Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies

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 June 2021) | Viewed by 66600

Special Issue Editor


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Guest Editor
Department of Ophthalmology, Otsu Red Cross Hospital, Otsu, Japan
Interests: vitreo-retinal disorders; pathogenesis; personalized medicine

Special Issue Information

Dear Colleagues,

Vitreo-retinal disorders are among the leading causes of visual impairment and blindness worldwide. Recently, their pathogenesis has been investigated by clinical and basic studies using advanced imaging analyses and genome analyses. Their diagnosis has changed through recently proposed classifications. New drugs under development and newly proposed surgical techniques will also change the treatment method and regimen for vitreo-retinal disorders. This Special Issue will address the most recent findings on vitreo-retinal disorders and review their pathogenesis, diagnosis, and therapies.

Prof. Kenji Yamashiro
Guest Editor

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Keywords

  • Age-related macular degeneration
  • Myopic macular degeneration
  • Diabetic retinopathy
  • Retinal vein occlusion
  • Diagnosis
  • Imaging
  • Epidemiology
  • Pathogenesis
  • Treatment
  • Personalized/precision medicine

Published Papers (21 papers)

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17 pages, 1538 KiB  
Article
Central and Branch Retinal Artery Occlusion—Do They Harbor the Same Risk of Further Ischemic Events?
by Joanna Roskal-Wałek, Paweł Wałek, Michał Biskup, Dominik Odrobina, Jerzy Mackiewicz, Stanisław Głuszek and Beata Wożakowska-Kapłon
J. Clin. Med. 2021, 10(14), 3093; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10143093 - 13 Jul 2021
Cited by 8 | Viewed by 2590
Abstract
Purpose: Retinal artery occlusion (RAO) is associated with an increased risk of cardiovascular events such as ischemic stroke and myocardial infarction, but whether different RAO subtypes such as central retinal artery occlusion (CRAO) or branch retinal artery occlusion (BRAO) carry similar risk of [...] Read more.
Purpose: Retinal artery occlusion (RAO) is associated with an increased risk of cardiovascular events such as ischemic stroke and myocardial infarction, but whether different RAO subtypes such as central retinal artery occlusion (CRAO) or branch retinal artery occlusion (BRAO) carry similar risk of these events is unclear. Our aim was to determine whether the risk of cardiovascular events differs between CRAO and BRAO. Methods: This single-center, retrospective study included 131 patients hospitalized in our clinic in 2010–2020 with CRAO or BRAO confirmed by ophthalmic examination. Data on demographics, previous ischemic stroke and myocardial infarction, comorbidities, the results of echocardiographic and ultrasound carotid artery examinations and laboratory tests were assessed. Data on ischemic stroke, myocardial infarction, and all-cause mortality occurring after RAO were obtained from the Polish National Health Service, which collects data on all publicly funded hospitalizations. Using these data, Kaplan-Meier analyses and Cox proportional hazard regression were performed. Results: Ischemic stroke occurred in 9.9% of patients after RAO: 10.6% in the CRAO group and 8.1% in the BRAO group (p = 0.662). Myocardial infarction occurred in 2.3% of patients after RAO: 2.1% in the CRAO group and 2.7% in the BRAO group (p = 0.843). All-cause mortality occurred in 22.9% of patients after RAO: 25.5% in the CRAO group and 16.2% in the BRAO group (p = 0.253). The composite endpoint of ischemic stroke, myocardial infarction, and all-cause mortality after RAO occurred in 28.2% of patients: 30.9% in the CRAO group and 21.6% in the BRAO group (p = 0.338). There was no difference between CRAO and BRAO in median time to ischemic stroke (32 vs. 76.4 months; p = 0.352), all-cause mortality (35.9 vs. 36.3 months; p = 0.876) or composite endpoint (37.5 vs. 41.5 months; p = 0.912) after RAO. The Kaplan-Meier analysis showed no differences between CRAO and BRAO in ischemic stroke, myocardial infarction, all-cause mortality, or the composite endpoint; similar results were obtained in analyses of patients with and without cardiovascular events before RAO. Conclusions: The prognosis for ischemic stroke, myocardial infarction, and all-cause mortality is similar in patients with CRAO and BRAO. Ischemic strokes occur with a similar frequency before and after RAO. Myocardial infarctions are observed significantly more frequently before an episode of RAO than after. The results of our study indicate that both CRAO and BRAO require expanded diagnostics to assess the risk of recurrent cardiovascular events, especially ischemic strokes, to implement appropriate prophylaxis and reduce mortality. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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8 pages, 1835 KiB  
Article
Assessment of Hypofluorescent Foci on Late-Phase Indocyanine Green Angiography in Central Serous Chorioretinopathy
by Ari Shinojima, Yoko Ozawa, Atsuro Uchida, Norihiro Nagai, Hajime Shinoda, Toshihide Kurihara, Misa Suzuki, Sakiko Minami, Kazuno Negishi and Kazuo Tsubota
J. Clin. Med. 2021, 10(10), 2178; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10102178 - 18 May 2021
Cited by 4 | Viewed by 1546
Abstract
To assess the hypofluorescent foci (HFF) on late-phase indocyanine green angiography (ICGA) in central serous chorioretinopathy (CSC) using short-wavelength fundus autofluorescence (SW-FAF), near-infrared autofluorescence (NIR-AF), and fluorescein angiography (FA). The HFF area on late-phase ICGA for at least 20 min was compared with [...] Read more.
