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PURPOSE: Changes in the foveal avascular zone (FAZ) metrics over time are key outcome measures for clinical trials in diabetic macular ischemia (DMI). However, artifacts and automatically delineated FAZ measurements may influence the results. We aimed to compare the artifact frequency and FAZ metrics on 3 × 3 versus 6 × 6 mm optical coherence tomography angiography (OCTA) macular scans in patients with DMI. DESIGN: Prospective, comparative image quality analysis with one-year follow-up. METHODS: Patients with diabetic retinopathy (DR) were recruited if they presented with OCTA evidence of DMI, defined as an automated FAZ (aFAZ) ≥0.5 mm2 or parafoveal capillary nonperfusion (CNP) ≥1 quadrant if the aFAZ <0.5 mm2. Only those who had both size scans were included in the analysis. The types of artifacts and FAZ delineation errors were graded before manual correction. After excluding scans with poor quality, the aFAZ, corrected FAZ (cFAZ), whole image superficial vessel density (wiSVD), and whole image deep vessel density (wiDVD) were compared on both size scans. RESULTS: Fifty-seven patients (81 eyes) with paired OCTA 3 × 3 and 6 × 6 mm scans at baseline were included in the image quality analysis. The 6 × 6 mm scan presented with more severe motion artifact (P = .02). Conversely, the 3 × 3 mm scans were more susceptible to mild decentration (P = .009). After removing all the poor-quality images, 55 eyes with both size scans entered the longitudinal analysis. The 3 × 3 mm FAZ was significantly larger than the 6 × 6 mm FAZ using either aFAZ or cFAZ (both P < .05). In contrast, the 6 × 6 mm wiSVD and wiDVD were remarkably higher than those on the 3 × 3 mm scans (both P < .001). There was a steady increase in cFAZ over one year on both size scans (both P < .01). However, the 3 × 3 mm aFAZ decreased numerically at 52 weeks (P = .02). After reviewing all the scans, poor identification of parafoveal CNP was the most common reason for erroneous aFAZ delineation. CONCLUSIONS: In DMI, the FAZ metrics are best evaluated on the 3 × 3 scan due to better resolution. However, manual correction of the FAZ margin is needed. The frequency of artifacts and aFAZ delineation errors suggest that further technical refinement is required.

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Diabetes mellitus is a chronic disease the microvascular complications of which include diabetic retinopathy and maculopathy. Diabetic macular edema, proliferative diabetic retinopathy, and diabetic macular ischemia pose a threat to visual acuity. Artificial intelligence can play an increasingly more important role in making the diagnosis and the treatment regimen of maculopathies in everyday clinical practice in the future. It can be used to automatically detect and quantify pathological parameters of the retina. The aim is to improve patient care in the clinical routine using so-called clinical decision support systems with personalized treatment algorithms. This review article outlines the current research regarding new biomarkers in diabetic maculopathy using optical coherence tomography (OCT) and OCT angiography (OCT-A).

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Background/Objectives: This one-year prospective observational study, conducted at two centers, aimed to report the natural history of retinal sensitivity (RS) loss in diabetic macular ischemia (DMI). Methods: Patients with stable-treated proliferative diabetic retinopathy (PDR) were recruited if there was evidence of DMI on optical coherence tomography angiography, defined as a foveal avascular zone ≥ 0.5 mm2 or parafoveal capillary dropout ≥ 1 quadrant. The minimal visual acuity required for performing microperimetry (MP) was ≥54 Early Treatment Diabetic Retinopathy Study letters (Snellen equivalent 20/80). The overall RS (oRS) and pointwise sensitivity (PWS) within the 3 × 3 mm macula were assessed at baseline and twelve months. A value <25 decibels (dB) was defined as impaired RS, and a decrease of 2 and 7 dB was regarded as mild and severe loss, respectively. Results: A total of 88 patients (97 eyes) were included. No statistically significant MP changes were detected at one year. However, 10% of the cohort lost oRS ≥ 2 dB, and 73% lost ≥2 dB PWS in ≥5 loci, whereas 1% lost oRS ≥ 7 dB, and 4% lost ≥7 dB PWS in ≥5 loci. The foveola and temporal parafovea were the most vulnerable to severe RS loss. Compared to their counterpart, eyes with baseline oRS ≥ 25 dB had significantly more RS loss in the macula and superior parafovea (55% versus 32% and 53% versus 28%, both p = 0.01). Conclusions: Rather than oRS loss, ≥2 dB loss in PWS in ≥5 loci is a more feasible outcome measure for clinical trials in DMI.

