Multidisciplinary Approaches for Managing Ophthalmic Complications of Diabetes

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Endocrinology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 12370

Special Issue Editor


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Guest Editor
Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
Interests: diabetes mellitus; retinal disease; vitrectomy

Special Issue Information

Dear Colleagues,

Diabetic retinopathy (DR) is a leading cause of blindness, and it is present in over one-half of patients with diabetes mellitus of >20 years duration. Various surgical or medical therapies have been used and panretinal photocoagulation (PRP) is a standard treatment with a long-term efficacy. Vitrectomy is also a standard treatment for advanced DR, e.g., proliferative diabetic retinopathy (PDR), and it also leads to better visual outcomes. Diabetic macular edema (DME) is the most common cause of the vision reduction in eyes with DR. Anti-vascular endothelial growth factor (VEGF) treatment have become the first-line therapy and nowadays, advance of technology improve the safety and visual outcome. PRP and vitrectomy archive as less invasive treatment. Anti-VEGF agents have changed DME prognosis and is also used for PDR to prevent its progression. In addition, new agents which contribute with better visual outcome will be commercialised soon e.g. faricimab and brolucizumab.

The aim of this special issue is to discuss the evidence for the the newly established treatments for DR and DME. We appreciate submission about the new aspect of the approaches for managing ophthalmic complications of DR and DME. 

Dr. Masahiko Sugimoto
Guest Editor

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Keywords

  • anti-vascular endothelial growth factor treatment
  • diabetes mellitus
  • diabetic macular edema
  • diabetic retinopathy
  • panretinal photocoagulation
  • vitrectomy

Published Papers (7 papers)