To assess the hypofluorescent foci (HFF) on late-phase indocyanine green angiography (ICGA) in central serous chorioretinopathy (CSC) using short-wavelength fundus autofluorescence (SW-FAF), near-infrared autofluorescence (NIR-AF), and fluorescein angiography (FA). The HFF area on late-phase ICGA for at least 20 min was compared with the area of abnormal foci on SW-FAF, NIR-AF, and FA. In 14 consecutive patients (12 men, including 1 with bilateral CSC; and 2 women with unilateral CSC), four kinds of images of 27 eyes were acquired. The mean age ± standard deviation (range) was 46 ± 9.2 years (31–69 years). The HFF on late-phase ICGA were found in 23 eyes (in all 15 CSC eyes and the contralateral 8 eyes). From the results of simple regression analysis, we obtained the following three formulas. The HFF area on ICGA = 1.058 × [abnormal SW-FAF area] + 0.135, the HFF area on ICGA = 1.001 × [abnormal NIR-AF area] + 0.015, and the HFF area on ICGA = 1.089 × [abnormal FA area] + 0.135. Compared to SW-FAF and FA, NIR-AF was found to be the easiest method to detect the HFF on late-phase ICGA, which may indicate melanin abnormalities, especially a decrease, in the retinal pigment epithelium. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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9 pages, 1127 KiB  
Article
Central Serous Chorioretinopathy and Blood Serotonin Concentrations
by Takeshi Kimura, Takashi Araki, Yuki Komuku, Hisashi Iwami and Fumi Gomi
J. Clin. Med. 2021, 10(4), 558; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10040558 - 03 Feb 2021
Cited by 5 | Viewed by 1898
Abstract
Background: To investigate blood serotonin (5-hydroxytryptamine (5-HT)) concentrations and their relationships with selected characteristics in patients with central serous chorioretinopathy (CSC). Methods: This was a prospective study including 93 patients with active CSC. Blood concentrations of 5-HT, adrenocorticotropic hormone, and cortisol were measured [...] Read more.
Background: To investigate blood serotonin (5-hydroxytryptamine (5-HT)) concentrations and their relationships with selected characteristics in patients with central serous chorioretinopathy (CSC). Methods: This was a prospective study including 93 patients with active CSC. Blood concentrations of 5-HT, adrenocorticotropic hormone, and cortisol were measured in patients with CSC. Selected patient characteristics, including disease history (acute or chronic), medication use, smoking history, mood status, best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SCT), findings on fluorescein and indocyanine green angiography, and anatomical changes were evaluated during follow-up. Results: Eleven of the 93 patients had low 5-HT concentrations (<57 ng/mL) (12%, eight men and three women; mean age 55 years); we identified no significant relationship with acute/chronic disease status. The patients with low 5-HT were significantly more likely to have five or more fluorescein leakage sites (p = 0.0275), recurrence of subretinal fluids (p < 0.0001), and failure to achieve significant improvement in BCVA during follow-up (p = 0.862) than patients with 5-HT within the normal range. Conclusions: Blood serotonin concentrations may influence the pathophysiology and prognosis of CSC. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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11 pages, 2143 KiB  
Article
Transient Increase and Delay of Multifocal Electroretinograms Following Laser Photocoagulations for Diabetic Macular Edema
by Yoshiaki Shimada, Masayuki Shibuya and Kei Shinoda
J. Clin. Med. 2021, 10(2), 357; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020357 - 19 Jan 2021
Cited by 3 | Viewed by 1807
Abstract
Background: The acute physiological changes induced by focal retinal photocoagulation (PC) have been largely unexplored. Methods: This was a case-series study. We recorded multifocal electroretinograms (mfERGs) just before PC, and mfERGs were also recorded 5′, 15′, one hour, 24 h, and one week [...] Read more.
Background: The acute physiological changes induced by focal retinal photocoagulation (PC) have been largely unexplored. Methods: This was a case-series study. We recorded multifocal electroretinograms (mfERGs) just before PC, and mfERGs were also recorded 5′, 15′, one hour, 24 h, and one week after the PCs. Transient changes of mfERGs were analyzed in eyes which underwent PCs to treat diabetic macular edema. The mfERGs recorded from the predominantly irradiated area and that from non-irradiated areas were analyzed separately. Results: Fifteen eyes of 15 patients were included in this study. The mfERGs elicited from non-irradiated areas did not change after PC, but the mfERGs elicited from the irradiated area changed with time; the amplitude was larger at 60′ than that before (p < 0.05) and at 5′ after PC (p < 0.01) and significantly smaller at 24 h and 1 week than that before and at 60′ after the PC (p < 0.01). The implicit time was significantly prolonged after PC. mfERG on irradiated area with the severe diabetic change was less altered after PCs. Conclusions: The transient increase in the amplitude at 60′ likely resulted from a biological amplification of partially damaged cells adjacent to the PC spots. The mfERGs manifested the dynamic alterations of the retinal function following PCs. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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12 pages, 1974 KiB  
Article
Retinal Microcirculation and Cytokines as Predictors for Recurrence of Macular Edema after Intravitreal Ranibizumab Injection in Branch Retinal Vein Occlusion
by Hidetaka Noma, Kanako Yasuda, Tatsuya Mimura, Noboru Suganuma and Masahiko Shimura
J. Clin. Med. 2021, 10(1), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10010058 - 26 Dec 2020
Cited by 9 | Viewed by 2388
Abstract
Purpose: To investigate the relationship between retinal blood flow, presence or absence of recurrence of macular edema, and levels of cytokines, after intravitreal ranibizumab injection (IRI) in patients with branch retinal vein occlusion (BRVO). Methods: In 47 patients with BRVO and macular edema, [...] Read more.
