Diabetic retinopathy (DR) is the most common microangiopathic complication of diabetes mellitus, representing a major cause of visual impairment in developed countries. Proliferative DR (PDR) ...represents the last stage of this extremely complex retinal disease, characterized by the development of neovascularization induced by the abnormal production and release of vascular endothelial growth factor (VEGF). The term VEGF includes different isoforms; VEGF-A represents one of the most important pathogenic factors of DR. Anti-VEGF intravitreal therapies radically changed the outcome of DR, due to combined anti-angiogenic and anti-edematous activities. Nowadays, several anti-VEGF molecules exist, characterized by different pharmacological features and duration. With respect to PDR, although anti-VEGF treatments represented a fundamental step forward in the management of this dramatic complication, a big debate is present in the literature regarding the role of anti-VEGF as substitute of panretinal photocoagulation or if these two approaches may be used in combination. In the present review, we provided an update on VEGF isoforms and their role in DR pathogenesis, on current anti-VEGF molecules and emerging new drugs, and on the current management strategies of PDR. There is an overall agreement regarding the relative advantage provided by anti-VEGF, especially looking at the management of PDR patients requiring vitrectomy, with respect to laser. Based on the current data, laser approaches might be avoided when a perfectly planned anti-VEGF therapeutic strategy can be adopted. Conversely, laser treatment may have a role for those patients unable to guarantee enough compliance to anti-VEGF injections.
Key messages
VEGF increased production, stimulated by retinal hypoperfusion and ischaemia, is a major pathogenic factor of neovascular complication onset in diabetic retinopathy and of DR stages progression.
Nowadays, several anti-VEGF molecules are available in clinical practice and other molecules are currently under investigation. Each anti-VEGF molecule is characterized by different targets and may interact with multiple biochemical pathways within the eye.
All the data agreed in considering anti-VEGF molecules as a first line choice for the management of diabetic retinopathy. Laser treatments may have a role in selected advanced cases and for those patients unable to guarantee enough compliance to intravitreal treatments schemes.
Abstract
Optical coherence tomography angiography (OCTA) provides several data regarding the status of retinal capillaries. This information can be further enlarged by employing quantitative metrics, ...such as vessel density (VD). A mandatory preliminary step of OCTA quantification is image binarization, a procedure used to highlight retinal capillaries on empty background. Although several binarization thresholds exist, no consensus is reached about the thresholding technique to be used. In this study, we tested thirteen binarization thresholds on a dataset made by thirty volunteers. The aim was to assess the impact of binarization techniques on: (I) detection of retinal capillaries, assessed by the calculation of overlapping percentages between binarized and original images; (II) quantitative OCTA metrics, including VD, vessel tortuosity (VT) and vessel dispersion (Vdisp); (III) foveal avascular zone (FAZ) detection. Our findings showed Huang, Li, Mean and Percentile as highly reliable binarization thresholds (p < 0.05), whereas the worst binarization thresholds were Intermodes, MaxEntropy, RenylEntropy and Yen (p < 0.05). All the thresholds variably underestimated VD metric and FAZ detection, with respect to the original OCTA images, whereas VT and Vdisp turned out to be more stable. The usage of a Fixed threshold resulted extremely useful to reduce VD and FAZ underestimations, although bound to operators’ experience.
Purpose
Extended depth-of-focus (EDOF) is a promising intraocular lens (IOL) technology for cataract surgery. The aim of the study was to report the real-life experience related to the implant of ...EDOF AcrySof® IQ Vivity® (Alcon Inc., USA) IOL.
Methods
The study was designed as a interventional, prospective, case series with 3 months of follow-up. Patients needing cataract surgery, without any other kind of ocular diseases, were recruited and implanted with AcrySof® IQ Vivity® IOL. We evaluated the refractive success of this IOL through complete ophthalmologic assessments and the administration of the Quality of Vision test. The main outcome measures were the refractive outcome; far, intermediate, and near vision; and Quality of Vision score.
Results
We included 108 eyes (54 patients; age 62 ± 5 years). Intra-operative and post-operative complications were 0%. Thirty out of 100 eyes (28%) required toric IOL. Best-corrected visual acuity improved from 0.4 ± 0.3 LogMAR to 0.0 ± 0.0 LogMAR (
p
< 0.01). Refractive outcome was very good for far and intermediate visions, whereas a spherical addition of at least + 1.0D was required for near vision. The mean Quality of Vision score was of 15.5 ± 6.5. The most complained visual disturbances were haloes and glares, although resulting well-tolerated. Dynamic pupillometry findings well-correlated with the amount of complained post-operative visual discomforts.