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9 pages, 1919 KiB  
Article
Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice
by Atsushi Ichio, Masahiko Sugimoto, Yuhki Koike, Yuji Toiyama and Mineo Kondo
Medicina 2023, 59(4), 809; https://doi.org/10.3390/medicina59040809 - 21 Apr 2023
Viewed by 1407
Abstract
Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct [...] Read more.
Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 μg/μL of aflibercept (Af), or 25 μg/μL of bevacizumab (Be), or 10 μg/μL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety. Full article
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8 pages, 3898 KiB  
Article
Short-Term Outcomes of Intravitreal Faricimab Injection for Diabetic Macular Edema
by Sentaro Kusuhara, Maya Kishimoto-Kishi, Wataru Matsumiya, Akiko Miki, Hisanori Imai and Makoto Nakamura
Medicina 2023, 59(4), 665; https://doi.org/10.3390/medicina59040665 - 27 Mar 2023
Cited by 3 | Viewed by 2467
Abstract
Background and Objectives: Faricimab is a novel bispecific antibody with Fab regions inhibiting both vascular endothelial growth factor-A and angiopoietin-2. Therefore, this study aimed to obtain short-term outcomes of intravitreal injection of faricimab (IVF) for the treatment of diabetic macular edema (DME) [...] Read more.
Background and Objectives: Faricimab is a novel bispecific antibody with Fab regions inhibiting both vascular endothelial growth factor-A and angiopoietin-2. Therefore, this study aimed to obtain short-term outcomes of intravitreal injection of faricimab (IVF) for the treatment of diabetic macular edema (DME) in daily clinical practice. Materials and Methods: A retrospective review was carried out on consecutive patients with DME who had been treated with IVF and were followed up for at least 1 month. Outcome measures included changes in logMAR best-corrected visual acuity (logMAR BCVA), central retinal thickness (CRT), number of IVF administrations, and safety. Clinical outcomes were also compared between the treatment-naïve and switch groups. Results: A total of 21 consecutive DME eyes from 19 patients were identified. The mean number of IVFs was 1.6 ± 0.8 during the mean follow-up time of 5.5 months. The overall mean logMAR BCVA following IVF was 0.236, 0.204, 0.190, and 0.224 at baseline, 1, 3, and 6 months, respectively, without a significant change from baseline to 1 month (p = 0.176) or for 6 months (p = 0.923). The overall mean CRT (μm) following IVF was 400.6, 346.6, 342.1, and 327.5 at baseline, 1, 3, and 6 months, respectively. CRT significantly decreased from baseline to 1 month (p = 0.001) but did not reach a significant level over 6 months following IVF (p = 0.070). No significant difference in BCVA or CRT was observed between the treatment-naïve and switch groups. No serious safety concerns were noted. Conclusions: IVF for the treatment of DME may preserve visual acuity and improve macular thickness without serious safety concerns in the short term in a real-world clinical setting. Full article
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9 pages, 2297 KiB  
Article
Morphological Changes in the Foveal Avascular Zone after Panretinal Photocoagulation for Diabetic Retinopathy Using OCTA: A Study Focusing on Macular Ischemia
by Ken Hoshiyama, Takao Hirano, Kazutaka Hirabayashi, Masumi Wakabayashi, Motoharu Tokimitsu and Toshinori Murata
Medicina 2022, 58(12), 1797; https://doi.org/10.3390/medicina58121797 - 06 Dec 2022
Cited by 1 | Viewed by 1652
Abstract
Background and objectives: This study aimed to analyze the morphological changes in the foveal avascular zone (FAZ) after panretinal photocoagulation (PRP) in patients with diabetic retinopathy, with a particular focus on the presence or absence of comorbid diabetic macular ischemia (DMI), using [...] Read more.
Background and objectives: This study aimed to analyze the morphological changes in the foveal avascular zone (FAZ) after panretinal photocoagulation (PRP) in patients with diabetic retinopathy, with a particular focus on the presence or absence of comorbid diabetic macular ischemia (DMI), using optical coherence tomography angiography (OCTA). Materials and Methods: Treatment-naïve 25 eyes of 16 patients who received PRP were examined in this retrospective case series. FAZ area, perimeter, and circularity were calculated on a 3 × 3-mm en-face OCTA image before PRP (baseline) and 1 and 3 months after PRP. The patients were divided into two groups according to coexisting DMI, and each group was statistically analyzed. Results: In patients with DMI (9 eyes), FAZ area significantly decreased from the baseline to 3 months after PRP (0.86 ± 0.56 to 0.61 ± 0.31 mm2, p = 0.018), whereas FAZ perimeter and circularity remained unchanged following treatment (p = 0.569 and 0.971, respectively). In patients without DMI (16 eyes), FAZ parameters did not show statistically significant changes across the 3-month follow-up period. Conclusion: PRP significantly reduces FAZ area in patients with DMI. Full article
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7 pages, 1810 KiB  
Article
Automatic Diagnosis of Diabetic Retinopathy Stage Focusing Exclusively on Retinal Hemorrhage
by Yoshihiro Tokuda, Hitoshi Tabuchi, Toshihiko Nagasawa, Mao Tanabe, Hodaka Deguchi, Yuki Yoshizumi, Zaigen Ohara and Hiroshi Takahashi
Medicina 2022, 58(11), 1681; https://doi.org/10.3390/medicina58111681 - 20 Nov 2022
Cited by 2 | Viewed by 1786
Abstract
Background and Objectives: The present study evaluated the detection of diabetic retinopathy (DR) using an automated fundus camera focusing exclusively on retinal hemorrhage (RH) using a deep convolutional neural network, which is a machine-learning technology. Materials and Methods: This investigation was [...] Read more.
Background and Objectives: The present study evaluated the detection of diabetic retinopathy (DR) using an automated fundus camera focusing exclusively on retinal hemorrhage (RH) using a deep convolutional neural network, which is a machine-learning technology. Materials and Methods: This investigation was conducted via a prospective and observational study. The study included 89 fundus ophthalmoscopy images. Seventy images passed an image quality review and were graded as showing no apparent DR (n = 51), mild nonproliferative DR (NPDR; n = 16), moderate NPDR (n = 1), severe NPDR (n = 1), and proliferative DR (n = 1) by three retinal experts according to the International Clinical Diabetic Retinopathy Severity scale. The RH numbers and areas were automatically detected and the results of two tests—the detection of mild-or-worse NPDR and the detection of moderate-or-worse NPDR—were examined. Results: The detection of mild-or-worse DR showed a sensitivity of 0.812 (95% confidence interval: 0.680–0.945), specificity of 0.888, and area under the curve (AUC) of 0.884, whereas the detection of moderate-or-worse DR showed a sensitivity of 1.0, specificity of 1.0, and AUC of 1.0. Conclusions: Automated diagnosis using artificial intelligence focusing exclusively on RH could be used to diagnose DR requiring ophthalmologist intervention. Full article
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7 pages, 983 KiB  
Article
Progress of Diabetic Macular Edema after Loading Injection of Anti-Vascular Endothelial Growth Factor Agents in Real-World Cases
