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New Advances in Retinal Research
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New Advances in Retinal Research

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 62800

Special Issue Editor

Prof. Dr. Giuseppe Querques

E-Mail Website
Guest Editor
Ophthalmology Department, San Raffaele University Hospital, 20132 Milan, Italy
Interests: ophthalmology; eye; ocular disorder; retina; retinal disorder

Special Issue Information

Dear Colleagues,

As we observe a dramatic increase in the number of persons affected by ocular disorders, the identification of mechanisms behind the pathophysiology and therapy of retinal diseases is an area of significant research efforts, attracting scientists from diverse fields, including neuroscience, pharmacology, and medicinal chemistry.

This Special Issue is aimed at highlighting the importance of the discovery and mechanistic characterization of novel drug targets, signaling pathways, and pathological mechanisms in different retinal diseases. In addition, this Special Issue will emphasize the importance of retinal imaging in the diagnosis and characterization of these disorders. Papers of interest include, but are not limited to, laboratory and clinical studies on retinal disorders.

Prof. Dr. Giuseppe Querques
Guest Editor

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Published Papers (19 papers)

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11 pages, 2276 KiB  
Article
Mid-Phase Hyperfluorescent Plaques Seen on Indocyanine Green Angiography in Patients with Central Serous Chorioretinopathy
by Elodie Bousquet, Julien Provost, Marta Zola, Richard F. Spaide, Chadi Mehanna and Francine Behar-Cohen
J. Clin. Med. 2021, 10(19), 4525; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10194525 - 30 Sep 2021
Cited by 11 | Viewed by 2357
Abstract
(1) Indocyanine green angiography (ICG-A) shows the presence of mid-phase hyperfluorescent area in central serous chorioretinopathy (CSCR). However, their exact meaning remains uncertain. (2) The clinical and multimodal imaging findings of 100 patients (133 eyes) with CSCR, including the enhanced-depth-imaging OCT (EDI-OCT), blue-light [...] Read more.
(1) Indocyanine green angiography (ICG-A) shows the presence of mid-phase hyperfluorescent area in central serous chorioretinopathy (CSCR). However, their exact meaning remains uncertain. (2) The clinical and multimodal imaging findings of 100 patients (133 eyes) with CSCR, including the enhanced-depth-imaging OCT (EDI-OCT), blue-light fundus autofluorescence (BAF), fluorescein and indocyanine green angiography (FA and ICG-A) findings were reviewed. Mid-phase hyperfluorescent plaques (MPHP) were defined as fairly well circumscribed hyperfluorescent regions during the midphase of the ICG-A. The association between MPHP and other clinical/imaging parameters was assessed using a multiple logistic regression analysis. (3) MPHP were detected in 59.4% of eyes with CSCR. The chronic form of the disease, the presence of irregular pigment epithelium detachments (PED) and the retinal pigment epithelium (RPE) changes seen on FA were associated with the presence of MPHP in the multivariate analysis (p = 0.015; p = 0.018 and p = 0.002; respectively). OCT showed RPE bulges or PED in 98.7% of areas with MPHP and BAF showed changes in 57.3% of areas with MPHP. (4) MPHP were associated with a chronic form of CSCR and colocated with PED or RPE bulges. MPHP should be recognized as a sign of early RPE dysfunction before it is detected with BAF. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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10 pages, 971 KiB  
Article
High Myopia and the Complement System: Factor H in Myopic Maculopathy
by Enrique García-Gen, Mariola Penadés, Salvador Mérida, Carmen Desco, Rafael Araujo-Miranda, Amparo Navea and F. Bosch-Morell
J. Clin. Med. 2021, 10(12), 2600; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10122600 - 12 Jun 2021
Cited by 13 | Viewed by 2221
Abstract
High myopia (HM) is both a medical problem and refractive error of the eye owing to excessive eyeball length, which progressively makes eye tissue atrophic, and is one of the main causes for diminishing visual acuity in developed countries. Despite its high prevalence [...] Read more.
High myopia (HM) is both a medical problem and refractive error of the eye owing to excessive eyeball length, which progressively makes eye tissue atrophic, and is one of the main causes for diminishing visual acuity in developed countries. Despite its high prevalence and many genetic and proteomic studies, no molecular pattern exists that explain the degenerative process underlying HM, which predisposes patients to other diseases like glaucoma, cataracts, retinal detachment and chorioretinal atrophy that affect the macular area. To determine the relation between complement Factors H (CFH) and D (CFD) and the maculopathy of patients with degenerative myopia, we studied aqueous humor samples that were collected by aspiration from 122 patients during cataract surgery. Eyes were classified according to eyeball axial length as high myopia (axial length > 26 mm), low myopia (axial length 23.5–25.9 mm) and control (axial length ˂ 23.4 mm). The degree of maculopathy was classified according to fundus oculi findings following IMI’s classification. Subfoveal choroid thickness was measured by optical coherence tomography. CFH and CFD measurements were taken by ELISA. CFH levels were significantly high in the high myopia group vs. the low myopia and control groups (p ˂ 0.05). Significantly high CFH values were found in those eyes with choroid atrophy and neovascularization (p ˂ 0.05). In parallel, the CFH concentration correlated inversely with choroid thickness (R = −0.624). CFD levels did not correlate with maculopathy. All the obtained data seem to suggest that CFH plays a key role in myopic pathology. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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8 pages, 254 KiB  
Article
The COVID-19 Pandemic Has Had Negative Effects on Baseline Clinical Presentation and Outcomes of Patients with Newly Diagnosed Treatment-Naïve Exudative AMD
by Enrico Borrelli, Marco Battista, Giovanna Vella, Domenico Grosso, Riccardo Sacconi, Lea Querques, Ilaria Zucchiatti, Francesco Prascina, Francesco Bandello and Giuseppe Querques
J. Clin. Med. 2021, 10(6), 1265; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10061265 - 18 Mar 2021
Cited by 9 | Viewed by 1663
Abstract
Purpose: To investigate whether the coronavirus disease 2019 (COVID-19) pandemic-associated postponement in care had effects on the baseline clinical presentation of patients with newly diagnosed treatment-naïve exudative neovascular age-related macular degeneration (AMD). Methods: We included the first 50 consecutive patients referred within the [...] Read more.
