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Clinical Management and Challenges in Diabetic Retinopathy
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Clinical Management and Challenges in Diabetic Retinopathy

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

Deadline for manuscript submissions: closed (25 October 2022) | Viewed by 25390

Special Issue Editor

Prof. Dr. Elisabetta Pilotto

E-Mail Website
Guest Editor
Department of Ophthalmology, University of Padova, Padova, Italy
Interests: diabetic retinopathy; age-related macular degeneration; retinal dystrophy; retinal imaging; microperimetry; OCT; OCT angiography; von Hippel-Lindau disease; geographic atrophy; retinal glial cells

Special Issue Information

Dear Colleagues,

Diabetic retinopathy (DR) is one of the main complications of diabetes mellitus and a leading cause of visual impairment. Diabetes mellitus affects a wide range of patients, from children to elderly people, and DR management requires a significant commitment for both patients and the healthcare system. Moreover, the complex systemic condition of these patients and the different resources available in different centers often make the pathway of care burdensome and not standardized. Furthermore, recent research advancements have underlined the multifactorial nature of DR, with different disease phenotypes and stages, requiring a progressively more personalized approach. Therefore, in this Special Issue, we aim to deal with the current clinical and research challenges involving DR, in different patients’ ages and with particular interest in the identification of early biomarkers of disease development and response to treatment, as well as innovations in the pathway of care, from diagnosis to treatment.

We believe that your participation in this Special Issue, aimed at the management and challenges in diabetic retinopathy, will be of great significance for the better understanding of the disease pathophysiology and features and for the improvement of its management and patients’ wellbeing.

Prof. Dr. Elisabetta Pilotto
Guest Editor

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Keywords

  • diabetic retinopathy
  • retinal glial cells
  • neurodegeneration
  • inflammation
  • diabetic macular edema
  • screening
  • pediatric diabetic retinopathy
  • biomarkers
  • pathway of care

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Published Papers (8 papers)

