Age and diabetes related changes of the retinal capillaries: an ultrastructural and immunohistochemical study

Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes

Retinal Tectonics after Macular Pucker Surgery: Thickness Changes and En-Face Displacement Recovery.

PURPOSE To study visual function, retinal layer thickness changes and tangential displacement after Pars Plana Vitrectomy (PPV) for EpiRetinal Membrane (ERM). METHODS Retrospective series of patients undergoing PPV for ERM, with 6-month follow-up including best-corrected visual acuity (BCVA), Optical Coherence Tomography (OCT), M-charts, ERM grading, and InfraRed fundus photo at time 0 (T0, pre-op) at month 1 (T1), 3 (T3), 6 (T6) post-op (±1 week). Retinal layer thickness and tangential (en-face) retinal displacement between successive times for the entire retinal surface and the central horizontal and vertical meridian were also measured. En-face displacement was calculated as optical flow of consecutive images. RESULTS Average BCVA improved from 0.28±0.08 logMAR at T0 to 0.16±0.25 at T6 (p=0.05), BCVA improvement correlated with BVCA at T0 (p<0.001). Vertical metamorphopsia decreased from 1.33°±0.70° at T0 to 0.82°±0.69° at T6 (p<0.05). Foveal thickness reduced from 453±53µm at T0 to 359±31µm at T6 (p<0.05) and reduction correlated with BCVA improvement (p<0.05). Foveal layers decreased (p<0.05) in all cases. Mean en-face deformation was 155.82±50.17µm and mostly occurred in the first month: T0-T1 displacement was 83.59±30.28µm, T1-T3 was 36.28±14.45µm, while T3-T6 was 39.11±22.79µm (p<0.001) on average. Peri-foveal and parafoveal deformation correlated with OCT foveal thickness reduction at all time intervals (1, 3, 6 months: p<0.01). CONCLUSION ERM peeling affects all retinal layer thickness and results in new force balance across the entire retina and tangential displacement. Both en-face and in-depth changes correlate with visual function

Human Vitreous Collagen Fragments Dimension As a Function of Vitrectomy Cut Rate

Purpose: To study the dimensions and distribution of human vitreous collagen type II fragments collected after vitrectomy performed at varying cut rates and to evaluate if increasing the cut rate produces smaller collagen fragments, thus reducing retinal traction and/or viscosity. Methods: Fluid was collected during core vitrectomies performed for macular surgery at cut rates from 1000 to 16,000 cuts per minute (CPM) and immediately refrigerated. Protein fractions were separated by molecular weight (MW; &gt;100 kDa, 50-100 kDa, 50-30 kDa, 30-10 kDa, and &lt;10 kDa) through centrifugal filters. The Human Collagen II ELISA Kit colorimetric assay was then used to measure the COL2A1 in unfiltered and filtered samples. Results: Vitreous samples collected after vitrectomy performed at 16,000 CPM contained a higher concentration of protein with MW over 100 kDa than at any other cutting frequency (P &lt; 0.01). No significant differences were found in fractions collected with a MW between 50 and 100 kDa. Collagen type II fragments over 100 kDa were significantly more represented than smaller fragments at each cut rate. The proportion of smaller (50-100 kDa) collagen fragments compared with those over 100 kDa was higher at 2000 CPM than at higher cut rates. Conclusions: Vitreous samples collected at different cut rates do not contain a significantly different proportion of collagen type II fragments of the tested MW. The extreme variability of vitreous flow through the cutter port may explain the uncertain predictability of collagen fragment MWs. Translational relevance: Increasing the cut rate does not produce vitreous fragments of proportionally smaller dimension. It is necessary to achieve an invariant instantaneous flow through the cutter port in order to decrease retinal traction during vitrectomy