Purpose: To investigate the relationship between retinal blood flow, presence or absence of recurrence of macular edema, and levels of cytokines, after intravitreal ranibizumab injection (IRI) in patients with branch retinal vein occlusion (BRVO). Methods: In 47 patients with BRVO and macular edema, we used laser speckle flowgraphy (LSFG) to measure the relative flow volume (RFV) of the retinal arteries and veins passing through the optic disc in the occluded and non-occluded regions of the retina before and after IRI. Aqueous humor samples were obtained at the time of IRI. Levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, IL-12 (p70), IL-13 and interferon-inducible 10-kDa protein (IP-10) were measured by the suspension array method. Patients were categorized into two groups on the basis of whether or not macular edema recurred at 2 months after IRI: the nonrecurrent group, n = 24; and the recurrent group, n = 23. Results: In the veins of the occluded region, RFV showed a significant difference between baseline and 1 month after IRI (p < 0.001) in the recurrent group and the percent change of RFV showed a significant difference between the recurrent and nonrecurrent groups (p = 0.005). Furthermore, we found a significant negative correlation between RFV in the veins of the occluded region and aqueous levels of MCP-1, IL-8 and IP-10 at baseline (p = 0.029, p = 0.035, and p = 0.039, respectively). In the recurrent group, the arteries and veins of the non-occluded and occluded regions showed no significant association between RFV and the aqueous levels of any factors. Conclusions: These findings suggested that a decrease in RFV in the veins of the occluded region might be associated with the recurrence of macular edema and that the recurrence might depend on the change in RFV in the veins of the occluded region rather than the levels of cytokines. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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7 pages, 1032 KiB  
Article
Improvement of Low Luminance Visual Acuity in Patients with Chronic Central Serous Chorioretinopathy after Half-Dose Verteporfin Photodynamic Therapy
by Kyoko Fujita, Kei Shinoda, Yutaka Imamura, Celso Soiti Matsumoto and Koichi Oda
J. Clin. Med. 2020, 9(12), 3980; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9123980 - 09 Dec 2020
Cited by 2 | Viewed by 1706
Abstract
Patients with central serous chorioretinopathy (CSC) often complain of visual difficulties under low luminance conditions. In this study, we evaluated low luminance visual acuity (LLVA) after half-dose verteporfin photodynamic therapy (hdPDT) in eyes with CSC. The study included eight eyes of eight patients [...] Read more.
Patients with central serous chorioretinopathy (CSC) often complain of visual difficulties under low luminance conditions. In this study, we evaluated low luminance visual acuity (LLVA) after half-dose verteporfin photodynamic therapy (hdPDT) in eyes with CSC. The study included eight eyes of eight patients with chronic CSC that underwent hdPDT. The best-corrected visual acuity, LLVA and optical coherence tomography (OCT) findings were evaluated at baseline, and at 1, 3, 6, 9, and 12 months after hdPDT. LLVA was measured at six levels of background luminance. Serous retinal detachment was completely resolved in all eyes. Although the mean LLVA at 1 month did not improve significantly compared to baseline at all luminance levels, significant improvements were observed at 3, 6, 9, and 12 months (p < 0.05). In OCT images, although the ellipsoid zone was not detectable in all eyes before hdPDT, it was observed in 2 eyes at 1 month, in 7 eyes at 3 months, and in all eyes from 6 months. The LLVA and the ellipsoid zone improved similarly with postoperative time courses. In conclusion, hdPDT improves LLVA in eyes with chronic CSC. The recovery of the ellipsoid zone may play a part in improving LLVA after hdPDT. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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16 pages, 11302 KiB  
Article
Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration
by Sander De Bruyne, Caroline Van den Broecke, Henk Vrielinck, Samira Khelifi, Olivier De Wever, Ken Bracke, Manon Huizing, Nezahat Boston, Jonas Himpe, Marijn Speeckaert, Anne Vral, Jo Van Dorpe, Elisabeth Van Aken and Joris R. Delanghe
J. Clin. Med. 2020, 9(9), 2869; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9092869 - 04 Sep 2020
Cited by 7 | Viewed by 3911
Abstract
Age-related macular degeneration is the leading cause of blindness in the developed world. Since advanced glycation end products (AGEs) are implicated in the pathogenesis of AMD through various lines of evidence, we investigated the potential of fructosamine-3-kinase (FN3K) in the disruption of retinal [...] Read more.
