Association of Bleb Formation With Peri-aneurysmal Contact in Unruptured Intracranial Aneurysms

The mechanism of bleb formation in unruptured intracranial aneurysms (UIAs) remains unclear. This study aimed to investigate the association between peri-aneurysmal contact (PAC) and bleb formation. Forty-five aneurysms were classified depending on the presence of blebs and PAC using computed tomographic angiography and magnetic resonance imaging. Aneurysmal hemodynamics were assessed using computational fluid dynamics. The independent variables associated with bleb formation were statistically assessed. Fourteen aneurysms (31.1%) had blebs, all of which were located at the site of PAC (group A). Thirty-one aneurysms (68.9%) had no bleb, of which 13 had a PAC (group B) and 18 had no PAC (group C). PAC was the only independent variable associated with bleb formation (p < 0.05). Aneurysmal volumes were significantly higher in group A, followed by groups B and C in series. Aneurysmal wall shear stress (WSS) tended to be lowest in group A, followed by groups B and C in series. The maximum WSS at the blebs was only 17% of the maximum WSS at the aneurysmal domes. This study demonstrated that bleb formation in UIAs was associated with the establishment of PAC during their growth, which may have more detrimental effects on bleb formation than hemodynamics.

Hemodynamic factor evaluation using computational fluid dynamics analysis for de novo bleb formation in unruptured intracranial aneurysms

Background Although bleb formation increases the risk of rupture of intracranial aneurysms, previous computational fluid dynamic (CFD) studies have been unable to identify robust causative hemodynamic factors, due to the morphological differences of prebleb aneurysm models and a small number of aneurysms with de novo bleb formation. This study investigated the influences of differences in the aneurysm-models and identify causative hemodynamic factors for de novo bleb formation. Materials and methods CFD analysis was conducted on three aneurysm models, actual prebleb, postbleb, and virtual prebleb models of two unruptured aneurysms with de novo bleb formation. A new multipoint method was introduced in this study. We evenly distributed points with a 0.5-mm distance on the aneurysm surface of the actual prebleb models (146 and 152 points in the individual aneurysm, respectively), and we statistically compared hemodynamics at the points in the areas with and without bleb formation (19 and 279 points, respectively). Results Visually, blebs formed on an aneurysm surface area with similar hemodynamic characteristics in the actual and virtual prebleb models. Statistical analysis using the multipoint method revealed that the de novo bleb formation area was significantly correlated with high pressure (p < 0.001), low wall shear stress (WSS) (p < 0.001), and the center of divergent WSS vectors (p = 0.025). Conclusions De novo bleb formation in intracranial aneurysms may occur in areas associated with the combination of high pressure, low WSS, and the center of divergent WSS vectors. The multipoint method is useful for statistical analysis of hemodynamics in a limited number of aneurysms.

Subconjunctival Bevacizumab as an Adjunct to 5-Fluorouracil Enhanced Trabeculectomy: 1 Year Outcomes

Purpose: To compare the results of trabeculectomy with subconjunctival Bevacizumab and 5-Fluorouracil (5-FU); with trabeculectomy with 5-FU alone; in terms of intraocular pressure (IOP) lowering, bleb formation, and complications, in the long term. Study Design: Quasi experimental study. Place and Duration of Study: Fauji Foundation Hospital, Rawalpindi, from December 2013 to August, 2019. Methods: A total of 30 eyes (15 in each group) with glaucoma were recruited. Exclusion criteria were previous trabeculectomy, congenital, traumatic, uveitic, neovascular glaucomas, aphakia, or ocular surface disease. Trabeculectomy with 5FU was performed in both groups. In one group, subconjunctival Bevacizumab was injected into the bleb at the end of surgery. The patients were observed for IOP control, bleb configuration, and complications for 1 year. Results: Primary open angle glaucoma was the predominant diagnosis in 17 (56.7%) eyes. The mean pre-operative IOP in the 5-FU group was 30.8 ± 17.03 mmHg, & in the 5-FU+Bevacizumab group it was 28.9 ± 18.9 mmHg. The mean IOPs of the 5-FU group at 1 Year was 14.5 ± 5.04 mmHg. In 5-FU+Bevacizumab group, mean IOPs at 1 year was 12.7 ± 4.38 mmHg. The differences between pre-operative and post-operative IOPs in both groups at 6, 9 and 12 months were statistically significant. However, differences in mean IOPs between the two groups, bleb morphology and complications were not statistically significant. Conclusion: No added benefit of subconjunctival Bevacizumab used as an adjunct to 5-FU enhanced trabeculectomy was found at the end of 1 year follow-up. Key Words: Trabeculectomy, 5-Fluorouracil, Bevacizumab, Glaucoma, Intraocular pressure.

