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Diagnostics (Basel, Switzerland) Apr 2024The imagistic evaluation of non-neovascular age-related macular degeneration (AMD) is crucial for diagnosis, monitoring progression, and guiding management of the... (Review)
Review
The imagistic evaluation of non-neovascular age-related macular degeneration (AMD) is crucial for diagnosis, monitoring progression, and guiding management of the disease. Dry AMD, characterized primarily by the presence of drusen and retinal pigment epithelium atrophy, requires detailed visualization of the retinal structure to assess its severity and progression. Several imaging modalities are pivotal in the evaluation of non-neovascular AMD, including optical coherence tomography, fundus autofluorescence, or color fundus photography. In the context of emerging therapies for geographic atrophy, like pegcetacoplan, it is critical to establish the baseline status of the disease, monitor the development and expansion of geographic atrophy, and to evaluate the retina's response to potential treatments in clinical trials. The present review, while initially providing a comprehensive description of the pathophysiology involved in AMD, aims to offer an overview of the imaging modalities employed in the evaluation of non-neovascular AMD. Special emphasis is placed on the assessment of progression biomarkers as discerned through optical coherence tomography. As the landscape of AMD treatment continues to evolve, advanced imaging techniques will remain at the forefront, enabling clinicians to offer the most effective and tailored treatments to their patients.
PubMed: 38611677
DOI: 10.3390/diagnostics14070764 -
Molecular Vision 2024Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2...
PURPOSE
Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2 Korean families.
METHODS
The regions associated with NCMD were analyzed with genome sequencing, and variants were filtered based on the minor allele frequency (0.5%) and heterozygosity. Non-coding variants were functionally annotated using multiple computational tools.
RESULTS
We identified two rare novel variants, chr6:g.99,598,914T>C (hg38; V17) and chr6:g.99,598,926G>A (hg38; V18) upstream of in families A and B, respectively. In Family 1, Grade 2 NCMD and a best-corrected visual acuity of 20/25 and 20/200 in the right and left eyes, respectively, were observed. In Family B, all affected individuals had Grade 1 NCMD with characteristic confluent drusen at the fovea and a best-corrected visual acuity of 20/20 in both eyes. These two variants are 10-22 bp downstream of the reported V10 variant within the DNase1 hypersensitivity site. This site is associated with progressive bifocal chorioretinal atrophy and congenital posterior polar chorioretinal hypertrophy and lies in the putative enhancer site of .
CONCLUSION
We identified two novel NCMD variants in the Korean population and further validated the regulatory role of the DNase1 hypersensitivity site upstream of .
Topics: Humans; Corneal Dystrophies, Hereditary; Fovea Centralis; Nucleotides; Pedigree; Republic of Korea
PubMed: 38601016
DOI: No ID Found -
Ophthalmology. Retina Apr 2024In this study, we identify risk factors that predict the progression of acquired vitelliform lesions (AVLs) over time.
PURPOSE
In this study, we identify risk factors that predict the progression of acquired vitelliform lesions (AVLs) over time.
DESIGN
Retrospective cohort study.
SUBJECTS
One hundred sixty-three eyes of 132 patients with a diagnosis of intermediate age-related macular degeneration (iAMD) with AVL.
METHODS
This retrospective study evaluated consecutive eyes with AMD from a retina clinic population and included 1181 patients and 2362 eyes. After excluding cases with associated geographic atrophy, macular neovascularization (MNV), vitreomacular traction, and those with <2 years of follow-up data, the final analysis cohort consisted of 163 eyes (132 patients) with ≥1 AVL. The first available visit in which an AVL was evident was considered the baseline visit, and follow-up data were collected from a visit 2 years (± 3 months) later. Progression outcomes at the follow-up visit were classified into 6 categories: resorbed, collapsed, MNV, stable, increasing, and decreasing. Subsequently, we analyzed the baseline characteristics for each category and calculated odds ratios (ORs) to predict these various outcomes.
