RETINAL ARTERIAL DILATION IS IMPAIRED IN EYES WITH DRUSEN AND RETICULAR PSEUDODRUSEN.

PURPOSE: To analyze static characteristics and dynamic functionality of retinal vessels in eyes with drusen and reticular pseudodrusen (RPD) using dynamic vessel analyzer. METHODS: Patients with clinical diagnosis of isolated RPD or medium-large drusen and healthy controls were enrolled in the study between July 2016 and May 2018. Participants underwent complete ophthalmologic examination, including enhanced depth imaging structural optical coherence tomography, dynamic retinal vessel analysis, and static retinal vessel analysis. RESULTS: Twenty-eight eyes of 23 patients with drusen (9 men, mean age 77 ± 6 years), 22 eyes of 16 patients with RPD (7 men, mean age: 76 ± 6 years), and 22 eyes of 22 control subjects (11 men, mean age of 75 ± 6 years) were enrolled. Static retinal vessel analysis did not show any significant difference between the three groups for the central retinal artery equivalent (P = 0.11), the central retinal vein equivalent (P = 0.27), and the arteriovenous ratio (P = 0.30). Dynamic vessel analysis showed significantly reduced arterial dilation in eyes with drusen (P = 0.0001) and RPD (P = 0.015) compared with control subjects. No significant difference was seen between drusen and RPD groups (P = 0.32). Dynamic vessel analysis of retinal veins showed no differences between the three groups (P = 0.10). CONCLUSION: Dynamic vessel analysis in eyes with drusen and RPD revealed an impaired retinal arterial dilation in response to flicker light stimulation, which further supports the relationship between cardiovascular risk and age-related macular degeneration.

Inter-method agreement in retinal blood vessels diameter analysis between Dynamic Vessel Analyzer and optical coherence tomography.

PURPOSE: To analyze the inter-methods agreement in arteriovenous ratio (AVR) evaluation between spectral-domain optical coherence tomography (SD-OCT) and Dynamic Vessel Analyzer (DVA). METHODS: Healthy volunteers underwent DVA and SD-OCT examination. AVR was measured by SD-OCT using the four external lines of the optic nerve head-centered 7-line cube and by DVA using an automated AVR estimation. The mean AVR was calculated, twice, separately by two independent readers for each tool. RESULTS: Twenty-two eyes of 11 healthy subjects (five women and six men, mean age 35) were included. AVR analysis by DVA showed high inter-observer agreement between reader 1 and 2, and high intra-observer agreement for both reader 1 and reader 2. With regard to AVR analysis on SD-OCT, we found high inter-observer agreement between reader 1 and 2, and low intra-observer agreement for reader 2 but high intra-observer agreement for reader 1. Overall, the mean AVR measured on SD-OCT turned out to be significantly higher than mean AVR measured through DVA (reader 1, 0.9023 ± 0.06 vs 0.8036 ± 0.08; p < 0.001, and reader 2, 0.9067 ± 0.06 vs 0.8083 ± 0.05; p= 0.003). CONCLUSIONS: No inter-method agreement in AVR could be detected in the present study due to bias in measurements (shift between DVA and SD-OCT). We found significant difference in the two noninvasive methods for AVR measurement, with a tendency for SD-OCT to overestimate retinal vascular caliber in comparison to DVA. This may be useful for achieving greater accuracy in the evaluation of retinal vessel in ocular as well as systemic diseases.

Comparison of the Performance of Two Different Spectral-Domain Optical Coherence Tomography Angiography Devices in Clinical Practice.

