María Nieves-Moreno

Background/Objectives: Pediatric orbital tumors are rare and complex, requiring multidisciplinary care at specialized centers. Contemporary treatment paradigms emphasize centralized care delivery through experienced multidisciplinary teams to optimize patient outcomes. Recent advances in surgical planning technologies and intraoperative navigation systems have substantially enhanced surgical safety through improvement in tumor resection and reconstruction and reduction in complications, including recurrence of the lesion. Computed-aided surgical technologies enable precise virtual planning, minimally invasive approaches and more precise reconstruction methods when necessary by mean of patient-specific cutting guides, premolded orbital plates or individual patient solutions (IPS) prosthesis. Three-dimensional biomodelling visualizes tumor architecture and aids localization while preserving neurovascular structures, and real-time neuronavigation improves safety and efficacy. Methods: We conducted a retrospective analysis of 98 pediatric patients with orbital tumors treated between 2014 and 2025 at a tertiary center to evaluate the use of computed-assisted surgical technologies and the indications for treatment. Inclusion criteria comprised all cases where computer-assisted techniques were employed. Patients were classified into two groups: Group 1—intraconal or extensive periorbital lesions with eye-sparing intent treated via craniofacial approaches; Group 2—periorbital tumors with orbital wall involvement, to analyze the use of the different technologies. Data collected included tumor age, type, location, technology used, adjunctive treatments, and postoperative outcomes. Results: Twelve patients underwent computer-assisted surgery. Technologies employed over the last six years included intraoperative navigation, 3D planning with/without tumor segmentation, orbital-wall reconstruction by mirroring, IPS or titanium mesh bending, and preoperative biomodelling. Patients were grouped by tumor location and treatment goals: Group 1—intraorbital lesions (primarily intraconal or 270–360° involvement), including one case of orbital encephalocele treated transcranially; Group 2—periorbital tumors with orbital-wall destruction, treated mainly via midfacial approaches. Intraoperative navigation was used in 10/12 cases (8/11 with tumor segmentation); in 3 cases with ill-defined margins, navigation localized residual tumor. Virtual surgery predominated in Group 2 (4 patients) and one in Group 1, combined with cutting guides for margins and Individual Prosthetic Solutions (IPS) prosthesis fitting (two patients: titanium and PEEK). In two cases, virtual plans were performed, STL models printed, and premolded titanium meshes used. No complications related to tumor persistence or orbital disturbance were observed. Conclusions: Advanced surgical technologies substantially enhance safety, efficiency, and outcomes in pediatric orbital tumors. Technology-assisted approaches represent a paradigm shift in this complex field. Additional studies are needed to establish evidence-based protocols for systematic integration of technology in pediatric orbital tumor management.

Objective: We assess the prevalence of myopia and its associated factors among schoolchildren in Madrid, Spain, where school-based data using cycloplegic refraction are currently scarce. Methods: A cross-sectional study was conducted in 39 randomly selected schools in Madrid, targeting children in the second (6–7 years) and sixth grades (11–12 years). Parents completed questionnaires detailing family ocular history, the child’s lifestyle, and screen time. Socio-economic status was inferred from the Human Development Index of school districts. Children were examined using a two-stage approach: initial screening with visual acuity testing and Plusoptix photorefraction (myopia screening cut-off ≤ 0.00 D spherical equivalent), followed by confirmatory cycloplegic autorefraction (three drops of cyclopentolate 1% administered at 10 min intervals), with myopia defined as spherical equivalent ≤ −0.50 D. Statistical analyses included chi-square tests and logistic regression models to evaluate associated factors. Results: Of 3680 children invited, 2489 (67.6%) were examined. Myopia prevalence was 6.5% in second grade and 18.7% in sixth grade. Family history of myopia was a significant risk factor (OR 2.04; 95% CI: 1.53–2.70; p < 0.001 for both parents). Outdoor activity during weekends was associated with lower myopia prevalence (OR 0.50; 95% CI: 0.37–0.66; p < 0.01 for 2–6 h). Screen time was not a significant factor in multivariate analysis. Conclusions: This large school-based study using cycloplegic refraction provides more accurate prevalence data for Spanish schoolchildren. It confirms family history as a major risk factor and highlights the association of outdoor activities with lower prevalence of myopia. These results underline the need for preventive measures and suggest areas for future interventional research.

Programs for Undiagnosed Rare Diseases (URD) with anonymized data sharing are contributing to the earlier genetic diagnosis of patients and to the identification and characterization of novel genetic disorders. Recently, de novo pathogenic variants in two non-coding spliceosomal small nuclear RNAs (snRNAs), RNU4-2 and RNU2-2 , key regulators of gene expression during neurodevelopment, have been linked to neurodevelopmental disorders (NDD). With the aim to identify individuals with causal genetic variants in known and novel snRNA genes, we analyzed WGS and clinical data of 1,708 probands with undiagnosed NDD enrolled in the Spanish URD Programs. Selected individuals underwent in-depth re-phenotyping including facial mask analyses (Face2Gene), and blood-DNA methylation profiling was obtained (Infinium methylation Epicv2 microarrays). We identified 38 patients (2.22%) with de novo pathogenic variants in snRNA genes, 28 in RNU4-2 (1.64%), 6 in RNU2-2 (0.35%), and 4 in RNU5B-1 (0,23%). A clinically recognizable NDD (ReNU syndrome) is caused by RNU4-2 variants, with dysmorphic features making a disease-associated facial mask, RNU2-2 associates an early onset epileptic encephalopathy, and RNU5-B1 a less defined NDD with overlapping features. A DNA methylomic episignature was also identified for RNU4-2 , which does not overlap with the other conditions. We have also defined autosomal recessive inheritance in 8 additional patients (0.47%) with NDD and biallelic variants in three snRNA genes (3 in RNU4-2 , 3 in RNU2-2 , and 2 in RNU4-1 ). Our study has facilitated the quick diagnosis, management, and genetic counselling of 2.69% previously undiagnosed patients with NDD, further reinforcing the value and utility of the URD Programs. GRAPHICAL

