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To compare the rates of complications in eyes that received a dexamethasone (DEX) implant (0.7 mg) or intravitreal triamcinolone (IVT) (2 mg) to treat post-vitrectomy macular edema (ME).Retrospective, comparative, case series.A total of 148 eyes (147 patients) were included. There were 75 eyes (75 patients) in the DEX group and 73 eyes (72 patients) in the IVT group.The medical records of patients who received an intravitreal DEX 0.7 mg (Ozurdex®) or triamcinolone (2 mg) (Triesence®) for post-vitrectomy ME between July 2014 and December 2021 with a minimum follow-up of three months were reviewed. Ocular hypotony and ocular hypertension were defined as intraocular pressure of6 mmHg and24 mm Hg, respectively.The types and rates of complications.The follow-up duration was 2.5 ± 1.6 years, with no significant difference between the groups (P = 0.398). The rate of transient ocular hypotony per eye and per injection was significantly higher in the DEX group (10 eyes [13%], 30/443 injections [7%]) compared with the IVT group (2 eyes [3%], 2/262 injections [0.8%]) (P = 0.039 and0.001, respectively). Mean visual acuity significantly decreased at the time of ocular hypotony (P = 0.031), but returned to pre-injection level following resolution of the hypotony after a median of 12 days. The incidence of ocular hypertension was higher in the DEX group (23 eyes [31%]) than the IVT group (16 eyes [22%]), but this was not statistically significant (P = 0.307). Ocular hypertension was controlled with observation or topical medication. There were no between-group differences in the incidence of vitreous hemorrhage (DEX, 3 eyes [4%]; IVT, 1 eye [1%]; P = 0.632) or rhegmatogenous retinal detachment (DEX, 3 eyes [4%]; IVT, 0 eyes [0%]; P = 0.253). Four eyes (5%) experienced migration of the DEX implant into the anterior chamber. No eye developed endophthalmitis.The incidence of ocular hypotony, which causes transient visual impairment, was significantly higher in vitrectomized eyes treated with DEX, compared with eyes treated with IVT. Injections other than the inferotemporal quadrant or rotating injection sites may be recommended.

We report a case of a patient with 18p deletion syndrome and concurrent FZD4 (frizzled-4) mutation. A 6-month-old boy with known 18p deletion syndrome presented with abnormal eye movements in both eyes and an inability to track objects. The patient had a history of laryngomalacia, hypotonia, and developmental delay. Examination showed bilateral total exudative and traction retinal detachment with anomalous retinal vascular development noted on widefield fluorescein angiography. Genetic analysis identified a concurrent FZD4 mutation (c.205C>T [p.H69Y]). Both eyes underwent 25-gauge limbal vitrectomy, lensectomy, and membrane peeling, and the posterior pole successfully reattached with improvement in visual function. The 18p region contains the LAMA1 , TGIF1 , and APCDD1 genes, which are involved in the vascular basement membrane and Wnt/β-catenin signaling, which may have potentiated the particularly severe familial exudative vitreoretinopathy phenotype. We present the clinical findings, imaging analyses, and surgical management of concurrent 18p deletion syndrome and FDZ4 mutation. The overlap in molecular mechanisms of the multiple gene products may potentiate the severe phenotype. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:284–290.]

Background and Objective: To utilize quantitative ultra widefield retinal imaging to investigate the risk factors associated with the incidence and severity of postoperative epiretinal membrane (ERM) in patients who underwent primary rhegmatogenous retinal detachment (RRD) repair. Patients and Methods: This retrospective study included patients who underwent pars plana vitrectomy (PPV) with scleral buckle (SB) for RRD, without a prior history of ERM, and who underwent ultra widefield imaging postoperatively between June 2020 and February 2022. The size and location (distance from the macula) of the drainage retinotomy and the area of peripheral pathology, including retinal breaks and laser scars, were quantitatively measured with cloud-based software. The severity of postoperative ERM formation at 6 months was graded from grade 1 to 4. We investigated the risk factors that were significantly associated with the incidence and severity of postoperative ERM at 6 months. Results: We included 80 eyes (80 patients) in this study. Postoperative ERM developed in 37 eyes (46%) at 6 months. The severity of ERM was grade 1 in 24 eyes (65%), grade 2 in 6 eyes (16%), grade 3 in 4 eyes (11%), and grade 4 in 3 eyes (8%). Postoperative ERM was not associated with the presence or the location of drainage retinotomy ( P = 0.836 and 0.820, respectively). However, it was significantly associated with larger surface area of drainage retinotomy ( P = 0.039). In addition, postoperative ERM was significantly associated with a larger area of peripheral pathology ( P = 0.012), a larger extent of RRD ( P = 0.013), vitreous hemorrhage ( P = 0.026), redetachment within 6 months ( P = 0.022), use of silicone oil as a tamponade ( P = 0.047), and number of surgeries within 6 months ( P = 0.027). These factors, in addition to 360° endolaser, were also significantly associated with the severity of postoperative ERM. In multivariable linear regression analysis, the only variable that remained statistically significant was the size of the drainage retinotomy ( P = 0.023). Conclusion: The pathogenesis of postoperative ERM is multifactorial. Large drainage retinotomies may increase the risk of ERM formation. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:206–216.]