PURPOSE: To compare the performance of two different spectral-domain optical coherence tomography angiography (OCTA) devices in clinical practice by evaluating examination execution time and the number of motion artifacts per image. METHODS: Seventy-six patients affected by different ocular diseases and 13 healthy subjects consecutively underwent assessments by two different OCTA devices: AngioPlex (Zeiss Meditec, Inc., Dublin, Calif., USA) and AngioVue (OptoVue, Inc., Fremont, Calif., USA). Two different operators (L.A.D.V. and L.B.) measured execution times, excluded low-quality images, and counted the number of motion artifacts per image. RESULTS: The mean execution time was shorter with AngioPlex than with AngioVue for all subjects (3 min 32 s ± 1 min 45 s vs. 4 min 35 s ± 1 min 11 s; p < 0.0001), for the healthy subjects (2 min 31 s ± 45 s vs. 4 min 1 s ± 53 s; p = 0.003), and for the patients (3 min 44 s ± 1 min 48 s vs. 4 min 42 s ± 1 min 13 s; p < 0.0001). The percentages of available images, low-signal-strength images, and images impossible to analyze of the total acquired images obtained using AngioPlex or AngioVue were 85, 6, and 9% and 56, 29, and 15%, respectively. The mean number of motion artifacts was significantly lower in images obtained using AngioPlex than in images obtained using AngioVue for all patients (6.5 ± 5.9 vs. 12.6 ± 8.5; p < 0.0001), for the healthy subjects (6.5 ± 4.6 vs. 10.9 ± 7.9; p = 0.0009), and for the patients (6.6 ± 6.3 vs. 13.1 ± 8.7; p < 0.0001). There was no correlation between the number of artifacts and execution time or patients' age. CONCLUSION: AngioPlex and AngioVue are useful devices in clinical practice. AngioPlex requires a shorter execution time and provides a higher number of images available for analysis with fewer motion artifacts.

Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON.

Benefits of micronutrient supplementation for reducing the risk of wet age-related macular disease and diabetic retinopathy: An update.

Age-related macular disease and diabetic retinopathy are chronic degenerative diseases characterised by progressive visual impairment. In Europe, age-related macular disease accounts for over 15% of blindness in adults over 50 years of age, and although the burden of diabetic retinopathy in terms of vision impairment is lower, vision loss associated with diabetic retinopathy is increasing with the rising prevalence of diabetes mellitus and the ageing of the population. Late-stage age-related macular disease can be subdivided into dry (non-neovascular) or wet (neovascular or exudative) forms. The large Age-Related Eye Disease Study 2 showed that supplementation with antioxidant nutrients reduces choroids neovascularisation and reduces the risk of progression of neovascular age-related macular disease. Antioxidant micronutrient supplements have also shown promising results in preventing the pathogenesis of retinopathy in animal models of diabetes. Age-related macular disease and diabetic retinopathy are understood to share some common pathophysiological characteristics, suggesting that micronutrients have an important role in ocular health in both conditions. This article will review the current evidence for the utility of micronutrients in preventing the development and progression of neovascular age-related macular disease and diabetic retinopathy.

Cytidine 5'-Diphosphocholine (Citicoline): Evidence for a Neuroprotective Role in Glaucoma.

Glaucoma, a heterogeneous set of progressively degenerative optic neuropathies characterized by a loss of retinal ganglion cells (RGCs) and typical visual field deficits that can progress to blindness, is a neurodegenerative disease involving both ocular and visual brain structures. Although elevated intraocular pressure (IOP) remains the most important modifiable risk factor of primary open-angle glaucoma (POAG) and is the main therapeutic target in treating glaucoma, other factors that influence the disease course are involved and reaching the optimal IOP target does not stop the progression of glaucoma, as the visual field continues to narrow. In addition to a managed IOP, neuroprotection may be beneficial by slowing the progression of glaucoma and improving the visual defects. Citicoline (cytidine 5'-diphosphocholine) is a naturally occurring endogenous compound that has been investigated as a novel therapeutic agent for the management of glaucoma. Citicoline has demonstrated activity in a range of central neurodegenerative diseases, and experimental evidence suggests a it performs a neuromodulator and neuroprotective role on neuronal cells, including RGCs, associated with improvement in visual function, extension of the visual field and central benefits for the patient. This review aims to critically summarize the current evidence for the neuroprotective properties of citicoline in glaucoma.

