Background: Germline knockout mice are invaluable in understanding the function of the targeted genes. Sometimes, however, unexpected phenotypes are encountered, due in part to the activation of compensatory mechanisms. Germline ablation of cardiac myosin light chain kinase (cMLCK) causes mild cardiac dysfunction with cardiomyocyte hypertrophy, whereas ablation in adult hearts results in acute heart failure with cardiomyocyte atrophy. We hypothesized that compensation after ablation of cMLCK is dependent on developmental staging and perinatal-onset of cMLCK ablation will result in more evident heart failure than germline ablation, but less profound when compared to adult-onset ablation.Methods and Results: The floxed-Mylk3 gene was ablated at the beginning of the perinatal stage using a single intra-peritoneal tamoxifen injection of 50 mg/kg into pregnant mice on the 19th day of gestation, this being the final day of gestation. The level of cMLCK protein level could no longer be detected 3 days after the injection, with these mice hereafter denoted as the perinatal Mylk3-KO. At postnatal day 19, shortly before weaning age, these mice showed reduced cardiac contractility with a fractional shortening 22.8 ± 1.0% (n = 7) as opposed to 31.4 ± 1.0% (n = 11) in controls. The ratio of the heart weight relative to body weight was significantly increased at 6.68 ± 0.28 mg/g (n = 12) relative to the two control groups, 5.90 ± 0.16 (flox/flox, n = 11) and 5.81 ± 0.33 (wild/wild/Cre, n = 5), accompanied by reduced body weight. Furthermore, their cardiomyocytes were elongated without thickening, with a long-axis of 101.8 ± 2.4 μm (n = 320) as opposed to 87.1 ± 1.6 μm (n = 360) in the controls.Conclusion: Perinatal ablation of cMLCK produces an increase of heart weight/body weight ratio, a reduction of contractility, and an increase in the expression of fetal genes. The perinatal Mylk3-KO cardiomyocytes were elongated in the absence of thickening, differing from the compensatory hypertrophy shown in the germline knockout, and the cardomyocyte thinning shown in adult-inducible knockout.
Purpose of Review:Incontinentia pigmenti (IP) is a rare X-linked dominant phakomatosis that predominately presents with dermatologic manifestations but can also cause central nervous system and ocular abnormalities. Awareness of the ocular complications of IP is crucial to identify ocular abnormalities early and prevent permanent vision loss.Recent Findings:There have been significant recent advances in ocular diagnostic imaging in IP. Optical coherence tomography (OCT) has helped characterize outer plexiform layer abnormalities in the macula, which can help explain central vision loss in IP patients. OCT angiography (OCT-A) also identifies macular vascular changes that induce these foveal structural abnormalities and may supplement fluorescein angiography, the current standard of care to identify peripheral retinal ischemia and neovascularization for infants with IP. Additionally, recent studies have presented excellent anatomic outcomes years after laser photocoagulation to ischemic retina. Early data indicates that antivascular endothelial growth factor therapy can induce retinal revascularization, but runs the risk of late recurrent neovascularization and requires long-term monitoring.Summary:Ophthalmic imaging is evolving in the evaluation of IP and is increasingly guiding treatment modalities. A particular focus on the ocular manifestations of IP has been the ideal treatment for retinopathy in this disorder.
Traumatic retinal detachments are a significant cause of morbidity. There are currently no evidence-based guidelines on the appropriate time to perform vitreoretinal surgery to repair a traumatic retinal detachment. Early intervention, within seven days of the inciting trauma, may decrease proliferative vitreoretinopathy and postoperative endophthalmitis. Later intervention may yield a reduced risk of inflammation and hemorrhage, particularly in cases of concomitant open globe injuries. This article reviews the literature on the management of retinal detachments associated with ocular trauma from the years 2006 to 2016. Particular focus was placed on the timing of surgery, concomitant open globe injury, anatomical success rates, visual acuity, and complication rates. In this review, anatomical success was not significantly related to timing of intervention when compared between early and delayed intervention in eyes with and without concomitant open globe injuries. Visual acuities postoperatively varied widely despite timing of intervention due to the large variation in mechanism and extent of ocular injuries. Proliferative vitreoretinopathy was a common complication. Preliminary data indicate that endophthalmitis rates may be lower when early vitreoretinal surgery is performed. There is insufficient data to conclude whether early or delayed surgery leads to improved outcomes, highlighting the need for further research in this domain.
Purpose: Retinopathy of prematurity (ROP) is considered a disease of the inner retina; however, there is increasing evidence that demonstrates choroidal vasculature loss in ROP, leading to degeneration of outer retinal function and visual deterioration. Central choroidal thinning is noted in children with history of ROP using optical coherence tomography (OCT) imaging. This study characterizes the presence and persistence of choroidal loss angiographically in eyes of infants treated with intravitreal bevacizumab (IVB) for stage 3 ROP. Methods: Retrospectively reviewed the fluorescein angiography (FA) images of 62 eyes of 31 infants treated with IVB monotherapy. The eyes with good quality early-, mid-, and late-phase imaging were included in this study. The presence of choroidal hypofluoresence involving the central and or peripheral retina were noted. In infants with multiple FAs, serial FAs were analyzed for persistence of choroidal hypofluorescence. Results: The mean age and birth weight of infants was 24.4 weeks PMA and 683 grams, respectively. All infants received IVB monotherapy. 24 of 62 angiography images of sufficient quality reviewed showed the presence of choroidal hypofluorescence involving central and peripheral lobular loss in the early phase and its persistence into mid and late phases. 12 eyes demonstrated persistent choroidal loss on sequential FA until three years chronological age. Conclusions: The study demonstrates the presence of choroidal vascular loss angiographically both central and peripheral fundus in infants with ROP. It highlights the critical role of choroidal involution in outer retinal function that could affect visual outcomes.
