Retinal Vascular Abnormalities Research Articles

Successful resolution of coats disease by photodynamic therapy: a case report

BackgroundCoats disease is a retinal disease characterized by exudative retinal detachment due to abnormal retinal blood vessels. Coats disease is generally treated using laser photocoagulation and cryotherapy to ablate the abnormal retinal blood vessels. However, if abnormal blood vessels are present near the posterior pole of the eye and there is a severe exudative change there, it is difficult to perform these standard treatments. We describe a case of Coats disease with severe exudative retinal change and retinal vascular abnormality near the posterior pole for which we performed photodynamic therapy and successfully suppressed the disease and improved vision.Case presentationA 15-year-old Japanese boy presented to hospital with a chief complaint of decreased vision in his right eye. At the initial examination, corrected visual acuity of the right eye was 20/100. On the right fundus, exudative retinal detachment with subretinal haemorrhage was observed from the upper intermediate periphery to the posterior pole. Abnormal telangiectatic vessels and microaneurysms were found at the nasal peripheral retina. From these findings, we diagnosed the case as Coats disease. We conducted photodynamic therapy for the right eye. At 10 months after treatment, both the subretinal haemorrhage and the exudative retinal detachment had disappeared completely. Further, the retinal structure of the macula had recovered, and right vision had improved to 20/20.ConclusionPhotodynamic therapy may be an effective and safe treatment for Coats disease in cases that present with abnormal retinal vessels close to the posterior pole of the eye.

Wide-Field Swept-Source OCT and Angiography in X-Linked Retinoschisis

Retinal vascular and structural changes, particularly outside of the central macula, are not well characterized in X-linked retinoschisis (XLRS). We aim to describe wide-field swept-source OCT (SS-OCT) and swept-source OCT angiography (SS-OCTA) findings in XLRS. Retrospective, cross-sectional study at a tertiary referral center. Nine consecutive male patients with molecularly confirmed XLRS. All patients underwent complete ophthalmic examination with multimodal imaging, including SS-OCT with SS-OCTA (PLEX Elite 9000; Carl-Zeiss Meditec Inc., Dublin, CA). Images were then reviewed by 2retinal specialists as independent graders to determine the frequency and distribution of retinal structural and vascular abnormalities. Structural and vascular abnormalities seen on SS-OCT and SS-OCTA in patients with XLRS, with attention to the retinal layers involved, the regional distribution of schitic spaces in the posterior pole, and vascular abnormalities within the superficial and deep capillary plexuses. Eighteen eyes from 9 male patients (mean age, 20 years; range 9-40) with molecularly confirmed XLRS were included. Median best-corrected visual acuity measured 20/63 (range, 20/25-10/300). A total of 17 of 18 eyes (94.4%) were noted to have schitic spaces on SS-OCT, and these were observed to be predominantly within the inner nuclear layer in all 17 eyes. A regional variation in the distribution of cysts was noted, with schitic spaces within the ganglion cell layer (13/17 eyes; 76.5%) observed to be perifoveal and those within the outer nuclear layer (8/17 eyes, 47.1%) observed to be mostly extramacular. All eyes had vascular abnormalities on SS-OCTA, including an irregular foveal avascular zone and flow loss within the deep capillary plexus corresponding to the distribution of the schisis. Wide-field SS-OCT and SS-OCTA provide detailed visualization of structural and vascular changes in XLRS and may be helpful for monitoring disease progression or treatment response in clinical trials for the disease.

EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most frequently occurring microvascular complications of diabetes. Recent evidence indicates that epidermal growth factor receptors (EGFRs) are critical pathogenic players in non-neoplastic diseases, including diabetic cardiomyopathy and DR. However, the precise pathogenic mechanism of EGFR in DR has yet to be fully understood. In this study, we developed a type 1 diabetic early-stage retinopathy mouse model using injections of streptozotocin and an oxygen-induced end-stage diabetic retinopathy (OIR) model characterized by hypoxia-induced revascularization. We tested the hypothesis that the pathogenesis of DR can be reduced by the classic EGFR inhibitor, AG1478, in the mouse models. Our data indicated that treatment of AG1478 prevented retinal dysfunction, and reduced impairment of retinal structures as well as mitochondrial structures in retinal blood vessels in diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no effects on revascularization at the avascular sites when compared to untreated littermates in the OIR model. Our findings provide strong evidence that EGFR critically promoted retinal dysfunction, retinal structural impairment, and retinal vascular abnormalities in models of DR. We conclude that EGFR can be a potential important therapeutic target for treatment of DR.

