Perfused and Nonperfused Microaneurysms Identified and Characterized by Structural and Angiographic OCT.

PURPOSE: Microaneurysms (MAs) have distinct, oval-shaped, hyperreflective walls on structural OCT, and inconsistent flow signal in the lumen with OCT angiography (OCTA). Their relationship to regional macular edema in diabetic retinopathy (DR) has not been quantitatively explored. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: A total of 99 participants, including 23 with mild, nonproliferative DR (NPDR), 25 with moderate NPDR, 34 with severe NPDR, and 17 with proliferative DR. METHODS: We obtained 3 × 3-mm scans with a commercial device (Solix, Visionix/Optovue) in 99 patients with DR. Trained graders manually identified MAs and their location relative to the anatomic layers from cross-sectional OCT. Microaneurysms were first classified as perfused if flow signal was present in the OCTA channel. Then, perfused MAs were further classified into fully and partially perfused MAs based on the flow characteristics in en face OCTA. The presence of retinal fluid based on OCT near MAs was compared between perfused and nonperfused types. We also compared OCT-based MA detection to fundus photography (FP)- and fluorescein angiography (FA)-based detection. MAIN OUTCOME MEASURES: OCT-identified MAs can be classified according to colocalized OCTA flow signal into fully perfused, partially perfused, and nonperfused types. Fully perfused MAs may be more likely to be associated with diabetic macular edema (DME) than those without flow. RESULTS: We identified 308 MAs (166 fully perfused, 88 partially perfused, 54 nonperfused) in 42 eyes using OCT and OCTA. Nearly half of the MAs identified in this study straddle the inner nuclear layer and outer plexiform layer. Compared with partially perfused and nonperfused MAs, fully perfused MAs were more likely to be associated with local retinal fluid. The associated fluid volumes were larger with fully perfused MAs compared with other types. OCT/OCTA detected all MAs found on FP. Although not all MAs seen with FA were identified with OCT, some MAs seen with OCT were not visible with FA or FP. CONCLUSIONS: OCT-identified MAs with colocalized flow on OCTA are more likely to be associated with DME than those without flow. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Turnover of Microaneurysms After Intravitreal Injections of Faricimab for Diabetic Macular Edema.

Purpose: Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF) therapy. This study aimed to investigate the effect of faricimab, a bispecific antibody against angiopoietin-2 and VEGF, on the number of MAs and their turnover in the treatment of DME. Methods: We included that patients with DME who underwent three monthly injections of faricimab in one eye, with the other eye as control. We examined central retinal thickness (CRT) based on optical coherence tomography (OCT) and best-corrected visual acuity. Turnover, including loss and newly formed MAs, and the total number of MAs were counted based on merged images of the OCT map and fluorescein angiography. Results: We enrolled 28 patients with DME. After 3 monthly injections of faricimab, CRT significantly improved, 66.0 ± 16.2% of MAs disappeared, and 6.71 ± 5.6% of new MAs were generated, resulting in total reduction to 40.7 ± 15.2%. In the treated eyes, MA disappearance (P < 0.0001) and turnover (P = 0.007) were significantly greater, and new formation was smaller (P < 0.0001) than in non-treated eyes. The size of the retained MAs decreased after treatment. Microaneurysm turnover was not significantly different between areas with and without edema before treatment. Conclusions: In the process of improving edema in DME with faricimab, MAs shrink and disappear, and formation of MAs are inhibited, resulting in decreased total number of MAs. Intravitreal administration of faricimab suppresses vascular permeability and improves vascular structure.

Diabetic microaneurysms detected by fluorescein angiography spatially correlate with regions of macular ischemia delineated by optical coherence tomography angiography.

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.

Morphology and fluorescein leakage in diabetic retinal microaneurysms: a study using multiple en face OCT angiography image averaging.