Cataract surgery practice patterns worldwide: a survey

Objective To report the results of a global survey on cataract practice patterns related to preoperative, intraoperative and postoperative care, surgical setting and personnel allocation.Methods and analysis An online 28 questions survey was sent to 240 ophthalmologists asking to describe prevailing trends in their institutions across 38 countries and 5 continents. Questions inquired country, institution, surgical volume and setting, anaesthesia, preoperative and intraoperative examination and postsurgical care. Statistical analysis used crosstabs lambda statistics for non-parametric nominal variables. P value less than 0.05 was considered statistically significant.Results 209/240 (87%) ophthalmologists responded: 38% representing public hospitals, 36% private practices and 26% academic sites; overall surgical volume was between 241 700 and 410 500 cataracts per year. There was a significant correlation between type of institution and surgical volume. Complete results available in online (https://freeonlinesurveys.com/r/W6BcLLxy).Conclusion Cataract surgery related patterns of perioperative care showed significant difference among respondents, regardless to type of institution, surgical volume and country. Many evidence-based procedures are unevenly practiced around the world and some widespread and expensive habits lack solid scientific evidence while consuming enormous amount of resources both monetary and human. There is a need to reach consensus and share evidence-based practice patterns

Superficial and Deep Capillary Plexuses: Potential Biomarkers of Focal Retinal Defects in Eyes Affected by Macular Idiopatic Epiretinal Membranes? A Pilot Study

Inner macular layers are the most involved in the retinal distortion caused by idiopathic epiretinal membrane (iERM). They represent the anatomical structures in which the superficial (SCP) and deep (DCP) capillary plexus are embedded. We quantified flow signal (FS) in these capillary plexuses using Swept Source OCT angiography to identify possible markers for postoperative outcome. The software ImageJ was used to quantify the FS in a 150 µm radius area around each point analyzed by MAIA microperimeter. In 16 patients with unilateral iERM, focal light sensitivity (FLS) in the para- and perimacular areas was measured to evaluate macular function in 24 points overlapping macular plexuses and compared with normal fellow eyes (FEs). t-Test for independent samples iERM eyes (iERMEs) vs. fellow eyes (FEs) and Pearson correlation coefficient of FS vs. FLS in each point were calculated. A level of p p p = 0.827, p = 0.791). Correlation in focal retinal areas between FLS and FS in ERMEs was significant in SCP (p = 0.002) and not significant in DCP (p = 0.205); in FEs was significant in both SCP (p p = 0.022). As previously described, these defective areas were located mainly in sites of distortion of retinal layers; therefore, it can be hypothesized that a focal change in FS, occurring mostly in SCP, could be involved in the onset of the functional defect

Short-Term Results of Ocriplasmin versus Prompt Vitrectomy for Macular Hole. Which Performs Better?

In this retrospective study, we compared the anatomical and functional changes in patients with vitreomacular traction associated with macular holes between the following groups: (1) Patients who were treated with a single intravitreal injection of ocriplasmin (the OCRIALONE group); (2) those who failed the ocriplasmin treatment and underwent vitrectomy one month later (the OCRIVIT group); and (3) patients who directly underwent par plana vitrectomy (VITREALONE group). A total of 38 patients, 19 in the OCRIALONE group + OCRIVIT group (seven and 12 patients, respectively) and 19 in the VITREALONE group with focal vitreomacular adhesion associated with macular holes were evaluated with spectral domain optical coherence tomography. Functional examinations included best-corrected visual acuity (BCVA) and microperimetry analysis. Visual function changes were compared between the OCRIALONE group + OCRIVIT group and VITREALONE group up to three months. Furthermore, a subgroup analysis compared the OCRIVIT group and the VITREALONE group. BCVA values and the mean retinal sensitivity showed statistically significant improvement in all groups (p &lt; 0.001). Specifically, the retinal sensitivity values at the end of the follow-up were significantly higher in the OCRIALONE group + OCRIVIT group than in the VITREALONE group. These functional findings were also confirmed when the statistical analysis was conducted between the OCRIVIT group and the VITREALONE group. Although the OCRIALONE group + OCRIVIT group exhibited faster retinal thinning than the VITREALONE group (p = 0.006), the analysis of the OCRIVIT group versus the VITREALONE group did not show any statistically significant difference. The better functional results and similar anatomical findings suggest that ocriplasmin can be used as a first-line treatment, and that prompt pars plana vitrectomy as primary surgery does not provide better outcomes in comparison with pars plana vitrectomy after ocriplasmin injection

Silicone Oil Tamponade-Retina Contact in Highly Myopic Eyes With and Without Encircling Bands: A Computational Fluid Dynamics Study