Incontinentia pigmenti-associated ocular anomalies of paediatric incontinentia pigmenti patients in China.

To characterize ocular manifestations in a cohort of paediatric patients with incontinentia pigmenti (IP) and to define the guidelines for grading of IP-associated retinopathy (IPR). This retrospective review was performed on patients under the age of 18years with a diagnosis of IP. Data included demographics, medical history, ocular examination, and accessory examination. Ocular and systemic physical examinations of the parents were carried out to determine the familial history. Sixty-one children (58 females and three males) with median age of 3.7months were observed consecutively. The median follow-up duration was 13.4months (range: 6.5-75.0months). A total of 47 patients had various ocular anomalies. Among them, 28 patients had bilateral ocular anomalies and 19 had unilateral anomalies. Vitreoretinal changes were noted in 73 of 122 eyes, including eight eyes with retinal pigment epithelium changes only (Stage 1), 22 eyes with retinal vascular abnormalities (Stage 2), five eyes with epiretinal membranes or fibrotic hyperplasia combined with avascularized zones (Stage 3), six eyes with retinal neovascularization (Stage 3), one eye with vitreous haemorrhage (Stage 3), 10 eyes with partial retinal detachment (RD) (Stage 4a), 15 eyes with total RD (Stage 4b) and eight eyes with phthisis bulbi and secondary glaucoma (Stage 5). Various vitreoretinal manifestations can be found in paediatric patients with IP and classified into five stages, which are characterized by retinal vasculopathy.

N,N-Dimethyl-3β-hydroxycholenamide Reduces Retinal Cholesterol via Partial Inhibition of Retinal Cholesterol Biosynthesis Rather Than its Liver X Receptor Transcriptional Activity

N,N-dimethyl-3β-hydroxycholenamide (DMHCA) is an experimental pharmaceutical and a steroidal liver X receptor (LXR) agonist, which does not induce undesired hepatic lipogenesis. Herein, DMHCA was evaluated for its retinal effects on normal C57BL/6J and Cyp27a1−/−Cyp46a1−/− mice; the latter having higher retinal total and esterified cholesterol in addition to retinal vascular abnormalities. Different doses and two formulations were used for DMHCA delivery either via drinking water (C57BL/6J mice) or by oral gavage (Cyp27a1−/−Cyp46a1−/− mice). The duration of treatment was 1 week for C57BL/6J mice and 2 or 4 weeks for Cyp27a1−/−Cyp46a1−/− mice. In both genotypes, the higher DMHCA doses (37–80 mg/kg of body weight/day) neither increased serum triglycerides nor serum cholesterol but altered the levels of retinal sterols. Total retinal cholesterol was decreased in the DMHCA-treated mice, mainly due to a decrease in retinal unesterified cholesterol. In addition, retinal levels of cholesterol precursors lanosterol, zymosterol, desmosterol, and lathosterol were changed in Cyp27a1−/−Cyp46a1−/− mice. In both genotypes, DMHCA effect on retinal expression of the LXR target genes was only moderate and gender-specific. Collectively, the data obtained provide evidence for a decrease in retinal cholesterol as a result of DMHCA acting in the retina as an enzyme inhibitor of cholesterol biosynthesis rather than a LXR transcriptional activator. Specifically, DMHCA appears to partially inhibit the cholesterol biosynthetic enzyme Δ24-dehydrocholesterol reductase rather than upregulate the expression of LXR target genes involved in reverse cholesterol transport. The identified DMHCA dosages, formulations, and routes of delivery as well as the observed effects on the retina should be considered in future studies using DMHCA as a potential therapeutic for age-related macular degeneration and diabetic retinopathy.

A Review on the Extraction of Quantitative Retinal Microvascular Image Feature.

