Impact of image averaging on vessel detection using optical coherence tomography angiography in eyes with macular oedema and in healthy eyes.

PURPOSE: To assess the repeatability of multiple automatic vessel density (VD) measurements and the effect of image averaging on vessel detection by optical coherence tomography angiography (OCTA). METHODS: An observational study was conducted in a series of healthy volunteers and patients with macular oedema. Five sequential OCTA images were acquired for each eye using the OptoVue HD device. The effect of the averaging of the 5 acquisitions on vessel detection was analysed quantitatively using a pixel-by-pixel automated analysis. In addition, two independent retina experts qualitatively assessed the change in vessel detection in averaged images segmented in 9 boxes and compared to the first non-averaged image. RESULTS: The automatic VD measurement in OCTA images showed a good repeatability with an overall mean intra-class correlation coefficient (ICC) of 0.924. The mean ICC was higher in healthy eyes compared to eyes with macular oedema (0.877 versus 0.960; p < 0.001) and in the superficial vascular plexus versus the deep vascular complex (0.967 versus 0.888; p = 0.001). The quantitative analysis of the effect of the averaging showed that averaged images had a mean gain of 790.4 pixels/box, located around or completing interruptions in the vessel walls, and a mean loss of 727.2 pixels/box. The qualitative analysis of the averaged images showed that 99.6% of boxes in the averaged images had a gain in vessel detection (i.e., vessels detected in the averaged image but not in the non-averaged image). The loss of pixels was due to a reduction in background noise and motion artifacts in all cases and no case of loss of vessel detection was observed. CONCLUSION: The automatic VD measurement using the OptoVue HD device showed a good repeatability in 5 acquisitions in a row setting. Averaging images increased vessel detection, and in about a third of boxes, decreased the background noise, both in healthy eyes and, in a greater proportion, in eyes with macular oedema.

Prevalence, severity stages, and risk factors of diabetic retinopathy in 1464 adult patients with type 1 diabetes.

PURPOSE: To determine the prevalence of diabetic retinopathy (DR) and its risk factors in adult type 1 diabetes (T1D) patients METHODS: In this cross-sectional study, all T1D patients followed in the University Center for Diabetes and its Complications of Lariboisière Hospital (Paris, France) between January 2017 and February 2019 were included. Ophthalmologic and systemic data were collected from electronic records. The association between DR (and each grade) and associated factors were estimated by univariate and multivariate analyses using logistic regression models. RESULTS: A total of 1464 patients (46.2% of women, mean age: 42.2 ± 15.8 years) were included. The mean hemoglobin A1c (HbA1c) was 7.8 ± 1.7% and the mean diabetes duration was 20.5 ± 13.5 years. DR prevalence was 50.1% (47.4-52.6) and the prevalence of mild, moderate, and severe non-proliferative DR and proliferative DR was 19.1%, 9.4%, 3.9%, and 17.6%, respectively. DR was significantly associated with male gender, an older age, former and current smoking status, a higher BMI, the presence of nephropathy and neuropathy, higher HBA1c, and longer diabetes duration. Patients with HbA1c > 10% had an adjusted odds ratio (OR) of 3.25 (1.77-6.01) of having DR compared to patients with HbA1c < 6.5%. Patients with a diabetes duration > 30 years had an adjusted OR of 24.87 (14.82-42.67) higher of having DR compared to patients with a diabetes duration < 10 years. CONCLUSION: In this study, 50.1% of adult T1D patients had DR and 17.6% had proliferative DR. Diabetes duration and HbA1c were major risk factors.

Ten-year incidence and assessment of safe screening intervals for diabetic retinopathy: the OPHDIAT study.

