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State-of-the-Art Research on Vitreoretinal Disorders

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Ophthalmology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 22010

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Special Issue Editors

Dr. Jiaxu Hong

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Department of Ophthalmology and Visual Science, Eye, and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Interests: gene therapy; choroid neovascularization; imaging; nanotechnology
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Yong Tao

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Department of Ophthalmology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
Interests: drug delivery; vitreoretinal diseases; uveitis; lab examination; exosome

Prof. Dr. Xiaodong Sun

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1. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2. Eye Research Institute, Shanghai Jiao Tong University, Shanghai, China
Interests: age-related macular degeneration; imaging; retina; gene therapy

Special Issue Information

Dear Colleagues,

Vitreoretinal diseases include age-related macular degeneration, diabetic retinopathy, retinal vascular disease, retinal pigmentosa, congenital retinopathy, Coats’ disease, and Stargardt disease, which are present in all ageing populations worldwide. Vitreoretinal diseases often impair vision and even lead to permanent blindness. Early diagnosis and treatments provide benefits for preventing vision impairment in those patients.

Recent progress on the understanding and treatment of vitreoretinal diseases has been revolutionary. Novel retinal imaging techniques and laboratory examinations, such as optical coherence tomography angiography (OCTA), ultra-wide-field fundus fluorescein angiography, and metagenomic next-generation sequencing, have been widely employed in the early detection and diagnosis of retinal disease. Anti-vascular endothelial growth factor (VEGF) has been used in the treatment of choroid neovascularization. Recombinant adeno-associated virus (AAV) vector-based gene therapy showed promising outcomes in phase I/II clinical trials and has been approved for treating RPE65-mutation-associated retinal dystrophies. Despite these advances in retinal disease, there is much left to unravel. To better understand vitreoretinal diseases, in-depth understandings of the mechanism, clinical features, and preclinical/clinical trial results are still warranted.

In this Special Issue, we welcome reviews and original articles which provide novel findings in vitreoretinal diseases, especially in potential novel diagnostic and therapeutic strategies. These include, but are not limited to, studies of genetic and molecular mechanisms, epidemiology, diagnostic evaluation, clinical investigation, preclinical research, and clinical trials. We look forward to your contributions.

Interests include, but are not limited to:

Age-related macular degeneration
Diabetic retinopathy
Retinal vascular disease
Retinal pigmentosa
Role of chronic inflammation in retinopathy
New biomarkers in vitreoretinal diseases
Congenital retinopathy
Pediatric retina vascular diseases
Cell therapy trials
Genotyping/phenotyping studies
Examination of intraocular fluids
Engineering exosome or gene therapy

Dr. Jiaxu Hong
Prof. Dr. Yong Tao
Prof. Dr. Xiaodong Sun
Guest Editors

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Keywords

retinal disease
diabetic retinopathy
macular disease
diagnosis
therapeutics

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Published Papers (8 papers)

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Research

10 pages, 1461 KiB

Open AccessArticle

A Modified Single-Armed Suture Technique for Traumatic Cyclodialysis Cleft with Vitreoretinal Injury

by Xueyong Zhang, Nan Wang, Guoli Zheng, Die Liu, Quyan Zhang, Wenbo Lei, Xiaobo Xia and Siqi Xiong