Digital image processing is one of the most widely used computer vision technologies in biomedical engineering. In the present modern ophthalmological practice, biomarkers analysis through digital fundus image processing analysis greatly contributes to vision science. This further facilitates developments in medical imaging, enabling this robust technology to attain extensive scopes in biomedical engineering platform. Various diagnostic techniques are used to analyze retinal microvasculature image to enable geometric features measurements such as vessel tortuosity, branching angles, branching coefficient, vessel diameter, and fractal dimension. These extracted markers or characterized fundus digital image features provide insights and relates quantitative retinal vascular topography abnormalities to various pathologies such as diabetic retinopathy, macular degeneration, hypertensive retinopathy, transient ischemic attack, neovascular glaucoma, and cardiovascular diseases. Apart from that, this noninvasive research tool is automated, allowing it to be used in large-scale screening programs, and all are described in this present review paper. This paper will also review recent research on the image processing-based extraction techniques of the quantitative retinal microvascular feature. It mainly focuses on features associated with the early symptom of transient ischemic attack or sharp stroke.

Intravitreal injection of ranibizumab in severe retinopathy of incontinentia pigmenti

Incontinentia pigmenti (IP) is a rare X-linked multisystem disorder that mainly affects females and is usually lethal to males in utero. Mutations in the NEMO gene on chromosome Xq28 (IKBKG, inhibitor of kB kinase gamma) have been shown to cause IP. Approximately 35% of patients have ophthalmic manifestations, and 20% develop vision-threatening diseases. Retinal vascular abnormalities, from peripheral retinal avascularity to neovascular proliferation, have been described in IP patients. Laser photocoagulation and cryotherapy are traditionally effective therapy for retinopathy of IP. However, some cases still progress to retinal detachment. We report 2 cases of IP infants treated with intravitreal ranibizumab with subsequent resolution of the vasculopathy.

Multimodal Retinal Imaging in Incontinentia Pigmenti Including Optical Coherence Tomography Angiography

Incontinentia pigmenti (IP) is a rare, X-linked dominant disease with potentially severe ocular complications that predominantly affect the peripheral retina. However, little is known about its effects on the macula. To describe the structural and vascular abnormalities observed in the maculas of patients with IP and to correlate these findings with peripheral pathologies. Prospective, cross-sectional study at Wilmer Eye Institute, Johns Hopkins University. Five participants with a clinical diagnosis of IP were included and underwent multimodal imaging with ultra-wide-field fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), and OCT angiography. The structural and vascular abnormalities observed on spectral-domain OCT and OCT angiography and their correlation with peripheral pathologies seen on ultra-wide-field FA. A total of 9 eyes from 5 patients (median age, 20.5 years; range, 8.4-54.2 years) were included. Median Snellen visual acuity was 20/32 (range, 20/16 to 20/63). ultra-wide-field FA-identified retinal vascular abnormalities in all 7 eyes in which FA was obtained. These abnormalities included microaneurysms, areas of nonperfusion, and vascular anastomoses, most of which were peripheral to the standard view of 30° FA with peripheral sweeps. Structural abnormalities were observed in 6 eyes on spectral-domain OCT, including inner retinal thinning and irregularities in the outer plexiform layer. Optical coherence tomography angiography abnormalities were noted in all 9 eyes, including decreased vascular density, abnormal vascular loops, and flow loss in the superficial and deep plexuses, which corresponded to areas of retinal thinning on spectral-domain OCT. Although our study is limited by the small sample size, the findings suggest that multimodal imaging is useful for detecting structural and vascular abnormalities that may not be apparent on ophthalmoscopy in patients with IP. Macular pathologies, especially a decrease in vascular density on OCT angiography, are common. Further studies are needed to characterize further the association between macular and peripheral abnormalities in patients with IP.

RETINAL VASCULAR ABNORMALITIES IN A LARGE COHORT OF PATIENTS AFFECTED BY NEUROFIBROMATOSIS TYPE 1: A Study Using Optical Coherence Tomography Angiography.

