Areas Of Atrophy Research Articles

Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months

Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials. To analyze the association between pegcetacoplan and consensus GA SD-OCT end points. This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023. Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month. The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal). Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month. These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors. ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

Correlation Between Blue Fundus Autofluorescence and SD-OCT Measurements of Geographic Atrophy in Dry Age-Related Macular Degeneration

To compare fundus autofluorescence (FAF) and spectral domain optical coherence tomography (OCT) measurements of geographic atrophy (GA) area and to analyze lesion area changes measured by spectral domain OCT in GATHER1. An assessment reliability analysis using prospective, randomized, double-masked phase 2/3 clinical trial data. GATHER1 examined the efficacy and safety of avacincaptad pegol (ACP) for GA treatment. A post hoc analysis was performed to identify correlations between FAF- and OCT-based measurements of GA. GA area was measured on blue-light FAF images using semiautomatic segmentation software with support from OCT and near-infrared imaging. Machine-learning enhanced, multilayer segmentation of OCT scans were reviewed by human readers, and segmentation errors were corrected as needed. GA area was defined as total RPE loss on cross-sectional B scans. Time points included Months 0, 6, 12, and 18. Additionally, OCT-based GA-area changes between ACP and sham were analyzed. There was a strong correlation (r = 0.93) between FAF and OCT GA area measurements that persisted through 18 months. Mean (SD) differences between OCT and FAF GA measurements were negligible: 0.11 mm2 (1.42) at Month 0, 0.03 mm2 (1.62) at Month 6, -0.17 mm2 (1.81) at Month 12, and -0.07 mm2 (1.78) at Month 18. OCT assessments of GA growth revealed a 30% and 27% reduction at Months 12 and 18, respectively, between ACP and sham, replicating FAF measurements from GATHER1. The strong correlation between blue FAF and OCT measurements of GA area supports OCT as a reliable method to measure GA lesion area in clinical trials.

Chorioretinal Atrophic Lesions Evolution in Patients with Quiescent Myopic Choroidal Neovascularization Followed for More Than 10 Years.

To evaluate the progression of chorioretinal atrophic areas associated with myopic choroidal neovascularization (CNV) in high myopic patients followed by a minimum period of 10 years. Patients with myopic CNV lesions that achieved clinical and structural remissions over 10 years of follow-up were included. Medical records were reviewed for CNV characterization and treatment, best-corrected visual acuity at baseline (BCVA0), immediately after the last treatment (BCVA1) and at the latest visit (BCVA2). Fundus autofluorescence (FAF) was used to quantify the amount of atrophic area increase per year associated with the treated myopic CNV lesion. The first FAF performed after treatment suspension (FAF1) was compared with the most recent exam (FAF2). Thirty-six eyes from 36 patients were included. Mean total follow-up was 12.38 ± 2.68 years. Mean number of intravitreal injections (IVI) was 12.50 ± 12.40 and 25% of the eyes had previous treatment with photodynamic therapy (PDT). Mean improvement between BCVA0 and BCVA1 was 5.58 ± 15.98 letters (p < 0.001). However, a drop of 8.03 ± 12.25 letters was noticed between BCVA1 and BCVA2. FAF1 was 6.34 ± 4.92mm2 and increased to 9.88 ± 7.56mm2 (3.54 ± 3.79mm2 variation p < 0.001). The mean growth rate of the atrophic area was 0.89 ± 0.84mm2 per year. BCVA2 negatively correlated with FAF2 (k = -0.498, p = 0.002) being worse in patients with higher atrophic area growth rate (k = -0.341, p = 0.042). Eyes treated with PDT needed less IVI (5.89 ± 5.21 vs 14.70 ± 13.36, p = 0.008) but had larger FAF1 (9.80 ± 5.33 vs 5.19 ± 4.27, p = 0.013) and FAF2 (16.05 ± 7.10 vs 7.83 ± 6.63, p = 0.003). Hypothyroidism was associated with higher atrophy growth rate (1.55 ± 1.15 vs 0.73 ± 0.67, p = 0.016). This research demonstrates the importance of chorioretinal atrophy progression after myopic CNV lesions regression and its impact on visual prognosis, reporting a mean yearly growth of 0.89 mm2 in atrophic areas. Previous treatment with PDT and hypothyroidism were identified as risk factors associated with larger atrophic areas and worse visual outcomes.