MAIN OUTCOME MEASURES
The study focused on identifying predictive factors influencing the evolution of AVL in iAMD eyes.
RESULTS
In total, 163 eyes with AVL had follow-up data at 2 years. The collapsed group demonstrated a significantly greater baseline AVL height and width compared with other groups (P < 0.001). With regard to qualitative parameters, subretinal drusenoid deposits (SDDs) and intraretinal hyperreflective foci (IHRF) at the eye level, AVL located over drusen, and IHRF and external limiting membrane disruption over AVL were significantly more prevalent in the collapsed group compared with other groups (P < 0.05 for all comparisons). Odds ratios for progressing to atrophy after 2 years of follow-up, compared with the resorbed group, were significant for SDD (OR, 2.82; P = 0.048) and AVL height (OR, 1.016; P = 0.006).
CONCLUSIONS
The presence of SDDs and greater AVL height significantly increases the risk of developing atrophy at the location of AVL after 2 years of follow-up. These findings may be of value in risk prognostication and defining patient populations for inclusion in future early intervention trials aimed at preventing progression to atrophy.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38599379
DOI: 10.1016/j.oret.2024.04.003 -
International Journal of Retina and... Apr 2024Artificial intelligence (AI) has emerged as a transformative technology across various fields, and its applications in the medical domain, particularly in ophthalmology,... (Review)
Review
Artificial intelligence (AI) has emerged as a transformative technology across various fields, and its applications in the medical domain, particularly in ophthalmology, has gained significant attention. The vast amount of high-resolution image data, such as optical coherence tomography (OCT) images, has been a driving force behind AI growth in this field. Age-related macular degeneration (AMD) is one of the leading causes for blindness in the world, affecting approximately 196 million people worldwide in 2020. Multimodal imaging has been for a long time the gold standard for diagnosing patients with AMD, however, currently treatment and follow-up in routine disease management are mainly driven by OCT imaging. AI-based algorithms have by their precision, reproducibility and speed, the potential to reliably quantify biomarkers, predict disease progression and assist treatment decisions in clinical routine as well as academic studies. This review paper aims to provide a summary of the current state of AI in AMD, focusing on its applications, challenges, and prospects.
PubMed: 38589936
DOI: 10.1186/s40942-024-00549-1 -
Ophthalmic Genetics Apr 2024To describe the phenotype and genotype of 10 Brazilian patients with variants in , posterior microphthalmos and retinal findings.
BACKGROUND
To describe the phenotype and genotype of 10 Brazilian patients with variants in , posterior microphthalmos and retinal findings.
METHODS
Complete ophthalmological evaluation was done at 4 different Brazilian centers. Genetic analysis was performed using commercial next generation sequencing panels for inherited retinal disorders.
RESULTS
Ages of the patients ranged from 10 to 65 years and visual acuities from 0,05 to no perception of light. All were hyperopes (+4,25 to + 17,50) with a short axial length (14,4 mm to 18 mm). Common posterior segment features, though not present in all, were optic disc drusen (5/10), foveoschisis (5/10) and retinal pigmentary changes (8/10). Isolated patients presented with macular atrophy, serous retinal detachment, and chorioretinal folds. The most common variant in found in our patients was a deletion in exon 5 (c.498delC; p.Asn267Thrfs *25), present in all except 2 patients. Other variants found were c.523C>T (p.Gln175*), c.298delG (p.Ala100Argfs *37), c.666del (p.Thr223Argfs *83) and the novel variant c.257C>A (p.Ala86Asp).
CONCLUSIONS
This is the first report of Brazilian patients with posterior microphthalmos and pathogenic variants in and the first describe of the variant p.Ala86Asp in literature. Our cases confirm the previously reported phenotype of high hyperopia, optic disc drusen, alterations in foveal architecture, retinal pigmentary changes with loss of photoreceptor function and visual field constriction. Report of such a rare condition is important to increase awareness to the phenotype of posterior microphthalmia with associated retinal conditions.
