Neovascular glaucoma (NVG) is a devastating secondary glaucoma characterized by the appearance of neovascular over the iris and the proliferation of fibrovascular tissue in the anterior chamber ...angle. Proliferative diabetic retinopathy (PDR) is one of the leading causes of NVG. Currently increasing diabetes population drive the prevalence rate of NVG into a fast-rising lane. The pathogenesis underlying NVG makes it refractory to routine management for other types of glaucoma in clinical practice. The combination of panretinal photocoagulation (PRP), anti-vascular endothelial growth factor (VEGF) injections, anti-glaucoma drugs, surgical intervention as well as blood glucose control is needed. Early diagnosis and aggressive treatment in time are crucial in halting the neovascularization process and preserving vision. This review provides an overview of NVG secondary to diabetic retinopathy (DR), including the epidemiology, pathogenesis and management, so as to provide a better understanding as well as potential therapeutic strategies for future treatment.
The reactions of the CH
2
XO
2
(X=F, Cl) with chlorine radical have been firstly investigated utilizing the BMC-CCSD//B3LYP method. The comprehensive calculations indicate that the ...association-elimination and S
N
2 displacement reaction mechanisms existed on the singlet potential energy surface (PES), and H-abstraction and S
N
2 displacement reaction mechanism existed on the triplet PES for the CH
2
XO
2
(X=F, Cl) + Cl reactions. On the triplet PES, the dominant reactions are production of P3
X
(CHXO
2
(X=F, Cl) + HCl) by direct H-abstraction. On the singlet PES, three energy-rich adducts, IM1
X
(CH
2
XOOCl (X=F, Cl)), IM2
X
(CH
2
XOClO (X=F, Cl)), and IM3
X
(CH
2
(OX)OCl (X=F, Cl)), are produced. RRKM-computed reveals that IM1
X
(CH
2
XOOCl (X=F, Cl)) produced by collisional stabilization occupied the reaction T ≤ 500 and 400 K, respectively, while P1
X
(CHXO (X=F, Cl) + HOCl) are forecasted to be the dominant products at high temperatures. The atmospheric lifetime of CH
2
FO
2
and CH
2
ClO
2
in Cl is around 1.18 and 2.50 weeks, respectively. Time-dependent density functional theory (TDDFT) computations imply that IM1
X
(CH
2
XOOCl (X=F, Cl)) will photolyze under the sunlight. The current results could guide us to well understand the mechanism of the CH
2
XO
2
(X=F, Cl) + Cl reactions and may be helpful to understand Cl-combustion chemistry.
Graphical Abstract
Predicted rate constant of the dominant pathways and the total rate constants at 760 Torr, N2 in the temperature region of 200-3000 K for the CH
2
XO
2
(X=F, Cl) + Cl reactions
Glaucoma is the second leading cause of blindness globally characterized by progressive loss of retinal ganglion cells (RGCs) and irreversible visual deficiency. As the most common type of glaucoma, ...primary open angle glaucoma (POAG) is currently an unmet medical need with limited therapy by lowering intraocular pressure (IOP). However, some patients continue to progress even though their IOP are controlled. Although early diagnosis and prompt treatment are crucial in preventing irreversible visual impairment, there are currently no biomarkers for screening POAG. Metabolomics has the advantages of illustrating the final downstream products of the genome and establishing the closest link to the phenotype. So far, there is no study investigating the metabolomic profiles in both aqueous humor and plasma of POAG patients. Therefore, to explore diagnostic biomarkers, unveil underlying pathophysiology and potential therapeutic strategies, a widely targeted metabolomic approach was applied using ultrahigh-resolution mass spectrometry with C18 liquid chromatography to characterize the metabolomic profiles in both aqueous humor and plasma of 28 POAG patients and 25 controls in our study. Partial least squares-discriminant analysis (PLS-DA) was performed to determine differentially expressed metabolites (DEMs) between POAG and age-matched controls. The area under the receiver operating characteristic curve (AUC) was calculated to assess the prediction accuracy of the DEMs. The correlation of DEMs with the clinical parameters was determined by Pearson correlation, and the metabolic pathways were analyzed using MetaboAnalyst 4.0. PLS-DA significantly separated POAG from controls with 22 DEMs in the aqueous humor and 11 DEMs in the plasma. Additionally, univariate ROC analysis and correlation analysis with clinical parameters revealed cyclic AMP (AUC = 0.87), 2-methylbenzoic acid (AUC = 0.75), 3'-sialyllactose (AUC = 0.73) in the aqueous humor and N-lac-phe (AUC = 0.76) in the plasma as potential biomarkers for POAG. Moreover, the metabolic profiles pointed towards the alteration in the purine metabolism pathway. In conclusion, the study identified potential and novel biomarkers for POAG by crosslinking the metabolomic profiles in aqueous humor and plasma and correlating with the clinical parameters. These findings have important clinical implications given that no biomarkers are currently available for glaucoma in the clinic, and the study provided new insights in exploring diagnostic biomarkers and potential therapeutic strategies of POAG by targeting metabolic pathways.
