Pub Date : 2023-12-11DOI: 10.3389/fopht.2023.1301410
Edward F. Linton, Thomas R. Tedeschi, Noor-Us-Sabah Ahmad, Jui-Kai Wang, Randy H. Kardon
The purpose of the study was to describe ocular blood flow changes in eyes affected by a carotid–cavernous fistula (CCF) using laser speckle flowgraphy. We hypothesized that imaging blood flow velocity waveforms in the retinal arterioles and venules simultaneously would reveal specific characteristics of an arteriovenous (AV) connection.The study was an observational case series, with a retrospective case–control analysis.Five patients with a CCF underwent measurement of ocular blood flow using laser speckle flowgraphy. The blood flow was compared retrospectively between a control group of healthy subjects (n = 32) and patients with an elevated intraocular pressure or venous outflow impairment without an AV fistula (n = 40). The outcomes were derived from the arteriole and venule blood flow velocity waveforms, including an A–V phase delay and flow pulsatility.The presence of an active CCF was associated with an increased delay in the peak velocity measured in the retinal venule (10.7% ± 2.2% of the cardiac cycle duration) compared with unaffected fellow eyes (1.8% ± 0.2%; p = 0.05) or control eyes of normal subjects (2.7% ± 0.3%; p = 0.02). This delay disappeared after fistula thrombosis and was not present in eyes with a central retinal vein occlusion (CRVO), glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), or papilledema. The venule blood flow velocity decreased during systole (and in some cases momentarily stopped), leading to a delayed pulse with a greater amplitude in the venules than in fellow eyes and normal controls after normalizing to the arteriole amplitude (1.71 ± 0.3 vs 0.54 ± 0.03 vs 0.59 ± 0.02; p = 8.0E-12). This specific AV delay could also be identified in a scanning laser ophthalmoscope (SLO; SPECTRALIS®) video.Laser speckle flowgraphy reveals dynamic retinal vascular changes in eyes affected by a CCF, which are not present in healthy controls or patients with other eye conditions, and which reverses with treatment.
{"title":"Retinal arterial–venous pulse delay: a new specific marker for a carotid–cavernous fistula","authors":"Edward F. Linton, Thomas R. Tedeschi, Noor-Us-Sabah Ahmad, Jui-Kai Wang, Randy H. Kardon","doi":"10.3389/fopht.2023.1301410","DOIUrl":"https://doi.org/10.3389/fopht.2023.1301410","url":null,"abstract":"The purpose of the study was to describe ocular blood flow changes in eyes affected by a carotid–cavernous fistula (CCF) using laser speckle flowgraphy. We hypothesized that imaging blood flow velocity waveforms in the retinal arterioles and venules simultaneously would reveal specific characteristics of an arteriovenous (AV) connection.The study was an observational case series, with a retrospective case–control analysis.Five patients with a CCF underwent measurement of ocular blood flow using laser speckle flowgraphy. The blood flow was compared retrospectively between a control group of healthy subjects (n = 32) and patients with an elevated intraocular pressure or venous outflow impairment without an AV fistula (n = 40). The outcomes were derived from the arteriole and venule blood flow velocity waveforms, including an A–V phase delay and flow pulsatility.The presence of an active CCF was associated with an increased delay in the peak velocity measured in the retinal venule (10.7% ± 2.2% of the cardiac cycle duration) compared with unaffected fellow eyes (1.8% ± 0.2%; p = 0.05) or control eyes of normal subjects (2.7% ± 0.3%; p = 0.02). This delay disappeared after fistula thrombosis and was not present in eyes with a central retinal vein occlusion (CRVO), glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), or papilledema. The venule blood flow velocity decreased during systole (and in some cases momentarily stopped), leading to a delayed pulse with a greater amplitude in the venules than in fellow eyes and normal controls after normalizing to the arteriole amplitude (1.71 ± 0.3 vs 0.54 ± 0.03 vs 0.59 ± 0.02; p = 8.0E-12). This specific AV delay could also be identified in a scanning laser ophthalmoscope (SLO; SPECTRALIS®) video.Laser speckle flowgraphy reveals dynamic retinal vascular changes in eyes affected by a CCF, which are not present in healthy controls or patients with other eye conditions, and which reverses with treatment.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138981798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-11DOI: 10.3389/fopht.2023.1307439
Adarsh Raja, Sunaina Bhimani, Hafsah Alim Ur Rahman, Madiha Salman, Afrah Saeed Shaikh, Sandesh Raja, Bushra Zafar Sayeed, Ahsan Feroze, Muhammad Ahmed
