Examining the Influence of Genes Linked to Comorbidities on the Development of Diabetic Retinopathy

Diabetic retinopathy (DR) is a complication in diabetic patients that can cause vision loss and even blindness12 {Healthline}. The condition causes bleeding in the blood vessels of the retina and ultimately interferes with the capture of photons and the transmission of neural signals to the brain3 {National Eye Institute}. Unfortunately, there is no cure available for the approximately 200,000 US citizens currently affected by DR8 {Lucas Research}. Current treatments are merely palliative and rarely restore vision. The best approach to combating DR is prevention. Understanding the root genetic causal links of DR is crucial to developing effective prevention plans. Unlike Huntington’s Disease, which has well defined genetic origins, no single gene has been pinpointed as a causative factor for DR, despite having been extensively researched. Since diabetes alone isn’t enough to predict the progression to DR4{NCBI}, one can hypothesize that a combination of diabetes and at least one other comorbidity, such as high blood pressure, high cholesterol, etc., may be essential to the development of DR. In this way, single nucleotide polymorphisms (SNPs) associated with other comorbidities could increase the likelihood of retinal bleeding in diabetic populations. The identification of these SNPs would offer valuable insight into the development of a genetically-driven prevention plan for diabetic retinopathy.

Focal superior quadrant haemorrhages in post COVID-19 patient: A target for personalized medicine

Purpose: To report a case of multiple superior quadrant intraretinal haemorrhages in post-COVID-19 patient. Case description: A 58-year-old male with a history of coronary artery disease and hypertension, presented with multiple superior quadrant intraretinal haemorrhages in the superonasal quadrant of the left eye 1 month after hospitalization for COVID-19. The right eye was normal. During his 10-day stay, he was treated with hydroxychloroquine, lopinavir + ritonavir, ceftriaxone, and his pre-existing antiplatelet therapy. During hospitalization, a complete medical work up showed an anomalous increase in D-dimer. He did not require intensive care support. Conclusions: In this report, we focused on the origin of retinal bleeding in a post COVID-19 patient, likely due to a focal occlusion of a vessel. Considering the nature of SARS-CoV-2 infection, we hypothesize that retinal haemorrhages were caused by a combination of factors including the patient’s antiplatelet therapy and the thrombotic microvascular injury caused by the virus.

Sirolimus plus nintedanib treats vascular pathology in HHT mouse models

ABSTRACTHereditary hemorrhagic telangiectasia (HHT), a genetic bleeding disorder leading to systemic arteriovenous malformations (AVMs), is caused by loss-of-function mutations in the ALK1-ENG-Smad1/5/8 pathway. Evidence suggests that HHT pathogenesis strongly relies on overactivated PI3K-Akt-mTOR and VEGFR2 pathways in endothelial cells (ECs). In the BMP9/10-immunoblocked (BMP9/10ib) neonatal mouse model of HHT, we report here that the mTOR inhibitor, sirolimus, and the receptor tyrosine-kinase inhibitor, nintedanib, could synergistically fully block, but also reversed, retinal AVMs to avert retinal bleeding and anemia. Sirolimus plus nintedanib prevented vascular pathology in the oral mucosa, lungs, and liver of the BMP9/10ib mice, as well as significantly reduced gastrointestinal bleeding and anemia in inducible ALK1-deficient adult mice. Mechanistically, in vivo in BMP9/10ib mouse ECs, sirolimus and nintedanib blocked the overactivation of mTOR and VEGFR2, respectively. Furthermore, we found that sirolimus activated ALK2-mediated Smad1/5/8 signaling in primary ECs—including in HHT patient blood outgrowth ECs—and partially rescued Smad1/5/8 activity in vivo in BMP9/10ib mouse ECs. These data demonstrate that the combined correction of endothelial Smad1/5/8, mTOR, and VEGFR2 pathways opposes HHT pathogenesis. Repurposing of sirolimus plus nintedanib might provide therapeutic benefit in HHT patients.

