Capillary Closure Research Articles

CENTRAL AND PERIPHERAL INVOLVEMENT OF THE RETINA IN THE INITIAL STAGES OF DIABETIC RETINOPATHY.

To determine the degree of central microvascular closure using optical coherence tomography angiography in eyes of patients with type 2 diabetes with visible lesions only in the central retina or only in the periphery. Cross-sectional study. All 127 eyes underwent ultra-widefield fundus photography 200° examinations with OPTOS California (Optos, Dunfermline, United Kingdom) and Cirrus Angioplex optical coherence tomography angiography 3 × 3 mm acquisitions (ZEISS, Dublin, CA). Twenty-five eyes showed visible lesions only in the central retina, 57 only in the peripheral retina, and 45 presented visible lesions in entire retina. The group with visible lesions only in the periphery showed definite closure in the superficial capillary plexus in 49% of the eyes, whereas the group with visible lesions only in the central seven-early treatment diabetic retinopathy study fields area showed a definite closure in 64%. Central capillary closure is already present in the initial stages of diabetic retinopathy even when lesions are only visible in the peripheral retina. Capillary closure in the superficial capillary plexus is three times more frequent than in the deep capillary plexus, demonstrating earlier closure of the superficial capillary plexus. Eyes with visible lesions only in the periphery show a milder form of retinopathy.

Stimulation of Cerebral Angiogenesis and Neurogenesis with Transcatheter Intracerebral Laser Photobiomodulation Therapy in Alzheimer’s Disease and Vascular Parkinsonism Aggravated by Dementia

AbstractBackgroundThe research is focused on the stimulation of cerebral angiogenesis and neurogenesis using Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) in patients with dementia in Alzheimer’s disease (AD) and patients with vascular parkinsonism (VP).MethodThe examination of 155 patients included assessment of CDR, The Tomography Dementia Rating scale (TDR), MMSE, cerebral CT, MRI, SG, rheoencephalography (REG) and cerebral MUGA.85 patients were selected, of whom:• 48 (30.97%) people suffering from AD, aged 34‐80 (mean age 67.5), men ‐ 17 (35.42%), women ‐ 31 (54.58%). According to dementia severity, patients were subdivided: preclinical stage (TDR‐0) ‐ 4, mild stage (TDR‐1) ‐ 16, moderately severe stage (TDR‐2) ‐ 21, severe stage (TDR‐3) ‐ 7 patients.• 37 (23.87%) people suffering from VP, aged 58‐80 (mean age 77), men 28 (75.68%), women ‐ 9 (24.32%). 19 (51.35%) had a mild dementia stage (CDR‐1).In hospital conditions, in a specialized cath lab, all patients underwent Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) (wavelength 632.8 nanometers).ResultAll 48 (100%) patients with AD underwent angiogenesis stimulation resulting in cerebral collateral capillary revascularization and closure of atreriovenous shunts.Simultaneously, patients showed a 10‐20% increase in cerebral temporal lobes volume, which indicates cerebral neurogenesis development and tissue regeneration. The process was accompanied by dementia level decrease and cognitive functions restoration. Consequently, patients were transferred to a milder TDR group. Depending on the initial dementia severity, the resulting positive effect was observed from 2 to 15 years.All 37 (100%) patients with VP underwent angiogenesis stimulation resulting in cerebral microcirculation improvement and cerebral involutive changes decrease, which indicates the neurogenesis development and tissue regeneration. The process was accompanied by decreased dementia and cognitive functions restoration. The resulting positive effect was observed over 10 years.ConclusionDespite the differences in AD and VP etiology, Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) is an effective treatment for dementia in these diseases. The method stimulates angiogenesis and improves blood supply to the brain, it stimulates neurogenesis and the restoration of normal tissue structures, which leads to improved mental and cognitive functions. The resulting effect persists for a long time.

