Pub Date : 2024-09-19DOI: 10.1016/j.xops.2024.100624
Marcony R. Santhiago MD, PhD , Larissa R. Stival MD, PhD , Daniella C. Araujo PhD , Rosalia Antunes-Foschini MD, PhD , Marcia C. Toledo MD , Ianne L.S. Nunes MS , Claudia R. Morgado MD , Newton Kara-Junior MD, PhD
<div><h3>Purpose</h3><div>To investigate the relationship of inflammatory biomarkers with corneal epithelial quantifiable metrics in patients with keratoconus and in healthy eyes.</div></div><div><h3>Design</h3><div>Prospective observational comparative study.</div></div><div><h3>Participants</h3><div>This study included 100 eyes of 100 patients: 48 eyes of 48 patients with keratoconus and 52 healthy eyes of 52 healthy controls.</div></div><div><h3>Methods</h3><div>The concentrations of tear cytokines were investigated in both groups: interleukin (IL) 1B, IL6, IL8, IL10, IL12p70, and tumor necrosis factor α (TNFα) were obtained by capillary flow and measured using flow cytometer. Cortisol concentrations were determined in both groups from the most proximal hair segment as an index of cumulative secretion and measured by liquid chromatography mass spectrometry. Epithelial variables were obtained with OCT. Pearson correlation (r) was used to measure linear dependence between 2 different variables.</div></div><div><h3>Main Outcome Measures</h3><div>Investigating the existence, strength, and significance of any correlation between inflammatory biomarkers (IL1B, IL6, IL8, IL10, IL12p70, TNFα, and hair cortisol concentration) and OCT corneal epithelial quantifiable variables such as minimum and maximum epithelial thickness of the map, difference between the minimum and maximum (Epithelial Min-Max) and standard deviation of the epithelial thickness of the map (Epithelial Std Dev), and average epithelial thickness of the superior and inferior regions of the map.</div></div><div><h3>Results</h3><div>Eyes with keratoconus presented statistically significantly higher levels of IL1b (<em>P</em> = 0.02), IL6 (<em>P</em> < 0.0001), IL8 (<em>P</em> < 0.0001), and TNFα (<em>P</em> < 0.0001) and hair cortisol concentration (<em>P</em> = 0.01) compared with healthy controls.</div><div>There was a significant correlation between IL6 and measurement Epithelium Min-Max [Pearson = −0.59 (−0.69, −0.47); <em>P</em> < 0.0001] and Epithelial Std Dev (Pearson = +0.56 [0.44, 0.67]; <em>P</em> < 0.0001). There was a significant correlation between hair cortisol concentration and Epithelium Min-Max (Pearson = −0.27 [−0.42, −0.1]; <em>P</em> < 0.0001]) and Epithelium Std Dev groups (Pearson = +0.2 [0.03, 0.36]; <em>P</em> = 0.021). There was also a significant correlation between TNFα and Epithelial Max (Pearson = −0.37 [−0.55, 0.17]; <em>P</em> < 0.0001). We found no significant correlation between the concentration of IL1b, IL8, IL10, and IL2p70 with any epithelium parameters.</div></div><div><h3>Conclusions</h3><div>The higher concentration of inflammatory markers (IL6 and hair cortisol) in eyes with keratoconus present a significant correlation with OCT metrics identifying epithelial variability, such as Epithelial Min-Max and Std Dev. These findings demonstrate the role of chronic inflammation in eyes with keratoconus, and that these epithelial change
{"title":"Relationship of Inflammatory Mediators (Interleukin and Cortisol Concentrations) with Corneal Epithelial Quantifiable Metrics","authors":"Marcony R. Santhiago MD, PhD , Larissa R. Stival MD, PhD , Daniella C. Araujo PhD , Rosalia Antunes-Foschini MD, PhD , Marcia C. Toledo MD , Ianne L.S. Nunes MS , Claudia R. Morgado MD , Newton Kara-Junior MD, PhD","doi":"10.1016/j.xops.2024.100624","DOIUrl":"10.1016/j.xops.2024.100624","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the relationship of inflammatory biomarkers with corneal epithelial quantifiable metrics in patients with keratoconus and in healthy eyes.</div></div><div><h3>Design</h3><div>Prospective observational comparative study.</div></div><div><h3>Participants</h3><div>This study included 100 eyes of 100 patients: 48 eyes of 48 patients with keratoconus and 52 healthy eyes of 52 healthy controls.</div></div><div><h3>Methods</h3><div>The concentrations of tear cytokines were investigated in both groups: interleukin (IL) 1B, IL6, IL8, IL10, IL12p70, and tumor necrosis factor α (TNFα) were obtained by capillary flow and measured using flow cytometer. Cortisol concentrations were determined in both groups from the most proximal hair segment as an index of cumulative secretion and measured by liquid chromatography mass spectrometry. Epithelial variables were obtained with OCT. Pearson correlation (r) was used to measure linear dependence between 2 different variables.</div></div><div><h3>Main Outcome Measures</h3><div>Investigating the existence, strength, and significance of any correlation between inflammatory biomarkers (IL1B, IL6, IL8, IL10, IL12p70, TNFα, and hair cortisol concentration) and OCT corneal epithelial quantifiable variables such as minimum and maximum epithelial thickness of the map, difference between the minimum and maximum (Epithelial Min-Max) and standard deviation of the epithelial thickness of the map (Epithelial Std Dev), and average epithelial thickness of the superior and inferior regions of the map.</div></div><div><h3>Results</h3><div>Eyes with keratoconus presented statistically significantly higher levels of IL1b (<em>P</em> = 0.02), IL6 (<em>P</em> < 0.0001), IL8 (<em>P</em> < 0.0001), and TNFα (<em>P</em> < 0.0001) and hair cortisol concentration (<em>P</em> = 0.01) compared with healthy controls.</div><div>There was a significant correlation between IL6 and measurement Epithelium Min-Max [Pearson = −0.59 (−0.69, −0.47); <em>P</em> < 0.0001] and Epithelial Std Dev (Pearson = +0.56 [0.44, 0.67]; <em>P</em> < 0.0001). There was a significant correlation between hair cortisol concentration and Epithelium Min-Max (Pearson = −0.27 [−0.42, −0.1]; <em>P</em> < 0.0001]) and Epithelium Std Dev groups (Pearson = +0.2 [0.03, 0.36]; <em>P</em> = 0.021). There was also a significant correlation between TNFα and Epithelial Max (Pearson = −0.37 [−0.55, 0.17]; <em>P</em> < 0.0001). We found no significant correlation between the concentration of IL1b, IL8, IL10, and IL2p70 with any epithelium parameters.</div></div><div><h3>Conclusions</h3><div>The higher concentration of inflammatory markers (IL6 and hair cortisol) in eyes with keratoconus present a significant correlation with OCT metrics identifying epithelial variability, such as Epithelial Min-Max and Std Dev. These findings demonstrate the role of chronic inflammation in eyes with keratoconus, and that these epithelial change","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100624"},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655029","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 : 2024-09-19DOI: 10.1016/j.xops.2024.100625
John D. Hong PhD , Jose A. Colmenarez MS , Elliot H. Choi MD, PhD , Alex Suh BS , Andrew Suh BS , Matthew Lam MD , Annette Hoskin PhD , Don S. Minckler MD, MS , Ken Y. Lin MD, PhD , Kourosh Shahraki MD , Rupesh Agrawal MD , Pengfei Dong PhD , Linxia Gu PhD , Donny W. Suh MD, MBA
Purpose
With the growing popularity of badminton worldwide, the incidence of badminton-related ocular injuries is expected to rise. The high velocity of shuttlecocks renders ocular traumas particularly devastating, especially with the possibility of permanent vision loss. This study investigated the mechanism behind ocular complications through simulation analyses of mechanical stresses and pressures upon shuttlecock impact.
