Atrophic Lesions Research Articles

Pharmacokinetic/pharmacodynamic analysis of geographic atrophy lesion area in patients receiving pegcetacoplan treatment or sham.

Pegcetacoplan is a complement C3/C3b inhibitor indicated for the treatment of geographic atrophy (GA). A population pharmacokinetic (PK)/pharmacodynamic (PD) analysis of pegcetacoplan used GA lesion area measurements from three clinical studies to determine the effect of pegcetacoplan exposure on GA progression. A base disease progression model was developed using data from sham-treated eyes and untreated fellow eyes, followed by treatment effect assessment in dose-response and PK/PD models. In total, 1501 patients from FILLY (NCT02503332), OAKS (NCT03525613), and DERBY (NCT03525600) received intravitreal pegcetacoplan 15 mg monthly or every other month (EOM) or sham treatment monthly or EOM and were included in the population analysis of lesion area. Disease progression over time was adequately described as linear-with-time over the 24-month maximal study duration. Disease-specific covariates associated with slower lesion growth were unilateral, unifocal, and subfoveal GA lesions and >20 intermediate or large drusen groups (≥63 μm) at baseline. The dose-response model estimated 0.80-fold (95% CI: 0.75, 0.84) and 0.83-fold (95% CI: 0.78, 0.87) reductions in GA lesion growth rate with pegcetacoplan monthly and EOM, respectively, versus sham. A relationship between vitreous humor concentration and GA lesion growth rate was quantified as 2.6% per unit of log-transformed vitreous pegcetacoplan concentration in the PK/PD model. PK/PD predictions of treatment effect based on exposure (pegcetacoplan monthly: 0.80 [90% CI: 0.77, 0.84]; pegcetacoplan EOM: 0.83 [90% CI: 0.80, 0.86]) were consistent with predictions based on dose response. These results support the benefit of pegcetacoplan administered monthly or EOM in slowing GA lesion growth.

The protective effect of Auricularia auricula polysaccharides on cyclophosphamide-induced immunosuppression and intestinal injury: A fecal microbiota transplantation study

Auricularia auricula polysaccharides (AHP) have potential immunomodulatory activities. However, the relationship between polysaccharides, intestinal microbiota, and immune activity remains unclear. Therefore, to explore this relationship, we performed immunosuppressive donor, fecal microbiota transplantation (FMT), and pseudo-sterile mouse validation experiments. Our results showed that AHP enhanced immunomodulatory activity, as evidenced by the alleviation of cyclophosphamide (Cy)-induced body weight loss, spleen and thymus atrophy, and splenic and colonic lesions. Additionally, AHP effectively regulated antioxidant enzyme activities (SOD, T-AOC, CAT, GSH-Px), lipid peroxidation product content (MDA), levels of immune factors (TNF-α, IFN-γ, IL-2, IL-4, IL-6), immunoglobulins (sIgA), and the expression of tight junction proteins (Muc2, ZO-1, Occuldin, and Claudin-1) in the colon of immunosuppressed mice. FMT results demonstrated that FAHP displayed superior immunomodulatory ability and could further affect the abundance of Dehydroepiandrosterone, Prostaglandin E2, Cholesterol and Pregnenolone by increasing the abundance of unclassified_Muribaculaceae, Desulfovibrio, Alloprevotella, and unclassified_Oscillospiraceae and decreasing that of Staphylococcus, Bacteroides, and Corynebacterium. Pseudo-sterilization experiments showed that AHP was unable to increase antioxidant enzyme activity, reduce lipid peroxidation content, or promote the release of immune factors. In brief, AHP did not alleviate Cy-induced immunosuppression after microbiota elimination. In summary, AHP exerted a protective effect against Cy-induced immunosuppression and intestinal damage by modulating intestinal microbiota and its metabolites. These findings provide new insights into the mechanisms by which AHP, as a functional food or drug, promotes immune response regulation and maintains intestinal health.