To assess preretinal abnormal tissue (PAT) using en face OCT in eyes with idiopathic macular holes (MHs).Retrospective, observational study.Patients with MH who received 6 × 6-mm spectral-domain-OCT scans.Preretinal abnormal tissue was detected by en face OCT images with a custom slab, defined with an anterior boundary of 6 μm anterior to the internal limiting membrane (ILM) and a posterior boundary at 3 μm posterior to the ILM. The PAT was defined as any abnormal tissues observed in en face OCT.Characteristics of preoperative and postoperative PAT.Sixty eyes with MH from 60 patients were included. Fifty-one eyes underwent preoperative analysis, and 46 eyes underwent postoperative examination. Before surgery, 48 (94%) eyes had a mean (standard deviation [SD]) PAT of 6.6 (9.8) mmEn face OCT revealed PAT in most eyes with MHs. Peri-MH PAT was associated with worse VA and was seen more frequently in male patients. Postoperative PAT proliferation may be triggered by ILM peeling, but it is not associated with worse VA.

To investigate the prevalence of vitreous cortex remnants (VCR) in primary rhegmatogenous retinal detachment (RRD) and the utility of VCR removal using diamond-dusted membrane scrapers (DDMS) during pars plana vitrectomy (PPV).One hundred and eighty-seven eyes (187 consecutive patients) were retrospectively studied. We evaluated the prevalence of VCR on the retinal surface extending from the macula to outside the vascular arcade in eyes that underwent PPV for primary RRD by a single surgeon between July 2014 and February 2021. The VCR outside the vascular arcade was completely removed using a DDMS. Preoperative factors and surgical outcomes were compared between eyes with VCR removed intraoperatively to those without VCR.VCR was present and removed (group A) in 86 (46%) eyes and absent (group B) in 101 (54%) eyes. Patients with VCR were significantly older than those without (Nearly half of the patients had VCR, which was more likely to occur in older patients. VCR removal resulted in favorable functional and anatomic outcomes similar to those in eyes without any VCR in patients with RRD.

We present a case of a congenital retinal macrovessel (CRM) with spontaneous resolution of cystoid macular edema. A 39-year-old woman with sudden decreased vision in her right eye was referred to our clinic and found to have a CRM with macular edema. Her visual acuity was 20/25. A week later, the macular edema disappeared without any treatment, and her visual acuity was 20/15. We performed optical coherence tomography angiography and fluorescein angiography (FA), which revealed no obstruction of retinal flow but a slight disturbance of retinal flow near the central fovea on FA. We encountered a case of spontaneous resolution of macular edema with abnormal vessel crossing near the central macula by a CRM, and multimodal imaging was useful for investigating the pathology of the disease.

Angiogenesis plays a crucial role in tumor growth, with an undisputed contribution of resident endothelial cells (EC) to new blood vessels in the tumor. Here, we report the definition of a small population of vascular-resident stem/progenitor–like EC that contributes predominantly to new blood vessel formation in the tumor. Although the surface markers of this population are similar to other ECs, those from the lung vasculature possess colony-forming ability in vitro and contribute to angiogenesis in vivo. These specific ECs actively proliferate in lung tumors, and the percentage of this population significantly increases in the tumor vasculature relative to normal lung tissue. Using genetic recombination and bone marrow transplant models, we show that these cells are phenotypically true ECs and do not originate from hematopoietic cells. After treatment of tumors with antiangiogenic drugs, these specific ECs selectively survived and remained in the tumor. Together, our results established that ECs in the peripheral vasculature are heterogeneous and that stem/progenitor–like ECs play an indispensable role in tumor angiogenesis as EC-supplying cells. The lack of susceptibility of these ECs to antiangiogenic drugs may account for resistance of the tumor to this drug type. Thus, inhibiting these ECs might provide a promising strategy to overcome antiangiogenic drug resistance. Cancer Res; 76(11); 3200–10. ©2016 AACR.

