Retinopathy of prematurity (ROP) is a leading cause of childhood blindness and intravitreal anti‐vascular endothelial growth factor (VEGF) injection is becoming a first‐line choice for treatment of ...ROP. However, there is a major concern that intravitreally injected anti‐VEGF agents could escape from the eye into the systemic circulation and impair systemic development. Moreover, escaped anti‐VEGF agents could have an effect on the retina of the fellow eye. In this study, we investigated the hematogenous effect of a single intravitreal anti‐VEGF injection in a mouse model of ROP. Here, we showed that single intravitreal aflibercept injection to one eye can affect body weight gain, the fellow eye, and renal vessels, although no apparent effect was observed in brain vessels. Furthermore, this hematogenous effect was dose‐dependent. Our results provide very important insights into the clinical use of anti‐VEGF agents for ROP treatment.
Purpose
To evaluate the changes in axial length (AL) and corneal astigmatism induced by scleral imbrication on all quadrants in pig eyes.
Study design
Experimental study
Methods
We produced scleral ...imbrications either on all quadrants or on 2 consecutive quadrants of 5 enucleated pig eyes. Scleral imbrications 8 mm wide were made at 8 mm from the limbus on each quadrant. We determined the AL using an electronic caliper and the corneal astigmatism using a keratometer before and after the 2 types of scleral imbrications and compared the changes in ocular AL and corneal astigmatism induced by the 2 surgical procedures.
Results
The AL reduction after the scleral imbrication on all quadrants (3.96 ± 0.56 mm) was larger than that on 2 quadrants (2.39 ± 0.41 mm) (
P
= .001). The change in corneal astigmatism induced by imbrication on all quadrants (2.98 ± 1.96 D) was less than that on 2 quadrants (5.95 ± 2.04 D) (
P
< .029).
Conclusions
Scleral imbrication on all quadrants induced a shorter AL and less corneal astigmatism than did a standard scleral imbrication on 2 quadrants. Therefore, the former could be a more effective operation for retinal disorders associated with high myopia, including macular hole retinal detachment and myopic foveoschisis.
To assess the interaction between ranibizumab, aflibercept, and mouse vascular endothelial growth factor (VEGF), both in vivo and in vitro.
In vivo, the effect of intravitreal injection of ...ranibizumab and aflibercept on oxygen induced retinopathy (OIR) and the effect of multiple intraperitoneal injections of ranibizumab and aflibercept on neonatal mice were assessed. In vitro, the interaction of mouse VEGF-A with aflibercept or ranibizumab as the primary antibody was analyzed by Western blot.
In both experiments using intravitreal injections in OIR mice and multiple intraperitoneal injections in neonatal mice, anti-VEGF effects were observed with aflibercept, but not with ranibizumab. Western blot analysis showed immunoreactive bands for mouse VEGF-A in the aflibercept-probed blot, but not in the ranibizumab-probed blot.
Aflibercept but not ranibizumab interacts with mouse VEGF, both in vivo and in vitro. When conducting experiments using anti-VEGF drugs in mice, aflibercept is suitable, but ranibizumab is not.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the effects of internal limiting membrane (ILM) peeling on visual acuity (VA) after rhegmatogenous retinal detachment (RRD) surgery.
This retrospective analysis examined the medical ...records of patients with RRD who underwent vitrectomy at 26 institutions. To detect prognostic factors of VA at 6 months postoperatively (post-VA), multivariate linear regression was performed with post-VA as the objective variable; ILM peeling, sex, age, preoperative VA (pre-VA), intraocular pressure, axial length, duration of RRD, and cataract surgery served as explanatory variables. Recurrence of RRD and epiretinal membrane formation within 6 months postoperatively were compared between groups of patients with and without ILM peeling, among patients with macula-on and macula-off RRD.
