Diabetic retinopathy, diabetic macular edema, and cardiovascular risk: the importance of a long-term perspective and a multidisciplinary approach to optimal intravitreal therapy

Diabetic retinopathy (DR), diabetic macular edema (DME), and cardiovascular disease (CVD) resulting from vascular damage from persistently elevated blood glucose levels are among the serious secondary pathologies associated with long-standing diabetes mellitus. The established link between DR and CVD suggests the need for appropriate and early management of patients with diabetes to minimize CV risk. This is of particular importance in patients with recent, or a history of, major CV events. Early management of DR is a complex task that requires comprehensive evaluation and a multidisciplinary approach to manage complications, risk factors, and interactions between different aspects of the disease. Anti-vascular endothelial growth factor (VEGF) agents have become an important therapeutic modality in ophthalmology. However, their use is contraindicated in patients with DR and/or DME with a CV event in the previous 3 months. In patients with DME, corticosteroids target the multifaceted inflammatory pathways involved in the pathogenesis of DR, with a broader spectrum of action than anti-VEGF agents. In this context, recent guidelines suggest the use of corticosteroids, and in particular dexamethasone intravitreal implant, as a well-tolerated and efficacious first-line treatment in patients with high CV risk, such as a history of or recent major CV events. This review focuses on the subset of diabetic patients with a prior CV event, DR, and DME and discusses the need for a holistic approach in evaluating the optimal therapeutic choice for the care of the individual patient, supported by real-world clinical experience on long-term dexamethasone intravitreal implant therapy

Infection control measures in ophthalmology during the COVID-19 outbreak: A narrative review from an early experience in Italy

Introduction: The novel coronavirus (SARS-CoV-2) is infecting people and spreading easily from person-to-person. Cases have been detected in most countries worldwide. Italy is one of the most affected countries as of 30 March 2020. Public health response includes a rapid reorganization of the Italian National Healthcare System in order to reduce transmission of COVID-19 within hospitals and healthcare facilities, while optimizing the assistance to patients with severe COVID-19 complications. Methods: We analysed the actions that were taken in three ophthalmology centres in northern Italy during the SARS-CoV-2 outbreak and how these measures affected patient\u2019s attendance. In addition, due to the rapidly evolving scenario, we reviewed the evidence available during the course of this pandemic. Results: A full reorganization of ophthalmology services is mandatory according to current existing infection containment measures in order to continue dispensing urgent procedures without endangering the community with amplification of the diffusion chain. Ophthalmologists are considered at elevated risk of exposure when caring patients and vice versa, due to their close proximity during eye examination. High volumes of procedures typically generated by ophthalmologists with concurrent implications on the risk of infection are considered when re-assessing healthcare facilities reorganization. Conclusion: Containment measures in the event of pandemic due to infective agents should be well known by healthcare professionals and promptly applied in order to mitigate the risk of nosocomial transmission and outbreak

Resolution of cystoid macular edema following arginine-restricted diet and vitamin B6 supplementation in a case of gyrate atrophy.

We report the outcome of 3 years of arginine-restricted diet and vitamin B6 supplementation in a boy who presented with gyrate atrophy of the choroid and retina and bilateral cystoid macular edema. The diagnosis of gyrate atrophy was made on the basis of clinical findings and increased plasma ornithine levels. Molecular genetic testing revealed a disease-causing homozygous mutation in the ornithine aminotransferase (OAT) gene. After 3 months of dietary modification and pyridoxine supplementation, visual acuity improved, and optical coherence tomography showed resolution of cystoid macular edema in both eyes. This anatomical and functional improvement was maintained during 3 years of follow-up

Total flow intensity, active flow intensity and volume related flow intensity as new quantitative metrics in optical coherence tomography angiography