Purpose
To compare the anatomical effects on anterior segment by lens extraction (LE, phacoemulsification with posterior chamber intraocular lens implantation) and laser peripheral iridotomy (LPI) in ...primary angle closure suspect (PACS) eyes.
Methods
This prospective comparative cohort trial included a total of 122 consecutive patients identified as PACS aged 52 to 80 years. LE or LPI was performed based on each patient’s choice. The anterior segment optical coherence tomography (ASOCT) and gonioscopy were conducted at baseline and 4 weeks post-operation. Outcome measures include percentage of residual angle closure, mean angle width (modified Shaffer grade), angle opening distance (AOD), trabecular iris angle (TIA), trabecular iris space area (TISA), anterior chamber depth (ACD), iris curvature (I-Curve), lens vault (LV), intraocular pressure (IOP), and best-corrected visual acuity (BCVA).
Results
All anterior angle parameters (AOD, TIA, and TISA) were significantly greater after LE than LPI (
P
< 0.001 for all). ACD (
P
< 0.001) increased, LV (
P
< 0.001) decreased, IOP (
P
< 0.001) decreased, and BCVA (
P
< 0.001) increased after LE. However, no significant changes were found in ACD (
P
= 0.782), LV (
P
= 0.616), IOP (
P
= 0.112), and BCVA (
P
= 0.131) after LPI. In both groups, I-Curve decreased after the operation, but the iris was flatter after LE than LPI (
P
< 0.001). Gonioscopically, the LE group achieved a larger post-operative angle width (modified Shaffer grade) than LPI (
P
< 0.001) and all anterior chamber angles were open (defined as posterior pigmented trabecular meshwork (PTM) visible with static gonioscopy) after operation. Nevertheless, after LPI, 12 eyes (20.0%) still had two or more quadrants and 32 eyes (53.3%) still had at least one quadrant in which the posterior PTM could not be observed.
Conclusions
Compared with LPI, LE resulted in a wider anterior chamber angle, a deeper anterior chamber, and a lower IOP in PACS eyes. Moreover, no residual angle closure was observed after LE, which could morphologically prevent the progress of angle closure.
Trial registration
ChiCTR1800016511
Laser peripheral iridotomy (LPI) is effective in primary angle-closure suspects (PACS); however, predictors for anterior segment alterations after LPI are limited. We aimed to evaluate the anterior ...segment biometric parameters before and after LPI in PACS using the recently developed, CASIA 2 device of anterior segment optical coherence tomography (AS-OCT).
We performed LPI in 52 PACS. Anterior segment parameters, including anterior chamber depth (ACD), anterior chamber width (ACW), anterior chamber volume (ACV), iris curvature (ICURVE), iridotrabecular contact (ITC), lens vault (LV), lens thickness (LT), radius of the lens, angle opening distance (AOD), angle recess area (ARA), trabecular iris space area (TISA), and trabecular iris angle (TIA) at different distances (i.e., 500 μm from the sclera spur), were evaluated before and after LPI using CASIA 2.
Eyes of PACS after LPI had a greater ACV, AOD, ARA, TISA, and TIA, and a lower ITC and ICURVE (all p < 0.001) than those before LPI. On a 360° scan, the anterior chamber angle in the superior quadrant increased the most after the LPI. A higher baseline LT was significantly associated with a greater postoperative increase in AOD 500, ARA 500, TISA 500, and TIA 500 (p = 0.001, p = 0.010, p = 0.004, and p < 0.001, respectively).
We found that LPI widens the anterior chamber angle in the PACS, especially, in the superior quadrant around the iridotomy hole. Eyes with a thicker lens are more likely to experience angle opening because of the LPI.
Introduction Acute primary angle closure (APAC) is an emergency ophthalmic presentation and a major cause of irreversible blindness in China. However, only a few studies have focused on the ...characteristics of optic disc hemorrhage (ODH) during an APAC attack, including its shape, depth, location, scope, and duration after intraocular pressure (IOP) control, along with changes in the optic nerve. This study aimed to analyze the characteristics of ODH and optic nerve changes in patients during their first APAC episode. Methods This retrospective study involved 32 eyes from 32 patients with APAC who received sequential treatment and analyzed the following parameters: the highest IOP and its duration, ODH, retinal nerve fiber layer thickness (RNFLT), and mean deviation (MD). We compared parameters obtained from the affected eye (ODH group) and contralateral unaffected eye (control group), as well as intragroup comparisons. Results The mean IOP in the ODH group was 64.28 ± 10.36 mmHg, with a duration of 4.44 ± 2.35 days. Flame and splinter shapes accounted for 84.38% of the ODH. The mean ODH duration was 4.81 ± 3.25 weeks. ODH during APAC was isolated to one sector in 59.38% of cases, mostly occurring in the temporal superior and temporal inferior (each accounting for 21.88% of the cases). There was a positive correlation between the extent of hemorrhage and the highest IOP duration ( p < 0.001). RNFLT was significantly thickened within 72 h post-IOP control but was thinned by 2 weeks. By 6 months, the thinning stabilized, and there was no difference noted between the ODH and control groups at 12 months. MD partly improved at 6 months post-IOP control, and ODH scope significantly affected the MD ( p < 0.001). The duration of high IOP was positively correlated to the ODH scope and MD damage. Discussion Timely and effective IOP management is essential for recovering visual function following an APAC attack.
