• DME
• Diabetic macular edema
• ILM peeling
• fundus autofluorescence
• subfoveal injection
• vitrectomy

• Humans
• Vitrectomy/methods
• Diabetic Retinopathy/surgery
• Diabetic Retinopathy/diagnosis
• Diabetic Retinopathy/therapy
• Diabetic Retinopathy/drug therapy
• Retrospective Studies
• Macular Edema/surgery
• Macular Edema/diagnosis
• Macular Edema/therapy
• Macular Edema/drug therapy
• Male
• Female
• Middle Aged
• Fluorescein Angiography
• Visual Acuity/physiology
• Basement Membrane/surgery
• Aged
• Fundus Oculi
• Tomography, Optical Coherence
• Sodium Chloride/administration & dosage
• Retinal Pigment Epithelium/pathology
• Fovea Centralis
• Acetates
• Drug Combinations
• Minerals

• center-involving diabetic macular edema
• clinically significant macular edema
• diabetic macular edema
• diabetic retinopathy
• disorganization of retinal inner layers
• fluorescein angiography
• fluorescein leakage
• fundus autofluorescence
• hard exudates
• hyperreflective foci
• optical coherence tomography
• optical coherence tomography angiography
• photoreceptor damage
• vascular hyperpermeability

• Anti-VEGF
• Best-corrected visual acuity
• Central macular thickness
• Diabetic macular edema

• Tasmanian Community Fund Tasmanian Community Fund
• GNT1116360 National Health and Medical Research Council (NHMRC) Australia Centre for Research Excellence
• Royal Hobart Hospital Research Foundation Royal Hobart Hospital Research Foundation
• Diabetes Tasmania Post graduate research scholarship Diabetes Tasmania Post graduate research scholarship
• Patricia F Gordon Top Up Scholarship Patricia F Gordon Top Up Scholarship
• Gerald Harvey Senior Research Fellowship Gerald Harvey Senior Research Fellowship
• Williams Oncology Royal Hobart Hospital Research Foundation Grant Williams Oncology Royal Hobart Hospital Research Foundation Grant

• macular degeneration
• retinal diseases

• Adult
• Aged
• Aged, 80 and over
• Ependymoglial Cells/pathology
• Female
• Fovea Centralis
• Glaucoma/surgery
• Humans
• Male
• Middle Aged
• Retinal Cone Photoreceptor Cells/pathology
• Retinal Detachment/diagnostic imaging
• Retinal Detachment/etiology
• Retinal Detachment/physiopathology
• Retrospective Studies
• Risk Factors
• Tomography, Optical Coherence
• Trabeculectomy/adverse effects
• Vision Disorders/etiology
• Vision Disorders/physiopathology
• Visual Acuity/physiology

To assess changes in reflectivity of the retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) on spectral domain-optical coherence tomography (SD-OCT) images and the effects of reflectivity changes on visual acuity improvement after vitrectomy in macular hole patients.

Twenty-four eyes of 24 patients with idiopathic full-thickness macular hole closed after vitrectomy were retrospectively reviewed. The “plot profile” function of the medical imaging software was used by a single masked physician to analyze RPE, EZ, and ELM reflectivity on OCT images at postoperative 1 month and 12 months.

Absolute and relative EZ reflectivity showed highly significant increases at postoperative 12 months compared to 1 month (p<0.001 and p<0.001, respectively). Absolute and relative EZ reflectivity changes from postoperative month 1 to month 12 after macular hole surgery were significantly correlated with best corrected visual acuity improvement (p=0.012 and p=0.020, respectively).

EZ reflectivity can be a predictor of functional and anatomical improvement after macular hole surgery.

• Absolute and relative reflectivity
• ellipsoid zone reflectivity
• macular hole
• vitrectomy

This paper aimed to present daily-practice recommendations for the management of diabetic macular edema (DME) patients based on available scientific evidence and the clinical experience of the consensus panel.

A group of Spanish retina experts agreed to discuss different aspects related with the clinical management of DME patients.