J. Clin. Med. 2023, 12(13), 4252; https://doi.org/10.3390/jcm12134252 - 25 Jun 2023

Cited by 2 | Viewed by 1349

Abstract

Our aim was to assess the therapeutic efficacy of a modified single-arm suture technique on traumatic cyclodialysis cleft with vitreoretinal injury. The procedure involved fixing a detached ciliary body using a single-armed 10-0 polypropylene suture under the assistance of a 29-gauge needle. Patients with a traumatic cyclodialysis cleft combined with an anterior and posterior segment injury who underwent modified internal cyclopexy together with vitreoretinal surgery were enrolled in this study. Ultrasound biomicroscopy (UBM) was used to diagnose and evaluate the cyclodialysis and anterior segment injury. B-scan ultrasonography was performed to assess the condition of the vitreous, retina and choroid. The surgical time and successful rate for repairing the cyclodialysis cleft were recorded. Preoperative and postoperative best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were documented for assessment. The study included 20 eyes. The extent of the cyclodialysis cleft was from 30° to 360°. Besides a traumatic cyclodialysis cleft, the included cases also combined this with vitreous hemorrhages, retinal detachment, macular holes, choroid avulsion, and suprachoroidal hemorrhage. All the clefts were anatomically closed in one surgery. The average surgical time for fixing the cyclodialysis cleft was 2.68 ± 0.54 min/30° cleft. A significant improvement in LogMAR BCVA was observed from 2.94 ± 0.93 preoperatively to 1.81 ± 1.11 at the 6-month follow-up. IOP was elevated from 10.90 ± 6.18 mmHg preoperatively to 14.45 ± 2.35 mmHg at the 6-month follow-up. The modified single-armed suture technique was proved to be an effective method to fix the traumatic cyclodialysis cleft, which could facilitate the use of the procedure to repair chorioretinal disorders. It improved the BCVA and maintained the IOP with less postoperative complications. Full article

(This article belongs to the Special Issue State-of-the-Art Research on Vitreoretinal Disorders)

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12 pages, 11246 KiB

Open AccessArticle

A 3-miRNA Risk Scoring Signature in Early Diabetic Retinopathy

by Jiali Wu, Ke Shi, Fang Zhang and Xiaodong Sun

J. Clin. Med. 2023, 12(5), 1777; https://doi.org/10.3390/jcm12051777 - 23 Feb 2023

Cited by 2 | Viewed by 1551

Abstract

Purpose: The aim of our study was to investigate a comprehensive profile of streptozotocin (STZ)-induced early diabetic retinopathy (DR) mice to identify a risk scoring signature based on micorRNAs (miRNAs) for early DR diagnosis. Methods: RNA sequencing was performed to obtain the gene expression profile of retinal pigment epithelium (RPE) in early STZ-induced mice. Differentially expressed genes (DEGs) were determined with log2|fold change (FC)| > 1 and p value < 0.05. Functional analysis was carried out based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the protein–protein interaction (PPI) network. We predicted the potential miRNAs via online tools and ROC curves were then conducted. Three potential miRNAs with AUC > 0.7 were explored via public datasets and a formula was further established to evaluate DR severity. Results: In total, 298 DEGs (200 up-regulating and 98 down-regulating) were obtained through RNA sequencing. Hsa-miR-26a-5p, hsa-miR-129-2-3p and hsa-miR-217 were three predicted miRNAs with AUC > 0.7, suggesting their potential to distinguish healthy controls from early DR. The formula of DR severity score = 19.257 − 0.004 × hsa-miR-217 + 5.09 × 10⁻⁵ × hsa-miR-26a-5p − 0.003 × hsa-miR-129-2-3p was established based on regression analysis. Conclusions: In the present study, we investigated the candidate genes and molecular mechanisms based on RPE sequencing in early DR mice models. Hsa-miR-26a-5p, hsa-miR-129-2-3p and hsa-miR-217 could work as biomarkers for early DR diagnosis and DR severity prediction, which was beneficial for DR early intervention and treatment. Full article

(This article belongs to the Special Issue State-of-the-Art Research on Vitreoretinal Disorders)

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14 pages, 2372 KiB

Open AccessArticle

iERM: An Interpretable Deep Learning System to Classify Epiretinal Membrane for Different Optical Coherence Tomography Devices: A Multi-Center Analysis

by Kai Jin, Yan Yan, Shuai Wang, Ce Yang, Menglu Chen, Xindi Liu, Hiroto Terasaki, Tun-Hang Yeo, Neha Gulab Singh, Yao Wang and Juan Ye

