Areas Of Atrophy Research Articles

Epidemiology, Tear Film, and Meibomian Gland Dysfunction in Facial Palsy: A Comparative Analysis.

To compare the meibographies and dry eye parameters of paretic vs non-paretic sides of patients with a facial palsy diagnosis. Twenty patients with unilateral facial palsy were recruited and the severity of the disease was staged using the House-Brackmann scale. A comprehensive dry eye evaluation was performed using the Oculus 5M Keratograph. A Pearson correlation coefficient was performed to determine correlation strength between House-Brackmann score and Meibomian gland atrophy. Meibographies were analyzed via ImageJ software to determine the affected area, and they were compared to the observer manual score. Cohen's Kappa coefficient was calculated to compare agreement between manual and ImageJ meibography scoring. Tear breakup time was reduced in the affected side (p = 0.21), tear meniscus height was much greater in the non-affected side (p = 0.02). Finally, Meibomian gland alterations were more evident in the affected side, with upper Meibomian glands having a loss of 29.55 ± 13.31% (p = 0.03) and lower glands presenting a loss of 44.44 ± 16.9% (p =< 0.001). Pearson correlation coefficient between House-Brackmann score and Meibomian gland atrophy was 0.841 (p < 0.001 [95% CI: 0.64-0.94]). Cohen's kappa coefficient was 0.643 (p < 0.001). A clear difference in Meibomian gland and tear film dynamics can be observed in paretic vs non-paretic sides. A greater House-Brackmann score was correlated with a greater Meibomian gland atrophy area. A strong positive correlation is seen between the House-Brackmann score and Meibomian gland atrophy. Software-based analysis also showed a greater glandular area loss when compared to clinician's analysis. The level of agreement was moderate, so disparities are observed, especially in grade 2 Meibomian gland dropout where the least level of agreement was seen in cross tabulation. This study further incentivizes multimodal patient evaluation, which has been a growing area of interest in healthcare.

Photoreceptor-RPE loss ratio and fundus autofluorescence patterns as predictive factors for lesion progression in geographic atrophy.

To assess the impact of the ratio between photoreceptor (PR) loss and retinal pigment epithelium (RPE) loss on the progression of geographic atrophy (GA) and to explore correlations between abnormal fundus autofluorescence (FAF) patterns and the PR-RPE loss ratio. Single-centre, retrospective case series. Multimodal images from 87 treatment-naïve patients with GA and a follow-up of 6-24 months were included. Geographic atrophy areas on FAF images and areas of PR-RPE loss on optical coherence tomography images at baseline were manually annotated, and FAF patterns were classified. The impact of these biomarkers on GA progression through month 24 as measured on FAF was evaluated using random slope and intercept models and Spearman correlation coefficients (ρ). Mean square-root GA growth rate was 0.27 ± 0.28 mm per year. Mean PR-RPE loss ratio at baseline was 2.16 ± 1.75. Fundus autofluorescence patterns "diffuse" and "diffuse trickling" showed higher PR-RPE loss ratios at baseline and contributed statistically significantly to the slope of GA progression (p = 0.01 and p = 0.0019). Baseline GA lesion size was negatively correlated to PR-RPE loss ratios at baseline (ρ = -0.47, p < 0.0001). Overall, GA growth was higher in patients with higher PR-RPE loss ratios at baseline (ρ = 0.35, p = 0.0011), and the ratio's contribution to the slope of GA progression was statistically significant (p = 0.0001). Eyes with higher PR-RPE loss ratios were more likely to exhibit FAF patterns "diffuse" and "diffuse trickling" and showed higher GA progression rates. Baseline characteristics derived from FAF and OCT images may thus offer information on lesion progression.

The CSF p-tau/β-amyloid 42 ratio correlates with brain structure and fibrillary β-amyloid deposition in cognitively unimpaired individuals at the earliest stages of pre-clinical Alzheimer's disease.

