Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that play a critical role in transmitting signals from cell-surface molecules to intracellular protein effectors. Key PI3Ks include PI3Kα, PI3Kβ, and PI3Kδ, which are regulated by receptors. The signaling pathway comprising the PI3Ks, along with a Ser/Thr kinase (AKT), a proto-oncogene product (mouse double minute (MDM)2), and a tumor suppressor protein (p53), plays an essential role in experimental proliferative vitreoretinopathy (PVR), which is a fibrotic blinding eye disorder. However, which PI3K isoforms are involved in PVR is unknown. A major characteristic of PVR is the formation of epi (or sub)-retinal membranes that consist of extracellular matrix and cells, including retinal pigment epithelium (RPE) cells, glial cells, and macrophages. RPE cells are considered key players in PVR pathogenesis. Using immunoblotting and immunofluorescence analyses, we herein provide the evidence that PI3Kδ is highly expressed in human RPEs when it is primarily expressed in leukocytes. We also found that PI3Kδ inactivation through two approaches, CRISPR/Cas9-mediated depletion and a PI3Kδ-specific inhibitor (idelalisib), not only blocks vitreous-induced activation of AKT and MDM2 but also abrogates a vitreous-stimulated decrease in p53. Furthermore, we demonstrate that PI3Kδ inactivation prevents vitreous-induced proliferation, migration, and contraction of human RPEs. These results suggest that PI3Kδ may represent a potential therapeutic target for RPE-related eye diseases, including PVR.

Importance: Gun violence represents a substantial public health issue, and firearm-related injuries rank second among the causes of injury-related deaths in children aged 0 to 17 years in the United States. Ocular trauma from firearm-related injuries can lead to devastating vision loss, but little is known to date about the specific demographics and characteristics of such injuries in children. Objective: To evaluate the epidemiologic pattern of pediatric firearm-related ocular injuries. Design, Setting, and Participants: This retrospective analysis used deidentified data from the National Trauma Data Bank, the largest national registry of hospitalized trauma cases in the United States. The firearm-related ocular injuries (n = 1972) of pediatric patients (defined as those younger than 21 years) hospitalized between January 1, 2008, and December 31, 2014, were analyzed. Statistical analyses were conducted from July 15, 2017, to June 15, 2019. Exposure: Firearm-related ocular trauma. Main Outcomes and Measures: Pediatric patients with firearm-related ocular injuries were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes and external causes of injury codes. Patient demographics (age, sex, and race/ethnicity), type of ocular injury, injury intent, geographic location, length of hospital admission, health insurance status, disposition at discharge, Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were collected. Results: A total of 8715 firearm-related ocular injuries were identified. Of these injuries, 1972 (22.6%) occurred in pediatric patients, most of whom were male (1678 [85.1%]) and adolescents (1037 [52.6%]), with a mean (SD) age of 15.2 (5) years. Common locations of injury were home (761 [38.6%]) and street (490 [24.8%]). Mean (SD) hospital length of stay was 7.6 (12) days, ISS was 16 (13.1), and GCS score was 11 (5.1). The most common types of firearm-related ocular injuries were open wound of the eyeball (820 [41.6%]) and ocular adnexa (502 [25.5%]), orbital injuries or fractures (591 [30.0%]), and contusion of the eye or adnexa (417 [21.1%]). Patients aged 0 to 3 years had greater odds of unintentional injuries (odds ratio [OR], 4.41; 95% CI, 2.51-7.75; P < .001) and injuries occurring at home (OR, 5.39; 95% CI, 2.81-10.38; P < .001), and those aged 19 to 21 years had greater odds of assault injuries (OR, 2.17; 95% CI, 1.77-2.66; P < .001) and injuries occurring on the street (OR, 1.61; 95% CI, 1.3-1.98; P < .001). Black patients had the greatest odds of having injuries with assault intention (OR, 4.53; 95% CI, 3.68-5.59; P < .001), and white patients had the greatest likelihood for self-inflicted injury (OR, 7.1; 95% CI, 5.92-9.51; P < .001). Traumatic brain injury resulted mostly from self-inflicted trauma (OR, 5.99; 95% CI, 4.16-8.63; P < .001), as did visual pathway injuries (OR, 2.86; 95% CI, 1.95-4.20; P < .001). The inpatient mortality rate was 12.2%. Conclusions and Relevance: This study found that pediatric firearm-related ocular injuries from 2008 through 2014 were predominantly sight-threatening and associated with traumatic brain injury. If the possible risk factors, including sex, age, race/ethnicity, and injury intention, can be confirmed for 2015 through 2019, these findings may be useful in developing strategies to prevent pediatric firearm-related ocular injuries.