Purpose: To investigate whether the coronavirus disease 2019 (COVID-19) pandemic-associated postponement in care had effects on the baseline clinical presentation of patients with newly diagnosed treatment-naïve exudative neovascular age-related macular degeneration (AMD). Methods: We included the first 50 consecutive patients referred within the COVID-19 pandemic with a diagnosis of treatment-naïve exudative neovascular AMD. Two groups of fifty consecutive patients with newly diagnosed neovascular exudative AMD presenting in 2018 and 2019 (control periods) were also included for comparisons. Results: Baseline visual acuity was statistically worse in patients referred during the COVID-19 pandemic period (0.87 ± 0.51 logarithm of the minimum angle of resolution (LogMAR)) as compared with both the “2019” (0.67 ± 0.48 LogMAR, p = 0.001) and “2018” (0.69 ± 0.54 LogMAR, p = 0.012) control periods. Data on the visual function after a loading dose of anti-vascular endothelial growth factor (VEGF) was available in a subset of patients (43 subjects in 2020, 45 in 2019 and 46 in 2018, respectively). Mean ± SD best corrected visual acuity (BCVA) at the 1-month follow-up visit after the third anti-VEGF injection was still worse in patients referred during the COVID-19 pandemic (0.82 ± 0.66 LogMAR) as compared with both the “2019” (0.60 ± 0.45 LogMAR, p = 0.021) and “2018” (0.55 ± 0.53 LogMAR, p = 0.001) control periods. On structural optical coherence tomography (OCT), the maximum subretinal hyperreflective material (SHRM) height and width were significantly greater in the COVID-19 pandemic patients. Conclusions: We demonstrated that patients with newly diagnosed treatment-naïve exudative neovascular AMD referred during the COVID-19 pandemic had worse clinical characteristics at presentation and short-term visual outcomes. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
13 pages, 3341 KiB  
Article
Deep Learning-Based Classification of Inherited Retinal Diseases Using Fundus Autofluorescence
by Alexandra Miere, Thomas Le Meur, Karen Bitton, Carlotta Pallone, Oudy Semoun, Vittorio Capuano, Donato Colantuono, Kawther Taibouni, Yasmina Chenoune, Polina Astroz, Sylvain Berlemont, Eric Petit and Eric Souied
J. Clin. Med. 2020, 9(10), 3303; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9103303 - 14 Oct 2020
Cited by 24 | Viewed by 3307
Abstract
Background. In recent years, deep learning has been increasingly applied to a vast array of ophthalmological diseases. Inherited retinal diseases (IRD) are rare genetic conditions with a distinctive phenotype on fundus autofluorescence imaging (FAF). Our purpose was to automatically classify different IRDs [...] Read more.
Background. In recent years, deep learning has been increasingly applied to a vast array of ophthalmological diseases. Inherited retinal diseases (IRD) are rare genetic conditions with a distinctive phenotype on fundus autofluorescence imaging (FAF). Our purpose was to automatically classify different IRDs by means of FAF images using a deep learning algorithm. Methods. In this study, FAF images of patients with retinitis pigmentosa (RP), Best disease (BD), Stargardt disease (STGD), as well as a healthy comparable group were used to train a multilayer deep convolutional neural network (CNN) to differentiate FAF images between each type of IRD and normal FAF. The CNN was trained and validated with 389 FAF images. Established augmentation techniques were used. An Adam optimizer was used for training. For subsequent testing, the built classifiers were then tested with 94 untrained FAF images. Results. For the inherited retinal disease classifiers, global accuracy was 0.95. The precision-recall area under the curve (PRC-AUC) averaged 0.988 for BD, 0.999 for RP, 0.996 for STGD, and 0.989 for healthy controls. Conclusions. This study describes the use of a deep learning-based algorithm to automatically detect and classify inherited retinal disease in FAF. Hereby, the created classifiers showed excellent results. With further developments, this model may be a diagnostic tool and may give relevant information for future therapeutic approaches. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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10 pages, 1921 KiB  
Article
Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: Correlation with Macular Function
by Maria C. Savastano, Benedetto Falsini, Grazia M. Cozzupoli, Alfonso Savastano, Gloria Gambini, Umberto De Vico, Angelo M. Minnella, Giorgio Placidi, Marco Piccardi and Stanislao Rizzo
J. Clin. Med. 2020, 9(9), 2973; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092973 - 15 Sep 2020
Cited by 5 | Viewed by 2409
Abstract
The purpose of this study was to investigate the relationship between the retinal pigment epithelium (RPE) and outer retina changes, expressed in terms of sub-RPE illumination (SRI) on optical-coherence tomography (OCT), and central retinal function, measured by visual acuity and focal electroretinogram (fERG), [...] Read more.
