PURPOSE:Collagen type 4 alpha 1 (COL4A1) and alpha 2 (COL4A2) chains, encoded by COL4A1 and COL4A2, are essential for basement membrane integrity, contributing to structural stability and cell regulation. Pathogenic variants in these genes cause a spectrum of autosomal dominant and, more rarely, autosomal recessive disorders, which are collectively known as COL4A1/A2-related disorders. These multisystem disorders can include neurologic, ophthalmologic, renal, and other organ system pathology and vary widely in symptoms, complicating diagnosis and management. METHODS:Using a modified eDelphi method, we obtained consensus from international experts across medical subspecialties on the evaluation and management of COL4A1/A2-related disorders, with consensus set at ≥70% agreement. RESULTS:Consensus was achieved on recommendations for evaluating and managing these conditions. CONCLUSION:Genetic testing and counseling are advised for individuals showing symptoms of COL4A1/A2-related disorders and for at-risk relatives. Given the complexity and rarity of these disorders, management requires a multidisciplinary approach informed by current understanding of disease mechanisms. Recommended care includes neurological and ophthalmological imaging and monitoring of cardiovascular and renal function. Ongoing research is critical to uncover genotype-phenotype links and potential modifiers, with clinical research participation encouraged to advance knowledge and treatments.

COL4A1/2 variants are associated with highly variable multiorgan manifestations. Depicting the whole clinical spectrum of COL4A1/2-related manifestations is challenging, and there is no consensus on management and preventative strategies. Based on a systematic review of current evidence on COL4A1/2-related disease, we developed a clinical questionnaire that we administered to 43 individuals from 23 distinct families carrying pathogenic variants. In this cohort, we extended ophthalmological and cardiological examinations to asymptomatic individuals and those with only limited or mild, often nonspecific, clinical signs commonly occurring in the general population (i.e., oligosymptomatic). The most frequent clinical findings emerging from both the literature review and the questionnaire included stroke (203/685, 29.6%), seizures or epilepsy (199/685, 29.0%), intellectual disability or developmental delay (168/685, 24.5%), porencephaly/schizencephaly (168/685, 24.5%), motor impairment (162/685, 23.6%), cataract (124/685, 18.1%), hematuria (63/685, 9.2%), and retinal arterial tortuosity (58/685, 8.5%). In oligosymptomatic and asymptomatic carriers, ophthalmological investigations detected retinal vascular tortuosity (5/13, 38.5%), dysgenesis of the anterior segment (4/13, 30.8%), and cataract (2/13, 15.4%), while cardiological investigations were unremarkable except for mild ascending aortic ectasia in 1/8 (12.5%). Our multimodal approach confirms highly variable penetrance and expressivity in COL4A1/2-related conditions, even at the intrafamilial level with neurological involvement being the most frequent and severe finding in both children and adults. We propose a protocol for prevention and management based on individualized risk estimation and periodic multiorgan evaluations.

Biallelic mutations in the RPE65 gene affect nearly 8% of Leber Congenital Amaurosis and 2% of Retinitis Pigmentosa cases. Voretigene neparvovec (VN) is the first gene therapy approach approved for their treatment. To date, real life experience has demonstrated functional improvements following VN treatment, which are consistent with the clinical trials outcomes. However, there is currently no consensus on the characteristics for eligibility for VN treatment. We reviewed relevant literature to explore whether recommendations on patient eligibility can be extrapolated following VN marketing. We screened 166 papers through six research questions, following scoping reviews methodology, to investigate: (1) the clinical and genetic features considered in VN treatment eligibility; (2) the psychophysical tests and imaging modalities used in the pre-treatment and follow-up; (3) the potential correlations between visual function and retinal structure that can be used to define treatment impact on disease progression; (4) retinal degeneration; (5) the most advanced testing modalities; and (6) the impact of surgical procedure on treatment outcomes. Current gaps concerning patients’ eligibility in clinical settings, such as pre-treatment characteristics and outcomes are not consistently reported across the studies. No upper limit of retinal degeneration can be defined as the univocal factor in patient eligibility, although evidence suggested that the potential for function rescue is related to the preservation of photoreceptors before treatment. In general, paediatric patients retain more viable cells, present a less severe disease stage and show the highest potential for improvements, making them the most suitable candidates for treatment.