Design
Computational simulation study.
Participants
None.
Methods
A 3-dimensional human eye model was reconstructed based on the physiological and biomechanical properties of various ocular tissues. Finite element analysis simulations involved a frontal collision with a shuttlecock projectile at 128.7 km/hour (80 mph). Intraocular pressure (IOP) changes and tissue stress were mapped and quantified in the following ocular structures: the limbus, ciliary body, zonular fibers, ora serrata, retina, and optic nerve head.
Main Outcome Measures
Intraocular pressure and tissue stress.
Results
Upon shuttlecock impact, compressive force was transferred to the anterior pole of the cornea, propagating posteriorly to the optic nerve head. Deflection of forces anteriorly contributed to refractory oscillations of compressive and tensile stress of ocular tissue. Initial impact led to a momentary (<1 ms) spike in IOP 5.66 MPa (42.5 × 103 mmHg) that radially distributed for a very brief instance (<1 ms) of pressure at the trabecular meshwork of the iridocorneal angle of 1.25 MPa (9.4 × 103 mmHg). The lens had a maximal posterior displacement of 1.5 mm with peak zonular fiber tensile strain of 52%. The limbus, ciliary body, and ora serrata had a peak tensile stress of 5.16 MPa, 1.90 MPa, and 0.62 MPa, respectively. Compressive force from the sclera concentrated at the optic nerve head for a peak stress of 5.97 MPa while peak pressure from vitreous humor was 7.99 MPa.
Conclusions
Shuttlecock impact led to a very brief, substantial rise in pressure and stress significant for tissue damage and subsequent complications, such as secondary glaucoma, angle recession, lens subluxation, hyphema, or retinal dialysis. Our findings offer valuable mechanistic insights into how ocular structures are affected by shuttlecock projectile impact to inform clinical assessments and treatment strategies, while highlighting the importance of protective eyewear in racket sports.
Financial Disclosures
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Finite Element Analysis of Mechanical Ocular Sequelae from Badminton Shuttlecock Projectile Impact","authors":"John D. Hong PhD , Jose A. Colmenarez MS , Elliot H. Choi MD, PhD , Alex Suh BS , Andrew Suh BS , Matthew Lam MD , Annette Hoskin PhD , Don S. Minckler MD, MS , Ken Y. Lin MD, PhD , Kourosh Shahraki MD , Rupesh Agrawal MD , Pengfei Dong PhD , Linxia Gu PhD , Donny W. Suh MD, MBA","doi":"10.1016/j.xops.2024.100625","DOIUrl":"10.1016/j.xops.2024.100625","url":null,"abstract":"<div><h3>Purpose</h3><div>With the growing popularity of badminton worldwide, the incidence of badminton-related ocular injuries is expected to rise. The high velocity of shuttlecocks renders ocular traumas particularly devastating, especially with the possibility of permanent vision loss. This study investigated the mechanism behind ocular complications through simulation analyses of mechanical stresses and pressures upon shuttlecock impact.</div></div><div><h3>Design</h3><div>Computational simulation study.</div></div><div><h3>Participants</h3><div>None.</div></div><div><h3>Methods</h3><div>A 3-dimensional human eye model was reconstructed based on the physiological and biomechanical properties of various ocular tissues. Finite element analysis simulations involved a frontal collision with a shuttlecock projectile at 128.7 km/hour (80 mph). Intraocular pressure (IOP) changes and tissue stress were mapped and quantified in the following ocular structures: the limbus, ciliary body, zonular fibers, ora serrata, retina, and optic nerve head.</div></div><div><h3>Main Outcome Measures</h3><div>Intraocular pressure and tissue stress.</div></div><div><h3>Results</h3><div>Upon shuttlecock impact, compressive force was transferred to the anterior pole of the cornea, propagating posteriorly to the optic nerve head. Deflection of forces anteriorly contributed to refractory oscillations of compressive and tensile stress of ocular tissue. Initial impact led to a momentary (<1 ms) spike in IOP 5.66 MPa (42.5 × 10<sup>3</sup> mmHg) that radially distributed for a very brief instance (<1 ms) of pressure at the trabecular meshwork of the iridocorneal angle of 1.25 MPa (9.4 × 10<sup>3</sup> mmHg). The lens had a maximal posterior displacement of 1.5 mm with peak zonular fiber tensile strain of 52%. The limbus, ciliary body, and ora serrata had a peak tensile stress of 5.16 MPa, 1.90 MPa, and 0.62 MPa, respectively. Compressive force from the sclera concentrated at the optic nerve head for a peak stress of 5.97 MPa while peak pressure from vitreous humor was 7.99 MPa.</div></div><div><h3>Conclusions</h3><div>Shuttlecock impact led to a very brief, substantial rise in pressure and stress significant for tissue damage and subsequent complications, such as secondary glaucoma, angle recession, lens subluxation, hyphema, or retinal dialysis. Our findings offer valuable mechanistic insights into how ocular structures are affected by shuttlecock projectile impact to inform clinical assessments and treatment strategies, while highlighting the importance of protective eyewear in racket sports.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100625"},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655115","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 : 2024-09-14DOI: 10.1016/j.xops.2024.100621
Niloofar Radgoudarzi BS, Shahin Hallaj MD, Michael V. Boland MD, PhD, Brian Stagg MD, Sophia Y. Wang MD, MS, Benjamin Xu MD, PhD, Swarup S. Swaminathan MD, Eric N. Brown MD, PhD, Aiyin Chen MD, Catherine Q. Sun MD, Dilru C. Amarasekera MD, Jonathan S. Myers MD, Murtaza Saifee MD, William Halfpenny MB BChir, MEng, Keri Dirkes MPH, Linda Zangwill PhD, Kerry E. Goetz PhD, MS, Michelle Hribar PhD, MS, Sally L. Baxter MD, MSc
{"title":"Barriers to Extracting and Harmonizing Glaucoma Testing Data: Gaps, Shortcomings, and the Pursuit of FAIRness","authors":"Niloofar Radgoudarzi BS, Shahin Hallaj MD, Michael V. Boland MD, PhD, Brian Stagg MD, Sophia Y. Wang MD, MS, Benjamin Xu MD, PhD, Swarup S. Swaminathan MD, Eric N. Brown MD, PhD, Aiyin Chen MD, Catherine Q. Sun MD, Dilru C. Amarasekera MD, Jonathan S. Myers MD, Murtaza Saifee MD, William Halfpenny MB BChir, MEng, Keri Dirkes MPH, Linda Zangwill PhD, Kerry E. Goetz PhD, MS, Michelle Hribar PhD, MS, Sally L. Baxter MD, MSc","doi":"10.1016/j.xops.2024.100621","DOIUrl":"10.1016/j.xops.2024.100621","url":null,"abstract":"","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"4 6","pages":"Article 100621"},"PeriodicalIF":3.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142416753","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 : 2024-09-14DOI: 10.1016/j.xops.2024.100623