Platelet-rich plasma applications in the larynx: snake oil or stupendous?

To explore and summarize recent work examining the use of platelet-rich plasma (PRP) applications for vocal fold disorder. Intrachordal PRP injections have recently emerged as a treatment option for patients with damage to the lamina propria of the vocal fold (scar, atrophy, sulcus and inflammatory lesions). Studies support significant improvements in patient-reported and clinician-reported outcomes, and objective phonatory parameters. PRP demonstrates a good safety profile, absence of immune reactions, affordable cost model and improvement in mucosal wave features with resultant improved voice quality up to 12 months following treatment. PRP injection of the vocal folds is a novel repurposing of a previously validated technique, and emerging data shows consistent results across multiple centres, increasing confidence in use of this freely available material. Current published studies confirm improved voice outcomes compared with pretreatment measures and high patient satisfaction. Further research is required to properly assign the role of and ideal candidate for PRP applications, and to delineate durability of treatment.

Complete retinal pigment epithelium and outer retinal atrophy: Is it really an end-stage atrophy?

Geographic atrophy (GA), a late manifestation of age-related macular degeneration (AMD), leads to irreversible vision loss. Early identification of precursor lesions, such as incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA), is crucial for predicting GA formation. The latter stage has been associated with irreversible and progressive changes, and the eventual development of a dense scotoma on the compromised area. We present an 80-year-old woman with AMD in both eyes, demonstrating progressive changes over a 2-year follow-up. While the right eye developed cRORA with vision decline, the left eye exhibited unexpected restoration of the outer retinal layers within the cRORA lesion. This finding challenges the notion of "end-stage atrophy" in GA development and highlights the potential reversibility of early atrophic lesions. Recognizing these dynamics has implications for the development of targeted therapies aimed at preserving vision in AMD's early stages.

Doppler ultrasound imaging and shear wave elastography for evaluation of interstitial fibrosis/tubular atrophy in IgA nephropathy.

The purpose of this study was to explore the value of Doppler ultrasound imaging and shear wave elastography (SWE) in evaluating renal interstitial fibrosis/tubular atrophy (IFTA). During April 2019 and November 2023, biopsy-proven IgA nephropathy (IgAN) patients were enrolled in our study. Conventional ultrasound, Doppler ultrasound imaging and SWE measurements were performed, and related parameters were collected. According to the Oxford classification of IgAN, interstitial fibrosis/tubular atrophy (T) lesions were grouped into T0, T1 and T2 group. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic accuracy of SWE in identifying IFTA. A total of 100 IgAN patients were enrolled in the final cohort. 67 patients were in the T0 group, and 33 patients were in the T1/T2 group. The average SWE values were 42.17 ± 9.11kPa in the T0 group and 36.83 ± 10.32kPa in the T1/T2 group (p = 0.01). Multivariate logistic regression revealed that the SWE value and end diastolic velocity (EDV) of the interlobar artery were found to be independent risk factors for IFTA. For the diagnosis of IFTA, the area under the ROC curve (AUC) of SWE alone was 0.652, whereas the AUC of SWE in combination with the EDV was 0.807 (p = 0.008). The combination of Doppler ultrasound imaging and SWE measurements could improve the diagnostic performance of quantitative assessment of IFTA in IgAN patients.