by Hiroko Enomoto, Masahiko Sugimoto, Shin Asami and Mineo Kondo
Medicina 2022, 58(10), 1318; https://doi.org/10.3390/medicina58101318 - 21 Sep 2022
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Abstract
Background and Objectives: To evaluate the recurrence of diabetic macular edema (DME) after loading an injection of anti-VEGF agents by a pro re nata (PRN) protocol using central retinal thickness (CRT) as a re-injection criterion. Materials and Methods: This is a [...] Read more.
Background and Objectives: To evaluate the recurrence of diabetic macular edema (DME) after loading an injection of anti-VEGF agents by a pro re nata (PRN) protocol using central retinal thickness (CRT) as a re-injection criterion. Materials and Methods: This is a retrospective, observational single-center study. DME patients with a central retinal thickness (CRT) over 350 μm received a PRN injection of anti-VEGF agents following one to three consecutive monthly loading injections (bevacizumab, ranibizumab, and aflibercept) for 6 months from January 2012 to June 2019. Results: We enrolled a total of 72 eyes for loading injections and the mean CRT improved from 434.04 ± 139.4 μm (before treatment) to 362.9 ± 125.0 μm after the loading injection. One week after injection, 36 eyes (50%) obtained a CRT of ≤350 μm. Fourteen eyes (19.4%) remained with a CRT of ≤350 μm for 6 months without additional injections. A total of 22 eyes (30.6%) had a CRT of >350 μm at 6 months. Fifteen eyes did not receive additional injections because of visual improvement. Conclusions: About 20% of DME patients can be maintained at a CRT of ≤350 μm for 6 months with only a loading injection. However, there is a tendency to delay additional injections for patients with recurrences using PRN protocol. Full article
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10 pages, 4097 KiB  
Article
Regional Variety of Reduction in Retinal Thickness of Diabetic Macular Edema after Anti-VEGF Treatment
by Yutaka Yamada, Yoshihiro Takamura, Takehiro Matsumura, Makoto Gozawa, Masakazu Morioka and Masaru Inatani
Medicina 2022, 58(7), 933; https://doi.org/10.3390/medicina58070933 - 14 Jul 2022
Cited by 5 | Viewed by 1491
Abstract
Background and Objectives: The presence of refractory cases resistant to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) is a problem in clinical practice. This study aimed to explore the less responsive area of optical coherence tomography (OCT) 3D [...] Read more.
Background and Objectives: The presence of refractory cases resistant to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) is a problem in clinical practice. This study aimed to explore the less responsive area of optical coherence tomography (OCT) 3D map the characteristics of naïve DME cases after their first anti-VEGF. Materials and Methods: In 46 patients with DME who received an intravitreal injection of anti-VEGF agents, retinal thickness in 100 sections of the macular area was measured by 3D-mapping mode using OCT before and 1 month after injection. The density of the microaneurysm (MA) was calculated using merged images of the OCT map and fluorescein angiography. Results: One month after injection, the central retinal thickness significantly decreased (p < 0.0001). In severe edema (retinal thickness more than 500 µm), the area percentages with a reduction rate of the retinal thickness greater than 30% and less than 5% were 6.4 ± 6.6% and 10.1 ± 4.6%, respectively. The reduction rate of the retinal thickness varied from section to section. The mutual distance between the areas of maximum thickness before and after the injection averaged 1.22 ± 0.62 mm apart. The reduction rate of retinal thickness in the thickest region before injection was significantly higher (p = 0.02), and that in the thickest region after injection was lower (p = 0.001) than in the other regions. MA density in the residual edema was significantly higher than in the edema-absorbed area (p = 0.03). Conclusion: DME has areas that show low response to the reduction in retinal thickness with anti-VEGF therapy. A high density of MA may be associated with this pathogenesis. Full article
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6 pages, 1273 KiB  
Case Report
Simultaneous Occurrence of Buckle Infection and Migration: A Case Report
by Yasuyoshi Motose, Hiroto Terasaki, Misaki Ichiki, Mahono Okawa, Naohisa Mihara, Narimasa Yoshinaga and Taiji Sakamoto
Medicina 2023, 59(3), 449; https://doi.org/10.3390/medicina59030449 - 23 Feb 2023
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Abstract
Background: When scleral buckling is performed using a #240 encircling band anterior to the equator for rhegmatogenous retinal detachment, buckle migration may occur anteriorly, eroding the rectus muscle. There are few cases of buckle migration occurring simultaneously with buckle infection. Notably, most [...] Read more.
Background: When scleral buckling is performed using a #240 encircling band anterior to the equator for rhegmatogenous retinal detachment, buckle migration may occur anteriorly, eroding the rectus muscle. There are few cases of buckle migration occurring simultaneously with buckle infection. Notably, most previous reports included inadequate data on the pathophysiology of buckle migration and did not include the Hess test and perioperative images. Case presentation: A 36-year-old man with a history of atopic dermatitis underwent scleral buckling for rhegmatogenous retinal detachment of the left eye with #287 and #240 encircling bands at Kagoshima University Hospital. Four years later, he developed discharge, redness, and diplopia of the left eye. He was then referred to our hospital because buckle infection was suspected. The buckle was partially visible on the lower nasal side. Optical coherence tomography of the anterior chamber revealed the buckle to be on the nasal side and overlying the medial rectus muscle. Buckle migration and infection in the left eye was diagnosed, and early buckle removal was recommended. Two weeks later, on the day before surgery, conjunctival melting progressed in the nasal and inferior areas, and the buckle was exposed to a greater extent. In the surgical video at the initial surgery, the silicone band was confirmed to pass under the four rectus muscles, specifically the inferior and medial rectus muscles. At the beginning of the second surgery, we confirmed that the buckles were over the inferior and medial rectus muscles. As far as could be observed after buckle removal, the inferior and medial rectus muscles were not present at the normal location. Postoperatively, ocular pain and discharge quickly resolved. The subjective symptoms of diplopia also improved, and the postoperative Hess chart showed an improved ocular movement in the upward and lateral directions. Conclusions: Buckle migration is a rare postoperative complication of scleral buckling; however, patients at risk of buckle migration, such as those with encircling scleral buckle anterior to the eyeball, should be monitored with caution. If a buckle infection develops, buckle migration may occur within a short period, and early buckle removal should be considered. Full article
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