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Optical coherence tomography angiography (OCTA) has become part of the clinical practice and its growing applications are in continuous development. Coherently with the growing concern about the human and economic cost of diabetes, diabetic retinopathy (DR) was the most popular topic for OCTA studies in the past year. The analysis of the literature reveals that applications of OCTA in DR are in continuous growth. In particular, ultrawide field (UWF) OCTA and artificial intelligence (AI) based on OCTA images are affirming as the new frontiers of scientific research in the field. Diagnostic accuracy of AI methods based on OCTA is equal or superior to the one based on OCT methods and also bears potential to detect systemic associations. UWF OCTA is noninvasive method that is reaching similar accuracy of FA in detection of neovascularization and intraretinal microvascular abnormalities (IRMAs) and has allowed better characterization of microvascular peripherical changes in DR. Lastly, deep capillary plexus (DCP) characteristics seem to play a pivotal role in the development of diabetic macular edema (DME) and refinement of biomarkers for different phenotypes of DME and diabetic macular ischemia (DMI) is currently on its way.

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Objective:To observe the changes of macular structure and microvessels in eyes with diabetes macular ischemia (DMI).Methods:A retrospective case study. From January 2023 to July 2023, 23 patients of 31 eyes diagnosed with DMI at Tangshan Ophthalmological Hospital were included in this study. Among them, there were 14 males with 23 eyes; Female cases with 8 eyes. Age were (59.5±4.6) years old. According to the DMI grading standard formulated by the research group for early treatment of diabetes retinopathy, the patients were divided into mild DMI group, moderate DMI group, and severe DMI group, with 8, 12, and 11 eyes respectively. The blood flow density (VD), perfusion area (FA), small vessel VD (SVD), inner retinal capillary plexus VD, FA, and outer retinal, choroidal, and ganglion cell complex (GCC) thickness within 1 mm of the macular fovea in retinal superficial vascular plexus (SVP)were measured using a scanning frequency light source optical coherence tomography instrument. The changes in macular structure and microvasculature in the affected eyes of different degrees of DMI groups were compared and observed. Inter group comparisons were conducted using one-way ANOVA or Kruskal Wallis H-test. Spearman correlation analysis was used to analyze the correlation between DMI severity and GCC, outer retina, choroid thickness, VD, FA and SVP VD, SVD and FA in inner retina. Results:The GCC ( F=70.670), outer retinal thickness ( H=12.393), VD ( F=105.506), SVD ( H=25.300), FA ( F=107.655), and VD ( H=24.098) and FA ( H=25.300) of the retinal SVP in the mild, moderate, and severe DMI groups were compared, and the differences were statistically significant ( P<0.05). There was no statistically significant difference in choroidal thickness ( H=2.441, P>0.05). Pairwise comparison between groups: VD, SVD, FA of GCC thickness and SVP, and VD of inner retina were statistically significant between severe DMI group and moderate DMI group, and between moderate DMI group and mild DMI group ( P<0.05). The thickness of outer retina was statistically significant between severe DMI group and moderate DMI group ( P<0.05). Inner retinal FA: there were statistically significant differences between severe DMI group, moderate DMI group and mild DMI group ( P<0.05). The correlation analysis results showed that GCC ( r s=-0.918), outer retinal thickness ( r s=-0.448), and inner retinal VD ( r s=-0.894) and FA ( r s=-0.918), as well as VD ( r s=-0.919), SVD ( r s=-0.924), and FA ( r s=-0.939) of retinal SVP, were all negatively correlated with the degree of DMI ( P<0.05). There was no correlation between choroidal thickness and degree of DMI ( r s=-0.081, P>0.05). Conclusion:The thickness of GCC, outer retina and choroid, the VD, SVD, and FA of the retinal SVP, the VD and FA of inner retina are all reduced in eyes with different degrees of DMI, while all of them are negatively correlated with the degree of DMI, except for choroid thickness.