Glaucoma is a leading cause of blindness worldwide. It is suggested that primary open angle glaucoma (POAG), the most common form of glaucoma, may be associated with significant metabolic ...alternations, but the systemic literature review and meta-analysis in the area have been missing. Altered metabolomic profiles in the aqueous humor and plasma may serve as possible biomarkers for early detection or treatment targets. In this article, we performed a systematic meta-analysis of the current literature surrounding the metabolomics of patients with POAG and metabolites associated with the disease. Results suggest several metabolites found to be specifically altered in patients with POAG, suggesting broad generalizability and pathways for future research.
Chlorine atoms initiated oxidation reactions are significant for the removal of typical volatile organic compounds (VOCs) in the atmosphere. The intrinsic mechanisms of CH
2
=CHCOOH + Cl reaction ...have been carried out at the CCSD(T)/cc-pVTZ//M06-2X/6-311++G(d,p) level. There are hydrogen abstraction and C-addition pathways on potential energy surfaces. By analyses, the addition intermediates of IM1(ClCH
2
CHCOOH) and IM2(CH
2
CHClCOOH) are found to be dominant. The secondary reactions of IM1 and IM2 have been discussed in the presence of O
3
, O
2
, NO, and NO
2
. And we have also investigated the degradation mechanisms of ClCH
2
CHO
2
COOH with NO, NO
2
, and self-reaction. Moreover, the atmospheric kinetics has been calculated by the variable reaction coordinate transition–state theory (VRC-TST). As a result, the rate constants show negative temperature and positive pressure dependence. The atmospheric lifetime and global warming potentials of acrylic acid have been calculated. Overall, the current study elucidates a new mechanism for the atmospheric reaction of chlorine atoms with acrylic acid.
The atmospheric reactions of alkylamino radicals, R1R2N, with O2 and NO2 were studied by theoretical methods to elucidate the possible pathways to imine formation at the atmospheric conditions. The ...calculations show that all relevant routes proceed via initial additions to the nitrogen atom of the amino radical, R1R2N–NO2, R1R2N–ONO and R1R2N–OO that then may undergo dissociation via five-center-ring transition states resulting in imines and HONO or HO2. The rate coefficient for amino radical reaction with O2 is shown to be several orders of magnitude smaller than the corresponding reaction with NO2. N-nitro amines are the major product in secondary amino radical reactions with NO2. For primary amino radical reactions with NO2 the amounts of N-nitro amines and imines will depend upon pressure and chain length. Results from TDDFT studies of N-nitro and N-nitrooxy amine photo stability indicate fast photolysis of N-nitrooxy amines at atmospheric conditions.
► The atmospheric formation of imines from RnNH2−n + NO2/O2 reactions were studied theoretically. ► The reaction starts from the addition to form RNOO, and then undergo dissociation to imines. ► The dominant product with NO2 reaction is nitroamines. ► Nitroamines are difficult to photolyze in the sunlight.
Retinal ischemia/reperfusion injury (RI) is a common cause of irreversible visual impairment and blindness in elderly and critical unmet medical need. While no effective treatment is available for ...RI, microglial activation and local immune responses in the retina are thought to play important roles in the pathophysiology of neurodegeneration. While survival and activation of microglia depend critically on colony-stimulating factor receptor (CSF-1R) signaling, it remains unclear if targeting the retinal immune microenvironments by CSF-1RAb after RI is sufficient to rescue vision and present a potentially effective therapy. Here we used rodent models of RI and showed that retinal ischemia induced by acute elevation of intraocular pressure triggered an early activation of microglia and macrophages in the retina within 12 h. This was followed by lymphocyte infiltration and increased production of pro-inflammatory cytokines. Intravitreal injection of CSF-1R neutralizing antibody (CSF-1RAb) after RI significantly blocked microglial activation and the subsequent T cell recruitment. This also led to improved retinal ganglion cell survival and function measured by cell quantification and electroretinogram positive scotopic threshold responses, as well as increased visual acuity and contrast sensitivity as assessed by optomotor reflex-based assays, when compared to the isotype-treated control group. Moreover, the administration of CSF-1RAb efficiently attenuated inflammatory responses and activation of human microglia in culture, suggesting a therapeutic target with human relevance. These results, together with the existing clinical safety profiles, support that CSF-1RAb may present a promising therapeutic avenue for RI, a currently untreatable condition, by targeting microglia and the immune microenvironment in the retina to facilitate neural survival and visual function recovery.
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