Corneal avascularity—the absence of blood vessels in the cornea—is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders1-4. But the molecular underpinnings of the avascular phenotype have until now remained obscure5-10 and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap11 by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/− mice12,13 and Pax6+/− patients with aniridia14 are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/− mice. Manatees, the only known creatures uniformly to have vascularized corneas15, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.

This is the first description of retinal SO2 in healthy, multiethnic subjects. Aging decreases SvO2 and SaO2 and should be accounted for when interpreting retinal oximetry measurements. Other demographic and clinical parameters studied did not seem to significantly influence retinal SO2 measurements.

IMPORTANCE Retinal telescreening for evaluation of diabetic retinopathy (DR) in the primary care setting may be useful in reaching rural and underserved patients.OBJECTIVES To evaluate telemedicine retinal screenings for patients with type 1 or 2 diabetes and identify factors for ophthalmology referral in the North Carolina Diabetic Retinopathy Telemedicine Network. DESIGN, SETTING, AND PARTICIPANTSA preimplementation and postimplementation evaluation was conducted from January 6, 2014, to November 1, 2015, at 5 primary care clinics serving rural and underserved populations in North Carolina among 1787 adult patients with type 1 or 2 diabetes who received primary care at the clinics and obtained retinal telescreening to determine the presence and severity of DR. A total of 1661 patients with complete data were included in the statistical analysis.INTERVENTION Nonmydriatic fundus photography with remote interpretation by an expert. MAIN OUTCOMES AND MEASURESNumber of patients recruited, level of detected DR, change in rates of screening, rate of ophthalmology referral, percentage of completed referrals, and patient characteristics associated with varying levels of DR. RESULTSOf the 1661 patients (1041 women and 620 men; mean [SD] age, 55.4 [12.7] years), 1323 patients (79.7%) had no DR, 183 patients (11.0%) had DR without a need for an ophthalmology referral, and 155 patients (9.3%) had DR with a need for an ophthalmology referral. The mean rate of screening for DR before implementation of the program was 25.6% (1512 of 5905), which increased to 40.4% (1884 of 4664) after implementation. A total of 93 referred patients (60.0%) completed an ophthalmology referral visit within the study period. Older patients (odds ratio [OR], 1.28; 95% CI, 1.11-1.48) and African American patients (OR, 1.84; 95% CI, 1.24-2.73) or other racial/ethnic minorities (OR, 2.19; 95% CI, 1.16-4.11) had greater odds of requiring an ophthalmology referral compared with white and/or younger patients. Patients with higher hemoglobin A 1c levels (OR, 1.19 per unit change; 95% CI, 1.13-1.25 per unit change) and longer duration of diabetes (OR, 1.76 per decade; 95% CI, 1.53-2.02 per decade) had greater odds of DR requiring an ophthalmology referral. History of stroke (OR, 1.65; 95% CI, 1.10-2.48) and kidney disease (OR, 1.59; 95% CI, 1.10-2.31) were strongly associated with DR and ophthalmology referral. CONCLUSIONS AND RELEVANCEWhen implemented in the primary care setting, retinal telescreening increased the rate of evaluation for DR for patients in rural and underserved settings. This strategy may also increase access to care for minorities and patients with DR requiring treatment.

PURPOSE. To estimate visual field (VF) sensitivity at which retinal nerve fiber layer (RNFL) thinning reaches the measurement floor and at which RNFL stops thinning (change points), the dynamic range of RNFL thickness, and the number of steps from normal to RNFL floor among three optical coherence tomography (OCT) devices. METHODS.Glaucomatous patients (n ¼ 58) and healthy subjects (n ¼ 55-60) prospectively underwent VF testing and RNFL thickness measurement with Cirrus, Spectralis, and RTVue. Change points and corresponding RNFL thicknesses were estimated with simple linear regression (SLR) and Bayesian change point (BCP) analyses. The dynamic range and number of steps to RNFL floor were determined.RESULTS. The average VF change points and corresponding residual thickness at the time RNFL stopped thinning were À22.2 dB and 57.0 lm (Cirrus), À25.3 dB and 49.2 lm (Spectralis), and À24.6 dB and 64.7 lm (RTVue). The RNFL dynamic ranges derived from SLR values were wider on Spectralis (52.6 lm) than on Cirrus (35.4 lm) and RTVue (35.5 lm); the corresponding number of steps to reach the RNFL floor were 9.0 on Cirrus, 10.6 on Spectralis, and 8.3 on RTVue.CONCLUSIONS. The relative VF sensitivity at which average RNFL thickness reaches the measurement floor, the residual layer thickness, and RNFL dynamic measurement range differ among the three devices. However, the number of steps from normal to the RNFL thickness floor is comparable.

sFlt is highly expressed in the human cornea and normally sequesters VEGF.

AMT helps in ocular surface reconstruction, promotes rapid epithelial healing and partially restores limbal stem cell function. It can be considered as an effective modality for the ocular surface restoration in chemical and thermal injuries in selected cases. Success rates in acute and chronic cases are comparable.

Flt-1 intraceptors, which are endoplasmic reticulum retention signal-coupled VEGF receptors, significantly suppress hypoxia-induced VEGF secretion by corneal epithelial cells in vitro. In vivo, delivery of naked plasmids expressing these intraceptors inhibits injury-induced upregulation of VEGF, leukocyte infiltration, and corneal neovascularization.

Albumin nanoparticles are not toxic to the cornea and can express intraceptors for extended periods that are effective in suppressing injury-induced corneal neovascularization.