Efficacy of anti-suppression therapy in improving binocular vision in children with small-angle Esotropia

Purpose: To evaluate the efficacy of anti-suppression exercises in children with small-angle esotropia in achieving binocular vision. Methods: A retrospective review of patients aged 3–8 years who underwent anti-suppression exercises for either monocular or alternate suppression between January 2016 and December 2021 was conducted. Patients with esotropia less than 15 prism diopters (PD) and visual acuity ≥ 6/12 were included. Patients with previous intra-ocular surgery or less than three-month follow-up were excluded. Success was defined as the development of binocular single vision (BSV) for distance, near, or both (measured clinically with either the 4 prism base out test or Worth four dot test) and maintained at two consecutive visits. Qualified success was defined as the presence of diplopia response for both distance and near. Additionally, improvement in near stereo acuity was measured using the Stereo Fly test. Results: Eighteen patients with a mean age of 5.4 ± 1.38 years (range 3–8 years) at the time of initiation of exercises were included in the study. The male female ratio was 10:8. The mean best corrected visual acuity was 0.18 LogMAR unit(s) and the mean spherical equivalent was +3.8 ± 0.14 diopters (D). The etiology of the esotropia was fully accommodative refractive esotropia (8), microtropia (1), post–operative infantile esotropia (4), partially accommodative esotropia (1), and post-operative partially accommodative esotropia (4). Patients received either office-based, home-based, or both modes of treatment for an average duration of 4.8 months (range 3–8). After therapy, BSV was achieved for either distance or near in 66.6 % of patients (95 % CI = 40.03–93.31 %). Binocular single vision for both distance and near was seen in 50 % of children. Qualified success was observed in 38.46% of patients. Persistence of suppression was observed in one patient (5.5 %)... (AU)

Progression rate of macular retinal pigment epithelium atrophy in geographic atrophy and selected inherited retinal dystrophies. A systematic review and meta-analysis.

PURPOSE: To compare the macular retinal pigment epithelium (RPE) atrophy progression rate of selected degenerative and macular inherited retinal diseases (IRD). DESIGN: Systematic review and meta-analysis. METHODS: The protocol was registered on the PROSPERO database. Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to 15/Sep/2023 for articles reporting the RPE atrophy growth rate in treatment-naïve eyes with geographic atrophy (GA), Stargardt disease (STGD1), Best disease, pseudoxanthoma elasticum (PXE), central areolar choroidal dystrophy (CACD), or pattern dystrophies with no previous or current macular neovascularization and a minimum follow-up time of 12 months. Meta-analyses determined mean RPE atrophy growth rates per disease, imaging modality (fundus autofluorescence [FAF], optical coherence tomography [OCT], or color fundus photography [CFP]) and metric (mm2/year or mm/year). The Newcastle-Ottawa scale and the Cochrane Risk-of-Bias tool assessed the risk of bias, and funnel plots were used to evaluate small-study effects. RESULTS: From 4354 publications, 85 were included for meta-analysis: 69 studies (7815 eyes) on GA, 15 (1367 eyes) on STGD1, and one on both. Two studies on PXE were only eligible for review. No studies for other diseases met our eligibility criteria. The overall mean RPE atrophy growth rate for GA using FAF was 1.65 mm2/year (95% confidence interval [CI], 1.49-1.81) and 0.35 mm/year (95% CI, 0.28-0.41); using OCT, it was 1.46 mm2/year (95% CI, 1.28-1.64) and 0.34 mm/year (95% CI, 0.28-0.40); and on CFP it was 1.76 mm2/year (95% CI, 1.56-1.97) and 0.30 mm/year (95% CI, 0.28-0.31). For STGD1, using FAF it was 1.0 mm2/year (95% CI, 0.77-1.23) and 0.20 mm/year (95% CI, 0.17-0.23); on OCT, it was 0.80 mm2/year (95% CI, 0.72-0.88). No studies on STGD1 reported the growth rate with other imaging modalities or metrics. Growth rates in GA were faster than in STGD1 (p<0.05). A larger baseline area of atrophy was generally associated with faster growth rates. CONCLUSION: The RPE atrophy growth rate in GA is faster than in STGD1 but with great variation between studies and imaging modalities. Limited information was available for other macular IRD, suggesting further research is needed.