Purpose: To investigate the behavior of silicone oil (SiO) at a steady equilibrium and during saccades in pseudophakic highly myopic eyes with posterior staphyloma with and without an encircling band and compare it to behavior in emmetropic eyes. The SiO-retina contact area and shear stress were calculated by computational fluid dynamics. Methods: A numerical model of an emmetropic eye and a myopic eye with and without scleral band underwent a saccade of 50 degrees/0.137 s. The vitreous chamber surface was divided into superior and inferior 180 degrees sectors: lens, pre-equator, post-equator, and macula. SiO-retina contact was evaluated as a function of fill percentages between 80% and 90% for standing, 45 degrees upward tilt, and supine patients. Maximum and average shear stress were calculated. Results: Overall, SiO-retina contact ranged between 40% and 83%; fill percentage varied between 80% and 95%. Neither the encircling scleral band nor the staphyloma significantly affected the SiO-retina contact area, although the presence of a scleral band proved disadvantageous when gazing 45 degrees upward. The inferior retina-SiO contact remained below 40% despite 95% SiO fill. The SS significantly increased at the scleral band indentation and decreased elsewhere. The staphyloma greatly reduced shear stress at the macula. Conclusions: The presence of a myopic staphyloma reduces shear stress at the macula but does not alter SiO-retina contact significantly. The apposition of a 360 degrees scleral band may reduce SiO-retina contact at least in some postures and increases the SS at the indentation. Translational Relevance: Assessing SiO-retina contact when vitreous chamber geometry changes according to pathologic or iatrogenic modifications allows accurate prediction of real-life tamponade behavior and helps explain surgical outcomes

Fellow Eye Findings of Highly Myopic Subjects Operated for Retinal Detachment Associated with a Macular Hole Materials and Methods

Purpose: To identity anatomic risk factors involved in the onset of retinal complications causing decrease of visual acuity (VA) in the fellow eyes of highly myopic patients operated for retinal detachment with macular hole (RDMH). Design: Cohort study. Participants: Ninety-eight patients (mean age, 51.5Ϯ8.0 years) with bilateral high myopia (mean myopia of the fellow eye, 20.4Ϯ5.5 diopters) affected by RDMH in the other eye at baseline. Methods: Evaluation of the anatomic features at baseline and during 84Ϯ2.7 months of follow-up by biomicroscopic examination, indirect binocular ophthalmoscopy, B-scan ultrasonography, and optical coherence tomography. Main Outcome Measures: Detection of anatomic features associated with onset of retinal complications causing decrease of VA during the follow-up period. Results: The fellow eyes were divided into 2 groups according to the clinical features of the RDMH eyes: Group 1, presence of posterior vitreous detachment (PVD); and Group 2, presence of posterior vitreous schisis (PVS). At baseline, the incidence of PVD in group 1 was 31 of 47 eyes (65.9%) and the incidence of PVS in Group 2 was 42 of 51 eyes (82.3%). At the end of follow-up, group 1 eyes had a lower incidence of retinal complications causing visual decrease than group 2 eyes (group 1, 2/47 eyes; group 2, 9/51 eyes). Eyes with high myopia (Ͼ6 diopters [D] and with a corresponding axial length usually Ͼ26 mm) 1 are reported to have a higher incidence of retinal detachment (RD) associated with macular hole (RDMH) compared to emmetropic eyes. -17 Some authors have already reported the risk and the incidence of bilateral RDMH in myopic fellow eyes 2,3 ; however, as far as we are aware, there is a lack of information regarding the anatomic factors that may be involved in the onset of the same or different retinal pathologies in fellow eyes of highly myopic patients affected by RDMH and with a similar degree of myopia. In a previous study, we reported the surgical techniques used for the repair of RDMH in highly myopic eyes. The studied eyes were divided into 2 groups on the basis of their vitreoretinal features. The choice of the surgical technique employed depended on the vitreous features of the eyes, the extent of the chorioretinal atrophic areas, and the presence of a posterior staphyloma; all these characteristics were related to the degree of myopia. 18 The fellow eyes of operated cases of RDMH were included in this work, and 18 are the object of the present study, with the aim of identifying anatomic risk factors involved in the onset of retinal complications causing a decrease of visual acuity (VA)