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Article ; Online: Presumed Ocular Histoplasmosis with Choroidal Neovascularization in a 4-year-old.

Sevgi, Duriye Damla / Haider, Kathryn M / Moorthy, Ramana S

Ophthalmology. Retina

2023 Volume 7, Issue 10, Page(s) 917

MeSH term(s)	Humans ; Child, Preschool ; Histoplasmosis/complications ; Histoplasmosis/diagnosis ; Choroidal Neovascularization/diagnosis ; Eye
Language	English
Publishing date	2023-05-22
Publishing country	United States
Document type	Journal Article
ISSN	2468-6530
ISSN (online)	2468-6530
DOI	10.1016/j.oret.2023.04.012
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Article ; Online: Molecular Genetic Mechanisms in Age-Related Macular Degeneration.

Shughoury, Aumer / Sevgi, Duriye Damla / Ciulla, Thomas A

Genes

2022 Volume 13, Issue 7

Abstract: Age-related macular degeneration (AMD) is among the leading causes of irreversible blindness worldwide. In addition to environmental risk factors, such as tobacco use and diet, genetic background has long been established as a major risk factor for the ... ...

Abstract	Age-related macular degeneration (AMD) is among the leading causes of irreversible blindness worldwide. In addition to environmental risk factors, such as tobacco use and diet, genetic background has long been established as a major risk factor for the development of AMD. However, our ability to predict disease risk and personalize treatment remains limited by our nascent understanding of the molecular mechanisms underlying AMD pathogenesis. Research into the molecular genetics of AMD over the past two decades has uncovered 52 independent gene variants and 34 independent loci that are implicated in the development of AMD, accounting for over half of the genetic risk. This research has helped delineate at least five major pathways that may be disrupted in the pathogenesis of AMD: the complement system, extracellular matrix remodeling, lipid metabolism, angiogenesis, and oxidative stress response. This review surveys our current understanding of each of these disease mechanisms, in turn, along with their associated pathogenic gene variants. Continued research into the molecular genetics of AMD holds great promise for the development of precision-targeted, personalized therapies that bring us closer to a cure for this debilitating disease.
MeSH term(s)	Complement Factor H/genetics ; Humans ; Macular Degeneration/genetics ; Molecular Biology ; Polymorphism, Single Nucleotide ; Proteins/genetics
Chemical Substances	Proteins ; Complement Factor H (80295-65-4)
Language	English
Publishing date	2022-07-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13071233
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Article: Molecular Genetic Mechanisms in Age-Related Macular Degeneration

Shughoury, Aumer / Sevgi, Duriye Damla / Ciulla, Thomas A.

Genes. 2022 July 12, v. 13, no. 7

2022

Abstract	Age-related macular degeneration (AMD) is among the leading causes of irreversible blindness worldwide. In addition to environmental risk factors, such as tobacco use and diet, genetic background has long been established as a major risk factor for the development of AMD. However, our ability to predict disease risk and personalize treatment remains limited by our nascent understanding of the molecular mechanisms underlying AMD pathogenesis. Research into the molecular genetics of AMD over the past two decades has uncovered 52 independent gene variants and 34 independent loci that are implicated in the development of AMD, accounting for over half of the genetic risk. This research has helped delineate at least five major pathways that may be disrupted in the pathogenesis of AMD: the complement system, extracellular matrix remodeling, lipid metabolism, angiogenesis, and oxidative stress response. This review surveys our current understanding of each of these disease mechanisms, in turn, along with their associated pathogenic gene variants. Continued research into the molecular genetics of AMD holds great promise for the development of precision-targeted, personalized therapies that bring us closer to a cure for this debilitating disease.
Keywords	angiogenesis ; blindness ; complement ; diet ; extracellular matrix ; genes ; genetic background ; lipid metabolism ; macular degeneration ; molecular genetics ; oxidative stress ; pathogenesis ; risk factors ; stress response ; tobacco use
Language	English
Dates of publication	2022-0712
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13071233
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Article ; Online: Contractile morning glory disk anomaly: analysis of the cyclic contractions and literature review.

Sevgi, Duriye Damla / Orge, Faruk H

Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus

2020 Volume 24, Issue 2, Page(s) 99.e1–99.e6

Abstract: Purpose: To investigate the contraction mechanism of morning glory disk anomaly using computer-assisted analysis of the cyclic contractions frame by frame and to review the literature on contractile morning glory disk anomaly cases.: Methods: The ... ...