The purpose of this study was to investigate the relationship between the retinal pigment epithelium (RPE) and outer retina changes, expressed in terms of sub-RPE illumination (SRI) on optical-coherence tomography (OCT), and central retinal function, measured by visual acuity and focal electroretinogram (fERG), in patients with non-exudative age-related macular degeneration (neAMD). In this retrospective study, 29 eyes of 29 patients affected by early (24.14%), intermediate (41.38%), and advanced (34.48%) neAMD were evaluated. All enrolled eyes were studied with OCT to measure the total area of SRI, by using an automated standardized algorithm. Visual acuity and fERG were assessed. The area of SRI was negatively correlated with fERG amplitude (r ≤ −0.4, p ≤ 0.02) and best-corrected visual acuity (BCVA) (r ≤ 0.4, p ≤ 0.04). Our results indicate that the severity of retinal pigment epithelium and outer retina atrophy (RORA), indirectly quantified through the detection of SRI areas by commercial OCT algorithms, is correlated with central retinal dysfunction, as determined by visual acuity and fERG, supporting the combined use of structural exams and functional tests as valid tools to detect the extent of RPE and photoreceptors’ disruption. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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18 pages, 1956 KiB  
Article
A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema
by Hwei Wuen Chan, Binxia Yang, Wendy Wong, Paul Blakeley, Ivan Seah, Queenie Shu Woon Tan, Haofei Wang, Mayuri Bhargava, Hazel Anne Lin, Charmaine HC Chai, Erlangga Ariadarma Mangunkusumo, Naing Thet, Yew Sen Yuen, Raman Sethi, Si Wang, Walter Hunziker, Gopal Lingam and Xinyi Su
J. Clin. Med. 2020, 9(9), 2920; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092920 - 10 Sep 2020
Cited by 10 | Viewed by 3584
Abstract
(1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF in DME. (2) Methods: Tear fluid, [...] Read more.
(1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF in DME. (2) Methods: Tear fluid, aqueous, and blood were collected from patients with treatment-naïve DME for miRNA expression profiling with quantitative polymerase chain reaction. Differentially expressed miRNAs between good and poor responders were identified from tear fluid. Bioinformatics analysis with the miEAA tool, miRTarBase Annotations, Gene Ontology categories, KEGG, and miRWalk pathways identified interactions between enriched miRNAs and biological pathways. (3) Results: Of 24 participants, 28 eyes received bevacizumab (15 eyes) or aflibercept (13 eyes). Tear fluid had the most detectable miRNA species (N = 315), followed by serum (N = 309), then aqueous humor (N = 134). MiRNAs that correlated with change in macular thickness were miR-214-3p, miR-320d, and hsa-miR-874-3p in good responders; and miR-98-5p, miR-196b-5p, and miR-454-3p in poor responders. VEGF-related pathways and the angiogenin-PRI complex were enriched in good responders, while transforming growth factor-β and insulin-like growth factor pathways were enriched in poor responders. (4) Conclusions: We reported a panel of novel miRNAs that provide insight into biological pathways in DME. Validation in larger independent cohorts is needed to determine the predictive performance of these miRNA candidate biomarkers. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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16 pages, 4141 KiB  
Article
Peripapillary Retinal Vascular Involvement in Early Post-COVID-19 Patients
by Alfonso Savastano, Emanuele Crincoli, Maria Cristina Savastano, Saad Younis, Gloria Gambini, Umberto De Vico, Grazia Maria Cozzupoli, Carola Culiersi, Stanislao Rizzo and Gemelli Against COVID-19 Post-Acute Care Study Group
J. Clin. Med. 2020, 9(9), 2895; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092895 - 08 Sep 2020
Cited by 59 | Viewed by 4690
Abstract
The ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2′s) to cause multi-organ ischemia and coronavirus-induced posterior segment eye diseases in mammals gave concern about potential sight-threatening ischemia in post coronavirus disease 2019 patients. The radial peripapillary capillary plexus (RPCP) is a sensitive [...] Read more.
The ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2′s) to cause multi-organ ischemia and coronavirus-induced posterior segment eye diseases in mammals gave concern about potential sight-threatening ischemia in post coronavirus disease 2019 patients. The radial peripapillary capillary plexus (RPCP) is a sensitive target due to the important role in the vascular supply of the peripapillary retinal nerve fiber layer (RNFL). Eighty patients one month after SARS-CoV-2 infection and 30 healthy patients were selected to undergo structural OCT (optical coherence tomography) and OCTA (optical coherence tomography angiography) exams. Primary outcome was a difference in RPCP perfusion density (RPCP-PD) and RPCP flow index (RPCP-FI). No significant difference was observed in age, sex, intraocular pressure (IOP) and prevalence of myopia. RPCP-PD was lower in post SARS-CoV-2 patients compared to controls. Within the post-COVID-19 group, patients with systemic arterial hypertension had lower RPCP-FI and age was inversely correlated to both RPCP-FI and RPCP-PD. Patients treated with lopinavir + ritonavir or antiplatelet therapy during admission had lower RPCP-FI and RPCP-PD. RNFL average thickness was linearly correlated to RPCP-FI and RPCP-PD within post-COVID-19 group. Future studies will be needed to address the hypothesis of a microvascular retinal impairment in individuals who recovered from SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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12 pages, 2099 KiB  
Article
Investigating Ganglion Cell Complex Thickness in Children with Chronic Heart Failure due to Dilated Cardiomyopathy
by Klaudia Rakusiewicz, Krystyna Kanigowska, Wojciech Hautz and Lidia Ziółkowska
J. Clin. Med. 2020, 9(9), 2882; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092882 - 07 Sep 2020
Cited by 1 | Viewed by 2042
Abstract
Purpose: To assess ganglion cell complex (GCC) thickness in children with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM) using optical coherence tomography (OCT). Methods: Sixty eyes of 30 patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM) and 60 [...] Read more.
Purpose: To assess ganglion cell complex (GCC) thickness in children with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM) using optical coherence tomography (OCT). Methods: Sixty eyes of 30 patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM) and 60 eyes of 30 age- and sex-matched healthy volunteers (control group) were enrolled. The mean age of the patients and controls was 9.9 ± 3.57 (range 5–17) years and 10.08 ± 3.41 (range 4–16) years, respectively. All patients underwent a complete ophthalmic assessment and OCT imaging using RTVue XR Avanti (Optovue). The following OCT-based parameters were analysed: average ganglion cell complex thickness (avgGCC), superior ganglion cell complex thickness (supGCC), inferior ganglion cell complex thickness (infGCC), global loss of volume (GLV) and focal loss of volume (FLV). Results: There were no significant differences in avgGCC (98.13 μm vs. 99.96 μm, p = 0.21), supGCC (97.17 μm vs. 99.29 μm, p = 0.13), infGCC (99.03 μm vs. 100.71 μm, p = 0.25), FVL (0.49% vs. 0.4%, p = 0.25) and GVL (2.1% vs. 1.3%, p = 0.09) between patients with chronic heart failure due to dilated cardiomyopathy and healthy children. There was no correlation between avgGCC, supGCC, infGCC, FLV, GLV and ocular biometry, refractive errors or age. There was no correlation between avgGCC, supGCC, infGCC, FLV, GLV and NT-proBNP or LVEF. There were no significant differences in the studied parameters between the sexes. There were no significant differences in the studied parameters between the left and right eye. Conclusion: Our study seems to be the first to analyse ganglion cell complex in paediatric patients with dilated cardiomyopathy. We have demonstrated no changes in the ganglion cell complex thickness parameters in children with chronic heart failure due dilated cardiomyopathy, as compared to their healthy peers. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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16 pages, 2554 KiB  
Article
Prediction of Function in ABCA4-Related Retinopathy Using Ensemble Machine Learning
by Philipp L. Müller, Tim Treis, Alexandru Odainic, Maximilian Pfau, Philipp Herrmann, Adnan Tufail and Frank G. Holz
J. Clin. Med. 2020, 9(8), 2428; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082428 - 29 Jul 2020
Cited by 10 | Viewed by 2564
Abstract
Full-field electroretinogram (ERG) and best corrected visual acuity (BCVA) measures have been shown to have prognostic value for recessive Stargardt disease (also called “ABCA4-related retinopathy”). These functional tests may serve as a performance-outcome-measure (PerfO) in emerging interventional clinical trials, but utility [...] Read more.
Full-field electroretinogram (ERG) and best corrected visual acuity (BCVA) measures have been shown to have prognostic value for recessive Stargardt disease (also called “ABCA4-related retinopathy”). These functional tests may serve as a performance-outcome-measure (PerfO) in emerging interventional clinical trials, but utility is limited by variability and patient burden. To address these limitations, an ensemble machine-learning-based approach was evaluated to differentiate patients from controls, and predict disease categories depending on ERG (‘inferred ERG’) and visual impairment (‘inferred visual impairment’) as well as BCVA values (‘inferred BCVA’) based on microstructural imaging (utilizing spectral-domain optical coherence tomography) and patient data. The accuracy for ‘inferred ERG’ and ‘inferred visual impairment’ was up to 99.53 ± 1.02%. Prediction of BCVA values (‘inferred BCVA’) achieved a precision of ±0.3LogMAR in up to 85.31% of eyes. Analysis of the permutation importance revealed that foveal status was the most important feature for BCVA prediction, while the thickness of outer nuclear layer and photoreceptor inner and outer segments as well as age of onset highly ranked for all predictions. ‘Inferred ERG’, ‘inferred visual impairment’, and ‘inferred BCVA’, herein, represent accurate estimates of differential functional effects of retinal microstructure, and offer quasi-functional parameters with the potential for a refined patient assessment, and investigation of potential future treatment effects or disease progression. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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9 pages, 997 KiB  
Article
Spectrally Resolved Fundus Autofluorescence in Healthy Eyes: Repeatability and Topographical Analysis of the Green-Emitting Fluorophores
by Enrico Borrelli, Marco Battista, Biancamaria Zuccaro, Riccardo Sacconi, Maria Brambati, Lea Querques, Francesco Prascina, SriniVas R. Sadda, Francesco Bandello and Giuseppe Querques
J. Clin. Med. 2020, 9(8), 2388; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082388 - 27 Jul 2020
Cited by 9 | Viewed by 1610
Abstract
The aim of this study was to report normal measurements of green-emitting fluorophores in the macula of healthy young individuals and to assess the repeatability of these quantitative metrics. To do so, healthy young volunteers were imaged twice (7 ± 3 days apart) [...] Read more.
