Dataset Information

Comparative Topographical Analysis of Choroidal Microvascular Dropout Between Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

ABSTRACT:

Purpose

To identify the presence of choroidal microvascular dropout (MvD) in nonarteritic anterior ischemic optic neuropathy (NAION) eyes and to characterize the topographical distribution for the mechanistic interpretation of MvD development.

Methods

We performed optical coherence tomography angiography on 47 open-angle glaucoma (OAG) and 19 NAION eyes with β-zone peripapillary atrophy (βPPA). We recorded the presence of MvD and compared between the peripapillary topographical measures of MvD, retinal nerve fiber layer (RNFL) defect, and βPPA in angular width and location.

Results

MvD was present in both diseases, marginally more frequently in NAION eyes (19/19, 100.0%) than in OAG eyes (38/47, 80.6%, P = 0.050), without a discernable difference in appearance. NAION eyes also showed wider MvD and RNFL defects compared to OAG eyes (both P < 0.001). In topographical measurements, the distribution of MvD showed a strong correspondence to superimposition areas of βPPA and RNFL defects, more distinctly than to RNFL defects (all P < 0.001). The outline of superimposition area also remarkably resembled the MvD area.

Conclusions

MvD was present in both the OAG and NAION groups. The βPPA-RNFL defect superimposition area topographically and morphologically matched MvD. Further investigations are needed to elucidate the role of RNFL defects in the pathogenesis of MvD and the clinical significance.

SUBMITTER: Lee EJ

PROVIDER: S-EPMC8556563 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Comparative Topographical Analysis of Choroidal Microvascular Dropout Between Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

Lee Eun Jung EJ Kee Hyun Joo HJ Park Kyung-Ah KA Han Jong Chul JC Kee Changwon C

Investigative ophthalmology & visual science 20211001 13

<h4>Purpose</h4>To identify the presence of choroidal microvascular dropout (MvD) in nonarteritic anterior ischemic optic neuropathy (NAION) eyes and to characterize the topographical distribution for the mechanistic interpretation of MvD development.<h4>Methods</h4>We performed optical coherence tomography angiography on 47 open-angle glaucoma (OAG) and 19 NAION eyes with β-zone peripapillary atrophy (βPPA). We recorded the presence of MvD and compared between the peripapillary topographical me ...[more]

PMID: 34705024

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Project description:ImportanceSemaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D).ObjectiveTo investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network.Design, setting, and participantsThis was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion and rate of NAION were calculated. Association between semaglutide and NAION was assessed using 2 approaches: an active-comparator cohort design comparing new users of semaglutide with those taking other GLP-1RAs and non-GLP-1RA drugs, and a self-controlled case-series (SCCS) analysis to compare individuals' risks during exposure and nonexposure periods for each drug. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). Network-wide HR and IRR estimates were generated using a random-effects meta-analysis model.ExposuresGLP-1RA and non-GLP-1RAs.Main outcomes and measuresNAION under 2 alternative definitions based on diagnosis codes: one more inclusive and sensitive, the other more restrictive and specific.ResultsThe study included 37.1 million individuals with T2D, including 810 390 new semaglutide users. Of the 43 620 new users of semaglutide in the Optum's deidentified Clinformatics Data Mart Database, 24 473 (56%) were aged 50 to 69 years, and 26 699 (61%) were female. The incidence rate of NAION was 14.5 per 100 000 person-years among semaglutide users. The HR for NAION among new users of semaglutide was not different compared with that of the non-GLP-1RAs using the sensitive NAION definition-empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25). The risk was higher only compared with patients taking empagliflozin (HR, 2.27; 95% CI, 1.16-4.46; P = .02) using the specific definition. SCCS analysis of semaglutide exposure showed an increased risk of NAION (meta-analysis IRR, 1.32; 95% CI, 1.14-1.54; P < .001).Conclusions and relevanceResults of this study suggest a modest increase in the risk of NAION among individuals with T2D associated with semaglutide use, smaller than that previously reported, and warranting further investigation into the clinical implications of this association.