Multimodal Chorioretinal Imaging in Erdheim-Chester Disease.

PURPOSE: To analyze the subclinical intraocular involvement using multimodal imaging approach in patients affected by Erdheim-Chester disease (ECD) without ocular symptoms. PATIENTS AND METHODS: In this prospective cross-sectional study, 18 eyes of 9 consecutive patients with ECD were enrolled. Each patient underwent comprehensive ocular examination and extensive multimodal chorioretinal imaging. RESULTS: None of the patients presented any evidence of chorioretinal localization of disease using multimodal imaging. One patient exhibited a choroidal nevus complicated by active polypoidal choroidal neovascularization. Subretinal hyperreflective material was seen in three eyes, mainly resembling acquired vitelliform lesion. One patient had an isolated intraretinal hemorrhage. Most patients exhibited peripheral vascular abnormalities (ie, microaneurysms, peripheral vascular leakage). Fundus autofluorescence showed faint hyperautofluorescence in eleven eyes. CONCLUSION: Intraocular involvement is an extremely rare event of an extremely rare disease. In patients affected by ECD without ocular symptoms, advance multimodal imaging examinations did not show signs of subclinical chorioretinal involvement related to the disease.

Early response to the treatment of choroidal neovascularization complicating central serous chorioretinopathy: a OCT-angiography study.

PURPOSE: To analyze the quantitative and qualitative early changes of choroidal neovascularization (CNV) associated with chronic central serous chorioretinopathy (CSC) after treatment using optical coherence tomography-angiography (OCT-A). METHODS: Charts of consecutive patients with diagnosis of chronic CSC complicated by CNV were retrospectively reviewed. Included patients were divided in photodynamic therapy (PDT) or aflibercept group on the basis of the treatment received (half-fluence PDT or aflibercept 2.0 mg/0.05 ml intravitreal injection). Main outcome measures included the changes between baseline and 1-month follow-up in CNV vessel density (VD) and area on OCT-A images after thresholding and binarization. RESULTS: A total of 30 eyes of 26 Caucasian patients were included: 17 eyes of 15 patients in PDT group (mean age 53 ± 11 years) and 13 eyes of 11 patients in aflibercept group (mean age 58 ± 8 years [p = 0.196]). In both PDT and aflibercept groups, best-corrected visual acuity improved at 1 month, and central macular thickness and subretinal fluid significantly decreased. VD did not change after the treatment in both groups (p = 0.502 and p = 0.086) although CNV area decreased significantly (from 0.586 ± 0.449 mm2 to 0.553 ± 0.453 mm2 [0.041]) in the PDT group, and nonsignificantly (from 0.767 ± 0.466 mm2 to 0.733 ± 0.472 mm2 [p = 0.095]) in the aflibercept group. The same results were confirmed in the subanalysis of the 18 treatment-naïve eyes. CONCLUSIONS: We demonstrated that, despite all patients showed a favorable clinical response, VD of CNVs complicating chronic CSC did not change after treatment. These findings support the idea that arteriogenesis is the main driving force of CNV in pachychoroid-related macular disorders.

Retinal vessels functionality in eyes with central serous chorioretinopathy.

PURPOSE: To analyse static characteristics and dynamic functionality of retinal vessels in eyes with central serous chorioretinopathy (CSCR) by means of Dynamic Vessel Analyzer (DVA). METHODS: Patients presenting with treatment-naïve CSCR and normal subjects (controls) matched for age and sex between May 2015 and November 2015 were enrolled in the study. Participants underwent a complete ophthalmological examination, including dynamic and static retinal vessels analysis by DVA. RESULTS: A total of 28 eyes of 28 subjects (14 eyes for each group) were included in the analysis. Dynamic analysis during stimulation by flickering light showed mean venous dilation of 3.3%±2.0% in patients with CSCR and 5.5%±2.6% in controls (p=0.0258); mean arterial dilation did not differ between patients and controls (3.2%±2.5% and 4.2%±1.5%, p=0.2). No differences were reported at static retinal analysis between patients with CSCR and control subjects. Subfoveal choroidal thickness as evaluated by optical coherence tomography was 438.6±86.1 µm in CSCR eyes, significantly increased compared with control subjects (301.5±72.5 µm, p=0.0001). CONCLUSIONS: Dynamic analysis revealed a reduced retinal venous dilation in response to flicker light stimulation in CSCR eyes. The decreased retinal vein response to flicker light stimulation, possibly due to increased sympathetic tone and potentially leading to venous stasis, together with the increased choroidal thickness may help understand CSCR and give insights in its pathogenesis.

