Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.

Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. DR has non-proliferative stages, characterized in part by retinal neuroinflammation and ischemia, and proliferative stages, characterized by retinal angiogenesis. Several systemic factors, including poor glycemic control, hypertension, and hyperlipidemia, increase the risk of DR progression to vision-threatening stages. Identification of cellular or molecular targets in early DR events could allow more prompt interventions pre-empting DR progression to vision-threatening stages. Glia mediate homeostasis and repair. They contribute to immune surveillance and defense, cytokine and growth factor production and secretion, ion and neurotransmitter balance, neuroprotection, and, potentially, regeneration. Therefore, it is likely that glia orchestrate events throughout the development and progression of retinopathy. Understanding glial responses to products of diabetes-associated systemic dyshomeostasis may reveal novel insights into the pathophysiology of DR and guide the development of novel therapies for this potentially blinding condition. In this article, first, we review normal glial functions and their putative roles in the development of DR. We then describe glial transcriptome alterations in response to systemic circulating factors that are upregulated in patients with diabetes and diabetes-related comorbidities; namely glucose in hyperglycemia, angiotensin II in hypertension, and the free fatty acid palmitic acid in hyperlipidemia. Finally, we discuss potential benefits and challenges associated with studying glia as targets of DR therapeutic interventions. In vitro stimulation of glia with glucose, angiotensin II and palmitic acid suggests that: 1) astrocytes may be more responsive than other glia to these products of systemic dyshomeostasis; 2) the effects of hyperglycemia on glia are likely to be largely osmotic; 3) fatty acid accumulation may compound DR pathophysiology by promoting predominantly proinflammatory and proangiogenic transcriptional alterations of macro and microglia; and 4) cell-targeted therapies may offer safer and more effective avenues for DR treatment as they may circumvent the complication of pleiotropism in retinal cell responses. Although several molecules previously implicated in DR pathophysiology are validated in this review, some less explored molecules emerge as potential therapeutic targets. Whereas much is known regarding glial cell activation, future studies characterizing the role of glia in DR and how their activation is regulated and sustained (independently or as part of retinal cell networks) may help elucidate mechanisms of DR pathogenesis and identify novel drug targets for this blinding disease.

Association of Socioeconomic, Demographic, and Health Care Access Disparities With Severe Visual Impairment in the US.

Importance: Approximately 13% of US adults are affected by visual disability, with disproportionately higher rates in groups impacted by certain social determinants of health (SDOH). Objective: To evaluate SDOH associated with severe visual impairment (SVI) to ultimately guide targeted interventions to improve ophthalmic health. Design, Setting, and Participants: This quality improvement study used cross-sectional data from a telephone survey from the Behavioral Risk Factor Surveillance System (BRFSS) that was conducted in the US from January 2019 to December 2020. Participants were noninstitutionalized adult civilians who were randomly selected and interviewed and self-identified as "blind or having serious difficulty seeing, even while wearing glasses." Exposures: Demographic and health care access factors. Main Outcomes and Measures: The main outcome was risk of SVI associated with various factors as measured by odds ratios (ORs) and 95% CIs. Descriptive and logistic regression analyses were performed using the Web Enabled Analysis Tool in the BRFFS. Results: During the study period, 820 226 people (53.07% female) participated in the BRFSS survey, of whom 42 412 (5.17%) self-identified as "blind or having serious difficulty seeing, even while wearing glasses." Compared with White, non-Hispanic individuals, risk of SVI was increased among American Indian/Alaska Native (OR, 1.63; 95% CI, 1.38-1.91), Black/African American (OR, 1.50; 95% CI, 1.39-1.62), Hispanic (OR, 1.65; 95% CI, 1.53-1.79), and multiracial (OR, 1.33; 95% CI, 1.15-1.53) individuals. Lower annual household income and educational level (eg, not completing high school) were associated with greater risk of SVI. Individuals who were out of work for 1 year or longer (OR, 1.78; 95% CI, 1.54-2.07) or who reported being unable to work (OR, 2.90; 95% CI, 2.66-3.16) had higher odds of SVI compared with the other variables studied. Mental health diagnoses and 14 or more days per month with poor mental health were associated with increased risk of SVI (OR, 1.87; 95% CI, 1.73-2.02). Health care access factors associated with increased visual impairment risk included lack of health care coverage and inability to afford to see a physician. Conclusions and Relevance: In this study, various SDOH were associated with SVI, including self-identification as being from a racial or ethnic minority group; low socioeconomic status and educational level; long-term unemployment and inability to work; divorced, separated, or widowed marital status; poor mental health; and lack of health care coverage. These disparities in care and barriers to health care access should guide targeted interventions.

Sphenofrontal intradiploic dermoid cyst with cutaneous dermal sinus tract.

We report the case of a 5-year-old boy who presented with a draining cutaneous pit temporal to the lateral canthus, with recurrent periorbital infections. MRI and CT revealed a sinus tract leading from the pit at the skin surface to a 5 mm lesion located in the sphenoid bone near the left sphenofrontal suture. Intraoperative facial nerve monitoring and a lacrimal probe inside the sinus tract were used to guide dissection to the cyst through a minimally invasive temporal approach, without need for neurosurgical intervention.