Age-related macular degeneration is the leading cause of blindness in the developed world. Since advanced glycation end products (AGEs) are implicated in the pathogenesis of AMD through various lines of evidence, we investigated the potential of fructosamine-3-kinase (FN3K) in the disruption of retinal AGEs, drusenoid material and drusenoid lesions in patients with AMD. AGE-type autofluorescence was measured to evaluate the effects of FN3K on glycolaldehyde-induced AGE-modified neural porcine retinas and unmodified human neural retinas. Eye pairs from cigarette-smoke- and air-exposed mice were treated and evaluated histologically. Automated optical image analysis of human tissue sections was performed to compare control- and FN3K-treated drusen and near-infrared (NIR) microspectroscopy was performed to examine biochemical differences. Optical coherence tomography (OCT) was used to evaluate the effect of FN3K on drusenoid deposits after treatment of post-mortem human eyes. FN3K treatment provoked a significant decrease (41%) of AGE-related autofluorescence in the AGE-modified porcine retinas. Furthermore, treatment of human neural retinas resulted in significant decreases of autofluorescence (−24%). FN3K-treated murine eyes showed less drusenoid material. Pairwise comparison of drusen on tissue sections revealed significant changes in color intensity after FN3K treatment. NIR microspectroscopy uncovered clear spectral differences in drusenoid material (Bruch’s membrane) and drusen after FN3K treatment. Ex vivo treatment strongly reduced size of subretinal drusenoid lesions on OCT imaging (up to 83%). In conclusion, our study demonstrated for the first time a potential role of FN3K in the disruption of AGE-related retinal autofluorescence, drusenoid material and drusenoid lesions in patients with AMD. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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11 pages, 2326 KiB  
Article
Long-Term Outcome of Epiretinal Membrane Surgery in Patients with Internal Limiting Membrane Dehiscence
by Min-Woo Lee, Il Jung, Yong-Yeon Song, Seung-Kook Baek and Young-Hoon Lee
J. Clin. Med. 2020, 9(8), 2470; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082470 - 01 Aug 2020
Cited by 7 | Viewed by 2857 | Correction
Abstract
Purpose: To identify the effect of internal limiting membrane (ILM) dehiscence on surgical outcomes in eyes that have undergone epiretinal membrane (ERM) removal. Methods: Consecutive eyes with performed vitrectomy for ERM removal were included. Subjects were divided into two groups: patients with ILM [...] Read more.
Purpose: To identify the effect of internal limiting membrane (ILM) dehiscence on surgical outcomes in eyes that have undergone epiretinal membrane (ERM) removal. Methods: Consecutive eyes with performed vitrectomy for ERM removal were included. Subjects were divided into two groups: patients with ILM dehiscence (group 1) and without ILM dehiscence (group 2). The best-corrected visual acuity (BCVA) and retinal layer thickness before and after surgery were compared between the two groups. Results: A total of 86 eyes were enrolled. Forty-six eyes (53.5%) showed ILM dehiscence before surgery. The baseline BCVAs were 0.46 ± 0.29 and 0.45 ± 0.25 in groups 1 and 2, respectively (p = 0.801). The BCVAs at 3, 6, and 12 months after surgery differed significantly between the two groups. The subfoveal thickness and inner retinal layer thickness (IRLT) of group 1 vs. 2 were 507.4 ± 80.0 vs. 417.6 ± 63.6 μm, and 270.2 ± 74.3 vs. 182.6 ± 60.4 μm, respectively (both p < 0.001). These differences between the groups remained significant until 12 months after surgery. In multivariate analyses, the location of ILM dehiscence (B = −0.105, p = 0.034) and final IRLT (B = 0.001, p = 0.046) were significant factors affecting the final BCVA. Conclusions: ILM dehiscence is a relatively common finding and associated with preoperative and postoperative increased IRLT, which results in worse surgical outcomes compared to the absence of ILM dehiscence in patients with ERM. Additionally, the final BCVA was significantly affected by its location and final IRLT in patients with ILM dehiscence. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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12 pages, 3536 KiB  
Article
Pachydrusen in Fellow Eyes Predict Response to Aflibercept Monotherapy in Patients with Polypoidal Choroidal Vasculopathy
by Yoshiko Fukuda, Yoichi Sakurada, Atsushi Sugiyama, Seigo Yoneyama, Mio Matsubara, Wataru Kikushima, Naohiko Tanabe, Ravi Parikh and Kenji Kashiwagi
J. Clin. Med. 2020, 9(8), 2459; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082459 - 31 Jul 2020
Cited by 6 | Viewed by 2254
Abstract
We investigated whether responses to as-needed intravitreal aflibercept injections (IAIs) for polypoidal choroidal vasculopathy (PCV) differed among patients based upon drusen characteristics in fellow eyes. 110 eyes from 110 patients with PCV received 3 monthly IAI and thereafter Pro re nata (PRN) IAI [...] Read more.
We investigated whether responses to as-needed intravitreal aflibercept injections (IAIs) for polypoidal choroidal vasculopathy (PCV) differed among patients based upon drusen characteristics in fellow eyes. 110 eyes from 110 patients with PCV received 3 monthly IAI and thereafter Pro re nata (PRN) IAI over 12 months. Patients were classified into 4 groups depending on fellow eye findings. Group 1 (n = 16): pachydrusen; Group 2 (n = 45): no drusen; Group 3 (n = 35): soft drusen; Group4 (n = 14) PCV/scarring. Best-corrected visual acuity improved at 12 months in all groups, but not significantly in Group 1 and Group 4; however, visual improvement was similar among the groups after adjusting baseline confounders. Group 1 had a significantly lower percentage of eyes needing retreatment (all p < 0.001; Group 1: 16.7%; Group 2: 50.8%; Group 3: 80%; Group 4: 85.7%). The mean number of retreatments was least in Group 1 among the groups (all p-value < 0.003; Group 1: 0.50 ± 1.32; Group 2: 1.73 ± 2.08; Group 3:2.71 ± 1.99; Group 3: 2.71 ± 2.16). Patients with pachydrusen in fellow eyes were less likely to require additional IAI following the loading dose and may be ideal candidates for aflibercept monotherapy in their first year. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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12 pages, 2020 KiB  
Article
Efficacy of Modified Treat-and-Extend Aflibercept Regimen for Macular Edema Due to Branch Retinal Vein Occlusion: 1-Year Prospective Study
by Yusuke Arai, Hidenori Takahashi, Satoru Inoda, Shinichi Sakamoto, Xue Tan, Yuji Inoue, Satoko Tominaga, Hidetoshi Kawashima and Yasuo Yanagi
J. Clin. Med. 2020, 9(8), 2360; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082360 - 23 Jul 2020
Cited by 9 | Viewed by 3728
Abstract
Purpose: To assess the efficacy and safety of a modified treat-and-extend (mTAE) regimen of aflibercept for macular edema (ME) due to branch retinal vein occlusion (BRVO). Methods: This prospective multicentre intervention study evaluated 50 eyes of 50 patients enrolled from October 2016 to [...] Read more.