Polypoidal Choroidal Vasculopathy

Polypoidal choroidal vasculopathy (PCV) is a disease of the choroidal vasculature that may result in sub-retinal hemorrhage and serous detachment of the retinal pigmented epithelium (RPE), leading to sub-retinal brosis and, sometimes, permanent vision loss. This report describes a case of PCV in an African-American female over the course of 1 year and demonstrates the progression of PCV, from being relatively asymptomatic to the development of a visually significant sub-retinal hemorrhage. She is currently being treated with Avastin intravitreal injections with some resolution of her symptoms and a reduction of sub-retinal bleeding.

Resolution of Retinal Bleeding And Exudative Retinal Detachment After Chemotherapy with Melphalan In Multiple Myeloma

Introduction: Multiple myeloma is the second most common hematologic cancer. It is characterized by the clonal proliferation of malignant plasma cells and associated organ dysfunction. Ophthalmic manifestations include hyperviscosity retinopathy and retinal detachment. The aim of this study is to report retinal manifestation in Multiple Myeloma. Methods: A man 45 years old, complained loss of vision on both eyes especially left eye over 1 month. He also feels weakness and 3 times spontaneous nose bleeding. His visual acquity is 6/12 on the right and 2/60 left eye with Retinal Bleeding and Retinal Detachment. His Laboratory examination result increase in WBC 65.91 x 103/µL (Neutrophil, Monocyte, Basophil and Lymphocyte) decrease RBC 3 x 106/µL, HGB 6.85 g/dL, normal PLT 193.60 103/µL, Normal Bleeding and Clotting Time and increase ESR 140 mm/hour. Multiple myeloma was diagnosed by Internal Department with bone marrow biopsy and increase of Gamma Globulin. Results: The patient was treated with melphalan 3 tablet 2 times a day and prednisone 4 mg 3 times a day for 5 days every 28 days. After 8 month the VA 6/6 on the right and 6/10 on the left with complete resolution of on the right eye and there are resolution on the left eye with fibrosis, the laboratory examination normal WBC 3.8 x 103/µL with Neutrophil 59.3%, Monocyte 6.1 %, Eosinophil 6.3 %, Basophil 0.3 % and Lymphocyte 28.0 %, normal RBC 4.6 x 106/µL, slightly decrease HGB 12.8 g/dL, normal PLT 177.0 x 103/µL and decrease Gamma Globulin. Discussion: This case of bilateral Retinal Bleeding and Exudative Retinal Detachment are remarkable for both its presentation and response to melphalan therapy. Treatment with melphalan and prednison alone was sufficient to clear the Retinal Bleeding and restoration of Exudative Retinal Detachment. Conclusion: Complication of Multiple Myeloma can caused organ disfunction such as retinal bleeding and exudative retinal detachment. Early Diagnosis is very crucial. In our case combination cemotheraphy with Melphalan and Prednison showed clinically significant resolution. Workship Internal Department and Ophthalmology Department are very important for management and monitoring ophthalmology manifestation in multiple myeloma.

Resolution of Retinal Bleeding And Exudative Retinal Detachment After Chemotherapy with Melphalan In Multiple Myeloma