PURPOSE: To investigate the relevance of microaneurysm morphology in optical coherence tomography angiography (OCTA) image averaging and fluorescein leakage in diabetic retinopathy (DR). METHODS: In 38 consecutive patients with DR, ten consecutive 3- × 3-mm fovea-centered OCTA (HS100, Canon Inc., Tokyo, Japan) and fluorescein angiography (FA) were performed, and averaged OCTA images were created based on the 10 images. After detecting all microaneurysms in FA images, the morphology was classified into four types (focal bulge, saccular/pedunculated, fusiform, and mixed) using averaged OCTA images. The correlation between microaneurysm leakage in FA, retinopathy stage, and microaneurysm morphology was estimated. RESULTS: Thirty-eight eyes (50.0%) of the 33 patients were available for analysis, and 370 (63.5%) of the 583 FA-detected microaneurysms were morphologically classifiable (focal bulge, 46; saccular/pedunculated, 143; fusiform, 29; and mixed, 152) in OCTA. There was a significant correlation between stage and percentage of microaneurysm morphology and between morphology and the presence of leakage (P < 0.0001 and P < 0.01, respectively). The proportion of focal bulges decreased with stage progression, while the other three types increased with stage progression. The percentage of FA leakage for focal bulge, saccular/pedunculated, fusiform, and mixed was 41.3%, 66.4%, 82.8%, and 66.4%, respectively, and the fusiform type showed significant FA leakage. CONCLUSION: Microaneurysm morphology is correlated with the DR stage and FA leakage. Microaneurysm morphology recognition using OCTA image averaging may be useful for the clinical evaluation of DR.

[Microaneurysms as a biomarker of diabetic retinopathy]. / Mikroanevrizmy kak marker diabeticheskoi retinopatii.

Diabetic retinopathy is a microvascular pathology, which is the most common complication of diabetes mellitus. Improvement of instrumental diagnostics of retinal pathologies has contributed to identification of various phenotypes of the progression of ocular fundus pathology in diabetes based on specific changes in the retina - biomarkers. In particular, microaneurysms initially described in diabetes, which are a manifestation of a wide range of systemic pathologies and retinal diseases, are an indicator of the severity of diabetic retinopathy. Dynamic changes in the number of microaneurysms are a confirmed prognostic biomarker of clinically significant macular edema. In diabetic retinopathy, microaneurysms are one of the earliest recognizable signs, and the dynamic of their formation and disappearance may serve as a predictor for the disease progression. This literature review presents the characteristics of microaneurysms based on various imaging techniques, and analyses the link between structural features and dynamic changes in microaneurysms, and progression of diabetic retinopathy.

Different retinopathy phenotypes in type 2 diabetes predict retinopathy progression.

PURPOSE: To characterize the progression in retinopathy severity of different phenotypes of mild nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes. DESIGN AND METHODS: Patients with type 2 diabetes and mild NPDR (ETDRS 20 or 35) were followed in a 5-year longitudinal study. Examinations, including color fundus photography (CFP) and optical coherence tomography (OCT and OCTA), were performed at baseline, 6 months and then annually. Phenotype classification was performed based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Phenotype A is characterized by low MAT (< 6) and normal CRT; Phenotype B by low MAT (< 6) and increased CRT; and Phenotype C by higher MAT (≥ 6) with or without increased CRT. ETDRS grading of seven fields CFP was performed at the initial and last visits. RESULTS: Analysis of ETDRS grade step changes showed significant differences in diabetic retinopathy (DR) progression between the different phenotypes (p < 0.001). Of the 66 participants with phenotype A only 2 eyes (3%) presented 2-or-more-step worsening. None of the 50 participants characterized as phenotype B developed 2-step worsening, whereas 13 eyes (23.2%) characterized as phenotype C had 2-or-more-steps worsening. Phenotype C presents the higher risk for 2-or-more step worsening (OR: 15.94 95% CI: 3.45-73.71; p < 0.001) and higher sensitivity, correctly identifying 86.7% of cases at risk (AUC: 0.84 95% CI: 0.72-0.96; p < 0.001). Diabetic retinopathy severity progression was associated with HbA1c (p = 0.019), LDL levels (p = 0.043), and ocular factors as MAT (p = 0.010), MA formation rate (p = 0.014) and MA disappearance rate (p = 0.005). Capillary closure at 5-year follow-up, identified by lower vessel density (VD) on OCTA, was also associated with diabetic DR severity progression (p = 0.035). CONCLUSIONS: Different DR phenotypes in type 2 diabetes show different risks of retinopathy progression. Phenotype C is associated with increased HbA1c values and presents a higher risk of a 2-or-more-step worsening of the ETDRS severity score.