PATHWAYS TO GEOGRAPHIC ATROPHY IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To characterize and quantify the precursor lesions of geographic atrophy in eyes with age-related macular degeneration. A retrospective study of eyes with a minimum of 6-month follow-up before developing geographic atrophy. Evaluations included color and autofluorescence imaging, along with spectral-domain optical coherence tomography, employing definitions from the Consensus of Atrophy Meeting Group and Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group. There were 55 eyes of 44 patients, who had a mean age of 81.3 years at onset of atrophy; 35 (63.6%) were female. The mean duration of follow-up before and after the advent of geographic atrophy was 4.9 years and 1.2 years, respectively. Geographic atrophy was preceded by collapse of a druse in 41 eyes (74.5%). Of these, 29 (70.7%) were drusenoid pigment epithelial detachments. Among the eyes with regressing drusen, there were 9 with overlying vitelliform deposit, and all had concurrent subretinal drusenoid deposit; however, 19 of 30 eyes with no vitelliform deposit overlying the druse had concurrent subretinal drusenoid deposit, a difference that was significant ( P < 0.001). Regression of subretinal drusenoid deposit was found in 4 eyes (7.3%), regression of vitelliform deposit associated with subretinal drusenoid deposit in 5 (9.1%), and regression of vitelliform deposit in eyes concurrently harboring drusen was found in 3 (5.4%) and regression of vitelliform deposit alone in 2 (3.6%) at the site of eventual development of geographic atrophy. Geographic atrophy appears to develop from multiple pathways as manifested by the many precursor lesions, all various forms of extracellular deposit, that upon regression, result in a common end-stage appearance.

Novel insights into presenilin 1 mutation associated with a distinctive dementia phenotype and cotton wool plaques.

The mutations in the presenilin 1 gene (PSEN1) are the main cause of familial Alzheimer's disease. PSEN1 mutations affect amyloid-beta peptide production, which accumulates in the brain as senile plaque and cotton wool plaques (CWPs) and relates to other neurodegenerative disorders. Here we report the second case of the PSEN1 G266S mutation, which showed distinctive neuropathological features, including abundant CWPs. Lewy body pathology, and altered amyloid-beta production. Using the proband's samples, we performed genetic analysis of the PSEN1, APP, MAPT, and APOE genes, histopathological and immunohistochemical analysis of the brain tissue, and biochemical analysis of Aβ production in COS cells transfected with wild-type or mutant PSEN1. The patient presented with memory loss, abnormal behavior, and visual hallucinations. Brain scans showed reduced blood flow, mild atrophy, and white matter lesions. Genetic analysis revealed a heterozygous mutation at codon 266 (G266S) of PSEN1 and polymorphism of MAPT (Q230R). The brain had many CWPs, severe cerebral amyloid angiopathy (CAA), senile plaque, Lewy bodies, and neurites. Electron microscopy displayed myelinated fiber degeneration, mitochondrial damage, and amyloid fibrils in the white matter. The production level of Aβ42 in PSEN1 G266S-transfected cells significantly increased. Our findings suggest that the PSEN1 G266S mutation may cause a heterogeneous clinical and pathological phenotype, influenced by other genetic or environmental factors.

Clinical, Dermoscopic, and Histopathological Analysis of Blaschko-Linear Atrophic Lichen Planopilaris (LPP) of the Face: A Case Series of a Rare Entity

ABSTRACT Blaschko-linear pigmented lesions over the face are encountered rarely, and may either be macular or atrophic. A descriptive clinical, dermoscopic, and histopathological analysis of six such cases of hyperpigmented atrophic lesions in a Blaschko-linear distribution that we saw recently in our outpatient department is presented emphasizing the potential of dermoscopy to facilitate prompt management thereby averting cicatrization.

Smartphone App to Detect Pathological Myopia Using Spatial Attention and Squeeze‐Excitation Network as a Classifier and Segmentation Encoder

