Developments in Non-Invasive Imaging to Guide Diagnosis and Treatment of Proliferative Diabetic Retinopathy: A Systematic Review

Diagnosis and management of proliferative diabetic retinopathy are reliant upon retinal imaging. A systematic literature review of non-invasive imaging to guide diagnosis and treatment of proliferative diabetic retinopathy was performed. There is a trend of moving away from invasive (e.g., fundus fluorescein angiography) to non-invasive (e.g., wide-field optical coherence tomography (OCT), OCT angiography and colour fundus photography) imaging modalities to allow for more objective assessments that can be readily repeated in a time-efficient manner without compromising patient safety. Such quantitative assessments generating large amounts of data could benefit from artificial intelligence approaches to aid clinical decision making. These non-invasive imaging modalities continue to improve both in terms of the quality of image acquisition and progress in image interpretation. It is important that newer non-invasive imaging modalities are appropriately validated in large-scale prospective observational studies or randomised clinical trials.

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Imaging in diabetic retinopathy

Diabetic Retinopathy: Screening to Treatment (Oxford Diabetes Library) ◽

10.1093/med/9780198834458.003.0018 ◽

2020 ◽

pp. 161-170

Author(s):

Sarita Jacob ◽

Ramesh R. Sivaraj

Keyword(s):

Optical Coherence Tomography ◽

Diabetic Retinopathy ◽

Prognostic Value ◽

Diabetic Macular Oedema ◽

Imaging Modalities ◽

Wide Field ◽

Optical Coherence ◽

Diabetic Maculopathy ◽

Fundus Fluorescein Angiography ◽

Diagnostic And Prognostic Value

Imaging in diabetic retinopathy (DR) has developed over the years and the advantages are multifold. Various imaging modalities are currently available, which is of great diagnostic and prognostic value in the management of DR. Optical coherence tomography (OCT) has revolutionized the management of diabetic maculopathy. OCT has now become indispensable for initiating and assessing diabetic macular oedema (DMO) while on treatment with intravitreal injections. Recent introduction of optical coherence tomography angiography (OCTA) has significantly reduced the need for fundus fluorescein angiography (FFA) for macular ischaemia and proliferative retinopathy. Ultra-wide field (UWF) imaging modalities for colour fundus and UWF FFA are very useful to document and assess overall retinal state highlighting the periphery. Bscan ultrasonography of the fundus is an useful tool to assess retinal status in proliferative DR with vitreous haemorrhage.

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Role of Optical Coherence Tomography Angiography to differentiate Intraretinal microvascular abnormalities and retinal neovascularization in Diabetic Retinopathy

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.38.1.3891 ◽

2021 ◽

Vol 38 (1) ◽

Author(s):

Abdul Sami Memon ◽

Nasir Ahmed Memon ◽

Pir Salim Mahar

Keyword(s):

Optical Coherence Tomography ◽

Diabetic Retinopathy ◽

Clinical Diagnosis ◽

Proliferative Diabetic Retinopathy ◽

Optical Coherence Tomography Angiography ◽

Retinal Neovascularization ◽

Wide Field ◽

Optical Coherence ◽

Fundus Fluorescein Angiography

Objective: To assess proliferative diabetic retinopathy (PDR) and to describe the difference in angiographic representation of new vessels (NVs) and Intra retinal microvascular abnormalities (IRMA) on optical coherence tomography angiography (OCTA). Methods: A cross-sectional observational study was performed at ISRA Postgraduate Institute of Ophthalmology, Karachi, from March 2018 to September 2018. Forty-two eyes of 21 patients with history of diabetes mellitus (DM) were examined. Twenty-eight eyes with a clinical diagnosis of severe non proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) according to early treatment diabetic retinopathy study (ETDRS) were included and evaluated using Swept source optical coherence tomography angiography (SS-OCTA). Then face wide ﬁeld SS-OCTA images and co registered structural optical coherence tomography (OCT) with ﬂow overlay were used to distinguish the features of IRMA and retinal NVs. Results: Forty-two eyes (21 patients) were examined clinically. Fourteen eyes had moderate NPDR, 15 had severe NPDR and 13 eyes had changes consistent with PDR. After clinical diagnosis, we included 28 eyes in our study based on inclusion criteria. These 28 eyes went through SS-OCTA evaluation and we observed 15 cases with PDR and 13 with severe NPDR changes. The OCTA and clinical diagnosis were similar except in 2 eyes, which is critical but not statically significant showing the importance of this noninvasive technology. Conclusions: Widefield OCTA can work as an alternative to fundus fluorescein angiography (FFA) in the diagnosis of diabetic retinopathy (DR). As it is a non-invasive and depth encoded technique so can be used frequently to monitor the retinal changes and their progression. doi: https://doi.org/10.12669/pjms.38.1.3891 How to cite this:Memon AS, Memon NA, Mahar PS. Role of Optical Coherence Tomography Angiography to differentiate Intraretinal microvascular abnormalities and retinal neovascularization in Diabetic Retinopathy. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.3891 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Changes in retinal venular oxygen saturation predict activity of proliferative diabetic retinopathy 3 months after panretinal photocoagulation