Relationship between retinal volume changes and the prognosis of BRVO-ME treated with ranibizumab.

Background: This study aimed to evaluate the efficacy of ranibizumab for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO-ME), changes in retinal volume and central retinal thickness (CRT) before and after therapy, and the connection between visual prognosis and changes in retinal volume. Methods: The 120 patients(121 eyes) of BRVO-ME were recruited from July 2020 to October 2022 at the Affiliated Hospital of Weifang Medical University. The clinical data of patients were retrospectively examined for changes in best-corrected visual acuity (BCVA), retinal volume, and CRT at 1 day, 1 week, 1 month, 3 months, 6 months and 1year after treatment. Findings: Visual acuity improved gradually and became steady approximately 1 months after treatment, whereas retinal volume decreased gradually in both the outer and full layers and stabilized around 6 month after treatment. The decline in retinal volume and CRT was more visible in the deeper layers than in the inner levels. A higher correlation was observed between retinal volume and BCVA than between CRT and BCVA. BCVA after one year of treatment had a high correlation with baseline outer retinal volume. Interpretation: Treatment of BRVO-ME with ranibizumab is highly effective, and the recovery of visual function was depends more on early treatment. The outer retina is the major site of edema. Changes in retinal volume may serve as a better predictor of visual prognosis than changes in CRT. Baseline ourter retinal volume is correlated with long-term visual prognosis.

Retinal Focal Nodular Gliosis (Vasoproliferative Tumors) Have Varied Clinical Courses Requiring Tailored Management: A Case Series.

Introduction: Retinal focal nodular gliosis (FNG), also known as vasoproliferative tumors (VPTs), are rare, benign vascular tumors associated with exudation with no current consensus on management. Herein, we describe the varied clinical course and management of 3 patients with retinal FNG, one of whom is associated with retinitis pigmentosa. Case Presentations: Case 1 is a 76-year-old female who presented with reduced vision and distortion secondary to a vitreous hemorrhage and epiretinal membrane (ERM) as complications of a known small peripheral retinal FNG. She underwent vitrectomy for the hemorrhage to relieve vascular traction and the ERM peel, and the tumor was kept under observation. Case 2 is a 24-year-old female with genetically uncharacterized retinitis pigmentosa-like phenotype who presented with gradual loss of central vision in one eye due to cystoid macular oedema (CMO). She was found to have two peripheral retinal areas of FNG located inferonasally. Tumors were treated with cryotherapy and adjuvant intraocular steroid implant to control the CMO. Case 3 is a 28-year-old female with retinitis pigmentosa secondary to genetically confirmed variant in CRB1 gene who presented with intractable right eye CMO and localized inferior serous retinal detachment secondary to a large inferotemporal FNG. Her left eye has no light perception vision due to previous extensive serous retinal detachment and anterior segment ischemia. The right eye tumor was managed with multiple rounds of cryotherapy and laser therapy to control the serous detachment. Despite this, the condition progressed and was ultimately treated with plaque brachytherapy. Unfortunately, this resulted in extensive retinal inflammation causing annular tractional retinal detachment which was treated with combined pars plana vitrectomy and scleral buckle. Conclusion: We characterized the retinal phenotype of 3 patients with retinal FNG (VPTs) and found them to have varied clinical courses requiring tailored surgical management. The case associated with retinitis pigmentosa had a known pathogenic variant in Crumbs homolog-1 (CRB1) gene affecting retinal structure and exhibited a more severe clinical course. It is therefore important for patients with retinal dystrophies to undergo thorough peripheral examinations and detect FNG early as they may require prompt, aggressive treatment.

Retinal ganglion cell complex thickness in subjects with diabetes mellitus and uncontrolled hypertension in China.