ABSTRACTPathological myopia (PM) is a worldwide visual health concern that can cause irreversible vision impairment. It affects up to 20 crore population, causing social and economic burdens. Initial screening of PM using computer‐aided diagnosis (CAD) can prevent loss of time and finances for intricate treatments later on. Current research works utilizes complex models that are too resource‐intensive or lack explanations behind the categorizations. To emphasize the significance of artificial intelligence for the ophthalmic usage and address the limitations of the current studies, we have designed a mobile‐compatible application for smartphone users to detect PM. For this purpose, we have developed a lightweight model, using the enhanced MobileNetV3 architecture integrated with spatial attention (SA) and squeeze‐excitation (SE) modules to effectively capture lesion location and channel features. To demonstrate its robustness, the model is tested against three heterogeneous datasets namely PALM, RFMID, and ODIR reporting the area under curve (AUC) score of 0.9983, 0.95, and 0.94, respectively. In order to support PM categorization and demonstrate its correlation with the associated lesions, we have segmented different forms of PM lesion atrophy, which gave us intersection over union (IOU) scores of 0.96 and fscore of 0.97 using the same SA+SE inclusive MobileNetV3 as an encoder. This lesion segmentation can aid ophthalmologists in further analysis and treatment. The optimized and explainable model version is calibrated to develop the smartphone application, which can identify fundus image as PM or normal vision. This app is appropriate for ophthalmologists seeking second opinions or by rural general practitioners to refer PM cases to specialists.

Hyperautofluorescent material inside areas of macular atrophy may reveal non-lipofuscin fluorophores in late stage AMD.

To characterize fundus autofluorescence (FAF) in complete (cRORA) and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) by fluorescence lifetime imaging ophthalmology (FLIO). Overall, 98 macular atrophy (MA) lesions in 42 eyes of 37 age-related macular degeneration (AMD) patients (mean age: 80.9 ± 5.8 years), 25 of them classified as iRORA and 73 as cRORA by OCT, were investigated by FLIO in a short (SSC: 498-560 nm) and a long wavelength channel (LSC: 560-720 nm). Differences of FAF lifetimes and peak emission wavelength (PEW) between atrophic lesions and intact retinal pigment epithelium (RPE) in the outer ring of the ETDRS grid were considered. FAF lifetimes in MA were longer and PEW were significantly (p < 0.001) shorter than in intact RPE by 112 ± 78 ps (SSC), 91 ± 64 ps (LSC), 27 ± 18 nm (PEW) in iRORA and by 227 ± 112 ps (SSC), 167 ± 81 ps (LSC), and 54 ± 17 nm (PEW) in cRORA. 37% of iRORA and 24% of cRORA were hyperautofluorescent in SSC. Persistent sub-RPE-BL material in MA was newly found as a hyperautofluorescent entity with lifetimes considerably longer than that of drusen and RPE. Despite RPE and, thus, lipofuscin are greatly absent in MA, considerable FAF, preferably at short wavelengths, was found in those lesions. Drusen, persistent sub-RPE-BL material, basal laminar deposits, persistent activated RPE, and sclera were identified as putative sources of this fluorescence. FLIO can help to characterize respective fluorophores.

DXA-Measured Abdominal Adipose Depots and Structural Brain Integrity in Postmenopausal Women.

This study extends prior research from the MRI substudy of the Women's Health Initiative Memory Study (WHIMS-MRI) linking BMI to reduced brain atrophy and ischemic lesion load by examining DXA-based measurements of total body fat, total abdominal adipose tissue (TAT), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, gynoid fat, and overall leg fat. The analytic sample consisted of 61 postmenopausal women (baseline mean age 69.5 [3.6]) enrolled in WHIMS-MRI who had undergone DXA scans. DXA scans were completed at years 0, 3, and 6, and MRI scans were conducted ~8 years after baseline. Adjusted linear regression models were used to analyze the association between adiposity averaged across the 3-time points and volumes of brain regions previously linked to dementia. Higher levels of total body fat, TAT, VAT, SAT, gynoid, and overall leg fat were associated with larger hippocampal volume (β 0.02 [95% CI, 0.004-0.04]; 0.11 [0.02-0.21]; 0.26 [0.04-0.47]; 0.18 [0.03-0.33]; 0.18 [0.05-0.30]; 0.07 [0.009-0.12], respectively). No other significant associations were observed. Higher levels of adiposity were positively associated with hippocampal volume. Additional research with larger sample sizes is needed to ascertain the significance of this association.

Optic Atrophy From Retrograde Transsynaptic Axonal Degeneration Following Pediatric Brain Injury.