Visual disturbances in a 12-year-old male patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome

Abstract: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare condition. Here, we present a case of a male patient with a very unique combination of symptoms that started at the age of 12. Transient symptoms manifested after 4 days of high fever and included lethargy, a loss of appetite, and an inability to recognize faces. After that, the patient was symptom-free for 4 years before he was hospitalized again with a working diagnosis of acute disseminated encephalomyelitis. The ophthalmic symptoms at this stage were photophobia and discrete horizontal nystagmus. One year later, the patient had another seizure and during hospitalization, predominantly displayed cerebral symptoms such as dystaxia, dysmetria, generalized muscle hypotrophy, and absent myotonic reflexes. Like before, an ophthalmic examination demonstrated a best-corrected visual acuity of 1.0 and a normal anterior segment. A fundus examination revealed a slightly rarefied retina, along with areas of perifoveal and parapapillary atrophy, in addition to increased vascular tortuosity. Optical coherence tomography scans of the macula and the optic disc depicted a mild thinning of the retinal layers. Visual field testing showed an isopter contraction with a predominant loss of the temporal visual field in both eyes. A genetic serum analysis was positive for mitochondrial mutation m.3243A&gt;G, and a diagnosis of MELAS was confirmed. The treatment included anticonvulsive drugs and dietary precautions. Patients with MELAS syndrome can manifest a wide range of visual disturbances, meaning that a detailed ophthalmic examination is required.

Peripapillary atrophy area predicts the decrease of macular choroidal thickness in young adults during myopia progression

ObjectiveThis study aimed to investigate the influence of peripapillary atrophy (PPA) area and axial elongation on the longitudinal changes in macular choroidal thickness (ChT) in young individuals with myopia.Methods and...

Oral lichen planus – an oral potentially malignant disorder (OPMD) of the oral cavity

Introduction. Oral lichen planus is a chronic inflammatory disease of unknown etiology, characterized by recurrent lesions, presenting as reticular lesions, sometimes accompanied by atrophic, erosive, and/or ulcerative areas. Despite being one of the most common conditions affecting the oral mucosa, oral lichen planus remains an ailment with undefined etiology and unclear pathogenesis, imprecise management, and uncertain premalignant potential. Materials and methods. A narrative literature review study was conducted. A bibliographic search was carried out in databases such as PubMed, Hinari, SpringerLink, the National Center of Biotechnology Information, and Medline. Articles published from 1990 to 2023 were selected using various combinations of keywords: “oral lichen planus,” and “epidemiology,” “etiology,” “pathogenesis,” “symptoms,” “management,” “histopathology,” and “malignant transformation.” After processing the data from these databases, 475 full articles were found. The final bibliography comprised 50 relevant sources, considered representative of the materials published on the topic of this synthesis article. Results. Oral lichen planus is an inflammatory condition associated with T-cell-mediated immune dysfunction. Triggers include autoimmune responses to local antigens, microorganisms, and stress. The disease results from a complex interplay of host factors, lifestyle, and environmental factors leading to T-cell-mediated immune dysregulation. Diagnosis of oral lichen planus is based on clinical features (multiple, bilateral, symmetrically distributed lesions, occurring most commonly on the buccal mucosa, dorsal tongue surface, and gingiva), histopathological findings (predominantly lymphocytic bandlike infiltrate in the lamina propria, presence of apoptotic cells in the basal cell layer, absence of epithelial dysplasia), and immune-related changes (deposition of fibrinogen along the basement membrane zone, presence of granular fluorescent deposits containing IgA, IgG, and IgM in colloid bodies). Conclusions. Oral lichen planus is a chronic inflammatory condition mediated by T-cells in response to various extrinsic antigens, modified autoantigens, or superantigens, with periods of remission and relapse and the potential for malignant transformation. The etiology and pathogenesis of this condition are complex, diagnosis relies on clinical features, histopathological findings, and immunological data, patient treatment is symptomatic, and the potential for malignant transformation varies. Nevertheless, prospective studies with large sample sizes, adequate treatment duration, and long-term follow-up are needed.

Montreal cognitive assessment in Brazilian adults with sickle cell disease: The burdens of poor sociocultural background.

Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients (n=124; 19-70 years; 56 men; 79 SS, 28 SC, 10 S/β0, 7 S/β+) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging. The Median MoCA score was 23 (8-30); 70% had a 25-or-less score, suggesting some level of cognitive impairment. There were no significant associations between MoCA results and any clinical or laboratory data in SS and SC patients; however, a significant correlation (P=0.03) with stroke was found in HbS/β-thalassemic patients. Correlations were further detected according to sociodemographic conditions, such as age (r=-0.316; P<0.001), age at first job (r=0.221; P=0.018), personal (r=0.23; P=0.012) andper capitafamiliar incomes (r=0.303; P=0.001), personal (r=0.61; P=0), maternal (r=0.536; P=0), and paternal educational status (r=0.441; P=0). We further sought independent predictors of performance using multivariable regressions and increased education was an independent predictor of better scores in MoCA (0.8099, 95% confidence interval [CI]: 0.509-1.111). Brain imaging analysis showed significant and progressive atrophy in important cerebral areas related to memory, learning, and executive function. These data point to the high prevalence and impact of cognitive decline in adult SCD patients, mirrored in brain atrophic areas. It is also possible to observe the influence of sociodemographic conditions on patients' cognitive performances and the need for creating focused therapeutic plans that address these deficiencies. Moreover, the absence of a significant correlation of MoCA values with stroke in the SS and SC groups may be related to the worst sociocultural and economic conditions of the Brazilian African descent population, in which the impact of low educational stimulation on cognitive function can outweigh even the anatomical damage caused by the disease.

Dose-Dependent Progression of Chorioretinal Atrophy at the Injection Site After Subretinal Injection of rAAV2/8 in Nonhuman Primates

ObjectiveProgressive retinal atrophy has been described after subretinal gene therapy utilizing the adeno-associated virus (AAV) vector platform. To elucidate whether thIS atrophy is a consequence of inherent properties of AAV, or if it is related to the surgical trauma of subretinal delivery, we analyzed data from an IND-enabling study for PDE6A gene therapy in non-human primates. DesignAnimal study (non-human primates), retrospective data analysis SubjectsForty eyes of thirty healthy non-human primates (macaca fascicularis) were included in the analysis. Two AAV dose levels (low: 1x10E11, high: 1x10E12) were compared to sham-injection (balanced saline solution; BSS). Twenty untreated eyes were not analysed. MethodsAnimals were treated with a sutureless 23G vitrectomy and single subretinal injections of AAV.PDE6A and/or BSS. The follow up period was 12 weeks. Atrophy development was followed using fundus-autofluorescence (AF), optical coherence tomography (OCT), fluorescence angiography (FA) and indocyanine green angiography (ICGA). Main Outcome MeasuresArea [mm2] of retinal pigment epithelium (RPE) atrophy on AF. Presence of outer retinal atrophy on OCT. Area [mm2] of hyperfluorescence in FA and hypofluorescence in ICGA. ResultsProgressive atrophy at the injection site developed in 54% of high dose, 27% of low dose, and 0% of sham-treated eyes. At the end of observation, the mean±SD area of atrophy in AF was 1.19±1.75 mm2, 0.25±0.50 mm2 and 0.0±0.0 mm2 respectively (sham x high dose: p=0.01). Atrophic lesions in AF (p=0.01) and FA (p=0.02) were significantly larger in high dose eyes, compared to sham-treated eyes. Rate of progression in high dose eyes was 4.1x higher compared to low dose eyes. ConclusionSubretinal injection of AAV.PDE6A induced dose-dependent, progressive retinal atrophy at the site of injection. Findings from multimodal imaging were in line with focal, transient inflammation within the retina and choroid and secondary atrophy. Atrophic changes after gene therapy with AAV-based vector systems are not primarily due to surgical trauma and increase with the dose given.

Human Protothecosis: Case Report of a Rare Algal Infection

Protothecosis: is a rare disease caused by opportunistic algae infection of the genus Prototheca. An 84-year-old female patient has presented with an erythematous, infiltrated, papulopustular plaque with areas of central atrophy on the left forearm for the past 10 months. Histopathology revealed structures similar to morulae, corresponding to algae, and culture was positive for Prototheca spp. Itraconazole 200 mg/day was prescribed, resulting in improvement of cutaneous lesions. Protothecosis has a high potential for underreporting and misdiagnosis due to its rarity and linical similarities with other dermatoses. The patient in this study presented a lesion in a typical area due to the ease of trauma and entry point, with a good therapeutic response to oral antifungal monotherapy.