PURPOSE: To assess the interactive relationship between blood pressure status and diabetic mellitus (DM) with ganglion cell complex (GCC) thickness in elderly individuals in rural China. METHODS: Participants aged 50 years and older in a rural area of Daxing District, Beijing, were recruited in this study from October 2018 to November 2018. All subjects underwent a comprehensive systemic and ocular examination. Blood pressure status was graded as normotension, controlled hypertension and uncontrolled hypertension according to blood pressure measurements and the use of any medication for hypertension treatment. GCC parameters were measured by spectral-domain optical coherence tomography (SD-OCT). Generalized linear models (GLM) adjusted for related potential confounders were used to assess the interaction between DM and blood pressure status. RESULTS: Among 1415 screened subjects (2830 eyes), a total of 1117 eyes were enrolled in the final analysis. GLM analysis showed a significant interactive relationship between DM with uncontrolled hypertension status (ß = 3.868, p = 0.011). GCC thickness would decrease 0.255 µm per year as the age increased (ß=-0.255, p < 0.001). In a subgroup of 574 subjects with uncontrolled hypertension, DM was associated with an increased average of GCC thickness (ß = 1.929, p = 0.022). CONCLUSIONS: The present results revealed a significant interactive relationship between blood pressure status and DM. The average GCC thickness increased in individuals with DM combined with uncontrolled hypertension, which should be considered in the measurement of GCC. Further studies are warranted to explore ganglion cells changes as a non-invasive method to detect neuron alterations in individuals with DM and uncontrolled hypertension. TRAIL REGISTRATION: The registration number of the present trial in the Chinese Clinical Trial Registry is ChiCTR2000037944.

The Formation and Renewal of Photoreceptor Outer Segments.

The visual system is essential for humans to perceive the environment. In the retina, rod and cone photoreceptor neurons are the initial sites where vision forms. The apical region of both cone and rod photoreceptors contains a light-sensing organelle known as the outer segment (OS), which houses tens of thousands of light-sensitive opsins. The OSs of photoreceptors are not static; they require rhythmic renewal to maintain normal physiological functions. Disruptions in OS renewal can lead to various genetic disorders, such as retinitis pigmentosa (RP). Understanding the patterns and molecular mechanisms of photoreceptor OS renewal remains one of the most intriguing topics in visual biology. This review aims to elucidate the structure of photoreceptor OSs, the molecular mechanisms underlying photoreceptor OS renewal, and the retinal diseases resulting from defects in this renewal process. Additionally, we will explore retinal diseases related to photoreceptor OS renewal and potential therapeutic strategies, concluding with a discussion on future research directions for OS renewal.

Temporal Transcriptomic Profiling of the Developing Xenopus laevis Eye.

Retinal progenitor cells (RPCs) are a multipotent and highly proliferative population that give rise to all retinal cell types during organogenesis. Defining their molecular signature is a key step towards identifying suitable approaches to treat visual impairments. Here, we performed RNA sequencing of whole eyes from Xenopus at three embryonic stages and used differential expression analysis to define the transcriptomic profiles of optic tissues containing proliferating and differentiating RPCs during retinogenesis. Gene Ontology and KEGG pathway analyses showed that genes associated with developmental pathways (including Wnt and Hedgehog signaling) were upregulated during the period of active RPC proliferation in early retinal development (Nieuwkoop Faber st. 24 and 27). Developing eyes had dynamic expression profiles and shifted to enrichment for metabolic processes and phototransduction during RPC progeny specification and differentiation (st. 35). Furthermore, conserved adult eye regeneration genes were also expressed during early retinal development, including sox2, pax6, nrl, and Notch signaling components. The eye transcriptomic profiles presented here span RPC proliferation to retinogenesis and include regrowth-competent stages. Thus, our dataset provides a rich resource to uncover molecular regulators of RPC activity and will allow future studies to address regulators of RPC proliferation during eye repair and regrowth.