Dynamic functionality and static changes of retinal vessels in diabetic patients treated with intravitreal ranibizumab.

AIMS: To investigate the short-term effects of intravitreal ranibizumab on retinal vessel functionality in patients with diabetic macular edema (DME) by Dynamic Vessel Analyzer (DVA). METHODS: Patients presenting with DME were enrolled in the study. All patients underwent a complete ophthalmic evaluation, including optical coherence tomography and dynamic and static vessel analysis, using the DVA before (baseline), 1 week and 1 month after administration of intravitreal ranibizumab. DME subject were compared with diabetic retinopathy (DR) without DME subjects, and with normal non diabetic subjects (controls) matched for age and sex. RESULTS: A total of 45 eyes of 45 subjects (15 eyes for each group) were included in the analysis. In DME patients, dynamic analysis showed a significant decrease in mean arterial dilation from baseline to 1 week. Mean central retinal artery equivalent (CRAE) of DR patients without DME was significantly different from baseline and week 1 of DME eyes. In healthy control subjects, CRAE was significantly different from CRAE at baseline and 1 week on DME patients, but not significantly different from DR patients without DME. CONCLUSIONS: Using DVA in patients with DME, dynamic analysis showed a significant decrease in mean arterial dilation from baseline to 1 week in DME eyes. A significant reduction in arterial vessels could be demonstrated in DME patients compared to DR patients without DME and controls.

Optical coherence tomography angiography analysis of retinal vascular plexuses and choriocapillaris in patients with type 1 diabetes without diabetic retinopathy.

AIMS: To analyze retinal vascular plexuses and choriocapillaris by optical coherence tomography angiography (OCT-A) and retinal nerve fiber layer and ganglion cell layer (GCL) by structural optical coherence tomography (OCT) in patients with type 1 diabetes mellitus (T1DM) without diabetic retinopathy (DR). METHODS: A total of 25 eyes of 25 consecutive T1DM patients without signs of DR were prospectively recruited and compared to 25 healthy subjects (control eyes). All patients underwent OCT-A (CIRRUS HD-OCT model 5000, Carl Zeiss Meditec, Dublin, CA) and structural OCT. Qualitative and quantitative analyses with vessel density were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris for all patients. RESULTS: By means of OCT-A, a rarefaction of the perifoveal capillary network in SCP was detected in 7 out of 25 eyes. No significant difference was found in FAZ area of both SCP and DCP comparing diabetic and control groups. By analyzing the DCP, diabetic eyes revealed a significant decreased vessel density compared to control eyes [0.464 ± 0.016 and 0.477 ± 0.014, respectively (p = 0.005)]. Instead, no significant difference was found in the vessel density of all-retina plexus, SCP and choriocapillaris. By RFNL and GCL thickness analysis, no significant differences were disclosed between diabetics and healthy subjects. CONCLUSIONS: We demonstrated the ability of OCT-A to disclose early vascular alterations in patients with T1DM diagnosed as without any signs of DR on the basis of fundus biomicroscopy. Our results also suggest that microvascular changes could precede detectable damage of diabetic neuroretinopathy.

Optical coherence tomography angiography findings in laser maculopathy.