Glaucoma is a leading cause of irreversible blindness globally and for decades, Molteno and Ahmed glaucoma implants, operating on different mechanisms, have been used to treat complicated glaucoma with varying success.To assess the safety and efficacy of the Molteno glaucoma implant (MGI) versus the Ahmed glaucoma valve (AGV) in patients with complicated glaucoma.We comprehensively searched PubMed, Google Scholar, Cochrane Library and Science Direct) from inception till July 2023 and studies comparing patients with MGI and those with AGV in patients with complicated glaucoma. The primary outcome was intra-ocular pressure reduction at different time intervals. Secondary outcomes included surgical success rate, hypertensive phase, anti-glaucoma medication (AGM) and total complications. In this meta-analysis, four studies were included with a patient population of 257 with refractory, neovascular or advanced uncontrolled glaucoma. Postoperative intra-ocular pressure reduction did not show significant difference between the two groups (MD: -1.34, 95% CI [-2.78, 0.09]). From the secondary outcomes, surgical success rate (RR: 0.88, 95% CI [0.51,1.53]), hypertensive phase (RR: 0.74, 95% CI [0.39,1.40]) were insignificant. Postoperative anti-glaucoma medication (MD: -0.07, 95% CI [-0.79, -0.65] and total complications (RR:1.36, 95% CI [1.07, 1.72]) were significant. No significant difference was observed between the patients with MGI and AGV for the primary outcome. From the secondary outcome, AGV was associated with reduced anti-glaucoma medication use and significantly lowered the number of complications.https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=475539, identifier CRD42023475539.
青光眼是导致全球不可逆失明的主要原因,数十年来,莫尔特诺青光眼植入物和艾哈迈德青光眼植入物以不同的机制被用于治疗复杂性青光眼,取得了不同的成功。我们全面检索了 PubMed、Google Scholar、Cochrane Library 和 Science Direct)从开始到 2023 年 7 月的资料,以及在复杂性青光眼患者中比较使用 MGI 和 AGV 患者的研究。主要结果是不同时间间隔的眼压降低情况。次要结果包括手术成功率、高血压期、抗青光眼药物(AGM)和总并发症。在这项荟萃分析中,共纳入了四项研究,研究对象包括 257 名患有难治性、新生血管性或晚期未控制青光眼的患者。两组患者术后眼压降低率无显著差异(MD:-1.34,95% CI [-2.78,0.09])。从次要结果来看,手术成功率(RR:0.88,95% CI [0.51,1.53])和高眼压期(RR:0.74,95% CI [0.39,1.40])均无显著差异。术后抗青光眼药物(MD:-0.07,95% CI [-0.79,-0.65])和总并发症(RR:1.36,95% CI [1.07,1.72])显著。在主要结果方面,MGI 和 AGV 患者之间未观察到明显差异。从次要结果来看,AGV与抗青光眼药物用量减少有关,并能显著降低并发症数量。https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=475539,标识符为CRD42023475539。
{"title":"Meta-analysis of Molteno glaucoma implants and Ahmed glaucoma valves: insights into efficacy and safety for complex glaucoma","authors":"Adarsh Raja, Sunaina Bhimani, Hafsah Alim Ur Rahman, Madiha Salman, Afrah Saeed Shaikh, Sandesh Raja, Bushra Zafar Sayeed, Ahsan Feroze, Muhammad Ahmed","doi":"10.3389/fopht.2023.1307439","DOIUrl":"https://doi.org/10.3389/fopht.2023.1307439","url":null,"abstract":"Glaucoma is a leading cause of irreversible blindness globally and for decades, Molteno and Ahmed glaucoma implants, operating on different mechanisms, have been used to treat complicated glaucoma with varying success.To assess the safety and efficacy of the Molteno glaucoma implant (MGI) versus the Ahmed glaucoma valve (AGV) in patients with complicated glaucoma.We comprehensively searched PubMed, Google Scholar, Cochrane Library and Science Direct) from inception till July 2023 and studies comparing patients with MGI and those with AGV in patients with complicated glaucoma. The primary outcome was intra-ocular pressure reduction at different time intervals. Secondary outcomes included surgical success rate, hypertensive phase, anti-glaucoma medication (AGM) and total complications. In this meta-analysis, four studies were included with a patient population of 257 with refractory, neovascular or advanced uncontrolled glaucoma. Postoperative intra-ocular pressure reduction did not show significant difference between the two groups (MD: -1.34, 95% CI [-2.78, 0.09]). From the secondary outcomes, surgical success rate (RR: 0.88, 95% CI [0.51,1.53]), hypertensive phase (RR: 0.74, 95% CI [0.39,1.40]) were insignificant. Postoperative anti-glaucoma medication (MD: -0.07, 95% CI [-0.79, -0.65] and total complications (RR:1.36, 95% CI [1.07, 1.72]) were significant. No significant difference was observed between the patients with MGI and AGV for the primary outcome. From the secondary outcome, AGV was associated with reduced anti-glaucoma medication use and significantly lowered the number of complications.https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=475539, identifier CRD42023475539.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138980701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-06DOI: 10.3389/fopht.2023.1327420
Hind M. Alkatan, Fawziah AlMana, Azza M. Y. Maktabi