Metabolic Deficits in the Retina of a Familial Dysautonomia Mouse Model.

Neurodegenerative retinal diseases such as glaucoma, diabetic retinopathy, Leber's hereditary optic neuropathy (LHON), and dominant optic atrophy (DOA) are marked by progressive death of retinal ganglion cells (RGC). This decline is promoted by structural and functional mitochondrial deficits, including electron transport chain (ETC) impairments, increased oxidative stress, and reduced energy (ATP) production. These cellular mechanisms associated with progressive optic nerve atrophy have been similarly observed in familial dysautonomia (FD) patients, who experience gradual loss of visual acuity due to the degeneration of RGCs, which is thought to be caused by a breakdown of mitochondrial structures, and a disruption in ETC function. Retinal metabolism plays a crucial role in meeting the elevated energetic demands of this tissue, and recent characterizations of FD patients' serum and stool metabolomes have indicated alterations in central metabolic processes and potential systemic deficits of taurine, a small molecule essential for retina and overall eye health. The present study sought to elucidate metabolic alterations that contribute to the progressive degeneration of RGCs observed in FD. Additionally, a critical subpopulation of retinal interneurons, the dopaminergic amacrine cells, mediate the integration and modulation of visual information in a time-dependent manner to RGCs. As these cells have been associated with RGC loss in the neurodegenerative disease Parkinson's, which shares hallmarks with FD, a targeted analysis of the dopaminergic amacrine cells and their product, dopamine, was also undertaken. One dimensional (1D) proton (1H) nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and retinal histology methods were employed to characterize retinae from the retina-specific Elp1 conditional knockout (CKO) FD mouse model (Pax6-Cre; Elp1LoxP/LoxP). Metabolite alterations correlated temporally with progressive RGC degeneration and were associated with reduced mitochondrial function, alterations in ATP production through the Cahill and mini-Krebs cycles, and phospholipid metabolism. Dopaminergic amacrine cell populations were reduced at timepoints P30-P90, and dopamine levels were 25-35% lower in CKO retinae compared to control retinae at P60. Overall, this study has expanded upon our current understanding of retina pathology in FD. This knowledge may apply to other retinal diseases that share hallmark features with FD and may help guide new avenues for novel non-invasive therapeutics to mitigate the progressive optic neuropathy in FD.

Severe hypoglycaemia-induced microglial inflammation damages microvascular endothelial cells, leading to retinal destruction.

Human microglia (HMC) are stress-induced inflammatory cells of the retina. It is unknown whether severe hypoglycaemia causes inflammation in microglia, affects the permeability of human retinal microvascular endothelial cells (HRMECs), and causes retinal damage. This study aimed to explore the effects of severe hypoglycaemia on retinal microglial inflammation and endothelial cell permeability and evaluate the damage caused by hypoglycaemia to the retina. The CCK-8 assay was used to measure cell viability. Western blotting was used to detect IL-1ß, IL-6, TNF- α, claudin-1, and occludin expression. ELISA was used to detect IL-1ß, IL-6, and TNF- α. Transmission electron microscopy (TEM) and haematoxylin and eosin staining were used to observe the retinal structure. Immunohistochemistry and immunofluorescence staining assays were also used to detect IL-1ß, IL-6, TNF- α, claudin-1, and occludin expression. Severe hypoglycaemia promoted inflammation in HMC3 cells. Inflammation caused by hypoglycaemia leads to the decreased expression of tight junction proteins. In vivo, severe hypoglycaemia induced structural damage to the retina, increased the expression of inflammatory factors, and decreased the expression of tight junction proteins. Our results suggest that severe hypoglycaemia leads to acute retinal inflammation, affecting the permeability of HRMECs and causing retinal damage.

Glue-Assisted Retinopexy for Retinal Detachments Study Report 2: Fibrin Glue As a Surgical Adjunct in Complex Rhegmatogenous Retinal Detachment.