BACKGROUND: To estimate the 10-year incidence of referable diabetic retinopathy (DR) in a French population with type 1 and 2 diabetes mellitus (DM). A secondary objective was the assessment of safe screening intervals in patients with diabetes without retinopathy. METHODS: Observational, prospective and multicentric study between June 2004 and September 2017 based on a regional screening programme for DR in the Paris region. The incidence of referable DR in patients without retinopathy at baseline was calculated by the Turnbull survival estimator. A safe screening interval was defined as a 95% probability of remaining without referable DR. RESULTS: Among the 25 745 participants with type 1 (n=6086) or type 2 (n=19 659) DM, the 10-year cumulative incidence of referable DR was 19.10% (95% CI 17.21% to 21.14%) and 17.03% (15.78% to 18.35%), median (IQR) follow-up=3.33 (4.24) years. The safe screening interval for patients without DR at the first examination for type 1 and 2 DM was 2.2 (95% CI 2.0 to 2.4) and 3.0 (2.9 to 3.1) years, respectively. In a subgroup of low-risk patients with type 2 DM, the safe screening interval was 4.2 (3.8 to 4.6) years. CONCLUSIONS: These data suggest that in Paris area, a 2-year, 3-year and 4-year screening interval was considered safe for type 1 DM, type 2 DM and for low-risk patients with type 2 DM, respectively, without DR at the first examination. While these data might be used to support the consideration of extending screening intervals, a randomised clinical trial would be suitable to confirm the safety for patients with DM.

Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study.

AIMS: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. METHODS: We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs.We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. RESULTS: In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800-1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. CONCLUSIONS: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.

Widefield OCT-Angiography and Fluorescein Angiography Assessments of Nonperfusion in Diabetic Retinopathy and Edema Treated with Anti-Vascular Endothelial Growth Factor.

PURPOSE: To assess change in retinal nonperfusion (NP) after anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) using 2 different imaging modalities: swept-source widefield (SS-WF) OCT angiography (OCTA) and ultra-widefield (UWF) fluorescein angiography (FA). DESIGN: Observational case series. PARTICIPANTS: Ten eyes of 9 patients with severe nonproliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) initiating 3 monthly anti-VEGF intravitreal injections for DME. METHODS: All eyes were imaged with UWF color fundus photographs (CFPs), UWF FA, and SS-WF OCTA at baseline (M0) and 1 month after the third anti-VEGF injection (M3). All images were aligned and divided into 16 boxes for analysis of NP areas by 2 blinded retina specialists. MAIN OUTCOME MEASURES: The number of discrepancies between SS-WF OCTA and UWF FA regarding the detection of NP areas and small vessels passing through NP areas; assessment of DR severity on UWF CFP; and change in each NP area between M0 and M3: number of boxes/eye with presence of at least 1 NP area, number of arterioles or venules that disappeared or reappeared, and number of NP areas in which capillaries disappeared or reappeared. RESULTS: The diabetic retinopathy (DR) severity score improved by at least 1 stage in 8 of 10 eyes, with a significant decrease in the mean number of microaneurysms and retinal hemorrhages on UWF CFP at M3 versus M0 (n = 40±28 vs. 121±57; P = 0.0020) and regression of fundus neovascularization when present. All NP areas detected on FA were seen on SS-WF OCTA, but additional NP areas were detected on SS-WF OCTA at M0 in 29% (46/160) of boxes. No reperfusion of arterioles or venules was observed at M3 on FA or SS-WF OCTA. Retinal capillaries were only visible on OCTA, and no reperfusion in NP areas was observed even when a reduction in dark areas was visible on FA. CONCLUSIONS: No reperfusion of vessels or capillary network was detected in NP areas using 2 imaging techniques, UWF FA and SS-WF OCTA, in eyes with DR after 3 anti-VEGF injections. The detection rate of NP areas was higher with SS-WF OCTA than with UWF FA.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY CAN IMPROVE DIABETIC RETINOPATHY SCORE WITHOUT CHANGE IN RETINAL PERFUSION.