Introduction: Multiple myeloma is the second most common hematologic cancer. It is characterized by the clonal proliferation of malignant plasma cells and associated organ dysfunction. Ophthalmic manifestations include hyperviscosity retinopathy and retinal detachment. The aim of this study is to report retinal manifestation in Multiple Myeloma. Methods: A man 45 years old, complained loss of vision on both eyes especially left eye over 1 month. He also feels weakness and 3 times spontaneous nose bleeding. His visual acquity is 6/12 on the right and 2/60 left eye with Retinal Bleeding and Retinal Detachment. His Laboratory examination result increase in WBC 65.91 x 103/µL (Neutrophil, Monocyte, Basophil and Lymphocyte) decrease RBC 3 x 106/µL, HGB 6.85 g/dL, normal PLT 193.60 103/µL, Normal Bleeding and Clotting Time and increase ESR 140 mm/hour. Multiple myeloma was diagnosed by Internal Department with bone marrow biopsy and increase of Gamma Globulin. Results: The patient was treated with melphalan 3 tablet 2 times a day and prednisone 4 mg 3 times a day for 5 days every 28 days. After 8 month the VA 6/6 on the right and 6/10 on the left with complete resolution of on the right eye and there are resolution on the left eye with fibrosis, the laboratory examination normal WBC 3.8 x 103/µL with Neutrophil 59.3%, Monocyte 6.1 %, Eosinophil 6.3 %, Basophil 0.3 % and Lymphocyte 28.0 %, normal RBC 4.6 x 106/µL, slightly decrease HGB 12.8 g/dL, normal PLT 177.0 x 103/µL and decrease Gamma Globulin. Discussion: This case of bilateral Retinal Bleeding and Exudative Retinal Detachment are remarkable for both its presentation and response to melphalan therapy. Treatment with melphalan and prednison alone was sufficient to clear the Retinal Bleeding and restoration of Exudative Retinal Detachment. Conclusion: Complication of Multiple Myeloma can caused organ disfunction such as retinal bleeding and exudative retinal detachment. Early Diagnosis is very crucial. In our case combination cemotheraphy with Melphalan and Prednison showed clinically significant resolution. Workship Internal Department and Ophthalmology Department are very important for management and monitoring ophthalmology manifestation in multiple myeloma.

Outcomes and factors associated with infant abusive head trauma in the US

OBJECT Head trauma is the leading cause of death in abused children, particularly prior to the age of 2 years. An awareness of factors associated with this condition as well as with a higher risk of mortality is important to improve outcomes and prevent the occurrence of these events. The objective of this study was to evaluate outcomes and factors associated with poor outcomes in infants with diagnosed abusive head trauma (AHT). Patient characteristics, socioeconomic factors, and secondary conditions such as retinal bleeding, contusion, and fractures were considered. METHODS Data were obtained from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality. From the Kids’ Inpatient Database (KID) sample, the authors identified infants no older than 23 months who had been diagnosed with AHT in 2000, 2003, 2006, and 2009. All statistical analyses were conducted in SAS 9.2. Descriptive statistics were provided, and multivariate logistic regression models were applied to evaluate factors associated with mortality and nonroutine discharge. RESULTS A total of 5195 infants were analyzed in this study. Most infants (85.5%) had ages ranging between 0 and 11 months and were male (61.6%). Overall mortality was 10.8%, with a rate of 9.8% in the 0- to 11-month-old cohort and 16.5% in the 12- to 23-month-olds (p = 0.0003). The overall nonroutine discharge rate of 25.6% increased significantly from 23.3% to 39.0% with increasing age (0–11 vs 12–23 months of age, p < 0.0001). Assuming a multivariate model that adjusted for multiple confounders, the authors found that older infants (12–23 vs 0–11 months, OR 1.81, 95% CI 1.18–2.77) with a secondary diagnosis of retinal bleeding (OR 2.85, 95% CI 2.02–4.00) or shaken baby syndrome (OR 2.09, 95% CI 1.48–2.94) had an increased risk of mortality; these factors were similarly associated with an increased odds of a nonroutine discharge. A higher income ($30,001–$35,000 vs $1–$24,999) was associated with a reduction in the odds of mortality (OR 0.46, 95% CI 0.29–0.72). In the subset of cases (1695 [32.6%]) that specified the perpetrator involved in infant injury, the authors found that the father, stepfather, or boyfriend was most frequently reported (67.4%). A trend for a higher AHT incidence was documented in the early ages (peak at 2 months) compared with older ages. CONCLUSIONS Despite the higher incidence of AHT among infants during the earlier months of life, higher mortality was documented in the 12- to 23-month-olds. Retinal bleeding and shaken baby syndrome were secondary diagnoses associated with higher mortality and nonroutine discharge. Males (67.4%) were overwhelmingly documented as the perpetrators involved in the injury of these infants.