Abstract	Purpose: To investigate the contraction mechanism of morning glory disk anomaly using computer-assisted analysis of the cyclic contractions frame by frame and to review the literature on contractile morning glory disk anomaly cases. Methods: The fundus video of the patient under anesthesia was recorded using RetCam C300 lens. Frames at 1 second intervals were extracted to quality-preserving TIFF images and manually selected areas of cup, disk, and pigmented ring were measured with image analysis software. Measurements were repeated twice, and estimated uncertainties were calculated. Results: Two full-contraction phases and 1 half- and 1 full-dilation phase were recorded and analyzed. At the end of the second dilation phase, cup, disk, and pigmented ring were dilated to 93.7%, 97.6%, and 98.3% of their areas after first dilation. At the end of the second contraction cup, disk and pigmented ring areas remained 1.24, 1.01, and 1.01 times larger, respectively, than the areas at the end of the first contraction. Conclusions: Ectopic cholinergic muscle contraction alone is unlikely to explain the cyclic contraction dilation movements under constant stimulus. Potentially present smooth muscle cells can be provoked by the stretch caused by the influx of fluid into the subretinal space. Change in spatial configuration and oscillations with decreasing magnitudes can be explained by decreasing contractions due to decreasing stretch with decreasing fluid influx in each cycle after the initial triggering of outside pressure, causing the greatest pressure gradient and the greatest fluid influx.
MeSH term(s)	Fundus Oculi ; Humans ; Muscle Contraction ; Optic Disk ; Optic Nerve
Language	English
Publishing date	2020-03-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1412476-2
ISSN	1528-3933 ; 1091-8531
ISSN (online)	1528-3933
ISSN	1091-8531
DOI	10.1016/j.jaapos.2020.01.009
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Article ; Online: Evaluating the utility of deep learning for predicting therapeutic response in diabetic eye disease.

Dong, Vincent / Sevgi, Duriye Damla / Kar, Sudeshna Sil / Srivastava, Sunil K / Ehlers, Justis P / Madabhushi, Anant

Frontiers in ophthalmology

2022 Volume 2

Abstract: Purpose: Deep learning (DL) is a technique explored within ophthalmology that requires large datasets to distinguish feature representations with high diagnostic performance. There is a need for developing DL approaches to predict therapeutic response, ... ...

Abstract	Purpose: Deep learning (DL) is a technique explored within ophthalmology that requires large datasets to distinguish feature representations with high diagnostic performance. There is a need for developing DL approaches to predict therapeutic response, but completed clinical trial datasets are limited in size. Predicting treatment response is more complex than disease diagnosis, where hallmarks of treatment response are subtle. This study seeks to understand the utility of DL for clinical problems in ophthalmology such as predicting treatment response and where large sample sizes for model training are not available. Materials and methods: Four DL architectures were trained using cross-validated transfer learning to classify ultra-widefield angiograms (UWFA) and fluid-compartmentalized optical coherence tomography (OCT) images from a completed clinical trial (PERMEATE) dataset (n=29) as tolerating or requiring extended interval Anti-VEGF dosing. UWFA images (n=217) from the Anti-VEGF study were divided into five increasingly larger subsets to evaluate the influence of dataset size on performance. Class activation maps (CAMs) were generated to identify regions of model attention. Results: The best performing DL model had a mean AUC of 0.507 ± 0.042 on UWFA images, and highest observed AUC of 0.503 for fluid-compartmentalized OCT images. DL had a best performing AUC of 0.634 when dataset size was incrementally increased. Resulting CAMs show inconsistent regions of interest. Conclusions: This study demonstrated the limitations of DL for predicting therapeutic response when large datasets were not available for model training. Our findings suggest the need for hand-crafted approaches for complex and data scarce prediction problems in ophthalmology.
Language	English
Publishing date	2022-08-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	3123828-2
ISSN	2674-0826 ; 2674-0826
ISSN (online)	2674-0826
ISSN	2674-0826
DOI	10.3389/fopht.2022.852107
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Article: Quantitative Imaging Biomarkers in Age-Related Macular Degeneration and Diabetic Eye Disease: A Step Closer to Precision Medicine.

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

Journal of personalized medicine

2021 Volume 11, Issue 11

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 ... ...

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 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.
Language	English
Publishing date	2021-11-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm11111161
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Article: 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.