The inclusion criteria were met by 523 eyes with a macula-on RRD and 364 eyes with a macula-off RRD. ILM peeling was performed in 85 eyes with a macula-on RRD and 57 eyes with a macula-off RRD. In eyes with a macula-on RRD, ILM peeling did not affect post-VA (p = 0.72). Vitrectomy without cataract surgery and poor pre-VA were significantly associated with poor post-VA (p = 0.01 and p < 0.001, respectively). In eyes with a macula-off RRD, ILM peeling, long duration of RRD, and poor pre-VA were significantly associated with poor post-VA (p = 0.037, p = 0.007, and p < 0.001, respectively). Recurrence of RRD and epiretinal membrane formation were similar between groups of patients with and without ILM peeling, among patients with macula-on and macula-off RRD. Retina sensitivity was not evaluated by microperimetry.
ILM peeling did not affect post-VA in eyes with a macula-on RRD, whereas post-VA was worse in eyes with ILM peeling than in eyes without peeling, among eyes with a macula-off RRD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
To create a model for prediction of postoperative visual acuity (VA) after vitrectomy for macular hole (MH) treatment using preoperative optical coherence tomography (OCT) images, using deep ...learning (DL)–based artificial intelligence.
Methods
This was a retrospective single-center study. We evaluated 259 eyes that underwent vitrectomy for MHs. We divided the eyes into four groups, based on their 6-month postoperative Snellen VA values: (A) ≥ 20/20; (B) 20/25–20/32; (C) 20/32–20/63; and (D) ≤ 20/100. Training data were randomly selected, comprising 20 eyes in each group. Test data were also randomly selected, comprising 52 total eyes in the same proportions as those of each group in the total database. Preoperative OCT images with corresponding postoperative VA values were used to train the original DL network. The final prediction of postoperative VA was subjected to regression analysis based on inferences made with DL network output. We created a model for predicting postoperative VA from preoperative VA, MH size, and age using multivariate linear regression. Precision values were determined, and correlation coefficients between predicted and actual postoperative VA values were calculated in two models.
Results
The DL and multivariate models had precision values of 46% and 40%, respectively. The predicted postoperative VA values on the basis of DL and on preoperative VA and MH size were correlated with actual postoperative VA at 6 months postoperatively (P < .0001 and P < .0001, r = .62 and r = .55, respectively).
Conclusion
Postoperative VA after MH treatment could be predicted via DL using preoperative OCT images with greater accuracy than multivariate linear regression using preoperative VA, MH size, and age.
To evaluate the short-term effect on body weight (BW) gain after intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP).
This was a retrospective 1:1 matched case-control study. Infants ...with ROP treated by IVB or photocoagulation (PC) at Shiga University of Medical Science Hospital between April 2010 and December 2019 were included in the study. To match BWs at treatment between the IVB and PC groups, 1:1 matching for BWs at treatment within 100 g was performed. The BW gains for the 7 days before treatment (pre-treatment week), the 7 days after treatment (first post-treatment week), and the period from 7 to 14 days after treatment (second post-treatment week) were compared between the IVB and PC groups.
Following 1:1 matching, 13 infants in both groups were enrolled in the analysis. The weekly BW gain for the first post-treatment week was significantly lower in the IVB group compared with the PC group (86 g vs. 145 g; P = 0.046), whereas the weekly BW gains for the pre-treatment week (173 g vs. 159 g; P = 0.71) and the second post-treatment week (154 g vs. 152 g; P = 0.73) were comparable between the two groups. The short-term inhibitive effect of IVB on BW gain was particularly observed in infants weighing less than 1500 g at treatment (<1500 g: 47 g vs. ≥1500 g: 132 g; P = 0.03).
IVB could have a short-term inhibitive effect on BW gain in infants with ROP, and this effect is more likely to occur in infants with a lower BW at the time of treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Imbalanced angiogenesis is a characteristic of several diseases. Rho GTPases regulate multiple cellular processes, such as cytoskeletal rearrangement, cell movement, microtubule dynamics, signal ...transduction and gene expression. Among the Rho GTPases, RhoA, Rac1 and Cdc42 are best characterized. The role of endothelial Rac1 and Cdc42 in embryonic development and retinal angiogenesis has been studied, however the role of endothelial RhoA is yet to be explored. Here, we aimed to identify the role of endothelial RhoA in endothelial cell functions, in embryonic and retinal development and explored compensatory mechanisms. In vitro, RhoA is involved in cell proliferation, migration and tube formation, triggered by the angiogenesis inducers Vascular Endothelial Growth Factor (VEGF) and Sphingosine-1 Phosphate (S1P). In vivo, through constitutive and inducible endothelial RhoA deficiency we tested the role of endothelial RhoA in embryonic development and retinal angiogenesis. Constitutive endothelial RhoA deficiency, although decreased survival, was not detrimental for embryonic development, while inducible endothelial RhoA deficiency presented only mild deficiencies in the retina. The redundant role of RhoA in vivo can be attributed to potential differences in the signaling cues regulating angiogenesis in physiological versus pathological conditions and to the alternative compensatory mechanisms that may be present in the in vivo setting.