Panel was mainly focused on therapeutic objectives in DME management; definition terms; and role of biomarkers as prognostic and predictive factors to intravitreal treatment response. The panel recommends to start DME treatment as soon as possible in those eyes with a visual acuity less than 20/25 (always according to the retina unit capacity). Naïve patient was defined, in a strict manner, as a patient who, up to that moment, had never received any treatment. A refractory DME patient may be defined as the one who did not achieve a complete resolution of the disease, regardless of the treatment administered. Different optical coherence tomography biomarkers, such as disorganization of the retinal inner layers, hyperreflective dots, and cysts, have been identified as prognostic factors.

This document has sought to lay down a set of recommendations and to identify key issues that may be useful for the daily management of DME patients.

• biomarkers
• consensus
• diabetes
• diabetic macular edema
• inflammation
• optical coherence tomography

• Diabetes
• Diabetic retinopathy
• Outer retina
• Photoreceptors
• Phototransduction
• RPE
• Vasculature
• Visual cycle

• Diabetes Mellitus
• Diabetic Retinopathy
• Humans
• Photoreceptor Cells
• Retina
• Retinal Pigment Epithelium

• IK6 BX003604 BLRD VA
• R01 EY022938 NEI NIH HHS
• R01 EY033002 NEI NIH HHS
• R24 EY024864 NEI NIH HHS

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy, affecting 1 in 15 patients with diabetes mellitus (DM). The disruption of the inner blood-retina barrier (BRB) has been largely investigated and attributed the primary role in the pathogenesis and progression in DME, but there is increasing evidence regarding the role of outer BRB, separating the RPE from the underlying choriocapillaris, in the occurrence and evolution of DME. The development of novel imaging technologies has led to major improvement in the field of in vivo structural analysis of the macula allowing us to delve deeper into the pathogenesis of DME and expanding our vision regarding this condition. In this review we gathered the results of studies that investigated specific outer BRB optical coherence tomography parameters in patients with DM with the aim to outline the current status of its role in the pathogenesis and progression of DME and identify new research pathways contributing to the advancement of knowledge in the understanding of this condition.

• Diabetic macular edema
• External limiting membrane
• Hyperreflective foci
• Inner segment/outer segment line
• Optical coherence tomography
• Outer retinal barrier

• Diabetic macular edema
• aflibercept
• optical coherence tomography
• predictive
• ranibizumab

Quantitative assessment of vascular density (VD) of retinal and choriocapillaris (CC) in various stages of diabetic retinopathy (DR) using spectral domain optical coherence tomography angiography (SD OCTA).

188 eyes of 97 participants were recruited in this cross-sectional study. The macular OCTA (3x3mm) scan was performed and the computer algorithm assessed VD at the level of superficial capillary plexus (SCP), deep capillary plexus (DCP) and CC.

All measured parameters were decreased in retinal VD at the more extreme stages of DR, with the exception of SCP foveal VD. There was a constant pattern of decrease in VD of CC from normal cases to cases of NDR and NPDR and then a slight increase occurred in the PDR stage but never touching the normal quantities. Age, fasting blood sugar, and years of diabetes mellitus were correlated with reduced VD in different segments. Multivariate linear regression analysis showed that best-corrected visual acuity (BCVA) was positively correlated with parafoveal VD at SCP and VD of foveal area at CC. VD of all subfields of macular area except foveal DCP VD showed reduced levels in diabetic macular edema (DME) patients compared to those without DME.

The findings of the study endorse retina VD changes as a potential biomarker for DR development before retinopathy becomes clinically evident. It seems that parafoveal VD of SCP and foveal VD of CC are good biomarkers to predict VA in the diabetic patients.

• Capillary plexus
• Choriocapillaris
• Diabetes
• Diabetic retinopathy
• Optical coherence tomography angiography
• Vascular density

• Anti-VEGF
• Diabetic macular edema
• Interdigitation and ellipsoid zones

To describe cystoid macular degeneration (CMD), which has no clear definition in diabetic macular edema (DME), and examine its features in optical coherence tomography (OCT) and fundus fluorescein angiography (FFA).