CSF concentrations of β-amyloid 42 (Aβ42) and phosphorylated tau (p-tau) are well-established biomarkers of Alzheimer's disease and have been studied in relation to several neuropathological features both in patients and in cognitively unimpaired individuals. The CSF p-tau/Aβ42 ratio, a biomarker combining information from both pathophysiological processes, has emerged as a promising tool for monitoring disease progression, even at pre-clinical stages. Here, we studied the association between the CSF p-tau/Aβ42 ratio with downstream markers of pre-clinical Alzheimer's disease progression including brain structure, glucose metabolism, fibrillary Aβ deposition and cognitive performance in 234 cognitively unimpaired individuals, who underwent cognitive testing, a lumbar puncture, MRI, 18F-fluorodeoxyglucose and 18F-flutemetamol PET scanning. We evaluated both main effects and interactions with Alzheimer's disease risk factors, such as older age, female sex and the apoliporoptein E (APOE)-ɛ4 allele, in a priori defined regions of interest and further examined the associations on the whole-brain using voxel-wise regressions. In addition, as the association between CSF Alzheimer's disease biomarkers and brain structure and function may be non-linear, we tested the interaction between the CSF p-tau/Aβ42 ratio and stages of pre-clinical Alzheimer's disease defined using the amyloid (A) and tau (T) classification. We found significantly positive associations between CSF p-tau/Aβ42 and both cortical Aβ deposition and regional grey matter volume while no effect was observed for brain metabolism. A significant interaction with age indicated that, for the same level of CSF p-tau/Aβ42, older individuals displayed both increased Aβ deposition and lower grey matter volume, in widespread cortical areas. In addition, we found that women compared with men had a greater Aβ fibrillary accumulation in midline cortical areas and inferior temporal regions, for the same level of the CSF biomarker. The impact of CSF p-tau/Aβ42 on grey matter volume was modulated by AT stages, with A+T+ individuals displaying significantly less positive associations in areas of early atrophy in the Alzheimer's continuum. Finally, we found that sex and APOE-ɛ4 modulated the association between the CSF biomarker and episodic memory as well as abstract reasoning, respectively. Our data indicate that the CSF p-tau/Aβ42 ratio is strongly associated with multiple downstream neuropathological events in cognitively unimpaired individuals and may thus serve as a potent biomarker to investigate the earliest changes in pre-clinical Alzheimer's disease. Given that its impact on both Aβ deposition and grey matter volume is modulated by specific risk factors, our results highlight the need to take into account such predisposing variables in both clinical practice and prevention trials.

A novel endoscopic artificial intelligence system to assist in the diagnosis of autoimmune gastritis: a multicenter study.

Autoimmune gastritis (AIG), distinct from Helicobacter pylori-associated atrophic gastritis (HpAG), is underdiagnosed due to limited awareness. This multicenter study aimed to develop a novel endoscopic artificial intelligence (AI) system for assisting in AIG diagnosis. Patients diagnosed with AIG, HpAG, or nonatrophic gastritis (NAG), were retrospectively enrolled from six centers. Endoscopic images with relevant demographic and medical data were collected for development of the AI-assisted system based on a multi-site feature fusion model. The diagnostic performance of the AI model was evaluated in internal and external datasets. Endoscopists' performance with and without AI support was tested and compared using Mann-Whitney U test. Heatmap analysis was performed to interpret AI model outputs. 18 828 endoscopy images from 1070 patients (294 AIG, 386 HpAG, 390 NAG) were collected. On testing datasets, AI identified AIG with 96.9 % sensitivity, 92.2 % specificity, and area under the receiver operating characteristic curve (AUROC) of 0.990 (internal), and 90.3 % sensitivity, 93.1 % specificity, and AUROC of 0.973 (external). The performance of AI (sensitivity 91.3 %) was comparable to that of experts (87.3 %) and significantly outperformed nonexperts (70.0 %; P = 0.01). With AI support, the overall performance of endoscopists was improved (sensitivity 90.3 % [95 %CI 86.0 %-93.2 %] vs. 78.7 % [95 %CI 73.6 %-83.2 %]; P = 0.008). Heatmap analysis revealed consistent focus of AI on atrophic areas. This novel AI system demonstrated expert-level performance in identifying AIG and enhanced the diagnostic ability of endoscopists. Its application could be useful in guiding biopsy sampling and improving early detection of AIG.

Multiwavelength photobiomodulation in atrophic age-related macular degeneration.