To evaluate the prevalence, the vascular features, and the clinical diagnostic implication of retinal vascular abnormalities (RVAs) associated with neurofibromatosis Type 1 (NF1) in a large cohort of patients. Two hundred and ninety-four patients affected by NF1 were consecutively enrolled. The presence of RVAs was detected by means of infrared confocal scanning laser ophthalmoscopy images. Three hundred age- and race-matched healthy subjects were enrolled as a healthy control group. Fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography were also performed in patients with RVAs. Retinal vascular abnormalities were detected in 18 patients with NF1 (6.1%) and in none of the healthy subjects. Retinal vascular abnormalities appeared in all cases as well-defined, small, tortuous retinal vessels with a spiral aspect, originating from small tributaries of retinal veins. The presence of RVAs did not correlate with the presence of other specific ocular or systemic NF1 features (P > 0.05). On optical coherence tomography angiography, RVAs appeared as an isolated tortuous vessel of the superficial vascular plexus in all cases, associated with localized anomalous crowded and congested capillary network of the deep vascular plexus in 75% of cases. Retinal vascular abnormalities are present in a limited proportion of patients affected by NF1 and can be considered an additional distinctive sign of the disease.

Three Cases of Congenital Retinal Macrovessel, One Coexisting with Cilioretinal Artery.

In this report, we describe three cases of retinal macrovessel. Two of the three patients presented to our clinic for annual eye exam and had no visual complaints. The third patient presented because of vision loss in the left eye. Two patients had 20/20 best corrected visual acuity in both eyes and the third patient had 20/20 in the right eye, 20/25 in the left eye. Pupillary exams were normal. Slit-lamp examinations of the anterior segment were unremarkable. Fundus examination revealed macrovessels in the left eyes of two patients and in the right eye of one patient. The patients underwent complete ophthalmological examinations including color fundus photography for all three patients and optic coherence tomography, fundus autoflorescence, and fundus fluorescein angiography for two of the patients. Cilioretinal artery coexisting with macrovessel was seen angiography in one case. Congenital retinal macrovessel is a rare vascular condition. It is often unilateral and the vessel is an aberrantly large branch of the retinal arteries or veins. They may cross the fovea and their visual impact is minimal. The coexistence of congenital retinal macrovessel and cilioretinal artery is very rare. Visual impairment may occur in congenital retinal macrovessel due to retinal cavernous hemangioma, foveal cysts, central serous retinopathy, and other retinal vascular abnormalities.

Glaucomatous optic neuropathy treatment options: the promise of novel therapeutics, techniques and tools to help preserve vision.

Peripheral vision loss followed by “tunnel vision” and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma (POAG) and normotensive glaucoma (NTG). These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells (RGCs) accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve. Since patients suffering from this glaucomatous optic neuropathy (GON) first notice visual impairment when they have lost > 40% of their RGCs, early diagnosis is the key to retard the progression of glaucoma. Elevated intraocular pressure (IOP), low cerebrospinal and/or low intracranial fluid pressure, advancing age, and ethnicity are major risk factors associated with POAG. However, retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic, inflammatory, oxidative and mechanical insults also contribute to vision loss in POAG/GON. Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs, combination drug products, and surgical interventions. Two recently approved multi-pharmacophoric drugs (e.g., rho kinase inhibitor, Netarsudil; a drug conjugate, Latanoprostene Bunod) and novel aqueous humor drainage devices (iStent and CyPass) are also gaining acceptance for treating POAG/ NTG. Neuroprotective and regenerative agents, coupled with electroceutical, mechanical support systems, stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON. The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures, thereby providing a gain of function of the visual system for the glaucoma patients.

Fluorescein Angiographic Abnormalities in the Contralateral Eye with Normal Fundus in Children with Unilateral Coats' Disease.

PurposeWe report the detection of peripheral retinal vascular abnormalities in the fellow eye with normal fundus in children with unilateral Coats' disease.MethodsThe clinical records of patients diagnosed with Coats' disease were retrospectively reviewed. We recorded the subjects' characteristics and obtained fundus photography and fluorescein angiography (FA) images. The main outcome measure was peripheral vascular abnormalities in the contralateral eye with normal fundus in children with unilateral Coats' disease, observed with FA.ResultsOut of 47 patients with Coats' disease, two (4.3%) were diagnosed with clinically bilateral Coats' disease. Of the 45 patients with presumed unilateral Coats' disease, four (8.9%) had bilateral abnormal peripheral vasculature in FA. The mean age of these four patients was 6.4 ± 5.4 years (range, 1 to 14 years), and three patients were male (75%). All four had peripheral retinal nonperfusion, and two (50%) received laser photocoagulation due to peripheral leakage with telangiectatic vessels.ConclusionsCoats' disease may more often be a bilateral disease with asymmetry than previously thought. Patients with Coats' disease should undergo careful examination of the fellow eye with FA in order to detect and treat vascular abnormalities that are not visible clinically.

