Pupil size measurements with a multifunctional aberrometer/coherence interferometer/tomographer and two infrared-based pupillometers.

PURPOSE: To compare precision of pupil size measurements of a multifunctional device (Pentacam AXL Wave [Pentacam]) and 2 infrared-based pupillometers (PupilX, Colvard) and to compare repeatability of Pentacam and PupilX. SETTING: Department of Ophthalmology, Goethe-University, Frankfurt am Main, Germany. DESIGN: Prospective, comparative trial. METHODS: Pupil diameter of healthy eyes was measured with Colvard once and Pentacam without glare (WO) and with glare (WG), PupilX in 0, 1, and 16 lux 3 times each. In a second series, measurements with Pentacam WO and PupilX in 0.06 and 0.12 lux were assessed. RESULTS: 36 eyes of participants aged 21 to 63 years were included. Mean pupil diameter was 6.05 mm with Colvard, 5.79 mm (first series), 5.50 mm (second series) with Pentacam WO, 3.42 mm WG, 7.26 mm PupilX in 0, 4.67 mm 1, 3.66 mm 16, 6.82 mm in 0.06, and 6.39 mm in 0.12 lux. Measurements with Pentacam WO were significantly different to PupilX in 0, 0.06, 0.12, and 1 lux (all P < .001), but not to Colvard ( P = .086). Pupil size measured with Pentacam WG and PupilX in 16 lux was not significantly different ( P = .647). Consecutive measurements with Pentacam WO and WG had mean SD of 0.23 mm and 0.20 mm, respectively, and with PupilX 0.11 in 0, 0.24 mm 1, and 0.20 mm in 16 lux. CONCLUSIONS: Pentacam provided good assessment of pupil size but was not equivalent to PupilX in low lighting conditions. Repeatability was more favorable for Pentacam.

Intolerance of a non-diffractive extended-depth-of-focus IOL with mini-monovision.

Purpose: The use of a non-diffractive extended-depth-of-focus (EDOF) intraocular lens (IOL) with slight myopia of -0.5 D on the non-dominant eye increases the spectacle independence and has good subjective tolerance with optical phenomena comparable to those of a monofocal IOL. This case report describes the course of a myopic patient who underwent refractive lens exchange, didn't tolerate mini-monovision and received IOL exchange therefore. Observations: A healthy, 62-year-old male with myopia of approximately -5 D underwent refractive lens exchange with a non-diffractive EDOF-IOL on both eyes with slight myopia on the non-dominant left eye (mini-monovision). The operation was performed without any complications, postoperative treatment was due to the clinic's standard procedure. Two weeks postoperative the patient presented with uncorrected distance visual acuity of 0.0 logMAR, a subjective refraction of -0.25/-0.25/142° and corrected distance visual acuity of 0.1 logMAR on the right eye. On the left eye, distance visual acuity was 0.4 logMAR with a subjective refraction of -0.5/-0.75/9° (intended mini-monovision) and corrected distance visual acuity of 0.0 logMAR. Binocular distance visual acuity was 0.0 logMAR. The patient complained about the occurrence of optical phenomena at dim light while driving a car and subjective reduced visual acuity. After an IOL exchange on the left eye with the implantation of the same type of non-diffractive EDOF-IOL aimed for emmetropia, the patient was symptom-free and reported no more subjective complaints. Conclusions: Despite the satisfying subjective and objective visual outcome which is proven in multiple studies, the subjective perception of a mini-monovision with a non-diffractive EDOF-IOL can vary individually. A preoperative assessment of the patient's needs and tolerance of a mini-monovision is crucial for a satisfying postoperative outcome.

Effect of Metformin on HIF-1α Signaling and Postoperative Adhesion Formation.

BACKGROUND: Peritoneal adhesion formation is common after abdominal surgery and results in severe complications. Tissue hypoxia is one of the main drivers of peritoneal adhesions. Thus, we determined the clinical role of hypoxia-inducible factor (HIF)-1 signaling in peritoneal adhesions and investigated whether the biguanide antidiabetic drug metformin shows HIF-inhibitory effects and could be repurposed to prevent adhesion formation. STUDY DESIGN: As part of the ReLap study (DRKS00013001), adhesive tissue from patients undergoing relaparotomy was harvested and graded using the adhesion grade score. HIF-1 signaling activity within tissue biopsies was determined and correlated with adhesion severity. The effect of metformin on HIF-1 activity was analyzed by quantification of HIF target gene expression and HIF-1 protein stabilization in human mesothelial cells and murine fibroblast under normoxia and hypoxia. Mice were treated with vehicle or metformin 3 days before and until 7 days after induction of peritoneal adhesions; alternatively, metformin treatment was discontinued 48 hours before induction of peritoneal adhesions. RESULTS: HIF-1 signaling activity correlated with adhesion severity in patient biopsies. Metformin significantly mitigated HIF-1 activity in vitro and in vivo. Oral treatment with metformin markedly prevented adhesion formation in mice even when the treatment was discontinued 48 hours before surgery. Although metformin treatment did not alter macrophage polarization, metformin reduced proinflammatory leucocyte infiltration and attenuated hypoxia-induced profibrogenic expression patterns and myofibroblast activation. CONCLUSIONS: Metformin mitigates adhesion formation by inhibiting HIF-1-dependent (myo)fibroblast activation, conferring an antiadhesive microenvironment after abdominal surgery. Repurposing the clinically approved drug metformin might be useful to prevent or treat postoperative adhesions.