Temporal progression of pancreatic cancer computed tomography findings until diagnosis: A large-scale multicenter study.

Focal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers. To ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them. A multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated. Out of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7years before diagnosis, and the next most common, MPD dilatation, 1.1years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis. This large-scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection.

Macrophage AHR-TLR4 cross-talk drives p-STAT3 (Ser727)-mediated mitochondrial oxidative stress and upregulates IDO/ICAM-1 in the steatohepatitis induced by aflatoxin B1

Aflatoxin B1 (AFB1) is a major mycotoxin contaminant showing in the environment and foods. In this study, the molecular initiating events (MIEs) of AFB1-induced steatohepatitis were explored in mice and human cell model. We observed dose-dependent steatohepatitis in the AFB1-treated mice, including triglyceride accumulation, fibrotic collagen secretion, enrichment of CD11b + and F4/80+ macrophages/Kupffer cells, cell death, lymphocytes clusters and remarkable atrophy areas. The gut barrier and gut-microbiota were also severely damaged after the AFB1 treatment and pre-conditioned colitis in the experimental mice aggravated the steatohepatitis phenotypes. We found that macrophages cells can be pro-inflammatorily activated to M1-like phenotype by AFB1 through an AHR/TLR4/p-STAT3 (Ser727)-mediated mitochondrial oxidative stress. The phenotypes can be rescued by AHR inhibitors in the mice model and human cell model. We further showed that this signaling axis is based on the cross-talk interaction between AHR and TLR4. Gene knock-up experiment found that the signaling is dependent on AFB1 ligand-binding with AHR, but not protein expressions of TLR4. The signaling elevated NLRP3 and two immune metabolic enzymes ICAM-1 and IDO that are associated with macrophage polarization. Results from intervention experiments with natural anti-oxidant and AHR inhibitor CH223191 suggest that the macrophage polarization may rely on AHR and ROS. Our study provides novel and critical references to the food safety and public health regulation of AFB1.

A Novel Grading System for Diffuse Chorioretinal Atrophy in Pathologic Myopia.

This study aims to quantitatively assess diffuse chorioretinal atrophy (DCA) in pathologic myopia and establish a standardized classification system utilizing artificial intelligence. A total of 202 patients underwent comprehensive examinations, and 338 eyes were included in the study. The methodology involved image preprocessing, sample labeling, employing deep learning segmentation models, measuring and calculating the area and density of DCA lesions. Lesion severity of DCA was graded using statistical methods, and grades were assigned to describe the morphology of corresponding fundus photographs. Hierarchical clustering was employed to categorize diffuse atrophy fundus into three groups based on the area and density of diffuse atrophy (G1, G2, G3), while high myopic fundus without diffuse atrophy was designated as G0. One-way analysis of variance (ANOVA) and nonparametric tests were conducted to assess the statistical association with different grades of DCA. On the basis of the area and density of DCA, the condition was classified into four grades: G0, G1 (0 < density ≤ 0.093), G2 (0.093 < density ≤ 0.245), and G3 (0.245 < density ≤ 0.712). Fundus photographs depicted a progressive enlargement of atrophic lesions, evolving from punctate-shaped to patchy with indistinct boundaries. DCA atrophy lesions exhibited a gradual shift in color from brown-yellow to yellow-white, originating from the temporal side of the optic disc and extending towards the macula, with severe cases exhibiting widespread distribution throughout the posterior pole. Patients with DCA were significantly older [34.00 (27.00, 48.00) vs 29.00 (26.00, 34.00) years], possessed a longer axial length (28.85 ± 1.57 vs 27.11 ± 1.01 mm), and exhibited a more myopic spherical equivalent [- 13.00 (- 16.00, - 10.50) vs - 9.09 ± 2.41 D] compared to those without DCA (G0) (all P < 0.001). In eyes with DCA, a trend emerged as grades increased from G1 to G3, showing associations with older age, longer axial length, deeper myopic spherical equivalent, larger area of parapapillary atrophy, and increased fundus tessellated density (all P < 0.001). The novel grading system for DCA, based on assessments of area and density, serves as a reliable measure for evaluating the severity of this condition, making it suitable for widespread application in the screening of pathologic myopia.