Drug-induced thrombotic microangiopathy

Abstract Introduction/Objective Drug-induced thrombotic microangiopathy is observed in the patient on the new cancer therapy. It shares similar pathologic changes, as seen in conventional thrombotic microangiopathy, and is characterized by a pentad of hemolytic anemia, thrombocytopenia, renal dysfunction, fever, and neurological dysfunction. However, some patients may not have full scope of the pentad. Instead, only “diad” (hemolytic anemia and thrombopenia) exists, which could be mistakenly attributed to the drug side effect of bone marrow suppression. Methods/Case Report A 71-year-old white male with a history of multiple myeloma (MM) and cardiomyopathy presented with nausea and vomiting following the second round of carfilzomib and pomalidomide chemotherapy. Laboratory tests showed anemia, thrombocytopenia, and peripheral blood abnormalities such as normocytic erythrocytes with occasional schistocytes, slight left shift in leukocytes, and decreased platelet count. Results (if a Case Study enter NA) The biopsy shows diffuse closure of glomerular capillaries, occasional microthrombi and fragmented red cells in glomerular capillaries. Under electron microscope, there are subendothelial space widening, mesangial interposition and wrinkling of glomerular basement membranes. These changes are consistent with acute or subacute thrombotic microangiopathy (TMA). Conclusion With the frequent use of advanced chemotherapy drugs, awareness of the drug-induced TMA should be emphasized. Early recognition is important to avoid development of more permanent kidney damage.

Characterization of One-Year Progression of Risk Phenotypes of Diabetic Retinopathy.

IntroductionWe characterized the progression of different diabetic retinopathy (DR) phenotypes in type 2 diabetes (T2D).MethodsA prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with three visits (baseline, 6 months, and 1 year). Demographic and systemic data included age, sex, diabetes duration, lipid profile, and hemoglobin A1c (HbA1c). Ophthalmological examinations included best-corrected visual acuity (BCVA), color fundus photography (CFP), and optical coherence tomography (OCT and OCTA). Phenotype classification was performed at the 6-month visit based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Only risk phenotypes B (MAT < 6 and increased CRT) and C (MAT ≥ 6 with or without increased CRT) were included. ETDRS grading was performed at the baseline visit based on seven-field CFP.ResultsA total of 133 T2D individuals were included in the study; 81 (60%) eyes were classified as phenotype B and 52 (40%) eyes as phenotype C. Of these, 128 completed the 1-year follow-up. At baseline, eyes with phenotype C showed greater capillary closure (superior capillary plexus, deep capillary plexus, and full retina, p < 0.001) and increased foveal avascular zone (FAZ) area (p < 0.001), indicating more advanced microvascular disease. Neurodegeneration represented by thinning of the ganglion cell layer + inner plexiform layer (GCL + IPL) was present in both phenotypes. When analyzing the 1-year progression of each phenotype, only phenotype C revealed a significant decrease in BCVA (p = 0.02) and enlargement of the FAZ (p = 0.03). A significant progressive decrease in the vessel density of the deep capillary layer and in MAT occurred in both phenotypes, but these changes were particularly relevant in phenotype C and ETDRS grades 43–47. During the 1-year period, both phenotypes B and C showed progression in GCL + IPL thinning (p < 0.001).ConclusionsIn the 1-year period of follow-up, both phenotypes B and C showed progression in retinal neurodegeneration, whereas phenotype C showed more marked disease progression at the microvascular level.

Swept-source OCTA quantification of capillary closure predicts ETDRS severity staging of NPDR

PurposeTo test whether a single or composite set of parameters evaluated with optical coherence tomography angiography (OCTA), representing retinal capillary closure, can predict non-proliferative diabetic retinopathy (NPDR) staging according to...

Different retinopathy phenotypes in type 2 diabetes predict retinopathy progression

PurposeTo characterize the progression in retinopathy severity of different phenotypes of mild nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes.Design and methodsPatients with type 2 diabetes and mild NPDR (ETDRS 20 or 35) were followed in a 5-year longitudinal study. Examinations, including color fundus photography (CFP) and optical coherence tomography (OCT and OCTA), were performed at baseline, 6 months and then annually. Phenotype classification was performed based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Phenotype A is characterized by low MAT (< 6) and normal CRT; Phenotype B by low MAT (< 6) and increased CRT; and Phenotype C by higher MAT (≥ 6) with or without increased CRT. ETDRS grading of seven fields CFP was performed at the initial and last visits.ResultsAnalysis of ETDRS grade step changes showed significant differences in diabetic retinopathy (DR) progression between the different phenotypes (p < 0.001). Of the 66 participants with phenotype A only 2 eyes (3%) presented 2-or-more-step worsening. None of the 50 participants characterized as phenotype B developed 2-step worsening, whereas 13 eyes (23.2%) characterized as phenotype C had 2-or-more-steps worsening. Phenotype C presents the higher risk for 2-or-more step worsening (OR: 15.94 95% CI: 3.45–73.71; p < 0.001) and higher sensitivity, correctly identifying 86.7% of cases at risk (AUC: 0.84 95% CI: 0.72–0.96; p < 0.001). Diabetic retinopathy severity progression was associated with HbA1c (p = 0.019), LDL levels (p = 0.043), and ocular factors as MAT (p = 0.010), MA formation rate (p = 0.014) and MA disappearance rate (p = 0.005). Capillary closure at 5-year follow-up, identified by lower vessel density (VD) on OCTA, was also associated with diabetic DR severity progression (p = 0.035).ConclusionsDifferent DR phenotypes in type 2 diabetes show different risks of retinopathy progression. Phenotype C is associated with increased HbA1c values and presents a higher risk of a 2-or-more-step worsening of the ETDRS severity score.

