Publications by authors named "Martin McKibbin"
Loss of glycogen myophosphorylase (PYGM) expression results in an inability to break down muscle glycogen, leading to McArdle disease-an autosomal recessive metabolic disorder characterized by exercise intolerance and muscle cramps. While previously considered relatively benign, this condition has recently been associated with pattern dystrophy in the retina, accompanied by variable sight impairment, secondary to retinal pigment epithelial (RPE) cell involvement. However, the pathomechanism of this condition remains unclear.
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- Biallelic mutations in the DRAM2 gene cause a form of vision loss called CORD21, which usually shows up between ages 30 and 60.
- Researchers studied retinal organoids and retinal pigment epithelium (RPE) cells from patients with CORD21 to understand the gene's role in retinal degeneration.
- They discovered that DRAM2 is involved in lipid metabolism, lysosomal function, and cellular processes, indicating its importance for the health of photoreceptors and RPE cells.
Objective: To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD).
Methods: Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response.
Purpose: To describe the prevalence of subretinal transient hyporeflectivity (STHR) in exudative neovascular age-related macular degeneration (nAMD) and its response to a loading phase of aflibercept.
Methods: Optical coherence tomography (OCT) scans of treatment-naïve nAMD patients captured at baseline and after a loading phase of aflibercept were graded for presence of STHR, defined as a small, well-defined, round, subretinal, hyporeflective area, delimited between the ellipsoid zone (EZ) and the retinal pigmented epithelium/Bruch membrane complex. OCT parameters recorded were macular neovascularisation (MNV) subtypes, location of retinal fluids (subretinal fluid, SRF and intraretinal fluid, IRF), central retinal and choroidal thickness.
Article Synopsis
- - The spliceosomal protein PRPF8's carboxy-terminus mutation is linked to retinitis pigmentosa-type 13, but its specific role in human splicing and tissue-specificity is not well understood.
- - Using patient-derived stem cells with a specific PRPF8 mutation, researchers observed retinal cell defects like photoreceptor loss and ciliary issues, highlighting retinal-specific endophenotypes.
- - Detailed analyses showed that PRPF8 influences spliceosome function, affecting 5'-splice site selection and leading to splicing abnormalities, which could provide insights for future therapeutic strategies for retinal diseases.
Article Synopsis
- The study aimed to evaluate visual acuity and structural biomarkers in individuals with neovascular age-related macular degeneration (nAMD) before and 24 months after standard treatment, focusing on both the first and newly affected second eye.
- Conducted as a prospective observational study across 22 centers, it included older adults with new onset nAMD in their first eye, utilizing various assessments like OCT and quality of life measurements.
- Results showed that the second eye, diagnosed early, had significantly better visual acuity and lower rates of certain structural issues compared to the first eye, although it experienced a higher prevalence of subretinal fluid after 24.9 months. *
Article Synopsis
- - The study aimed to compare baseline characteristics of patients with and without early residual fluid (ERF) following treatment for neovascular age-related macular degeneration (nAMD) using aflibercept.
- - Out of 2128 patients, 50% experienced ERF after the loading phase, with specific characteristics like increased central subfield thickness (CST) and certain forms of fluid observed to correlate with the presence of ERF.
- - The findings suggest that patients with CST greater than or equal to 418 microns and certain fluid types may need additional monthly treatments before changing their treatment schedule.
Purpose: To study associations of optical coherence tomography (OCT) features with presenting visual acuity (VA) in treatment naive neovascular age-related macular degeneration (nAMD).
Methods: Patients with nAMD initiated on aflibercept therapy were recruited from December 2019 to August 2021. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA (VA ≥ 68 ETDRS letters, Snellen ≥ 6/12) and poor VA (VA < 54 letters, Snellen < 6/18) were analysed using Generalised Estimating Equations to account for inter-eye correlation.
Introduction: RPGR ORF15 is an exon present almost exclusively in the retinal transcript of RPGR. It is purine-rich, repetitive and notoriously hard to sequence, but is a hotspot for mutations causing X-linked retinitis pigmentosa.
Methods: Long-read nanopore sequencing on MinION and Flongle flow cells was used to sequence RPGR ORF15 in genomic DNA from patients with inherited retinal dystrophy.
Patients diagnosed with exudative neovascular age-related macular degeneration are commonly treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, response to treatment is heterogeneous, without a clinical explanation. Predicting suboptimal response at baseline will enable more efficient clinical trial designs for novel, future interventions and facilitate individualised therapies.
View Article and Find Full Text PDFShort-read next-generation sequencing has revolutionized our ability to identify variants underlying inherited diseases; however, it does not allow the phasing of variants to clarify their diagnostic interpretation. The advent of widespread, increasingly accurate long-read sequencing has opened up new applications not currently available through short-read next-generation sequencing. One such use is the ability to phase variants to clarify their diagnostic interpretation and to investigate the increasingly prevalent role of cis-acting variants in the pathogenesis of the inherited disease, so-called complex alleles.