PURPOSE: To compare the changes in retinal perfusion on ultra-wide-field fluorescein angiography with the changes in diabetic retinopathy lesions observed on ultra-wide-field fundus color photographs after 3 monthly anti-vascular endothelial growth factor injections. METHODS: Retrospective interventional cohort study analyzing the files of 14 patients with DR (18 eyes). UWF color photos and FA were analyzed at baseline (M0) and 1 month after the third anti-VEGF injection (M3). The main outcomes included the count of the number of red dots (microaneurysms, hemorrhages) and assessment of DR severity score (DRSS); the analysis of non-perfusion areas and disappearance or reappearance of arterioles or venules in the non-perfusion areas on FA. RESULTS: Eighteen eyes of 14 diabetic patients, with mean age of 63 ± 5 years, were included. The DRSS score improved by at least one stage in 11/18 (61%) eyes. The mean number of red dots significantly decreased at M3 (n = 80 ± 85) compared with M0 (n = 139 ± 130) (P < 0.0001). No reperfusion of arterioles or venules was observed in or around nonperfusion areas. CONCLUSION: After anti-vascular endothelial growth factor injections, the improvement in the DRSS score based on color fundus photographs can occur without retinal reperfusion on ultra-wide-field fluorescein angiography.

Optical Coherence Tomography Angiography of Familial Retinal Arteriolar Tortuosity.

BACKGROUND AND OBJECTIVE: To analyze the location of familial retinal arterial tortuosity (fRAT) in the three-dimensional structure of retinal capillaries. PATIENTS AND METHODS: Retrospective observational study. Twelve eyes of six patients (two of whom were brothers) were imaged by optical coherence tomography angiography (OCTA). The data from their ocular and systemic examinations were recorded. RESULTS: OCTA imaging clearly showed increased tortuosity of second- and third-order retinal arteries in all cases, visible in the superficial vascular plexus (SVP) up to the arteriole termination in the capillaries. No change was visible in the deep capillary plexus (DCP). CONCLUSIONS: OCTA shows that fRAT affects all the course of the arterioles up to the capillaries in the SVP. The DCP does not show arteriolar tortuosity because it does not contain arterioles. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:397-401.].

Association Between Vessel Density and Visual Acuity in Patients With Diabetic Retinopathy and Poorly Controlled Type 1 Diabetes.

Importance: Capillary dropout is a hallmark of diabetic retinopathy, but its role in visual loss remains unclear. Objective: To examine how macular vessel density is correlated with visual acuity (VA) in patients younger than 40 years who have type 1 diabetes without macular edema but who have diabetic retinopathy requiring panretinal photocoagulation. Design, Settings, and Participants: Retrospective cohort study of VA and optical coherence tomography angiography data collected from consecutive patients during a single visit to Lariboisière Hospital, a tertiary referral center in Paris, France. The cohort included 22 eyes of 22 patients with type 1 diabetes without macular edema but with bilateral rapidly progressive diabetic retinopathy that was treated with panretinal photocoagulation between August 15, 2015, and December 30, 2016. Eyes were classified into 2 groups by VA: normal (logMAR, 0; Snellen equivalent, 20/20) and decreased (logMAR, >0; Snellen equivalent, <20/20). The control group included 12 eyes from age-matched healthy participants with normal vision. Main Outcomes and Measures: Visual acuity and mean vessel density in 4 retinal vascular plexuses: the superficial vascular plexus and the deep capillary complex, which comprises the intermediate capillary plexus and the deep capillary plexus. Results: Of the 22 participants, 11 (50%) were men, mean (SD) age was 30 (6) years, and mean (SD) hemoglobin A1c level was 8.9% (1.6%). Of the 22 eyes with diabetic retinopathy, 13 (59%) had normal VA and 9 (41%) had decreased VA (mean [SD]: logMAR, 0.12 [0.04]; Snellen equivalent, 20/25). Mean [SE] vessel density was lower for eyes with diabetic retinopathy and normal VA compared with the control group in the superficial vascular plexus (44.1% [0.9%] vs 49.1% [0.9%]; difference, -5.0% [1.3%]; 95% CI, -7.5% to -2.4%; P < .001), in the deep capillary complex (44.3% [1.2%] vs 50.6% [1.3%]; difference, -6.3% [1.8%]; 95% CI, -9.9% to -2.7%; P = .001), in the intermediate capillary plexus (43.8% [1.2%] vs 49.3% [1.2%]; difference, -5.5% [1.7%]; 95% CI, -9.0% to -2.0%; P = .003), and in the deep capillary plexus (24.5% [1.0%] vs 30.5% [1.0%]; difference, -6.1% [1.4%]; 95% CI, -8.9% to -3.2%; P < .001). Mean vessel density was lower in eyes with diabetic retinopathy and decreased VA compared with eyes with diabetic retinopathy and normal VA; the mean (SE) loss was more pronounced in the deep capillary complex (34.6% [1.5%] vs 44.3% [1.2%]; difference, -9.6% [1.9%]; 95% CI, -13.6% to -5.7%; P < .001), especially in the deep capillary plexus (15.2% [1.2%] vs 24.5% [1.0%]; difference, -9.3% [1.5%]; 95% CI, -12.4% to -6.1%; P < .001), than in the superficial vascular plexus (39.6% [1.1%] vs 44.1% [0.9%]; difference, -4.5% [1.4%]; 95% CI, -7.3% to -1.7%; P = .002). Conclusions and Relevance: These data suggest that in patients with type 1 diabetes without macular edema but with severe nonproliferative or proliferative diabetic retinopathy, decreased VA may be associated with the degree of capillary loss in the deep capillary complex.