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Research

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12 pages, 276 KiB  
Article
Prognostic Imaging Biomarkers in Diabetic Macular Edema Eyes Treated with Intravitreal Dexamethasone Implant
by Eliana Costanzo, Daniela Giannini, Daniele De Geronimo, Serena Fragiotta, Monica Varano and Mariacristina Parravano
J. Clin. Med. 2023, 12(4), 1303; https://doi.org/10.3390/jcm12041303 - 6 Feb 2023
Cited by 2 | Viewed by 1749
Abstract
Background: The aim was to evaluate predictive value of baseline optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in diabetic macular edema (DME) treated with dexamethasone implant (DEXi). Methods: OCT and OCTA parameters were collected: central macular thickness (CMT), vitreomacular abnormalities (VMIAs), [...] Read more.
Background: The aim was to evaluate predictive value of baseline optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in diabetic macular edema (DME) treated with dexamethasone implant (DEXi). Methods: OCT and OCTA parameters were collected: central macular thickness (CMT), vitreomacular abnormalities (VMIAs), intraretinal and subretinal fluid (mixed DME pattern), hyper-reflective foci (HRF), microaneurysms (MAs) reflectivity, ellipsoid zone disruption, suspended scattering particles in motion (SSPiM), perfusion density (PD), vessel length density, and foveal avascular zone. Responders’ (RES) and non-responders’ (n-RES) eyes were classified considering morphological (CMT reduction ≥ 10%) and functional (BCVA change ≥ 5 ETDRS letters) changes after DEXi. Binary logistic regression OCT, OCTA, and OCT/OCTA-based models were developed. Results: Thirty-four DME eyes were enrolled (18 treatment-naïve). OCT-based model combining DME mixed pattern + MAs + HRF and OCTA-based model combining SSPiM and PD showed the best performance to correctly classify the morphological RES eyes. In the treatment-naïve eyes, VMIAs were included with a perfect fit for n-RES eyes. Conclusion: The presence of DME mixed pattern, a high number of parafoveal HRF, hyper-reflective MAs, SSPiM in the outer nuclear layers, and high PD represent baseline predictive biomarkers for DEXi treatment responsiveness. The application of these models to treatment-naïve patients allowed a good identification of n-RES eyes. Full article
(This article belongs to the Special Issue Clinical Management and Challenges in Diabetic Retinopathy)
12 pages, 1486 KiB  
Article
Influence of Intravitreal Therapy on Choroidal Thickness in Patients with Diabetic Macular Edema
by Patricia Udaondo Mirete, Carmen Muñoz-Morata, César Albarrán-Diego and Enrique España-Gregori
J. Clin. Med. 2023, 12(1), 348; https://doi.org/10.3390/jcm12010348 - 1 Jan 2023
Viewed by 2496
Abstract
Objective: This study aimed to analyze the variation in subfoveal choroidal thickness (SFCT) and its relationship with the variation in central macular thickness (CME) in response to intravitreal therapy with an antiangiogenic (anti-VEGF) drug or corticosteroid in type 2 diabetic patients with diabetic [...] Read more.
Objective: This study aimed to analyze the variation in subfoveal choroidal thickness (SFCT) and its relationship with the variation in central macular thickness (CME) in response to intravitreal therapy with an antiangiogenic (anti-VEGF) drug or corticosteroid in type 2 diabetic patients with diabetic macular edema (DME). Material and methods: This retrospective study included 70 eyes of 35 patients: 26 eyes received 4−5 intravitreal injections of aflibercept, 26 eyes were treated with a single intravitreal implant injection of dexamethasone, and 18 eyes without DME did not receive intravitreal therapy. SPECTRALIS® optical coherence tomography (OCT) (Heidelberg Engineering, Heidelberg, Germany) was used to measure the SFCT and CME before and at the end of the follow-up period. Results: The mean reductions in CME were 18.8 +/− 14.7% (aflibercept) and 29.7 +/− 16.9% (dexamethasone). The mean reductions in SFCT were 13.8 +/− 13.1% (aflibercept) and 19.5 +/− 9.6% (dexamethasone). The lowering effects of both parameters were significantly greater in the group treated with the dexamethasone implant (p = 0.022 and p = 0.046 for CMT and SFCT, respectively). Both therapies significantly decreased both CME and SFCT, independent of factors such as age, sex, previous intravitreal therapy, antidiabetic treatment, and the time of diabetes progression. There were no changes in the mean values of CME and SFCT in the untreated eyes. Conclusions: SFCT significantly decreased in response to intravitreal therapy with anti-VEGF or corticosteroids, irrespective of age, sex, previous intravitreal therapy, antidiabetic treatment, and the time of diabetes progression. There was a correlation between the changes in CME and SFCT after intravitreal therapy with aflibercept or dexamethasone implantation. SFCT was not a good predictor of the CME response but could be used to monitor the response to treatment. Local intravitreal therapy only affected the treated eye. Full article
(This article belongs to the Special Issue Clinical Management and Challenges in Diabetic Retinopathy)