Visualization of microaneurysms in macular telangiectasia type 1 on optical coherence tomography angiography before and after photocoagulation.

PURPOSE: To evaluate changes in the visualization of microaneurysms (MAs) in cases of macular telangiectasia (Mac Tel) type 1 on optical coherence tomography angiography (OCTA) before and after treatment with direct photocoagulation and to evaluate their relationship with treatment efficacy. METHODS: The study included 12 eyes from 12 patients (8 men, 4 women; mean age 72.1 years) with Mac Tel type 1 accompanied by cystoid macular edema. OCTA for the evaluation of MAs was performed before and 15 min and 6, 12, and 24 weeks after photocoagulation. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were also evaluated. RESULTS: A total of 73 MAs were detected within the areas of macular edema on OCTA, and 39 of these underwent photocoagulation. At 15 min after treatment, 17 MAs were no longer visible on OCTA. At 6 weeks, two MAs had reappeared, whereas five additional MAs were no longer visible. The CRT in eyes with resolved MA was significantly less than that in eyes with persistent MAs (p = 0.016). At 24 weeks, seven eyes had no visible MAs, and the BCVA was not significantly different from baseline. CONCLUSION: OCTA can monitor changes in the visualization of MAs associated with Mac Tel type 1 after direct photocoagulation. Eyes in which MAs disappeared after treatment could recover from cystoid macular edema.

Microaneurysm density in residual oedema after anti-vascular endothelial growth factor therapy for diabetic macular oedema.

PURPOSE: To investigate the relationship between microaneurysm (MA) density and residual oedema after intravitreal injection of an anti-vascular endothelial growth factor agent for the treatment of diabetic macular oedema (DMO). METHODS: Patients with DMO were divided into those with residual oedema (RO) and those with no residual oedema (NRO) by the presence and absence of oedema at 1 month after intravitreal injection of either aflibercept or ranibizumab. We then compared MA density, best corrected visual acuity (BCVA), central retinal thickness (CRT) and size of the severely thickened area, as indicated by a white area (WA) on optical coherence tomography. RESULTS: We examined 48 eyes in the RO group and 25 eyes in the NRO group (n = 73). In both groups, the CRT and WA size significantly decreased and BCVA improved at 1 month and thereafter. CRT was significantly higher and BCVA was poor in the RO group at 1 and 3 months, while WA size was larger at 1, 3 and 6 months compared with the NRO group (p < 0.05). The number of injections in the RO group (3.62 ± 1.75) was larger than the NRO group (1.89 ± 0.97; p < 0.0001). At 1 and 6 months, the MA density in the area with persistent oedema was significantly higher than in the area with improved oedema (1 month: p = 0.0001, 6 months: p = 0.029). CONCLUSION: High MA density and extensive swelling may be characteristic of RO following treatment for DMO with intravitreal injection of either aflibercept or ranibizumab.

Characteristic distribution of microaneurysms and capillary dropouts in diabetic macular edema.

PURPOSE: To investigate the distribution pattern of microaneurysms (MAs) and capillary dropouts (CDOs) related to retinal thickness in patients with diabetic macular edema (DME). METHODS: We designed a cross-sectional observational study in which we manually merged fluorescein angiography and optical coherence tomography (OCT) map and located MAs and CDOs areas. The density of MAs, the width and the length of circumference of CDOs, and the number of MAs adjacent to CDOs were compared between highly thickened (white area (WA) in OCT map) and border areas (red area (RA)). RESULTS: We examined 115 eyes of 115 patients with DME. The density of MAs in RA (1.086 ± 0.616) was significantly higher than that in WA (0.8601 ± 1.086) (p = 0.002). The MA rates adjacent to CDOs in WA and RA were 79.1% and 80.7%, respectively. In the RA, the size of CDO adjacent to MAs was smaller (p = 0.013), but its circumference was longer (p = 0.018), and the number of MAs adjacent to CDOs was larger than those in WA (p = 0.002). The total length of circumference of CDOs was significantly correlated with the number of MAs adjacent to CDOs in WA (p = 0.011, R2 = 0.68) and RA (p = 0.008, R2 = 0.81). CONCLUSION: Smaller but more CDOs with longer circumference adjacent to MAs contribute to the higher density of MAs in the surrounding areas of DME.