A mathematical model for bleb regulation in zebrafish primordial germ cells

Blebs are cell protrusions generated by local membrane–cortex detachments followed by expansion of the plasma membrane. Blebs are formed by some migrating cells, e.g. primordial germ cells of the zebrafish. While blebs occur randomly at each part of the membrane in unpolarized cells, a polarization process guarantees the occurrence of blebs at a preferential site and thereby facilitates migration toward a specified direction. Little is known about the factors involved in the controlled and directed bleb generation, yet recent studies revealed the influence of an intracellular flow and the stabilizing role of the membrane–cortex linker molecule Ezrin. Based on this information, we develop and analyse a coupled bulk-surface model describing a potential cellular mechanism by which a bleb could be induced at a controlled site. The model rests upon intracellular Darcy flow and a diffusion–advection–reaction system, describing the temporal evolution from a homogeneous to a strongly anisotropic Ezrin distribution. We prove the well-posedness of the mathematical model and show that simulations qualitatively correspond to experimental observations, suggesting that indeed the interaction of an intracellular flow with membrane proteins can be the cause of the Ezrin redistribution accompanying bleb formation.

A novel finding related to bulla and bleb formation in patients with primary spontaneous pneumothorax

Background Spontaneous pneumothorax is a common problem globally. Bullas and blebs have been implicated in this problem, but the etiology of their formation is unknown. We aim to show the relation between a novel clinical finding, the pulmonary delayed inflation (PDI) sign, and the etiology of bulla and bleb formation in young patients. Methods We retrospectively analyzed data from 111 patients with pneumothorax and a control group of 27 patients. We evaluated the relation between the PDI sign and other clinical factors. Results The PDI sign was observed in 78 patients. Of these, 75 exhibited the PDI sign in only the upper lobe. Regardless of smoking status, patients 34 years of age or younger had a significantly higher incidence of the PDI sign than, patients 55 years of age or older and control patients. The inflation time in patients 34 years of age or younger, regardless of smoking status, was significantly longer than in patients 55 years of age or older and patients in the control group. There was no significant association between inflation time and the presence of asthma. Conclusions The novel PDI sign is seen in patients 34 years of age or younger. Because this sign may indicate a peripheral bronchial abnormality and may be related to the formation of blebs and bullae in young patients with spontaneous pneumothorax, it is possible that it can be used to develop effective treatments for pneumothorax in young patients.

Numerical Model for Formation and Evolution of the Bleb

The morphology of a bleb and its changes are critical to the amoeboid migration of a cell. By releasing bonds between the membrane and the cortex of a cell, the formation of a bleb can be observed experimentally, but the mechanism that affects the size and shape of a bleb during amoeboid migration requires further study. In this study, by adapting the governing equations and discrete equations of the two-dimensional fluid–solid coupling model recommended by Strychalski and Guy [2013 “A computational model of bleb formation,” Mathematical Medicine and Biology 30(2), 115–130], we overcome the defect that the bleb by traditional means is always too small compared with experimental results, and simulate the behaviors of cell blebs successfully. The effects of various parameters such as the number of broken bonds, the viscosity coefficient of the cortex, and the cell’s membrane modulus on the size and the shape of the bleb are investigated. Numerical results show that the model effectively simulates the formation and evolution of a bleb, thus, the contributions of several factors to bleb shape and size are successfully derived.