Blocking endothelial apoptosis revascularizes the retina in a model of ischemic retinopathy.

Aberrant, neovascular retinal blood vessel growth is a vision-threatening complication in ischemic retinal diseases. It is driven by retinal hypoxia frequently caused by capillary nonperfusion and endothelial cell (EC) loss. We investigated the role of EC apoptosis in this process using a mouse model of ischemic retinopathy, in which vessel closure and EC apoptosis cause capillary regression and retinal ischemia followed by neovascularization. Protecting ECs from apoptosis in this model did not prevent capillary closure or retinal ischemia. Nonetheless, it prevented the clearance of ECs from closed capillaries, delaying vessel regression and allowing ECs to persist in clusters throughout the ischemic zone. In response to hypoxia, these preserved ECs underwent a vessel sprouting response and rapidly reassembled into a functional vascular network. This alleviated retinal hypoxia, preventing subsequent pathogenic neovascularization. Vessel reassembly was not limited by VEGFA neutralization, suggesting it was not dependent on the excess VEGFA produced by the ischemic retina. Neutralization of ANG2 did not prevent vessel reassembly, but did impair subsequent angiogenic expansion of the reassembled vessels. Blockade of EC apoptosis may promote ischemic tissue revascularization by preserving ECs within ischemic tissue that retain the capacity to reassemble a functional network and rapidly restore blood supply.

High resolution imaging of radiation retinopathy

AbstractWe explored by fundus photographs, OCT and adaptive optics ophthalmoscopy (AOO) the vessels of eyes after proton beam therapy for uveal melanoma in 10 eyes. We observed strong fluctuations of diameters in both arteries and veins, without significant changes in vascular wall thickness suggesting that vasoconstriction was involved in this process. Reduction of lumen diameter could be focal or diffuse, and could lead in some cases to branch retinal vein occlusion unrelated to arteriovenous crossings. The ensuing collateral circulation could lead to the development of TelCaps (capillary macroaneurysms), successfully treated by targeted laser in one case. Many areas of capillary closure followed a vascular perfusion or drainage scheme, suggesting that vasoconstriction played a role in the complex pattern of radiation retinopathy. This may provide the basis for therapeutic trials based on the modulation of vasomotricity.

Panretinal photocoagulation versus intravitreal injection of bevacizumab as a preoperative adjuvant before vitrectomy in the management of proliferative diabetic retinopathy

Background Proliferative diabetic retinopathy (PDR) characterized by neovascularization of the optic disk, retina, and/or iris may be an aberrant attempt to alleviate hypoxia in eyes with severe capillary closure or other retinal ischemia. The new vessels grow perpendicular to the plane of the retina into the scaffolding provided by the vitreous cortex, typically from venules at the junction of the perfused and nonperfused retina. Objective This work aims to study the effect of panretinal photocoagulation (PRP) versus intravitreal injection of bevacizumab (Avastin) before vitrectomy in the management of PDR. Patients and methods Our clinical study was conducted on 60 eyes in 40 patients with PDR with indications of vitrectomy (vitreous hemorrhage, tractional retinal detachment involving or threatening the macula, combined tractional/rhegmatogenous retinal detachment and fibrovascular membranes covering and distorting the macula, persistent macular edema with viteromacular traction) managed by parsplana vitrectomy after preoperative preparation by intravitreal injection of bevacizumab (Avastin) or PRP used as an adjunct was grouped into two groups: group A and group B; FFA was done previtrectomy for all cases. Results Intraoperative using of endodiathermy is reported as once in eight cases, twice in 15 cases, three times in seven cases in group A, while once in 14 cases, twice in six cases, and not used in 10 cases in group B. Intraoperative use of endolaser is reported as less than 1500 shoots in seven cases, and more than 1500 shoots in 23 cases in group A, while less than 1500 shoots in 29 cases, and more than 1500 shoots in one case in group B. Therefore, bevacizumab or PRP induces regression of active fibrovascular proliferation decreasing the extent of bleeding during tissue segmentation and delamination. The lesser intraoperative bleeding makes visualization of the surgical plane better, which in turn facilitates a precise separation of the proliferative tissue from the retina and helps avoid accidental retinal vascular damage and iatrogenic retinal breaks and make the surgery and the results better than conventional surgery (without using any adjuvants). Conclusion Use of both adjuvants before vitrectomy enhances the outcome of vitrectomy when best indicated rather than without using. The shorter time of surgery and less use of endodiathermy or endolaser is with the PRP group, although postoperative best-corrected visual acuity gaining is not significant. So, accurate clinical differences between two adjuvants need more researches.