Project description:ImportanceThe association between nonarteritic anterior ischemic optic neuropathy (NAION) and an increased risk of stroke has been a subject of debate. However, multinational studies on this topic are scarce.ObjectiveTo evaluate the short-term and long-term stroke risk after NAION compared with a matched control group.Design, setting, and participantsThis global, retrospective, population-based cohort study used aggregated electronic health records from January 1, 2004, through March 19, 2024, sourced from the Global Collaborative Network of TriNetX, which includes data from over 152 million patients across 17 countries. Patients in the study were followed up for a maximum duration of 10 years. Patients with NAION and age-related cataract were included in the analysis. Those with stroke before the diagnosis of NAION and age-related cataract were excluded. Propensity score matching was applied to balance age, sex, race, ethnicity, comorbidities, and medication use.ExposureInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis code for NAION or age-related cataract.Main outcomes and measuresThe primary outcome was the relative risk (RR) of stroke (ICD-10 code I60-63) in the NAION cohort vs the matched controls. Multivariable logistic regression analyses were applied to identify potential clinical factors associated with stroke within the NAION cohort.ResultsA total of 89 811 patients were identified in both the NAION (mean [SD] age, 57.2 [18.5] years; 38 678 men [43.1%]) and control (mean [SD] age, 57.0 [17.9] years; 40 014 men [44.6%]) cohorts after matching. The NAION cohort demonstrated a significantly higher all-stroke risk at all time points: 1 month (RR, 5.04; 95% CI, 4.41-5.78), 3 months (RR, 3.79; 95% CI, 3.40-4.21), 1 year (RR, 2.50; 95% CI, 2.32-2.70), 5 years (RR, 1.54; 95% CI, 1.45-1.63), and 10 years (RR, 1.33; 95% CI, 1.23-1.43). Sensitivity analysis in patients without comorbidities similarly revealed a significantly increased all-stroke risk across all intervals: 1 month (RR, 7.55; 95% CI, 4.74-12.03), 3 months (RR, 6.70; 95% CI, 4.48-10.04), 1 year (RR, 3.96; 95% CI, 2.94-5.34), 5 years (RR, 2.85; 95% CI, 2.18-3.72), and 10 years (RR, 1.68; 95% CI, 1.25-2.26). Among all the clinical factors of interest, only hypertension was consistently associated with all subtypes of stroke following NAION.Conclusions and relevanceThis cohort study of patients with NAION found a significantly elevated risk of stroke compared with matched controls, independently of comorbidities. These findings underscore the importance of regular stroke workups following the onset of NAION.

Project description:Anterior ischemic optic neuropathy (AION) can be divided into nonarteritic (NAION) and arteritic (AAION) forms. NAION makes up ~85% of all cases of AION, and until recently was poorly understood. There is no treatment for NAION, and its initiating causes are poorly understood, in part because NAION is not lethal, making it difficult to obtain fresh, newly affected tissue for study. In-vivo electrophysiology and post-mortem studies reveal specific responses that are associated with NAION. New models of NAION have been developed which enable insights into the pathophysiological events surrounding this disease. These models include both rodent and primate species, and the power of a 'vertically integrated' multi-species approach can help in understanding the common cellular mechanisms and physiological responses to clinical NAION, and to identify potential approaches to treatment. The models utilize laser light to activate intravascular photoactive dye to induce capillary vascular thrombosis, while sparing the larger vessels. The observable optic nerve changes associated with rodent models of AION (rAION) and primate NAION (pNAION) are indistinguishable from that seen in clinical disease, including sectoral axonal involvement, and in-vivo electrophysiological data from these models are consistent with clinical data. Early post-infarct events reveal an unexpected inflammatory response, and changes in intraretinal gene expression for both stress response, while sparing outer retinal function, which occurs in AAION models. Histologically, the NAION models reveal an isolated loss of retinal ganglion cells by apoptosis. There are changes detectable by immunohistochemistry suggesting that other retinal cells mount a brisk response to retinal ganglion cell distress without themselves dying. The optic nerve ultimately shows axonal loss and scarring. Inflammation is a prominent early histological feature. This suggests that clinically, specific modulation of inflammation may be a useful approach to NAION treatment early in the course of the disease.

Dataset Information

Comparative Topographical Analysis of Choroidal Microvascular Dropout Between Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

Purpose

Methods

Results

Conclusions

Publications

Comparative Topographical Analysis of Choroidal Microvascular Dropout Between Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

Similar Datasets

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