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11 pages, 787 KiB  
Article
Intravitreal Dexamethasone Implant (IDI) Alone and Combined with Navigated 577 nm Subthreshold Micropulse Laser (SML) for Diabetic Macular Oedema
by Lisa Toto, Rossella D’Aloisio, Alberto Quarta, Daniele Libertini, Giada D’Onofrio, Chiara De Nicola, Anna Romano and Rodolfo Mastropasqua
J. Clin. Med. 2022, 11(17), 5200; https://doi.org/10.3390/jcm11175200 - 2 Sep 2022
Cited by 3 | Viewed by 1394
Abstract
Background: The anatomical and functional changes after intravitreal dexamethasone implant (IDI) alone and combined with navigated subthreshold micropulse laser (NSML) in diabetic macular oedema (DMO) were compared. Methods: Patients with a clinically confirmed diagnosis of non-proliferative diabetic retinopathy (NPDR) and DMO were enrolled [...] Read more.
Background: The anatomical and functional changes after intravitreal dexamethasone implant (IDI) alone and combined with navigated subthreshold micropulse laser (NSML) in diabetic macular oedema (DMO) were compared. Methods: Patients with a clinically confirmed diagnosis of non-proliferative diabetic retinopathy (NPDR) and DMO were enrolled in this prospective study and were randomly assigned to two different treatment groups: thirty patients were treated with IDI (IDI group), and the other 30 patients received IDI combined with NSML treatment (combined IDI/NSML group). All patients during a 6-month follow-up underwent best corrected visual acuity (BCVA) evaluation and spectral domain optical coherence tomography (SD OCT). The main outcome measures were: BCVA, central macular thickness (CMT); (3) choroidal vascularity index (CVI), subfoveal choroidal thickness (SCHT); and time to retreatment between IDI at baseline and the second implant in both groups. Results: BCVA, CMT, and SCHT significantly decreased starting from the 1-month follow-up and CVI from 3 months in both groups. The between-group differences were significantly different from 1-month follow-up for BCVA, from 5-month follow-up for CMT and SCHT, and from 4-month follow-up for CVI. The Needed to Treat analysis indicated that six patients would have to be treated with SML after IDI in order for just one person to receive a benefit. Conclusions: the combined treatment showed good anatomical and functional outcomes for the treatment of DMO. In addition, IDI/SML seems to reduce injection frequency over time, improving patients’ quality of life and reducing the socio-economic burden. Full article
(This article belongs to the Special Issue Clinical Management and Challenges in Diabetic Retinopathy)
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14 pages, 276 KiB  
Article
Clinical and Molecular Characteristics of Diabetic Retinopathy and Its Severity Complications among Diabetic Patients: A Multicenter Cross-Sectional Study
by Hamzeh Al Zabadi, Ibrahim Taha and Rami Zagha
J. Clin. Med. 2022, 11(14), 3945; https://doi.org/10.3390/jcm11143945 - 7 Jul 2022
Cited by 5 | Viewed by 2075
Abstract
Background: Diabetic retinopathy (DR) is a complication associated with uncontrolled DM. It is a leading preventable cause of visual impairment in the world and a cause of blindness in those under 75 years old in developing countries. We aimed to explore the prevalence [...] Read more.
Background: Diabetic retinopathy (DR) is a complication associated with uncontrolled DM. It is a leading preventable cause of visual impairment in the world and a cause of blindness in those under 75 years old in developing countries. We aimed to explore the prevalence and associated risk factors of DR among diabetic patients in the West Bank. Materials and Methods:A quantitative multicenter cross-sectional study was conducted in all West Bank cities. Nearly, 385 patients underwent a comprehensive eye examination in addition to blood and urine tests. A previously validated questionnaire for ocular examination classification was used together with a socio-demographic and past medical history information sheet. Results: The prevalence of all DR in the West Bank was 41.8%. The prevalence of non-proliferative diabetic retinopathy (NPDR) was 50.3% (38.5% for mild NPDR, 10.6% for moderate NPDR and 1.2% for severe NPDR). The prevalence of proliferative diabetic retinopathy (PDR) was 9.9% and 39.7% for diabetic macular edema (DME) (17.4% for mild, 15.5% for moderate and 6.8% for severe DME). The prevalence of vision-threatening PDR and DME was 49.7% for both. In a univariate analysis, DR was significantly associated with body mass index; BMI (p = 0.035), DM duration (p = 0.002), Low-density lipoprotein (LDL) (p = 0.034), glutamic-oxaloacetic transaminase (GOT) level (p = 0.016) andblood urea (BU) (p = 0.044). A multivariate analysis showed a strong significant association between DR andpatients who had DM for 10-19years (adjusted odds ratio; AOR (95%CI); 1.843 (1.05–3.22)), abnormal levels of LDL (AOR (95%CI); 0.50 (0.30–0.83)), abnormal levels of GOT (AOR (95%CI); 0.49 (0.27–0.89)), and overweight (AOR (95%CI); 0.39 (0.19–0.80)). Conclusions: We found that the prevalence of DR in Palestine was higher than the global prevalence. Referral coordination between ophthalmologists and internal physicians is necessary to better follow up with DR patients. An interventional educational program by clinicians and public health professionals is recommended. Full article