This study was conducted using OCT images of patients who were followed in Gazi University between November 2011 and March 2015. A total of 259 eyes (187 patients) found to have cystic changes on OCT were included. Macular ischemia, peripheral ischemia, and type of edema were identified on FFA. Vitreomacular interface abnormalities, foveal contour integrity, internal reflectivity of the cysts, and outer retinal layer defects were analyzed from OCT images. The horizontal and vertical diameters of the largest cyst within 1000 μm of the foveal center were measured for the definition of CMD. Cut-offs for these values were determined by receiver operating characteristic curve analysis. Cystoid macular edema (CME) and CMD groups were created and their characteristics were analyzed.

The horizontal and vertical diameters of the largest cyst were moderately positively correlated with visual acuity (rs=0.349, r=0.419, respectively). Eyes with horizontal diameter of the largest cyst ≥450 μm were classified as CMD; in this group, sensitivity in the prediction of visual acuity ≤20/60 was 58%. Eyes with horizontal diameter of the largest cyst <450 μm were classified as CME; in this group, specificity in the prediction of visual acuity >20/60 was 73%. For the threshold of 300 μm determined for vertical diameter of the largest cyst, sensitivity was 62% and specificity was 69%. The CME and CMD groups were formed according to these cut-off values. Compared to the CME group, the CMD group had greater central subfield thickness and higher prevalence of outer retinal damage, severe disruption of foveal contour, macular ischemia, and diffuse/mixed type edema.

In eyes with DME, CMD can be defined as the largest cyst within 1000 μm of the foveal center having a horizontal diameter of ≥450 μm and vertical diameter ≥300 μm, especially if associated with macular ischemia, outer retinal damage, loss of foveal contour, and diffuse/mixed type edema.

• Diabetic macular edema
• diabetic retinopathy
• cystoid macular degeneration
• chronic macular edema
• optical coherence tomography

To quantitatively explore the correlation between optical coherence tomography (OCT) parameters and vision impairment in patients with diabetic macular edema (DME).

This study was a retrospective observational case series. One-hundred eyes from 66 patients with DME were retrospectively included. OCT parameters, including central macular thickness (CMT), height of intraretinal cystoid, subretinal fluid and sponge-like retinal swelling, density of hyperreflective foci (HRF), and integrity of the ellipsoidal zone (EZ), were assessed. Correlation analyses and multiple linear regression analysis were performed to quantitatively explore the relationship between best-corrected visual acuity (BCVA) and OCT parameters.

Among all OCT parameters, CMT, height of intraretinal cystoid, height of sponge-like retinal swelling, and density of HRF and EZ integrity were significantly correlated with BCVA (r = −0.550, −0.526, −0.411, −0.277, and −0.501, respectively; P < 0.01). In multiple linear regression analysis, CMT, density of HRF, and EZ integrity fit a significant linear equation (β = 0.482, 0.184, and 0.447, respectively), with the adjusted R square reaching 0.522 (P < 0.001). In eyes without SRF, the height of intraretinal cystoid, density of HRF, and EZ integrity were included in the model and an adjusted R square of 0.605 (P < 0.001) was obtained.

In DME eyes, OCT parameters, including the density of HRF, the EZ integrity together with CMT, or the height of intraretinal cystoid, could explain 52.2% to 60.5% of the variation in BCVA and were weighted approximately 2 : 1 : 2, respectively.

Anti-VEGF drugs are as the first-line therapies for diabetic macular edema (DME). In this study, we investigated the association between hyperreflective foci in the outer retinal layers and functional efficacy in DME patients who received intravitreal ranibizumab (IVR) injections. We retrospectively reviewed 77 eyes of 71 patients with DME treated with pro re nata IVR injections for at least 12 months. We evaluated how baseline hyperreflective foci in the outer retinal layers on spectral domain optical coherence tomography images were associated with an improvement in logarithm of the minimum angle of resolution visual acuity (logMAR VA) at 12 months. Forty-three eyes with hyperreflective foci in the outer retinal layers had greater VA improvement than 34 eyes without such foci at 12 months. Multivariate analyses demonstrated that both logMAR VA and hyperreflective foci in the outer retinal layers at baseline were associated with VA improvement. Structural analyses revealed that the central subfield thickness was decreased and that the ellipsoid zone of photoreceptors was improved more significantly in eyes with hyperreflective foci in the outer layers than eyes without such lesions. Baseline hyperreflective foci in the outer retinal layers predict the functional efficacy of IVR injections for DME.

