Journal of Personalized Medicine

Editorial

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4 pages, 165 KiB

Open AccessEditorial

Age-Related Macular Degeneration and Diabetic Retinopathy

by Andreas Ebneter and Peter D. Westenskow

J. Pers. Med. 2022, 12(4), 581; https://doi.org/10.3390/jpm12040581 - 05 Apr 2022

Cited by 1 | Viewed by 1075

Abstract

More than 15 years ago, the results of the pivotal trials supporting the intravitreal use of ranibizumab were published [...] Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

Research

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10 pages, 2050 KiB

Open AccessArticle

Correlation of Volume of Macular Edema with Retinal Tomography Features in Diabetic Retinopathy Eyes

by Santosh Gopi Krishna Gadde, Arpita Kshirsagar, Neha Anegondi, Thirumalesh B. Mochi, Stephane Heymans, Arkasubhra Ghosh and Abhijit Sinha Roy

J. Pers. Med. 2021, 11(12), 1337; https://doi.org/10.3390/jpm11121337 - 09 Dec 2021

Cited by 1 | Viewed by 1770

Abstract

Optical coherence tomography (OCT) enables the detection of macular edema, a significant pathological outcome of diabetic retinopathy (DR). The aim of the study was to correlate edema volume with the severity of diabetic retinopathy and response to treatment with intravitreal injections (compared to [...] Read more.

Optical coherence tomography (OCT) enables the detection of macular edema, a significant pathological outcome of diabetic retinopathy (DR). The aim of the study was to correlate edema volume with the severity of diabetic retinopathy and response to treatment with intravitreal injections (compared to baseline). Diabetic retinopathy (DR; n = 181) eyes were imaged with OCT (Heidelberg Engineering, Germany). They were grouped as responders (a decrease in thickness after intravitreal injection of Bevacizumab), non-responders (persistent edema or reduced decrease in thickness), recurrent (recurrence of edema after injection), and treatment naïve (no change in edema at follow-up without any injection). The post-treatment imaging of eyes was included for all groups, except for the treatment naïve group. All eyes underwent a 9 × 6 mm raster scan to measure the edema volume (EV). Central foveal thickness (CFT), central foveal volume (CFV), and total retinal volume (TRV) were obtained from the early treatment diabetic retinopathy study (ETDRS) map. The median EV increased with DR severity, with PDR having the greatest EV (4.01 mm³). This correlated positively with TRV (p < 0.001). Median CFV and CFT were the greatest in severe NPDR. Median EV was the greatest in the recurrent eyes (4.675 mm³) and lowest (1.6 mm³) in the treatment naïve group. Responders and non-responders groups had median values of 3.65 and 3.93 mm³, respectively. This trend was not observed with CFV, CFT, and TRV. A linear regression yielded threshold values of CFV (~0.3 mm³), CFT (~386 µm), and TRV (~9.06 mm³), above which EV may be detected by the current scanner. In this study, EV provided a better distinction between the response groups when compared to retinal tomography parameters. The EV increased with disease severity. Thus, EV can be a more precise parameter to identify subclinical edema and aid in better treatment planning. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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10 pages, 2134 KiB

Open AccessArticle

miRNA Levels as a Biomarker for Anti-VEGF Response in Patients with Diabetic Macular Edema

by Maartje J. C. Vader, Yasmin I. Habani, Reinier O. Schlingemann and Ingeborg Klaassen

J. Pers. Med. 2021, 11(12), 1297; https://doi.org/10.3390/jpm11121297 - 04 Dec 2021

Cited by 1 | Viewed by 1840

Abstract

Background: The aim of this study was to investigate whether miRNA levels in the circulation could serve as a predictive biomarker for responsiveness to anti-vascular endothelial growth factor (VEGF) therapy in patients with diabetic macular edema. Methods: Whole blood samples were collected at [...] Read more.