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Purpose: To characterize the relationship between diabetic macular ischemia (DMI) delineated by optical coherence tomography angiography (OCTA) and microaneurysms (MAs) identified by fundus fluorescein angiography (FFA). Methods: Patients with diabetic retinopathy (DR) who underwent OCTA and FFA were retrospectively identified. FFA images were cropped and aligned with their respective OCTA images using i2k Align Retina software (Dual-Align, Clifton Park, NY, USA). Foveal avascular zone (FAZ) and ischemic areas were manually delineated on OCTA images, and MAs were marked on the corresponding FFA images before overlaying paired scans for analysis (ImageJ; National Institutes of Health, Bethesda, MD, USA). Results: Twenty-eight eyes of 20 patients were included. The average number of MAs identified in cropped FFA images was 127 ± 42. More DMI was noted in the superficial capillary plexus (SCP; 36 ± 13%) compared to the deep capillary plexus (DCP; 28 ± 14%, P < 0.001). Similarly, more MAs were associated with ischemic areas in SCP compared to DCP (92.0 ± 35.0 vs. 76.8 ± 36.5, P < 0.001). Most MAs bordered ischemic areas; fewer than 10% localized inside these regions. As DMI area increased, so did associated MAs (SCP: r = 0.695, P < 0.001; DCP: r = 0.726, P < 0.001). Density of MAs surrounding FAZ (7.7 ± 6.0 MAs/mm2) was similar to other DMI areas (SCP: 7.0 ± 4.0 MAs/mm2, P = 0.478; DCP: 9.2 ± 10.9 MAs/mm2, P = 0.394). Conclusion: MAs identified in FFA strongly associate with, and border areas of, DMI delineated by OCTA. Although more MAs are localized to SCP ischemia, the concentration of MAs associated with DCP ischemia is greater. By contrast, few MAs are present inside low-flow regions, likely because capillary loss is associated with their regression.

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There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications. A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies. Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary.

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Capillary non-perfusion (CNP) is one of the key hallmarks of diabetic retinopathy (DR), which may develop both in the periphery and at the posterior pole. Our perspectives on CNP have extended with the introduction of optical coherence tomography angiography (OCTA) and ultra-widefield imaging, and the clinical consequences of peripheral and macular CNP have been well characterized. Fluorescein angiography (FA) continues to be the gold standard for detecting and measuring CNP, particularly when ultra-widefield imaging is available. OCTA, on the other hand, is a quicker, non-invasive approach that allows for a three-dimensional examination of CNP and may soon be regarded as an useful alternative to FA. In this review, we provide an updated scenario regarding the characteristics, clinical impact, and management of central and peripheral CNP in DR.

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Optical coherence tomography angiography (OCT-A) provides depth-resolved visualization of the retinal microvasculature without intravenous dye injection. It facilitates investigations of various retinal vascular diseases and glaucoma by assessment of qualitative and quantitative microvascular changes in the different retinal layers and radial peripapillary layer non-invasively, individually, and efficiently. Deep learning (DL), a subset of artificial intelligence (AI) based on deep neural networks, has been applied in OCT-A image analysis in recent years and achieved good performance for different tasks, such as image quality control, segmentation, and classification. DL technologies have further facilitated the potential implementation of OCT-A in eye clinics in an automated and efficient manner and enhanced its clinical values for detecting and evaluating various vascular retinopathies. Nevertheless, the deployment of this combination in real-world clinics is still in the "proof-of-concept" stage due to several limitations, such as small training sample size, lack of standardized data preprocessing, insufficient testing in external datasets, and absence of standardized results interpretation. In this review, we introduce the existing applications of DL in OCT-A, summarize the potential challenges of the clinical deployment, and discuss future research directions.

