Treatment outcomes of PCR-positive acute retinal necrosis.

BACKGROUND: Acute retinal necrosis (ARN) is a progressive necrotizing retinitis caused by viral infection. Optimal management strategies have not been established for this detrimental disease. Previous literature published suggests that Varicella-zoster virus (VZV) and Herpes simplex virus-1 (HSV1) are the most common promoters of acute retinal necrosis (ARN). AIMS: The purpose of our study was to investigate the viral distribution, demographic, and treatment outcomes of ARN. METHODS: A retrospective chart review evaluated data from PCR-positive ARN patients diagnosed between 2009 and 2018. RESULTS: Analysis of fourteen eyes from 12 patients found CMV and VZV as the commonest causes of ARN. Patients on 1 g of valacyclovir three times a day (V1T) had worse vision between first and final visits (mean difference of 1.25 ± 0.65, n = 2) compared with patients treated with 2 g of valacyclovir three times a day (V2T), or 900 mg twice a day of valganciclovir (V9B) (mean difference of - 0.067 ± 0.13, n = 6, and 0.067 ± 0.067, n = 6, respectively). Both V1T patients developed retinal detachments (RD). Both CMV patients treated with intravitreal triamcinolone developed ARN, elevated IOP, and one developed multiple RD. CONCLUSIONS: Our review found increased incidence of CMV-positive ARN. Patients with zone 1 disease had worse initial visual acuity. Moreover, patients had more favorable outcomes with V2T and V9B compared to V1T. CMV-positive patients clinically worsened after intravitreal steroid injections, further underscoring the value of a PCR diagnosis to tailor the patients' treatment plan accordingly.

CONVERSION OF FOCAL CHOROIDAL EXCAVATION WITH THE ONSET OF CENTRAL SEROUS CHORIORETINOPATHY: REPORT OF 2 CASES AND REVIEW OF THE LITERATURE.

PURPOSE: To describe two cases of focal choroidal excavation (FCE) conversion in patients with central serous chorioretinopathy. METHODS: Case report and literature review of cases of FCE conversion. RESULTS: A 35-year-old asymptomatic pregnant patient was found to have conforming FCE on spectral domain optical coherence tomography of the right eye during hydroxychloroquine screening. Three months later, she presented with decreased vision in the right eye and subretinal fluid in both eyes secondary to central serous chorioretinopathy. Spectral domain optical coherence tomography revealed that her FCE had changed to nonconforming type. A 40-year-old male patient was found to have nonconforming FCE and subretinal fluid in his right eye on spectral domain optical coherence tomography. On follow-up, spectral domain optical coherence tomography demonstrated resolution of subretinal fluid and conversion of nonconforming FCE to conforming type. Literature review showed that most cases of FCE remain stable over time. Conversion from nonconforming FCE to conforming type has been described after photodynamic therapy or anti-vascular endothelial growth factor therapy. Conversion from conforming to nonconforming type has been described in 2 cases that developed subretinal fluid in the setting of acute central serous chorioretinopathy. CONCLUSION: Our cases and literature review suggest that nonconforming FCE is the result of persistent subretinal fluid. Further studies are necessary to determine whether symptomatic nonconforming SRF needs treatment to reduce subretinal fluid.

Strengths-based inquiry of resiliency factors among refugees in Metro Vancouver: A comparison of newly-arrived and settled refugees.

STRENGTHS-BASED INQUIRY OF RESILIENCY FACTORS AMONG REFUGEES IN METRO VANCOUVER: A comparison of newly-arrived and settled refugees. OBJECTIVE: To identify the resiliency factors among refugees in the Metro Vancouver area, and compare these factors between newly-arrived and settled refugees. DESIGN: Semi-structured individual interviews. SETTING: Vancouver, British Columbia, and surrounding suburban communities. PARTICIPANTS: 13 key informants from resettlement, healthcare, and public education sectors who work closely with refugees, 13 refugees who have resided less than five years in Canada (LTFYRs), and 8 refugees who have resided greater than five years in Canada (GTFYRs). Refugee source countries were Syria, Iraq, Afghanistan, Iran, Kenya, Vietnam, Somalia, and Mexico. MAIN FINDINGS: Key informants stated that knowledge from this study would help create and improve current supports for refugees, inform policy, increase understanding of refugee perspectives, and promote strengths-based resettlement strategies. Resiliency factors were grouped into themes, which were categorized as internal or external resiliency factors. Internal resiliency factors included fixed characteristics (age at arrival, female gender, and past education/skills), positive coping strategies (acceptance and positivity), proactivity, and integration (personal identity and adaptation). External resiliency factors identified were support systems, employment and finances, living environment, and societal encouragement of refugees. Comparison of responses between LTFYRs and GTFYRs revealed overall consistency in resiliency factors, but with LTFYRs identifying characteristics that assisted with acute integration, such as age at arrival, more often than GTFYRs. Comparison of responses between refugees and key informants revealed that key informants less frequently identified internal resiliency factors. CONCLUSION: This study qualitatively describes several internal and external resiliency factors of refugees in Vancouver. Awareness and promotion of these resiliency factors in refugee populations, in collaboration with healthcare providers, settlement organizations and education systems, may improve refugee resettlement. These findings will also help generate the groundwork for local interventions that can support refugee resiliency in the population studied.