Background: The aim of this study was to investigate whether miRNA levels in the circulation could serve as a predictive biomarker for responsiveness to anti-vascular endothelial growth factor (VEGF) therapy in patients with diabetic macular edema. Methods: Whole blood samples were collected at baseline from 135 patients who were included in the BRDME study, a randomized controlled comparative trial of monthly bevacizumab or ranibizumab treatment for 6 months in patients with diabetic macular edema (Trialregister.nl, NTR3247). Best corrected visual acuity letter score (BCVA) and retinal central area thickness (CAT) were measured monthly during the 6-month follow-up. Levels of selected miRNAs were quantified. Results: Following linear regression analysis, the levels of four miRNAs were negatively associated with baseline CAT. Multivariable regression analysis confirmed this association for miR-181a. No associations with changes in CAT after 3 or 6 months of anti-VEGF treatment were found. In addition, no associations with miRNA levels with baseline BCVA or change in BCVA after 3 or 6 months of anti-VEGF treatment were found. Conclusions: Circulating miR-181a levels were negatively associated with CAT at baseline. However, no associations between miRNA levels and the response to anti-VEGF therapy were found. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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22 pages, 3665 KiB

Open AccessArticle

Semi-Quantitative Multiplex Profiling of the Complement System Identifies Associations of Complement Proteins with Genetic Variants and Metabolites in Age-Related Macular Degeneration

by I. Erkin Acar, Esther Willems, Eveline Kersten, Jenneke Keizer-Garritsen, Else Kragt, Bjorn Bakker, Tessel E. Galesloot, Carel B. Hoyng, Sascha Fauser, Alain J. van Gool, Yara T. E. Lechanteur, Elod Koertvely, Everson Nogoceke, Jolein Gloerich, Marien I. de Jonge, Laura Lorés-Motta and Anneke I. den Hollander

J. Pers. Med. 2021, 11(12), 1256; https://doi.org/10.3390/jpm11121256 - 25 Nov 2021

Cited by 5 | Viewed by 2273

Abstract

Age-related macular degeneration (AMD) is a major cause of vision loss among the elderly in the Western world. The complement system has been identified as one of the main AMD disease pathways. We performed a comprehensive expression analysis of 32 complement proteins in [...] Read more.

Age-related macular degeneration (AMD) is a major cause of vision loss among the elderly in the Western world. The complement system has been identified as one of the main AMD disease pathways. We performed a comprehensive expression analysis of 32 complement proteins in plasma samples of 255 AMD patients and 221 control individuals using mass spectrometry-based semi-quantitative multiplex profiling. We detected significant associations of complement protein levels with age, sex and body-mass index (BMI), and potential associations of C-reactive protein, factor H related-2 (FHR-2) and collectin-11 with AMD. In addition, we confirmed previously described associations and identified new associations of AMD variants with complement levels. New associations include increased C4 levels for rs181705462 at the C2/CFB locus, decreased vitronectin (VTN) levels for rs11080055 at the TMEM97/VTN locus and decreased factor I levels for rs10033900 at the CFI locus. Finally, we detected significant associations between AMD-associated metabolites and complement proteins in plasma. The most significant complement-metabolite associations included increased high density lipoprotein (HDL) subparticle levels with decreased C3, factor H (FH) and VTN levels. The results of our study indicate that demographic factors, genetic variants and circulating metabolites are associated with complement protein components. We suggest that these factors should be considered to design personalized treatment approaches and to increase the success of clinical trials targeting the complement system. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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9 pages, 387 KiB

Open AccessArticle

Specific Autoantibodies in Neovascular Age-Related Macular Degeneration: Evaluation of Morphological and Functional Progression over Five Years

by Michelle Prasuhn, Caroline Hillers, Felix Rommel, Gabriela Riemekasten, Harald Heidecke, Khaled Nassar, Mahdy Ranjbar, Salvatore Grisanti and Aysegül Tura

J. Pers. Med. 2021, 11(11), 1207; https://doi.org/10.3390/jpm11111207 - 16 Nov 2021

Cited by 1 | Viewed by 1352

Abstract

(1) Background: Altered levels of autoantibodies (aab) and their networks have been identified as biomarkers for various diseases. Neovascular age-related macular degeneration (nAMD) is a leading cause for central vision loss worldwide with highly variable inter- and intraindividual disease courses. Certain aab networks [...] Read more.