The aim of this study was to report normal measurements of green-emitting fluorophores in the macula of healthy young individuals and to assess the repeatability of these quantitative metrics. To do so, healthy young volunteers were imaged twice (7 ± 3 days apart) using a confocal blue-light fundus autofluorescence (FAF) device with a shorter excitation wavelength (peak at 450 nm) and the capability for separately detecting the red and green components of the emission spectrum. The main outcome measure was the percentage of area occupied by green-emitting fluorophores in the macula. In addition, this measure was performed in separate regions providing a topographical assessment in the foveal, parafoveal and perifoveal regions. Furthermore, the level of agreement between repeated measurements was evaluated. Thirty eyes from 30 healthy volunteers were included in this analysis. Mean age was 26.2 ± 2.8 years (median: 25.0 years; range: 23.0–32.0 years). Median (interquartile range—IQR) area occupied by green-emitting fluorophores was 3.6% (1.9–4.7%) in the macular region. In the topographical analysis, this percentage was higher in the foveal area (median = 33.3%, IQR = 21.9–41.2%), as compared with both the parafoveal (median = 5.3%; IQR = 2.4–8.1%; p < 0.0001) and perifoveal (median = 0.5%, IQR = 0.2–0.8%; p < 0.0001) regions. The coefficient of variation (CV; ranging from 1.1% to 1.7% in the analyzed regions) and the intraclass correlation coefficient (ICC; ranging from 0.93 to 0.97) indicated high levels of repeatability. In conclusion, the assessment of green-emitting fluorophores is repeatable. The distribution of these fluorophores is highest in the foveal region. Assuming that flavin adenine dinucleotide (FAD) emits in the green autofluorescence spectrum, this variability could be secondary to an increased quantity of mitochondria in the foveal region. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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8 pages, 2063 KiB  
Article
Choroidal Rift: A New OCT Finding in Eyes with Central Serous Chorioretinopathy
by Marco Battista, Enrico Borrelli, Chiara Veronese, Francesco Gelormini, Riccardo Sacconi, Lea Querques, Francesco Prascina, Giovanna Vella, Antonio P Ciardella, Francesco Bandello and Giuseppe Querques
J. Clin. Med. 2020, 9(7), 2260; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072260 - 16 Jul 2020
Cited by 5 | Viewed by 4388
Abstract
Central serous chorioretinopathy (CSC) is a complex and not entirely understood retinal disease. The aim of our research was to describe a novel optical coherence tomography (OCT) finding named “choroidal rift”, which may be identified in the choroid of eyes with CSC. We [...] Read more.
Central serous chorioretinopathy (CSC) is a complex and not entirely understood retinal disease. The aim of our research was to describe a novel optical coherence tomography (OCT) finding named “choroidal rift”, which may be identified in the choroid of eyes with CSC. We collected data from 357 patients (488 eyes) with CSC who had structural OCT and OCT angiography (OCTA) scans obtained. Choroidal rifts were identified as polygonal (and not round-shaped) hyporeflective lesions without hyperreflective margins. Choroidal rifts had to be characterized by a size superior to that of the largest choroidal vessel. Finally, hyporeflective lesions were graded as choroidal rifts only if these lesions had a main development perpendicular to the retinal pigment epithelium. OCT analysis allowed the identification of choroidal rifts in ten eyes from nine patients, all with chronic CSC, with an estimated prevalence rate of 2.1%. In three out of ten cases with choroidal rifts, these lesions spanned all the choroidal layers. In the remaining cases, choroidal rifts only partially spanned the choroidal thickness. In OCTA, choroidal rifts were characterized by the absence of flow. Combining structural OCT and OCTA information, we hypothesized that choroidal rifts may represent interruptions of the choroidal stroma in correspondence of fragile regions (in between expanded larger-sized choroidal vessels). Choroidal rift represents a novel OCT feature, which may characterize eyes with chronic CSC and may have a role in the development of irreversible chorio-retinal changes. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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18 pages, 12296 KiB  
Article
HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration
by Sunao Sugita, Michiko Mandai, Yasuhiko Hirami, Seiji Takagi, Tadao Maeda, Masashi Fujihara, Mitsuhiro Matsuzaki, Midori Yamamoto, Kyoko Iseki, Naoko Hayashi, Ayumi Hono, Shoko Fujino, Naoshi Koide, Noriko Sakai, Yumiko Shibata, Motoki Terada, Mitsuhiro Nishida, Hiromi Dohi, Masaki Nomura, Naoki Amano, Hirokazu Sakaguchi, Chikako Hara, Kazuichi Maruyama, Takashi Daimon, Masataka Igeta, Toshihiko Oda, Utako Shirono, Misato Tozaki, Kota Totani, Satoshi Sugiyama, Kohji Nishida, Yasuo Kurimoto and Masayo Takahashiadd Show full author list remove Hide full author list
J. Clin. Med. 2020, 9(7), 2217; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072217 - 13 Jul 2020
Cited by 87 | Viewed by 7224
Abstract
Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. [...] Read more.
Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient’s blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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13 pages, 3277 KiB  
Article
Multimodal Imaging in the Management of Choroidal Neovascularization Secondary to Central Serous Chorioretinopathy
by Ahmed M. Hagag, Shruti Chandra, Hagar Khalid, Ali Lamin, Pearse A. Keane, Andrew J. Lotery and Sobha Sivaprasad
J. Clin. Med. 2020, 9(6), 1934; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061934 - 21 Jun 2020
Cited by 9 | Viewed by 2895
Abstract
The diagnosis and treatment of choroidal neovascularization (CNV) in eyes with chronic central serous chorioretinopathy (CSCR) can be challenging. The purpose of this study was to classify eyes with suspected CNV using multimodal imaging. The effect of intravitreal anti-vascular endothelial growth factor (VEGF) [...] Read more.
The diagnosis and treatment of choroidal neovascularization (CNV) in eyes with chronic central serous chorioretinopathy (CSCR) can be challenging. The purpose of this study was to classify eyes with suspected CNV using multimodal imaging. The effect of intravitreal anti-vascular endothelial growth factor (VEGF) was assessed and compared to controls. This retrospective study included chronic CSCR patients with suspected secondary CNV who received intravitreal bevacizumab. Eyes were divided into “definite CNV” and “no CNV” based on optical coherence tomography angiography (OCTA). Eyes that did not undergo OCTA imaging were considered as “presumed CNV”. One-year outcome in visual acuity (VA) and central foveal thickness (CFT) were investigated and compared to non-treated control patients to assess the response to anti-VEGF. Logistic regression analysis was used to explore predictive biomarkers of CNV detection and improvement after anti-VEGF. Ninety-two eyes with chronic CSCR from 88 participants were included in this study. Sixty-one eyes received bevacizumab and 31 eyes were non-treated control subjects. The presence of subretinal hyperreflective material (SHRM) and shallow irregular retinal pigment epithelium (RPE) elevation (SIRE) with sub-RPE hyperreflectivity on OCT was associated with a significantly increased risk of detecting CNV on OCTA. Intravitreal anti-VEGF caused significant functional and anatomical improvement in patients with neovascular CSCR as compared to non-treated eyes. In contrast, VA and CFT changes were not significantly different between treated and non-treated CSCR with no evidence of CNV on OCTA. No clinical or anatomical biomarkers were found to be associated with response to treatment. In conclusion, OCTA should be used to confirm the presence CNV in suspected chronic CSCR patients. Intravitreal anti-VEGF treatment resulted in a significantly better one-year outcome in patients with definitive OCTA evidence of CNV. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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12 pages, 1466 KiB  
Article
Relationships among Retinal Nonperfusion, Neovascularization, and Vascular Endothelial Growth Factor Levels in Quiescent Proliferative Diabetic Retinopathy
by Ho Ra, Jae Hyun Park, Jin Uk Baek and Jiwon Baek
J. Clin. Med. 2020, 9(5), 1462; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051462 - 13 May 2020
Cited by 19 | Viewed by 2102
Abstract
Purpose: To investigate the relationships among the retinal nonperfusion (NP) area, neovascularization (NV) area, and aqueous humor vascular endothelial growth factor (VEGF) levels in quiescent proliferative diabetic retinopathy (PDR). Methods: Forty-seven eyes from 47 patients with treatment-naïve PDR that did not show macular [...] Read more.
Purpose: To investigate the relationships among the retinal nonperfusion (NP) area, neovascularization (NV) area, and aqueous humor vascular endothelial growth factor (VEGF) levels in quiescent proliferative diabetic retinopathy (PDR). Methods: Forty-seven eyes from 47 patients with treatment-naïve PDR that did not show macular edema or vitreous hemorrhage were enrolled. NP area, NV number, and NV area were quantitatively measured using ultra-widefield fluorescein angiography in an automated manner. Aqueous humor VEGF level was measured using a bead assay. Results: The NP areas of the total, posterior pole, peripheral retinae, and NV area positively correlated with each other (all p < 0.034). NV number correlated with total NP area, peripheral NP area, and NV area (all p ≤ 0.001). VEGF levels were significantly positively correlated with total, posterior polar, and peripheral NP areas and NV area (r = 0.575, 0.422, 0.558, and 0.362, respectively; all p ≤ 0.012). In eyes with NV in the disc area, the VEGF level was higher compare to eyes without NV in the disc area (208.89 ± 192.77 pg/mL vs. 103.34 ± 132.66, p = 0.010). A multiple linear regression model using NP area, NV area, and NVD demonstrated good prediction for VEGF level (R2 = 0.417, p < 0.001) and revealed a significant contribution of the peripheral NP area in predicting the VEGF level (β = 0.497, p = 0.002). Conclusions: Aqueous humor VEGF levels in quiescent PDR eyes were associated with NP and NV areas, which had positive correlations with each other. In addition, the NP area of the peripheral retina was the most important predictor of VEGF level. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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11 pages, 753 KiB  
Article
Retinopathy Phenotypes in Type 2 Diabetes with Different Risks for Macular Edema and Proliferative Retinopathy
by Ines P. Marques, Maria H. Madeira, Ana L. Messias, Torcato Santos, António C-V. Martinho, João Figueira and José Cunha-Vaz
J. Clin. Med. 2020, 9(5), 1433; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051433 - 12 May 2020
Cited by 21 | Viewed by 2596
Abstract
Our group reported that three diabetic retinopathy (DR) phenotypes: A, characterized by low microaneurysm turnover (MAT < 6) and normal central retinal thickness (CRT); B, low MAT (<6) and increased CRT, and C, high MAT (≥6), present different risks for development of macular [...] Read more.