• Diabetic macular oedema
• EZ/ELM
• ILM
• SD OCT
• vital dye staining

• Diabetic retinopathy
• Disorganization of inner retinal layer (DRIL)
• Imaging biomarkers
• Macular thickness parameters
• Retinal nerve fiber layer (RNFL) thickness
• Spectral domain optical coherence tomography (SD-OCT)

• Cross-Sectional Studies
• Diabetes Mellitus, Type 2/complications
• Diabetic Retinopathy/pathology
• Diabetic Retinopathy/physiopathology
• Female
• Humans
• Macula Lutea/pathology
• Male
• Middle Aged
• Nerve Fibers/physiology
• Retina/pathology
• Retina/physiopathology
• Tomography, Optical Coherence
• Visual Acuity

• Diabetic macular edema
• Disorganization of the retinal inner layers
• Metamorphopsia
• Spectral-domain optical coherence tomography
• Visual acuity

• Adult
• Aged
• Aged, 80 and over
• Cross-Sectional Studies
• Diabetic Retinopathy/complications
• Diabetic Retinopathy/diagnosis
• Diabetic Retinopathy/physiopathology
• Female
• Fluorescein Angiography/methods
• Follow-Up Studies
• Fundus Oculi
• Humans
• Macular Edema/complications
• Macular Edema/diagnosis
• Macular Edema/physiopathology
• Male
• Middle Aged
• Retinal Ganglion Cells/pathology
• Retrospective Studies
• Severity of Illness Index
• Tomography, Optical Coherence/methods
• Vision Disorders/diagnosis
• Vision Disorders/etiology
• Vision Disorders/physiopathology
• Visual Acuity

• Intravitreal aflibercept
• Plaque brachytherapy
• Radiation maculopathy

• Anti-fumarase antibody
• Autoantibody
• Complement
• Diabetic macular oedema
• Optical coherence tomography
• Photoreceptor damage
• Serum biomarker

• Autoantibodies/immunology
• Diabetic Retinopathy/immunology
• Diabetic Retinopathy/pathology
• Female
• Fumarate Hydratase/immunology
• Humans
• Immunoglobulin G
• Macular Edema/immunology
• Macular Edema/pathology
• Male
• Photoreceptor Cells, Vertebrate/pathology

• P30 DK020572 NIDDK NIH HHS
• P30 EY007003 NEI NIH HHS
• R01 EY020895 NEI NIH HHS

• Ozurdex
• dexamethasone
• macular edema
• retinal vein occlusion
• treatment-resistant
• vitrectomy

Diabetes is known to cause alterations in retinal microvasculature and tissue that progressively lead to visual impairment. Optical coherence tomography (OCT) is useful for assessment of total retinal thickening due to diabetic macular edema (DME). In the current study, we determined associations between visual acuity (VA) and retinal layer thickness, reflectance, and interface disruption derived from enface OCT images in subjects with and without DME.

Best corrected VA was measured and high-density OCT volume scans were acquired in 149 diabetic subjects. A previously established image segmentation method identified retinal layer interfaces and locations of visually indiscernible (disrupted) interfaces. Enface thickness maps and reflectance images of the nerve fiber layer (NFL), combined ganglion cell and inner plexiform layer (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE) were generated in the central macular subfield. The associations among VA and retinal layer metrics were determined by multivariate linear regressions after adjusting for covariates (age, sex, race, HbA1c, diabetes type, and duration) and correcting for multiple comparisons.

In DME subjects, increased GCLIPL and OPL thickness and decreased OSL thickness were associated with reduced VA. Furthermore, increased NFL reflectance and decreased OSL reflectance were associated with reduced VA. Additionally, increased areas of INL and ONL interface disruptions were associated with reduced VA. In subjects without DME, increased INL thickness was associated with reduced VA, whereas in subjects without DME but with previous antivascular endothelium growth factor treatment, thickening of OPL was associated with reduced VA.

Alterations in retinal layer thickness and reflectance metrics derived from enface OCT images were associated with reduced VA with and without presence of DME, suggestive of their potential for monitoring development, progression, and treatment of DME.