The patterns of optic atrophy due to retrograde transsynaptic degeneration (RTSD) have not been well characterized in children. This study aimed to characterize optic atrophy in pediatric patients with focal intracerebral lesions. A retrospective review of children with optic atrophy and focal intracerebral lesions was conducted. Ophthalmic data were recorded, including visual acuity, color vision, formal automated visual fields and optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell layer. Six patients (83.33% male) were included. The mean visual acuity (VA) of all eyes was 0.30 logMAR (20/40 Snellen), with no significant difference in the mean logMAR VA in the ipsilateral eye to the location of the lesion compared with the contralateral eye (0.30 vs 0.30, P = 1.000). Color vision (available in 5 patients) was normal in 2, mildly reduced in one and markedly reduced in 2. Bitemporal optic disc pallor was observed in 5 out of 6 patients. OCT data revealed that pRNFL thickness was most significantly diminished in the temporal (95% CI: -44.71 to -14.18 µm, P = 0.0021), inferotemporal (95% CI: -75.06 to -5.17 µm, P = 0.0294), and superotemporal (95% CI: -76.82 to -18.51 µm, P = 0.0055) sectors. Average pRNFL thickness was significantly reduced compared with normative data in both the ipsilateral (95% CI: -40.76 to -11.69 µm, P = 0.0003) and the contralateral eye (95% CI: -38.46 to -5.83 µm, P = 0.0063). When only nasal and temporal data were analyzed, mean pRNFL thickness was still diminished compared with normative data (95% CI: -33.01 to -9.77 µm, P = 0.0012). Children presenting with optic atrophy, particularly with bitemporal optic atrophy, should have neuroimaging to exclude any underlying serious intracranial pathology.

C5 inhibitor avacincaptad pegol treatment for geographic atrophy: A comprehensive review.

Geographic atrophy (GA) remains a leading cause of central vision loss with no known cure. Until recently, there were no approved treatments for GA, often resulting in poor quality of life for affected patients. GA is characterized by atrophic lesions on the retina that may eventually threaten the fovea. Emerging treatments have demonstrated the ability to reduce the rate of lesion growth, potentially preserving visual function. Avacincaptad pegol (ACP; Astellas Pharma Inc), a complement component 5 inhibitor, is an FDA-approved treatment for GA that has been evaluated in numerous clinical trials. Here we review the current clinical trial landscape of ACP, including critical post hoc analyses that suggest ACP may reduce the risk of severe loss among patients with GA.

An exploratory study of the damage markers NfL, GFAP, and t-Tau, in cerebrospinal fluid and other findings from a patient cohort enriched for suspected autoimmune psychiatric disease

There is growing evidence suggesting that immunological mechanisms play a significant role in the development of psychiatric symptoms in certain patient subgroups. However, the relationship between clinical red flags for suspected autoimmune psychiatric disease and signs of central nervous system (CNS) pathology (e.g., routine cerebrospinal fluid (CSF) alterations, CNS damage markers, neurophysiological or neuroimaging findings) has received limited attention. Here, we aimed to describe the prevalence and distribution of potential CNS pathologies in psychiatric patients in relation to clinical red flags for autoimmune psychiatric disease and psychiatric symptoms. CSF routine findings and CNS damage markers; neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAP) and total Tau (t-Tau), in CSF from 127 patients with psychiatric disease preselected for suspected immunological involvement were related to recently proposed clinical red flags, psychiatric features, and MRI and EEG findings. Twenty-one percent had abnormal routine CSF findings and 27% had elevated levels of CNS damage markers. Six percent had anti-neuronal antibodies in serum and 2% had these antibodies in the CSF. Sixty-six percent of patients examined with MRI (n = 88) had alterations, mostly atrophy or nonspecific white matter lesions. Twenty-seven percent of patients with EEG recordings (n = 70) had abnormal findings. Elevated NfL levels were associated with comorbid autoimmunity and affective dysregulation symptoms. Elevated t-Tau was associated with catatonia and higher ratings of agitation/hyperactivity. Elevated GFAP was associated with acute onset, atypical presentation, infectious prodrome, tics, depressive/anxiety symptom ratings and overall greater psychiatric symptom burden. In conclusion, preselection based on suspected autoimmune psychiatric disease identifies a population with a high prevalence of CSF alterations suggesting CNS pathology. Future studies should examine the value of these markers in predicting treatment responses.