To evaluate photobiomodulation (PBM) safety and efficacy in patient with atrophic AMD and to explore tissue effects using Spectrally Resolved Autofluorescence (SrAF) to identify a potential biomarker indicative of mitochondrial activity, the primary PBM target. This retrospective, non-comparative case series involved six eyes of five patients with atrophic AMD, conducted at the Medical Retina and Imaging Unit, IRCCS San Raffaele Hospital in Milan, Italy. At baseline and follow-ups (after one and three months) a complete ophthalmological assessment and multimodal imaging, including spectrally resolved autofluorescence (SrAF), were performed. PBM treatment (Valeda Light Delivery System - LumiThera) was administered in nine sessions over three weeks. The SrAF images were analyzed to evaluate the effect of the treatment. Six eyes of five patients with atrophic AMD received PBM at baseline. Best corrected visual acuity (BCVA), mean central macular thickness (CMT), mean retinal sensitivity on microperimetry and the atrophic area have remained stable. No eyes developed foveal atrophy after the treatment. The image analysis in SrAF showed an increase in the highlighted area of 4.89% after one month and 17.11% after three months. No adverse systemic or local side effects were reported. PBM is a safe treatment for the human retina. The evaluation of the retinal area within the green light spectrum (575 nm) in SrAF is a potential indirect biomarker of mitochondrial activity and could be used to assess treatment efficacy in clinical studies.

Macular Outer Retinal Atrophy Following Vitrectomy and Hypotony: Two Cases.

To characterize two cases of focal outer retinal atrophy and hypotony after vitrectomy. Retrospective chart review of two patients' records between 2019 and 2023. Patient 1 underwent vitrectomy, epiretinal membrane peel, and cataract extraction for visually significant macular pucker. She developed hypotony without a wound leak and was noted to have a focal parafoveal area of ellipsoid zone disruption by 1 week post-operatively, which evolved into outer retinal and chorioretinal atrophy within 6 weeks after surgery. This area of atrophy remained stable in size, but the patient later reported a paracentral scotoma. Patient 2 had multiple previous surgeries for retinal detachment with proliferative vitreoretinopathy. Seven years later, the IOL dislocated and was exchanged with scleral fixation of a new IOL. On post-operative day 1, he had hypotony with macular folds secondary to a leaking sclerotomy wound. The sclerotomies were sutured on post-operative day 3, and his intraocular pressure normalized. However, he developed a central, focal area of chorioretinal atrophy within 1 week of the initial surgery. The size of this area of atrophy remained stable over years but resulted in reduced central vision. Hypotony following vitrectomy may rarely predispose patients to the development of focal chorioretinal atrophy.

Rheumatic fever and long-term use of benzathine penicillin as possible risk factors for extensive macular atrophy with pseudodrusen in a Brazilian cohort

BackgroundAlthough there has been a large increase in the number of extensive macular atrophy with pseudodrusen (EMAP) cases, the basic aspects of this disease remain unknown. Brazilian patients have a common past history of rheumatic fever (RF) and/or benzathine penicillin (BP) treatment possibly related to the disease. We analyzed how RF and BP might be correlated with EMAP in Brazilian patients.DesignObservational, retrospective, case-control study.MethodsThe databases of three private eye clinics in Brazil were searched for patients with an EMAP-like appearance. Each patient was asked about a previous history of RF and/or long-term use of BP. Patients underwent best-corrected visual acuity (BCVA) measurement, color fundus imaging, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT) imaging, and electroretinography (ERG). The following characteristics were analyzed: subretinal drusenoid deposits (SDD), pigment mottling, retinal pigment epithelial/basement membrane (RPE/BM) separation, outer retinal or RPE atrophy, and identification of a paving stone-like appearance. The choroidal thickness was measured using enhanced depth imaging OCT. The central atrophic area was measured manually on ultra-wide-field FAF.ResultsA total of 154 eyes of 77 patients (women, 66.2%; mean age, 58.6 years) with EMAP were included; 90.9% of patients were diagnosed with RF; 94.8% had been treated with BP and treatment was started at an average age of 7.3 years (mean duration, 11.8 years). The treatment duration was significant for the area of atrophy (P = 0.027) in which each 1-year increase in treatment duration led to an average reduction of 6.91 mm2 in area. The age at diagnosis of RF was significant (P = 0.026) for SDD. The increase of 1 year in the diagnosis of RF (late disease) led to a reduction of 24% in the chance of central SDD being present. On OCT, 65.5% eyes had SDD and more than 70% had a split RPE/BM and outer retinal or RPE atrophy. The choroidal thickness in patients with EMAP was significantly (P < 0.001) thinner than the control group. The ERG was abnormal in all eyes.ConclusionThese findings may suggest a relation between RF and EMAP in Brazilian patients. Patients with EMAP should be questioned about a history of RF.

