Parapapillary choroidal microvascular density in acute primary angle-closure and primary open-angle glaucoma: an optical coherence tomography angiography study

Back ground/aims To determine whether parapapillary choroidal microvasculature (PPCMv) density, measured by optical coherence tomography angiography, differed between acute primary angle-closure (APAC), primary open-angle glaucoma (POAG) and controls.Methods This is a prospective, cross-sectional, observational study. Data from 149 eyes from two academic referral centres were analysed. Automated PPCMv density was calculated in inner and outer annuli around the optic nerve region in addition to the peripapillary superficial vasculature, using customised software. A generalised estimating equation was used to compare vessel densities among groups, adjusted for confounders.Results Data from 40 eyes with APAC, 65 eyes with POAG and 44 eyes in healthy controls were gathered and analysed. Global radial peripapillary capillary densities were reduced in eyes with APAC and POAG compared with controls (p=0.027 and 0.136, respectively). Mean outer annular PPCMv density in the POAG group was lower vs the APAC group by 3.6% (95% CI 0.6% to 6.5%) (p=0.018) in the multivariable model adjusted for confounders. The mean difference in inner and outer superior PPCMv between the POAG and APAC groups was 5.9% and 4.4% (95% CI 1.9% to 9.9% and 1.0% to 7.7%, respectively; both p<0.010). Furthermore, POAG and APAC groups both had significantly lower PPCMv compared with controls (both, p<0.001).Conclusions While superficial peripapillary vessels were affected to similar degrees in POAG and APAC, PPCMv drop-out was greater with POAG versus APAC, suggesting that choroidal vessel density may be affected to a lesser extent following an acute increase in intraocular pressure before glaucoma develops

Qualitative and quantitative evaluation of acute angle-closure mechanisms

Abstract Background To evaluate ocular biometric parameters in different subtypes of acute angle closure and compared to fellow eyes of AAC and PACS eyes. Methods This is a retrospective chart review study. A total of 167 eyes (96 patients) consisting of 71 AAC eyes, 71 fellow eyes of AAC, and 25 PACS eyes were recruited. All patients underwent ocular examination and biometry. The mechanism of AAC was confirmed by ultrasound biomicroscopy. We then subdivided AAC eyes into four subgroups: crowded-angle (CR), lens subluxation (LS) pupillary block (PB), and plateau iris syndrome (PL). Outcome variables included anterior chamber depth (ACD), lens thickness (LT), vitreal length (VL), axial length (AL), lens position and relative lens position (LP and RLP, respectively), and lens axial length factor (LAF). Results Among the three groups, ACD was shallower in AAC eyes than fellow eyes of AAC and PACS eyes (p < 0.01 for both) and AAC eyes demonstrated a lesser LP and RLP. The LT, VL, AL, and LAF were not significantly different among the three groups. Among the four subgroups, LS displayed the most shallow ACD (p = 0.01). The lens position in PL was greater than in CR and LS (p < 0.05 and <0.01, respectively). Conclusions AAC eyes had a more anterior lens position than fellow eyes and PACS eyes, though lens thickness did not differ among the groups. As such, an anterior lens position may offer more sensitive prognostication regarding future development of AAC compared to lens thickness

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

Light and electron microscopic features of preclinical pseudoexfoliation syndrome

Purpose This 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). Design Cross-sectional, prospective, and observational case series. Methods We 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. Results This 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). Conclusions LM 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