(1) Background: Altered levels of autoantibodies (aab) and their networks have been identified as biomarkers for various diseases. Neovascular age-related macular degeneration (nAMD) is a leading cause for central vision loss worldwide with highly variable inter- and intraindividual disease courses. Certain aab networks could help in daily routine to identify patients with a high disease activity who need to be visited and treated more regularly. (2) Methods: We analyzed levels of aab against Angiotensin II receptor type 1 (AT1-receptor), Protease-activated receptors (PAR1), vascular endothelial growth factor (VEGF) -A, VEGF-B, and VEGF-receptor 2 in sera of 164 nAMD patients. In a follow-up period of five years, we evaluated changes in functional and morphological characteristics. Using correlation analyses, multiple regression models, and receiver operator characteristics, we assessed whether the five aab have a clinical significance as biomarkers that correspond to the clinical properties. (3) Results: Neither the analyzed aab individually nor taken together as a network showed statistically significant results that would allow us to draw conclusions on the clinical five-year course in nAMD patients. (4) Conclusions: The five aab that we analyzed do not correspond to the clinical five-year course of nAMD patients. However, larger, prospective studies should reevaluate different and more aab to gain deeper insights. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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17 pages, 2355 KiB

Open AccessArticle

The 2-Year Leakage Index and Quantitative Microaneurysm Results of the RECOVERY Study: Quantitative Ultra-Widefield Findings in Proliferative Diabetic Retinopathy Treated with Intravitreal Aflibercept

by Amy S. Babiuch, Charles C. Wykoff, Sari Yordi, Hannah Yu, Sunil K. Srivastava, Ming Hu, Thuy K. Le, Leina Lunasco, Jamie Reese, Muneeswar G. Nittala, SriniVas R. Sadda and Justis P. Ehlers

J. Pers. Med. 2021, 11(11), 1126; https://doi.org/10.3390/jpm11111126 - 01 Nov 2021

Cited by 6 | Viewed by 2327

Abstract

Eyes with proliferative diabetic retinopathy (PDR) have been shown to improve in the leakage index and microaneurysm (MA) count after intravitreal aflibercept (IAI) treatment. The authors investigated these changes via automatic segmentation on ultra-widefield fluorescein angiography (UWFA). Forty subjects with PDR were randomized [...] Read more.

Eyes with proliferative diabetic retinopathy (PDR) have been shown to improve in the leakage index and microaneurysm (MA) count after intravitreal aflibercept (IAI) treatment. The authors investigated these changes via automatic segmentation on ultra-widefield fluorescein angiography (UWFA). Forty subjects with PDR were randomized to receive either 2 mg IAI every 4 weeks (Arm 1) or every 12 weeks (Arm 2) through Year 1. After Year 1, Arm 1 switched to quarterly IAI and Arm 2 to monthly IAI through Year 2. By Year 2, the Arm 1 leakage index decreased by 43% from Baseline (p = 0.03) but increased by 59% from Year 1 (p = 0.04). Arm 2 decreased by 61% from Baseline (p = 0.008) and by 31% from Year 1 (p = 0.12). Both cohorts exhibited a significant decline in MAs from Baseline to Year 2 (871 to 410; p < 0.001; 776 to 207; p < 0.001, respectively). Subjects with an improved leakage and MA count showed a more significant improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. Moreover, central subfield thickness (CST) was positively associated with changes in the leakage index. In conclusion, the leakage index and MA counts significantly improved from Baseline following IAI treatment, and monthly injections provided a more rapid and sustained reduction in these parameters compared with quarterly injections. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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7 pages, 3084 KiB

Open AccessArticle

Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

by Timothy Y. Y. Lai and Ricky Y. K. Lai

J. Pers. Med. 2021, 11(10), 1024; https://doi.org/10.3390/jpm11101024 - 14 Oct 2021

Cited by 6 | Viewed by 1657

Abstract

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear [...] Read more.

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman’s ρ = 0.54, p < 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: −2.5 letters, quartile 4: −9.5 letters; p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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13 pages, 2945 KiB

Open AccessArticle

Real-Time Diabetic Retinopathy Severity Score Level versus Ultra-Widefield Leakage Index-Guided Management of Diabetic Retinopathy: Two-Year Outcomes from the Randomized PRIME Trial

by Hannah J. Yu, Justis P. Ehlers, Duriye Damla Sevgi, Margaret O’Connell, Jamie L. Reese, Sunil K. Srivastava and Charles C. Wykoff

J. Pers. Med. 2021, 11(9), 885; https://doi.org/10.3390/jpm11090885 - 04 Sep 2021

Cited by 2 | Viewed by 2859

Abstract

The prospective PRIME trial applied real-time, objective imaging biomarkers to determine individualized retreatment needs with intravitreal aflibercept injections (IAI) among eyes with diabetic retinopathy (DR). 40 eyes with nonproliferative or proliferative DR without diabetic macular edema received monthly IAI until a DR severity [...] Read more.