Association of sarcopenia with regional brain atrophy and white matter lesions in a general older population: the Hisayama Study.

Sarcopenia has been reported to be associated with cognitive decline and the risk of dementia. However, few studies have addressed the association between sarcopenia and brain morphological changes in the general population. A total of 1373 community-dwelling participants aged ≥ 65years underwent brain MRI. Sarcopenia was defined based on the Asian Working Group for Sarcopenia's criteria. The pattern of regional gray matter volume loss associated with sarcopenia were assessed using a voxel-based morphometry (VBM) analysis. Regional brain volumes, intracranial volumes (ICV), and white matter lesions volumes (WMLV) were also measured using FreeSurfer. An analysis of covariance was used to examine the associations of sarcopenia with regional brain volumes in proportion to ICV. Of the participants, 112 had sarcopenia. The participants with sarcopenia had significantly lower total brain volume/ICV and total gray matter volume/ICV and higher WMLV/ICV than those without sarcopenia after adjusting for confounders. In VBM, sarcopenia was associated with lower gray matter volume in the frontal lobe, insula, cingulate gyrus, hippocampus, amygdala, and basal ganglia. Using FreeSurfer, we confirmed that the participants with sarcopenia had significantly lower frontal, insular, cingulate, and hippocampal volumes than those without sarcopenia. The current study showed that participants with sarcopenia had significantly lower volume in the frontal lobe, insula, cingulate, and hippocampus and higher WMLV than participants without sarcopenia. As these brain regions are likely to play an important role in cognitive function, these changes may suggest a shared underlying mechanism for the progression of sarcopenia and cognitive decline.

Platelet Rich plasma injection of the vocal folds in benign vocal pathologies

PurposeThere are few options for treatment of dysphonia secondary to vocal pathology related to lamina propria scar, atrophy, sulcus, or inflammatory disorders. Platelet rich plasma (PRP) may provide anti-inflammatory and regenerative properties seen with other tissue engineering therapies without the risks associated with these treatments. We evaluated vocal fold (VF) injection of PRP for feasibility, phonatory effects, patient satisfaction and durability.MethodsPatients with dysphonia secondary to vocal fold scar, atrophy, sulcus and inflammatory lesions were included. PRP injections were administered in office, to bilateral vocal folds. Patients were followed up at 1 week, 1 month, 3 months and 6 months to assess outcomes (GRBAS scale, maximum phonation time, vocal fatigue index (VFI), voice handicap index (VHI-10) and stroboscopy).Results75 intracordal PRP injections were administered to 48 patients. All injections were completed, and no adverse reactions were experienced. Improvements in VHI-10 scores at 1,3,6 months were seen (mean VHI 21.73 at baseline, 15.62 at six months, p < 0.001). 72.3% rated improvement at 7 or above on Likert scale. 95.7% of patients would consider a future PRP injection. Secondary outcomes VFI, MPT, and GRBAS also demonstrated significant improvements over time. Patients receiving a single PRP injection (n = 26) still demonstrated significant VHI-10 improvements at 1,3 and 6 months.ConclusionsVF office PRP injections are feasible and safe and can provide phonatory benefit and reduce vocal effort in benign VF disorders. A single PRP injection is sufficient to provide sustained benefit in some cases.Level of evidenceLevel III: prospective cohort study.