Benton Chuter MS , Justin Huynh MS , Shahin Hallaj MD , Evan Walker MS , Jeffrey M. Liebmann MD , Massimo A. Fazio PhD , Christopher A. Girkin MD, MSPH , Robert N. Weinreb MD , Mark Christopher PhD , Linda M. Zangwill PhD
Purpose
To evaluate RETFound, a foundation artificial intelligence model, using a diverse clinical research dataset to assess its accuracy in detecting glaucoma using optic disc photographs. The model's accuracy for glaucoma detection was evaluated across race, age, glaucoma severity, and various training cycles (epochs) and dataset sample sizes.
Design
Evaluation of a diagnostic technology.
Participants
The study included 9787 color fundus photographs (CFPs) from 2329 participants of diverse race (White [73.4%], Black [13.6%] and other [13%]), disease severity (21.8% mild glaucoma, 7.2% moderate or advanced glaucoma, 60.3% not glaucoma, and 10.7% unreported), and age (48.8% <60 years, 51.1% >60 years) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. All fundus photographs were graded as "Glaucomatous" or "Non-glaucomatous."
Methods
The study employed RETFound, a self-supervised learning model, to perform binary glaucoma classification. The diagnostic accuracy of RETFound was iteratively tested across different combinations of dataset sample sizes (50–2000 optic disc photographs), training cycles (5–50), and study subpopulations stratified by severity of glaucoma, age, and race).
Main Outcome Measures
Diagnostic accuracy area under the receiver operating characteristic curve (AUC) for classifying CFP as "Glaucomatous" or "Non-glaucomatous."
Results
Performance increased with larger training datasets and more training cycles, improving from 50 training images and 5 epochs (AUC: 0.52) to 2000 training images and 50 epochs (AUC: 0.86), with reduced gain in performance from approximately 500 and 1000 training images (AUC of 0.82 and 0.83, respectively). Performance was consistent across race and age for all training size and cycle number combinations: Black (AUC = 0.87) vs. other (AUC = 0.86), and >60 years (AUC = 0.84) vs. <60 years (AUC = 0.87). Performance was significantly higher in patients with moderate to severe vs. mild glaucoma (AUC = 0.95 vs. 0.84, respectively).
Conclusions
Good RETFound performance was observed with a relatively small sample size of optic disc photographs used for fine-tuning and across differences in race and age. RETFound’s ability to adapt across a range of CFP training conditions and populations suggests it is a promising tool to automate glaucoma detection in a variety of use cases.
Financial Disclosures
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Evaluating a Foundation Artificial Intelligence Model for Glaucoma Detection Using Color Fundus Photographs","authors":"Benton Chuter MS , Justin Huynh MS , Shahin Hallaj MD , Evan Walker MS , Jeffrey M. Liebmann MD , Massimo A. Fazio PhD , Christopher A. Girkin MD, MSPH , Robert N. Weinreb MD , Mark Christopher PhD , Linda M. Zangwill PhD","doi":"10.1016/j.xops.2024.100623","DOIUrl":"10.1016/j.xops.2024.100623","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate RETFound, a foundation artificial intelligence model, using a diverse clinical research dataset to assess its accuracy in detecting glaucoma using optic disc photographs. The model's accuracy for glaucoma detection was evaluated across race, age, glaucoma severity, and various training cycles (epochs) and dataset sample sizes.</div></div><div><h3>Design</h3><div>Evaluation of a diagnostic technology.</div></div><div><h3>Participants</h3><div>The study included 9787 color fundus photographs (CFPs) from 2329 participants of diverse race (White [73.4%], Black [13.6%] and other [13%]), disease severity (21.8% mild glaucoma, 7.2% moderate or advanced glaucoma, 60.3% not glaucoma, and 10.7% unreported), and age (48.8% <60 years, 51.1% >60 years) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. All fundus photographs were graded as \"Glaucomatous\" or \"Non-glaucomatous.\"</div></div><div><h3>Methods</h3><div>The study employed RETFound, a self-supervised learning model, to perform binary glaucoma classification. The diagnostic accuracy of RETFound was iteratively tested across different combinations of dataset sample sizes (50–2000 optic disc photographs), training cycles (5–50), and study subpopulations stratified by severity of glaucoma, age, and race).</div></div><div><h3>Main Outcome Measures</h3><div>Diagnostic accuracy area under the receiver operating characteristic curve (AUC) for classifying CFP as \"Glaucomatous\" or \"Non-glaucomatous.\"</div></div><div><h3>Results</h3><div>Performance increased with larger training datasets and more training cycles, improving from 50 training images and 5 epochs (AUC: 0.52) to 2000 training images and 50 epochs (AUC: 0.86), with reduced gain in performance from approximately 500 and 1000 training images (AUC of 0.82 and 0.83, respectively). Performance was consistent across race and age for all training size and cycle number combinations: Black (AUC = 0.87) vs. other (AUC = 0.86), and >60 years (AUC = 0.84) vs. <60 years (AUC = 0.87). Performance was significantly higher in patients with moderate to severe vs. mild glaucoma (AUC = 0.95 vs. 0.84, respectively).</div></div><div><h3>Conclusions</h3><div>Good RETFound performance was observed with a relatively small sample size of optic disc photographs used for fine-tuning and across differences in race and age. RETFound’s ability to adapt across a range of CFP training conditions and populations suggests it is a promising tool to automate glaucoma detection in a variety of use cases.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100623"},"PeriodicalIF":3.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704139","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 : 2024-09-12DOI: 10.1016/j.xops.2024.100622
Ishani Kapoor BS , Swara M. Sarvepalli MD, MS , Dilraj S. Grewal MD , Majda Hadziahmetovic MD