J. Clin. Med. 2023, 12(2), 400; https://doi.org/10.3390/jcm12020400 - 4 Jan 2023

Cited by 27 | Viewed by 3819

Abstract

Background: Epiretinal membranes (ERM) have been found to be common among individuals >50 years old. However, the severity grading assessment for ERM based on optical coherence tomography (OCT) images has remained a challenge due to lacking reliable and interpretable analysis methods. Thus, this study aimed to develop a two-stage deep learning (DL) system named iERM to provide accurate automatic grading of ERM for clinical practice. Methods: The iERM was trained based on human segmentation of key features to improve classification performance and simultaneously provide interpretability to the classification results. We developed and tested iERM using a total of 4547 OCT B-Scans of four different commercial OCT devices that were collected from nine international medical centers. Results: As per the results, the integrated network effectively improved the grading performance by 1–5.9% compared with the traditional classification DL model and achieved high accuracy scores of 82.9%, 87.0%, and 79.4% in the internal test dataset and two external test datasets, respectively. This is comparable to retinal specialists whose average accuracy scores are 87.8% and 79.4% in two external test datasets. Conclusion: This study proved to be a benchmark method to improve the performance and enhance the interpretability of the traditional DL model with the implementation of segmentation based on prior human knowledge. It may have the potential to provide precise guidance for ERM diagnosis and treatment. Full article

(This article belongs to the Special Issue State-of-the-Art Research on Vitreoretinal Disorders)

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14 pages, 1414 KiB

Open AccessArticle

Genome-Wide Pleiotropy Study Identifies Association of PDGFB with Age-Related Macular Degeneration and COVID-19 Infection Outcomes

by Jaeyoon Chung, Viha Vig, Xinyu Sun, Xudong Han, George T. O’Connor, Xuejing Chen, Margaret M. DeAngelis, Lindsay A. Farrer and Manju L. Subramanian

J. Clin. Med. 2023, 12(1), 109; https://doi.org/10.3390/jcm12010109 - 23 Dec 2022

Cited by 4 | Viewed by 6850

Abstract

Age-related macular degeneration (AMD) has been implicated as a risk factor for severe consequences from COVID-19. We evaluated the genetic architecture shared between AMD and COVID-19 (critical illness, hospitalization, and infections) using analyses of genetic correlations and pleiotropy (i.e., cross-phenotype meta-analysis) of AMD (n = 33,976) and COVID-19 (n ≥ 1,388,342) and subsequent analyses including expression quantitative trait locus (eQTL), differential gene expression, and Mendelian randomization (MR). We observed a significant genetic correlation between AMD and COVID-19 infection (r_G = 0.10, p = 0.02) and identified novel genome-wide significant associations near PDGFB (best SNP: rs130651; p = 2.4 × 10⁻⁸) in the pleiotropy analysis of the two diseases. The disease-risk allele of rs130651 was significantly associated with increased gene expression levels of PDGFB in multiple tissues (best eQTL p = 1.8 × 10⁻¹¹ in whole blood) and immune cells (best eQTL p = 7.1 × 10⁻²⁰ in T-cells). PDGFB expression was observed to be higher in AMD cases than AMD controls {fold change (FC) = 1.02; p = 0.067}, as well as in the peak COVID-19 symptom stage (11–20 days after the symptom onset) compared to early/progressive stage (0–10 days) among COVID-19 patients over age 40 (FC = 2.17; p = 0.03) and age 50 (FC = 2.15; p = 0.04). Our MR analysis found that the liability of AMD risk derived from complement system dysfunction {OR (95% CI); hospitalization = 1.02 (1.01–1.03), infection = 1.02 (1.01–1.03) and increased levels of serum cytokine PDGF-BB {β (95% CI); critical illness = 0.07 (0.02–0.11)} are significantly associated with COVID-19 outcomes. Our study demonstrated that the liability of AMD is associated with an increased risk of COVID-19, and PDGFB may be responsible for the severe COVID-19 outcomes among AMD patients. Full article

(This article belongs to the Special Issue State-of-the-Art Research on Vitreoretinal Disorders)