Our group reported that three diabetic retinopathy (DR) phenotypes: A, characterized by low microaneurysm turnover (MAT < 6) and normal central retinal thickness (CRT); B, low MAT (<6) and increased CRT, and C, high MAT (≥6), present different risks for development of macular edema (DME) and proliferative retinopathy (PDR). To test these findings, 212 persons with type 2 diabetes (T2D) and mild nonproliferative retinopathy (NPDR), one eye per person, were followed for five years with annual visits. Of these, 172 completed the follow-up or developed an outcome: PDR or DME (considering both clinically significant macular edema (CSME) and center-involved macular edema (CIME)). Twenty-seven eyes (16%) developed either CSME (14), CIME (10), or PDR (4), with one eye developing both CSME and PDR. Phenotype A showed no association with development of vision-threatening complications. Seven eyes with phenotype B and three with phenotype C developed CIME. Phenotype C showed higher risk for CSME development, with 17.41 odds ratio (p = 0.010), compared with phenotypes A + B. All eyes that developed PDR were classified as phenotype C. Levels of HbA1c and triglycerides were increased in phenotype C (p < 0.001 and p = 0.018, respectively). In conclusion, phenotype C identifies eyes at higher risk for development of CSME and PDR, whereas phenotype A identifies eyes at very low risk for vision-threatening complications. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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11 pages, 1055 KiB  
Article
Age-Related Macular Degeneration Staging by Color Fundus Photography vs. Multimodal Imaging—Epidemiological Implications (The Coimbra Eye Study—Report 6)
by Cláudia Farinha, Maria Luz Cachulo, Rita Coimbra, Dalila Alves, Sandrina Nunes, Isabel Pires, João Pedro Marques, José Costa, Amélia Martins, Isa Sobral, Patrícia Barreto, Inês Laíns, João Figueira, Luisa Ribeiro, José Cunha-Vaz and Rufino Silva
J. Clin. Med. 2020, 9(5), 1329; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051329 - 02 May 2020
Cited by 10 | Viewed by 3300
Abstract
Epidemiology of age-related macular degeneration (AMD) is based on staging systems relying on color fundus photography (CFP). We aim to compare AMD staging using CFP to multimodal imaging with optical coherence tomography (OCT), infra-red (IR), and fundus autofluorescence (FAF), in a large cohort [...] Read more.
Epidemiology of age-related macular degeneration (AMD) is based on staging systems relying on color fundus photography (CFP). We aim to compare AMD staging using CFP to multimodal imaging with optical coherence tomography (OCT), infra-red (IR), and fundus autofluorescence (FAF), in a large cohort from the Epidemiologic AMD Coimbra Eye Study. All imaging exams from the participants of this population-based study were classified by a central reading center. CFP images were graded according to the International Classification and Grading System for AMD and staged with Rotterdam classification. Afterward, CFP images were reviewed with OCT, IR, and FAF and stage update was performed if necessary. Early and late AMD prevalence was compared in a total of 1616 included subjects. In CFP-based grading, the prevalence was 14.11% for early AMD (n = 228) and 1.05% (n = 17) for late AMD, nine cases (0.56%) had neovascular AMD (nAMD) and eight (0.50%) geographic atrophy (GA). Using multimodal grading, the prevalence increased to 14.60% for early AMD (n = 236) and 1.61% (n = 26) for late AMD, with 14 cases (0.87%) of nAMD and 12 (0.74%) of GA. AMD staging was more accurate with the multimodal approach and this was especially relevant for late AMD. We propose that multimodal imaging should be adopted in the future to better estimate and compare epidemiological data in different populations. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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13 pages, 3020 KiB  
Article
Enhanced Visualization of Retinal Microvasculature in Optical Coherence Tomography Angiography Imaging via Deep Learning
by Shin Kadomoto, Akihito Uji, Yuki Muraoka, Tadamichi Akagi and Akitaka Tsujikawa
J. Clin. Med. 2020, 9(5), 1322; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051322 - 02 May 2020
Cited by 29 | Viewed by 4284
Abstract
Background: To investigate the effects of deep learning denoising on quantitative vascular measurements and the quality of optical coherence tomography angiography (OCTA) images. Methods: U-Net-based deep learning denoising with an averaged OCTA data set as teacher data was used in this study. One [...] Read more.