<div><h3>Topic</h3><div>Autoimmune retinopathy (AIR) is a group of rare inflammatory diseases treated with immunosuppression; however, there is no treatment consensus. This meta-analysis and review aims to investigate treatment effectiveness in slowing AIR progression.</div></div><div><h3>Clinical Relevance</h3><div>Autoimmune retinopathy is a group of diseases characterized by progressive vision loss that is both difficult to diagnose and treat. While there is some consensus regarding diagnostic criteria, evidence-based treatment consensus remains poorly understood. Current first-line treatment is systemic steroids and conventional steroid-sparing agents. However, patients often experience treatment failure and systemic adverse effects with these medications. Understanding the effect of medications on slowing multiple visual outcomes in AIR can help to guide future treatment protocols.</div></div><div><h3>Methods</h3><div>PubMed, Cochrane Library, Embase, and ClinicalTrials.gov were systematically searched from inception to November 2023. Included studies treated patients with AIR with systemic, local, and biologic therapy and reported visual acuity (VA), visual field (VF), cystoid macular edema (CME), electroretinogram, central retinal thickness (CRT), and/or ellipsoid zone (EZ) loss. Risk of bias was assessed using the Critical Appraisal Skills Programme checklist. Data for meta-analysis were pooled using a random-effects model.</div></div><div><h3>Results</h3><div>Analysis of 40 case reports demonstrated that treatment type significantly affects the improvement of VA in patients with nonparaneoplastic retinopathy. Meta-analysis of 12 studies demonstrated that any treatment decreases the risk of progression of all 6 outcomes. Systemic therapy slows VA loss (risk ratio [RR] = 0.04, 95% confidence interval [0.00, 0.91], <em>P</em> = 0.04), VF loss (RR = 0.01, 95% confidence interval [0.00, 0.14], <em>P</em> = 0.0007), and CME (RR = 0.02, 95% confidence interval [0.00, 0.34], <em>P</em> = 0.007). Local therapy slows VA loss (RR = 0.02, 95% confidence interval [0.00, 0.12], <em>P</em> < 0.00001), CME (RR = 0.06, 95% confidence interval [0.01, 0.43], <em>P</em> = 0.005), CRT loss (RR = 0.02, 95% confidence interval [0.00, 0.36], <em>P</em> = 0.007), and EZ loss (RR = 0.31, 95% confidence interval [0.14, 0.70], <em>P</em> = 0.004). Biologics slow VA loss (RR = 0.28, 95% confidence interval [0.12, 0.65], <em>P</em> = 0.003), VF loss (RR = 0.25, 95% confidence interval [0.15, 0.42], <em>P</em> < 0.00001), and CRT loss (RR = 0.19, 95% confidence interval [0.04, 0.79], <em>P</em> = 0.02).</div></div><div><h3>Conclusion</h3><div>Systemic therapy significantly reduces the risk of progressive visual loss. Local therapy significantly decreases the risk of both progressive visual loss and retinal morphology loss, and therefore may offer precise targeting of the retina. Biologics significantly reduce both functional and morphological retinal changes. Im
{"title":"Clinical Outcomes of Therapeutic Interventions for Autoimmune Retinopathy: A Meta-analysis and Systematic Review","authors":"Ishani Kapoor BS , Swara M. Sarvepalli MD, MS , Dilraj S. Grewal MD , Majda Hadziahmetovic MD","doi":"10.1016/j.xops.2024.100622","DOIUrl":"10.1016/j.xops.2024.100622","url":null,"abstract":"<div><h3>Topic</h3><div>Autoimmune retinopathy (AIR) is a group of rare inflammatory diseases treated with immunosuppression; however, there is no treatment consensus. This meta-analysis and review aims to investigate treatment effectiveness in slowing AIR progression.</div></div><div><h3>Clinical Relevance</h3><div>Autoimmune retinopathy is a group of diseases characterized by progressive vision loss that is both difficult to diagnose and treat. While there is some consensus regarding diagnostic criteria, evidence-based treatment consensus remains poorly understood. Current first-line treatment is systemic steroids and conventional steroid-sparing agents. However, patients often experience treatment failure and systemic adverse effects with these medications. Understanding the effect of medications on slowing multiple visual outcomes in AIR can help to guide future treatment protocols.</div></div><div><h3>Methods</h3><div>PubMed, Cochrane Library, Embase, and ClinicalTrials.gov were systematically searched from inception to November 2023. Included studies treated patients with AIR with systemic, local, and biologic therapy and reported visual acuity (VA), visual field (VF), cystoid macular edema (CME), electroretinogram, central retinal thickness (CRT), and/or ellipsoid zone (EZ) loss. Risk of bias was assessed using the Critical Appraisal Skills Programme checklist. Data for meta-analysis were pooled using a random-effects model.</div></div><div><h3>Results</h3><div>Analysis of 40 case reports demonstrated that treatment type significantly affects the improvement of VA in patients with nonparaneoplastic retinopathy. Meta-analysis of 12 studies demonstrated that any treatment decreases the risk of progression of all 6 outcomes. Systemic therapy slows VA loss (risk ratio [RR] = 0.04, 95% confidence interval [0.00, 0.91], <em>P</em> = 0.04), VF loss (RR = 0.01, 95% confidence interval [0.00, 0.14], <em>P</em> = 0.0007), and CME (RR = 0.02, 95% confidence interval [0.00, 0.34], <em>P</em> = 0.007). Local therapy slows VA loss (RR = 0.02, 95% confidence interval [0.00, 0.12], <em>P</em> < 0.00001), CME (RR = 0.06, 95% confidence interval [0.01, 0.43], <em>P</em> = 0.005), CRT loss (RR = 0.02, 95% confidence interval [0.00, 0.36], <em>P</em> = 0.007), and EZ loss (RR = 0.31, 95% confidence interval [0.14, 0.70], <em>P</em> = 0.004). Biologics slow VA loss (RR = 0.28, 95% confidence interval [0.12, 0.65], <em>P</em> = 0.003), VF loss (RR = 0.25, 95% confidence interval [0.15, 0.42], <em>P</em> < 0.00001), and CRT loss (RR = 0.19, 95% confidence interval [0.04, 0.79], <em>P</em> = 0.02).</div></div><div><h3>Conclusion</h3><div>Systemic therapy significantly reduces the risk of progressive visual loss. Local therapy significantly decreases the risk of both progressive visual loss and retinal morphology loss, and therefore may offer precise targeting of the retina. Biologics significantly reduce both functional and morphological retinal changes. Im","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100622"},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721690","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 : 2024-09-12DOI: 10.1016/j.xops.2024.100619
Rahul M. Dhodapkar MD , Eric Jung MD , Sun Young Lee MD, PhD
Purpose
To perform a review of research, funding, and clinical translation efforts for extracellular vesicles (EVs) within vision science.