Temporal artery (TA) biopsy is commonly used for the diagnosis of giant cell arteritis (GCA). However, a positive biopsy is no longer mandatory for diagnosis. This study aims to correlate the histopathological findings of TA biopsies in suspected cases of GCA to the clinical presentation in an ophthalmic tertiary eye care center to draw useful conclusions and advocate the possible implementation of guidelines for TA biopsy.Data was collected from patients’ medical records including, demographics, clinical data, and histopathological findings and diagnosis. The 2022 American College of Rheumatology/ European Alliance of Associations for Rheumatology (ACR/EULAR) criteria have been used and partially adopted as a guide to compare the variables between TA biopsy-positive and negative groups as well as the TA biopsy-positive group and the group of patients with TA biopsy showing atherosclerosis.Out of the total 35 patients who underwent a TA biopsy during the period of 23 years, 22.9% of patients had histopathological findings consistent with GCA and 42.9% had TA atherosclerotic changes, while the remaining 34.3% had histologically unremarkable TA. The mean age of all patients was 66 ± 10.9 years. Slightly more than half were females (54.3%) and the remaining were males (45.7%). In the group with positive TA biopsies, the mean age was 71 ± 8.4 years with a higher female predominance (female-to-male ratio of 5:3). The mean diagnostic clinical score used in our study was higher (7.5 ± 2.33) in the GCA-positive group when compared to the other groups with statistical significance (mean of 4.85 ± 2.01 in patients with overall GCA-negative biopsies and 5.13 ± 2.10 in the group with atherosclerosis). Other three clinical variables that were found to be statistically significant in the GCA biopsy-positive group were scalp tenderness, jaw claudication, and optic nerve pallor.The mean age (71 ± 8.4 years) and the female predominance of GCA in our group of patients with positive TA biopsy (62.5%) was like other reports. In our study 22.9% of performed TA biopsies over the period of the study were positive confirming the diagnosis of GCA on histological exam, which was similar to another report and is considered to be relatively low. The incorporation of increased clinically focused assessments and algorithms, with the aid of the ACR/EULAR criteria, may decrease the frequency of TA biopsies that carries unnecessary cost and risk of procedure-related morbidity. We highly recommend applying the age of ≥ 50 years as an initial criterion for diagnosis, followed by the consideration of the statistically significant clinical features: scalp tenderness, jaw claudication, and optic nerve pallor.
{"title":"Giant cell temporal arteritis: a clinicopathological study with emphasis on unnecessary biopsy","authors":"Hind M. Alkatan, Fawziah AlMana, Azza M. Y. Maktabi","doi":"10.3389/fopht.2023.1327420","DOIUrl":"https://doi.org/10.3389/fopht.2023.1327420","url":null,"abstract":"Temporal artery (TA) biopsy is commonly used for the diagnosis of giant cell arteritis (GCA). However, a positive biopsy is no longer mandatory for diagnosis. This study aims to correlate the histopathological findings of TA biopsies in suspected cases of GCA to the clinical presentation in an ophthalmic tertiary eye care center to draw useful conclusions and advocate the possible implementation of guidelines for TA biopsy.Data was collected from patients’ medical records including, demographics, clinical data, and histopathological findings and diagnosis. The 2022 American College of Rheumatology/ European Alliance of Associations for Rheumatology (ACR/EULAR) criteria have been used and partially adopted as a guide to compare the variables between TA biopsy-positive and negative groups as well as the TA biopsy-positive group and the group of patients with TA biopsy showing atherosclerosis.Out of the total 35 patients who underwent a TA biopsy during the period of 23 years, 22.9% of patients had histopathological findings consistent with GCA and 42.9% had TA atherosclerotic changes, while the remaining 34.3% had histologically unremarkable TA. The mean age of all patients was 66 ± 10.9 years. Slightly more than half were females (54.3%) and the remaining were males (45.7%). In the group with positive TA biopsies, the mean age was 71 ± 8.4 years with a higher female predominance (female-to-male ratio of 5:3). The mean diagnostic clinical score used in our study was higher (7.5 ± 2.33) in the GCA-positive group when compared to the other groups with statistical significance (mean of 4.85 ± 2.01 in patients with overall GCA-negative biopsies and 5.13 ± 2.10 in the group with atherosclerosis). Other three clinical variables that were found to be statistically significant in the GCA biopsy-positive group were scalp tenderness, jaw claudication, and optic nerve pallor.The mean age (71 ± 8.4 years) and the female predominance of GCA in our group of patients with positive TA biopsy (62.5%) was like other reports. In our study 22.9% of performed TA biopsies over the period of the study were positive confirming the diagnosis of GCA on histological exam, which was similar to another report and is considered to be relatively low. The incorporation of increased clinically focused assessments and algorithms, with the aid of the ACR/EULAR criteria, may decrease the frequency of TA biopsies that carries unnecessary cost and risk of procedure-related morbidity. We highly recommend applying the age of ≥ 50 years as an initial criterion for diagnosis, followed by the consideration of the statistically significant clinical features: scalp tenderness, jaw claudication, and optic nerve pallor.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138595542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-05DOI: 10.3389/fopht.2023.1306019