Yu, Hannah J / Ehlers, Justis P / Sevgi, Duriye Damla / O'Connell, Margaret / Reese, Jamie L / Srivastava, Sunil K / Wykoff, Charles C

Journal of personalized medicine

2021 Volume 11, Issue 9

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 ... ...

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 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% (
Language	English
Publishing date	2021-09-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm11090885
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Article ; Online: Real-Time Photographic- and Fluorescein Angiographic-Guided Management of Diabetic Retinopathy: Randomized PRIME Trial Outcomes.

Yu, Hannah J / Ehlers, Justis P / Sevgi, Duriye Damla / Hach, Jenna / O'Connell, Margaret / Reese, Jamie L / Srivastava, Sunil K / Wykoff, Charles C

American journal of ophthalmology

2021 Volume 226, Page(s) 126–136

Abstract: Purpose: To assess the safety and efficacy of as-needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by the real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes ... ...

Abstract	Purpose: To assess the safety and efficacy of as-needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by the real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes without diabetic macular edema (DME). Design: Prospective, randomized phase 2 trial (PRIME). Methods: A total of 40 eyes with nonproliferative (NPDR) or proliferative DR (PDR) received monthly IAIs until a DRSS improvement of ≥2 steps was achieved and eyes were randomized (1:1) to DRSS-guided or PLI-guided management strategies graded by a central reading center. Main outcome measurements included safety and changes in DRSS and PLI. Results: Through week 52, 95% of eyes achieved a DRSS improvement of ≥2 steps. Following DRSS improvement, 97% of eyes required at least 1 PRN IAI. In eyes requiring PRN IAI and completing week 52, 100% and 59% experienced DRSS worsening (P = .01) in the DRSS- and PLI-guided arms, respectively. Through week 52, mean PLI decreased 18.2% (P = .49) and 54.6% (P <.0001), respectively, in the DRSS- and PLI-guided arms. NPDR versus PDR eyes at baseline achieved a DRSS improvement of ≥2 steps after a mean 4.9 and 3.6 IAIs (P = .03). Two eyes developed a PDR event at week 52 following 5 months of quiescence. Conclusions: The randomized PRIME study analyzed 2 imaging-based biomarkers to guide PRN management with IAI of DR without DME: DRSS level and PLI. Within the context of this study with limitations, most patients required IAI re-treatment every 3-4 months, and deterioration of PLI appeared to precede DRSS level worsening. Finally, these findings reaffirm the fact that close clinical follow-up is important even among eyes that achieve substantial DRSS improvements with apparently quiescent disease.
MeSH term(s)	Adult ; Aged ; Angiogenesis Inhibitors/therapeutic use ; Computer Systems ; Diabetic Retinopathy/diagnosis ; Diabetic Retinopathy/drug therapy ; Diabetic Retinopathy/physiopathology ; Female ; Fluorescein Angiography ; Follow-Up Studies ; Humans ; Intravitreal Injections ; Male ; Middle Aged ; Photography ; Prospective Studies ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity/physiology
Chemical Substances	Angiogenesis Inhibitors ; Recombinant Fusion Proteins ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; aflibercept (15C2VL427D) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1)
Language	English
Publishing date	2021-01-30
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	80030-2
ISSN	1879-1891 ; 0002-9394
ISSN (online)	1879-1891
ISSN	0002-9394
DOI	10.1016/j.ajo.2021.01.024
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Article ; Online: LONGITUDINAL ELLIPSOID ZONE DYNAMICS AFTER MACULAR HOLE REPAIR IN THE DISCOVER STUDY: Structure-Function Assessment.

Sevgi, Duriye Damla / Yee, Philina S / Srivastava, Sunil K / Le, Thuy K / Abraham, Joseph R / Reese, Jamie / Ehlers, Justis P

Retina (Philadelphia, Pa.)

2021 Volume 41, Issue 5, Page(s) 915–920

Abstract: Purpose: To evaluate association of the baseline macular hole (MH) geometric features and longitudinal ellipsoid zone integrity with the visual acuity outcome after surgical repair.: Methods: This was a post-hoc analysis of eyes in the DISCOVER study ...