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Purpose: The present study aims to determine the macular and choroidal optical coherence tomography angiography (OCTA) biomarkers in the assessment and monitoring of diabetic macular edema (DME) and diabetic macular ischemia (DMI) in patients with non-proliferative diabetic retinopathy (NPDR). Methods: In this cohort study, a total of 176 eyes of 110 patients with NPDR were investigated at our institute over a period of 10 months. Eyes were divided into four groups based on the severity of NPDR. Each eye was subjected to OCTA (Topcon 3D OCT-1 Maestro2) macula 6 × 6 mm2 en face. It features IMAGEnet 6 software for dynamic viewing of OCTA and imaging data. Four OCTA biomarkers for the macula were identified: foveal avascular zone area (FAZ area), foveal avascular zone contour irregularity (FAZ-CI), capillary dropout areas (CDA), and perifoveal intercapillary areas (PICA). The choroidal OCTA biomarker was the number of choroidal circulation flow voids (CCFV). For all analyses, P < 0.05 was considered statistically significant. Results: Increase in FAZ area and number of CDA were statistically significant (p < 0.0001) with an increase in central foveal thickness, suggesting a correlation of ischemic changes with an increase in DME. FAZ-CI, enlarged PICA, and CCFV were significantly associated with more severe NPDR patients. Conclusion: A correlation between DME and DMI in a patient of NPDR and its progression can be evaluated in a single visit. A unique feature of our study is it revealed novel diagnostic biomarkers of OCTA for DMI and DME.

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OBJECTIVE: To investigate the relative effect of disorganization of the retinal inner layers (DRIL) and ellipsoid zone (EZ) loss on visual function in diabetic macular ischemia (DMI). DESIGN: Prospective cross-sectional observational study. PARTICIPANTS: Patients with stable treated proliferative diabetic retinopathy (PDR) without center-involved diabetic macular edema were recruited at the Moorfields Eye Hospital from December 2019 to November 2021. The main inclusion criteria were best-corrected visual acuity (BCVA) of ≥ 40 ETDRS letters (Snellen equivalent 20/160) with OCT angiography (OCTA) evidence of DMI in ≥ 1 eye. METHODS: Each eligible eye of the recruited patients was assessed for BCVA, OCT, and OCTA metrics. The prespecified OCT parameters were DRIL and subfoveal EZ loss. Generalized estimating equations were used. MAIN OUTCOMES MEASURES: The frequency of DRIL and EZ loss, their relative contributions to vision loss, and their associations with microvascular alterations were evaluated. RESULTS: A total of 125 eyes of 86 patients with PDR were enrolled; 104 (83%) eyes had a BCVA of ≥ 70 letters. Disorganization of the retinal inner layers was more prevalent than EZ loss (46% [58 eyes] vs. 19% [24 eyes]). On average, the presence of DRIL had a more pronounced impact on vision, retinal thickness, and microvascular parameters than EZ loss. After multivariable adjustment, the odds of coexisting DRIL increased by 12% with every letter decrease in BCVA; however, there was no statistically significant association of subfoveal EZ loss with BCVA. In eyes with DRIL in the absence of EZ loss, the BCVA declined significantly by 6.67 letters compared with eyes with no DRIL nor EZ loss (95% confidence interval [CI], -9.92 to -3.41; P < 0.001). However, if DRIL and EZ loss coexisted, the resultant BCVA was 13.22 letters less than eyes without these structural abnormalities (95% CI, -18.85 to -7.59; P < 0.001). CONCLUSIONS: In patients with DMI with a Snellen visual acuity of 20/160 or better, eyes with DRIL were associated with more visual function loss and retinal blood circulation alterations than those with subfoveal EZ loss only.

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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.