Purpose: To present the successful application of fibrin glue as a surgical adjunct in the management of complex rhegmatogenous retinal detachment (RRD). Methods: In this retrospective case series, fibrin glue was used as a surgical adjunct in 5 cases of complex RRD. In each case, standard pars plana vitrectomy and laser retinopexy were performed by the same surgeon. Fibrin glue was used intraoperatively as a tamponade to seal the breaks because the isolated use of conventional tamponade agents was not feasible given the variable nature of the complex RRDs, the anatomy of the eye, or an inability to maintain postoperative positioning. Results: In 1 patient previously treated for a large corneoscleral tear, fibrin glue was used to seal a large iatrogenic retinal break caused by a fragmatome-related surge that led to a quadrantic RD. In 2 patients treated for combined RRD, fibrin glue was used with silicone oil to manage recurrent RRD with incompletely drained thick subretinal fluid and blood. In 2 other cases, fibrin glue was applied to manage RRD in congenital aniridia with advanced glaucoma and aphakia. In all cases, retinal attachment without serious adverse effects was attained over a follow-up ranging from 4 to 6 months. Conclusions: Fibrin glue is an effective, safe surgical adjunct in complex RRD. It can be used to transiently seal a retinal break when use of a conventional tamponade agent is not possible or not sufficient alone.

Biological and Methodological Variability in Retinal Nerve Fiber Layer OCT: The Framingham Heart Study.

Objective: To explore participant-level biological attributes and scan-level methodological attributes associated with retinal nerve fiber layer (RNFL) thickness variability in a population-based sample of elderly United States adults. Design: Cross-sectional analysis using data from the Framingham Heart Study. Participants: One thousand three hundred forty-seven eyes from 825 participants with ≥1 OCT scan and axial length data were included. Methods: Three or more successive RNFL scans of each eye of each participant were obtained in a single session. Multivariable linear mixed models were employed to explore the associations between average RNFL thickness with participant-level biological attributes (age, gender, race, ethnicity, and axial length) and scan-level attributes (signal strength [SS]) as independent variables in the whole population as well as a subsample of adults with no self-reported history of glaucoma. Similar analyses were designed to assess methodological variability with average within-eye standard deviation (SD) for repeated scans as the dependent variable. Main Outcomes Measures: (1) Biological variability: average RNFL thickness, and (2) methodological variability: average within-participant SD across repeated scans. Results: Age (ß =  - 0.19 microns/year, [95% confidence interval {CI}: - 0.29, - 0.09]), female gender (ß = +1.48 microns vs. male, [95% CI: 0.09, 2.86]), axial length (ß =  - 1.24 microns/mm of greater length, [95% CI: - 1.80, - 0.67]), and SS (ß = +1.62 microns/1 unit greater SS, [95% CI: 1.16, 2.09]) were significantly associated with RNFL thickness, while race and ethnicity were not (P > 0.05). In analyses designed to assess methodological variability, higher RNFL thickness (ß = +0.02 per micron increase, [95% CI: 0.01, 0.03]), and lower SS (ß = +0.19 per 1 unit lower SS, [95% CI: 0.10, 0.27]) were significantly associated with greater RNFL variability. In adults with no self-reported history of glaucoma (n of eyes = 1165, n of participants = 712), female gender was not associated with RNFL, while African American race was associated with thicker RNFL (ß = +4.65 microns vs. Whites, [95% CI: 1.28, 8.03]). Conclusions: Retinal nerve fiber layer thickness is lower with older age, male gender, greater axial length, lower SS, and Whites (as compared with African Americans) without self-reported glaucoma. Measurement variability (SD) is higher with greater RNFL thickness and lower SS. Understanding these biological and methodological variations is important to aid in OCT interpretation. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Characterization of Retinal Microvascular Abnormalities in Birdshot Chorioretinopathy Using OCT Angiography.