PURPOSE: Handheld laser pointer thermal injury affects primarily the retinal pigment epithelium (RPE). However, so far no study has reported on the possible effects of laser pointers in the deeper layers, beneath the RPE. Here, we describe the spectral-domain optical coherence tomography angiography findings in the choriocapillaris of a patient with laser maculopathy. METHODS: A 13-year-old boy presented to our department with decreased vision in the left eye 12 hours after having stared at the beam of a laser pointer. RESULTS: Structural optical coherence tomography (OCT) showed 2 focal hyperreflective columns at the fovea extending from the RPE, involving all outer retinal layers, and terminating at the outer plexiform layer. The patient also underwent OCT angiography (OCT-A), which in the choriocapillary segmentation revealed 2 hypointense lesions in correspondence of the focal hyperreflectivities detected on structural OCT. We hypothesize that the OCT-A findings could represent a rarefaction of the choriocapillaris. However, the choriocapillary OCT-A findings could also represent artifacts due to the overlaying hyperreflective lesions. CONCLUSIONS: It is known that the RPE is primarily damaged by the laser injury. Our findings suggest that the thermal injury could involve also the choriocapillaris, and thus not limited to the RPE. Multimodal imaging in laser maculopathy including OCT-A may lead to a better comprehension of the pathogenesis of laser retinal damages.

Sudden visual loss after cardiac resynchronization therapy device implantation.

PURPOSE: To report a case of sudden decrease in visual acuity possibly due to a cardiogenic embolism in a patient who underwent cardiac resynchronization therapy (CRT) device implantation. METHODS: A 62-year-old man with severe left ventricular systolic dysfunction and a left bundle branch block was referred to our department because of a sudden decrease in visual acuity. Nine days earlier, he had undergone cardiac transapical implantation of a CRT device, which was followed, 2 days later, by an inflammatory reaction. The patient underwent several general and ophthalmologic examinations, including multimodal imaging. RESULTS: At presentation, right eye (RE) best-corrected visual acuity (BCVA) was counting fingers and RE pupil was hyporeactive. Fundus examination revealed white-centered hemorrhagic dots suggestive of Roth spots. Fluorescein angiography showed delay in vascular perfusion during early stage, late hyperfluorescence of the macula and optic disk, and peripheral perivascular leakage. The first visual field test showed complete loss of vision RE and a normal left eye. Due to suspected giant cell arteritis, temporal artery biopsy was performed. Thirty minutes after the procedure, an ischemic stroke with right hemisyndrome and aphasia occurred. The RE BCVA worsened to hands motion. Four months later, RE BCVA did not improve, despite improvement in fluorescein angiography inflammatory sign. CONCLUSIONS: We report a possible cardiogenic embolism secondary to undiagnosed infective endocarditis causing monocular visual loss after CRT device implantation. It remains unclear how the embolus caused severe functional damage without altering the retinal anatomical structure.

Photobleaching by Spectralis Fixation Target.

IMPORTANCE: The aim of this study is to determine whether the cross-shaped fixation target in a spectral-domain optical coherence tomography instrument (Spectralis; Heidelberg Engineering) could produce a cross-shaped increase fundus autofluorescence artifact on subsequent imaging. OBSERVATIONS: Thirty eyes of 15 healthy volunteers (8 women and 7 men; mean [SD] age 24 [3] years) were included in the study, which was conducted between October 2015 and December 2015. In all eyes, a cross-shaped increase in macular autofluorescence with variable intensity occurred after Spectralis spectral-domain optical coherence tomography acquisition. This peculiar pattern was also detected on confocal scanning laser ophthalmoscope infrared reflectance and MultiColor imaging. Interestingly, no changes in macular fundus autofluorescence pattern were evident after optical coherence tomography acquisition with either Cirrus HD-OCT 5000 or RTVue XR Avanti. CONCLUSIONS AND RELEVANCE: In an era characterized by extensive use of optical coherence tomography examination in clinical practice, the potential deleterious effects related to photopigments consumption by Spectralis optical coherence tomography fixation point deserve further investigation.