The prospective PRIME trial applied real-time, objective imaging biomarkers to determine individualized retreatment needs with intravitreal aflibercept injections (IAI) among eyes with diabetic retinopathy (DR). 40 eyes with nonproliferative or proliferative DR without diabetic macular edema received monthly IAI until a DR severity scale (DRSS) level improvement of ≥2 steps was achieved. Eyes were randomized 1:1 to DRSS- or PLI- guided management. At the final 2-year visit, DRSS level was stable or improved compared to baseline in all eyes, and mean PLI decreased by 11% (p = 0.73) and 23.6% (p = 0.25) in the DRSS- and PLI-guided arms. In both arms, the percent of pro re nata (PRN) visits requiring IAI was significantly higher in year 2 versus 1 (p < 0.0001). The percent of PRN visits receiving IAI during year 1 was significantly correlated with the percent of PRN visits with IAI during year 2 (p < 0.0001). Through week 104, 77.4% of instances of DRSS level worsening in the DRSS-guided arm were preceded by or occurred alongside an increase of PLI. Overall, consistent IAI re-treatment interval requirements were observed longitudinally among individual patients. Additionally, PLI increases appeared to precede DRSS level worsening, highlighting PLI as a valuable biomarker in the management of DR. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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12 pages, 2069 KiB

Open AccessArticle

Characterization of Risk Profiles for Diabetic Retinopathy Progression

by José Cunha-Vaz and Luís Mendes

J. Pers. Med. 2021, 11(8), 826; https://doi.org/10.3390/jpm11080826 - 23 Aug 2021

Cited by 9 | Viewed by 2631

Abstract

Diabetic retinopathy (DR) is a frequent complication of diabetes and, through its vision-threatening complications, i.e., macular edema and proliferative retinopathy, may lead to blindness. It is, therefore, of major relevance to identify the presence of retinopathy in diabetic patients and, when present, to [...] Read more.

Diabetic retinopathy (DR) is a frequent complication of diabetes and, through its vision-threatening complications, i.e., macular edema and proliferative retinopathy, may lead to blindness. It is, therefore, of major relevance to identify the presence of retinopathy in diabetic patients and, when present, to identify the eyes that have the greatest risk of progression and greatest potential to benefit from treatment. In the present paper, we suggest the development of a simple to use alternative to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system, establishing disease severity as a necessary step to further evaluate and categorize the different risk factors involved in the progression of diabetic retinopathy. It needs to be validated against the ETDRS classification and, ideally, should be able to be performed automatically using data directly from the examination equipment without the influence of subjective individual interpretation. We performed the characterization of 105 eyes from 105 patients previously classified by ETDRS level by a Reading Centre using a set of rules generated by a decision tree having as possible inputs a set of metrics automatically extracted from Swept-source Optical Coherence Tomography (SS-OCTA) and Spectral Domain- OCT (SD-OCT) measured at different localizations of the retina. When the most relevant metrics were used to derive the rules to perform the organization of the full pathological dataset, taking into account the different ETDRS grades, a global accuracy equal to 0.8 was obtained. In summary, it is now possible to envision an automated classification of DR progression using noninvasive methods of examination, OCT, and SS-OCTA. Using this classification to establish the severity grade of DR, at the time of the ophthalmological examination, it is then possible to identify the risk of progression in severity and the development of vision-threatening complications based on the predominant phenotype. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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14 pages, 1227 KiB

Open AccessArticle

Glycemic Gap as a Useful Surrogate Marker for Glucose Variability and Progression of Diabetic Retinopathy

by Shi-Chue Hsing, Chin Lin, Jiann-Torng Chen, Yi-Hao Chen and Wen-Hui Fang

J. Pers. Med. 2021, 11(8), 799; https://doi.org/10.3390/jpm11080799 - 16 Aug 2021

Cited by 5 | Viewed by 2266

Abstract

(1) Background: Recent studies have reported that the glucose variability (GV), irrespective of glycosylated hemoglobin (HbA1c), could be an additional risk factor for the development of diabetic retinopathy (DR). However, measurements for GV, such as continuous glucose monitoring (CGM) and fasting plasma glucose [...] Read more.