Purpose: To assess the efficacy and safety of a modified treat-and-extend (mTAE) regimen of aflibercept for macular edema (ME) due to branch retinal vein occlusion (BRVO). Methods: This prospective multicentre intervention study evaluated 50 eyes of 50 patients enrolled from October 2016 to September 2017. The patients received intravitreal aflibercept (IVA) injections on an mTAE regimen for a total of 12 months. The main outcome measures were best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 12 months. Results: The baseline BCVA and CST were 0.33 (0.27) and 488 (171) µm (mean (standard deviation)), respectively. The BCVA and CST were significantly improved at month 12 (0.067 (0.19) LogMAR and 295 (110) µm; both p < 0.0001, paired t-test). The mean number of clinic visits and IVA injections was 6.71 (1.41) and 4.26 (0.71), respectively. The time to first recurrence from the first injection was most frequently 3 months. Conclusion: The mTAE regimen of IVA injections for ME due to BRVO effectively improved BCVA and reduced CST, and thus might be an effective therapy to reduce the number of injections and visits. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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16 pages, 5364 KiB  
Article
Receptor-Associated Prorenin System in the Trabecular Meshwork of Patients with Primary Open-Angle Glaucoma and Neovascular Glaucoma
by Erdal Tan Ishizuka, Atsuhiro Kanda, Yasuhiro Shinmei, Takeshi Ohguchi, Yoshiaki Tagawa, Keitaro Hase, Taku Yamamoto, Kousuke Noda, Shinki Chin and Susumu Ishida
J. Clin. Med. 2020, 9(8), 2336; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082336 - 22 Jul 2020
Viewed by 2047
Abstract
The receptor-associated prorenin system (RAPS) is associated with several pathologic conditions, including diabetic retinopathy, age-related macular degeneration, and uveitis. Here, we show the involvement of RAPS in the trabecular meshwork (TM) from patients with primary open-angle glaucoma (POAG) and neovascular glaucoma (NVG) due [...] Read more.
The receptor-associated prorenin system (RAPS) is associated with several pathologic conditions, including diabetic retinopathy, age-related macular degeneration, and uveitis. Here, we show the involvement of RAPS in the trabecular meshwork (TM) from patients with primary open-angle glaucoma (POAG) and neovascular glaucoma (NVG) due to proliferative diabetic retinopathy. Anterior chamber (AC) levels of prorenin significantly increased in both POAG and NVG, as did those of angiotensin II in NVG alone, compared to cataract. In surgically excised TM tissues, (pro)renin receptor ((P)RR) and angiotensin II type 1 receptor (AT1R) co-localized with prorenin and angiotensinogen, respectively. In screening for various genes related to glaucoma, prorenin stimulation to human TM cells exclusively upregulated cell junction constituents connexin 43 and zona occludens 1, while downregulating an extracellular matrix-degrading enzyme tissue plasminogen activator, all of which were reversed by (P)RR blockade. In contrast, angiotensin II application upregulated a pro-angiogenic factor placental growth factor alone, which was abolished by AT1R blockade. Consistently, (P)RR and AT1R co-localized with these corresponding proteins in patient TM tissues. Oxidative stress, a known etiology for glaucoma, induced the expression of prorenin and angiotensinogen in human TM cells. These data suggest the contribution of RAPS to the molecular pathogenesis of POAG and NVG through TM tissue remodeling and AC angle angiogenesis. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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14 pages, 3091 KiB  
Article
Blockade of Platelet-Derived Growth Factor Signaling Inhibits Choroidal Neovascularization and Subretinal Fibrosis in Mice
by Ye Liu, Kousuke Noda, Miyuki Murata, Di Wu, Atsuhiro Kanda and Susumu Ishida
J. Clin. Med. 2020, 9(7), 2242; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072242 - 15 Jul 2020
Cited by 10 | Viewed by 2438
Abstract
Neovascular age related macular degeneration (nAMD) leads to severe vision loss worldwide and is characterized by the formation of choroidal neovascularization (CNV) and fibrosis. In the current study, we aimed to investigate the effect of blockade for platelet derived growth factor receptor-β (PDGFR-β) [...] Read more.
Neovascular age related macular degeneration (nAMD) leads to severe vision loss worldwide and is characterized by the formation of choroidal neovascularization (CNV) and fibrosis. In the current study, we aimed to investigate the effect of blockade for platelet derived growth factor receptor-β (PDGFR-β) on the formation of choroidal neovascularization and fibrosis in the laser-induced CNV model in mice. Firstly, the presence of PDGFR-β in CNV lesions were confirmed. Intravitreal injection of PDGFR-β neutralizing antibody significantly reduced the size of CNV and subretinal fibrosis. Additionally, subretinal hyperreflective material (SHRM), a landmark feature on OCT as a risk factor for subretinal fibrosis formation in nAMD patients was also suppressed by PDGFR-β blockade. Furthermore, pericytes were abundantly recruited to the CNV lesions during CNV formation, however, blockade of PDGFR-β significantly reduced pericyte recruitment. In addition, PDGF-BB stimulation increased the migration of the rat retinal pericyte cell line, R-rPCT1, which was abrogated by the neutralization of PDGFR-β. These results indicate that blockade of PDGFR-β attenuates laser-induced CNV and fibrosis through the inhibition of pericyte migration. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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11 pages, 1135 KiB  
Article
Effects of Prolonged Type 2 Diabetes on the Inner Retinal Layer and Macular Microvasculature: An Optical Coherence Tomography Angiography Study
by Min-Woo Lee, Woo-Hyuk Lee, Cheon-Kuk Ryu, Tae-Yeon Kim, Hyung-Bin Lim, Young-Hoon Lee and Jung-Yeul Kim
J. Clin. Med. 2020, 9(6), 1849; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061849 - 13 Jun 2020
Cited by 25 | Viewed by 2158
Abstract
Purpose: To identify the effects of prolonged type 2 diabetes (T2DM) on macular microcirculation and the inner retinal layer in diabetic eyes without clinical diabetic retinopathy (DR). Methods: 97, 92, and 57 eyes in the control, patients with T2DM < 10 years (DM [...] Read more.