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

Update of intravitreal steroids for the treatment of diabetic macular edema

Diabetic macular edema is considered the most important factor related to visual impairment in patients with diabetic retinopathy. Together with the use of grid and focal laser photocoagulation, today the intravitreal administration of pharmacotherapies represents the standard of care for the treatment of this complication: anti-vascular endothelium growth factor agents and steroids are the drugs currently used for this aim. Differently from laser therapy, which prevents visual deterioration, the intravitreal approach allows the promotion of visual recovery. However, the intravitreal injections require to be repeated with high frequency, and this carries the risk of drug- and procedure-related adverse effects

Optical coherence tomography angiography findings in pigmented paravenous chorioretinal atrophy

Purpose:To analyze the retino-choroidal vascular characteristics of patients affected by pigmented paravenous chorio-retinal atrophy by means of optical coherence tomography (OCT) angiography.Methods:This study was designed as an observational, cross-sectional case series. Multimodal imaging included fundus autofluorescence, structural OCT, and OCT angiography. The quantitative OCT angiography analyses included the calculation of the vessel density and choriocapillaris porosity.Results:Overall, 12 patients (24 eyes) affected by pigmented paravenous chorio-retinal atrophy were recruited. Structural OCT of the areas involved by pigmented paravenous chorio-retinal atrophy as visualized on the fundus autofluorescence showed a complete ellipsoid zone and external limiting membrane absence, with thinning of ganglion cell complex, outer nuclear layer, and outer plexiform layer, but associated with the optical partial preservation of the retinal pigment epithelium. Optical coherence tomography angiography quantitative assessment of the retinal regions affected by PPRCA, as visualized by fundus autofluorescence, was characterized by normal vessel density at the level of superficial capillary plexus but significantly altered vessel density of deep capillary plexus and choriocapillaris, with higher choriocapillaris porosity. The presence of macular atrophy was significantly correlated with worse deep capillary plexus and choriocapillaris vessel density values. Furthermore, a statistically significant correlation between the fundus autofluorescence patterns and the retinal vascular status was found.Conclusion:Optical coherence tomography angiography quantitative analyses in pigmented paravenous chorio-retinal atrophy demonstrate a specific impairment at the level of the deep capillary plexus, which could in turn bring about a thinning of ganglion cell complex and outer nuclear layer. The alterations at the level of the choriocapillaris and the choroid, in general, could then represent a secondary effect

Macular Microcysts in Mitochondrial Optic Neuropathies: Prevalence and Retinal Layer Thickness Measurements.

PurposeTo investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON).MethodsAll patients with molecularly confirmed MON, i.e. Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections.ResultsMM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7μm vs 122.3±9μm in MM patients (p<0.01) and 128.5±8μm vs. 122.3±9μm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mμ) compared to patients without MM [77.5±8mμ (p<0.001)] and controls [78.4±7mμ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls.ConclusionThe prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces

Extrafoveal Müller cells detection in vivo in the human retina: a pilot study based on optical coherence tomography

Müller cells (MC) represent a key element for the metabolic and functional regulation of the vertebrate retina. The aim of the present study was to test the feasibility of a new method for the in-vivo detection and quantification of extrafoveal MC in human retina. We developed a new approach to isolate and analyse extrafoveal MC in vivo, starting from structural optical coherence tomography data. Our pilot investigation was based on the optical properties of MC, which are known to not interfere with the light reaching the outer retinal structures. We reconstructed MC in the macular region of 18 healthy subjects and the quantitative analyses revealed ~42,000/9 mm2 cells detected. Furthermore, we included 2 patients affected by peripheral intraocular melanoma, with macular sparing, needing surgical enucleation. We used these two eyes to perform a qualitative comparison between our reconstructions and histological findings. Our study represents the first pilot investigation dedicated on the non-invasive isolation and quantification of MC, in-vivo, in human retina. Although we are aware that our study has several limitations, first of all related with the proper detection of foveal MC, because of the peculiar z-shape morphology, this approach may open new opportunities for the non-invasive in vivo analysis of MC, providing also potential useful perspectives in retinal diseases