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-310576 ◽

2017 ◽

Vol 102 (3) ◽

pp. 383-387 ◽

Cited By ~ 7

Author(s):

Thomas Lee Torp ◽

Ryo Kawasaki ◽

Tien Yin Wong ◽

Tunde Peto ◽

Jakob Grauslund

Keyword(s):

Diabetic Retinopathy ◽

Oxygen Saturation ◽

Proliferative Diabetic Retinopathy ◽

Panretinal Photocoagulation ◽

Wide Field ◽

Non Invasive ◽

Venous Oxygen Saturation ◽

Treatment Naïve ◽

Angiographic Findings ◽

Retinal Oximetry

Background/AimsProliferative diabetic retinopathy (PDR) is a severe blinding condition. We investigated whether retinal metabolism, measured by retinal oximetry, may predict PDR activity after panretinal laser photocoagulation (PRP).MethodsWe performed a prospective, interventional, clinical study of patients with treatment-naive PDR. Wide-field fluorescein angiography (OPTOS, Optomap) and global and focal retinal oximetry (Oxymap T1) were performed at baseline (BL), and 3 months (3M) after PRP. Angiographic findings were used to divide patients according to progression or non-progression of PDR after PRP. We evaluated differences in global and focal retinal oxygen saturation between patients with and without progression of PDR after PRP treatment.ResultsWe included 45 eyes of 37 patients (median age and duration of diabetes were 51.6 and 20 years). Eyes with progression of PDR developed a higher retinal venous oxygen saturation than eyes with non-progression at 3M (global: +5.9% (95% CI –1.5 to 12.9), focal: +5.4%, (95% CI –4.1 to 14.8)). Likewise, progression of PDR was associated with a lower arteriovenular (AV) oxygen difference between BL and 3M (global: –6.1%, (95% CI –13.4 to –1.4), focal: –4.5% (95% CI –12.1 to 3.2)). In a multiple logistic regression model, increment in global retinal venular oxygen saturation (OR 1.30 per 1%-point increment, p=0.017) and decrement in AV oxygen saturation difference (OR 0.72 per 1%-point increment, p=0.016) at 3M independently predicted progression of PDR.ConclusionDevelopment of higher retinal venular and lower AV global oxygen saturation independently predicts progression of PDR despite standard PRP and might be a potential non-invasive marker of angiogenic disease activity.

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Application of Creative Quantitative Measurement of Iris Angiography in Diabetic Retinopathy

10.21203/rs.3.rs-275696/v1 ◽

2021 ◽

Author(s):

Qi Zhao ◽

Weiting An ◽

Jindong Han ◽

Longli Zhang

Keyword(s):