Purpose: To identify the effects of prolonged type 2 diabetes (T2DM) on macular microcirculation and the inner retinal layer in diabetic eyes without clinical diabetic retinopathy (DR). Methods: 97, 92, and 57 eyes in the control, patients with T2DM < 10 years (DM group one), and patients with T2DM ≥ 10 years (DM group two) were enrolled. The ganglion cell-inner plexiform layer (GC-IPL) thickness and superficial vessel density (VD) were compared. Linear regression analyses were performed to identify factors associated with VD in T2DM patients. Results: GC-IPL thicknesses in the control, DM group one, and DM group two were 84.58 ± 0.89, 83.49 ± 0.70, and 79.04 ± 0.96 μm, respectively (p < 0.001). The VDs of the full area were 20.32 ± 0.15, 19.46 ± 0.17, and 18.46 ± 0.23 mm−1 (p < 0.001). Post-hoc analyses revealed that the VDs of the full area was significantly different in the control vs. DM group one (p = 0.001), control vs. DM group two (p < 0.001), and DM group one vs. DM group two (p = 0.001). Multivariate linear regression analyses revealed that DM duration (p = 0.037), visual acuity (p = 0.013), and GC-IPL thickness (p < 0.001) were significantly associated with the VD of T2DM patients. Conclusions: We confirmed GC-IPL thinning and decreased superficial VD in the macular areas using OCTA in T2DM patients. Patients with T2DM ≥ 10 years exhibited significantly more severe macular microcirculation impairment compared to patients with T2DM < 10 years and normal controls. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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Review

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13 pages, 337 KiB  
Review
Platelet and Thrombophilia-Related Risk Factors of Retinal Vein Occlusion
by Adrianna Marcinkowska, Slawomir Cisiecki and Marcin Rozalski
J. Clin. Med. 2021, 10(14), 3080; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10143080 - 12 Jul 2021
Cited by 10 | Viewed by 2391
Abstract
Retinal vein occlusion (RVO) is a heterogenous disorder in which the formation of a thrombus results in the retinal venous system narrowing and obstructing venous return from the retinal circulation. The pathogenesis of RVO remains uncertain, but it is believed to be multifactorial [...] Read more.
Retinal vein occlusion (RVO) is a heterogenous disorder in which the formation of a thrombus results in the retinal venous system narrowing and obstructing venous return from the retinal circulation. The pathogenesis of RVO remains uncertain, but it is believed to be multifactorial and to depend on both local and systemic factors, which can be divided into vascular, platelet, and hypercoagulable factors. The vascular factors include dyslipidaemia, high blood pressure, and diabetes mellitus. Regarding the platelet factors, platelet function, mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (PLCR) play key roles in the diagnosis of retinal vein occlusion and should be monitored. Nevertheless, the role of a hypercoagulable state in retinal vein occlusion remains unclear and requires further studies. Therefore, the following article will present the risk factors of RVO associated with coagulation disorders, as well as the acquired and genetic risk factors of thrombophilia. According to Virchow’s triad, all factors mentioned above lead to thrombus formation, which causes pathophysiological changes inside venous vessels in the fundus of the eye, which in turn results in the vessel occlusion. Therefore, a diagnosis of retinal vein occlusion should be based on both eye examination and general examination, including laboratory tests. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
14 pages, 85559 KiB  
Review
Recent Advances and Clinical Application of Color Scanning Laser Ophthalmoscope
by Hiroto Terasaki, Shozo Sonoda, Masatoshi Tomita and Taiji Sakamoto
J. Clin. Med. 2021, 10(4), 718; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10040718 - 11 Feb 2021
Cited by 9 | Viewed by 5208
Abstract
Scanning laser ophthalmoscopes (SLOs) have been available since the early 1990s, but they were not commonly used because their advantages were not enough to replace conventional color fundus photography. In recent years, color SLOs have improved significantly, and the colored SLO images are [...] Read more.