Brain Networks for Cortical Atrophy and Responsive Neurostimulation in Temporal Lobe Epilepsy

Drug-resistant temporal lobe epilepsy (TLE) has been associated with hippocampal pathology. Most surgical treatment strategies, including resection and responsive neurostimulation (RNS), focus on this disease epicenter; however, imaging alterations distant from the hippocampus, as well as emerging data from responsive neurostimulation trials, suggest conceptualizing TLE as a network disorder. To assess whether brain networks connected to areas of atrophy in the hippocampus align with the topography of distant neuroimaging alterations and RNS response. This retrospective case-control study was conducted between July 2009 and June 2022. Data collection for this multicenter, population-based study took place across 4 tertiary referral centers in Montréal, Canada; Querétaro, México; Nanjing, China; and Salt Lake City, Utah. Eligible patients were diagnosed with TLE according to International League Against Epilepsy criteria and received either neuroimaging or neuroimaging and RNS to the hippocampus. Patients with encephalitis, traumatic brain injury, or bilateral TLE were excluded. Spatial alignment between brain network topographies. Of the 110 eligible patients, 94 individuals diagnosed with TLE were analyzed (51 [54%] female; mean [SD] age, 31.3 [10.9] years). Hippocampal thickness maps in TLE were compared to 120 healthy control individuals (66 [55%] female; mean [SD] age, 29.8 [9.5] years), and areas of atrophy were identified. Using an atlas of normative connectivity (n = 1000), 2 brain networks were identified that were functionally connected to areas of hippocampal atrophy. The first network was defined by positive correlations to temporolimbic, medial prefrontal, and parietal regions, whereas the second network by negative correlations to frontoparietal regions. White matter changes colocalized to the positive network (t93 = -3.82; P = 2.44 × 10-4). In contrast, cortical atrophy localized to the negative network (t93 = 3.54; P = 6.29 × 10-3). In an additional 38 patients (20 [53%] female; mean [SD] age, 35.8 [11.3] years) treated with RNS, connectivity between the stimulation site and atrophied regions within the negative network was associated with seizure reduction (t212 = -2.74; P = .007). The findings in this study indicate that distributed pathology in TLE may occur in brain networks connected to the hippocampal epicenter. Connectivity to these same networks was associated with improvement following RNS. A network approach to TLE may reveal therapeutic targets outside the traditional target in the hippocampus.

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR)- the new lacunae: a case report

BackgroundMicrocephaly with or without chorioretinopathy, lymphedema, or mental retardation is a rare autosomal dominant disease caused by mutations in KIF11 which disrupt EG5 protein function, impacting the development and maintenance of retinal and lymphatic structures due to its expression in the retinal photoreceptor cilia. The primary ocular finding in MCLMR is chorioretinopathy. Additional features can include microphthalmia, angle-closure glaucoma, persistent hyperplastic primary vitreous, cataract, pseudo-coloboma, persistent hyaloid artery, and myopic or hypermetropic astigmatism. The appearance of the chorioretinal lesions as white to pinkish, round, non-elevated atrophic areas devoid of blood vessels resembles the lacunae in Aicardy syndrome. Due to the lack of systematic description of the lesions and significant phenotypical variability, there is an impending need for a detailed report of each case.Case presentationA child with microcephaly detected in the third trimester of gestation began her following in the ophthalmology department due to a non-visually significant cataract. Shortly after, she developed nystagmus and large-angle alternating esotropia with cross-fixation. Her fundus initially showed a pallid optic disc and pigmentary changes, developing thereafter retinal lacunae and a retinal fold. Her differential diagnosis accompanied the dynamic changes in her fundus, which included congenital infections, Leber´s Congenital Amaurosis and Aicardy syndrome. At 19 months old, genetic testing identified a heterozygous mutation (c.1159 C > T, p.Arg387*) in the KIF11 gene. The patient underwent bilateral medial rectus muscle recession surgery at 2 years old for persistent esotropia, with significant improvement. Refraction revealed a hyperopic astigmatism in both eyes (+ 0.25 -2.50 × 180 OD and + 0.75 -2.00 × 170 OS). She continues to require right eye patching for 2 hours daily.ConclusionsThis case report expands the phenotypic spectrum of MCLMR by demonstrating a unique combination of retinal features which sheds new light on differential diagnosis from Aicardy syndrome. Our findings emphasize the significant phenotypic variability associated with MCLMR, particularly regarding ocular involvement. This underscores the importance of detailed clinical evaluation and comprehensive reporting of cases to improve our understanding of the disease spectrum and genotype-phenotype correlations.