High myopia is the most severe and pathological form of myopia. It occurs when the spherical refractive error exceeds –6.00 spherical diopters (SDs) or the axial length (AL) of the eye is greater than 26 mm. This article focuses on early-onset high myopia, an increasingly common condition that affects children under 10 years of age and can lead to other serious ocular pathologies. Through the genetic analysis of 21 families with early-onset high myopia, this study seeks to contribute to a better understanding of the role of genetics in this disease and to propose candidate genes. Whole-exome sequencing studies with a panel of genes known to be involved in the pathology were performed in families with inconclusive results: 3% of the variants found were classified as pathogenic, 6% were likely pathogenic and the remaining 91% were variants of uncertain significance. Most of the families in this study were found to have alterations in several of the proposed genes. This suggests a polygenic inheritance of the pathology due to the cumulative effect of the alterations. Further studies are needed to validate and confirm the role of these alterations in the development of early-onset high myopia and its polygenic inheritance.

Keratoconus is a corneal dystrophy that is one of the main causes of corneal transplantation and for which there is currently no effective treatment for all patients. The presentation of this disease in pediatric age is associated with rapid progression, a worse prognosis and, in 15–20% of cases, the need for corneal transplantation. It is a multifactorial disease with genetic variability, which makes its genetic study difficult. Discovering new therapeutic targets is necessary to improve the quality of life of patients. In this manuscript, we present the results of whole-exome sequencing (WES) of 24 pediatric families diagnosed at the University Hospital La Paz (HULP) in Madrid. The results show an oligogenic inheritance of the disease. Genes involved in the structure, function, cell adhesion, development and repair pathways of the cornea are proposed as candidate genes for the disease. Further studies are needed to confirm the involvement of the candidate genes described in this article in the development of pediatric keratoconus.

Non-syndromic pediatric cataracts are defined as opacification of the crystalline lens that occurs during the first years of life without affecting other organs. Given that this disease is one of the most frequent causes of reversible blindness in childhood, the main objective of this study was to propose new responsible gene candidates that would allow a more targeted genetic approach and expand our genetic knowledge about the disease. We present a whole exome sequencing (WES) study of 20 Spanish families with non-syndromic pediatric cataracts and a previous negative result on an ophthalmology next-generation sequencing panel. After ophthalmological evaluation and collection of peripheral blood samples from these families, WES was performed. We were able to reach a genetic diagnosis in 10% of the families analyzed and found genes that could cause pediatric cataracts in 35% of the cohort. Of the variants found, 18.2% were classified as pathogenic, 9% as likely pathogenic, and 72.8% as variants of uncertain significance. However, we did not find conclusive results in 55% of the families studied, which suggests further studies are needed. The results of this WES study allow us to propose LONP1, ACACA, TRPM1, CLIC5, HSPE1, ODF1, PIKFYVE, and CHMP4A as potential candidates to further investigate for their role in pediatric cataracts, and AQP5 and locus 2q37 as causal genes.

A clinical and genetic study was conducted with pediatric patients and their relatives with optic atrophy 1 (OPA1) mutations to establish whether there is a genotype–phenotype correlation among the variants detected within and between families. Eleven children with a confirmed OPA1 mutation were identified during the study period. The main initial complaint was reduced visual acuity (VA), present in eight patients of the cohort. Eight of eleven patients had a positive family history of optic atrophy. The mean visual acuity at the start of the study was 0.40 and 0.44 LogMAR in the right and left eye, respectively. At the end of the study, the mean visual acuity was unchanged. Optical coherence tomography during the first visit showed a mean retinal nerve fiber layer thickness of 81.6 microns and 80.5 microns in the right and left eye, respectively; a mean ganglion cell layer of 52.5 and 52.4 microns, respectively, and a mean central macular thickness of 229.5 and 233.5 microns, respectively. The most common visual field defect was a centrocecal scotoma, and nine out of eleven patients showed bilateral temporal disc pallor at baseline. Sequencing of OPA1 showed seven different mutations in the eleven patients, one of which, NM_130837.3: c.1406_1407del (p.Thr469LysfsTer16), has not been previously reported. Early diagnosis of dominant optic atrophy is crucial, both for avoiding unnecessary consultations and/or treatments and for appropriate genetic counseling.

Early-onset high myopia (EoHM) is a disease that causes a spherical refraction error of ≥−6 diopters before 10 years of age, with potential multiple ocular complications. In this article, we report a clinical and genetic study of 43 families with EoHM recruited in our center. A complete ophthalmological evaluation was performed, and a sample of peripheral blood was obtained from proband and family members. DNA was analyzed using a customized next-generation sequencing panel that included 419 genes related to ophthalmological disorders with a suspected genetic cause, and genes related to EoHM pathogenesis. We detected pathogenic and likely pathogenic variants in 23.9% of the families and detected variants of unknown significance in 76.1%. Of these, 5.7% were found in genes related to non-syndromic EoHM, 48.6% in genes associated with inherited retinal dystrophies that can include a syndromic phenotype, and 45.7% in genes that are not directly related to EoHM or retinal dystrophy. We found no candidate genes in 23% of the patients, which suggests that further studies are needed. We propose a systematic genetic analysis for patients with EoHM because it helps with follow-up, prognosis and genetic counseling.