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BACKGROUND: To analyze the changes in foveal avascular zone (FAZ) area, perimeter, and circularity in the superficial (SCP) and deep (DCP) capillary plexuses in eyes with diabetic macular edema (DME) treated with intravitreal anti-VEGF using optical coherence tomography angiography (OCTA). METHODS: This prospective observational study included 56 eyes from 32 patients with DME that received intravitreal anti-VEGF. OCTA images were obtained at baseline and 1, 3, and 6 months of follow-up. The outcome measures were FAZ area, perimeter, and circularity in both the SCP and DCP, as well as central subfield thickness (CST) and best-corrected visual acuity (BCVA). RESULTS: The mean number of intravitreal anti-VEGF injections received during the observation period was 4.60 ± 0.82 (range: 3-6). The FAZ area, perimeter, and circularity were statistically unchanged at all observation points in both the SCP (p = 0.772, p = 0.405, p = 0.157, respectively) and the DCP (p = 0.620, p = 0.769, p = 0.481, respectively). Despite having no change in the FAZ parameters, there was still a statistically significant decrease in CST (p < 0.001) as well as a statistically significant increase in BCVA (p = 0.004) during the observation period. CONCLUSIONS: The FAZ area, perimeter, and circularity in the SCP and DCP as measured by OCTA remained stable during the first 6 months of intravitreal anti-VEGF therapy in eyes with DME. While there were no significant changes in the FAZ, treatment with intravitreal anti-VEGF still resulted in decreased CST and improved BCVA.

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Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy (DR) that can result in progressive and irreversible vision loss. DMI is associated with damage in the vessels that supply blood to the retina and the enlargement of the foveal avascular zone. Currently, there are no approved treatments specifically for DMI. Furthermore, there is limited published information about the prognosis, prevalence or outcomes of DMI, and there is no consensus regarding diagnostic criteria. It is vital to ensure that there is sufficient, accessible and accurate information available to support patients, caregivers and physicians. To lay the foundation for more research into DMI and its impact on patients, we (a patient with DMI and an expert ophthalmologist) have worked together to interweave our personal perspectives and clinical experiences with a review of currently available literature on DMI. The development of a set of confirmed diagnostic criteria for DMI would assist both patients and physicians, allowing patients to access validated information about their condition and supporting the development of clinical trials for treatments of DMI. Training for physicians must continue to emphasise the importance of treating a patient holistically, rather than only treating their symptoms. Most importantly, developing trust and a healthy rapport between a patient and their physician is important in managing health anxiety and ensuring adherence to beneficial treatments or lifestyle adjustments; physicians must cultivate an open and flexible management approach with their patients. Finally, holistic educational programmes for patients, physicians and the general public around DMI and how it can affect daily functioning would facilitate general understanding and disease awareness.

Diabetic macular ischemia (DMI) is a common problem for patients with diabetic retinopathy that can lead to sight loss. There is very little information available about DMI, particularly from a patient's point of view. To address the lack of information about DMI, we (a person with DMI and her eye doctor) have worked together to examine what it is like to live with DMI. It is important to provide clear and accessible information about diseases to patients and carers. The lack of information about DMI may be upsetting for some people, and should be addressed with more research. Developing of a set of confirmed signs and symptoms for the diagnosis of DMI would allow people to be more confident in the information that they receive about their disease, and support the development of treatments for DMI. The support of others is central to the wellbeing of people with vision loss. Although people with vision loss may also lose independence, care from loved ones can help to improve quality of life. Most importantly, developing trust between a patient and their doctor is central to managing people's fears about their eyesight, and making sure that they follow helpful advice. Doctors must use an open and flexible approach with their patients, providing information in an honest and understandable way. Living Without a Diagnosis: A Patient's Perspective on Diabetic Macular Ischemia; Audioslides. (MP4 23566 kb).

