therapieoption bei therapieresistenten Epitheldefekten dar. Es zeigt auf dem TPL eine hohe Erfolgsrate bei zugleich höherer Rezidivneigung. Bei simultaner AMT ist wegen der erhöhten Komplexität des zugrunde liegenden Problems mit geringeren Erfolgsraten zu rechnen. Das AS ist bei verschiedenen Grunderkrankungen erfolgreich einsetzbar, mit Limitationen bei der kongenitalen Aniridie.

Congenital aniridia is a rare ocular disorder characterized by iris malformation. We present a 3-year-old boy with bilateral anterior-segment dysgenesis, congenital aniridia, congenital aphakia, secondary glaucoma, limbal stem cell deficiency, and band keratopathy. As the intraocular pressure was uncontrolled with antiglaucoma medications, the patient underwent multiple bilateral traditional cyclophotocoagulation (CPC), in addition to micropulse CPC. To the best of our knowledge, aniridia association with congenital aphakia and congenital glaucoma has been very rarely reported.

This review updates the knowledge about the morphological assessment of the foveal hypoplasia in congenital aniridia and resumes the reported genotype-phenotype correlations known to date. Congenital aniridia is a pan ocular disease. Although iris absence is considered the hallmark of this entity, foveal hypoplasia is present in 94.7%-84% of patients. A foveal morphology assessed by optical coherence tomography in which external retina structures can be identified, with presence of the lengthening of photoreceptors outer segment and a greater external retinal thickness, is associated with a better visual outcome, regardless a foveal pit is identified or not. This analysis can be performed once the external retina has completed its differentiation, by 6 years old. PAX6 mutations that introduce premature termination codon, C terminal extension or PAX6 involving deletions have been related to lesser foveal differentiation. Better foveal differentiation has been associated to non-coding PAX6 mutations.