Peripapillary Atrophy Area as an Indicator of Glaucomatous Structural and Functional Progression.

To determine whether peripapillary atrophy (PPA) area is an indicator of glaucomatous structural and functional damage and progression. In this retrospective longitudinal analysis from ongoing prospective study we qualified 71 eyes (50 subjects) with glaucoma. All subjects had a comprehensive ophthalmic examination, visual field (VF), and spectral-domain optical coherence tomography (OCT) testing in at least three visits. PPA was manually delineated on en face OCT optic nerve head scans, while observing the corresponding cross-sectional images, as the hyper-reflective area contiguous with the optic disc. The mean follow-up duration was 4.4 ± 1.4years with an average of 6.8 ± 2.2 visits. At baseline, PPA area was significantly associated only with VF's mean deviation (MD; P = 0.041), visual field index (VFI; P = 0.041), superior ganglion cell inner plexiform layer (GCIPL; P = 0.011), and disc area (P = 0.011). Longitudinally, PPA area was negatively and significantly associated with MD (P = 0.015), VFI (P = 0.035), GCIPL (P = 0.009), superior GCIPL (P = 0.034), and disc area (P = 0.007, positive association). Longitudinal change in PPA area is an indicator of glaucomatous structural and functional progression but PPA area at baseline cannot predict future progression. Longitudinal changes in peripapillary atrophy area measured by OCT can be an indicator of structural and functional glaucoma progression.

Increased Cortical Thickness in Alzheimer's Disease.

Patients with Alzheimer's disease (AD) have diffuse brain atrophy, but some regions, such as the anterior cingulate cortex (ACC), are spared and may even show increase in size compared to controls. The extent, clinical significance, and mechanisms associated with increased cortical thickness in AD remain unknown. Recent work suggested neural facilitation of regions anticorrelated to atrophied regions in frontotemporal dementia. Here, we aim to determine whether increased thickness occurs in sporadic AD, whether it relates to clinical symptoms, and whether it occur in brain regions functionally connected to-but anticorrelated with-locations of atrophy. Cross-sectional clinical, neuropsychological, and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed to investigate cortical thickness in AD subjects versus controls. Atrophy network mapping was used to identify brain regions functionally connected to locations of increased thickness and atrophy. AD patients showed increased thickness in the ACC in a region-of-interest analysis and the visual cortex in an exploratory analysis. Increased thickness in the left ACC was associated with preserved cognitive function, while increased thickness in the left visual cortex was associated with hallucinations. Finally, we found that locations of increased thickness were functionally connected to, but anticorrelated with, locations of brain atrophy (r = -0.81, p < 0.05). Our results suggest that increased cortical thickness in Alzheimer's disease is relevant to AD symptoms and preferentially occur in brain regions functionally connected to, but anticorrelated with, areas of brain atrophy. Implications for models of compensatory neuroplasticity in response to neurodegeneration are discussed. ANN NEUROL 2024;95:929-940.

RDH12-associated retinal degeneration caused by a homozygous pathogenic variant of 146C>T and literature review.

To describe the clinical, electrophysiological, and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant. The patient underwent a complete ophthalmologic examination including best-corrected visual acuity, anterior segment and dilated fundus, visual field, spectral-domain optical coherence tomography (OCT) and electroretinogram (ERG). The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result. Then we reviewed the characteristics of the patients reported with the same variant. A 30-year male presented with severe early retinal degeneration who complained night blindness, decreased visual acuity, vitreous floaters and amaurosis fugax. The best corrected vision was 0.04 OD and 0.12 OS, respectively. The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye. Autofluorescence shows bilateral symmetrical hypo-autofluorescence. ERG revealed that the amplitudes of a- and b-wave were severely decreased. Multifocal ERG showed decreased amplitudes in the local macular area. A homozygous missense variant c.146C>T (chr14:68191267) was found. The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied. An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported. The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.

Histologic and Immunohistochemical Characterization of GA-Like Pathology in the Rat Subretinal Sodium Iodate Model.

Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration with multifactorial etiology and no well-established treatment. A model recapitulating the hallmarks would serve as a key to understanding the underlying pathologic mechanisms better. In this report, we further characterized our previously reported subretinal sodium iodate model of GA. Retinal degeneration was induced in rats (6-8weeks old) by subretinal injections of NaIO3 as described previously. Animals were sacrificed at 3, 8 and 12weeks after injection and eyes were fixed or cryopreserved. Some choroids were processed as flatmounts while other eyes were cryopreserved, sectioned, and immunolabeled with a panel of antibodies. Finally, some eyes were prepared for transmission electron microscopic (TEM) analysis. NaIO3 subretinal injection resulted in a well-defined focal area of retinal pigment epithelium (RPE) degeneration surrounded by viable RPE. These atrophic lesions expanded over time. RPE morphologic changes at the border consisted of hypertrophy, multilayering, and the possible development of a migrating phenotype. Immunostaining of retinal sections demonstrated external limiting membrane descent, outer retinal tubulation (ORT), and extension of Müller cells toward RPE forming a glial membrane in the subretinal space of the atrophic area. TEM findings demonstrated RPE autophagy, cellular constituents of ORT, glial membranes, basal laminar deposits, and defects in Bruch's membrane. In this study, we showed pathologic features of a rodent model resembling human GA in a temporal order through histology, immunofluorescence, and TEM analysis and gained insights into the cellular and subcellular levels of the GA-like phenotypes. Despite its acute nature, the expansion of atrophy and the GA-like border in this rat model makes it ideal for studying disease progression and provides a treatment window to test potential therapeutics for GA.

NONEXUDATIVE INTRARETINAL FLUID IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

To describe the occurrence of nonexudative intraretinal fluid (IRF) in intermediate age-related macular degeneration. A retrospective study was designed to include consecutive cases with intermediate age-related macular degeneration associated with IRF. A multimodal imaging approach was used to confirm diagnosis of IRF in intermediate age-related macular degeneration. Multimodal imaging included color fundus photograph, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography. Ten eyes of 10 patients (2 male and 8 female patients, ages 68-80 years) showing IRF in intermediate age-related macular degeneration were included in the study. The mean best-corrected visual acuity was 20/40 Snellen equivalent. Multimodal imaging including fluorescein angiography/indocyanine green angiography and optical coherence tomography demonstrated the absence of macular neovascularization in all cases; optical coherence tomography-angiography did not detect any abnormal flow signal associated with IRF. Seven of 10 patients developed IRF in correspondence of pigment epithelium detachment. Three of 10 patients presented IRF in correspondence of an area of nascent geographic atrophy. Nonexudative intraretinal fluid in intermediate age-related macular degeneration is a novel, distinctive feature that is characterized by the presence of IRF with no evidence of macular neovascular lesions. The authors described different phenotypes of IRF in intermediate age-related macular degeneration. The definite diagnosis of this condition requires further studies with thorough application of multimodal imaging.

Safety Results for Geographic Atrophy Associated with Age-Related Macular Degeneration Using Subretinal Cord Blood Platelet-Rich Plasma