Relationship of intercapillary area with visual acuity in diabetes mellitus: an optical coherence tomography angiography study

AimTo examine the correlation of best-corrected visual acuity (BCVA) with intercapillary area (ICA) measured from optical coherence tomography angiography (OCT-A) in patients with diabetes, and to compare the strength of...

Ophthalmic Formulation Containing Nilvadipine Nanoparticles Prevents Retinal Dysfunction in Rats Injected with Streptozotocin.

Retinopathy leads to irreparable vision loss via capillary closure and areas of nonperfusion. However, the current instillation systems do not allow a sufficient amount of drug required to treat retinopathy to reach the posterior segment (retina); therefore, a new formulation targeting the posterior segment is expected as therapy for retinopathy. We prepared ophthalmic formulations containing nilvadipine nanoparticles (NILnano), and demonstrated whether the instillation of NILnano can prevent retinal dysfunction in rats injected with excessive streptozotocin (STZ rats) in this study. NILnano (mean particle size, 77 nm) was prepared by wet bead mill treatment, with the inclusion of various additives (2-hydroxypropyl-β-cyclodextrin, benzalkonium chloride, d-mannitol, and methylcellulose). Retinal dysfunction was observable two weeks after rats received intraperitoneal injections of streptozotocin (100 mg/kg × 2, consecutive days, STZ rat). Changes in retinal function were evaluated by electroretinogram (ERG) and immunological methods. The retinal thickness, measured as the distance between the ganglion cell layer and the distal border of the outer nuclear layer, increased two weeks after the injection of streptozotocin, resulting in decreases in the levels of a-waves, b-waves, and oscillatory potential amplitudes in ERG of rats. The instillation of NILnano allowed the topical supplement of nilvadipine into the retina, and repeated instillation of NILnano (2 times/day) attenuated the retinal disorders led by the excessive streptozotocin. In conclusion, we found that retinal dysfunction in rats injected with streptozotocin can be prevented by the NILnano instillation. These results are useful in further studies aimed at the therapeutic treatment of retinopathy.

ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy

In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.

Reactive infiltration: identifying the role of chemical reactions, capillarity, viscosity and gravity

A wealth of experimental data indicate that while capillarity controlled infiltration gives an infiltration length that varies with the square root of time, reactive infiltration is characterised by a linear relationship between the two magnitudes. In addition the infiltration rate in the latter is at least two orders of magnitude greater than in the former. This work is addressed to investigate imbibition of a non-wetting, albeit reactive, liquid into a capillary, within the framework of a simple model that includes capillarity effects, viscosity and gravity. The capillary radius is allowed to vary, due to reaction, with both position and time, according to either an interface or a diffusion law. The model allows for capillary closure when reaction kinetics dominates imbibition. At short times, and depending on whether infiltration is capillarity or gravity controlled, the infiltrated length varies either as the square root or linearly with time. This suggest the following track for reactive infiltration: i) In most cases, the contact angle is initially larger than $90^\circ$, ii) after some time, reaction gradually replaces the interface liquid/preform by the liquid/reaction product interface and, concomitantly, the contact angle gets closer to $90^\circ$, iii) beyond that time, gravity triggers infiltration (actually the contact angle does not need to be smaller than $90^\circ$ for the initiation of infiltration due to the metallostatic pressure exerted by the liquid metal on top of the porous preform), iv) thereafter infiltration is controlled by viscosity and gravity, provided that, due to reaction, the contact angle remains close to that at which infiltration was initiated.