Purpose: To report a case of a boy with acute keratoplasty rejection manifesting 12 days after receiving BNT162b2 messenger RNA (mRNA) vaccine for COVID-19. Study design: A case report. Results: A 15-year-old boy with a history of penetrating keratoplasty due to acanthamoeba keratitis developed corneal decompensation 12 days after BNT162b2 messenger RNA vaccine for COVID-19 disease. One-week treatment with topical Dexamethasone 2% eye drops resulted in a complete resolution of corneal edema. Conclusions: This case suggests that BNT162b2 messenger RNA (mRNA) vaccine can be associated with acute keratoplasty rejection in children, which responds completely to topical steroids. Ophthalmologists should be aware of this risk of cornea decompensation after COVID-19 vaccine in children who received a cornea transplant.

Interdural dermoid cysts (DCs).of the cavernous sinus (CS), located between the outer (dural) and inner layer (membranous) of the CS lateral wall, are rare lesions in children. The authors report on a 5-year-old boy with third cranial nerve palsy and exophthalmos who underwent gross-total removal of an interdural DC of the right CS via a frontotemporal approach. The patient had a good outcome and no recurrence at the 12-month follow-up. To the best of the authors' knowledge this is the second pediatric case of interdural DC described in the literature.

Pore pressure variation resulting from geological CO2 storage may compromise reservoir, caprock and fault integrity. Therefore, we investigate the mechanical impact of industrial-scale CO2 storage at a prospective Danish site by coupled 3D hydro-mechanical simulations carried out by two independent modelling groups. Even though the two chosen modelling strategies are not identical, simulation results demonstrate that storage integrity is maintained at any time. Vertical displacements are mainly determined by hydraulic fault conductivity influencing spatial pore pressure elevation. The introduced fault zone implementation in the hydro- mechanical model allows for localization of potential leakage pathways for formation fluids along the fault plane.

Vaporisation of water during dry CO2 injection can cause salt precipitation and lead to significant reduction in injectivity. Research described in this paper aimed at improving the understanding of the halite scaling process through experimental and numerical investigations. Experimental results indicated porosity reductions of about 3 - 5% and permeability reduction between 13 to 75%. Numerical simulation results have shown that halite scaling can have a significant impact on field operations. They also suggested that, salt precipitation can occur at the caprock interface increasing the sealing capacity around the wellbore.

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Carbon Capture and Storage (CCS) is recognised as one of the most effective technologies for reducing CO2 emissions in the short to medium term. From a capacity point of view, deep saline aquifers offer the greatest potential. As supercritical CO2 is injected in the aquifer, a variety of strongly coupled physical and chemical processes occur. Among these various mechanisms, vaporisation of water requires particular attention as it can cause salt precipitation, which reduces the porosity and the permeability of the reservoir in the vicinity of the wellbore. This can lead to significant reduction in injectivity. Research described in this paper aims to provide a relationship between porosity changes and resulting permeability variations representing the effect of salt precipitation due to vaporisation. Supercritical CO2 core flooding experiments were conducted on a St. Bees sandstone core with fully saturated saline water obtaining several levels of alteration due to halite scaling. Porosity reduction ranged from around 4 to 29% of the initial value. Permeability impairments ranged from 30 to 86%. Results were used to calibrate a Verma-Pruess “tube-in-series” model which can be used to obtain more accurate results from numerical simulations.

Carbon dioxide capture and storage (CCS) technology is gaining credibility as the best short to medium term solution for significantly reducing net carbon emissions into the atmosphere. From a capacity point of view, deep saline aquifers offer the greatest potential for CO2 storage. In this respect, well injectivity is considered a key technical and economical issue. Rock/fluid interactions - dissolution/precipitation of minerals, in particular carbonates - are currently considered as one of the principal reasons for wellbore injectivity changes in aquifers.This research investigated the mechanisms involved in injectivity losses through experimental and theoretical methods. The impact on injectivity of permeability changes occurring at various distances from the wellbore was studied using an idealised CO2 injection well flow model. A new experimental set-up was used to investigate the effect on dissolution/precipitation mechanisms of the pressure and temperature changes that the fluid is subjected to as it advances from the wellbore.Numerical modelling of the injection wellbore has shown that changes in the petrophysical properties of the reservoir several metres away from the wellbore can still have a significant impact on injectivity. As indicated by the experimental research carried out, pressure and temperature gradients that exist inside the reservoirs may lead to re-precipitation in the far field, however no significant permeability and porosity changes were detected to suggest major losses of injectivity due to these effects. (C) 2010 Elsevier Ltd. All rights reserved.