PurposeTo evaluate the safety of subretinal injection of cord blood platelet-rich plasma (CB-PRP) and its possible effect in eyes affected by geographic atrophy (GA) associated with dry age-related macular degeneration (d-AMD). DesignInterventional, open-label study started in January 2021 with at 12 months of follow-up (the Si.Cord Study). This study was a single-center, nonrandomized, sequential-assigned clinical trial conducted in Rome, Italy, at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (ClinicalTrials.gov_NCT04636853). Subjects, Participants, and ControlsThirteen patients (26 eyes) with bilateral d-AMD-related GA were enrolled. One eye from each patient (with more advanced GA) underwent CB-PRP treatment, and the fellow eye was considered the control. All patients participated in follow-up at 12 months. InterventionAll 13 eyes received 23-gauge (G) vitrectomy and subretinal injection of CB-PRP using a 41-G needle. Main Outcomes and MeasuresBest corrected visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study (ETDRS) letters, central macular thickness using optical coherence tomography (OCT) and atrophic area measured on en-face OCT images were assessed at baseline, 1, 3, 6 and 12 months. ResultsThe BCVA in the treated group was 34.46 ± 20.8 ETDRS at baseline; 40.84 ± 20.52 at 1 month; 40.07 ± 20.34 at 3 months; 39.38 ± 19.84 at 6 months and 35.84 ± 18.38 at 12 months. In the untreated group, the BCVA was 53 ± 21.1 ETDRS letters at baseline; 51.54 ± 20.99 at 1 month; 46.62 ± 19.47 at 3 months; 46.85 ± 18.58 at 6 months and 43.92 ± 17.97 at 12 months (two-way ANOVA: interaction of treatment by eye or time, p= -0.084). Central macular thickness (CMT) did not show a significant inter-eye difference at 12 months (p=0.97). The atrophic geographic areas tended to increase in both treated and fellow eyes at 12 months (p<0.0001). No inflammatory reaction, endophthalmitis, retinal detachment, uveitis, or other complications due to the subretinal injection of CB-PRP were observed during the follow-up. ConclusionsSubretinal injection of CB-PRP could be safely used for d-AMD in its GA form. Despite its safety, a larger cohort of patients, and probably a new way of administration, will be needed in order to understand whether the CB-PRP could have a role in the GA treatment.

Clinical, phenotypic and genetic characteristics of macula‐sparing stargardt disease

Aims/Purpose: Fundus flavimaculatus and Stargardt's disease are monogenic but heterogeneous disease entities leading to loss of central vision in adolescence, caused by more than 490 mutations in the ABCA4 gene. We herein report the clinical, phenotypic and genetic characteristics of adult onset fovea sparing Stargardt's disease.Methods: Two Caucasian males in their 40s presenting with complaints of paracentral scotomata underwent complete ophthalmic exam, visual field testing, optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), electroretinography (ERG) and genetic testing.Results: Visual acuity was 20/20 in both patients with normal IOP. Anterior segments were unremarkable. Posterior segment examination revealed pigment mottling in the macula with ring‐shaped perifoveal chorioretinal atrophy and numerous white deposits in the mid‐periphery. Visual fields confirmed the paracentral ring scotomata. OCT demonstrated concentric perifoveal loss of outer retinal layers with foveal sparing simulating oedema. Extensive hyperautofluorescence in the area of chorioretinal atrophy was revealed by FAF. Full‐field ERG confirmed incomplete loss of cone bioelectrical activity with preserved morphology of the foveal peak and normal rod function. Genetic testing discovered several pathogenic mutations in both patients with shared ABCA4 c.5603A&gt;T, p.(Asn1868Ile), a risk factor mutation. None of the mutations of our patients were previously reported in foveal sparing Stargardt's disease.Conclusions: The variant ABCA4 c.5603A&gt;T, p.(Asn1868Ile) might be associated with foveal sparing Stargardt's disease. Further population studies are need to confirm this association.

Multimodal Retinal Imaging Reveals New Pathogenic Insights in Central Areolar Choroidal Dystrophy: A Case Series.

To describe novel imaging findings in a family affected by central areolar choroidal dystrophy (CACD). Case series with multimodal retinal imaging assessment. A 19-year-old asymptomatic woman was referred for bilateral macular defects of the retinal pigment epithelium (RPE). Blue-light autofluorescence (BAF) of her right eye revealed a speckled pattern in the macular area with a ring of decreased autofluorescence using near-infrared autofluorescence (NIR-AF). Multimodal assessment of her left eye disclosed a single parafoveal spot of decreased pigmentation that was clearly visible as hyper-autofluorescent using BAF and as hypo-autofluorescent using NIR-AF. Optical coherence tomography angiography (OCT-A) revealed several tiny areas of flow voids in correspondence of the RPE alterations of both eyes.Three family members were recently diagnosed with presumed age-related macular degeneration and demonstrated well-demarcated areas of RPE atrophy surrounded by yellowish deposits and a hypo-pigmented halo.Next-generation genetic analysis for inherited macular dystrophies was performed on the index case and the affected family members and revealed a p.Arg172Gln missense mutation in PRPH2 gene, leading to the diagnosis of CACD. Multimodal imaging can reveal new pathogenic insights in CACD. Of notice, NIR-AF and OCT-A are able to detect RPE hypopigmentation and choriocapillaris rarefaction, respectively, since the earliest stages of the disease.