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15 pages, 1230 KiB

Open AccessArticle

Adalimumab plus Conventional Therapy versus Conventional Therapy in Refractory Non-Infectious Scleritis

by Binyao Chen, Shizhao Yang, Lei Zhu, Xuening Peng, Daquan He, Tianyu Tao and Wenru Su

J. Clin. Med. 2022, 11(22), 6686; https://doi.org/10.3390/jcm11226686 - 11 Nov 2022

Cited by 2 | Viewed by 1716

Abstract

Long-term systemic glucocorticoids and non-specific immunosuppressants remain the mainstay of treatment for refractory scleritis, and result in serious side-effects and repeated inflammation flares. To assess the efficacy and safety of additional adalimumab, patients diagnosed with refractory non-infectious scleritis were enrolled. They were assigned to the conventional-therapy (CT, using systemic glucocorticoids and other immunosuppressants) group or the adalimumab-plus-conventional-therapy (ACT) group according to the treatments they received. The primary outcome was time to achieve sustained remission, assessed by a reduction in modified McCluskey’s scleritis scores. Other outcomes included changes in McCluskey’s scores, scleritis flares, best-corrected visual acuity, and spared glucocorticoid dosage. Patients in the ACT group achieved faster remission than those in the CT group, as the median periods before remission were 4 months vs. 2.5 months (p = 0.016). Scleritis flares occurred in 11/11 eyes in the CT group and 5/12 eyes in the ACT group (p = 0.005). Successful glucocorticoid sparing was realized in both groups, but the ACT group made it faster. No severe adverse events were observed. Data suggest that adalimumab plus conventional therapy could shorten the time to remission, reduce disease flares, and accelerate glucocorticoid withdrawal compared with conventional therapy alone. Full article

(This article belongs to the Special Issue State-of-the-Art Research on Vitreoretinal Disorders)

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14 pages, 7770 KiB

Open AccessArticle

Increased Macrophage-like Cell Density in Retinal Vein Occlusion as Characterized by en Face Optical Coherence Tomography

by Wenyu Wang, Gongpeng Sun, Lu He and Changzheng Chen

J. Clin. Med. 2022, 11(19), 5636; https://doi.org/10.3390/jcm11195636 - 24 Sep 2022

Cited by 7 | Viewed by 2091

Abstract

Objectives: to quantitatively analyze macrophage-like cells (MLCs) at the vitreoretinal interface in retinal vein occlusion (RVO) using swept-source optical coherence tomography angiography (SS-OCTA) and en face optical coherence tomography (OCT). Methods: The study included 72 RVO patients, with 43 acute patients and 29 chronic patients. For a normal control, 64 fellow eyes were included. MLCs were visualized in a 5 μm en face OCT slab above the vitreoretinal interface centered on the fovea. After semi-automatic binarization and quantification, we evaluated the MLC count and density among groups. We also investigated the MLC density and distribution relative to retinal edema. Results: Morphological changes and congregation of MLCs appeared in RVO eyes. The MLC density of both the acute and chronic groups was significantly higher than that of the control eyes (p < 0.001). In the acute group, the MLC density of the edematous region was lower than both the non-edematous region (p < 0.001) and the whole image (p < 0.01). The MLC density in acute eyes was negatively correlated to central fovea thickness (CFT) (r = −0.352, p < 0.05). The MLC density in chronic eyes was positively correlated to CFT and mean retina thickness (MRT) (r = 0.406, p < 0.05; r = 0.412, p < 0.05, respectively). Conclusions: SS-OCTA is a viable and simple method for the characterization of MLCs at the vitreoretinal interface. A significant increase in the MLC density in both acute and chronic eyes implicates the activation and recruitment of MLCs in RVO and that the MLC density and distribution can be affected by retinal edema. Full article

(This article belongs to the Special Issue State-of-the-Art Research on Vitreoretinal Disorders)