View Article and Find Full Text PDFBackground: The widespread adoption of exome sequencing has greatly increased the rate of genetic diagnosis for inherited conditions. However, the detection and validation of large deletions remains challenging. While numerous bioinformatics approaches have been developed to detect deletions from whole - exome sequencing and targeted panels, further work is typically required to define the physical breakpoints or integration sites.
View Article and Find Full Text PDFRetinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability.
View Article and Find Full Text PDFAims: The aim of the study was to investigate non-persistence with treatment for neovascular age-related macular degeneration (NvAMD) before day 720 (24 months) after initiation, explore associations with baseline characteristics and variation between sites.
Methods: Anonymised demographic and clinical data were extracted from electronic medical records at treating National Health Service (NHS) Trusts for NvAMD eyes starting intra-vitreal therapy from 2017 to 2018. Time to non-persistence with treatment, defined as no recorded attendance for either monitoring or treatment for a period ≥6 months, was visualised with a Kaplan-Meier survival plot.
Purpose: To study the treatment patterns, visual outcomes and safety profile of intravitreal dexamethasone implant (IDI) used for the treatment of macular edema secondary to retinal vein occlusion.
Methods: Up to 2 years of routinely collected anonymized data within electronic medical record systems were remotely extracted from 16 centers. The outcome measures include visual outcome, number of injections, and safety measures, including the rate of intraocular pressure (IOP) rise, frequency of IOP-lowering medication usage, and cataract surgery rates.
Article Synopsis
- Macular dystrophies are inherited retinal disorders that lead to central vision loss and are identified as rare individually but common overall.
- A specialized genetic testing method called Single molecule Molecular Inversion Probes (smMIPs) was successfully used to analyze 57 cases of macular dystrophy in the UK, revealing a high solve rate of 63.2%.
- The study found that most variants in Caucasian STGD1 cases are well-known, and it established that associated diseases can often be differentiated from other macular dystrophies through thorough clinical evaluation.
Purpose: To assess the visual outcome of cataract surgery in patients with retinitis pigmentosa (RP).
Design: Retrospective, noncomparative clinical study.
Methods: Preoperative, intraoperative, and postoperative data of patients with RP who were undergoing cataract surgery were collected from several expertise centers across Europe.
Objective: To record visual acuity outcomes after 12 months of treatment for neovascular age-related macular degeneration (NvAMD), investigate variation between sites and explore associations with baseline characteristics and care processes.
Methods And Analysis: Anonymised demographic and clinical data were extracted from electronic medical records at treating National Health Service (NHS) Trusts. Associations with acuity outcomes were investigated using multivariate linear and logistic regression.
Article Synopsis
- - The study aimed to identify the characteristics and causes of macular disease in a group of patients from six families, ranging from ages 20 to 78, including one case of age-related macular degeneration.
- - All eight patients were found to carry the same genetic deletion affecting three specific genes, which was not present in a large control group, indicating a potential link between this deletion and their macular disease.
- - The findings suggest that, contrary to previous beliefs about the CRX gene, a complete deletion of the gene is associated with a dominant form of late-onset macular disease, challenging earlier understandings of its role.
Purpose: To describe the clinical phenotype and genetic basis of non-syndromic retinitis pigmentosa (RP) in one family and two sporadic cases with biallelic mutations in the transcription factor neural retina leucine zipper (.
Methods: Exome sequencing was performed in one affected family member. Microsatellite genotyping was used for haplotype analysis.
Purpose: To investigate the molecular basis of recessively inherited congenital cataract, microcornea, and corneal opacification with or without coloboma and microphthalmia in two consanguineous families.
Methods: Conventional autozygosity mapping was performed using single nucleotide polymorphism (SNP) microarrays. Whole-exome sequencing was completed on genomic DNA from one affected member of each family.
Objective: To describe the spectrum of Leber congenital amaurosis (LCA) and cone-rod dystrophy (CORD) associated with the GUCY2D gene and to identify potential end points and optimal patient selection for future therapeutic trials.
Design: International, multicenter, retrospective cohort study.
Subjects: Eighty-two patients with GUCY2D-associated LCA or CORD from 54 families.
Prevalence of Dark without Pressure and Angioid Streaks in Sickle Cell Disease.
Ophthalmic Surg Lasers Imaging Retina
November 2021
Article Synopsis
- * In a group of 77 adults with SCD, DWOP was found in 25% of the patients, with different forms, while AS appeared in 3.9% of cases, more frequently in older patients.
- * The findings suggest that the prevalence of DWOP is higher than previously thought, and recognizing the signs can lessen the need for further tests.