The structure and function of tumor blood vessels profoundly affects the tumor microenvironment. Signals mediated through the lysophosphatidic acid receptor 4 (LPA4) promote vascular network formation to restore normal vascular barrier function in subcutaneous tumors and thus improve drug delivery. However, the characteristics of the vasculature vary by organ and tumor types, and how drug delivery and leukocyte trafficking are affected by modification of vascular function by LPA in different cancers is unclear. Here, we show that LPA4 activation promotes the formation of fine vascular structures in brain tumors. RhoA/ROCK signaling contributed to LPA-induced endothelial cell–cell adhesion, and RhoA/ROCK activity following LPA4 stimulation regulated expression of VCAM-1. This resulted in increased lymphocyte infiltration into the tumor. LPA improved delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of anti–programmed cell death-1 antibody therapy. These results indicate the effects of LPA on vascular structure and function apply not only to chemotherapy but also to immunotherapy.Significance:These findings demonstrate that lysophosphatidic acid, a lipid mediator, promotes development of a fine capillary network in brain tumors by inducing tightening of endothelial cell-to-cell adhesion, facilitating improved drug delivery, and lymphocyte penetration.

Supplementary Figure 1. Coverage of pericyte and the basal membrane by LPA. Expression of LPA4 in several tumors. Supplementary Figure 2. Survival of wild-type and LPA4-KO mice harboring LLC brain tumors treated with or without LPA in the presence or absence of 5-FU. Supplementary Figure 3. Junctional protein expressioon in vascular endothelial cells by LPA. Supplementary Figure 4. LPA induces ICAM-1 expression but doesn't alter the expression of an HEV marker protein on endothelial cells Supplementary Figure 5. Investigation of LPA mediated VCAM-1 expression in MS-1 cells by using several inhibitors. Supplementary Figure 6. PD-L1 expression in GL261 brain tumors and LLC subcutaneous tumors. HE staining of the brain after anti-PD-1 antibody and LPA treatment.

Supplementary figure legend for supplementary figure S1

EC-SP and -MP cells are in the active phase of the cell cycle in the tumor microenvironment.

Supplementary Materials and Methods

To investigate the global practice patterns for the management of exogenous endophthalmitis. This cross-sectional study was conducted to assess global practice patterns for the management of exogenous endophthalmitis. An online survey comprised of questions regarding the management of exogenous endophthalmitis was distributed to institutions who are members of International Globe and Adnexal Trauma Epidemiology Study Group (IGATES) or invited affiliates of the American Society of Ophthalmic Trauma and the Asia Pacific Ophthalmic Trauma Society. Responses were gathered from August 2020 to January 2021. Of 42 institutions, 36 responses were received (86% response rate), of which 33 (79%) were included in the analysis. Included centers were from Asia (36%), North America (36%), South America (12%), Africa (9%), Europe (3%), and Australia (3%). Oral antibiotics were administered in 19 (58%) institutions, with moxifloxacin as the preferred agent (n = 9, 27%). The preferred method for obtaining cultures was vitreous tap (n = 25, 76%). Most institutions (n = 26, 79%) routinely administered intravitreal vancomycin and ceftazidime, while intravitreal steroids were routinely administered at 11 centers (33%). Indications for performing vitrectomy included; decreased visual acuity (n = 14, 39%); all cases of exogenous endophthalmitis (n = 4, 12%); non-response to medical therapy (n = 4, 12%); or no view of the fundus (n = 4, 12%), indicating significant variation in surgical indications. More than half (n = 17, 52%) of responding institutions routinely admitted patients with exogenous endophthalmitis to the hospital. Institutions in the United States were less likely to administer oral antibiotics (27% vs. 73%, P = .024) and to admit patients (9% vs. 73%, P This study highlights the global variations in the management of exogenous endophthalmitis, especially as it pertains to surgical indications. Further establishment of evidence-based guidelines may be beneficial to provide more uniform guidance to optimize outcomes.

Steric bulkiness – the metric of the robustness of the self-photosensitized, single metal-active-site catalysis, elucidated in CO2 photoreduction.

A novel mononuclear ruthenium (Ru) complex bearing a PNNP-type tetradentate ligand is introduced here as a self-photosensitized catalyst for the reduction of carbon dioxide (CO2). When the pre-activation of the Ru complex by reaction with a base was carried out, an induction period of catalyst almost disappeared and the catalyst turnover numbers (TONs) over a reaction time of 144 h reached 307 and 489 for carbon monoxide (CO) and for formic acid (HCO2H), respectively. The complex has a long lifespan as a dual photosensitizer and reduction catalyst, due to the sterically bulky and structurally robust (PNNP)Ru framework. Isotope-labeling experiments under 13CO2 atmosphere indicate that CO and HCO2H were both produced from CO2.