Diabetic hyperreflective foci in the outer retinal layers are a clinically relevant finding on optical coherence tomography (OCT) images, although their characteristics remain to be elucidated. Here we investigated the decorrelation signal around hyperreflective foci on OCT angiography (OCTA) images in diabetic retinopathy (DR). We retrospectively reviewed sufficient quality OCTA images from 102 eyes of 66 patients that were obtained using split-spectrum amplitude-decorrelation angiography algorithm. Most confluent hyperreflective foci were randomly deposited or appeared in a radiating array on the en-face structural OCT images in the inner nuclear layer (INL) or Henle’s fiber layer (HFL), respectively. Within the INL, hyperreflective foci were not accompanied by decorrelation signals and attached to capillaries on OCTA images. Decorrelation signals were sometimes delineated in hyperreflective foci in the HFL and other times appeared to be pseudopod-like or wrapping around hyperreflective foci, referred to as reflectance-decorrelated foci. The decorrelation signal intensity of hyperreflective foci in the HFL was associated with logMAR VA (R = 0.553, P < 0.001) and central subfield thickness (R = 0.408, P < 0.001) but not with DR severity. These data suggest that reflectance-decorrelated foci on OCTA images are clinically relevant as well as shed lights on the properties in diabetic hyperreflective foci.

To evaluate the therapeutic efficacy of subretinal BSS injections done during vitrectomy for refractory diabetic macular edema (DME) resistant to other modes of treatment including previous vitrectomy.

A prospective, interventional noncomparative case series in which cases had refractory DME with a central macular thickness (CMT) ≥ 300 μm, despite previous anti-VEGF therapy (ranibizumab or bevacizumab with shifting to aflibercept). Some cases even received intravitreal triamcinolone acetonide injection, before attempting this solution. The study included group 1, surgically naïve eyes, and group 2, cases with persistent edema despite a previous vitrectomy (7 eyes (25%)). The cases were also divided into group a, eyes with normal vitreomacular interface, and group b, with abnormal vitreomacular attachment (VMA) (6 (21.4%)). The 1ry endpoint for this study was the change in CMT after 9–12 months from surgery. The 2ry endpoints were change in BCVA, recurrence of DME, and surgical complications.

The study included 28 eyes, 6 (21.4%) of which suffered from edema recurrence. The mean recorded CMT was 496 ± 88.7 μm and 274.1 ± 31.6 μm preoperatively and postoperatively, respectively. In all eyes, the preoperative mean BCVA in decimal form was 0.2 ± 0.11, which improved significantly to 0.45 ± 0.2. In the end, the CMT of groups 1 and 2 measured 239 μm and 170.8 μm, respectively (p = 0.019). The preoperative BCVA in groups 1 and 2 was 0.16 ± 0.07 and 0.37 ± 0.14, respectively, which improved to a mean of 0.34 ± 0.09 and 0.7 ± 0.16 postoperatively, respectively (p = 0.185).

Vitrectomy with a planned foveal detachment technique was shown to be a promising solution for refractory DME cases with rapid edema resolution. CMT was shown to improve more in eyes where conventional vitrectomy was not attempted. Moreover, cases with VMA resistant to pharmacotherapy was shown to respond well to this technique. The study has been registered in Contact ClinicalTrials.gov PRS Identifier: NCT03345056.

• Cystoid spaces
• Diabetic macular edema
• Hyperreflective foci
• Ranibizumab
• Spectral-domain optical coherence tomography

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors/administration & dosage
• Diabetic Retinopathy/complications
• Diabetic Retinopathy/diagnosis
• Diabetic Retinopathy/drug therapy
• Dose-Response Relationship, Drug
• Female
• Fluorescein Angiography/methods
• Follow-Up Studies
• Fovea Centralis/pathology
• Fundus Oculi
• Humans
• Intravitreal Injections
• Macular Edema/diagnosis
• Macular Edema/drug therapy
• Macular Edema/etiology
• Male
• Middle Aged
• Ranibizumab/administration & dosage
• Retrospective Studies
• Time Factors
• Tomography, Optical Coherence/methods
• Treatment Outcome
• Visual Acuity

• Automated
• Ellipsoid Zone
• Image processing
• Macular edema
• Optical Coherence Tomography
• Retinal vein occlusion