Quantification of Retinal Microvascular Density in Optical Coherence Tomographic Angiography Images in Diabetic Retinopathy

ImportanceQuantitative measurements based on optical coherence tomographic angiography (OCTA) may have value in managing diabetic retinopathy (DR), but there is limited information on the ability of OCTA to distinguish eyes with DR.ObjectiveTo evaluate the ability of measurements of retinal microvasculature using OCTA to distinguish healthy eyes from eyes with DR.Design, Setting, and ParticipantsIn this prospective cross-sectional study, OCTA was used to examine the eyes of participants with type 2 diabetes with or without DR and the eyes of participants without diabetes from September 17, 2015, to April 6, 2016. Density maps based on superficial retinal layer (SRL) and deeper retinal layer (DRL) images were generated after a method to remove decorrelation tails was applied to the DRL images.ExposuresBoth eyes of each participant were examined by means of a 3-mm OCTA scan and 7-field fundus photography using the Diabetic Retinopathy Severity Scale.Main Outcomes and MeasuresTwo measures were examined: perfusion density, based on the area of vessels, and vessel density, based on a map with vessels of 1-pixel width. The size of the foveal avascular zone was also calculated automatically, and so was the area under the receiver operating characteristic curve.ResultsA total of 50 eyes from 26 participants with diabetes (10 women and 16 men; mean [SD] age, 64.9 [7.5] years) and 50 healthy eyes from 25 participants without diabetes (14 women and 11 men; mean [SD] age, 64.0 [7.1] years) were imaged. All participants were white. Vessel density measured in the SRL had the highest area under the receiver operating characteristic curve (0.893 [95% CI, 0.827-0.959]), compared with perfusion density in the SRL (0.794 [95% CI, 0.707-0.881]), foveal avascular zone area (0.472 [95% CI, 0.356-0.588]), and vessel density in the DRL (0.703 [95% CI, 0.601-0.805]). Vessel density in the SRL negatively correlated with best-corrected visual acuity (r = –0.28; P = .05) and severity of DR (r = –0.46; P = .001). Density metrics correlated with age. No correlation was detected between vascular density or foveal avascular zone metrics and hemoglobin A1C or duration of diabetes.Conclusions and RelevanceVessel density measured by OCTA provides a quantitative metric of capillary closure that correlates with severity of DR and may allow staging, diagnosis, and monitoring that do not require subjective evaluation of fundus images.

OCT Angiography of the Peripapillary Retina in Primary Open-Angle Glaucoma.

The purpose of this study was to investigate the topographic relationship between the decreased parapapillary retinal microvasculature as assessed by optical coherence tomography angiography (OCTA) and retinal nerve fiber layer (RNFL) defect in eyes with primary open-angle glaucoma (POAG) and a localized RNFL defect. The peripapillary retinal circulation was evaluated using the OCTA centered on the optic nerve head in 98 POAG eyes having a localized RNFL defect and 45 healthy control eyes. A vascular impairment (VI) was identified in OCTA by the presence of a sign indicating decreased microvasculature. The frequencies of VI were compared between the POAG and control groups, and the topographic correlation between the VI and the RNFL defect identified in red-free fundus photographs was determined in the POAG group. The VI was observed as an area of decreased density of the microvascular network of the retina in 100% of the POAG eyes. The VI exactly coincided with the RNFL defect evident in red-free fundus photographs in terms of both the location and extent (Pearson's correlation coefficient = 0.997 and 0.988, respectively, all P < 0.001). None of the control eyes exhibited VI in OCTA. Decreased parapapillary microvasculature of the retina determined by OCTA was found at the location of RNFL defect in POAG patients. This finding suggests that the decreased retinal microvasculature is likely secondary loss or closure of capillaries at the area of glaucomatous RNFL atrophy.

Stem cell therapies in the treatment of diabetic retinopathy and keratopathy.

Nonproliferative diabetic retinopathy (DR) is characterized by multiple degenerative changes that could be potentially corrected by stem cell therapies. Most studies so far have attempted to alleviate typical abnormalities of early retinopathy, including vascular hyperpermeability, capillary closure and pericyte dropout. Success was reported with adult stem cells (vascular progenitors or adipose stem cells), as well as induced pluripotent stem cells from cord blood. The cells were able to associate with damaged vessels in both pericyte and endothelial lining positions in models of DR and ischemia-reperfusion. In some diabetic models, functional amelioration of vasculature and electroretinograms was noted. Another approach for endogenous progenitor cell therapy is to normalize dysfunctional diabetic bone marrow and residing endothelial progenitors using NO donors, PPAR-δ and -γ agonists, or inhibition of TGF-β. A potentially important strategy would be to reduce neuropathy by stem cell inoculations, either naïve (e.g., paracrine-acting adipose stem cells) or secreting specific neuroprotectants, such as ciliary neurotrophic factor or brain-derived neurotrophic factor that showed benefit in amyotrophic lateral sclerosis and Parkinson's disease. Recent advances in stem cell therapies for diabetic retinal microangiopathy may form the basis of first clinical trials in the near future. Additionally, stem cell therapies may prove beneficial for diabetic corneal disease (diabetic keratopathy) with pronounced epithelial stem cell dysfunction.