A novel surgical technique for the treatment of a filtration bleb extending over 180° after Xen gel stent implantation

Purpose: To describe a novel surgical treatment option for managing a symptomatic filtration bleb extending into the three quadrants with adequate IOP control after Xen gel stent implantation. Methods: A 62-year-old female with pseudoexfoliative glaucoma with an IOP of 34 mmHg underwent implantation of a Xen to reduce the IOP in her right eye. The IOP responded well to the procedure, but the patient developed a persistent giant filtration bleb with foreign body sensation and pain. A huge filtering bleb of over 180° after Xen implant surgery was managed by splitting the giant bleb into two parts, posterior dissection into the intermuscular space, a biodegradable collagen device implantation, and suturing the conjunctiva in two parts with absorbable and nonabsorbable sutures. Results: Before the operation for treatment of a giant bleb, the patient had an IOP of 12 mmHg, a best-corrected visual acuity (BCVA) of 20/40, corneal dellen, and no antiglaucoma medication. Following the bleb recession procedure, the IOP was 16 mmHg, BCVA improved to 20/20, there were no corneal dellen and the patient reported resolution of her bleb discomfort. The IOP and BCVA remained stable through 18 months of follow-up and no antiglaucoma medications or additional surgical procedures were required. Conclusion: The novel technique described here can be one option to treat this rare (over 180°) bleb formation after Xen Gel Stent implantation without adversely affecting IOP control.

Needling revision with marking maneuver to locate the scleral flap

Purpose: To report a variation of the classical needle revision maneuver with an external marking of the scleral flap, augmented with mitomycin C (MMC) in failed non penetrating deep sclerectomy (NPDS). Method: This observational prospective pilot study included five consecutive patients who underwent an MMC needling revision of failed NPDS with the external marking of the scleral flap. All participants underwent a complete ophthalmologic examination and data were collected preoperatively as well as 1 day, 1 week and 1 month after the surgery. The surgical site was also evaluated during the procedure. Results: A significant reduction of IOP and antiglaucomatous medication from preoperative levels was detected at the end of the follow-up period. Regarding the surgical site, we succeed in locating the scleral flap and observing the bleb formation in all cases. No significant subconjunctival bleeding was detected. Conclusion: This variation of the classical needling technique seems to improve intrasurgical visualization and reduces complications, which might lead to an improvement in surgical success.

Hemodynamic conditions that favor bleb formation in cerebral aneurysms

BackgroundAlthough it is generally believed that blebs represent weaker spots in the walls of intracranial aneurysms (IAs), it is largely unknown which aneurysm characteristics favor their development.ObjectiveTo investigate possible associations between aneurysm hemodynamic and geometric characteristics and the development of blebs in intracranial aneurysms.MethodsA total of 270 IAs in 199 patients selected for surgical clipping were studied. Blebs were visually identified and interactively marked on patient-specific vascular models constructed from presurgical images. Blebs were then deleted from the vascular reconstruction to approximate the aneurysm before bleb formation. Computational fluid dynamics studies were performed in these models and in cases without blebs. Hemodynamic and geometric characteristics of aneurysms with and without blebs were compared.ResultsA total of 173 aneurysms had no blebs, while 97 aneurysms had a total of 122 blebs. Aneurysms favoring bleb formation had stronger (p<0.0001) and more concentrated inflow jets (p<0.0001), higher flow velocity (p=0.0061), more complex (p<0.0001) and unstable (p=0.0157) flow patterns, larger maximum wall shear stress (WSS; p<0.0001), more concentrated (p=0.0005) and oscillatory (p=0.0004) WSS distribution, and a more heterogeneous WSS field (p<0.0001), than aneurysms without blebs. They were also larger (p<0.0001), more elongated (p<0.0001), had wider necks (p=0.0002), and more distorted and irregular shapes (p<0.0001).ConclusionsStrong and concentrated inflow jets, high-speed, complex, and unstable flow patterns, and concentrated, oscillatory, and heterogeneous WSS patterns favor the formation of blebs in IAs. Blebs are more likely to form in large, elongated, and irregularly shaped aneurysms. These adverse characteristics could be considered signs of aneurysm instability when evaluating aneurysms for conservative observation or treatment.