In vivo Retinal Fluorescence Imaging With Curcumin in an Alzheimer Mouse Model.

Alzheimer's disease (AD) is characterized by amyloid beta (Aß) plaques in the brain detectable by highly invasive in vivo brain imaging or in post-mortem tissues. A non-invasive and inexpensive screening method is needed for early diagnosis of asymptomatic AD patients. The shared developmental origin and similarities with the brain make the retina a suitable surrogate tissue to assess Aß load in AD. Using curcumin, a FluoroProbe that binds to Aß, we labeled and measured the retinal fluorescence in vivo and compared with the immunohistochemical measurements of the brain and retinal Aß load in the APP/PS1 mouse model. In vivo retinal images were acquired every 2 months using custom fluorescence scanning laser ophthalmoscopy (fSLO) after tail vein injections of curcumin in individual mice followed longitudinally from ages 5 to 19 months. At the same time points, 1-2 mice from the same cohort were sacrificed and immunohistochemistry was performed on their brain and retinal tissues. Results demonstrated cortical and retinal Aß immunoreactivity were significantly greater in Tg than WT groups. Age-related increase in retinal Aß immunoreactivity was greater in Tg than WT groups. Retinal Aß immunoreactivity was present in the inner retinal layers and consisted of small speck-like extracellular deposits and intracellular labeling in the cytoplasm of a subset of retinal ganglion cells. In vivo retinal fluorescence with curcumin injection was significantly greater in older mice (11-19 months) than younger mice (5-9 months) in both Tg and WT groups. In vivo retinal fluorescence with curcumin injection was significantly greater in Tg than WT in older mice (ages 11-19 months). Finally, and most importantly, the correlation between in vivo retinal fluorescence with curcumin injection and Aß immunoreactivity in the cortex was stronger in Tg compared to WT groups. Our data reveal that retina and brain of APP/PS1 Tg mice increasingly express Aß with age. In vivo retinal fluorescence with curcumin correlated strongly with cortical Aß immunohistochemistry in Tg mice. These findings suggest that using in vivo fSLO imaging of AD-susceptible retina may be a useful, non-invasive method of detecting Aß in the retina as a surrogate indicator of Aß load in the brain.

Blau syndrome following a bacterial infection.

An 11-month-old girl presented with dermatitis, boggy arthritis, and keratitis shortly after her hospitalization for bacterial pneumonia. A skin biopsy and genetic testing led to a diagnosis of Blau syndrome. Her symptoms persisted despite a stepwise increase in immune-modulating therapies. Her ocular findings advanced to include bilateral panuveitis, optic disk edema, and hypopigmented chorioretinitis. We speculate that the bacterial infection triggered an inflammatory reaction throughout her body that was facilitated by the pathogenic NOD2 variant.

SPONTANEOUS IMPROVEMENT OF SYPHILIS CHORIORETINITIS: CASE REPORT AND REVIEW OF THE LITERATURE.

PURPOSE: To describe a case of spontaneous improvement of syphilis chorioretinitis and review the literature. METHODS: Case report and literature review of cases with untreated syphilis chorioretinitis. RESULTS: A 58-year-old man presented to the emergency department with counting fingers vision, normal fundus, and disruption of the outer retinal layers on optical coherence tomography of the right eye. Examination by a retina specialist 3 weeks later revealed visual acuity of 20/50 and partial restoration of outer retinal layers on optical coherence tomography. Workup showed positive serology for syphilis and human immunodeficiency virus. Treatment with intravenous penicillin resulted in further vision improvement. Literature review showed six cases of spontaneous improvement of syphilis chorioretinitis. CONCLUSION: Spontaneous improvement of syphilis chorioretinitis is possible. Clinicians should keep a high index of suspicion and consider syphilis chorioretinitis in diseases that affect the outer retina even with spontaneous improvement.