To report a case of peripapillary subretinal fluid associated with a ridge-shaped morphology surrounding the optic disc, which we termed ridge-shaped peripapilla.Case report.A 6-year old girl with mild to moderate myopia was referred for an abnormal fundus appearance of the left eye. Fundus examination of the left eye showed a vertical whitish elevation just temporal to the disc with pigment clumping. Spectral domain optical coherence tomography (OCT) of the left eye showed an elevation of the fundus at the temporal edge of the disc with thinning of the choroid overlying the thickened scleral protrusion and a serous subretinal fluid. Fluorescein angiography (FA) of the left eye showed a hyperfluorescent area without leakage at the temporal edge of the disc, indicative of retinal pigment epithelium (RPE) atrophy. There was no sign of choroidal neovascularization. Based on the FA and OCT findings, the protrusion of the sclera seemed to result in overlying choroidal thinning with choroidal blood flow disturbances, and consequent RPE atrophy, leading to the subretinal fluid.This case highlights an unusual presentation of ridge-shaped peripapilla, characterized by inward convexity of the peripapillary area with a ridge-shaped morphology and localized thickening of the peripapillary sclera, in eyes with myopia.

Background During panretinal photocoagulation (PRP), the outer retina, especially the photoreceptors, are destroyed. During such procedures, the impact of the retinal photocoagulation, which is performed in the same photocoagulated area, may change if it is applied to different locations with different photoreceptor densities. Thus, we aimed to evaluate the influence of photoreceptor density on PRP. Methods We constructed a three-dimensional (3D) average distribution of photoreceptors with 3D computer-aided design (CAD) software using previously derived photoreceptor density data and calculated the number of photoreceptors destroyed by scatter PRP and full-scatter PRP (size 400-μm on the retina, spacing 1.0 spot) using a geometry-based simulation. To investigate the impact of photoreceptor density on PRP, we calculated the ratio of the number of photoreceptors destroyed to the total number of photoreceptors, termed the photoreceptor destruction index. Results In this 3D simulation, the total number of photoreceptors was 96,571,900. The total number of photoreceptors destroyed by scatter PRP and full-scatter PRP were 15,608,200 and 19,120,600, respectively, and the respective photoreceptor destruction indexes were 16.2 and 19.8%, respectively. Conclusions Scatter PRP is expected to have 4/5 of the number of photoreceptors destroyed by full-scatter PRP.

To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV).We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months.The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (RIntravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement.

A highly efficient tetradentate PNNP-type Ir photocatalyst, Mes-IrPCY2, was developed for the reduction of carbon dioxide. The photocatalyst furnished formic acid (HCO2H) with 87% selectivity toget...

Purpose To investigate the intraocular lens (IOL) position and refractive outcomes after cataract surgery and phacovitrectomy using swept-source anterior segment OCT (SS-ASOCT). Design Retrospective case series. Participants Patients underwent cataract surgery (group A: 34 eyes), phacovitrectomy without gas tamponade (group B: 20 eyes), and phacovitrectomy with gas tamponade (group C: 22 eyes). Methods Various parameters associated with the anterior chamber and lens were measured by SS-ASOCT (CASIA2; Tomey Corp, Nagoya, Japan) before and after surgery. Axial lengths were measured by optical biometry (IOLMaster; Carl Zeiss, Oberkochen, Germany). The refraction (spherical equivalent) was measured 1 week and 1 month after surgery. Main Outcome Measures Refractive outcomes and the parameters measured by SS-ASOCT were statistically evaluated. Results The overall mean median absolute error (MedAE) was 0.34 diopters (D) at 1 month postoperatively. The MedAE was greater in group C (0.47 D) than in group A (0.31 D) and group B (0.20 D). The overall mean refractive prediction error (ME) was −0.22±0.62 D at 1 month postoperatively. The ME was significantly greater in group C (−0.82±0.64 D) than in group A (0.08±0.39 D) and group B (−0.07±0.45 D) (P Conclusions Forward fixation of the IOL caused myopic refractive errors even after the gas had disappeared in eyes that underwent phacovitrectomy with gas tamponade.