(1) Background: Recent studies have reported that the glucose variability (GV), irrespective of glycosylated hemoglobin (HbA1c), could be an additional risk factor for the development of diabetic retinopathy (DR). However, measurements for GV, such as continuous glucose monitoring (CGM) and fasting plasma glucose (FPG) variability, are expensive and time consuming. (2) Methods: This present study aims to explore the correlation between the glycemic gap as a measurement of GV, and DR. In total, 2565 patients were included in this study. We evaluated the effect of the different types of glycemic gaps on DR progression. (3) Results: We found that the area under the curve (AUC) values of both the glycemic gap and negative glycemic gap showed an association with DR progression. (4) Conclusions: On eliminating the possible influences of chronic blood glucose controls, the results show that GV has deleterious effects that are associated with the progression of DR. The glycemic gap is a simple measurement of GV, and the predictive value of the negative glycemic gap in DR progression shows that GV and treatment-related hypoglycemia may cause the development of DR. Individual treatment goals with a reasonable HbA1c and minimal glucose fluctuations may help in preventing DR. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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17 pages, 753 KiB

Open AccessArticle

Ethnic Disparities in the Development of Sight-Threatening Diabetic Retinopathy in a UK Multi-Ethnic Population with Diabetes: An Observational Cohort Study

by Manjula D. Nugawela, Sarega Gurudas, A Toby Prevost, Rohini Mathur, John Robson, Wasim Hanif, Azeem Majeed and Sobha Sivaprasad

J. Pers. Med. 2021, 11(8), 740; https://doi.org/10.3390/jpm11080740 - 28 Jul 2021

Cited by 9 | Viewed by 2239

Abstract

There is little data on ethnic differences in incidence of DR and sight threatening DR (STDR) in the United Kingdom. We aimed to determine ethnic differences in the development of DR and STDR and to identify risk factors of DR and STDR in [...] Read more.

There is little data on ethnic differences in incidence of DR and sight threatening DR (STDR) in the United Kingdom. We aimed to determine ethnic differences in the development of DR and STDR and to identify risk factors of DR and STDR in people with incident or prevalent type II diabetes (T2DM). We used electronic primary care medical records of people registered with 134 general practices in East London during the period from January 2007–January 2017. There were 58,216 people with T2DM eligible to be included in the study. Among people with newly diagnosed T2DM, Indian, Pakistani and African ethnic groups showed an increased risk of DR with Africans having highest risk of STDR compared to White ethnic groups (HR: 1.36 95% CI 1.02–1.83). Among those with prevalent T2DM, Indian, Pakistani, Bangladeshi and Caribbean ethnic groups showed increased risk of DR and STDR with Indian having the highest risk of any DR (HR: 1.24 95% CI 1.16–1.32) and STDR (HR: 1.38 95% CI 1.17–1.63) compared with Whites after adjusting for all covariates considered. It is important to optimise prevention, screening and treatment options in these ethnic minority groups to avoid health inequalities in diabetes eye care. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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20 pages, 7784 KiB

Open AccessFeature PaperArticle

Accuracy of a Machine-Learning Algorithm for Detecting and Classifying Choroidal Neovascularization on Spectral-Domain Optical Coherence Tomography

by Andreas Maunz, Fethallah Benmansour, Yvonna Li, Thomas Albrecht, Yan-Ping Zhang, Filippo Arcadu, Yalin Zheng, Savita Madhusudhan and Jayashree Sahni

J. Pers. Med. 2021, 11(6), 524; https://doi.org/10.3390/jpm11060524 - 08 Jun 2021

Cited by 5 | Viewed by 2740

Abstract

Background: To evaluate the performance of a machine-learning (ML) algorithm to detect and classify choroidal neovascularization (CNV), secondary to age-related macular degeneration (AMD) on spectral-domain optical coherence tomography (SD-OCT) images. Methods: Baseline fluorescein angiography (FA) and SD-OCT images from 1037 treatment-naive study eyes [...] Read more.