Correlation of posterior segment lesions with anterior segment biometric parameters and FBN1 genotype in patients with Marfan syndrome

Objective: To investigate the characteristics of posterior segment lesions in Marfan syndrome (MFS) patients and their relationship with anterior segment biometric parameters and FBN1 genotype. Methods: A cross-sectional study was conducted. A total of 121 MFS patients, 76 males and 45 females, with an average age of (11.72±11.66) years, who visited the Department of Ophthalmology, Eye & ENT Hospital of Fudan University from January 2013 to March 2023 were included. The presence of posterior scleral staphyloma was observed using B-mode ultrasound, and macular lesions were identified and classified using the atrophy-traction-neovascularization system based on ultra-widefield fundus images, color fundus images, and optical coherence tomography scans. Anterior segment biometric parameters, including axial length of the eye, average corneal curvature, corneal astigmatism, horizontal corneal diameter, anterior chamber depth, and lens thickness, were collected, and the direction and extent of lens dislocation were observed. Molecular genetic analysis of FBN1 gene mutations in patients was performed using next-generation sequencing based on a panel of ocular genetic diseases, and the impact of the genotype and anterior segment biometric parameters on the posterior segment manifestations was analyzed. Results: Sixty patients exhibited posterior segment lesions, including retinal detachment (4 cases, 3.31%), macular lesions (47 cases, 38.84%), and posterior scleral staphyloma (54 cases, 44.63%). There was statistically significant difference in axial length of the eye between patients with and without posterior scleral staphyloma [23.09 (22.24, 24.43) and 27.04 (25.44, 28.88) mm], between patients with and without macular lesions [23.16 (22.24, 24.61) and 27.04 (25.74, 28.78) mm], and between patients with and without atrophic macular lesions [23.16 (22.24, 24.61) and 27.04 (25.74, 28.79) mm] (all P<0.001). There was statistically significant difference in anterior chamber depth between patients with and without macular lesions [3.11 (2.75, 3.30) and 3.34 (3.09, 3.60) mm] (P<0.05). There was also statistically significant difference in corneal astigmatism between patients with and without posterior scleral staphyloma [2.15 (1.20, 2.93) and 1.40 (1.00, 2.20) diopters] (P<0.05). The location and region of the FBN1 gene mutation not only showed statistically significant difference from the positive rates of posterior scleral staphyloma and macular lesions (all P<0.05), but also influenced the occurrence of atrophic macular lesions (both P<0.05). Patients with FBN1 mutations located in the transforming growth factor β regulatory sequence had the highest proportion of posterior scleral staphyloma and macular lesions (both 10/11). Conclusions: Posterior scleral staphyloma and macular lesions have a relatively high incidence in MFS patients and tend to progress to more severe grades. The age, axial length of the eye, anterior chamber depth, corneal astigmatism, and location and region of the FBN1 gene mutation are factors affecting the posterior segment lesions in MFS patients.

Natural History of Visual Acuity and Microperimetry-Based Functional Outcome Measures of the Macula in Patients with Geographic Atrophy: A Retrospective Chart Review Study in Germany.

Background/Objectives: Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) leading to the progressive and irreversible loss of visual function. Characteristics of GA include atrophic lesions resulting from the loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. During GA progression, atrophic lesions typically advance from the macular periphery to the center, affecting foveal light sensitivity and visual acuity. This study analyzed changes in light sensitivity and visual acuity during the natural course of GA progression using the topographic analysis of structural and functional changes based on Early Treatment Diabetic Retinopathy Study (ETDRS) charts, multimodal imaging, and microperimetry assessment. Methods: Medical chart data of GA patients between 2014 and 2022 from the Internationale Innovative Ophthalmochirurgie GbR (I.I.O.) research center (Düsseldorf, Germany) were retrospectively analyzed. All patient eyes fulfilling the phase 3 OAKS study inclusion criteria were included and followed up for 60 months. The imputation of missing measurements and dropouts was performed by linear mixed models. Results: A total of 20 GA eyes from 13 GA patients were included in the study. At the index, 53.8% of patients had bilateral GA, with 70.0% of the eyes showing multifocal GA and 30.0% subfoveal encroachment (SFE). A total of 35.0% of the eyes had 2-5, and 15.0% over 20, areas of atrophy. Over time, the GA lesion size increased from 6.4 mm2 to 11.8 mm2 (1.08 mm2/year). After an average observation time of 2.9 years, 78.6% of the initially unaffected study eyes developed SFE. The percentage of study eyes without visual impairment decreased from 55.0% to 30.0%, with mean normal-luminance best-corrected visual acuity (NL-BCVA) reducing from 63.7 to 55.7 ETDRS letters. The share of absolute scotoma points in microperimetry assessment increased from 15.7% to 43.5% while overall average macular sensitivity declined from 15.7 dB to 7.4 dB. Conclusions: The substantial deterioration of macular outcomes and visual function was comprehensively detected. The results were a documentation of structural and functional aspects of the natural progression of GA for a 60-month follow-up, providing a typical outline for AMD patients with GA.