Conclusions
AcrySof® IQ Vivity® IOL is a well-tolerated choice to correct far and intermediate vision. Spectacles are needed to optimize near vision. Our data strongly suggest dynamic pupillometry as a useful investigation to optimize post-operative refractive success.
The management of exudative retinal diseases underwent a revolution due to the introduction of intravitreal treatments. There are two main classes of intravitreal drugs, namely anti-vascular ...endothelial growth factors (anti-VEGF) and corticosteroids molecules. The clinical course and the outcome of retinal diseases radically changed thanks to the efficacy of these molecules in determining the regression of the exudation and the restoration of the macular profile. In this review, we described the molecular features of classic retinal drugs, highlighting the main therapeutic targets, and we provided an overview of new emerging molecules. We performed a systematic review of the current literature available in the MEDLINE library, focusing on current intravitreal molecules and on new emerging therapies. The anti-VEGF molecules include Bevacizumab, Pegaptanib, Ranibizumab, Aflibercept, Conbercept, Brolucizumab, Abicipar-pegol and Faricimab. The corticosteroids approach is mainly based on the employment of triamcinolone acetonide, dexamethasone and fluocinolone acetonide molecules. Many clinical trials and real-life reports demonstrated their efficacy in exudative retinal diseases, highlighting differences in terms of molecular targeting and pharmacologic profiles. Furthermore, several new molecules are currently under investigation. Intravitreal drugs focus their activity on a wide range of therapeutic targets and are safe and efficacy in managing retinal diseases.
Retinal microaneurysms (MAs) are among the earliest signs of diabetic retinopathy (DR) and are typically detected by fluorescein angiography (FA). Confocal MultiColor is a noninvasive-imaging ...technique able to analyze different retinal features by capturing three simultaneous reflectance images. The main aim of the present study was to characterize morphological features of MAs by means of MultiColor images and to compare these with spectral domain optical coherence tomography (SD-OCT) and FA findings.
A cross-sectional, observational study setting was chosen. Multimodal imaging included MultiColor, SD-OCT and FA images. We performed a qualitative analysis in order to assess the relationship between MultiColor and its green- and red-reflectance components, SD-OCT (hyperreflective, hyporeflective and mixed reflectivity) and FA findings. MAs detected on our MultiColor images were then categorized in accordance with a previously published histological classification.
In our study FA images were used to detect 153 MAs in 30 eyes displaying DR. MultiColor was able to distinguish 122 MAs (80%). We identified green (16%), red (19%), and mixed (65%) MAs, corresponding to different reflectivity features detected by SD-OCT. MAs not visualized on MultiColor images corresponded to tiny hyperreflective lesions on SD-OCT. We compared our imaging findings with a histological MA classification reported in the literature. Our findings showed a strict relationship between MA subtypes and SD-OCT, suggesting that the composition of MAs (cells + endothelium + fibrosis) may influence the signal detected in MultiColor images.
MultiColor appears to be a useful technique for investigating MA features in patients with DR.
To evaluate vascular abnormalities at superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris (CC) in patients with Best vitelliform macular dystrophy (BVMD) by means of optical ...coherence tomography angiography (OCT-A).
Cross-sectional case series.
Sixty-six eyes of 33 patients with BVMD (16 male) and 33 controls were consecutively enrolled. Patients were subdivided into classic stages and underwent best-corrected visual acuity (BCVA), fundus autofluorescence and spectral domain-optical coherence tomography, and 4.5 × 4.5-mm swept-source OCT-A. Choroidal neovascularization (CNV) and capillary dilations were qualitatively assessed by 2 masked ophthalmologists. Each OCT-A slab was imported into ImageJ 1.50 and digitally binarized for quantitative analyses. Foveal avascular zone (FAZ) area was measured manually; vessel density was then quantified after the exclusion of the FAZ pixels. Eyes classified as stages 3 and 4 were evaluated together.
Nineteen eyes (28.8%) revealed capillary dilations at DCP, 15 of which were in stages 1 and 2. Interestingly, CNV was detected in 24 eyes (36.4%). Quantitative analysis disclosed that stages 3–4 and 5 carry significant impairment at both SCP (P < .0001 and P = .02, respectively) and DCP (P < .0001 and P = .0004, respectively) compared to controls. FAZ area was enlarged at the DCP (P = .001). Only DCP vessel density significantly correlated with the stage and BCVA.