(This article belongs to the Special Issue Clinical Management and Challenges in Diabetic Retinopathy)
11 pages, 458 KiB  
Article
Handheld Fundus Camera for Diabetic Retinopathy Screening: A Comparison Study with Table-Top Fundus Camera in Real-Life Setting
by Edoardo Midena, Luca Zennaro, Cristian Lapo, Tommaso Torresin, Giulia Midena, Elisabetta Pilotto and Luisa Frizziero
J. Clin. Med. 2022, 11(9), 2352; https://doi.org/10.3390/jcm11092352 - 22 Apr 2022
Cited by 11 | Viewed by 3768
Abstract
The aim of the study was to validate the performance of the Optomed Aurora® handheld fundus camera in diabetic retinopathy (DR) screening. Patients who were affected by diabetes mellitus and referred to the local DR screening service underwent fundus photography using a [...] Read more.
The aim of the study was to validate the performance of the Optomed Aurora® handheld fundus camera in diabetic retinopathy (DR) screening. Patients who were affected by diabetes mellitus and referred to the local DR screening service underwent fundus photography using a standard table-top fundus camera and the Optomed Aurora® handheld fundus camera. All photos were taken by a single, previously unexperienced operator. Among 423 enrolled eyes, we found a prevalence of 3.55% and 3.31% referable cases with the Aurora® and with the standard table-top fundus camera, respectively. The Aurora® obtained a sensitivity of 96.9% and a specificity of 94.8% in recognizing the presence of any degree of DR, a sensitivity of 100% and a specificity of 99.8% for any degree of diabetic maculopathy (DM) and a sensitivity of 100% and specificity of 99.8% for referable cases. The overall concordance coefficient k (95% CI) was 0.889 (0.828–0.949) and 0.831 (0.658–1.004) with linear weighting for DR and DM, respectively. The presence of hypertensive retinopathy (HR) was recognized by the Aurora® with a sensitivity and specificity of 100%. The Optomed Aurora® handheld fundus camera proved to be effective in recognizing referable cases in a real-life DR screening setting. It showed comparable results to a standard table-top fundus camera in DR, DM and HR detection and grading. The Aurora® can be integrated into telemedicine solutions and artificial intelligence services which, in addition to its portability and ease of use, make it particularly suitable for DR screening. Full article
(This article belongs to the Special Issue Clinical Management and Challenges in Diabetic Retinopathy)
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11 pages, 1895 KiB  
Article
Early Microvascular and Oscillatory Potentials Changes in Human Diabetic Retina: Amacrine Cells and the Intraretinal Neurovascular Crosstalk
by Edoardo Midena, Tommaso Torresin, Evelyn Longhin, Giulia Midena, Elisabetta Pilotto and Luisa Frizziero
J. Clin. Med. 2021, 10(18), 4035; https://doi.org/10.3390/jcm10184035 - 7 Sep 2021
Cited by 17 | Viewed by 1909
Abstract
To analyze the early microvascular retinal changes and oscillatory potentials alterations secondary to diabetic retinal damage, 44 eyes of 22 diabetic patients without and with mild diabetic retinopathy (DR) and 18 eyes of 9 healthy controls were examined. All subjects underwent spectral domain [...] Read more.
To analyze the early microvascular retinal changes and oscillatory potentials alterations secondary to diabetic retinal damage, 44 eyes of 22 diabetic patients without and with mild diabetic retinopathy (DR) and 18 eyes of 9 healthy controls were examined. All subjects underwent spectral domain optical coherence tomography (SD-OCT), OCT angiography (OCTA), and electroretinography of oscillatory potentials (OPs). At OCTA, vessel area density (VAD), vessel length fraction (VLF), and fractal dimension (FD) were significantly reduced in the superficial vascular plexus (SVP), VLF and FD in the intermediate capillary plexus (ICP), and FD in the deep capillary plexus (DCP) in the diabetic group compared to the control group. The amplitude (A) of OP2, OP3, OP4 and the sum of OPs were significantly reduced in the diabetic group versus the controls, and the last two parameters were reduced also in patients without DR versus the controls. Moreover, in the diabetic group, a significant direct correlation was found between the A of OP1, OP2, OP3 and sOP and the VLF and FD in the SVP, while a statistically significant inverse correlation was found between the A of OP3 and OP4 and the VDI in the ICP and DCP. The reduced oscillatory potentials suggest a precocious involvement of amacrine cells in diabetic eyes, independently of DR presence, and their correlation with vascular parameters underlines the relevance of the crosstalk between these cells and vascular components in the pathophysiology of this chronic disease. Full article
(This article belongs to the Special Issue Clinical Management and Challenges in Diabetic Retinopathy)
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Review