Pathophysiology of Diabetic Retinopathy: The Old and the New.

Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities—including hyperpermeability, hypoperfusion, and neoangiogenesis—that eventually lead to anatomical and functional alterations in retinal neurons and glial cells. Recent advances in retinal imaging systems using optical coherence tomography technologies and pharmacological treatments using anti-vascular endothelial growth factor drugs and corticosteroids have revolutionized the clinical management of DR. However, the cellular and molecular mechanisms underlying the pathophysiology of DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects of subclinical and early DR. Conversely, non-diabetic mouse models that represent the hallmark vascular disorders in DR, such as pericyte deficiency and retinal ischemia, have provided clues toward an understanding of the sequential events that are responsible for vision-impairing conditions. In this review, we summarize the clinical manifestations and treatment modalities of DR, discuss current and emerging concepts with regard to the pathophysiology of DR, and introduce perspectives on the development of new drugs, emphasizing the breakdown of the blood-retina barrier and retinal neovascularization.

Incidental branch retinal artery occlusion on optical coherence tomography angiography presenting as segmental optic atrophy in a child: a case report

BackgroundRetinal artery occlusion is extremely rare in the pediatric population and most patients have risk factors. We report a case of a healthy child with segmental optic atrophy, complicated by incidental branch retinal artery occlusion (BRAO).Case presentationA 10-year-old boy who had a history of his mother’s gestational diabetes presented with an inferonasal visual field defect in the left eye. His best-corrected visual acuities were 20/20 in both eyes (OU). Fundoscopic examination revealed segmental pallor of the left optic disc, thinning of the superotemporal rim, a relative superior entrance of the central retinal artery and superior peripapillary scleral halo. Fluorescein angiography showed patchy filling delays in the corresponding disc area without retinal vascular abnormalities. Spectral domain optical coherence tomography (SD OCT) via automated segmentation analysis demonstrated sectoral absence of the ganglion cell layer and retinal nerve fiber layer with thinning of the inner plexiform layer, inner nuclear layer and outer plexiform layer in the corresponding retina. OCT angiography (OCTA) showed focal attenuation of superficial and intermediate/deep capillary plexuses in the corresponding areas. Systemic evaluation was unremarkable. The patient was diagnosed with segmental optic atrophy caused by incidental BRAO.ConclusionsRetinal vascular occlusions are rare in childhood, and may present as segmental optic atrophy mimicking congenital anomalies. OCTA allows the detection of previous microvascular abnormalities in the chronic phase. To the best of our knowledge, this is the first report of a child with segmental optic atrophy presumably caused by BRAO, which was documented by SD OCT and OCTA in detail.

Ocular findings in Loeys-Dietz syndrome

BackgroundLoeys-Dietz syndrome (LDS), an autosomal-dominant connective tissue disorder, is characterised by systemic manifestations including arterial aneurysm and craniofacial dysmorphologies. Although ocular involvement in LDS has been reported, detailed information on...

Segmented swept source optical coherence tomography angiography assessment of the perifoveal vasculature in patients with X-linked juvenile retinoschisis: a serial case report

PurposeTo describe perifoveal microvascular changes occurring in X-linked juvenile retinoschisis (XLRS) using swept source optical coherence tomography angiography (SS OCTA).Patients and methodsThis is a serial case report of three patients. Retrospective data of patients affected by XLRS were collected. Structural optical coherence tomography (OCT) and color fundus photography (CFPh) were carried out with Topcon® OCT 2000 3D OCT as part of the standard care. Two patients were imaged on Topcon Atlantis® SS OCTA and one on Topcon Triton® SS OCTA. SS OCTA images were acquired using the 3 × 3 mm fovea-centered cubes scanning protocol. Analysis of both perifoveal superficial vascular plexus (pSVP) and perifoveal deep vascular plexus (pDVP) was performed by two observers after automated segmentation.ResultsFour eyes of three males (mean age 14 ± 3.8 years) were analyzed. All eyes showed foveoschisis on CFPh images. OCT B-scans of three eyes showed schistic cysts in the ganglion cell layer, inner nuclear layer (INL) and outer nuclear layer (ONL); in one eye, cysts were depicted in INL and ONL only. In two eyes, SS OCTA showed abnormal foveal avascular zone (FAZ) shape in the pSVP, and in the other two, FAZ shape was abnormal in both plexuses. In all eyes, retinal vascular abnormalities (ie, microvascular protrusions) were present in pDVP.ConclusionSS OCTA can depict perifoveal microvascular changes in young patients affected by XLRS. In this study, the structural and vascular changes seem to be more evident in the pDVP and may represent a useful biomarker of prognosis.