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.

Measuring Geographic Atrophy Area Using Column-Based Machine Learning Software on Spectral-Domain Optical Coherence Tomography versus Fundus Auto Fluorescence.

The purpose of this study was to compare geographic atrophy (GA) area semi-automatic measurement using fundus autofluorescence (FAF) versus optical coherence tomography (OCT) annotation with the cRORA (complete retinal pigment epithelium and outer retinal atrophy) criteria. GA findings on FAF and OCT were semi-automatically annotated at a single time point in 36 pairs of FAF and OCT scans obtained from 36 eyes in 24 patients with dry age-related macular degeneration (AMD). The GA area, focality, perimeter, circularity, minimum and maximum Feret diameter, and minimum distance from the center were compared between FAF and OCT annotations. The total GA area measured on OCT was 4.74 ± 3.80 mm2. In contrast, the total GA measured on FAF was 13.47 ± 8.64 mm2 (p < 0.0001), with a mean difference of 8.72 ± 6.35 mm2. Multivariate regression analysis revealed a significant correlation between the difference in area between OCT and FAF and the total baseline lesion perimeter and maximal lesion diameter measured on OCT (adjusted r2: 0.52; p < 0.0001) and the total baseline lesion area measured on FAF (adjusted r2: 0.83; p < 0.0001). We report that the GA area measured on FAF differs significantly from the GA area measured on OCT. Further research is warranted in order to determine the clinical relevance of these findings.

Interreader and Intermodality Variability in Macular Atrophy Quantification in Neovascular Age-related Macular Degeneration: Comparison of 6 Imaging Modalities

Macular atrophy is a common complication in neovascular age-related macular degeneration (AMD) and is associated with poorer visual outcomes. This study evaluated interreader and intermodality variability in measuring macular atrophy in previously treated neovascular AMD eyes without exudation using 6 imaging modalities. Prospective, cohort study. Thirty participants with previously treated neovascular AMD showing no signs of exudation at the time of enrollment and exhibiting macular atrophy. During the same clinic visit, patients were imaged using 6 different imaging modalities: color fundus photography (CFP; Clarus, Carl Zeiss Meditec), near-infrared imaging (NIR; Spectralis, Heidelberg Engineering), structural OCT (Spectralis, Heidelberg Engineering), green fundus autofluorescence (GAF; Clarus, Carl Zeiss Meditec), blue fundus autofluorescence (BAF; Spectralis, Heidelberg Engineering), and pseudocolor imaging (MultiColor; Spectralis, Heidelberg Engineering). Two readers independently measured the macular atrophy area. Interreader and intermodality agreement. The 95% coefficient of repeatability was 5.98 mm2 for CFP, 4.46 mm2 for MultiColor, 3.90 mm2 for BAF, 3.92 mm2 for GAF, 4.86 mm2 for NIR, and 3.55 mm2 for OCT. Similarly, the coefficient of variation was lowest for OCT-based grading at 0.08 and highest for NIR-based grading at 0.28. Accordingly, the intraclass correlation coefficient was 0.742 for CFP, 0.805 for MultiColor, 0.857 for BAF, 0.850 for GAF, 0.755 for NIR, and 0.917 for OCT. The 6 different imaging modalities presented measurements with different mean values, with only a limited number of comparisons not significantly different between the instruments, although measurements were correlated. The largest size of macular atrophy was measured with structural OCT-based grading (median= 4.65 mm2; interquartile range [IQR]= 4.78 mm2) and the smallest was with CFP-based grading (median= 3.86 mm2; IQR= 5.06 mm2). Inconsistencies arose from various factors. In patients with neovascular AMD, macular atrophy measurements vary significantly depending on the imaging technique used. Color fundus photography-based assessments yielded the smallest macular atrophy sizes, whereas structural OCT-based assessments produced the largest. These discrepancies stem from both the inherent limitations of each modality in assessing retinal pigment epithelial atrophy and factors related to neovascularization, such as the coexistence of fibrosis. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Assessing Glaucoma Severity and Progression in Individuals with Asymmetric Axial Length: An Intrapatient Comparative Study