• Diabetic macular edema
• Diabetic retinopathy
• Expert opinion
• Multidisciplinary treatment
• Vascular endothelial growth factor

• Angiogenesis Inhibitors/therapeutic use
• Combined Modality Therapy
• Diabetic Retinopathy/diagnosis
• Diabetic Retinopathy/therapy
• Glucocorticoids/therapeutic use
• Humans
• Laser Coagulation
• Macular Edema/diagnosis
• Macular Edema/therapy
• Vascular Endothelial Growth Factor A/antagonists & inhibitors
• Vitrectomy

• cystoid macular edema
• cystotomy
• diabetic retinopathy
• intraoperative OCT

• Central retinal thickness
• Diabetic macular edema
• Diabetic retinopathy
• Ellipsoid zone
• External limiting membrane
• Implicit time
• Multifocal electroretinogram
• Retinal density of response
• Total macular volume

To evaluate the efficacy and safety of sustained-delivery fluocinolone acetonide (FAc) intravitreal implant for diabetic macular edema (DME).

Prospective study in patients with DME insufficiently responsive to laser and anti-vascular endothelial growth factor (anti-VEGF). Patients with history of rise of intraocular pressure after intravitreal corticosteroids were excluded.

The macular edema rapidly decreased both in group 1 (prior laser only; n=7 eyes) and group 2 (prior laser and ≥3 monthly anti-VEGF therapy; n=10 eyes) and central subfield thickness was reduced by −299 μm (P=0.008) and −251 μm (P=0.016) at 12 months, respectively. Mean area under the curve from baseline to last value for pseudophakic eyes was +4.2 letters in group 1 and +9.5 letters in group 2. Overall, the FAc implant was well tolerated.

This prospective study confirms the efficacy of the FAc implant in DME patients insufficiently responsive to laser and anti-VEGF. Moreover, with a careful patient selection, our safety results would support an earlier use of FAc in the DME treatment pathway.

• corticosteroid intravitreal implant
• diabetic macular edema
• fluocinolone acetonide
• intravitreal corticosteroid

• Autofluorescence
• Diabetic macular edema
• En-face optical coherence tomography
• Microperimetry
• Optical coherence tomography

• Diabetic Retinopathy/complications
• Diabetic Retinopathy/diagnosis
• Fluorescein Angiography
• Fundus Oculi
• Humans
• Macular Edema/diagnosis
• Macular Edema/etiology
• Multimodal Imaging/methods
• Retina/diagnostic imaging
• Tomography, Optical Coherence

• diagnostic study
• diagnostic technique
• retinal disease
• retinal imaging

• Diabetic macular edema
• diabetic retinopathy
• ellipsoid zone
• interdigitation zone
• optical coherence
• tomography

To present a method for image segmentation and generation of enface thickness maps and reflectance images of retinal layers in healthy and diabetic retinopathy (DR) subjects.

High density spectral domain optical coherence tomography (SDOCT) images were acquired in 10 healthy and 4 DR subjects. Customized image analysis software identified 5 retinal cell layer interfaces and generated thickness maps and reflectance images of the total retina (TR), inner retina (IR), outer retina (OR), and the inner segment ellipsoid (ISe) band. Thickness maps in DR subjects were compared to those of healthy subjects by generating deviation maps which displayed retinal locations with thickness below, within, and above the normal 95% confidence interval.

In healthy subjects, TR and IR thickness maps displayed the foveal depression and increased thickness in the parafoveal region. OR and ISe thickness maps showed increased thickness at the fovea, consistent with normal retinal anatomy. In DR subjects, thickening and thinning in localized regions were demonstrated on TR, IR, OR, and ISe thickness maps, corresponding to retinal edema and atrophy, respectively. TR and OR reflectance images showed reduced reflectivity in regions of increased thickness. Hard exudates appeared as hyper-reflective spots in IR reflectance images and casted shadows on the deeper OR and ISe reflectance images. The ISe reflectance image clearly showed the presence of focal laser scars.

Enface thickness mapping and reflectance imaging of retinal layers is a potentially useful method for quantifying the spatial and axial extent of pathologies due to DR.