The cornea and its adnexa pose a unique situation of a tightly defined set of requirements for its function. This includes: transparency, perfect built to obtain appropriate refractive power, protective barrier from microbial invaders. Moreso, the cornea also endures extreme external physical conditions (temperature, high and low humidity, winds and alike). All these functions are maintained while preserving a constant state of homogenous wetting. Toward that end the cornea is equipped with an elaborated network of sensory neural network. While enabling the blinking reflex and maintaining the physiological steady state of wetting, this neural network also makes the cornea prone to the discomfort that with or without associated changes seen on medical examination. ISOPT Clinical 2018 discussion touched upon this hypercomplex situation, addressing the role of inflammation and its resulting discomfort in dry eye conditions. The discussion also engulfed the emerging neuropathic pain syndrome that is recently gaining more attention. Another related topic was the utilization of autologous serum tears and its ability to provide amelioration to desperate patients. Finally, the panel discussed the issue of treating corneal infection, including when and how to utilize steroids in the course of therapy. We assume the reader will find interest in this discussion that directly addresses issues seen day in and day out in our busy clinics.

PURPOSE OF REVIEW: To summarize recent advances in the diagnosis of giant cell arteritis (GCA). RECENT FINDINGS: Less common manifestations of GCA include corneal edema, proptosis from lacrimal gland ischemia and sensorineuronal hearing loss. Histology studies have suggested that temporal artery biopsies (TAB) with fixed specimen lengths of 15 mm may be adequate to prevent false negative biopsies. In centers with appropriate radiologic expertise, a European rheumatology consensus guideline has proposed Doppler ultrasound as a first-line confirmatory test for GCA in lieu of temporal artery biopsy. Finding extracranial large vessel disease can help to diagnose GCA. Statistical prediction rules can help risk stratify patients with suspected GCA. Age and platelet level when maintained as continuous variables are the strongest predictors for GCA. SUMMARY: GCA can present with diverse ophthalmic and systemic presentations and expedient recognition of same can avoid diagnostic delay and possible vision loss, among other complications. TAB remains the conventional diagnostic standard test for GCA. The use of statistical prediction models and increased expertise in noninvasive imaging techniques such as ultrasound may decrease reliance on TAB, especially in patients determined to be at low risk for GCA.

Meibomian gland dysfunction (MGD) is the leading cause of evaporative dry eye disease and is one of the most common conditions encountered by eye care providers. MGD is characterized by obstruction of the meibomian gland terminal ducts and/or changes in their glandular secretion, resulting in changes in tear film stability, inflammation, and symptoms of irritation. There is no gold standard treatment for MGD, but rather a diversity of options. Conservative measures include warm compresses and lid hygiene, but there is growing interest and need for medical treatments and procedures. Potential medical treatments include antibiotics, non-steroidal and steroidal anti-inflammatory agents, essential fatty acid supplementation, hormone therapy, and control of Demodex infestation. Procedures include intraductal meibomian gland probing, the use of electronic heating devices, intense pulsed light therapy, and intranasal neurostimulation. We provide an update on MGD treatments based on recent studies.

The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface.

The light-sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body. Both physiological and pathological retinal vascular growth and regression are controlled by photoreceptor energy demands. It is critical to understand the energy demands of photoreceptors and fuel sources supplying them to understand neurovascular diseases. Retinas are very rich in lipids, which are continuously recycled as lipid-rich photoreceptor outer segments are shed and reformed and dietary intake of lipids modulates retinal lipid composition. Lipids (as well as glucose) are fuel substrates for photoreceptor mitochondria. Dyslipidemia contributes to the development and progression of retinal dysfunction in many eye diseases. Here, we review photoreceptor energy demands with a focus on lipid metabolism in retinal neurovascular disorders.

Purpose: To report a postmenopausal patient with keratoconus who experienced significant progression after using hormone replacement therapy. Observations: A 51-year-old woman with previously stable keratoconus presented with acute disease progression following hormone replacement therapy in the context of prophylactic hysterectomy and bilateral ovariosalpingectomy. Over a 14-month period after starting hormone therapy, the steepest K increased from 63.7D to 71.5D in the right eye and from 65.8D to 78.1D in the left eye. Conclusions: Hormone replacement therapy may amplify progression of keratoconus.