Disparity of microaneurysm count between ultrawide field colour imaging and ultrawide field fluorescein angiography in eyes with diabetic retinopathy.

AIMS: To compare microaneurysm (MA) counts using ultrawide field colour images (UWF-CI) and ultrawide field fluorescein angiography (UWF-FA). METHODS: Retrospective study including patients with type 1 or 2 diabetes mellitus receiving UWF-FA and UWF-CI within 2 weeks. MAs were manually counted in individual Early Treatment Diabetic Retinopathy Study (ETDRS) and extended UWF zones. Fields with MAs ≥20 determined diabetic retinopathy (DR) severity (0 fields=mild, 1-3=moderate, ≥4=severe). UWF-FA and UWF-CI agreement was determined and UWF-CI DR severity sensitivity analysis adjusting for UWF-FA MA counts performed. RESULTS: In 193 patients (288 eyes), 2.4% had no DR, 29.9% mild non-proliferative DR (NPDR), 32.6% moderate (NPDR), 22.9% severe NPDR and 12.2% proliferative DR. UWF-FA MA counts were 3.5-fold higher (p<0.001) than UWF-CI counts overall, 3.2x-fold higher in ETDRS fields (p<0.001) and 5.3-fold higher in extended ETDRS fields (p<0.001) and higher in type 1 versus type 2 diabetes (p<0.001). In eyes with NPDR on UWF-CI (n=246), UWF-FA images had 1.6x-3.5x more fields with ≥20 MAs (p<0.001). Fair agreement existed between imaging modalities (k=0.221-0.416). In ETDRS fields, DR severity agreement increased from k=0.346 to 0.600 when dividing UWF-FA counts by a factor of 3, followed by rapid decline in agreement thereafter. Total UWF area agreement increased from k=0.317 to 0.565 with an adjustment factor of either 4 or 5. CONCLUSIONS: UWF-FA detects threefold to fivefold more MAs than UWF-CI and identifies 1.6-3.5-fold more fields affecting DR severity. Differences exist at all DR severity levels, thus limiting direct comparison between the modalities. However, correcting UWF-FA MA counts substantially improves DR severity agreement between the modalities.

Decrease in the number of microaneurysms in diabetic macular edema after anti-vascular endothelial growth factor therapy: implications for indocyanine green angiography-guided detection of refractory microaneurysms.

PURPOSE: We evaluated changes in the numbers of microaneurysms (MAs) on fluorescein angiography (FA) and indocyanine green angiography (IA) in eyes with diabetic macular edema (DME) following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. METHODS: Twenty-one eyes of 16 patients with DME were included in this retrospective study. All patients received an initial loading dose of three monthly injections of anti-VEGF agents; thereafter, they received a pro re nata regimen for at least 12 months of follow-up. FA and IA images were obtained before and at 6 months after the initial injection. RESULTS: The median numbers of MAs significantly decreased from six (interquartile range [IQR] 3-7) MAs in early-phase FA, three (IQR 3-5) leaky MAs in late-phase FA, and two (IQR 1-4) MAs in late-phase IA at baseline to two (IQR 1-3) MAs in early-phase FA, one (IQR 0-2) leaky MA in late-phase FA, and one (IQR 0-2) MA in late-phase IA at 6 months (P < 0.0001 for all). Only the median numbers of MAs in late-phase IA at baseline and at 6 months were significantly higher in the recurrent DME group (13 eyes) than in the non-recurrent DME group (five eyes) (three [IQR 2-4] vs one [IQR 1-2], one [IQR 0.5-2] vs zero [P = 0.0185 and P = 0.009]). CONCLUSION: Intravitreal injection of anti-VEGF agents reduced the numbers of MAs in patients with DME. The numbers of MAs detected by late-phase IA might be useful predictors of DME recurrence.