Objective: To characterize changes in the retinal microvasculature in eyes with birdshot chorioretinopathy (BCR) using OCT angiography (OCTA). Design: Retrospective, observational, single center. Subjects: Twenty-eight patients (53 eyes) with BCR and 59 age-matched controls (110 eyes). Methods: En face OCTA images of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of each eye were assessed for the presence of microvascular abnormalities and used to measure the vessel and foveal avascular zone (FAZ) areas. A longitudinal analysis was performed with a representative cohort of 23 BCR eyes (16 patients) at baseline and at a 2-year time point. Main Outcome Measures: Whole-image vessel density (VD, %), extrafoveal avascular zone (extra-FAZ) VD (%), and FAZ area (%) were calculated and compared between control and BCR eyes. The frequency of microvascular abnormalities in BCR eyes was recorded. Results: In the SCP, increased intercapillary space and capillary loops were common features present on OCTA images. Whole-image and extra-FAZ VD were lower in the BCR group compared with controls (P < 0.0001 [SCP and DCP]). Foveal avascular zone area was enlarged in BCR eyes (P = 0.0008 [DCP]). Worsening best-corrected visual acuity was associated with a decrease in whole-image and extra-FAZ VD in the SCP (P < 0.0001 for both) and the DCP (P < 0.005 for both). Multivariable analysis, with vessel analysis parameters as outcomes, demonstrated that increasing age, increasing disease duration, lower central subfield thickness, and treatment-naive eyes (compared with those on only biologics) were associated with a significant decrease in both DCP whole-image and extra-FAZ VD. Increasing disease duration was associated with a significant decrease in both SCP whole-image and extra-FAZ VD. Longitudinal analysis demonstrated no significant difference in any vessel analysis parameters except for an increase in DCP FAZ area. Conclusions: Our results demonstrate a significant a decrease in VD in BCR eyes and an association on multivariable analysis with disease duration. Quantifying VD in the retinal microvasculature may be a useful biomarker for monitoring disease severity and progression in patients with BCR. Further studies with extended longitudinal follow-up are needed to characterize its utility in monitoring disease progression and treatment response. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Suppression of inner blood-retinal barrier breakdown and pathogenic Müller glia activation in ischemia retinopathy by myeloid cell depletion.

Ischemic retinopathies including diabetic retinopathy are major causes of vision loss. Inner blood-retinal barrier (BRB) breakdown with retinal vascular hyperpermeability results in macular edema. Although dysfunction of the neurovascular unit including neurons, glia, and vascular cells is now understood to underlie this process, there is a need for fuller elucidation of the underlying events in BRB dysfunction in ischemic disease, including a systematic analysis of myeloid cells and exploration of cellular cross-talk. We used an approach for microglia depletion with the CSF-1R inhibitor PLX5622 (PLX) in the retinal ischemia-reperfusion (IR) model. Under non-IR conditions, PLX treatment successfully depleted microglia in the retina. PLX suppressed the microglial activation response following IR as well as infiltration of monocyte-derived macrophages. This occurred in association with reduction of retinal expression of chemokines including CCL2 and the inflammatory adhesion molecule ICAM-1. In addition, there was a marked suppression of retinal neuroinflammation with reduction in expression of IL-1b, IL-6, Ptgs2, TNF-a, and Angpt2, a protein that regulates BRB permeability. PLX treatment significantly suppressed inner BRB breakdown following IR, without an appreciable effect on neuronal dysfunction. A translatomic analysis of Müller glial-specific gene expression in vivo using the Ribotag approach demonstrated a strong suppression of Müller cell expression of multiple pro-inflammatory genes following PLX treatment. Co-culture studies of Müller cells and microglia demonstrated that activated microglia directly upregulates Müller cell-expression of these inflammatory genes, indicating Müller cells as a downstream effector of myeloid cells in retinal IR. Co-culture studies of these two cell types with endothelial cells demonstrated the ability of both activated microglia and Müller cells to compromise EC barrier function. Interestingly, quiescent Müller cells enhanced EC barrier function in this co-culture system. Together this demonstrates a pivotal role for myeloid cells in inner BRB breakdown in the setting of ischemia-associated disease and indicates that myeloid cells play a major role in iBRB dysregulation, through direct and indirect effects, while Müller glia participate in amplifying the neuroinflammatory effect of myeloid cells.