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The thresholds of macular microvasculature parameters associated with mild visual impairment in diabetic macular ischemia (DMI) patients are unclear. Therefore, this prospective observational study is aimed at demonstrating the optical coherence tomography angiography parameters that best correlate with mild visual impairment (<70 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, Snellen equivalent 20/40) in DMI. The study was completed at the Moorfields Eye Hospital from December 2019 to August 2021. A total of 123 eyes of 87 patients with stable-treated proliferative diabetic retinopathy following panretinal photocoagulation were recruited. DMI was defined as an irregular foveal avascular zone (FAZ) area ≥ 0.5 mm2 or a smaller FAZ area with parafoveal capillary dropout in at least one quadrant. The analysis showed that the whole image deep vascular complex vessel density (DVC VD) in the 3 × 3 mm area had the best discriminatory ability to identify participants with mild visual impairment at 41.9% (area under the curve = 0.77, sensitivity 94%, specificity 54%, likelihood ratio [LR] = 2.04), and the FAZ area had the greatest post-test LR = 4.21 at 0.64 mm2. The 3 × 3 mm whole image DVC VD and FAZ area cutoffs are useful for screening vision-threatening DMI, but DVC VD has low specificity.

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AIM: Since its relevance on diagnosis and prognosis of diabetic retinopathy (DR), this review will examine a multimodal imaging approach to detect diabetic macular ischemia (DMI). METHODS: A PubMed engine search was carried out using the term "macular ischemia" paired with "diabetes," and "diabetic macular ischemia" paired to "fluorescein angiography," "ultra-wide field fluorescein angiography," "optical coherence tomography angiography," "octa," "2D octa," "ultra-wide field octa," "3D octa," "visual acuity." All studies published in English up to October 2021 irrespective of their publication status were reviewed, and relevant publications were included in this review. RESULTS: Recently, new technologies have been proposed as an alternative to fluorescein angiography (FA), which is an actual diagnostic gold standard technique. Nowadays, optical coherence tomography angiography (OCTA) has emerged as the most promising and reliable procedure able to provide a qualitative and quantitative description of DMI. Newer three-dimensional (3D) OCTA approach will be discussed too. Moreover, we will discuss how OCTA might identify preclinical alterations before the onset of DR and allow prediction about the progression of disease. CONCLUSION: OCTA has significantly expanded our knowledge on diabetic macular ischemia.

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PURPOSE: To quantitatively compare microvascular features in the macula of patients with diabetic retinopathy (DR) using fluorescein angiography (FA) and optical coherence tomography angiography (OCTA). METHODS: Patients with DR were recruited from the Cairo University Hospital. FA was performed using a Topcon TRC-50DX or Heidelberg Spectralis HRA+OCT. OCTA was performed using an Optovue RTVue-XR Avanti. FA images were cropped and aligned to the corresponding OCTA images using i2k Align Retina software. The foveal avascular zone (FAZ), area of ischemia, and microaneurysms (MAs) were manually quantified using ImageJ. The fractal dimension (FD) was calculated from each skeletonized image using the FracLac plugin of ImageJ after retinal vascular segmentation. RESULTS: Twenty-four eyes of 17 patients were evaluated, but only 18 eyes were successfully aligned. There was no difference in FAZ area measured for FA and OCTA images. Compared with OCTA images, FD was significantly less for FA images (1.66 ± 0.048 versus 1.72 ± 0.023, p < .001). Significantly more MAs were identified on FA images (102 ± 27.5) compared with OCTA (47.5 ± 11.7, p < .0001). The number of MAs on FA correlated with decreasing best corrected visual acuity (r2 = 0.315, p = .015) and increasing central macular thickness (r2 = 0.492, p = .001). No such associations were found with MAs detected on OCTA. Nevertheless, the area of ischemia in the FA images (8.5 ± 4.1%) was significantly smaller compared with the area measured in both the superficial (30.7 ± 9.5%) and deep capillary plexus (21.6 ± 10.9%) of the OCTA (p < .001). Interestingly, number of MAs in the FA images correlated with increasing area of ischemia in the FA (r2 = 0.568, p < .001) but only the superficial segment of the depth-resolved OCTA scans (r2 = 0.539, p < .001). CONCLUSIONS: OCTA is a non-invasive tool capable of resolving the retinal vasculature in greater detail when compared with FA but detects significantly fewer MAs. Automatic alignment facilitates quantitative comparison of the microvascular features in DR.