PurposeTo investigate whether there is a difference in inter-eye glaucoma severity and progression in patients with asymmetric axial length DesignLong-term observational study ParticipantsPatients over 20 years of age who had been diagnosed with glaucoma at Seoul National University Hospital, Seoul, Korea, between 2010 and 2020. MethodsPatients diagnosed with glaucoma in both eyes with an axial length difference of more than 1.0 mm were included. Each individual’s eyes were classified into “longer eye” and “shorter eye,” and the baseline and follow-up clinical data were analyzed using the paired test. Main Outcome MeasuresDifferences in clinical characteristics in patients with asymmetric axial length ResultsA total of 190 eyes of 95 glaucoma patients with asymmetric axial length were included in the study. The patients’ mean age was 51.2 ± 12.3 years, and the mean follow-up period was 10.1 ± 3.9 years. There was no difference in the baseline intraocular pressure (IOP) or central corneal thickness (CCT) between longer eyes and shorter eyes. Among the baseline disc parameters, ovality index, beta-zone and gamma-zone parapapillary atrophy (PPA) area were larger in the longer eyes. In the baseline OCT data, the retinal nerve fiber layer (RNFL) thickness and ganglion cell-inner plexiform layer (GCIPL) thickness were thinner in the longer eyes. According to a baseline visual field (VF) test, the mean deviation (MD) and visual field index (VFI) values were significantly lower in the longer eyes. Based on an analysis of glaucoma progression, the rate of change of superior GCIPL (longer eyes : -0.65 μm/yr, shorter eyes : -0.40 μm/yr) , MD (longer eyes : -0.40 dB/yr, shorter eyes : -0.21 dB/yr) , and VFI (longer eyes : -0.92 %/yr, shorter eyes : -0.46 %/yr) were larger in the longer eyes. The greater the difference between the mean IOP and beta-zone PPA area between inter-eyes, the greater the difference in the rate of change of RNFL and GCIPL. Additionally, the greater the difference in IOP fluctuation, the greater the difference in the rate of change between MD and VFI. ConclusionsWhen there was an axial length difference of more than 1.0 mm, glaucoma tended to be more severe and to progress faster in the longer eyes. The inter-eye difference in glaucoma progression rate is related to both mean IOP and IOP fluctuation.

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.

Case report of a child with nephronophthisis from South Africa

BackgroundNephronophthisis (NPHP) is an autosomal recessive disorder with a subset of patients presenting with extrarenal manifestations such as retinal degeneration, cerebella ataxia, liver fibrosis, skeletal abnormalities, cardiac malformations, and lung bronchiectasis. However, the involvement of other organ systems has also been documented. Extrarenal manifestations occur in approximately 10–20% of patients. In developed countries, it has been reported as one of the most common causes of monogenic chronic kidney failure (CKF) during the first three decades of life, with more than 25 genes associated with this condition. The current treatment options for managing NPHP include supportive care, management of complications, and kidney replacement therapy when necessary.The index patient is a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain. Her elder sister, TN, who was 17 years old, was diagnosed with CKF and noted to have persistently elevated liver enzymes (gamma-glutamyl transferase, alanine, and aspartate transaminases). Following genetic testing, her elder sister was shown to have Nephronophthisis Type 3, and a liver biopsy showed early fibrotic changes. Subsequent genetic testing confirmed the index patient as having NPHP Type 3. A kidney biopsy showed focal sclerosed glomeruli with patchy areas of tubular atrophy and related tubulointerstitial changes in keeping with NPHP. We present the first confirmatory case of NPHP from South Africa based on histopathology and genetic testing in a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain, whose elder sister also presented with CKF and early liver fibrosis, confirmed on biopsy and genetic testing.ConclusionIn low-middle-income countries, genetic testing should be undertaken whenever possible to confirm the diagnosis of NPHP, especially in those with a suggestive biopsy or if there is CKF of unknown aetiology with or without extra-renal manifestations.