Shubha Subramanya, Moloy T. Goswami, Nick Miller, Eric Weh, Sraboni Chaudhury, Li Zhang, A. Andren, Heather Hager, Katherine M. Weh, C. Lyssiotis, C. Besirli, T. Wubben
Photoreceptor cell death is the cause of vision loss in many forms of retinal disease. Metabolic dysfunction within the outer retina has been shown to be an underlying factor contributing to photoreceptor loss. Therefore, a comprehensive understanding of the metabolic pathways essential to photoreceptor health and function is key to identifying novel neuroprotective strategies. Glutamic-oxaloacetic transaminase 1 (Got1) encodes for a cytosolic aspartate aminotransferase that reversibly catalyzes the transfer of an amino group between glutamate and aspartate and is an important aspect of the malate-aspartate shuttle (MAS), which transfers reducing equivalents from the cytosol to the mitochondrial matrix. Previous work has demonstrated that the activity of this enzyme is highest in photoreceptor inner segments. Furthermore, ex vivo studies have demonstrated that the retina relies on aspartate aminotransferase for amino acid metabolism. Importantly, aspartate aminotransferase has been suggested to be an early biomarker of retinal degeneration in retinitis pigmentosa and a possible target for neuroprotection. In the present study, we characterized the effect of Got1 deletion on photoreceptor metabolism, function, and survival in vivo by using a rod photoreceptor-specific, Got1 knockout mouse model. Loss of the GOT1 enzyme from rod photoreceptors resulted in age-related photoreceptor degeneration with an accumulation of retinal aspartate and NADH and alterations in the expression of genes involved in the MAS, the tricarboxylic acid (TCA) cycle, and redox balance. Hence, GOT1 is critical to in vivo photoreceptor metabolism, function, and survival.
{"title":"Rod photoreceptor-specific deletion of cytosolic aspartate aminotransferase, GOT1, causes retinal degeneration","authors":"Shubha Subramanya, Moloy T. Goswami, Nick Miller, Eric Weh, Sraboni Chaudhury, Li Zhang, A. Andren, Heather Hager, Katherine M. Weh, C. Lyssiotis, C. Besirli, T. Wubben","doi":"10.3389/fopht.2023.1306019","DOIUrl":"https://doi.org/10.3389/fopht.2023.1306019","url":null,"abstract":"Photoreceptor cell death is the cause of vision loss in many forms of retinal disease. Metabolic dysfunction within the outer retina has been shown to be an underlying factor contributing to photoreceptor loss. Therefore, a comprehensive understanding of the metabolic pathways essential to photoreceptor health and function is key to identifying novel neuroprotective strategies. Glutamic-oxaloacetic transaminase 1 (Got1) encodes for a cytosolic aspartate aminotransferase that reversibly catalyzes the transfer of an amino group between glutamate and aspartate and is an important aspect of the malate-aspartate shuttle (MAS), which transfers reducing equivalents from the cytosol to the mitochondrial matrix. Previous work has demonstrated that the activity of this enzyme is highest in photoreceptor inner segments. Furthermore, ex vivo studies have demonstrated that the retina relies on aspartate aminotransferase for amino acid metabolism. Importantly, aspartate aminotransferase has been suggested to be an early biomarker of retinal degeneration in retinitis pigmentosa and a possible target for neuroprotection. In the present study, we characterized the effect of Got1 deletion on photoreceptor metabolism, function, and survival in vivo by using a rod photoreceptor-specific, Got1 knockout mouse model. Loss of the GOT1 enzyme from rod photoreceptors resulted in age-related photoreceptor degeneration with an accumulation of retinal aspartate and NADH and alterations in the expression of genes involved in the MAS, the tricarboxylic acid (TCA) cycle, and redox balance. Hence, GOT1 is critical to in vivo photoreceptor metabolism, function, and survival.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138599909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-05DOI: 10.3389/fopht.2023.1327883
Kalpana Rajanala, Farokh Dotiwala, Arun K. Upadhyay
Geographic atrophy (GA) is an advanced stage of age-related macular degeneration (AMD) that leads to gradual and permanent vision loss. GA is characterized by the loss of photoreceptor cells and retinal pigment epithelium (RPE), leading to distinct atrophic patches in the macula, which tends to increase with time. Patients with geographic atrophy often experience a gradual and painless loss of central vision, resulting in difficulty reading, recognizing faces, or performing activities that require detailed vision. The primary risk factor for the development of geographic atrophy is advanced age; however, other risk factors, such as family history, smoking, and certain genetic variations, are also associated with AMD. Diagnosis is usually based on a comprehensive eye examination, including imaging tests such as fundus photography, optical coherence tomography (OCT), and fluorescein angiography. Numerous clinical trials