Abstract	Purpose: To evaluate association of the baseline macular hole (MH) geometric features and longitudinal ellipsoid zone integrity with the visual acuity outcome after surgical repair. Methods: This was a post-hoc analysis of eyes in the DISCOVER study undergoing vitrectomy repair for MH. Anatomical and functional data were collected through one year postoperatively. An automated retinal layer segmentation platform was used for the assessment of outer retinal metrics and volumetric reconstruction of MH. Association of longitudinal ellipsoid zone features and baseline MH height, width, and volume with VA outcomes were investigated. Results: Eighty-four eyes with MH were included. The mean baseline VA was 20 of 114 and increased to 20 of 45 (P < 0.001) at postoperative Month 12 (N = 45). Successful MH closure was achieved in 98.8% of cases. Ellipsoid zone integrity metrics significantly improved from baseline (P = 0.002) and postoperative Month 1 (P < 0.001) to post-operative Month 12. Ellipsoid zone metrics independently correlated with VA at all follow-up visits (P < 0.05). Increased baseline MH width and volume negatively correlated with the VA at postoperative Month 12 (P < 0.001). Preoperative VA and EZ integrity on optical coherence tomography were predictors for postoperative VA. Conclusion: Baseline MH volumetric parameters and EZ parameters were associated with VA outcomes after repair.
MeSH term(s)	Aged ; Feasibility Studies ; Female ; Follow-Up Studies ; Fovea Centralis/diagnostic imaging ; Humans ; Male ; Postoperative Period ; Prospective Studies ; Retinal Perforations/diagnosis ; Retinal Perforations/physiopathology ; Retinal Perforations/surgery ; Tomography, Optical Coherence/methods ; Visual Acuity ; Vitrectomy/methods
Language	English
Publishing date	2021-04-21
Publishing country	United States
Document type	Clinical Study ; Journal Article
ZDB-ID	603192-4
ISSN	1539-2864 ; 0275-004X
ISSN (online)	1539-2864
ISSN	0275-004X
DOI	10.1097/IAE.0000000000002983
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Zs.A 1724: Show issues

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Article ; Online: Multi-Compartment Spatially-Derived Radiomics From Optical Coherence Tomography Predict Anti-VEGF Treatment Durability in Macular Edema Secondary to Retinal Vascular Disease: Preliminary Findings.

Sil Kar, Sudeshna / Sevgi, Duriye Damla / Dong, Vincent / Srivastava, Sunil K / Madabhushi, Anant / Ehlers, Justis P

IEEE journal of translational engineering in health and medicine

2021 Volume 9, Page(s) 1000113

Abstract: Objective: Diabetic macular edema (DME) and retinal vein occlusion (RVO) are the leading causes of visual impairments across the world. Vascular endothelial growth factor (VEGF) stimulates breakdown of blood-retinal barrier that causes accumulation of ... ...

Abstract	Objective: Diabetic macular edema (DME) and retinal vein occlusion (RVO) are the leading causes of visual impairments across the world. Vascular endothelial growth factor (VEGF) stimulates breakdown of blood-retinal barrier that causes accumulation of fluid within macula. Anti-VEGF therapy is the first-line treatment for both the diseases; however, the degree of response varies for individual patients. The main objective of this work was to identify the (i) texture-based radiomics features within individual fluid and retinal tissue compartments of baseline spectral-domain optical coherence tomography (SD-OCT) images and (ii) the specific spatial compartments that contribute most pertinent features for predicting therapeutic response. Methods: A total of 962 texture-based radiomics features were extracted from each of the fluid and retinal tissue compartments of OCT images, obtained from the PERMEATE study. Top-performing features selected from the consensus of different feature selection methods were evaluated in conjunction with four different machine learning classifiers: Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Random Forest (RF), and Support Vector Machine (SVM) in a cross-validated approach to distinguish eyes tolerating extended interval dosing (non-rebounders) and those requiring more frequent dosing (rebounders). Results: Combination of fluid and retinal tissue features yielded a cross-validated area under receiver operating characteristic curve (AUC) of 0.78±0.08 in distinguishing rebounders from non-rebounders. Conclusions: This study revealed that the texture-based radiomics features pertaining to IRF subcompartment were most discriminating between rebounders and non-rebounders to anti-VEGF therapy. Clinical Impact: With further validation, OCT-based imaging biomarkers could be used for treatment management of DME patients.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Diabetic Retinopathy/complications ; Humans ; Intravitreal Injections ; Macular Edema/diagnostic imaging ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/therapeutic use ; Visual Acuity
Chemical Substances	Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2021-07-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2696555-0
ISSN	2168-2372 ; 2168-2372
ISSN (online)	2168-2372
ISSN	2168-2372
DOI	10.1109/JTEHM.2021.3096378
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