Daily Intake of Grape Powder Prevents the Progression of Kidney Disease in Obese Type 2 Diabetic ZSF1 Rats.

Individuals living with metabolic syndrome (MetS) such as diabetes and obesity are at high risk for developing chronic kidney disease (CKD). This study investigated the beneficial effect of whole grape powder (WGP) diet on MetS-associated CKD. Obese diabetic ZSF1 rats, a kidney disease model with MetS, were fed WGP (5%, w/w) diet for six months. Kidney disease was determined using blood and urine chemical analyses, and histology. When compared to Vehicle controls, WGP intake did not change the rat bodyweight, but lowered their kidney, liver and spleen weight, which were in parallel with the lower serum glucose and the higher albumin or albumin/globin ratio. More importantly, WGP intake improved the renal function as urination and proteinuria decreased, or it prevented kidney tissue damage in these diabetic rats. The renal protection of WGP diet was associated with up-regulation of antioxidants (Dhcr24, Gstk1, Prdx2, Sod2, Gpx1 and Gpx4) and downregulation of Txnip (for ROS production) in the kidneys. Furthermore, addition of grape extract reduced H2O2-induced cell death of cultured podocytes. In conclusion, daily intake of WGP reduces the progression of kidney disease in obese diabetic rats, suggesting a protective function of antioxidant-rich grape diet against CKD in the setting of MetS.

YAP/TAZ Are Mechanoregulators of TGF-ß-Smad Signaling and Renal Fibrogenesis.

Like many organs, the kidney stiffens after injury, a process that is increasingly recognized as an important driver of fibrogenesis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are related mechanosensory proteins that bind to Smad transcription factors, the canonical mediators of profibrotic TGF-ß responses. Here, we investigated the role of YAP/TAZ in the matrix stiffness dependence of fibroblast responses to TGF-ß In contrast to growth on a stiff surface, fibroblast growth on a soft matrix led to YAP/TAZ sequestration in the cytosol and impaired TGF-ß-induced Smad2/3 nuclear accumulation and transcriptional activity. YAP knockdown or treatment with verteporfin, a drug that was recently identified as a potent YAP inhibitor, elicited similar changes. Furthermore, verteporfin reduced YAP/TAZ levels and decreased the total cellular levels of Smad2/3 after TGF-ß stimulation. Verteporfin treatment of mice subjected to unilateral ureteral obstruction similarly reduced YAP/TAZ levels and nuclear Smad accumulation in the kidney, and attenuated renal fibrosis. Our data suggest that organ stiffening cooperates with TGF-ß to induce fibrosis in a YAP/TAZ- and Smad2/3-dependent manner. Interference with this YAP/TAZ and TGF-ß/Smad crosstalk likely underlies the antifibrotic activity of verteporfin. Finally, through repurposing of a clinically used drug, we illustrate the therapeutic potential of a novel mechanointerference strategy that blocks TGF-ß signaling and renal fibrogenesis.

Recombinant N-Terminal Slit2 Inhibits TGF-ß-Induced Fibroblast Activation and Renal Fibrosis.

Fibrosis and inflammation are closely intertwined injury pathways present in nearly all forms of CKD for which few safe and effective therapies exist. Slit glycoproteins signaling through Roundabout (Robo) receptors have been described to have anti-inflammatory effects through regulation of leukocyte cytoskeletal organization. Notably, cytoskeletal reorganization is also required for fibroblast responses to TGF-ß Here, we examined whether Slit2 also controls TGF-ß-induced renal fibrosis. In cultured renal fibroblasts, which we found to express Slit2 and Robo-1, the bioactive N-terminal fragment of Slit2 inhibited TGF-ß-induced collagen synthesis, actin cytoskeletal reorganization, and Smad2/3 transcriptional activity, but the inactive C-terminal fragment of Slit2 did not. In mouse models of postischemic renal fibrosis and obstructive uropathy, treatment with N-terminal Slit2 before or after injury inhibited the development of renal fibrosis and preserved renal function, whereas the C-terminal Slit2 had no effect. Our data suggest that administration of recombinant Slit2 may be a new treatment strategy to arrest chronic injury progression after ischemic and obstructive renal insults by not only attenuating inflammation but also, directly inhibiting renal fibrosis.