are underway, targeting identified molecular pathways associated with GA that are promising. Recent approvals of Syfovre and Izervay by the FDA for the treatment of GA provide hope to affected patients. Administration of these drugs resulted in slowing the rate of progression of the disease. Though these products provide treatment benefits to the patients, they do not offer a cure for geographic atrophy and are limited in efficacy. Considering these safety concerns and limited treatment benefits, there is still a significant need for therapeutics with improved efficacy, safety profiles, and better patient compliance. This comprehensive review discusses pathophysiology, currently approved products, their limitations, and potential future treatment strategies for GA.
{"title":"Geographic atrophy: pathophysiology and current therapeutic strategies","authors":"Kalpana Rajanala, Farokh Dotiwala, Arun K. Upadhyay","doi":"10.3389/fopht.2023.1327883","DOIUrl":"https://doi.org/10.3389/fopht.2023.1327883","url":null,"abstract":"Geographic atrophy (GA) is an advanced stage of age-related macular degeneration (AMD) that leads to gradual and permanent vision loss. GA is characterized by the loss of photoreceptor cells and retinal pigment epithelium (RPE), leading to distinct atrophic patches in the macula, which tends to increase with time. Patients with geographic atrophy often experience a gradual and painless loss of central vision, resulting in difficulty reading, recognizing faces, or performing activities that require detailed vision. The primary risk factor for the development of geographic atrophy is advanced age; however, other risk factors, such as family history, smoking, and certain genetic variations, are also associated with AMD. Diagnosis is usually based on a comprehensive eye examination, including imaging tests such as fundus photography, optical coherence tomography (OCT), and fluorescein angiography. Numerous clinical trials are underway, targeting identified molecular pathways associated with GA that are promising. Recent approvals of Syfovre and Izervay by the FDA for the treatment of GA provide hope to affected patients. Administration of these drugs resulted in slowing the rate of progression of the disease. Though these products provide treatment benefits to the patients, they do not offer a cure for geographic atrophy and are limited in efficacy. Considering these safety concerns and limited treatment benefits, there is still a significant need for therapeutics with improved efficacy, safety profiles, and better patient compliance. This comprehensive review discusses pathophysiology, currently approved products, their limitations, and potential future treatment strategies for GA.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138600318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01eCollection Date: 2023-01-01DOI: 10.3389/fopht.2023.1332312
Makoto Ishikawa, Yukitoshi Izumi, Kota Sato, Taimu Sato, Charles F Zorumski, Hiroshi Kunikata, Toru Nakazawa
[This corrects the article DOI: 10.3389/fopht.2023.1132011.].
[此处更正了文章 DOI:10.3389/fopht.2023.1132011]。
{"title":"Corrigendum: Glaucoma and microglia-induced neuroinflammation.","authors":"Makoto Ishikawa, Yukitoshi Izumi, Kota Sato, Taimu Sato, Charles F Zorumski, Hiroshi Kunikata, Toru Nakazawa","doi":"10.3389/fopht.2023.1332312","DOIUrl":"https://doi.org/10.3389/fopht.2023.1332312","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fopht.2023.1132011.].</p>","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-28DOI: 10.3389/fopht.2023.1290465
Anne Rombaut, R. Brautaset, Pete A. Williams, James R. Tribble
Glaucoma is the leading cause of irreversible blindness. Current treatment options are limited and often only slow disease progression. Metabolic dysfunction has recently been recognized as a key early and persistent mechanism in glaucoma pathophysiology. Several intrinsic metabolic dysfunctions have been identified and treated in retinal ganglion cells to provide neuroprotection. Growing pre-clinical and clinical evidence has confirmed that metabolic alterations in glaucoma are widespread, occurring across visual system tissues, in ocular fluids, in blood/serum, and at the level of genomic and mitochondrial DNA. This suggests that metabolic dysfunction is not constrained to retinal ganglion cells and that metabolic alterations extrinsic to retinal ganglion cells may contribute to their metabolic compromise. Retinal ganglion cells are reliant on glial metabolic support under normal physiological conditions, but the implications of metabolic dysfunction in glia are underexplored. We highlight emerging evidence that has demonstrated metabolic alterations occurring within glia in glaucoma, and how this may affect neuro-glial metabolic coupling and the metabolic vulnerability of retinal ganglion cells. In other neurodegenerative diseases which share features with glaucoma, several other glial metabolic alterations have been identified, suggesting that similar mechanisms and therapeutic targets may exist in glaucoma.
