Retinal Degeneration Associated With Biallelic RDH12 Variants: Longitudinal Evaluation of Retinal Structure and Visual Function in Pediatric Patients.

Purpose: The purpose of this study was to determine the natural history of the photoreceptor disease in a large group of pediatric patients with RHD12-associated Leber congenital amaurosis (RDH12-LCA), to estimate the changes expected over the duration of a clinical trial, and to define the relationship between the photoreceptor loss and visual dysfunction.

Methods: Forty-six patients representing 36 families were included. The great majority of patients were under the age of 18 years.

Retinal prolactin isoform PRLΔE1 sustains rod disease in inherited retinal degenerations.

PRLΔE1, a retina-specific isoform of prolactin, is expressed in multiple and diverse forms of canine inherited retinal degeneration (IRD). We find that while PRLΔE1 expression in rods is not associated with the initial phase of disease characterized by acute photoreceptor cell death, it is associated with the protracted phase of slow cell loss. Restoration of photoreceptors to a healthy state by gene-specific replacement therapy of individual IRDs successfully suppresses PRLΔE1 expression.

Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study.

Background: Leber congenital amaurosis 1 (LCA1), caused by mutations in GUCY2D, is a rare inherited retinal disease that typically causes blindness in early childhood. The aim of this study was to evaluate the safety and preliminary efficacy of ascending doses of ATSN-101, a subretinal AAV5 gene therapy for LCA1.

Methods: 15 patients with genetically confirmed biallelic mutations in GUCY2D were included in this phase 1/2 study.

Managing Undernutrition in Pediatric Oncology: A Consensus Statement Developed Using the Delphi Method by the Polish Society for Clinical Nutrition of Children and the Polish Society of Pediatric Oncology and Hematology.

"Managing Undernutrition in Pediatric Oncology" is a collaborative consensus statement of the Polish Society for Clinical Nutrition of Children and the Polish Society of Pediatric Oncology and Hematology. The early identification and accurate management of malnutrition in children receiving anticancer treatment are crucial components to integrate into comprehensive medical care. Given the scarcity of high-quality literature on this topic, a consensus statement process was chosen over other approaches, such as guidelines, to provide comprehensive recommendations.

Retinal response to light exposure in BEST1-mutant dogs evaluated with ultra-high resolution OCT.

Mutations in BEST1 cause an autosomal recessive disease in dogs where the earliest changes localize to the photoreceptor-RPE interface and show a retina-wide micro-detachment that is modulated by light exposure. The purpose of this study was to define the spatial and temporal details of the outer retina and its response to light with ultra-high resolution OCT across a range of ages and with different BEST1 mutations. Three retinal regions were selected in each eye: near the fovea-like area, near the optic nerve, both in the tapetal area, and inferior to the optic nerve in the non-tapetal area.

Inherited Retinal Degeneration Caused by Dehydrodolichyl Diphosphate Synthase Mutation-Effect of an Modifier Variant.

Modern advances in disease genetics have uncovered numerous modifier genes that play a role in the severity of disease expression. One such class of genetic conditions is known as inherited retinal degenerations (IRDs), a collection of retinal degenerative disorders caused by mutations in over 300 genes. A single missense mutation (K42E) in the gene encoding the enzyme dehydrodolichyl diphosphate synthase (DHDDS), which is required for protein N-glycosylation in all cells and tissues, causes -IRD (retinitis pigmentosa type 59 (RP59; OMIM #613861)).

Ophthalmic applicator displacement as a method of treating large diffuse uveal melanomas.

Purpose: The presentation of results of an ophthalmic plaque displacement as a brachytherapy treatment method of large diffuse uveal melanomas.

Material And Methods: This was a retrospective analysis of treatment results of 9 patients with large diffuse uveal melanomas using ophthalmic plaque displacement. Patients were treated with this method in our center between 2012 and 2021 (last follow-up visit in 2023).

Durable vision improvement after a single intravitreal treatment with antisense oligonucleotide in 90-LCA: Replication in two eyes.

Purpose: An intravitreally injected antisense oligonucleotide, sepofarsen, was designed to modulate splicing within retinas of patients with severe vision loss due to deep intronic c.2991 + 1655A > G variant in the gene. A previous report showed vision improvements following a single injection in one eye with unexpected durability lasting at least 15 months.

Photoreceptor Function and Structure in Autosomal Dominant Vitelliform Macular Dystrophy Caused by BEST1 Mutations.

Purpose: The purpose of this study was to evaluate rod and cone function and outer retinal structure within macular lesions, and surrounding extralesional areas of patients with autosomal dominant Best vitelliform macular dystrophy caused by BEST1 mutations.