Design
Retrospective analysis of publication, funding, and clinical trials data.
Methods
A pretrained large language model (Jina2) was used to create semantic embeddings for 41 282 abstracts from articles related to EVs archived on EMBASE and published between January 1966 and January 2024. The articles were projected and clustered according to semantic embedding similarity, and research subdomains for EVs were determined through inspection of term frequency-inverse document frequency weighted word clouds. Mann–Kendall trend analysis was performed to identify current areas of growth within EV research. Additionally, National Institutes of Health funding data from RePORT Expenditures and Results and clinical trials data from ClinicalTrials.gov were analyzed to correlate publication trends with funding support and clinical translation efforts.
Results
Unsupervised clustering and Mann–Kendall trend analysis identified wound healing/regeneration (P = 0.030) and neurodegenerative disease (P = 0.049) as significantly accelerating in growth of publication over time. Ophthalmology-restricted subset analysis identified that publications in age-related macular degeneration (P = 0.191) and clinical applications (P = 0.086) are no longer growing at a significant rate. Analysis of funding data identified that the National Cancer Institute was the top funding institution overall, but that the National Institute on Aging is rapidly advancing in terms of funding EV research and trials. Analysis of ClinicalTrials.gov data highlights a dearth of clinical trials within ophthalmology despite a growing number of studies in other medical subfields.
Conclusions
Extracellular vesicles remain a promising substrate for both the identification and treatment of vision-threatening diseases. A better understanding of the current landscape of research and funding trends should help to inform future funding and translational efforts.
Financial Disclosures
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"An Eye on Extracellular Vesicles: Trends and Clinical Translations in Vision Research","authors":"Rahul M. Dhodapkar MD , Eric Jung MD , Sun Young Lee MD, PhD","doi":"10.1016/j.xops.2024.100619","DOIUrl":"10.1016/j.xops.2024.100619","url":null,"abstract":"<div><h3>Purpose</h3><div>To perform a review of research, funding, and clinical translation efforts for extracellular vesicles (EVs) within vision science.</div></div><div><h3>Design</h3><div>Retrospective analysis of publication, funding, and clinical trials data.</div></div><div><h3>Methods</h3><div>A pretrained large language model (Jina2) was used to create semantic embeddings for 41 282 abstracts from articles related to EVs archived on EMBASE and published between January 1966 and January 2024. The articles were projected and clustered according to semantic embedding similarity, and research subdomains for EVs were determined through inspection of term frequency-inverse document frequency weighted word clouds. Mann–Kendall trend analysis was performed to identify current areas of growth within EV research. Additionally, National Institutes of Health funding data from RePORT Expenditures and Results and clinical trials data from ClinicalTrials.gov were analyzed to correlate publication trends with funding support and clinical translation efforts.</div></div><div><h3>Results</h3><div>Unsupervised clustering and Mann–Kendall trend analysis identified wound healing/regeneration (<em>P</em> = 0.030) and neurodegenerative disease (<em>P</em> = 0.049) as significantly accelerating in growth of publication over time. Ophthalmology-restricted subset analysis identified that publications in age-related macular degeneration (<em>P</em> = 0.191) and clinical applications (<em>P</em> = 0.086) are no longer growing at a significant rate. Analysis of funding data identified that the National Cancer Institute was the top funding institution overall, but that the National Institute on Aging is rapidly advancing in terms of funding EV research and trials. Analysis of ClinicalTrials.gov data highlights a dearth of clinical trials within ophthalmology despite a growing number of studies in other medical subfields.</div></div><div><h3>Conclusions</h3><div>Extracellular vesicles remain a promising substrate for both the identification and treatment of vision-threatening diseases. A better understanding of the current landscape of research and funding trends should help to inform future funding and translational efforts.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100619"},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655081","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 : 2024-09-12DOI: 10.1016/j.xops.2024.100620
Abu Tahir Taha BS , Liangbo Linus Shen MD , Antonio Diaz BS , Noor Chahal BS , Jasmeet Saroya BS , Mengyuan Sun PhD , Michael J. Allingham MD, PhD , Sina Farsiu PhD , Glenn Yiu MD, PhD , Jeremy D. Keenan MD, MPH , Jay M. Stewart MD
Purpose
To investigate the association between rim area focal hyperautofluorescence (RAFH) signals and geographic atrophy (GA) growth rates, as well as the impact of oral metformin on the longitudinal change of RAFH.
Design
Secondary analysis of a randomized controlled trial.
Participants
Seventy-one eyes from 44 participants with GA and ≥6 months of follow-up in the METformin for the MINimization of geographic atrophy progression study.
Methods
Fundus autofluorescence images were captured using a 488 nm excitation wavelength. Two masked graders identified and measured RAFH lesions using proprietary semiautomatic segmentation software and ImageJ. We calculated RAFH by dividing the areas of hyperautofluorescence within a 450-μm rim circumscribing the GA by the total area enclosed within this rim.
Main Outcome Measures
Longitudinal changes in RAFH and GA area.