青光眼是导致不可逆失明的主要原因。目前的治疗方案有限,往往只能延缓疾病的发展。最近,人们认识到代谢功能障碍是青光眼病理生理学中一个关键的早期和持续机制。在视网膜神经节细胞中发现并治疗了几种内在代谢功能障碍,以提供神经保护。越来越多的临床前和临床证据证实,青光眼的代谢改变非常广泛,发生在视觉系统组织、眼液、血液/血清以及基因组和线粒体 DNA 水平。这表明新陈代谢功能障碍并不局限于视网膜神经节细胞,视网膜神经节细胞外部的新陈代谢改变也可能导致其新陈代谢功能受损。视网膜神经节细胞在正常生理条件下依赖于神经胶质的代谢支持,但神经胶质代谢功能障碍的影响尚未得到充分探索。我们重点介绍新出现的证据,这些证据表明青光眼患者的神经胶质细胞发生了新陈代谢改变,以及这可能如何影响神经胶质细胞的新陈代谢耦合和视网膜神经节细胞的新陈代谢脆弱性。在与青光眼具有相同特征的其他神经退行性疾病中,也发现了其他几种神经胶质代谢改变,这表明青光眼中可能存在类似的机制和治疗目标。
{"title":"Glial metabolic alterations during glaucoma pathogenesis","authors":"Anne Rombaut, R. Brautaset, Pete A. Williams, James R. Tribble","doi":"10.3389/fopht.2023.1290465","DOIUrl":"https://doi.org/10.3389/fopht.2023.1290465","url":null,"abstract":"Glaucoma is the leading cause of irreversible blindness. Current treatment options are limited and often only slow disease progression. Metabolic dysfunction has recently been recognized as a key early and persistent mechanism in glaucoma pathophysiology. Several intrinsic metabolic dysfunctions have been identified and treated in retinal ganglion cells to provide neuroprotection. Growing pre-clinical and clinical evidence has confirmed that metabolic alterations in glaucoma are widespread, occurring across visual system tissues, in ocular fluids, in blood/serum, and at the level of genomic and mitochondrial DNA. This suggests that metabolic dysfunction is not constrained to retinal ganglion cells and that metabolic alterations extrinsic to retinal ganglion cells may contribute to their metabolic compromise. Retinal ganglion cells are reliant on glial metabolic support under normal physiological conditions, but the implications of metabolic dysfunction in glia are underexplored. We highlight emerging evidence that has demonstrated metabolic alterations occurring within glia in glaucoma, and how this may affect neuro-glial metabolic coupling and the metabolic vulnerability of retinal ganglion cells. In other neurodegenerative diseases which share features with glaucoma, several other glial metabolic alterations have been identified, suggesting that similar mechanisms and therapeutic targets may exist in glaucoma.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139222421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-24DOI: 10.3389/fopht.2023.1258734
David M. G. Anderson, A. Kotnala, Lukasz G. Migas, N. H. Patterson, Léonore E. M. Tideman, Dongfeng Cao, Bibek Adhikari, J. Messinger, T. Ach, Sara Tortorella, Raf Van de Plas, C. Curcio, K. Schey
Age related macular degeneration (AMD) causes legal blindness worldwide, with few therapeutic targets in early disease and no treatments for 80% of cases. Extracellular deposits, including drusen and subretinal drusenoid deposits (SDD; also called reticular pseudodrusen), disrupt cone and rod photoreceptor functions and strongly confer risk for advanced disease. Due to the differential cholesterol composition of drusen and SDD, lipid transfer and cycling between photoreceptors and support cells are candidate dysregulated pathways leading to deposit formation. The current study explores this hypothesis through a comprehensive lipid compositional analysis of SDD.Histology and transmission electron microscopy were used to characterize the morphology of SDD. Highly sensitive tools of imaging mass spectrometry (IMS) and nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) in positive and negative ion modes were used to spatially map and identify SDD lipids, respectively. An interpretable supervised machine learning approach was utilized to compare the lipid composition of SDD to regions of uninvolved retina across 1873 IMS features and to automatically discern candidate markers for SDD. Immunohistochemistry (IHC) was used to localize secretory phospholipase A2 group 5 (PLA2G5). Among the 1873 detected features in IMS data, three lipid classes, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lysophosphatidic acid (LysoPA) were observed nearly exclusively in SDD while presumed precursors, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidic acid (PA) lipids were detected in SDD and adjacent photoreceptor outer segments. Molecular signals specific to SDD were found in central retina and elsewhere. IHC results indicated abundant PLA2G5 in photoreceptors and retinal pigment epithelium (RPE). The abundance of lysolipids in SDD implicates lipid remodeling or degradation in deposit formation, consistent with ultrastructural evidence of electron dense lipid-containing structures distinct from photoreceptor outer segment disks and immunolocalization of secretory PLA2G5 in photoreceptors and RPE. Further studies are required to understand the role of lipid signals observed in and around SDD.