Bone-Conduction Hearing Aids

Bone-Conduction Hearing Aids

Effets des vasoconstricteurs sur la microcirculation

Physiology and animal models often predict microvascular negative effects of excessive vasoconstriction. The following are among them: a drop in capillary pressure (even closure of capillaries), a drop in microvascular haematocrit, a possible drop in flow, a possible decrease in capillary density. In fact, the impact of usual vasoconstrictors is difficult to predict, e.g. norepinephrine is an alpha agonist, which simultaneously increases arteriolar but also venular resistances together with a possible increase in cardiac output by beta stimulation or thanks to preload effect. Concerning norepinephrine and probably terlipressin, the effects on splanchnic, renal and most often sublingual microcirculation are globally either positive or neutral if a deep hypovolemia is treated before perfusion of the drug and if mean arterial pressure goal is below 75 mmHg. Phenylephrine seems deleterious and difficult to use. Vasopressin requires more studies concerning microcirculation. Careful titration and even decrementation of the drugs in case of tissue dysoxia (mottling of the skin, the increase of lactate levels) seems to be common sense.

Experimental retinal vein occlusion, a model of non‐neovascular microvascular remodeling

AbstractThe main cause of visual loss after retinal vein occlusion and diabetes is microvascular remodelling, a spectrum of functional and morphological changes affecting vessels. Some are beneficial, such as collateral vessel development. The other manifestations of microvascular remodelling are usually detrimental such as chronic rupture of the blood‐retinal barrier, capillary closure or macroaneurysms. The processes underlying microvascular remodelling are poorly understood, in part because of the absence of a clinically meaningful animal model. We have been investigating the effet of retinal vein occlusion in rodents using laser photocoagulation, which eanbled us to reproduce many of the features of human microvascular remodelling. Based on our experience, we will discuss issues related to interspecies variability and clinical relevance.

Neutralization of Vascular Endothelial Growth Factor Slows Progression of Retinal Nonperfusion in Patients with Diabetic Macular Edema

To determine the effect of suppression of vascular endothelial growth factor (VEGF) by monthly injection of ranibizumab on posterior retinal nonperfusion (RNP) in patients with diabetic macular edema (DME). Unplanned retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials. Six hundred sixty-six patients with DME. An independent reading center measured the area of RNP on fluorescein angiograms obtained in the phase 3 RISE and RIDE trials. The percentage of patients with no posterior RNP. The percentage of patients with no posterior RNP decreased in the sham group between baseline and month 24, but remained relatively stable in the 2 ranibizumab groups. After month 24, the sham group crossed over to receive monthly injections of ranibizumab 0.5 mg, and the differences between the sham and ranibizumab groups were reduced. The percentage of patients who showed an increase in posterior RNP from baseline increased over time in all 3 groups, but at a faster rate in the sham group, resulting in statistically significant differences at every time point between months 3 (9.6% vs. 18.5%; P = 0.016) and 24 (16.1% vs. 37.6%; P<0.0001) for ranibizumab 0.5 mg versus sham and from months 6 (12.3% vs. 23.0%; P = 0.013) through 24 (15.0% vs. 37.6%; P<0.0001) for ranibizumab 0.3 mg. Initiation of ranibizumab in the sham group at month 24 was followed by reduction in the percentage of patients with an increase in posterior RNP from baseline at months 30 and 36, whereas the 2 ranibizumab groups continued their gradual rise. Just as high VEGF levels contribute to progression of retinal nonperfusion in retinal vein occlusion, the same is true in patients with DME, suggesting that regardless of the underlying disease process, high levels of VEGF can cause closure of retinal vessels. However, our data also suggest that VEGF-induced worsening of retinal perfusion in DME is superimposed on another cause of more gradually worsening perfusion, possibly glucotoxicity. Thus, monthly injections of ranibizumab can slow, but not completely prevent, retinal capillary closure in patients with DME.