VEGF-A165a and angiopoietin-2 differently affect the barrier formed by retinal endothelial cells.

Exposure to VEGF-A165a over several days leads to a persistent dysfunction of the very tight barrier formed by immortalized endothelial cells of the bovine retina (iBREC). Elevated permeability of the barrier is indicated by low cell index values determined by electric cell-substrate impedance measurements, by lower amounts of claudin-1, and by disruption of the homogenous and continuous staining of vascular endothelial cadherin at the plasma membrane. Because of findings that suggest modulation of VEGF-A's detrimental effects on the inner blood-retina barrier by the angiogenic growth factor angiopoietin-2, we investigated in more detail in vitro whether this growth factor indeed changes the stability of the barrier formed by retinal endothelial cells or modulates effects of VEGF-A. In view of the clinical relevance of anti-VEGF therapy, we also studied whether blocking VEGF-A-driven signaling is sufficient to prevent barrier dysfunction induced by a combination of both growth factors. Although angiopoietin-2 stimulated proliferation of iBREC, the formed barrier was not weakened at a concentration of 3 nM: Cell index values remained high and expression or subcellular localization of claudin-1 and vascular endothelial cadherin, respectively, were not affected. Angiopoietin-2 enhanced the changes induced by VEGF-A165a and this was more pronounced at lower concentrations of VEGF-A165a. Specific inhibition of the VEGF receptors with tivozanib as well as interfering with binding of VEGF-A to its receptors with bevacizumab prevented the detrimental effects of the growth factors; dual binding of angiopoietin-2 and VEGF-A by faricimab was marginally more efficient. Uptake of extracellular angiopoietin-2 by iBREC can be efficiently prevented by addition of faricimab which is also internalized by the cells. Exposure of the cells to faricimab over several days stabilized their barrier, confirming that inhibition of VEGF-A signaling is not harmful to this cell type. Taken together, our results confirm the dominant role of VEGF-A165a in processes resulting in increased permeability of retinal endothelial cells in which angiopoietin-2 might play a minor modulating role.

Demographic profile, prevalence, pattern, and risk factors for retinal vein occlusion in Liberia: A retrospective study.

PURPOSE: This study aims to describe the demographic profile, prevalence, pattern, and risk factors for retinal vein occlusion (RVO) in patients over 40 years of age presenting to the Liberia Eye Centre, John F Kennedy Memorial Medical Centre, Monrovia, Liberia. SUBJECTS AND METHODS: A retrospective study was conducted on patients presenting to Liberia Eye Centre from July 2017 to February 2021. A total of 17506 new patients were examined during this period out of which 10813 patients were over 40 years of age. Data were collected from the electronic medical record system database. The variables in the collected data included age, gender, location, laterality of eye affected, uncorrected visual acuity, best-corrected visual acuity, intraocular pressure, ocular diagnosis, systemic risk factors, and associated complications. RESULTS: Of the 10813 patients, RVO was found in 111 patients with an overall prevalence rate of 1.03% (95% confidence interval 0.80-1.2). Central RVO (CRVO) was more common than branch RVO (BRVO) in the defined population with similar proportions of both genders. The mean age for any RVO was 64.45 ± 12.27 standard deviation (SD) years (P = 0.734). Majority of the cases of RVO were from Lofa (n = 20; 18%). Fifty-five (61.1%) patients had hypertension, 5 (5.6%) had diabetes mellitus, and 6 (6.7%) had dyslipidemia. More than one systemic risk factor was present in 24 (26.7%) patients. However, none of the systemic risk factors were statistically significant. Visual acuity was most affected in patients with CRVO, with a visual acuity of <3/60 in 45 (63.4%) patients compared to 12 (30.0%) in BRVO patients. Glaucoma was present in 34 (30.6%) patients. The most common ocular complication was macular edema (n = 62, 55.8%) followed by vitreous hemorrhage (n = 8, 7.2%). CONCLUSIONS: RVO was detected in 1.03% of the study population over the age of 40 years in Liberia, CRVO being more common than BRVO. The clinical presentation of RVO in the Liberian population for the first time provides insight into the burden of the disease and opportunity for further research.