Structural en face optical coherence tomography imaging for identification of leaky microaneurysms in diabetic macular edema.

PURPOSE: To study the correspondence between fluorescein angiography (FA) and structural en face optical coherence tomography (OCT) in the identification of leaky microaneurysms in diabetic macular edema (DME). METHODS: Fourteen eyes of eight patients with DME (6 males and 2 females, mean age 67.3 ± 8.5) were included. For all eyes, a 6 × 6 mm structural en face image of the middle retina was obtained and superimposed on a FA image. The reflectivity, capsulation, and association with intraretinal cystic fluid (IRCF) of microaneurysms on en face were evaluated depending on their leaky status on FA. RESULTS: Out of the 320 leaky microaneurysms evaluated, 280 (89.0 ± 8.2%) coincided with those on en face OCT image. Twenty-nine (10.6 ± 6.9%) and 20 (6.5 ± 7.8%) out of all leaky microaneurysms were hyperreflective and demonstrated capsular appearance, respectively. A majority of leaky microaneurysms (97.9 ± 3.2%) were associated with IRCF. From 146 microaneurysms which were found only on en face images, 130 (88.2% ± 15.7%) were hyperreflective, 33 (23.9% ± 15.6%) demonstrated capsular structure, and 13 (9.2% ± 15.0%) demonstrated no associated IRCF. After exclusion of microaneurysms of the inner retina, 95.4 ± 5.4% of leaky microaneurysms were identified on en face image. En face imaging demonstrated 83.5% sensitivity and 89.4% specificity (the area under the curve 0.87) in the identification of leaky microaneurysms. CONCLUSIONS: Structural en face imaging is comparable to FA in identification of leaky microaneurysms in diabetic macular edema. Moderate reflectivity, the absence of capsular structure, and neighboring intraretinal cystic fluid indicate leaky microaneurysms.

In vivo rotational three-dimensional OCTA analysis of microaneurysms in the human diabetic retina.

The aim of this study was to explore whether rotational three-dimensional (3D) visualization of optical coherence tomography angiography (OCTA) volume data may yield valuable information regarding diabetic retinal microaneurysm (MA) characteristics. In this retrospective, observational study, we collected data from 20 patients (20 eyes) with diabetic retinopathy. Subjects were imaged with the SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). The OCTA volume data were processed with a volume projection removal algorithm and then exported to imageJ in order to obtain a 3D visualization of the analyzed MAs. The rotational three-dimensional OCTA images were qualitatively and quantitatively investigated. A total of 52 MAs were included in the analysis. On rotational 3D OCTA images, the number of vessels associated with each MA varied between 1 and 4, and most MAs (59.6%) were associated with 2 vessels. Moreover, in 20 MAs (38.4%) these vessels seem to originate from the SCP, while 26 MAs (50.0%) had associated vessels originating from the DVC, and 6 MAs had associated vessels arising from both the SCP and DVC (11.6%). Most MAs (31/52) had a 'saccular' shape. The number of retinal layers occupied by each MA ranged between 1 and 3 and the inner nuclear layer was the retinal layer most frequently occupied by MAs. In conclusion, this study used an algorithm to obtain rotational three-dimensional visualization of retinal MAs. The MAs' architecture is complex and 3D visualization may clarify the true vascular origin of these lesions, which is often mistaken using en face OCTA images.

Multiple Effects of Intravitreal Aflibercept on Microvascular Regression in Eyes with Diabetic Macular Edema.