Background: To evaluate the performance of a machine-learning (ML) algorithm to detect and classify choroidal neovascularization (CNV), secondary to age-related macular degeneration (AMD) on spectral-domain optical coherence tomography (SD-OCT) images. Methods: Baseline fluorescein angiography (FA) and SD-OCT images from 1037 treatment-naive study eyes and 531 fellow eyes, without advanced AMD from the phase 3 HARBOR trial (NCT00891735), were used to develop, train, and cross-validate an ML pipeline combining deep-learning–based segmentation of SD-OCT B-scans and CNV classification, based on features derived from the segmentations, in a five-fold setting. FA classification of the CNV phenotypes from HARBOR was used for generating the ground truth for model development. SD-OCT scans from the phase 2 AVENUE trial (NCT02484690) were used to externally validate the ML model. Results: The ML algorithm discriminated CNV absence from CNV presence, with a very high accuracy (area under the receiver operating characteristic [AUROC] = 0.99), and classified occult versus predominantly classic CNV types, per FA assessment, with a high accuracy (AUROC = 0.91) on HARBOR SD-OCT images. Minimally classic CNV was discriminated with significantly lower performance. Occult and predominantly classic CNV types could be discriminated with AUROC = 0.88 on baseline SD-OCT images of 165 study eyes, with CNV from AVENUE. Conclusions: Our ML model was able to detect CNV presence and CNV subtypes on SD-OCT images with high accuracy in patients with neovascular AMD. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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9 pages, 721 KiB

Open AccessArticle

Diabetic Macular Edema Treated with 577-nm Subthreshold Micropulse Laser: A Real-Life, Long-Term Study

by Luisa Frizziero, Andrea Calciati, Tommaso Torresin, Giulia Midena, Raffaele Parrozzani, Elisabetta Pilotto and Edoardo Midena

J. Pers. Med. 2021, 11(5), 405; https://doi.org/10.3390/jpm11050405 - 13 May 2021

Cited by 20 | Viewed by 3152

Abstract

The aim of this study was to evaluate the long-term efficacy and safety of 577-nm subthreshold micropulse laser (SMPL) treatment in a large population of patients affected by mild diabetic macular edema (DME) in a real-life setting. We retrospectively evaluated 134 eyes affected [...] Read more.

The aim of this study was to evaluate the long-term efficacy and safety of 577-nm subthreshold micropulse laser (SMPL) treatment in a large population of patients affected by mild diabetic macular edema (DME) in a real-life setting. We retrospectively evaluated 134 eyes affected by previously untreated center-involving mild DME, and treated with 577-nm SMPL, using fixed parameters. Retreatment was performed at 3 months, in case of persistent retinal thickening. Optical coherence tomography (OCT), along with short and near-infrared fundus autofluorescence, were used to confirm long-term safety. At the end of at least one year follow-up, a significant improvement in visual acuity was documented, compared to baseline (77.3 ± 4.5 and 79.4 ± 4.4 ETDRS score at baseline and at final follow-up, respectively), as well as a reduction in the mean retinal thickness of the thickest ETDRS macular sector at baseline. A reduction in the central retinal thickness and the mean thickness of the nine ETDRS sectors was also found, without reaching statistical significance. No patients required intravitreal injections. No adverse effects were detected. This study suggests that 577-nm SMPL is a safe and repeatable treatment for mild DME that may be applied to real-life clinical settings using fixed parameters and protocols. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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Review

Jump to: Editorial, Research

20 pages, 1333 KiB

Open AccessReview

Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature

by Thomas L. Maurissen, Georgios Pavlou, Colette Bichsel, Roberto Villaseñor, Roger D. Kamm and Héloïse Ragelle

J. Pers. Med. 2022, 12(2), 148; https://doi.org/10.3390/jpm12020148 - 24 Jan 2022

Cited by 7 | Viewed by 4142

Abstract

Blood-neural barriers regulate nutrient supply to neuronal tissues and prevent neurotoxicity. In particular, the inner blood-retinal barrier (iBRB) and blood–brain barrier (BBB) share common origins in development, and similar morphology and function in adult tissue, while barrier breakdown and leakage of neurotoxic molecules [...] Read more.