Results
Baseline RAFH was positively associated with the baseline square root of GA area 0.065/year (P < 0.001). In the entire study cohort, higher baseline RAFH was associated with a faster GA area growth rate in mm2/year (Spearman’s ρ = 0.53; P < 0.001). The association became weaker in square root-transformed GA area growth (ρ = 0.19, P = 0.11) and perimeter-adjusted GA growth rate (ρ = 0.28, P = 0.02), achieving statistical significance only in the latter. When this analysis was stratified into 3 baseline GA tertiles, the first and second tertiles showed weak to moderate association with statistical significance in all 3 modes of GA growth rates. Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (P < 0.01). Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (P < 0.01). The use of oral metformin was not significantly associated with the change in RAFH over time compared with the observation group (0.023/year vs. 0.016/year; P = 0.29).
Conclusions
Increased baseline RAFH is associated with faster GA area progression. However, the effect size of this association may depend on the baseline GA lesion size such that small to medium-sized GA lesions display this relationship regardless of the mode of the calculation of GA growth rate.
Financial Disclosures
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
目的研究边缘区局灶性高自荧光（RAFH）信号与地理萎缩（GA）生长率之间的关联，以及口服二甲双胍对RAFH纵向变化的影响。方法使用488 nm激发波长采集Fundus自荧光图像。两名蒙面分级人员使用专有的半自动分割软件和 ImageJ 识别并测量 RAFH 病变。我们计算 RAFH 的方法是，将环绕 GA 的 450 微米边缘内的高荧光区域除以该边缘内的总面积。结果基线 RAFH 与 GA 面积的基线平方根 0.065/年呈正相关（P < 0.001）。在整个研究队列中，基线 RAFH 越高，GA 面积的增长速度越快，单位为 mm2/年（Spearman's ρ = 0.53; P <0.001）。这种关联在经平方根转换的 GA 面积增长率（ρ = 0.19，P = 0.11）和周长调整后的 GA 增长率（ρ = 0.28，P = 0.02）中变得较弱，仅在后者中达到统计学意义。当该分析被分为 3 个基线 GA 三等分时，第一和第二等分显示出弱到中等程度的关联性，在所有 3 种 GA 增长率模式中均有统计学意义。边缘区局灶性高自荧光随着时间的推移略有增加，但显著性为 0.020/年（P < 0.01）。边缘区局灶性高自荧光略有增加，但随着时间的推移显著增加，0.020/年（P <0.01）。与观察组相比，口服二甲双胍与 RAFH 随时间的变化无显著相关性（0.023/年 vs. 0.016/年；P = 0.29）。然而，这种关联的效应大小可能取决于基线GA病变的大小，因此无论GA生长率的计算模式如何，中小型GA病变都会显示出这种关系。
{"title":"Association of Hyperautofluorescence Signals with Geographic Atrophy Progression in the METformin for the MINimization of Geographic Atrophy Progression Trial","authors":"Abu Tahir Taha BS , Liangbo Linus Shen MD , Antonio Diaz BS , Noor Chahal BS , Jasmeet Saroya BS , Mengyuan Sun PhD , Michael J. Allingham MD, PhD , Sina Farsiu PhD , Glenn Yiu MD, PhD , Jeremy D. Keenan MD, MPH , Jay M. Stewart MD","doi":"10.1016/j.xops.2024.100620","DOIUrl":"10.1016/j.xops.2024.100620","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the association between rim area focal hyperautofluorescence (RAFH) signals and geographic atrophy (GA) growth rates, as well as the impact of oral metformin on the longitudinal change of RAFH.</div></div><div><h3>Design</h3><div>Secondary analysis of a randomized controlled trial.</div></div><div><h3>Participants</h3><div>Seventy-one eyes from 44 participants with GA and ≥6 months of follow-up in the METformin for the MINimization of geographic atrophy progression study.</div></div><div><h3>Methods</h3><div>Fundus autofluorescence images were captured using a 488 nm excitation wavelength. Two masked graders identified and measured RAFH lesions using proprietary semiautomatic segmentation software and ImageJ. We calculated RAFH by dividing the areas of hyperautofluorescence within a 450-μm rim circumscribing the GA by the total area enclosed within this rim.</div></div><div><h3>Main Outcome Measures</h3><div>Longitudinal changes in RAFH and GA area.</div></div><div><h3>Results</h3><div>Baseline RAFH was positively associated with the baseline square root of GA area 0.065/year (<em>P</em> < 0.001). In the entire study cohort, higher baseline RAFH was associated with a faster GA area growth rate in mm<sup>2</sup>/year (Spearman’s ρ = 0.53; <em>P</em> < 0.001). The association became weaker in square root-transformed GA area growth (ρ = 0.19, <em>P</em> = 0.11) and perimeter-adjusted GA growth rate (ρ = 0.28, <em>P</em> = 0.02), achieving statistical significance only in the latter. When this analysis was stratified into 3 baseline GA tertiles, the first and second tertiles showed weak to moderate association with statistical significance in all 3 modes of GA growth rates. Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (<em>P</em> < 0.01). Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (<em>P</em> < 0.01). The use of oral metformin was not significantly associated with the change in RAFH over time compared with the observation group (0.023/year vs. 0.016/year; <em>P</em> = 0.29).</div></div><div><h3>Conclusions</h3><div>Increased baseline RAFH is associated with faster GA area progression. However, the effect size of this association may depend on the baseline GA lesion size such that small to medium-sized GA lesions display this relationship regardless of the mode of the calculation of GA growth rate.</div></div><div><h3>Financial Disclosures</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100620"},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655030","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 : 2024-09-11DOI: 10.1016/j.xops.2024.100618
Ferenc B. Sallo MD, PhD , Chantal Dysli MD, PhD , Franz Josef Holzer MD , Emmanuelle Ranza MD , Michel Guipponi MD , Stylianos E. Antonarakis MD , Francis L. Munier MD , Alan C. Bird MD , Daniel F. Schorderet MD , Beatrice Rossillion MD , Veronika Vaclavik MD
Purpose
To report the retinal phenotype in 2 patients simulating type 2 macular telangiectasis with new variants in CYP2U1 implicated in hereditary spastic paraplegia type 56 (HSP 56).
Design
Cross sectional case series study.
Participants
Five members of a non-consanguineous family (parents and 3 male children) were investigated.