Methods: Seventeen patients from seven families were examined with dark- and light-adapted chromatic perimetry and optical coherence tomography. Subsets of patients had long-term follow-up (14-22 years, n = 6) and dark-adaptation kinetics measured (n = 5).

Photoreceptor function and structure in retinal degenerations caused by biallelic BEST1 mutations.

The only approved retinal gene therapy is for biallelic RPE65 mutations which cause a recessive retinopathy with a primary molecular defect located at the retinal pigment epithelium (RPE). For a distinct recessive RPE disease caused by biallelic BEST1 mutations, a pre-clinical proof-of-concept for gene therapy has been demonstrated in canine eyes. The current study was undertaken to consider potential outcome measures for a BEST1 clinical trial in patients demonstrating a classic autosomal recessive bestrophinopathy (ARB) phenotype.

Night vision restored in days after decades of congenital blindness.

Signaling of vision to the brain starts with the retinal phototransduction cascade which converts visible light from the environment into chemical changes. Vision impairment results when mutations inactivate proteins of the phototransduction cascade. A severe monogenically inherited blindness, Leber congenital amaurosis (LCA), is caused by mutations in the gene, leading to a molecular defect in the production of cyclic GMP, the second messenger of phototransduction We studied two patients with -LCA who were undergoing gene augmentation therapy.

Restoration of Cone Sensitivity to Individuals with Congenital Photoreceptor Blindness within the Phase 1/2 Sepofarsen Trial.

Purpose: To understand consequences of reconstituting cone photoreceptor function in congenital binocular blindness resulting from mutations in the () gene.

Design: Phase 1b/2 open-label, multicenter, multiple-dose, dose-escalation trial.

Participants: A homogeneous subgroup of 5 participants with light perception (LP) vision at the time of enrollment (age range, 15-41 years) selected for detailed analyses.

Guidelines regarding ineffective maintenance of organ functions (futile therapy) in paediatric intensive care units.

In Poland, guidelines for the management of ineffective treatment of children in neonatal and paediatric departments developed by the Polish Neonatal Society and the Polish Paediatric Society, have been published. The specific problems of futile therapy in paediatric anaesthesiology and intensive care units should be defined and solved separately. For this purpose, the guidelines presented below were prepared.

Neurological Complications of Biological Treatment of Psoriasis.

In the available literature, little attention has been paid to the assessment of psoriasis and the biological therapy used for it and the nervous system. The purpose of this article is to discuss the relationship between psoriasis and the nervous system as well as to analyze the mechanisms that lead to neurological complications during anticytokine therapies in psoriasis. However, this connection requires further analysis.

Crosstalk between Statins and Cancer Prevention and Therapy: An Update.

The importance of statins in cancer has been discussed in many studies. They are known for their anticancer properties against solid tumors of the liver or lung, as well as diffuse cancers, such as multiple myeloma or leukemia. Currently, the most commonly used statins are simvastatin, rosuvastatin and atorvastatin.

Macular Rod Function in Retinitis Pigmentosa Measured With Scotopic Microperimetry.

Purpose: To investigate the validity and reliability of macular rod photoreceptor function measurement with a microperimeter.

Methods: Macular sensitivity in dark-adapted retinitis pigmentosa (RP) patients (22 eyes; 9-67 years of age) and controls (five eyes; 22-55 years of age) was assessed with a modified Humphrey field analyzer (mHFA), as well as a scotopic microperimeter (Nidek MP-1S). Sensitivity loss (SL) was estimated at rod-mediated locations.

Measures of Function and Structure to Determine Phenotypic Features, Natural History, and Treatment Outcomes in Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) are at the forefront of innovative gene-specific treatments because of the causation by single genes, the availability of microsurgical access for treatment delivery, and the relative ease of quantitative imaging and vision measurement. However, it is not always easy to choose a priori, from scores of potential measures, an appropriate subset to evaluate efficacy outcomes considering the wide range of disease stages with different phenotypic features. This article reviews measurements of visual function and retinal structure that our group has used over the past three decades to understand the natural history of IRDs.

Home Artificial Nutrition in Polish Children: An Analysis of 9-Year National Healthcare Provider Data.

Background: Home artificial nutrition (HAN) is a developing method of treatment that reduces the need for hospitalizations. The epidemiology of pediatric HAN in Poland has not yet been covered in detail. This study is a longitudinal nationwide analysis of incidence, prevalence, and patients' profile for HAN in Polish children.

Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report.

Leber congenital amaurosis due to CEP290 ciliopathy is being explored by treatment with the antisense oligonucleotide (AON) sepofarsen. One patient who was part of a larger cohort (ClinicalTrials.gov NCT03140969 ) was studied for 15 months after a single intravitreal sepofarsen injection.