Scanning laser ophthalmoscopes (SLOs) have been available since the early 1990s, but they were not commonly used because their advantages were not enough to replace conventional color fundus photography. In recent years, color SLOs have improved significantly, and the colored SLO images are obtained by combining multiple SLO images taken by lasers of different wavelengths. A combination of these images of different lasers can create an image that is close to that of the real ocular fundus. One advantage of the advanced SLOs is that they can obtain images with a wider view of the ocular fundus while maintaining a high resolution even through non-dilated eyes. The current SLOs are superior to the conventional fundus photography in their ability to image abnormal alterations of the retina and choroid. Thus, the purpose of this review was to present the characteristics of the current color SLOs and to show how that can help in the diagnosis and the following of changes after treatments. To accomplish these goals, we will present our findings in patients with different types of retinochoroidal disorders. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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32 pages, 9053 KiB  
Review
Multimodal Imaging of Microvascular Abnormalities in Retinal Vein Occlusion
by Yoshio Hirano, Norihiro Suzuki, Taneto Tomiyasu, Ryo Kurobe, Yusuke Yasuda, Yuya Esaki, Tsutomu Yasukawa, Munenori Yoshida and Yuichiro Ogura
J. Clin. Med. 2021, 10(3), 405; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10030405 - 21 Jan 2021
Cited by 27 | Viewed by 7654
Abstract
The technologies of ocular imaging modalities such as optical coherence tomography (OCT) and OCT angiography (OCTA) have progressed remarkably. Of these in vivo imaging modalities, recently advanced OCT technology provides high-resolution images, e.g., histologic imaging, enabling anatomical analysis of each retinal layer, including [...] Read more.
The technologies of ocular imaging modalities such as optical coherence tomography (OCT) and OCT angiography (OCTA) have progressed remarkably. Of these in vivo imaging modalities, recently advanced OCT technology provides high-resolution images, e.g., histologic imaging, enabling anatomical analysis of each retinal layer, including the photoreceptor layers. Recently developed OCTA also visualizes the vascular networks three-dimensionally, which provides better understanding of the retinal deep capillary layer. In addition, ex vivo analysis using autologous aqueous or vitreous humor shows that inflammatory cytokine levels including vascular endothelial growth factor (VEGF) are elevated and correlated with the severity of macular edema (ME) in eyes with retinal vein occlusion (RVO). Furthermore, a combination of multiple modalities enables deeper understanding of the pathology. Regarding therapy, intravitreal injection of anti-VEGF drugs provides rapid resolution of ME and much better visual improvements than conventional treatments in eyes with RVO. Thus, the technologies of examination and treatment for managing eyes with RVO have progressed rapidly. In this paper, we review the multimodal imaging and therapeutic strategies for eyes with RVO with the hope that it provides better understanding of the pathology and leads to the development of new therapies. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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27 pages, 1251 KiB  
Review
Translational Research in Retinopathy of Prematurity: From Bedside to Bench and Back Again
by Mitsuru Arima, Yuya Fujii and Koh-Hei Sonoda
J. Clin. Med. 2021, 10(2), 331; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020331 - 18 Jan 2021
Cited by 7 | Viewed by 3478
Abstract
Retinopathy of prematurity (ROP), a vascular proliferative disease affecting preterm infants, is a leading cause of childhood blindness. Various studies have investigated the pathogenesis of ROP. Clinical experience indicates that oxygen levels are strongly correlated with ROP development, which led to the development [...] Read more.
Retinopathy of prematurity (ROP), a vascular proliferative disease affecting preterm infants, is a leading cause of childhood blindness. Various studies have investigated the pathogenesis of ROP. Clinical experience indicates that oxygen levels are strongly correlated with ROP development, which led to the development of oxygen-induced retinopathy (OIR) as an animal model of ROP. OIR has been used extensively to investigate the molecular mechanisms underlying ROP and to evaluate the efficacy of new drug candidates. Large clinical trials have demonstrated the efficacy of anti-vascular endothelial growth factor (VEGF) agents to treat ROP, and anti-VEGF therapy is presently becoming the first-line treatment worldwide. Anti-VEGF therapy has advantages over conventional treatments, including being minimally invasive with a low risk of refractive error. However, long-term safety concerns and the risk of late recurrence limit this treatment. There is an unmet medical need for novel ROP therapies, which need to be addressed by safe and minimally invasive therapies. The recent progress in biotechnology has contributed greatly to translational research. In this review, we outline how basic ROP research has evolved with clinical experience and the subsequent emergence of new drugs. We discuss previous and ongoing trials and present the candidate molecules expected to become novel targets. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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23 pages, 618 KiB  
Review
Omics in Myopia
by Emil Tomasz Grochowski, Karolina Pietrowska, Tomasz Kowalczyk, Zofia Mariak, Adam Kretowski, Michal Ciborowski and Diana Anna Dmuchowska
J. Clin. Med. 2020, 9(11), 3464; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9113464 - 28 Oct 2020
Cited by 16 | Viewed by 2446
Abstract
Myopia is a globally emerging issue, with multiple medical and socio-economic burdens and no well-established causal treatment thus far. A better insight into altered biochemical pathways and underlying pathogenesis might facilitate early diagnosis and treatment of myopia, ultimately leading to the development of [...] Read more.
Myopia is a globally emerging issue, with multiple medical and socio-economic burdens and no well-established causal treatment thus far. A better insight into altered biochemical pathways and underlying pathogenesis might facilitate early diagnosis and treatment of myopia, ultimately leading to the development of more effective preventive and therapeutic measures. In this review, we summarize current data about the metabolomics and proteomics of myopia in humans and present various experimental approaches and animal models, along with their strengths and weaknesses. We also discuss the potential applicability of these findings to medical practice and suggest directions for future research. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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16 pages, 1686 KiB  
Review
Cytokines and Pathogenesis of Central Retinal Vein Occlusion
by Hidetaka Noma, Kanako Yasuda and Masahiko Shimura
J. Clin. Med. 2020, 9(11), 3457; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9113457 - 27 Oct 2020
Cited by 45 | Viewed by 6278
Abstract
Central retinal vein occlusion (CRVO) causes macular edema and subsequent vision loss and is common in people with diseases such as arteriosclerosis and hypertension. Various treatments for CRVO-associated macular edema have been trialed, including laser photocoagulation, with unsatisfactory results. However, when the important [...] Read more.