{"title":"Lysolipids are prominent in subretinal drusenoid deposits, a high-risk phenotype in age-related macular degeneration","authors":"David M. G. Anderson, A. Kotnala, Lukasz G. Migas, N. H. Patterson, Léonore E. M. Tideman, Dongfeng Cao, Bibek Adhikari, J. Messinger, T. Ach, Sara Tortorella, Raf Van de Plas, C. Curcio, K. Schey","doi":"10.3389/fopht.2023.1258734","DOIUrl":"https://doi.org/10.3389/fopht.2023.1258734","url":null,"abstract":"Age related macular degeneration (AMD) causes legal blindness worldwide, with few therapeutic targets in early disease and no treatments for 80% of cases. Extracellular deposits, including drusen and subretinal drusenoid deposits (SDD; also called reticular pseudodrusen), disrupt cone and rod photoreceptor functions and strongly confer risk for advanced disease. Due to the differential cholesterol composition of drusen and SDD, lipid transfer and cycling between photoreceptors and support cells are candidate dysregulated pathways leading to deposit formation. The current study explores this hypothesis through a comprehensive lipid compositional analysis of SDD.Histology and transmission electron microscopy were used to characterize the morphology of SDD. Highly sensitive tools of imaging mass spectrometry (IMS) and nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) in positive and negative ion modes were used to spatially map and identify SDD lipids, respectively. An interpretable supervised machine learning approach was utilized to compare the lipid composition of SDD to regions of uninvolved retina across 1873 IMS features and to automatically discern candidate markers for SDD. Immunohistochemistry (IHC) was used to localize secretory phospholipase A2 group 5 (PLA2G5). Among the 1873 detected features in IMS data, three lipid classes, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lysophosphatidic acid (LysoPA) were observed nearly exclusively in SDD while presumed precursors, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidic acid (PA) lipids were detected in SDD and adjacent photoreceptor outer segments. Molecular signals specific to SDD were found in central retina and elsewhere. IHC results indicated abundant PLA2G5 in photoreceptors and retinal pigment epithelium (RPE). The abundance of lysolipids in SDD implicates lipid remodeling or degradation in deposit formation, consistent with ultrastructural evidence of electron dense lipid-containing structures distinct from photoreceptor outer segment disks and immunolocalization of secretory PLA2G5 in photoreceptors and RPE. Further studies are required to understand the role of lipid signals observed in and around SDD.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139241360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meibomian gland dysfunction (MGD) is a prevalent worldwide eye disorder that causes eye irritation, inflammation, chronic dryness, and blurred vision. Traditional therapies offer temporary improvement, but their efficacy varies in severe MGD cases. Ocular intense pulsed light (IPL) has emerged as a novel therapy, providing long-term symptom relief and shorter treatment durations compared to traditional approaches. However, the impact of IPL on the bacterial community within the eyes remains limited. To address this, we conducted a preliminary study using metagenomics and next-generation sequencing. We compared the bacterial eyelash communities of Thai females with severe MGD before and after 2-4 IPL treatments, and against a group of healthy females. Our findings revealed higher bacterial diversity in healthy individuals compared to severe MGD cases. IPL treatments increased diversity in the MGD group, making their core bacterial community more similar to that of healthy subjects. Notably, the presence of Koribacteraceae in severe MGD and Bifidobacterium in healthy individuals and post-IPL-treated MGD exemplified this shift. Clustering analysis showed a closer relationship between post-IPL-treated MGH and healthy subjects, while the pre-IPL treatment group formed a separate branch. These results suggest that IPL treatment can reshape the eyelash microbiome in MGD cases, but further research is needed to understand the implications and the microbiome’s role in MGD pathogenesis and treatment response.