Précis: Bleb-related endophthalmitis (BRE) is a serious complication of glaucoma filtration surgery. The current study reports similar visual and intraocular pressure (IOP) outcomes in eyes treated with pars plana vitrectomy (PPV) compared with vitreous biopsy and injection of intravitreal antibiotics (TI). Purpose: The purpose of this study was to investigate the isolated organisms, visual acuity (VA), and IOP outcomes associated with delayed-onset BRE in eyes treated with PPV versus TI. Patients and Methods: A retrospective chart review was conducted at the Bascom Palmer Eye Institute (Miami, Florida) and the University of Florida (Gainesville, FL) identifying patients treated for BRE with at least 1 month of follow-up from the inception of an electronic health record (2014 and 2011, respectively) through 2021. All patients had undergone bleb-forming glaucoma surgery at least 1 month before endophthalmitis diagnosis. Results: Thirty-nine eyes from 39 patients (33 from Bascom Palmer, 6 from University of Florida) were included. Trabeculectomy was performed in 34 of 39 eyes (87.2%). Streptococcus species (9 eyes, 23.1%) and Staphylococcus species (8 eyes, 20.5%) were the most common isolated organisms and were similar in both treatment groups (P=0.49). Baseline VA was worse in the PPV group (logarithm of the minimum angle of resolution: 2.51 vs. 2.16, P=0.04), but VA at last follow-up was similar (P=0.48) in both groups. After recovery from BRE, the average IOP in the PPV group was 15.1 mm Hg on 0.9 IOP-lowering medications compared with 12.6 mm Hg on 1.2 medications in the TI group (IOP: P=0.56; medications: P=0.80). Additional glaucoma surgery was performed in 44.4% of the PPV eyes and 16.7% of the TI eyes (P=0.09). Conclusion: In eyes with delayed-onset BRE, isolated organisms, visual outcomes, and IOP control were similar after initial PPV compared with TI.
Objective: This study quantifies the change in intraocular pressure (IOP) secondary to wearing neck seals in scuba diving drysuits. Previous work demonstrates significant pressures exerted by these seals; we hypothesize that they would reduce craniofacial venous drainage and increase IOP through elevation of episcleral venous pressure. Methods: IOP was measured in 33 divers before and while wearing a drysuit using rebound tonometry. The drysuit neck seal pressures were measured using a manometer. A paired two-sample t-test was used to compare IOP before and after drysuit donning. Pearson correlation coefficients were calculated between neck sealing pressures and IOP by side. Results: The mean IOP in the right eye was similar pre- and post-drysuit donning, with baseline mean 15.9 mmHg (3.7 mmhg) versus 15.4 mmHg (4.3 mmHg), p=0.4074. Similarly, the mean IOP in the left eye was also similar, with mean pre-donning IOP 15.6 (3.8 mmHg) versus 15.4 mmHg (4.7 mmHg) post-donning, p=0.7467. The mean right and left neck seal pressures were 23.66 (10.60) mmHg and 23.67 (7.87) mmHg, respectively. Only correlation between right neck sealing pressure for silicone neck seals and right IOP, pre- and post-donning was significant (pre: 0.97, p-value 0.0284, post: 0.98, p-value 0.0187). Conclusion: No significant difference overall was detected in IOP with drysuit donning.
Glaucoma drainage device (GDD)-related endophthalmitis is a devastating complication of device implantation. There are no guidelines in the literature to assist clinicians in deciding if the GDD should be explanted or if patients require pars plana vitrectomy (PPV). This study compares the outcomes of GDD explantation with device retention and also independently compares the outcomes of PPV versus intravitreal antibiotics alone in patients with GDD-related endophthalmitis. A literature search for studies discussing GDD-related endophthalmitis from 2005 to 2019 was performed; 30 articles were included. The visual acuity/anatomical outcomes were compared between GDD explantation and retention, and between patients that received a PPV and those that did not. These outcomes were combined with a medical records review of 13 patients with GDD-related endophthalmitis from an academic institution. A total of 88 eyes were included. 70.5% underwent GDD explantation, while 37.8% received a PPV. GDD explantation was associated with a lower rate of evisceration/ enucleation when compared to GDD retention (4.8% versus 19.2%, OR 0.22, 95% CI 0.05-1.01, p = 0.05), but visual acuity outcomes were similar. No eyes that received an immediate vitrectomy became phthisic or required evisceration/enucleation, compared an evisceration/enucleation rate of 15.2% in eyes treated solely with intravitreal antibiotics (OR 1.18, 95% CI 1.04-1.33, p = 0.04). Explantation of the GDD and immediate vitrectomy are both associated with better anatomical outcomes in GDD-related endophthalmitis. Further research is needed to provide more definitive guidelines in the ideal management of these patients.
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