Retinal Vascular Morphological Changes in Patients with Extremely Severe Obstructive Sleep Apnea Syndrome.

Background:Obstructive sleep apnea syndrome (OSAS) has been shown to generate hypertension and endothelial dysfunction. Retinal vessel is the only vessel that can be observed directly and noninvasively; retinal vascular abnormalities can serve as a predictive marker for the occurrence, clinical course, and prognosis of cardiovascular and cerebrovascular diseases. The objective of this study was to identify the effect of OSAS severity on the morphological changes of retinal vessels.Methods:Adult patients complained of snoring were included in this study. The patients’ general information, polysomnography, and fundus photography parameters including central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) were collected. Patients were divided into four groups according to their apnea-hypopnea index (AHI) results: Group I, AHI ≤5/h; Group II, 5/h < AHI ≤30/h; Group III, 30/h < AHI ≤60/h; and Group IV, AHI >60/h.Results:A total of 133 patients were included in this study with 111 males (83.5%) and 22 females (16.5%). Mean age was 41.6 ± 9.9 years, and the mean body mass index was 28.1 ± 4.0 kg/m2. AHI ranged between 0 and 130.8/h with a mean of 39.1 ± 30.7/h. There were 24, 34, 35, and 40 patients in Group I, Group II, Group III, and Group IV, respectively. Significant differences were found for AHI (F = 388.368, P < 0.001), minimal pulse oxygen saturation (F = 91.902, P < 0.001), and arousal index (F = 31.014, P < 0.001) among four groups; no significant differences were found for CRAE (F = 0.460, P = 0.599) and CRVE (F = 0.404, P = 0.586) among groups; there were significant differences for AVR between Group I and Group IV (63.6 ± 5.1% vs. 67.2 ± 5.5%, P = 0.010) Group II and Group IV (64.5 ± 6.0% vs. 67.2 ± 5.5%, P = 0.030), and Group III and Group IV (64.7 ± 4.1% vs. 67.2 ± 5.5%, P = 0.043). A main group-by-AHI effect was found on the AVR: patients with higher AHI showed higher AVR results (r = 0.225, P = 0.009). Multivariate logistic regression analysis was used for multi-variable factors. A group-by-age effect was found on the AVR: younger patients showed higher AVR results (β = −0.001, P = 0.020).Conclusions:This study indicated that increased AVR of retinal vessel can be observed in extremely severe OSAS patients. For patients with OSAS, retinal vascular abnormalities may become an early indication for further cardiovascular abnormalities.

Emphasis on the study of correlation between retinal vascular abnormalities and systemic vascular diseases

The abnormalities of retinal vessels such as retinal arteriolar narrowing, arteriovenous nicking, micro-aneurysms, retinal hemorrhages, and cotton wool spot are closely related to systemic diseases including hypertension, diabetes mellitus, cardiovascular disorders, stroke and renal diseases. The modern retinal vessels examination technology has features of quick noninvasive, quantitative standardized and intelligent analysis. Taking advantage of these to fully discover the retinal vascular abnormalities and get deeper understanding of the relationship between its′ mechanism and systemic vascular diseases is not only helpful to better diagnose and treat retinal vascular diseases, but also contributes to predicting the risk and prognosis of systemic diseases. We suggest emphasizing on the study of correlation between retinal vascular abnormalities and systemic vascular diseases using modern retinal vessels examination technology. It will provide the preventive clue of diseases of circulatory system by finding out the retinopathy. Meanwhile, correctly treating systemic diseases would get a better prognosis of the retinopathy. They exist side by side and play a part together for providing a better prognosis, which would be a new direction for the doctors and scientists in the new era. Key words: Retinal vessels/ injuries; Vascular diseases/prevention & control; Tomography, optical coherence; Editorial