Methods
All family members underwent a full ophthalmic evaluation and multimodal retinal imaging. Two family members demonstrating retinal anomalies underwent additional OCT angiography, dual wavelength autofluorescence and fluorescence lifetime imaging ophthalmoscopy, kinetic perimetry, fundus-correlated microperimetry, electroretinography, and electro-oculography. Whole-exome sequencing was performed in all 5 family members.
Main Outcome Measures
To characterize the retinal phenotype in affected patients with variants in CYP2U1, using multimodal imaging: dual-wavelength autofluorescence, fluorescence lifetime, OCT angiography.
Results
The 2 siblings with compound heterozygous novel variants c.452C>T; p.(Pro151Leu), c.943C>T; p.(Gln315Ter) in CYP2U1 demonstrated parafoveal loss of retinal transparency and hyperreflectivity to blue light, redistribution of macular pigment to the parafoveal edge, photoreceptor loss, and fluorescence lifetime imaging ophthalmoscopy anomalies: a pattern compatible with that seen in macular telangiectasia type 2 (MacTel). One had manifest neurological abnormalities since early childhood; the second had no neurological abnormalities. Each parent and the third sibling were heterozygous for 1 variant and were neurologically and ophthalmically normal.
Conclusions
These CYP2U1 variants are associated with a retinal phenotype very similar to that otherwise specific for MacTel, suggestive of possible links in the etiology and pathogenesis of these diseases.
Financial Disclosure(s)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
{"title":"Characterization of the Retinal Phenotype Using Multimodal Imaging in Novel Compound Heterozygote Variants of CYP2U1","authors":"Ferenc B. Sallo MD, PhD , Chantal Dysli MD, PhD , Franz Josef Holzer MD , Emmanuelle Ranza MD , Michel Guipponi MD , Stylianos E. Antonarakis MD , Francis L. Munier MD , Alan C. Bird MD , Daniel F. Schorderet MD , Beatrice Rossillion MD , Veronika Vaclavik MD","doi":"10.1016/j.xops.2024.100618","DOIUrl":"10.1016/j.xops.2024.100618","url":null,"abstract":"<div><h3>Purpose</h3><div>To report the retinal phenotype in 2 patients simulating type 2 macular telangiectasis with new variants in <em>CYP2U1</em> implicated in hereditary spastic paraplegia type 56 (HSP 56).</div></div><div><h3>Design</h3><div>Cross sectional case series study.</div></div><div><h3>Participants</h3><div>Five members of a non-consanguineous family (parents and 3 male children) were investigated.</div></div><div><h3>Methods</h3><div>All family members underwent a full ophthalmic evaluation and multimodal retinal imaging. Two family members demonstrating retinal anomalies underwent additional OCT angiography, dual wavelength autofluorescence and fluorescence lifetime imaging ophthalmoscopy, kinetic perimetry, fundus-correlated microperimetry, electroretinography, and electro-oculography. Whole-exome sequencing was performed in all 5 family members.</div></div><div><h3>Main Outcome Measures</h3><div>To characterize the retinal phenotype in affected patients with variants in <em>CYP2U1</em>, using multimodal imaging: dual-wavelength autofluorescence, fluorescence lifetime, OCT angiography.</div></div><div><h3>Results</h3><div>The 2 siblings with compound heterozygous novel variants c.452C>T; p.(Pro151Leu), c.943C>T; p.(Gln315Ter) in <em>CYP2U1</em> demonstrated parafoveal loss of retinal transparency and hyperreflectivity to blue light, redistribution of macular pigment to the parafoveal edge, photoreceptor loss, and fluorescence lifetime imaging ophthalmoscopy anomalies: a pattern compatible with that seen in macular telangiectasia type 2 (MacTel). One had manifest neurological abnormalities since early childhood; the second had no neurological abnormalities. Each parent and the third sibling were heterozygous for 1 variant and were neurologically and ophthalmically normal.</div></div><div><h3>Conclusions</h3><div>These <em>CYP2U1</em> variants are associated with a retinal phenotype very similar to that otherwise specific for MacTel, suggestive of possible links in the etiology and pathogenesis of these diseases.</div></div><div><h3>Financial Disclosure(s)</h3><div>The author(s) have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100618"},"PeriodicalIF":3.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655114","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}
To evaluate the severity scales of diabetic macular ischemia (DMI) by analyzing the quantity and distribution of capillary nonperfusion using OCT angiography (OCTA) images.
Design
A single-center, prospective case series.
Participants
Three hundred one eyes from 301 patients with diabetic retinopathy.
Methods
We acquired 3 × 3-mm swept-source OCTA images and created en face images within a central 2.5-mm circle. The circle was divided into 15 × 15-pixel squares and nonperfusion squares (NPSs) were defined as those without retinal vessels. Eyes with high-dimensional spatial data were arranged on a 2-dimensional space using the uniform manifold approximation and projection (UMAP) algorithm and classified by clustering into 5 groups: Initial, Mild, Superficial, Moderate, and Severe.
Main Outcome Measures
Development of a severity scale for DMI.
Results
Eyes arranged on a 2-dimensional UMAP space were divided into 5 clusters, based on the similarity of nonperfusion area distribution. Nonperfusion square counts in the deep layer increased in eyes of the Initial, Mild, Moderate, and Severe groups in a stepwise manner. In contrast, there were no significant changes in superficial NPS counts between eyes of the Initial and Mild groups. In the intermediate stage, eyes of the Superficial group exhibited higher NPS counts in the central sector of the superficial layer compared with those of the Moderate group. The foveal avascular zone extended into the temporal subfield of the deep layer in eyes of the Moderate group. Eyes of the Severe group had significantly poorer visual acuity that was more frequently accompanied with proliferative diabetic retinopathy.
Conclusions
The application of dimensionality reduction and clustering has facilitated the development of a novel severity scale for DMI based on the distribution of capillary nonperfusion in OCTA images.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any materials discussed in this article.