ACUTE PSEUDOPHAKIC CYSTOID MACULAR EDEMA IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study macular capillary changes and vessel density in acute pseudophakic cystoid macular edema (PCME) before and after treatment using optical coherence tomography angiography. METHODS: Retrospective observational case-control study of seven consecutive patients (eight eyes) with PCME and eight age-matched control eyes imaged with optical coherence tomography angiography (RTVue XR Avanti; Optovue, Inc, Fremont, CA) using Projection Removal Artifacts software. Vessel density was calculated. RESULTS: The mean time to diagnosis of PCME was 2.3 ± 0.9 months after surgery. At initial examination, the superficial capillary plexus pattern was near-normal in all PCME eyes, although it was attenuated in the deep capillary plexus. The mean vessel density of the superficial capillary plexus in PCME eyes was slightly but significantly lower than in control eyes (47.8 ± 3.8% vs. 52.9 ± 4.0%, P = 0.01), the difference being greater in the deep capillary plexus (44.1 ± 7.4% vs. 54.2 ± 3.2%, P = 0.007). After resolution of the edema, the deep capillary plexus completely recovered its normal pattern and the vessel density in both plexuses was no longer different from that observed in control eyes. CONCLUSION: Macular vessel density after resolution of an acute PCME did not differ from that of normal control eyes in both the superficial capillary plexus and deep capillary plexus, unlike macular edema in retinal vaso-occlusive diseases.

Three Different Optical Coherence Tomography Angiography Measurement Methods for Assessing Capillary Density Changes in Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: To compare capillary density (CD) changes assessed by optical coherence tomography angiography (OCTA) during diabetic retinopathy (DR) progression using three previously published methods: binarization, skeletonization, and automated flow density (AFD). PATIENTS AND METHODS: Retrospective study of 98 eyes of 74 patients with diabetes and 18 control eyes imaged using OCTA. The macular CD at each stage of DR was assessed using the three methods and were compared to control eyes. RESULTS: AFD was the only method that detected differences between controls and severe nonproliferative DR eyes. The three methods showed a significant difference in CD between controls and eyes with proliferative DR, except for the "fovea" area. CONCLUSION: Only one of the three methods allowed for the detection of changes from the normal capillary density as early as at the "severe nonproliferative DR" stage due to several refinements from the basic technique. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:378-384.].

Comparing Parafoveal Cone Photoreceptor Mosaic Metrics in Younger and Older Age Groups Using an Adaptive Optics Retinal Camera.

BACKGROUND AND OBJECTIVE: To analyze cone mosaic metrics on adaptive optics (AO) images as a function of retinal eccentricity in two different age groups using a commercial flood illumination AO device. PATIENTS AND METHODS: Fifty-three eyes of 28 healthy subjects divided into two age groups were imaged using an AO flood-illumination camera (rtx1; Imagine Eyes, Orsay, France). A 16° × 4° field was obtained horizontally. Cone-packing metrics were determined in five neighboring 50 µm × 50 µm regions. Both retinal (cones/mm2 and µm) and visual (cones/degrees2 and arcmin) units were computed. RESULTS: Results for cone mosaic metrics at 2°, 2.5°, 3°, 4°, and 5° eccentricity were compatible with previous AO scanning laser ophthalmoscopy and histology data. No significant difference was observed between the two age groups. CONCLUSIONS: The rtx1 camera enabled reproducible measurements of cone-packing metrics across the extrafoveal retina. These findings may contribute to the development of normative data and act as a reference for future research. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:45-50.].