Diabetic Retinopathy ◽

Proliferative Diabetic Retinopathy ◽

Quantitative Measurement ◽

Onset Time ◽

Vascular Leakage ◽

Fundus Photography ◽

Wide Field ◽

Slit Lamp ◽

Cross Sectional ◽

The Difference

Abstract Background: To explore the application of a creative quantitative measurement of iris angiography (IA) in diabetic retinopathy (DR). Methods: This was a single-center cross-sectional study. From May 2016 to December 2019, 30 consecutive patients (60 eyes) with severe non-proliferative diabetic retinopathy (NPDR) and 30 consecutive patients (60 eyes) with proliferative diabetic retinopathy (PDR) who underwent IA in Tianjin Medical University Eye Hospital were enrolled prospectively in the study. All of the patients underwent ophthalmologic examination including visual acuity, intraocular pressure, slit-lamp microscopy, slit-lamp anterior lens, ultra-wide-field fundus photography and IA. IA included iris fluorescein angiography (IFA) and iris indocyanine green angiography (IICGA). The onset time of iris vascular leakage should be recorded and the circumference range of pupil margin fluorescein leakage was measured by self-developed software. Independent sample t-test and chi-square test were used to compare and analyze the difference of the onset time and range of iris vascular leakage between severe NPDR and PDR groups. Results: IFA showed that the onset time of iris vascular leakage was 30.38±6.40s in severe NPDR group and 26.50±5.41s in PDR group. The difference between two groups was statistically significant (p=0.006). The range of iris vascular leakage was 49.09±59.27 degrees in severe NPDR group and 137.71±95.53 degrees in PDR group. There was significant statistically difference between two groups (p=0.032). No neovascularization of the iris (NVI) was found in all patients with PDR by slit-lamp microscope examination, while NVI was detected in 8 eyes by IFA and IICGA examination.Conclusions: The creative quantitative measurement of IA can evaluate the severity of diabetic iridopathy (DI), monitor the progress of DR, and detect NVI invisible to the naked eye as soon as possible, so as to provide a basis for the formulation of personalized treatment for patients with DR.

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Intravitreal Anti-Vascular Endothelial Growth Factor Agents for the Treatment of Diabetic Retinopathy: A Review of the Literature

Pharmaceutics ◽

10.3390/pharmaceutics13081137 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1137

Author(s):

Irini Chatziralli ◽

Anat Loewenstein

Keyword(s):

Diabetic Retinopathy ◽

Vitreous Hemorrhage ◽

Fundus Photography ◽

Panretinal Photocoagulation ◽

Wide Field ◽

Vascular Endothelial ◽

Keywords Diabetic Retinopathy ◽

Anti Vegf ◽

The Impact

Background: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population. The purpose of this review is to gather the existing literature regarding the use of the approved anti-vascular endothelial growth (anti-VEGF) agents in the treatment of DR. Methods: A comprehensive literature review in PubMed engine search was performed for articles written in English language up to 1 July 2021, using the keywords “diabetic retinopathy”, “ranibizumab”, “aflibercept”, and “anti-VEGF”. Emphasis was given on pivotal trials and recent robust studies. Results: Intravitreal anti-VEGF agents have been found to significantly improve visual acuity and reduce retinal thickness in patients with diabetic macular edema (DME) in a long-term follow-up ranging from 1 to 5 years and are considered the standard-of-care in such patients. Regarding DR, intravitreal anti-VEGF agents provided ≥2-step improvement in DR severity on color fundus photography in about 30–35% of patients with NPDR at baseline, in the majority of clinical trials originally designed to evaluate the efficacy of intravitreal anti-VEGF agents in patients with DME. Protocol S and CLARITY study have firstly reported that intravitreal anti-VEGF agents are non-inferior to panretinal photocoagulation (PRP) in patients with proliferative DR (PDR). However, the use of new imaging modalities, such as optical coherence tomography-angiography and wide-field fluorescein angiography, reveals conflicting results about the impact of anti-VEGF agents on the regression of retinal non-perfusion in patients with DR. Furthermore, one should consider the high “loss to follow-up” rate and its devastating consequences especially in patients with PDR, when deciding to treat the latter with intravitreal anti-VEGF agents alone compared to PRP. In patients with PDR, combination of treatment of intravitreal anti-VEGF agents and PRP has been also supported. Moreover, in the specific case of vitreous hemorrhage or tractional retinal detachment as complications of PDR, intravitreal anti-VEGF agents have been found to be beneficial as an adjunct to pars plana vitrectomy (PPV), most commonly given 3–7 days before PPV, offering reduction in the recurrence of vitreous hemorrhage. Conclusions: There is no general consensus regarding the use of intravitreal anti-VEGF agents in patients with DR. Although anti-VEGF agents are the gold standard in the treatment of DME and seem to improve DR severity, challenges in their use exist and should be taken into account in the decision of treatment, based on an individualized approach.

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Multiplexed Non-invasive in vivo Imaging to Assess Metabolism and Receptor Engagement in Tumor Xenografts

10.1101/758383 ◽

2019 ◽

Author(s):

Alena Rudkouskaya ◽

Nattawut Sinsuebphon ◽

Marien Ochoa ◽

Joe E. Mazurkiewicz ◽

Xavier Intes ◽

...

