Light and electron microscopic features of preclinical pseudoexfoliation syndrome.

PurposeThis study sought to explore the features of the anterior lens capsule in patients with preclinical pseudoexfoliation syndrome (pPEX) via light microscopy (LM) and transmission electron microscopy (TEM).DesignCross-sectional, prospective, and observational case series.MethodsWe recruited consecutive patients with and without pPEX who underwent routine cataract surgery at Ramathibodi Hospital, between April 2018 and November 2020. pPEX can be characterized by pigmented spoke-wheel deposition (P) on the anterior lens capsule, midperiphery cleft/lacunae (C), faint central disc present within the photopic pupil (D), white-spoke pattern (W) noted at the midperiphery, and a combination of at least two signs (Co). LM and TEM were used to examine anterior lens capsule specimens for the presence of characteristic pseudoexfoliation material (PXM). The features of the anterior lens capsule in pPEX explored via LM and TEM were recorded.ResultsThis study included a total of 96 patients (101 excised anterior lens capsules); among them, 34 (35 excised anterior lens capsules) exhibited pPEX signs (pPEX group) but 62 (66 excised anterior lens capsules) did not (control group). The patients had a mean age of 74 ± 7 (range, 58-89) years. LM and TEM revealed no definite PXM in any patient. In the pPEX group, LM analysis identified two capsule specimens with suspected PXM; PXM precursors were observed in 1 of the 34 excised capsule specimens analyzed via TEM. Furthermore, 39 eyes (59.09%) exhibited signs of true exfoliation syndrome (TEX) in LM analysis (12.82%, 25.64%, 10.26%, 10.26%, and 41.03% for patients exhibiting P, D, C, W, and Co, respectively). However, no TEX signs were observed in the control group. We found that the anterior lens capsules exhibiting C and D were significantly associated with TEX (odds ratio = 5.4 and 7.9; P = 0.007 and 0.004, respectively).ConclusionsLM analysis revealed no definite PXMs were detected in the excised anterior lens capsules, whereas TEM analysis showed PXM precursors in one specimen (2.94%). Notably, a significant association was observed between C and D signs and TEX

Differentiating Glaucomatous Optic Neuropathy from Non-Glaucomatous Optic Neuropathies Using Deep Learning Algorithms

Purpose : A deep learning framework to differentiate glaucomatous optic disc changes (GON) from non-glaucomatous optic neuropathy-related disc changes (NGON). Design : Cross-sectional study. Method : A deep-learning system was trained, validated, and externally tested to classify optic discs as normal, GON, or NGON using 2,183 digital color fundus photographs. A Single-Center data set of 1,822 images–660 images of NGON, 676 images of GON, and 486 images of normal optic discs–was used for training and validation, whereas 361 photographs from four different data sets were used for external testing. Our algorithm removed the redundant information from the images using an optic disc segmentation (OD-SEG) network, following which we performed transfer learning with various pre-trained networks. Finally, we calculated sensitivity, specificity, F1-score, and precision to show the performance of the discrimination network in the validation and independent external data set. Results : For classification, the algorithm with the best performance for the Single-Center data set was DenseNet121, with a sensitivity of 95.36%, precision of 95.35%, specificity of 92.19%, and F1 score of 95.40%. For the external validation data, the sensitivity and specificity of our network for differentiating GON from NGON were 85.53% and 89.02%, respectively. The glaucoma specialist who diagnosed those cases in masked fashion, had a sensitivity of 71.05% and a specificity of 82.21%. Conclusions : The proposed algorithm for the differentiation of GON from NGON yields results that have a higher sensitivity than those of a glaucoma specialist, and its application for unseen data thus is extremely promising

Genetic Association Study Of Exfoliation Syndrome Identifies A Protective Rare Variant At Loxl1 And Five New Susceptibility Loci

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 x 10(-14)) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10(-8)). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.Wo