CORRELATION BETWEEN CYSTOID SPACES IN CHRONIC DIABETIC MACULAR EDEMA AND CAPILLARY NONPERFUSION DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study the relationship between the location of cystoid spaces and retinal capillary nonperfusion areas in diabetic cystoid macular edema (DCME). METHODS: In this retrospective study, 24 eyes of 21 patients with chronic DCME were followed using optical coherence tomography angiography. The capillary density of the superficial capillary plexus and deep capillary plexus was measured using AngioAnalytics software in all DCME eyes and in 20 healthy controls. Diabetic cystoid macular edema improved spontaneously or after treatment in 11 eyes. RESULTS: The intraretinal cystoid spaces were surrounded by capillary-flow void areas in the superficial capillary plexus in 71% of cases and in the deep capillary plexus in 96% of cases. The deep capillary plexus had lost its regular pattern in all cases. The capillary density was decreased in both plexus (mean decrease of -23.0% in the superficial capillary plexus and -12.4% in the deep capillary plexus vs. normal). In the 11 cases with DCME resolution, the capillary did not reperfuse in areas of resolved cystoid spaces, and the capillary density did not change significantly. CONCLUSION: In chronic DCME, cystoid spaces were located within capillary dropout areas. No reperfusion occurred after DCME resolution. The impact of the severity of this nonperfusion on the risk of recurrence of DCME remains to be clarified.

Symmetry in early response to intravitreal ranibizumab in bilateral diabetic macular oedema.

PURPOSE: To study the symmetry in response to bilateral diabetic macular oedema (DME) treated with bilateral intravitreal injections of ranibizumab (IVR). METHODS: The charts of 36 eyes of 18 patients treated with a loading dose of three monthly IVR in both eyes were retrospectively reviewed. Favourable anatomical response was defined as a decrease by more than 10% in baseline central macular thickness (CMT), and favourable functional response was defined as an increase in visual acuity (VA) ≥5 letters. A symmetric response was defined as a similar anatomical and/or functional response in the first (FE) and second (SE) treated eyes. RESULTS: The VA improved significantly after ranibizumab treatment in both eyes (p < 0.01). A statistically significant positive correlation was found for the functional response to ranibizumab between the FE and the SE (R(2)  = 0.26, p = 0.03). The mean CMT decreased significantly in both eyes (p < 0.01). A strong positive correlation was observed between the anatomical response to ranibizumab in the FE and the SE (R(2)  = 0.37, p = 0.01). Symmetric favourable anatomical and functional responses were observed in 13 patients (72%). In two additional patients, an asymmetric functional response was observed despite a decrease in retinal thickness in both eyes. CONCLUSION: Symmetric anatomical and functional responses were observed in 72% of patients with DME after three initial IVR in each eye. This finding could be of clinical interest in the decision to treat the fellow eye, in a disease where a bilateral involvement is frequent.

Relevance of Retinal Thickness Changes in the OCT Inner and Outer Rings to Predict Progression to Clinical Macular Edema: An Attempt of Composite Grading of Macular Edema.

PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were included in a 12-month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used. A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield is the best predictor for the development of clinical macular edema, with 85.7% sensitivity and 71.9% specificity (OR: 2.57, 95% CI: 0.82-7.99). However, the involvement of the inner and outer rings is a cumulative predictor of progression to clinical macular edema (OR: 8.69, 95% CI: 2.85-26.52). CONCLUSIONS: A composite OCT grading of macular edema taking into account the retinal thickness changes in the inner and outer macular rings offers a simple way to characterize macular edema, with added clinical value.