Deep Learning‐Enabled Vasculometry Depicts Phased Lesion Patterns in High Myopia Progression

PurposeTo investigate the potential phases in myopic retinal vascular alterations for further elucidating the mechanisms underlying the progression of high myopia (HM). MethodsFor this retrospective study, participants diagnosed with high myopia at Beijing Tongren Hospital were recruited. Based on bionic mechanisms of human vision, an intelligent image processing model was developed and utilized to extract and quantify the morphological characteristics of retinal vasculatures in different regions measured by papilla-diameter (PD), including vascular caliber, arteriole-to-venule ratio (AVR), tortuosity, the angle of the vascular arch (AVA), the distance of the vascular arch (DVA), density, fractal dimension, and venular length. In addition, the optic disc and the area of peripapillary atrophy (PPA) were also quantified. The characteristics of the overall population, as well as patients aged less than 25 years old, were compared by different genders. Univariate and multiple linear regression analyses were conducted to investigate the correlation of retinal vasculature parameters with PPA width, and detailed trends of the vascular indicators were analyzed to explore the potential existence of staged morphological changes. FindingsThe study included 14,066 fundus photographs of 5775 patients (aged 41.2 ± 18.6 years), of whom 7379 (61.2 %) were female. The study included 12,067 fundus photographs of 5320 patients (aged 41.2 ± 18.6 years). Significant variations in the morphological parameters of retinal vessels were observed between males and females. After adjusting for age and sex, multiple linear regression analysis showed that an increased PPA width ratio was associated with lower AVA (1PD), DVA (1PD), vascular caliber (0.5–1.0 PD), tortuosity (0.5–1.0 PD), density and fractal dimension (all P < 0.001, Spearman’s ρ < 0). Overall, the changes in retinal vascular morphology showed two phases: tortuosity (0.5–1.0PD) and AVA (1PD) decreased rapidly in the first stage but significantly more slowly in the second stage, while vascular density and fractal dimension showed a completely opposite trend with an initial slow decline followed by a rapid decrease. ConclusionsThis study identified two distinct phases of retinal vascular morphological changes during the progression of HM. Traction lesions were predominant in the initial stage, while atrophic lesions were predominant in the later stage. These findings provide further insight into the development mechanism of HM from the perspective of retinal vasculature.

Clinicoradiological Factors for Predicting and Monitoring the Progression of Multiple Sclerosis

As knowledge of pathophysiology and treatment options for multiple sclerosis has been expanding, decisions about when and which drugs we should start and switch appropriately have became important. It should be based upon individuals’ baseline clinical, environmental, demographical, and radiological biomarkers that correlate with long-term disability. In addition, a timely assessment of treatment response and adverse effect should be followed after the initial treatment. Several prognostication tools were developed and large longitudinal studies validated them. They consisted of composition of demographical factors, clinical relapse rate, relapse severity, involvement of specific functional system, magnetic resonance imaging activity and characteristic findings (gadolinium enhancement, brain atrophy, and paramagnetic rim lesion, etc.).