CD157 (also known as Bst1) positive vascular endothelial stem cells (VESCs), which contribute to vascular regeneration, have been recently identified in mouse organs, including the retinas, brain, liver, lungs, heart, and skin. However, VESCs have not been identified in the choroid. The purpose of this study was to identify VESCs in choroidal vessels and to establish the protocol to isolate retinal and choroidal VESCs.We established an efficient protocol to create single-cell suspensions from freshly isolated mouse retina and choroid by enzymatic digestion using dispase, collagenase, and type II collagenase. CD157-positive VESCs, defined as CD31+CD45-CD157+ cells, were sorted using fluorescence-activated cell sorting (FACS).In mouse retina, among CD31+CD45- endothelial cells (ECs), 1.6 ± 0.2% were CD157-positive VESCs, based on FACS analysis. In mouse choroid, among CD31+CD45- ECs, 4.5 ± 0.4% were VESCs. The CD157-positive VESCs generated a higher number of EC networks compared with CD157-negative non-VESCs under vascular endothelial growth factor (VEGF) in vitro cultures. The EC network area, defined as the ratio of the CD31-positive area to the total area in each field, was 4.21 ± 0.39% (retinal VESCs) and 0.27 ± 0.12% (retinal non-VESCs), respectively (P0.01). The EC network area was 8.59 ± 0.78% (choroidal VESCs) and 0.14 ± 0.04% (choroidal non-VESCs), respectively (P0.01). The VESCs were located in large blood vessels but not in the capillaries.We confirmed distinct populations of CD157-positive VESCs in both mouse retina and choroid. VESCs are located in large vessels and have the proliferative potential. The current results may open new avenues for the research and treatment of ocular vascular diseases.

This review aims to introduce stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) and its differential diagnosis. We summarize findings from case reports and series published in the last few years on the clinical and imaging findings in SNIFR.SNIFR presents as either a unilateral or bilateral macular star on fundus examination without clinical or imaging evidence of exudation or frank vitreomacular traction. optical coherence tomography (OCT) imaging shows schisis cavities in the Henle fibre and outer plexiform layers that correspond to the stellate en face findings. Visual acuity is usually minimally affected, and the presence of significant vision loss should prompt high clinical suspicion for alternate diagnoses.SNIFR is a recently characterized clinical entity that serves as an important addition to the differential diagnosis of a macular star. It is a diagnosis of exclusion and should be distinguished from other causes of macular star such as neuroretinitis, vitreomacular traction, ocular manifestations of malignant hypertension, congenital juvenile X-linked macular schisis, myopic maculopathy, optic pit maculopathy, nicotinic acid maculopathy or taxane maculopathy among others.

Retinopathy of prematurity (ROP) remains the leading cause of childhood blindness worldwide. Recent advances in ROP imaging have significantly improved our understanding of the pathogenesis and pathophysiological course of ROP including the acute phase, regression, reactivation, and late complications, known as adult ROP. Recent progress includes various contact and noncontact wide-field imaging devices for fundus imaging, smartphone-based fundus photography, wide-field fluorescein angiography, handheld optical coherence tomography (OCT) devices for wide-field en face OCT images, and OCT angiography. Images taken by those devices were incorporated in the recently updated guidelines of ROP, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3). ROP imaging has also allowed the real-world adoption of telemedicine- and artificial intelligence (AI)-based screening. Recent study demonstrated proof of concept that AI has a high diagnostic performance for the detection of ROP in a real-world screening. Here, we summarize the recent advances in ROP imaging and their application for screening, diagnosis, and management of ROP.

Progression of vascular abnormalities was assessed between resolved and persistent macular edema (ME) in branch retinal vein occlusion. Progression was more common in eyes with resolved ME, suggesting that resolved ME may not signify stability.

Endothelial cells (ECs) are fundamental components of the blood vessels that comprise the vascular system; facilitate blood flow; and regulate permeability, angiogenesis, inflammatory responses and homeostatic tissue maintenance. Accumulating evidence suggests there is EC heterogeneity in vivo. However, isolation of fresh ECs from adult mice to investigate this further is challenging. Here, we describe an easy and reproducible protocol for isolation of different types of ECs and CD157+ vascular-resident endothelial stem cells (VESCs) by mechano-enzymatic tissue digestion followed by fluorescence-activated cell sorting. The procedure was established on liver tissue but can be used to isolate ECs from other organs with minimal modification. Preparation of single-cell suspensions can be completed in 2.5 h. We also describe assays for EC clonal and network formation, as well as transcriptomic analysis of isolated ECs. The protocol enables isolation of primary ECs and VESCs that can be used for a wide range of downstream analyses in vascular research. Various types of endothelial cells and CD157+ vascular-resident endothelial stem cells are isolated from mice by mechano-enzymatic tissue digestion followed by fluorescence-activated cell sorting.