Background: To investigate the effects of deep learning denoising on quantitative vascular measurements and the quality of optical coherence tomography angiography (OCTA) images. Methods: U-Net-based deep learning denoising with an averaged OCTA data set as teacher data was used in this study. One hundred and thirteen patients with various retinal diseases were examined. An OCT HS-100 (Canon inc., Tokyo, Japan) performed a 3 × 3 mm2 superficial capillary plexus layer slab scan centered on the fovea 10 times. A single-shot image was defined as the original image and the 10-frame averaged image and denoised image generated from the original image using deep learning denoising for the analyses were obtained. The main parameters measured were the OCTA image acquisition time, contrast-to-noise ratio (CNR), peak signal-to-noise ratio (PSNR), vessel density (VD), vessel length density (VLD), vessel diameter index (VDI), and fractal dimension (FD) of the original, averaged, and denoised images. Results: One hundred and twelve eyes of 108 patients were studied. Deep learning denoising removed the background noise and smoothed the rough vessel surface. The image acquisition times for the original, averaged, and denoised images were 16.6 ± 2.4, 285 ± 38, and 22.1 ± 2.4 s, respectively (P < 0.0001). The CNR and PSNR of the denoised image were significantly higher than those of the original image (P < 0.0001). There were significant differences in the VLD, VDI, and FD (P < 0.0001) after deep learning denoising. Conclusions: The deep learning denoising method achieved high speed and high quality OCTA imaging. This method may be a viable alternative to the multiple image averaging technique. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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11 pages, 1553 KiB  
Article
Changes in Iris Perfusion Following Scleral Buckle Surgery for Rhegmatogenous Retinal Detachment: An Anterior Segment Optical Coherence Tomography Angiography (AS-OCTA) Study
by Rossella D’Aloisio, Pasquale Viggiano, Enrico Borrelli, Mariacristina Parravano, Aharrh-Gnama Agbèanda, Federica Evangelista, Giada Ferro, Lisa Toto and Rodolfo Mastropasqua
J. Clin. Med. 2020, 9(4), 1231; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9041231 - 24 Apr 2020
Cited by 13 | Viewed by 3119
Abstract
Purpose: To investigate iris vasculature changes following scleral buckling (SB) surgery in eyes with rhegmatogenous retinal detachment (RRD) with anterior-segment (AS) optical coherence tomography angiography (OCTA). Methods: In this prospective study, enrolled subjects were imaged with an SS-OCTA system (PLEX Elite 9000, Carl [...] Read more.
Purpose: To investigate iris vasculature changes following scleral buckling (SB) surgery in eyes with rhegmatogenous retinal detachment (RRD) with anterior-segment (AS) optical coherence tomography angiography (OCTA). Methods: In this prospective study, enrolled subjects were imaged with an SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). Image acquisition of the iris was obtained using an AS lens and a manual focusing adjustment in the iris using the retina imaging software. The quantitative analysis was performed in eight different iris regions: (i) superior, (ii) supero-temporal, (iii) supero-nasal, (iv) nasal, (v) temporal, (vi) inferior, (vii) infero-temporal, (viii) infero nasal which, were defined as squares with area of 1.5 mm2. Results: Fifteen eyes of 15 patients (six females; nine males) were included. Anterior segment optical coherence tomography angiography (AS-OCTA) parameters of the iris were statistically compared at baseline (preoperatively), 1 week, 1 month and 6 months after SB. At post-operative 1 week, perfusion density (PD) showed a significant decrease from 66.8 ± 13.2% to 58.55 ± 12.0% in the iris supero-nasal region (p = 0.016). However, at the 1-month follow-up visit, iris PD was significantly lower in all the analyzed iris regions, apart from the superior one. Conclusions: This study is the first description of AS-OCTA in patients undergoing SB. Our results showed a uniform reduction of the iris vessel network at 1 month after surgery, supporting the clinical use of AS-OCTA to identify early iris perfusion changes as potential predictive biomarkers of vascular disorders. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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Review

Jump to: Research

18 pages, 1131 KiB  
Review
Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa
by Spencer M. Moore, Dorota Skowronska-Krawczyk and Daniel L. Chao
J. Clin. Med. 2020, 9(7), 2224; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072224 - 13 Jul 2020
Cited by 15 | Viewed by 4097
Abstract
Retinitis pigmentosa (RP) is an inherited retinal dystrophy (IRD) with a prevalence of 1:4000, characterized by initial rod photoreceptor loss and subsequent cone photoreceptor loss with accompanying nyctalopia, visual field deficits, and visual acuity loss. A diversity of causative mutations have been described [...] Read more.
Retinitis pigmentosa (RP) is an inherited retinal dystrophy (IRD) with a prevalence of 1:4000, characterized by initial rod photoreceptor loss and subsequent cone photoreceptor loss with accompanying nyctalopia, visual field deficits, and visual acuity loss. A diversity of causative mutations have been described with autosomal dominant, autosomal recessive, and X-linked inheritance and sporadic mutations. The diversity of mutations makes gene therapy challenging, highlighting the need for mutation-agnostic treatments. Neural leucine zipper (NRL) and NR2E3 are factors important for rod photoreceptor cell differentiation and homeostasis. Germline mutations in NRL or NR2E3 leads to a loss of rods and an increased number of cones with short wavelength opsin in both rodents and humans. Multiple groups have demonstrated that inhibition of NRL or NR2E3 activity in the mature retina could endow rods with certain properties of cones, which prevents cell death in multiple rodent RP models with diverse mutations. In this review, we summarize the literature on NRL and NR2E3, therapeutic strategies of NRL/NR2E3 modulation in preclinical RP models, as well as future directions of research. In summary, inhibition of the NRL/NR2E3 pathway represents an intriguing mutation agnostic and disease-modifying target for the treatment of RP. Full article
(This article belongs to the Special Issue New Advances in Retinal Research)
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