{"title":"Potential impact of ocular intense pulsed light on eyelash microbiome in severe meibomian gland dysfunction: report of 2 cases","authors":"N. Somboonna, Lampet Wongsaroj, Attawut Watthanathirakawi, Nattawut Wanumkarng, Anchana Iam-a-non, Krit Pongpirul","doi":"10.3389/fopht.2023.1240627","DOIUrl":"https://doi.org/10.3389/fopht.2023.1240627","url":null,"abstract":"Meibomian gland dysfunction (MGD) is a prevalent worldwide eye disorder that causes eye irritation, inflammation, chronic dryness, and blurred vision. Traditional therapies offer temporary improvement, but their efficacy varies in severe MGD cases. Ocular intense pulsed light (IPL) has emerged as a novel therapy, providing long-term symptom relief and shorter treatment durations compared to traditional approaches. However, the impact of IPL on the bacterial community within the eyes remains limited. To address this, we conducted a preliminary study using metagenomics and next-generation sequencing. We compared the bacterial eyelash communities of Thai females with severe MGD before and after 2-4 IPL treatments, and against a group of healthy females. Our findings revealed higher bacterial diversity in healthy individuals compared to severe MGD cases. IPL treatments increased diversity in the MGD group, making their core bacterial community more similar to that of healthy subjects. Notably, the presence of Koribacteraceae in severe MGD and Bifidobacterium in healthy individuals and post-IPL-treated MGD exemplified this shift. Clustering analysis showed a closer relationship between post-IPL-treated MGH and healthy subjects, while the pre-IPL treatment group formed a separate branch. These results suggest that IPL treatment can reshape the eyelash microbiome in MGD cases, but further research is needed to understand the implications and the microbiome’s role in MGD pathogenesis and treatment response.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139245359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-23DOI: 10.3389/fopht.2023.1273575
Jaeyoung Yang, Jason Myers, Malcolm M. Slaughter
Retinal sensitivity to a variety of artificial sweeteners was tested by monitoring changes in internal free calcium in isolated retinal neurons using Fluo3. Several ligands, including aspartame and saccharin elevated internal free calcium. The effects of these ligands were mediated by both ligand-gated membrane channels and G-protein coupled receptors. We explored the receptors responsible for this phenomenon. Surprisingly, mRNA for subunits of the sweet taste receptor dimer (T1R2 and T1R3) were found in retina. Interestingly, knockdown of T1R2 reduced the response to saccharin but not aspartame. But TRPV1 channel antagonists suppressed the responses to aspartame. The results indicate that artificial sweeteners can increase internal free calcium in the retinal neurons through multiple pathways. Furthermore, aspartame reduced the b-wave, but not the a-wave, of the electroretinogram, indicating disruption of communication between photoreceptors and second order neurons.
通过使用 Fluo3 监测离体视网膜神经元内部游离钙的变化,测试了视网膜对各种人造甜味剂的敏感性。包括阿斯巴甜和糖精在内的几种配体使内部游离钙升高。这些配体的作用由配体门控膜通道和 G 蛋白偶联受体介导。我们探索了导致这一现象的受体。令人惊讶的是,在视网膜中发现了甜味受体二聚体(T1R2 和 T1R3)亚基的 mRNA。有趣的是,敲除 T1R2 会降低对糖精的反应,但不会降低对阿斯巴甜的反应。但 TRPV1 通道拮抗剂抑制了对阿斯巴甜的反应。结果表明,人工甜味剂可通过多种途径增加视网膜神经元内部的游离钙。此外,阿斯巴甜能降低视网膜电图的 b 波,但不能降低 a 波,这表明光感受器和二阶神经元之间的交流受到了干扰。
{"title":"Saccharin and aspartame excite rat retinal neurons","authors":"Jaeyoung Yang, Jason Myers, Malcolm M. Slaughter","doi":"10.3389/fopht.2023.1273575","DOIUrl":"https://doi.org/10.3389/fopht.2023.1273575","url":null,"abstract":"Retinal sensitivity to a variety of artificial sweeteners was tested by monitoring changes in internal free calcium in isolated retinal neurons using Fluo3. Several ligands, including aspartame and saccharin elevated internal free calcium. The effects of these ligands were mediated by both ligand-gated membrane channels and G-protein coupled receptors. We explored the receptors responsible for this phenomenon. Surprisingly, mRNA for subunits of the sweet taste receptor dimer (T1R2 and T1R3) were found in retina. Interestingly, knockdown of T1R2 reduced the response to saccharin but not aspartame. But TRPV1 channel antagonists suppressed the responses to aspartame. The results indicate that artificial sweeteners can increase internal free calcium in the retinal neurons through multiple pathways. Furthermore, aspartame reduced the b-wave, but not the a-wave, of the electroretinogram, indicating disruption of communication between photoreceptors and second order neurons.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139244389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}