Keyword(s):

Drug Delivery ◽

Targeted Delivery ◽

Near Infrared ◽

Metabolic Response ◽

Imaging Modalities ◽

Wide Field ◽

Receptor Ligand ◽

Non Invasive ◽

Intracellular Drug Delivery

AbstractFollowing an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. To date, non-invasive quantitative imaging modalities that can comprehensively assess simultaneous cellular drug delivery efficacy and therapeutic response are lacking. In this regard, Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imaging offers a unique method to robustly quantify receptor-ligand engagement in vivo and subsequent intracellular internalization, which is critical to assess the delivery efficacy of targeted therapeutics. However, implementation of multiplexing optical imaging with FRET in vivo is challenging to achieve due to spectral crowding and cross-contamination. Herein, we report on a strategy that relies on a dark quencher that enables simultaneous assessment of receptor-ligand engagement and tumor metabolism in intact live mice. First, we establish that IRDye QC-1 (QC-1) is an effective NIR dark acceptor for the FRET-induced quenching of donor Alexa Fluor 700 (AF700) using in vitro NIR FLI microscopy and in vivo wide-field MFLI imaging. Second, we report on simultaneous in vivo imaging of the metabolic probe IRDye 800CW 2-deoxyglucose (2-DG) and MFLI-FRET imaging of NIR-labeled transferrin FRET pair (Tf-AF700/Tf-QC-1) uptake in tumors. Such multiplexed imaging revealed an inverse relationship between 2-DG uptake and Tf intracellular delivery, suggesting that 2-DG signal may predict the efficacy of intracellular targeted delivery. Overall, our methodology enables for the first time simultaneous non-invasive monitoring of intracellular drug delivery and metabolic response in preclinical studies.

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Wide-field imaging in proliferative diabetic retinopathy

International Journal of Retina and Vitreous ◽

10.1186/s40942-019-0170-2 ◽

2019 ◽

Vol 5 (S1) ◽

Cited By ~ 1

Author(s):

T. Y. Alvin Liu ◽

J. Fernando Arevalo

Keyword(s):

Diabetic Retinopathy ◽

Proliferative Diabetic Retinopathy ◽

Vision Loss ◽

Current Data ◽

Panretinal Photocoagulation ◽

Main Body ◽

Wide Field ◽

Fundus Imaging ◽

Field Imaging ◽

Wide Field Imaging

Abstract Background Diabetic retinopathy (DR) is one of the leading causes of vision loss worldwide. For decades, 7-field 30-degree fundus imaging has been the gold standard for DR classification. The aim of this review article is to discuss how the advent of ultra-wide-field (UWF) fundus imaging has changed the management of proliferative diabetic retinopathy (PDR). Main body Current data suggests that UWF imaging, as compared to conventional Early Treatment Diabetic Retinopathy Study (ETDRS) fields, detects additional and more extensive PDR pathologies. DR lesions, captured by UWF imaging outside of ETDRS fields, likely carry prognostication value. Conclusion UWF imaging represents a major advancement in the detection and management of DR. It remains unclear whether, when and how patients, with PDR changes only peripheral to standard ETDRS fields, should be treated. A larger, prospective, randomized clinical trial is also needed to compare the efficacy of UWF image-guided targeted laser photocoagulation with that of conventional panretinal photocoagulation.

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Optical coherence tomography angiography of foveal neovascularisation in proliferative diabetic retinopathy

BMJ Case Reports ◽

10.1136/bcr-2019-230382 ◽

2019 ◽

Vol 12 (8) ◽

pp. e230382

Author(s):

Deven Dhurandhar ◽

Padmaja Kumari Rani

Keyword(s):

Optical Coherence Tomography ◽

Diabetic Retinopathy ◽

Proliferative Diabetic Retinopathy ◽

Optical Coherence Tomography Angiography ◽

Imaging Modality ◽

Diabetic Macular Oedema ◽

Hypertensive Retinopathy ◽

Optical Coherence ◽

Non Invasive

A 52-year-old man, a known case of type 2 diabetes mellitus and hypertension, who presented to us with bilateral diminution of vision since 1 year. He was diagnosed as a case of bilateral proliferative diabetic retinopathy and hypertensive retinopathy. A non-invasive imaging modality, optical coherence tomography angiography (OCTA), detected foveal neovascularisation in a background of diffuse diabetic macular oedema which would have been obscured by other investigations like fluorescein angiography.