Efficacy of dexamethasone intravitreal implant for the treatment of diabetic macular edema.

PURPOSE: To assess the efficacy of a single dexamethasone intravitreal implant (Dex-I) injection for the treatment of diabetic macular edema (DME). METHODS: This was a retrospective chart review of 39 eyes (34 consecutive patients). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and increase in intraocular pressure (IOP) (gt;24 mm Hg) were analyzed before treatment and 2 and 4 months after injection. RESULTS: Preoperative mean CMT was 559 ± 111 µm and decreased to 338 ± 84 and 477 ± 140 µm 2 and 4 months after injection, respectively. Although all eyes showed a significant decrease in CMT 2 months after injection (p<0.0001), a recurrence of the macular edema was observed 4 months after injection in 79% of eyes. Mean BCVA improvement (logMAR) was 0.13 ± 0.18 (p<0.0001) and 0.07 ± 0.21 (p = 0.049) 2 and 4 months after injection, respectively, without significant difference between vitrectomized and nonvitrectomized eyes. Eight eyes (21%) developed reversible increase in IOP 2 months after injection. CONCLUSIONS: Thirty percent of DME eyes had gained more than 2 logMAR lines 2 months after Dex-I injection and safety was good. Visual acuity gain was maintained 4 months after injection despite a recurrence of edema in most cases.

Correlation between ganglion cell layer thinning and poor visual function after resolution of diabetic macular edema.

PURPOSE: To assess the thickness of the ganglion cell-inner plexiform layer (GCIPL) in eyes with resolved diabetic macular edema (DME), using spectral-domain optical coherence tomography (SD-OCT), and its relationship with the visual function. METHODS: This retrospective observational case-control cohort study included eyes of diabetic patients with resolved DME (r-DME eyes), that is, normal central macular thickness (CMT) after treatment of DME, and eyes of aged-matched diabetic patients without maculopathy (no-DME eyes). The GCIPL thickness was measured on a macular cube SD-OCT scan using a specific automatic segmentation algorithm. Linear regression analyses were performed to determine the association between the GCIPL thickness and the visual acuity (VA) measured at the time of the OCT measurement. RESULTS: Average GCIPL thickness was reduced in r-DME eyes compared with no-DME eyes (74 ± 14 µm versus 83.2 ± 6 µm, P = 0.0189), whereas no significant difference in mean CMT was observed (260.0 ± 34 µm versus 265.7 ± 22 µm, P = 0.847). Visual acuity significantly correlated with the average GCIPL thickness (r = 0.8, P < 0.0001) and minimum GCIPL thickness (r = 0.84, P < 0.0001) in r-DME eyes. CONCLUSIONS: Despite favorable anatomic response and restoration of a CMT in the range of normal values after resolution of DME, the GCIPL thickness in r-DME eyes was lower than that in no-DME eyes and correlated with the VA. These results suggest that inner retinal alterations occurring in patients with DME and diabetic retinopathy may lead to visual deficiency persisting after treatment.

Exudate detection in color retinal images for mass screening of diabetic retinopathy.

The automatic detection of exudates in color eye fundus images is an important task in applications such as diabetic retinopathy screening. The presented work has been undertaken in the framework of the TeleOphta project, whose main objective is to automatically detect normal exams in a tele-ophthalmology network, thus reducing the burden on the readers. A new clinical database, e-ophtha EX, containing precisely manually contoured exudates, is introduced. As opposed to previously available databases, e-ophtha EX is very heterogeneous. It contains images gathered within the OPHDIAT telemedicine network for diabetic retinopathy screening. Image definition, quality, as well as patients condition or the retinograph used for the acquisition, for example, are subject to important changes between different examinations. The proposed exudate detection method has been designed for this complex situation. We propose new preprocessing methods, which perform not only normalization and denoising tasks, but also detect reflections and artifacts in the image. A new candidates segmentation method, based on mathematical morphology, is proposed. These candidates are characterized using classical features, but also novel contextual features. Finally, a random forest algorithm is used to detect the exudates among the candidates. The method has been validated on the e-ophtha EX database, obtaining an AUC of 0.95. It has been also validated on other databases, obtaining an AUC between 0.93 and 0.95, outperforming state-of-the-art methods.