PubMed: 38557281
DOI: 10.1080/13816810.2024.2322650 -
European Journal of Ophthalmology Mar 2024Demonstrate through objective multidisciplinary imaging that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to both coexistent...
BACKGROUND/AIMS
Demonstrate through objective multidisciplinary imaging that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to both coexistent valvular heart disease (VHD) and reduced systemic perfusion via cardiac index (CI).
METHODS
Post-hoc analysis of cross-sectional study. 200 intermediate AMD (iAMD) subjects were assigned by masked readers to two groups: SDD (with or without drusen) and drusen (only) based on multimodal ophthalmic imaging. 65 transthoracic echocardiograms (TTEs) reports were available for cardiologist evaluation of VHD severity of the four cardiac valves and the presences of precursor lesions of aortic sclerosis (ASc) and mitral annular calcification (MAC). Necessary parameters to calculate CI were also obtained. Univariate testing was performed using Fisher's Exact test and t-test.
RESULTS
82.6% (19/23) of the iAMD subjects with at least one moderate/severe VHD had concurrent SDDs ( = 0.0040). All cases of aortic regurgitation (6/6, = 0.0370) and mitral regurgitation (13/13, = 0.0004) were found with coexisting SDDs. Stenotic VHD was not significantly associated with SDDs, however 70.7% of subjects with ASc (29/41, = 0.0108) and 76.0% of subjects with MAC (19/25, 0.0377) had coexisting SDDs. CI was available in 48 subjects and was significantly below normal levels in the SDD cohort (mean CI SDD 1.95 ± 0.60 L/min/m, non-SDD 2.71 ± 0.73 L/min/m, = 0.0004).
CONCLUSIONS
Several specific VHDs have been found associated with the SDD form of AMD. Decreased systemic perfusion as measured by CI was also associated with SDDs, which supports a perfusion hypothesis of SDD pathogenesis. Further research is warranted to understand the relationship between cardiovascular disease and SDDs.
PubMed: 38545630
DOI: 10.1177/11206721241244413 -
Acta Ophthalmologica Mar 2024To examine age-related macular degeneration (AMD) and retinal pigment epithelium (RPE)-Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs.
PURPOSE
To examine age-related macular degeneration (AMD) and retinal pigment epithelium (RPE)-Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs.
METHODS
In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35-degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age-Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE-BrM complex volume was calculated with the Orion™ software. The worse eye according to AREDS classification was used for the analysis.
RESULTS
Twenty-nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2-4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3-4) versus the other being unaffected (AREDS 1). The within-pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418-0.792). In multivariate analysis intermediate and late AMD as well as age associated with RPE-BrM complex volume. RPE-BrM complex volume showed a within twin pair correlation, r = 0.430 (95% confidence interval 0.172-0.688, p < 0.01).
CONCLUSION
A substantial proportion of monozygotic twin pairs are discordant with regard to age-related macular degeneration phenotype. RPE-BrM complex volume associated with age and intermediate and late AMD.
PubMed: 38528623
DOI: 10.1111/aos.16671 -
Biological & Pharmaceutical Bulletin 2024Recently, mitochondrial dysfunction has gained attention as a causative factor in the pathogenesis and progression of age-related macular degeneration (AMD)....