Blood-neural barriers regulate nutrient supply to neuronal tissues and prevent neurotoxicity. In particular, the inner blood-retinal barrier (iBRB) and blood–brain barrier (BBB) share common origins in development, and similar morphology and function in adult tissue, while barrier breakdown and leakage of neurotoxic molecules can be accompanied by neurodegeneration. Therefore, pre-clinical research requires human in vitro models that elucidate pathophysiological mechanisms and support drug discovery, to add to animal in vivo modeling that poorly predict patient responses. Advanced cellular models such as microphysiological systems (MPS) recapitulate tissue organization and function in many organ-specific contexts, providing physiological relevance, potential for customization to different population groups, and scalability for drug screening purposes. While human-based MPS have been developed for tissues such as lung, gut, brain and tumors, few comprehensive models exist for ocular tissues and iBRB modeling. Recent BBB in vitro models using human cells of the neurovascular unit (NVU) showed physiological morphology and permeability values, and reproduced brain neurological disorder phenotypes that could be applicable to modeling the iBRB. Here, we describe similarities between iBRB and BBB properties, compare existing neurovascular barrier models, propose leverage of MPS-based strategies to develop new iBRB models, and explore potentials to personalize cellular inputs and improve pre-clinical testing. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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15 pages, 1073 KiB

Open AccessReview

Quantitative Imaging Biomarkers in Age-Related Macular Degeneration and Diabetic Eye Disease: A Step Closer to Precision Medicine

by Gagan Kalra, Sudeshna Sil Kar, Duriye Damla Sevgi, Anant Madabhushi, Sunil K. Srivastava and Justis P. Ehlers

J. Pers. Med. 2021, 11(11), 1161; https://doi.org/10.3390/jpm11111161 - 08 Nov 2021

Cited by 13 | Viewed by 3808

Abstract

The management of retinal diseases relies heavily on digital imaging data, including optical coherence tomography (OCT) and fluorescein angiography (FA). Targeted feature extraction and the objective quantification of features provide important opportunities in biomarker discovery, disease burden assessment, and predicting treatment response. Additional [...] Read more.

The management of retinal diseases relies heavily on digital imaging data, including optical coherence tomography (OCT) and fluorescein angiography (FA). Targeted feature extraction and the objective quantification of features provide important opportunities in biomarker discovery, disease burden assessment, and predicting treatment response. Additional important advantages include increased objectivity in interpretation, longitudinal tracking, and ability to incorporate computational models to create automated diagnostic and clinical decision support systems. Advances in computational technology, including deep learning and radiomics, open new doors for developing an imaging phenotype that may provide in-depth personalized disease characterization and enhance opportunities in precision medicine. In this review, we summarize current quantitative and radiomic imaging biomarkers described in the literature for age-related macular degeneration and diabetic eye disease using imaging modalities such as OCT, FA, and OCT angiography (OCTA). Various approaches used to identify and extract these biomarkers that utilize artificial intelligence and deep learning are also summarized in this review. These quantifiable biomarkers and automated approaches have unleashed new frontiers of personalized medicine where treatments are tailored, based on patient-specific longitudinally trackable biomarkers, and response monitoring can be achieved with a high degree of accuracy. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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12 pages, 249 KiB

Open AccessReview

Indicators of Visual Prognosis in Diabetic Macular Oedema

by Sagnik Sen, Kim Ramasamy and Sobha Sivaprasad

J. Pers. Med. 2021, 11(6), 449; https://doi.org/10.3390/jpm11060449 - 22 May 2021

Cited by 12 | Viewed by 3232

Abstract

Diabetic macular oedema (DMO) is an important cause of moderate vision loss in people with diabetes. Advances in imaging technology have shown that a significant proportion of patients with DMO respond sub-optimally to existing treatment options. Identifying associations and predictors of response before [...] Read more.

Diabetic macular oedema (DMO) is an important cause of moderate vision loss in people with diabetes. Advances in imaging technology have shown that a significant proportion of patients with DMO respond sub-optimally to existing treatment options. Identifying associations and predictors of response before treatment is initiated may help in explaining visual prognosis to patients and aid the development of personalized treatment strategies. Imaging features, such as central subfoveal thickness, photoreceptor integrity, disorganization of retinal inner layers, choroidal changes, and macular perfusion, have been reported to be prognostic factors of visual acuity (VA) in DMO. In this review we evaluated each risk factor to understand their relative importance in visual prognostication of DMO eyes post-treatment. Although individually, some of these factors may not be significant predictors, in combination they may form phenotypes that can inform visual prognosis. Stratification based on these phenotypes needs to be developed to progress to personalized medicine for DMO. Full article

(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)

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