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.

Age-related macular degeneration: suitability of optogenetic therapy for geographic atrophy.

Age-related macular degeneration (AMD) is a growing public health concern given the aging population and it is the leading cause of blindness in developed countries, affecting individuals over the age of 55 years. AMD affects the retinal pigment epithelium (RPE) and Bruch's membrane in the macula, leading to secondary photoreceptor degeneration and eventual loss of central vision. Late AMD is divided into two forms: neovascular AMD and geographic atrophy (GA). GA accounts for around 60% of late AMD and has been the most challenging subtype to treat. Recent advances include approval of new intravitreally administered therapeutics, pegcetacoplan (Syfovre) and avacincaptad pegol (Iveric Bio), which target complement factors C3 and C5, respectively, which slow down the rate of enlargement of the area of atrophy. However, there is currently no treatment to reverse the central vision loss associated with GA. Optogenetics may provide a strategy for rescuing visual function in GA by imparting light-sensitivity to the surviving inner retina (i.e., retinal ganglion cells or bipolar cells). It takes advantage of residual inner retinal architecture to transmit visual stimuli along the visual pathway, while a wide range of photosensitive proteins are available for consideration. Herein, we review the anatomical changes in GA, discuss the suitability of optogenetic therapeutic sensors in different target cells in pre-clinical models, and consider the advantages and disadvantages of different routes of administration of therapeutic vectors.

Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector.

To report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector. Single-center, retrospective chart review. In this case series, four patients between the ages of six and 11years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated. Three out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector. We observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes. Caution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.

Additively manufactured custom-made subperiosteal implant rehabilitation for severely atrophic maxillary molar area: A technical note

Implant-prosthetic rehabilitations of severely atrophic posterior maxillary sectors currently is challenging, often requiring multiple surgeries and long rehabilitation times. Recently, graftless techniques (e.g. zygomatic, pterygoid and nasal implants) have gained popularity as they offer a reduction in rehabilitation time, aligning more closely with patient preferences but may not be feasible for sectorial rehabilitations. Subperiosteal implants, suggested for full-arch rehabilitations of atrophic maxilla, haven't been explored for sectorial rehabilitations. In this report we present the case of a patient with maxillary molar edentulism, rehabilitated with a subperiosteal implant.

Optic Disc Drusen in Pseudoxanthoma Elasticum Are Associated with the Extent of Bruch's Membrane Calcification.

Background/Objectives: To assess the frequency, extent, localization and potential progression of optic disc drusen (ODD) and the correlation with the angioid streak (AS) length and retinal atrophy in patients with pseudoxanthoma elasticum (PXE). Methods: This retrospective study included patient data from a dedicated PXE clinic at the Department of Ophthalmology, University of Bonn, Germany (observation period from February 2008 to July 2023). Two readers evaluated the presence, localization, and the extent of the ODD on fundus autofluorescence (FAF) imaging at baseline and the follow-up assessments. Additionally, we measured the length of the longest AS visible at baseline and follow-up and the area of atrophy at baseline, both on FAF. Results: A total of 150 eyes of 75 PXE patients (median age at baseline 51.8 years, IRQ 46.3; 57.5 years, 49 female) underwent retrospective analysis. At baseline, 23 of 75 patients exhibited ODD in a minimum of one eye, resulting in an ODD prevalence of 30.7% in our cohort of PXE patients. Among these, 14 patients showed monocular and 9 binocular ODD that were localized predominantly nasally (46.9%). During the observational period (mean 97.5 ± 44.7 months), only one patient developed de novo ODD in one eye and one other patient showed a progression in the size of the existing ODD. The group of patients with ODD had significantly longer ASs (median 7020 µm, IQR 4604; 9183, vs. AS length without ODD: median 4404 µm, IQR 3512; 5965, p < 0.001). No association with the size of the atrophy was found at baseline (p = 0.27). Conclusions: This study demonstrates a prevalence of ODD of 30.7%. ODD presence is associated with longer ASs (an indicator of the severity and extent of ocular Bruch's membrane calcification), suggesting that ODD formation is tightly related to ectopic calcification-possibly secondary to calcification of the lamina cribrosa. Prospective studies investigating the impact of ODD (in conjunction with intraocular pressure) on visual function in PXE warrant consideration.