LRP-1 Pathway Targeted Inhibition of Vascular Abnormalities in the Retina of Diabetic Mice

ABSTRACTPurpose: The cell surface LDL (low-density lipoprotein) receptor-related protein-1 (LRP-1) is important for lipid transport and several cell signaling processes. Human apolipoprotein E (apoE) is a ligand of LRP-1. We previously reported that a short peptide (apoEdp) mimicking the LRP-1 binding region of apoE prevents hyperglycemia-induced retinal endothelial cell dysfunction in vitro. The in-vivo outcome of apoE-based peptidomimetic inhibition of LRP-1 in the treatment of diabetic retinopathy is unknown.Methods: Six months after streptozotocin induction of diabetes, male C57Bl/6 mice were intravitreally inoculated with apoEdp in a controlled release formulation. On the 15th day post-apoEdp treatment, mouse retinas were harvested to examine (1) blood–retinal–barrier (BRB) permeability by Evans blue dye, inflammatory leukostasis by concanavalin staining of leukocytes and LRP-1 pathway-related protein expression by Western blot analysis and gelatin zymography.Results: Intravitreal apoEdp treatment of diabetic mice significantly reduced Evans blue extravasation and the number of adherent leukocytes in the diabetic mouse retinas. ApoEdp treatment inhibited the expression of extracellular matrix (ECM) degrading proteases heparanase and MMP-2, and restores the BRB tight junction proteins occludin and ZO-1. ApoEdp treatment also inhibited Wnt/β-catenin-related expression of pro-inflammatory molecules ICAM-1, HIF-1α, and VEGF through negative regulation by LRP-1.Conclusion: Intravitreal apoEdp treatment of diabetic mice resulted a significant decrease in retinal vascular abnormalities through downregulation of LRP-1-related ECM protein degradation and Wnt/β-catenin-related pro-angiogenic molecules.

Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration (MERLOT): A Phase 3 Randomized Controlled Trial

To assess the safety and efficacy of epimacular brachytherapy (EMB) for patients with chronic, active, neovascular age-related macular degeneration (AMD). Phase 3 randomized controlled trial. Patients (n= 363) with neovascular AMD already receiving intravitreal ranibizumab injections. Either pars plana vitrectomy with 24-gray EMB and ongoing pro re nata (PRN) ranibizumab (n=224) or ongoing PRN ranibizumab monotherapy (n= 119). The coprimary outcomes, at 12 months, were the number of PRN ranibizumab injections and Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (VA). Secondary outcomes included the proportion of participants losing fewer than 15 ETDRS letters, angiographic total lesion size, choroidal neovascularization (CNV) size, and optical coherence tomography (OCT) foveal thickness. A predefined subgroup analysis tested the influence of baseline ocular characteristics on the response to EMB. The mean number of PRN ranibizumab injections was 4.8 in the EMB arm and 4.1 in the ranibizumab monotherapy arm (P= 0.068). The mean VA change was-4.8 letters in the EMB arm and-0.9 letters in the ranibizumab arm (95% confidence interval of difference between groups,-6.6 to-1.8 letters). The proportion of participants losing fewer than 15 letters was 84% in the EMB arm and 92% in the ranibizumab arm (P= 0.007). In the EMB arm, the mean total lesion size increased by 1.2 mm(2) versus 0.4 mm(2) in the ranibizumab arm (P= 0.27). The CNV size decreased by 0.5 mm(2) in the EMB arm and by 1.3 mm(2) in the ranibizumab arm (P= 0.27). The OCT foveal thickness decreased by 1.0 μm in the EMB arm and by 15.7 μm in the ranibizumab arm (P= 0.43). Most subgroups favored ranibizumab monotherapy, some significantly so. One participant showed retinal vascular abnormality attributed to radiation, but otherwise safety was acceptable. These results do not support the use of EMB for chronic, active, neovascular AMD. Safety isacceptable out to 12 months, but radiation retinopathy can occur later, so further follow-up is planned.