Central retinal vein occlusion (CRVO) causes macular edema and subsequent vision loss and is common in people with diseases such as arteriosclerosis and hypertension. Various treatments for CRVO-associated macular edema have been trialed, including laser photocoagulation, with unsatisfactory results. However, when the important pathogenic role of vascular endothelial growth factor (VEGF) in macular edema was identified, the treatment of CRVO was revolutionized by anti-VEGF therapy. However, despite the success of intraocular injection of anti-VEGF agents in many patients with CRVO, some patients continue to suffer from refractory or recurring edema. In addition, the expression of inflammatory cytokines increases over time, causing more severe inflammation and a condition that is increasingly resistant to anti-VEGF therapy. This indicates that the pathogenesis of macular edema in CRVO is more complex than originally thought and may involve factors or cytokines associated with inflammation and ischemia other than VEGF. CRVO is also associated with leukocyte abnormalities and a gradual reduction in retinal blood flow velocity, which increase the likelihood of it developing from the nonischemic type into the more severe ischemic type; in turn, this results in excessive VEGF expression and subsequent neovascular glaucoma. Here, we review the role of different factors and cytokines involved in CRVO pathogenesis and propose a mechanism that holds promise for the development of novel therapies. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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35 pages, 3934 KiB  
Review
Characteristics of Pachychoroid Diseases and Age-Related Macular Degeneration: Multimodal Imaging and Genetic Backgrounds
by Kenji Yamashiro, Yoshikatsu Hosoda, Masahiro Miyake, Sotaro Ooto and Akitaka Tsujikawa
J. Clin. Med. 2020, 9(7), 2034; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072034 - 29 Jun 2020
Cited by 37 | Viewed by 5164
Abstract
The emergence of pachychoroid disease is changing the concept of age-related macular degeneration (AMD). The concept of pachychoroid diseases was developed through clinical observation of multimodal images of eyes with AMD and central serous chorioretinopathy; however, recent genetic studies have provided a proof [...] Read more.
The emergence of pachychoroid disease is changing the concept of age-related macular degeneration (AMD). The concept of pachychoroid diseases was developed through clinical observation of multimodal images of eyes with AMD and central serous chorioretinopathy; however, recent genetic studies have provided a proof of concept for pachychoroid spectrum disease, which should be differentiated from drusen-driven AMD. The genetic confirmation of pachychoroid concept further provides novel viewpoints to decode previously reported findings, which facilitates an understanding of the true nature of pachychoroid diseases and AMD. The purpose of this review was to elucidate the relationship between pachychoroid diseases and AMD by interpreting previous findings on pachychoroid diseases and AMD from the novel viewpoints of genetic associations. We confirmed that previous genetic studies supported the concept of pachychoroid diseases. From a genetic viewpoint, the presence of thick choroid and the presence of choroidal vascular hyperpermeability were important characteristics of pachychoroid spectrum diseases. Previous studies have also suggested the classification of polypoidal choroidal vasculopathy (PCV) into two subtypes, pachychoroid neovasculopathy and drusen-driven PCV. Genetic viewpoints will be beneficial to rearrange subtypes of drusen-driven AMD and pachychoroid spectrum diseases. Further genetic studies are needed to investigate pachyvessels, pachydrusen and the significance of polypoidal lesions in pachychoroid neovasculopathy and drusen-driven AMD/PCV. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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Other

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9 pages, 240 KiB  
Concept Paper
The Ophthalmology Surgical Competency Assessment Rubric for Intravitreal Injections (ICO-OSCAR:IVI)
by Sieh Yean Kiew, Ian Yew San Yeo, Karl C Golnik, María A Muriel-Herrero, Vanesa Fuertes-Barahona and Andrzej Grzybowski
J. Clin. Med. 2021, 10(7), 1476; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10071476 - 02 Apr 2021
Cited by 3 | Viewed by 1400
Abstract
(1) Background: Intravitreal injections (IVIs) are the most commonly performed intraocular procedure worldwide. Ensuring correct learning is essential to avoid complications. Our purpose was to develop an internationally valid tool to assess skill in performing IVIs. (2) Methods: A panel of six content [...] Read more.
(1) Background: Intravitreal injections (IVIs) are the most commonly performed intraocular procedure worldwide. Ensuring correct learning is essential to avoid complications. Our purpose was to develop an internationally valid tool to assess skill in performing IVIs. (2) Methods: A panel of six content experts designed a rubric for assessing the IVI procedure by using a modified Dreyfus scale of skill acquisition, dividing it into steps and providing objective behavioral descriptors for each level of skill in each category, following the International Council of Ophthalmology (ICO) guidance. The rubric draft was then critically reviewed by 12 international content experts, and their constructive comments were considered for the final rubric. (3) Results: The Ophthalmology Surgical Competency Assessment Rubric for IVI (ICO-OSCAR:IVI) is the proposed tool for assessing healthcare professionals training to perform IVI. (4) Conclusions: The ICO-OSCAR:IVI is the result of the consensus of an international expert panel. The methodology used for its development provides this rubric with face and content validity. It can be used globally to assess healthcare professionals training to perform IVI, as well as the impact of different teaching methods on performance. Further studies are required to establish intra- and inter-rater reliability, as well as the predictive validity of this tool. Full article
(This article belongs to the Special Issue Vitreo-Retinal Disorders: Pathogenesis, Diagnosis and Therapies)
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