Patients with BVMD show significant vascular impairment at both superficial and deep retinal plexuses, correlating with functional outcomes. These findings, especially at DCP, may improve our understanding about the pathogenesis, and may help in predicting BVMD treatment efficacy.
AimTo describe the optical coherence tomography angiography (OCT-A) features of patients affected by acute macular neuroretinopathy (AMN).Methods This is a prospective, observational, cross-sectional ...study. Multimodal imaging, including spectral domain OCT (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany) and 6×6 mm swept source OCT-A (ZEISS PLEX Elite 9000; ZEISS, Dublin, California), was performed on all patients. The primary outcome measure was assessment of the vascular alterations of the superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris (CC). A segmentation of the AMN lesions using enface OCT images of photoreceptors-retinal pigment epithelium complex was used to discriminate intralesional and extralesional regions on the OCT-A enface slabs of the DCP and CC reconstructions. Each OCT-A slab was imported into ImageJ V.1.50 and digitally binarised for quantitative analyses.ResultsOverall, seven patients (mean age 19.4±3.2 years, six women) affected by AMN were included. The mean best-corrected visual acuity was 0.00±0.00 logarithm of the minimum angle of resolution. Twelve healthy age-matched subjects (mean age 22±3.4 years, 10 women) represented the control group. The quantitative analysis of global vessel densities showed that the CC vessel density was significantly lower in patients with AMN (0.495±0.03) compared with the age-matched controls (0.545±0.02) (corrected p=0.0003). The intralesional vessel density of the DCP was 0.349±0.04 in AMN and vs 0.497±0.02 in the controls (corrected p=0.0002).ConclusionsOur study confirmed inner choroidal vascular flow void as a possible pathogenetic mechanism of AMN. We also found a focal impairment of the DCP within the AMN lesions. Future studies are needed to clarify which is the primary location of the vascular insult in this condition.
To compare clinical and imaging characteristics of extensive macular atrophy with pseudodrusen-like appearance (EMAP) versus diffuse-trickling geographic atrophy (DTGA) and non-diffuse-trickling ...geographic atrophy (nDTGA) phenotypes of age-related macular degeneration. Prospective, observational study performed in the Ophthalmology Department of IRCCS San Raffaele Hospital between January 2015 and January 2021. Patients examination included fundus autofluorescence (FAF) and optical coherence tomography at baseline and follow-up visits. We measured subfoveal choroidal thickness (SCT), Sattler/choroid ratio (SCR), choroidal vascularity index and ellipsoid zone disruption distance on OCT scans. We calculated progression rates and circularity of the atrophic lesions on FAF images. These variables were compared between the three groups and correlations with progression rates and visual acuity were assessed. Sixty-three eyes from 63 patients were included: 18 with EMAP, 18 with DTGA and 27 with nDTGA. Mean follow-up was 3.73 ± 2.12 years. EMAP and DTGA shared a faster progression, lower circularity and SCR, and higher EZ disruption distance than nDTGA, while SCT and CVI were similar between the three groups. Baseline circularity and SCR correlated with progression rates. EMAP and DTGA show similar OCT and FAF characteristics, which differ from nDTGA.
Optical coherence tomography (OCT) angiography (OCTA) is a non-invasive tool for the in-vivo study of the intraretinal vascular network. It is based on the analysis of motion particles within the ...retina to reconstruct the paths followed by the erythrocytes, i.e. retinal capillaries. To date, qualitative and quantitative information are based on the morphological features disclosed by retinal capillaries. In the present study, we proposed new quantitative functional metrics, named Total Flow Intensity (TFI), Active Flow Intensity (AFI), and Volume-related Flow Intensity (VFI), based on the processing of the blood flow signal detected by OCTA. We studied these metrics in a cohort of healthy subjects, and we assessed their clinical utility by including a cohort of age-matched patients affected by Stargardt disease. Moreover, we compared TFI, AFI, and VFI to the widely used vessel density (VD) parameter. TFI, AFI, and VFI were able to describe in detail the different properties of the retinal vascular compartment. In particular, TFI was intended as the overall amount of volumetric retinal blood flow. AFI represented a selective measure of voxels disclosing blood flow signal. VFI was developed to put in relationship the volumetric blood flow information with the not vascularized retinal volume. In conclusion, TFI, AFI, and VFI were proposed as feasible functional OCTA biomarkers based on the analysis of retinal blood flow signal.
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