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21 pages, 3121 KiB  
Review
Retinal Ischaemia in Diabetic Retinopathy: Understanding and Overcoming a Therapeutic Challenge
by Ajay A. Mohite, Jennifer A. Perais, Philip McCullough and Noemi Lois
J. Clin. Med. 2023, 12(6), 2406; https://doi.org/10.3390/jcm12062406 - 21 Mar 2023
Cited by 7 | Viewed by 2553
Abstract
Background: Retinal ischaemia is present to a greater or lesser extent in all eyes with diabetic retinopathy (DR). Nonetheless, our understanding of its pathogenic mechanisms, risk factors, as well as other characteristics of retinal ischaemia in DR is very limited. To date, there [...] Read more.
Background: Retinal ischaemia is present to a greater or lesser extent in all eyes with diabetic retinopathy (DR). Nonetheless, our understanding of its pathogenic mechanisms, risk factors, as well as other characteristics of retinal ischaemia in DR is very limited. To date, there is no treatment to revascularise ischaemic retina. Methods: Review of the literature highlighting the current knowledge on the topic of retinal ischaemia in DR, important observations made, and underlying gaps for which research is needed. Results: A very scarce number of clinical studies, mostly cross-sectional, have evaluated specifically retinal ischaemia in DR. Interindividual variability on its natural course and consequences, including the development of its major complications, namely diabetic macular ischaemia and proliferative diabetic retinopathy, have not been investigated. The in situ, surrounding, and distance effect of retinal ischaemia on retinal function and structure and its change over time remains also to be elucidated. Treatments to prevent the development of retinal ischaemia and, importantly, to achieve retinal reperfusion once capillary drop out has ensued, are very much needed and remain to be developed. Conclusion: Research into retinal ischaemia in diabetes should be a priority to save sight. Full article
(This article belongs to the Special Issue Clinical Management and Challenges in Diabetic Retinopathy)
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19 pages, 12967 KiB  
Review
Updates on the Current Treatments for Diabetic Retinopathy and Possibility of Future Oral Therapy
by Yohei Tomita, Deokho Lee, Kazuo Tsubota, Kazuno Negishi and Toshihide Kurihara
J. Clin. Med. 2021, 10(20), 4666; https://doi.org/10.3390/jcm10204666 - 12 Oct 2021
Cited by 48 | Viewed by 7950
Abstract
Diabetic retinopathy (DR) is a complication of diabetes and one of the leading causes of vision loss worldwide. Despite extensive efforts to reduce visual impairment, the prevalence of DR is still increasing. The initial pathophysiology of DR includes damage to vascular endothelial cells [...] Read more.
Diabetic retinopathy (DR) is a complication of diabetes and one of the leading causes of vision loss worldwide. Despite extensive efforts to reduce visual impairment, the prevalence of DR is still increasing. The initial pathophysiology of DR includes damage to vascular endothelial cells and loss of pericytes. Ensuing hypoxic responses trigger the expression of vascular endothelial growth factor (VEGF) and other pro-angiogenic factors. At present, the most effective treatment for DR and diabetic macular edema (DME) is the control of blood glucose levels. More advanced cases require laser, anti-VEGF therapy, steroid, and vitrectomy. Pan-retinal photocoagulation for non-proliferative diabetic retinopathy (NPDR) is well established and has demonstrated promising outcomes for preventing the progressive stage of DR. Furthermore, the efficacy of laser therapies such as grid and subthreshold diode laser micropulse photocoagulation (SDM) for DME has been reported. Vitrectomy has been performed for vitreous hemorrhage and tractional retinal detachment for patients with PDR. In addition, anti-VEGF treatment has been widely used for DME, and recently its potential to prevent the progression of PDR has been remarked. Even with these treatments, many patients with DR lose their vision and suffer from potential side effects. Thus, we need alternative treatments to address these limitations. In recent years, the relationship between DR, lipid metabolism, and inflammation has been featured. Research in diabetic animal models points to peroxisome proliferator-activated receptor alpha (PPARα) activation in cellular metabolism and inflammation by oral fenofibrate and/or pemafibrate as a promising target for DR. In this paper, we review the status of existing therapies, summarize PPARα activation therapies for DR, and discuss their potentials as promising DR treatments. Full article
(This article belongs to the Special Issue Clinical Management and Challenges in Diabetic Retinopathy)
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