PURPOSE: To evaluate the effects of intravitreal aflibercept (IVA) on the number of microaneurysms and sizes of nonperfused areas (NPAs) in eyes with diabetic macular edema (DME). DESIGN: Interventional, prospective study. PARTICIPANTS: Twenty-five eyes of 25 DME patients (average age, 64.0±8.8 years) were treated with 3 consecutive monthly IVA injections. METHODS: Fluorescein angiography (FA) and OCT were performed before the IVA injections (baseline) and at 1 week after the IVA treatment. The number of microaneurysms and the ischemic index (ISI), a measure of NPA, were determined. The correlations between central retinal thickness (CRT) and number of microaneurysms and the ISI were also determined. MAIN OUTCOME MEASURES: The mean number of microaneurysms and NPA evaluated as the ISI. RESULTS: At baseline, the mean CRT was 485.7±90.6 µm. After treatment, the mean CRT was reduced significantly to 376.9±81.6 µm (P = 0.1 × 10-5, repeated analysis of variance). The mean number of microaneurysms was decreased significantly from 49.6±33.2 at baseline to 24.8±18.1 at 3 months after the initial treatment. This was a 50.4±21.2% reduction (P = 0.3 × 10-5, paired t test). The mean ISI was also decreased significantly from 55.5±20.4% at baseline to 28.8±16.8% after treatment (P = 0.3 × 10-5, paired t test). This was a reduction of 43.3±28.5%. A significant correlation was found between the CRT and number of microaneurysms at both baseline (r = 0.56; P = 0.004) and after treatment (r = 0.53; P = 0.006). A significant correlation was found between CRT and ISI at baseline (r = -0.39; P = 0.03) but not after treatment (r = -0.06; P = 0.79). CONCLUSIONS: The reduction in the number of microaneurysms was correlated with reduction in CRT.

Life Style Intervention Improves Retinopathy Status-The Finnish Diabetes Prevention Study.

The aim of the study was to find out whether participation in earlier intervention had an effect on the occurrence of retinopathy in study participants. We also examined risk factors (age, sex, weight, fasting and 2 h glucose, fasting insulin, blood pressure, serum lipids) for early retinal changes. The study included 522 individuals (mean 55 years old, range 40-64 years) with impaired glucose tolerance who were randomized into intervention (weight loss, healthy diet, and physical activity, N = 265) and control groups (N = 257). Intervention lasted for median of four years in 1993-2000, after which annual follow-up visits at study clinics were conducted. In the years 2002-2006 (at least five years after stopping intervention), fundus photography was offered for all study participants in four of five study clinics. Photographs were assessed by two experienced ophthalmologists (A.A. and K.K.), masked for the group assignment. After exclusion of poor quality photographs, the data of 211 individuals (N = 113 for intervention and N = 98 for control group) were included in the present study. The occurrence of microaneurysms was significantly higher in the control (37/98, 38%) than in the intervention group (27/113, 24%; p = 0.029). In the model, including age, sex, diabetes diagnosis before the retinal assessment, body mass index (BMI), and treatment group, the odds ratio for microaneurysms was markedly lower in intervention group (OR 0.52; 0.28-0.97, p = 0.039). The only risk factor that predicted the occurrence of microaneurysms was serum triglycerides at baseline (mean ± SD 1.9 ± 0.9 vs. 1.6 ± 0.7, mmol/L, with and without microaneurysms, respectively, p = 0.003). Triglycerides associated with decreased microaneurysms in regression analysis for age, sex, fasting glucose, and intervention group (OR 1.92, p = 0.018). Lifestyle intervention in overweight and obese individuals with impaired glucose tolerance showed decreased occurrence of retinal microaneurysms. Elevated serum triglycerides were associated to the development of early diabetic microangiopathy.

Microaneurysm detection using fully convolutional neural networks.

BACKROUND AND OBJECTIVES: Diabetic retinopathy is a microvascular complication of diabetes that can lead to sight loss if treated not early enough. Microaneurysms are the earliest clinical signs of diabetic retinopathy. This paper presents an automatic method for detecting microaneurysms in fundus photographies. METHODS: A novel patch-based fully convolutional neural network with batch normalization layers and Dice loss function is proposed. Compared to other methods that require up to five processing stages, it requires only three. Furthermore, to the best of the authors' knowledge, this is the first paper that shows how to successfully transfer knowledge between datasets in the microaneurysm detection domain. RESULTS: The proposed method was evaluated using three publicly available and widely used datasets: E-Ophtha, DIARETDB1, and ROC. It achieved better results than state-of-the-art methods using the FROC metric. The proposed algorithm accomplished highest sensitivities for low false positive rates, which is particularly important for screening purposes. CONCLUSIONS: Performance, simplicity, and robustness of the proposed method demonstrates its suitability for diabetic retinopathy screening applications.