{"title":"Severity Scale of Diabetic Macular Ischemia Based on the Distribution of Capillary Nonperfusion in OCT Angiography","authors":"Miyo Yoshida MD, Tomoaki Murakami MD, PhD, Keiichi Nishikawa MD, Kenji Ishihara MD, PhD, Yuki Mori MD, PhD, Akitaka Tsujikawa MD, PhD","doi":"10.1016/j.xops.2024.100603","DOIUrl":"10.1016/j.xops.2024.100603","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the severity scales of diabetic macular ischemia (DMI) by analyzing the quantity and distribution of capillary nonperfusion using OCT angiography (OCTA) images.</div></div><div><h3>Design</h3><div>A single-center, prospective case series.</div></div><div><h3>Participants</h3><div>Three hundred one eyes from 301 patients with diabetic retinopathy.</div></div><div><h3>Methods</h3><div>We acquired 3 × 3-mm swept-source OCTA images and created en face images within a central 2.5-mm circle. The circle was divided into 15 × 15-pixel squares and nonperfusion squares (NPSs) were defined as those without retinal vessels. Eyes with high-dimensional spatial data were arranged on a 2-dimensional space using the uniform manifold approximation and projection (UMAP) algorithm and classified by clustering into 5 groups: <em>Initial</em>, <em>Mild</em>, <em>Superficial</em>, <em>Moderate</em>, and <em>Severe</em>.</div></div><div><h3>Main Outcome Measures</h3><div>Development of a severity scale for DMI.</div></div><div><h3>Results</h3><div>Eyes arranged on a 2-dimensional UMAP space were divided into 5 clusters, based on the similarity of nonperfusion area distribution. Nonperfusion square counts in the deep layer increased in eyes of the <em>Initial</em>, <em>Mild</em>, <em>Moderate</em>, and <em>Severe</em> groups in a stepwise manner. In contrast, there were no significant changes in superficial NPS counts between eyes of the <em>Initial</em> and <em>Mild</em> groups. In the intermediate stage, eyes of the <em>Superficial</em> group exhibited higher NPS counts in the central sector of the superficial layer compared with those of the <em>Moderate</em> group. The foveal avascular zone extended into the temporal subfield of the deep layer in eyes of the <em>Moderate</em> group. Eyes of the <em>Severe</em> group had significantly poorer visual acuity that was more frequently accompanied with proliferative diabetic retinopathy.</div></div><div><h3>Conclusions</h3><div>The application of dimensionality reduction and clustering has facilitated the development of a novel severity scale for DMI based on the distribution of capillary nonperfusion in OCTA images.</div></div><div><h3>Financial Disclosure(s)</h3><div>The authors have no proprietary or commercial interest in any materials discussed in this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100603"},"PeriodicalIF":3.2,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666914524001398/pdfft?md5=9fd86bd124fe988794885bc8b18f64b7&pid=1-s2.0-S2666914524001398-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314355","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 : 2024-09-05DOI: 10.1016/j.xops.2024.100616
Verônica Vilasboas-Campos MD , Alessandro A. Jammal MD, PhD , Carolina P.B. Gracitelli MD, PhD , Gustavo R. Gameiro MD , Vital P. Costa MD, PhD , Felipe A. Medeiros MD, PhD
Purpose
To evaluate the effect of aging on estimated retinal ganglion cell (RGC) counts over time in healthy eyes, obtained from a combination of structural and functional information.
Design
Longitudinal observational cohort study.
Participants
One hundred healthy eyes of 50 subjects.
Methods
Estimated RGC counts were obtained by a previously described method using standard automated perimetry sensitivity thresholds and OCT retinal nerve fiber layer thickness measurements. Linear mixed-effects models were applied to investigate the effect of aging, as well as other covariates, on rates of change in estimated RGC counts over time.
Main Outcome Measures
Rates of change in estimated RGC counts in healthy eyes.
Results
Subjects had a mean age of 49.6 ± 15.7 years at baseline (range 22.8–89.9 years) and were followed up for 3.5 ± 2.5 years. Thirty-three (66%) patients were female and 11 (22%) self-identified as Black. At baseline, the eyes had an average estimated RGC count of 1 144 010 ± 222 084 cells. After adjusting for confounding factors, the mean rate of change in estimated RGC counts was –6769 RGC/year (95% confidence interval: –10 994 to –2544 RGC/year; P = 0.002), or 0.6%/year. Older age and longer axial length were significantly associated with lower RGC counts at baseline.
Conclusions
A significant age-related decline in estimated RGC counts was found in healthy subjects with a combined metric integrating imaging and functional testing. The estimated mean age-related decline was remarkably similar to estimates from previous histologic studies in cadaver eyes, reinforcing the validity of the proposed combined metric and highlighting the importance of considering age when evaluating RGC count changes over time for monitoring glaucoma progression.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
{"title":"Estimated Rates of Retinal Ganglion Cell Loss with Aging","authors":"Verônica Vilasboas-Campos MD , Alessandro A. Jammal MD, PhD , Carolina P.B. Gracitelli MD, PhD , Gustavo R. Gameiro MD , Vital P. Costa MD, PhD , Felipe A. Medeiros MD, PhD","doi":"10.1016/j.xops.2024.100616","DOIUrl":"10.1016/j.xops.2024.100616","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the effect of aging on estimated retinal ganglion cell (RGC) counts over time in healthy eyes, obtained from a combination of structural and functional information.</div></div><div><h3>Design</h3><div>Longitudinal observational cohort study.</div></div><div><h3>Participants</h3><div>One hundred healthy eyes of 50 subjects.</div></div><div><h3>Methods</h3><div>Estimated RGC counts were obtained by a previously described method using standard automated perimetry sensitivity thresholds and OCT retinal nerve fiber layer thickness measurements. Linear mixed-effects models were applied to investigate the effect of aging, as well as other covariates, on rates of change in estimated RGC counts over time.</div></div><div><h3>Main Outcome Measures</h3><div>Rates of change in estimated RGC counts in healthy eyes.</div></div><div><h3>Results</h3><div>Subjects had a mean age of 49.6 ± 15.7 years at baseline (range 22.8–89.9 years) and were followed up for 3.5 ± 2.5 years. Thirty-three (66%) patients were female and 11 (22%) self-identified as Black. At baseline, the eyes had an average estimated RGC count of 1 144 010 ± 222 084 cells. After adjusting for confounding factors, the mean rate of change in estimated RGC counts was –6769 RGC/year (95% confidence interval: –10 994 to –2544 RGC/year; <em>P</em> = 0.002), or 0.6%/year. Older age and longer axial length were significantly associated with lower RGC counts at baseline.</div></div><div><h3>Conclusions</h3><div>A significant age-related decline in estimated RGC counts was found in healthy subjects with a combined metric integrating imaging and functional testing. The estimated mean age-related decline was remarkably similar to estimates from previous histologic studies in cadaver eyes, reinforcing the validity of the proposed combined metric and highlighting the importance of considering age when evaluating RGC count changes over time for monitoring glaucoma progression.</div></div><div><h3>Financial Disclosure(s)</h3><div>Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 1","pages":"Article 100616"},"PeriodicalIF":3.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655076","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}
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