Recently, mitochondrial dysfunction has gained attention as a causative factor in the pathogenesis and progression of age-related macular degeneration (AMD). Mitochondrial damage plays a key role in metabolism and disrupts the balance of intracellular metabolic pathways, such as oxidative phosphorylation (OXPHOS) and glycolysis. In this study, we focused on oxidized low-density lipoprotein (ox-LDL), a major constituent of drusen that accumulates in the retina of patients with AMD, and investigated whether it could be a causative factor for metabolic alterations in retinal pigment epithelial (RPE) cells. We found that prolonged exposure to ox-LDL induced changes in fatty acid β-oxidation (FAO), OXPHOS, and glycolytic activity and increased the mitochondrial reactive oxygen species production in RPE cells. Notably, the effects on metabolic alterations varied with the concentration and duration of ox-LDL treatment. In addition, we addressed the limitations of using ARPE-19 cells for retinal disease research by highlighting their lower barrier function and FAO activity compared to those of induced pluripotent stem cell-derived RPE cells. Our findings can aid in the elucidation of mechanisms underlying the metabolic alterations in AMD.
Topics: Humans; Retinal Pigment Epithelium; Macular Degeneration; Lipoproteins, LDL; Oxidative Stress; Epithelial Cells; Retinal Pigments
PubMed: 38508744
DOI: 10.1248/bpb.b23-00849 -
Graefe's Archive For Clinical and... Mar 2024Age-related macular degeneration (AMD) is the leading sight-threatening disease in developed countries. On the other hand, recent studies indicated an ethnic variation... (Review)
Review
The hypothetical molecular mechanism of the ethnic variations in the manifestation of age-related macular degeneration; focuses on the functions of the most significant susceptibility genes.
Age-related macular degeneration (AMD) is the leading sight-threatening disease in developed countries. On the other hand, recent studies indicated an ethnic variation in the phenotype of AMD. For example, several reports demonstrated that the incidence of drusen in AMD patients is less in Asians compared to Caucasians though the reason has not been clarified yet. In the last decades, several genome association studies have disclosed many susceptible genes of AMD and revealed that the association strength of some genes was different among races and AMD phenotypes. In this review article, the essential findings of the clinical studies and genome association studies for the most significant genes CFH and ARMS2/HTRA1 in AMD of different races are summarized, and theoretical hypotheses about the molecular mechanisms underlying the ethnic variation in the AMD manifestation mainly focused on those genes between Caucasians and Asians are discussed.
PubMed: 38507046
DOI: 10.1007/s00417-024-06442-9 -
BMC Ophthalmology Mar 2024In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency decreases after the first year, while outcomes remain primarily related to...
INTRODUCTION
In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency decreases after the first year, while outcomes remain primarily related to the number of injections. To the best of our knowledge, there are no reports of maintaining the best corrected visual acuity (BCVA) for more than 7 years in extension studies.
OBJECTIVE
To report a 12-year follow-up of a real-world case of nAMD where BCVA was preserved from declining.
CASE DESCRIPTION
A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. Examination showed a BCVA of 85 letters (L) in the right eye (RE) and 35 L in the LE. Fundus examination showed drusen in the macula of both eyes. Macular edema, loss of the macular lutein pigment, macular hypo/hyperpigmentation were observed in the LE. A diagnosis of Type 2 choroidal neovascular membrane (CNV) in the LE was established and within two months a Type 1 CNV developed in the RE. She undergone 9 injections of bevacizumab (six) and ranibizumab (three) within the first year of treatment in the LE and seven injections of ranibizumab within the first year in the RE.
RESULTS
The LE had a mean of 5.2 injections per year, and the RE had a mean of 7.5 injections per year, from 2010 to 2022. RE's BCVA dropped by 8L (85L to 77L) and central retinal thickness (CRT) increased by 16 μm (276 μm to 292 μm) while LE's BCVA increased by 28L (35L to 63L) and CRT decreased by 369 μm (680 μm to 311 μm), at the twelfth year.
CONCLUSIONS
Although the final visual outcome depends on baseline BCVA and lesion type or size, the number of injections is paramount in preserving BCVA and achieving favorable functional outcomes in nAMD, even after 12 years of treatment.
Topics: Humans; Female; Aged; Ranibizumab; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Intravitreal Injections; Macular Edema; Choroidal Neovascularization; Visual Acuity
PubMed: 38494487
DOI: 10.1186/s12886-024-03387-9