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Differential distribution of manifest lesions in diabetic retinopathy by fundus fluorescein angiography and fundus photography

BMC Ophthalmology ◽

10.1186/s12886-020-01740-2 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Xiaoli Li ◽

Jie Xie ◽

Liang Zhang ◽

Ying Cui ◽

Guanrong Zhang ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Fluorescein Angiography ◽

Posterior Pole ◽

Chinese Patients ◽

Fundus Photography ◽

Peripheral Retina ◽

Multiple Logistic Regression ◽

Fundus Fluorescein Angiography ◽

Differential Distribution ◽

Nonproliferative Diabetic Retinopathy

Abstract Background To analyze the distribution of manifest lesions of diabetic retinopathy (DR) by fundus fluorescein angiography (FFA) and color fundus photography (FP). Methods A total of 566 eyes of 324 Chinese patients diagnosed with DR were included in this retrospective study. DR severity was graded by the international grading criterion. The distributions of microaneurysms (MA), intraretinal hemorrhages/exudates (He/Ex), intraretinal microvascular abnormality (IRMA), capillary nonperfusion areas (NPA), and neovascularization (NV) were estimated by multiple logistic regression analyse based on nine-field FFA and FP images. Results In mild nonproliferative diabetic retinopathy (NPDR), the highest frequency of MA was found in the posterior pole (67.7%), followed by the inferior nasal (59.4%), and the nasal (55.4%) fields. In moderate NPDR, MA frequently distributed in the posterior pole (98.0%), nasal (97.0%), superior (96.0%), inferior nasal (94.9%), and inferior (92.9%) fields, whereas He/Ex were most prevalent in the posterior pole (69.7%). In severe NPDR and proliferative DR, IRMA, NPA, and NV were more frequent in the nasal field, particularly in the inferior nasal field (60.3, 38.7, and 76.0%, respectively). All lesions were more observed in the combined posterior pole, nasal, and inferior nasal fields than in the posterior pole or combined two fields in the early and severe stages of DR (P < 0.05). Conclusions The manifest lesions of DR were common in the nasal field besides the posterior pole in Chinese patients. A combined examination of the posterior pole, nasal, and inferior nasal mid-peripheral retina would help to detect different retinal lesions of DR. Trial registration ClinicalTrial. gov, NCT03528720. Registered 18 May 2018 - Retrospectively registered.

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Probucol Prevents Diabetes-Induced Retinal Neuronal Degeneration through Upregulating Nrf2

BioMed Research International ◽

10.1155/2020/3862509 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Heng-Wei Liu ◽

Yong Luo ◽

Yu-Fan Zhou ◽

Zhong-Ping Chen

Keyword(s):

Diabetic Retinopathy ◽

Neuronal Degeneration ◽

Fundus Photography ◽

Control Group ◽

Ros Generation ◽

Fundus Fluorescein Angiography ◽

Diabetic Retina ◽

Nrf2 Signaling Pathway ◽

Retinal Structure ◽

Nrf2 Expression

Diabetic retinopathy (DR) is a sight-threatening complication of diabetes. This study investigated the therapeutic effect of probucol in a mouse model of diabetic retinopathy. C57BL/6 mice were rendered diabetic through Streptozotocin (STZ) intraperitoneal injection. Mice were treated with probucol (150 mg/kg, gavage administration) or vehicle (DMSO) for 12 weeks. Optical coherence tomography (OCT), fundus photography (FP), and fundus fluorescein angiography (FFA) were conducted to evaluate retinal structure and damage. Eyes were collected for histology, reactive oxygen species (ROS) assay, apoptotic cells count, and western blot. After STZ injection, all mice developed hyperglycemia. Compared with the retina of the control group, the retina of diabetic mice showed enhanced arterial reflex and beaded vein dilatation. Besides, reduced inner and middle retinal thickness and significantly fewer nuclei were found in diabetic retina. Moreover, the diabetic retina also presented increased ROS generation and more TUNEL-positive cells. Probucol treatment prevented diabetes-induced lesions. In addition, the treatment also upregulated Nrf2 expression in diabetic retina. It was suggested that probucol attenuated diabetes-induced retinal neuronal degeneration via upregulating the Nrf2 signaling pathway possibly. Probucol may be repurposed for DR management.

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