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10 pages, 2236 KiB

Open AccessArticle

Oral Fluorescein Angiography with Ultra-Wide-Field Scanning Laser Ophthalmoscopy in Pediatric Patients Precis: Oral Fluorescein Angiography in Children

by Zhaoxin Jiang, Limei Sun, Aohan Hou, Ting Zhang, Yanting Lai, Li Huang and Xiaoyan Ding

J. Clin. Med. 2022, 11(18), 5421; https://doi.org/10.3390/jcm11185421 - 15 Sep 2022

Cited by 4 | Viewed by 2055

Abstract

Aims: To investigate the success rate of oral fluorescein angiography (oral FA) in children with ultrawide scanning laser ophthalmoscopy (SLO) system and whether it can provide images of sufficient quality compared with intravenous FA (IVFA). Methods: In this comparative case series study, a series of 40 consecutive pediatric patients of the age of 3–18 with retinal vascular diseases, in whom FA was needed for the diagnosis or treatment, were enrolled in this study. IVFA and oral FA were performed within one week and images were obtained with the SLO system. The image quality was scored blindly and compared based on: (I) visualization of the branch retinal vessel, (II) the foveal avascular zone (FAZ), and (III) clinically important findings, such as the presence of microaneurysms, neovascularization, leakage, or significant nonperfusion. All these were scored using a three-point scale. Results: In preschoolers (three to six years), all 19 children complete oral FA (100%), while only 7 (36.84%) complete IVFA (p < 0.0001). With the SLO system, the branch retinal vessels were well visualized both in oral and IV FA (all images were two scores). The visualization of FAZ was similar between oral and IV FA (p = 0.8972). The clinically important findings were well visualized in both groups (p > 0.9999). The overall image quality was similar between the two groups (p = 0.2500). Conclusion: Oral FA is more acceptable to preschoolers than IVFA owing to the needle-free procedure. With the SLO system, oral FA provided high-quality angiograms similar to IVFA. Oral FA is an effective alternative to IVFA and may be considered the first option for FA in pediatric patients, especially in preschoolers. Full article

(This article belongs to the Special Issue State-of-the-Art Research on Vitreoretinal Disorders)

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7 pages, 844 KiB

Open AccessArticle

The Relationship between the Aqueous VEGF Level and the Severity of Type 1 Retinopathy of Prematurity

by Tianwei Liang, Zhuyun Qian, Yong Tao, Yaguang Peng, Yanhui Cui, Chengyue Zhang, Chunxia Peng, Lili Liu, Man Hu, Li Li and Ningdong Li

J. Clin. Med. 2022, 11(18), 5361; https://doi.org/10.3390/jcm11185361 - 13 Sep 2022

Cited by 3 | Viewed by 1404

Abstract

Purpose: To analyze the relationship between the severity of type 1 retinopathy of prematurity (ROP) and the level of vascular endothelial growth factor (VEGF) in aqueous fluid. Methods: The aqueous VEGF levels of 49 patients (88 eyes) with type 1 ROP were retrospectively analyzed. These eyes were categorized into three groups according to the severity of disease: aggressive retinopathy of prematurity (A-ROP), threshold of ROP (T-ROP), and type 1 pre-threshold ROP (P-T-1). The differences in aqueous VEGF levels among these three groups were compared. The relationship between the aqueous VEGF level and the retinal changes of ROP, including the vessel tortuosity in zone I, and the location and stage of the ROP lesions, were also analyzed. Results: The aqueous VEGF level of the A-ROP group was the highest among the three groups, followed by those of the T-ROP and P-T-1 groups. The aqueous VEGF level was negatively correlated with the zone and the stage of the ROP diseases, while it was positively correlated with the venous tortuosity in zone I and had no relevance with the artery tortuosity in zone I. Conclusions: The aqueous VEGF level in A-ROP was the highest in type I ROP. The location of the ROP lesions and the venous tortuosity in zone I correlated with the aqueous VEGF level and could indicate the severity of ROP. Full article

(This article belongs to the Special Issue State-of-the-Art Research on Vitreoretinal Disorders)

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