Efficacy and safety of large-scale use of vancomycin injection in infusion bottle during vitreoretinal procedures.

PURPOSE: The purpose of this study was to assess the safety and efficacy of large-scale use of vancomycin injection in an infusion bottle during vitreoretinal procedures. MATERIALS AND METHODS: This was a retrospective evaluation of all vitreoretinal procedures done in the last 70 months, where intraoperatively vancomycin injection (0.2 mg/mL) was used in an infusion bottle prophylactically as standard care. Vitreoretinal procedures were categorized as major (duration >30 min), minor (duration <30 min), and silicone oil removal. Postoperatively, a detailed ocular examination was done to rule out hemorrhagic occlusive retinal vasculitis (HORV) or signs of postoperative bacterial endophthalmitis. RESULTS: Over the last 70 months, a total of 31,720 vitreoretinal procedures were performed, which included 24,371 major vitreoretinal procedures, 1401 minor vitreoretinal procedures, and 5948 silicone oil removal cases. None of these cases developed HORV or bacterial endophthalmitis. CONCLUSION: Vancomycin (0.2 mg/mL) in infusion fluid during vitreoretinal procedures is safe and can be advocated as a prophylactic measure against postvitrectomy bacterial infections.

Analysis of Microtubule Polymerization During Axon Outgrowth Using Fluorescently Labeled Microtubule Plus-End Tracking Proteins.

The study of microtubules arrangements and dynamics during axon outgrowth and pathfinding has gained scientific interest during the last decade, and numerous technical resources for its visualization and analysis have been implemented. In this chapter, we describe the cell culture protocols of embryonic cortical and retinal neurons, the methods for transfecting them with fluorescent reporters of microtubule polymerization, and the procedures for time-lapse imaging and quantification in order to study microtubule dynamics during axon morphogenesis.

The association between taurine concentrations and dog characteristics, clinical variables, and diet in English cocker spaniels: The Canine taURinE (CURE) project.

BACKGROUND: Occurrence of low blood taurine concentrations (B-TauC) and predisposing factors to taurine deficiency in English Cocker Spaniels (ECS) are incompletely understood. OBJECTIVES: Investigate the occurrence of low B-TauC in a Swedish population of ECS and evaluate the association between B-TauC and dog characteristics, clinical variables, and diet composition. ANIMALS: One-hundred eighty privately owned ECS. METHODS: Dogs were prospectively recruited and underwent physical examination, blood analyses, and echocardiographic and ophthalmic examinations. Dogs with clinical signs of congestive heart failure (CHF) also underwent thoracic radiography. Taurine concentrations were analyzed in plasma (EDTA and heparin) and whole blood. Diets consumed by the dogs at the time of the examination were analyzed for dietary taurine- (D-TauC), cysteine- (D-CysC), and methionine concentrations (D-MetC). RESULTS: Fifty-three of 180 dogs (29%) had low B-TauC, of which 13 (25%) dogs had clinical and radiographic signs of CHF, increased echocardiographic left ventricular (LV) dimensions and volumes, and impaired LV systolic function. Five (9%) dogs with low B-TauC had retinal abnormalities. Dietary MetC, dietary animal protein source (red/white meat), and age were associated with B-TauC in the final multivariable regression model (P < .001, R2 adj = .39). CONCLUSIONS AND CLINICAL IMPORTANCE: Low B-TauC suggests that taurine deficiency may play a role in the development of myocardial failure and CHF in ECS. Low D-MetC and diets with red meat as the animal protein source were associated with low B-TauC. Dogs with B-TauC below the normal reference range were older than dogs with normal concentrations.