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Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy that can lead to progressive and irreversible visual loss. Despite substantial clinical burden, there are no treatments for DMI, no validated clinical trial endpoints, and few clinical trials focusing on DMI. Therefore, generating consensus on validated endpoints that can be used in DMI for the development of effective interventions is vital. In this review, we discuss potential endpoints appropriate for use in clinical trials of DMI, and consider the data required to establish acceptable and meaningful endpoints. A combination of anatomical, functional, and patient-reported outcome measures will provide the most complete picture of changes that occur during the progression of DMI. Potential endpoint measures include change in size of the foveal avascular zone measured by optical coherence tomography angiography and change over time in best-corrected visual acuity. However, these endpoints must be supported by further research. We also recommend studies to investigate the natural history and progression of DMI. In addition to improving understanding of how patient demographics and comorbidities such as diabetic macular edema affect clinical trial endpoints, these studies would help to build the consensus definition of DMI that is currently missing from clinical practice and research.

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BACKGROUND: Functional and anatomical evaluation of patients with ischemic diabetic macular edema after monthly injections of Bevacizumab. METHODS: Five eyes from five patients with diabetic macular edema associated with macular ischemia in fluorescein angiography (FA), received 6 monthly intravitreal injections of Bevacizumab. All subjects underwent SD-OCT, FA, OCT angiography (OCTA) and microperimetry at baseline and after 6 months follow-up. Primary outcome measures were improvement of best corrected visual acuity (BCVA), microperimetry and assessment of macular perfusion (foveal avascular zone size and capillary loss). RESULTS: Five patients completed the follow-up. BCVA improved from 20/180 to 20/74 (p = 0.01) and macular sensitivity improved from 11.66 to 16.26 dB (p < 0.007). We also observed that areas of ischemia on OCTA represented areas of lower macular sensitivity on microperimetry. No changes in macular perfusion status were noted. CONCLUSIONS: Monthly intravitreal Bevacizumab in patients with ischemic diabetic macular edema improved BCVA and macular sensitivity without compromise of perfusion in the macula. Capillary dropout areas in OCTA correlated with lower retinal sensitivity on microperimetry.

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Objectives: To evaluate the relationship between cyst characteristics and macular and peripheral ischemia in diabetic macular edema (DME). Materials and Methods: We retrospectively reviewed eyes with DME and included those with clinically significant macular edema as defined by ETDRS (Early Treatment Diabetic Retinopathy Study) and cystoid spaces in optical coherence tomography scans in this study. Central subfield thickness (CSFT), horizontal and vertical diameters of the largest cyst, cyst area, and the remaining retinal thickness outside the cyst were determined. The presence and number of hyperreflective foci in the cyst wall and the internal reflectivity of the cyst were analyzed. Outer retinal damage was graded. Fluorescein angiography was used to determine the areas of macular and peripheral ischemia, which were graded as mild or severe. Correlations between macular and peripheral ischemia and cyst-related measurements and structural changes in the retina were evaluated. Results: This retrospective study included 250 eyes of 186 patients with DME. Mean CSFT was significantly greater in eyes with macular ischemia (510.4±144.7 µm) compared to eyes without macular ischemia (452.1±114.6 µm) (p=0.001). Horizontal and vertical diameter of the largest cyst increased with the presence and severity of macular ischemia (p=0.045 and p=0.016, respectively). Remaining retinal thickness increased with the presence and severity of peripheral ischemia (p=0.009). There was a statistically significant relationship between the number of the hyperreflective foci in the cyst wall and internal reflectivity of the cyst (p=0.007). Patients with greater CSFT had a 1.04-times higher odds of having macular ischemia and 0.25-times higher odds of having outer retinal damage. Conclusion: The likelihood of macular ischemia increases with larger cyst diameter, CSFT, and extent of outer retinal damage. Thickness of the noncystic area is increased in the presence of peripheral ischemia.

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