Influence of pulse pressure and spontaneous variations of macular thickness in patients with diabetic macular oedema.

PURPOSE: To study spontaneous variations of central macular thickness (CMT) and its relation to blood pressure (BP) in patients with diabetic macular oedema (DME). METHODS: 23 diabetic patients presenting with DME with a CMT ≥ 260 µm on optical coherence tomography (OCT-3, Carl Zeiss Meditec, CA) were followed every 2 weeks for 3 months. At baseline, ambulatory 24H-BP monitoring (ABPM) was performed, as well as five CMT measurements (9 am, 12 am, 3 pm, 6 pm and 9 am the day after). During follow-up, BP and CMT were simultaneously measured at 9 am. RESULTS: Significant spontaneous variations in CMT (at least one change in CMT greater than 11% compared to the median CMT value) were observed over 3 months in 48% of patients. Mean CMT decreased over the day and increased during the night, but not significantly (p = 0.1). During the 6 visits, the CMT at 9 am positively correlated with the pulse pressure (PP) measured at the same time (r = 0.29, p = 0.0008). In addition, the mean 24H-CMT was positively correlated with the mean 24H- PP (r = 0.48, p = 0.02). CONCLUSION: Significant spontaneous changes in CMT of patients with DME were observed in nearly half of cases over 3 months. Retinal thickness was correlated to PP levels (patients with higher CMT had higher PP levels). This high variability of macular oedema, and the influence of BP on retinal thickness, should be taken into consideration by practitioners when evaluating the benefit of a therapy in DME.

Decreased retinal sensitivity after internal limiting membrane peeling for macular hole surgery.

AIMS: To compare the retinal sensitivity and frequency of microscotomas found by spectral domain optical coherence tomography (SD-OCT) combined with scanning laser ophthalmoscopy (SLO) microperimetry after idiopathic macular hole closure, in eyes that underwent internal limiting membrane (ILM) peeling and eyes that did not. METHODS: This was a retrospective, non-randomised, comparative study. Combined SD-OCT and SLO microperimetry was performed in 16 consecutive eyes after closure of an idiopathic macular hole. A customised microperimetry pattern with 29 measurement points was used. The ILM was peeled in 8/16 eyes. The main outcome measure was mean retinal sensitivity. RESULTS: Mean retinal sensitivity (in dB) was lower after peeling: 9.80 ± 2.35 dB with peeling versus 13.19 ± 2.92 without (p=0.0209). Postoperative microscotomas were significantly more frequent after ILM peeling: 11.3 ± 6.6 points with retinal sensitivity below 10 dB in eyes that underwent peeling versus 2.9 ± 4.6 in those that did not (p=0.0093). CONCLUSIONS: These results suggest that ILM peeling may reduce retinal sensitivity, and significantly increase the incidence of microscotomas. Until a prospective trial confirming or not these results, it seems justified to avoid peeling the ILM when its potential benefit seems minor or unproved, and when peeling is carried out, to limit the surface peeled to the bare minimum.

A multiple-instance learning framework for diabetic retinopathy screening.

A novel multiple-instance learning framework, for automated image classification, is presented in this paper. Given reference images marked by clinicians as relevant or irrelevant, the image classifier is trained to detect patterns, of arbitrary size, that only appear in relevant images. After training, similar patterns are sought in new images in order to classify them as either relevant or irrelevant images. Therefore, no manual segmentations are required. As a consequence, large image datasets are available for training. The proposed framework was applied to diabetic retinopathy screening in 2-D retinal image datasets: Messidor (1200 images) and e-ophtha, a dataset of 25,702 examination records from the Ophdiat screening network (107,799 images). In this application, an image (or an examination record) is relevant if the patient should be referred to an ophthalmologist. Trained on one half of Messidor, the classifier achieved high performance on the other half of Messidor (A(z)=0.881) and on e-ophtha (A(z)=0.761). We observed, in a subset of 273 manually segmented images from e-ophtha, that all eight types of diabetic retinopathy lesions are detected.