Background
To investigate the effectiveness of vitrectomy for diffuse diabetic macular edema (DDME) and its dependence on optical coherence tomography (OCT) findings.
Methods
The records of 65 ...patients and 81 eyes who received vitrectomy for DDME and followed up for at least 6 months were retrospectively reviewed. All eyes were classified according to their morphological characteristics on OCT including sponge-like diffuse retinal thickening (SDRT:
n
= 13), cystoid macular edema (CME:
n
= 42), serous retinal detachment (SRD:
n
= 13), and the combination of all morphological characteristics (FULL:
n
= 13). The best-corrected visual acuity (BCVA) and spectral domain OCT were investigated preoperatively and at 1, 3, and 6 months postoperatively.
Results
At six months after surgery, BCVA in logMAR units was significantly improved in all groups except the SDRT group. The improvement was −0.04 ± 0.20 in the SDRT group (
P
= 0.504), −0.16 ± 0.24 in the CME group (
P
< 0.01), −0.32 ± 0.32 in the SRD group (
P
< 0.01), and −0.26 ± 0.19 in the FULL group (
P
< 0.01), and significantly better in eyes with subretinal fluid (SRF; the SRD and FULL groups) than in eyes without SRF (the SDRT and CME groups,
P
= 0.003).
Conclusions
Vitrectomy can be a useful treatment option for DDME, particularly for eyes with SRF.
Primary cilia are sensory organelles crucial for organ development. The pivotal structure of the primary cilia is a microtubule that is generated via tubulin polymerization reaction that occurs in ...the basal body. It remains to be elucidated how molecules with distinct physicochemical properties contribute to the formation of the primary cilia.
Here we show that brain expressed X-linked 1 (Bex1) plays an essential role in tubulin polymerization and primary cilia formation. The Bex1 protein shows the physicochemical property of being an intrinsically disordered protein (IDP). Bex1 shows cell density-dependent accumulation as a condensate either in nucleoli at a low cell density or at the apical cell surface at a high cell density. The apical Bex1 localizes to the basal body. Bex1 knockout mice present ciliopathy phenotypes and exhibit ciliary defects in the retina and striatum. Bex1 recombinant protein shows binding capacity to guanosine triphosphate (GTP) and forms the condensate that facilitates tubulin polymerization in the reconstituted system.
Our data reveals that Bex1 plays an essential role for the primary cilia formation through providing the reaction field for the tubulin polymerization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cellular adaptation to low oxygen tension triggers primitive pathways that ensure proper cell function. Conditions of hypoxia and low glucose are characteristic of injured tissues and hence ...successive waves of inflammatory cells must be suited to function under low oxygen tension and metabolic stress. While Hypoxia-Inducible Factor (HIF)-1α has been shown to be essential for the inflammatory response of myeloid cells by regulating the metabolic switch to glycolysis, less is known about how HIF1α is triggered in inflammation. Here, we demonstrate that cells of the innate immune system require activity of the inositol-requiring enzyme 1α (IRE1α/XBP1) axis in order to initiate HIF1α-dependent production of cytokines such as IL1β, IL6 and VEGF-A. Knockout of either HIF1α or IRE1α in myeloid cells ameliorates vascular phenotypes in a model of retinal pathological angiogenesis driven by sterile inflammation. Thus, pathways associated with ER stress, in partnership with HIF1α, may co-regulate immune adaptation to low oxygen.