Inhibition of HIF-prolyl hydroxylases improves healing of intestinal anastomoses.

Anastomotic leakage (AL) accounts for a major part of in-house mortality in patients undergoing colorectal surgery. Local ischemia and abdominal sepsis are common risk factors contributing to AL and are characterized by upregulation of the hypoxia-inducible factor (HIF) pathway. The HIF pathway is critically regulated by HIF-prolyl hydroxylases (PHDs). Here, we investigated the significance of PHDs and the effects of pharmacologic PHD inhibition (PHI) during anastomotic healing. Ischemic or septic colonic anastomoses were created in mice by ligation of mesenteric vessels or lipopolysaccharide-induced abdominal sepsis, respectively. Genetic PHD deficiency (Phd1-/-, Phd2+/-, and Phd3-/-) or PHI were applied to manipulate PHD activity. Pharmacologic PHI and genetic PHD2 haplodeficiency (Phd2+/-) significantly improved healing of ischemic or septic colonic anastomoses, as indicated by increased bursting pressure and reduced AL rates. Only Phd2+/- (but not PHI or Phd1-/-) protected from sepsis-related mortality. Mechanistically, PHI and Phd2+/- induced immunomodulatory (M2) polarization of macrophages, resulting in increased collagen content and attenuated inflammation-driven immune cell recruitment. We conclude that PHI improves healing of colonic anastomoses in ischemic or septic conditions by Phd2+/--mediated M2 polarization of macrophages, conferring a favorable microenvironment for anastomotic healing. Patients with critically perfused colorectal anastomosis or abdominal sepsis could benefit from pharmacologic PHI.

Loss of Prolyl-Hydroxylase 1 Protects against Biliary Fibrosis via Attenuated Activation of Hepatic Stellate Cells.

Liver fibrosis, eventually progressing to cirrhosis necessitating liver transplantation, poses a significant clinical problem. Oxygen shortage (hypoxia) and hypoxia-inducible transcription factors (HIFs) have been acknowledged as important drivers of liver fibrosis. The significance of oxygen-sensing HIF prolyl-hydroxylase (PHD) enzymes in this context has, however, remained elusive. In this study, we demonstrate that loss of PHD1 (PHD1-/-) attenuates the development of liver fibrosis in mice subjected to chronic bile duct injury, induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine. This effect was accompanied with reduced recruitment of inflammatory leukocytes and attenuated occurrence of profibrotic myofibroblasts in PHD1-/- livers. Further analyses focused on the significance of PHD1 in the activation of hepatic stellate cells (HSCs), which represent the driving force in liver fibrosis. Primary HSCs isolated from PHD1-/- mice displayed significantly attenuated myofibroblast differentiation and profibrogenic properties compared with HSCs isolated from wild-type mice. Consistently, the expression of various profibrogenic and promitogenic factors was reduced in PHD1-/- HSCs, without alterations in HIF-1α protein levels. Of importance, PHD1 protein was expressed in HSCs within human livers, and PHD1 transcript expression was significantly increased with disease severity in hepatic tissue from patients with liver fibrosis. Collectively, these findings indicate that PHD1 deficiency protects against liver fibrosis and that these effects are partly due to attenuated activation of HSCs. PHD1 may represent a therapeutic target to alleviate liver fibrosis.

Pharmacological HIF-inhibition attenuates postoperative adhesion formation.

Peritoneal adhesions represent a common complication of abdominal surgery, and tissue hypoxia is a main determinant in adhesion formation. Reliable therapeutic options to reduce peritoneal adhesions are scarce. We investigated whether the formation of postsurgical adhesions can be affected by pharmacological interference with hypoxia-inducible factors (HIFs). Mice were treated with a small molecule HIF-inhibitor, YC-1 (3-[5'-Hydroxymethyl-2'-furyl]-1-benzyl-indazole), or vehicle three days before and seven days after induction of peritoneal adhesions or, alternatively, once during induction of peritoneal adhesions. Pretreatment or single intraperitoneal lavage with YC-1 significantly reduced postoperative adhesion formation without prompting systemic adverse effects. Expression analyses of cytokines in peritoneal tissue and fluid and in vitro assays applying macrophages and peritoneal fibroblasts indicated that this effect was cooperatively mediated by various putatively HIF-1α-dependent mechanisms, comprising attenuated pro-inflammatory activation of macrophages, impaired recruitment and activation of peritoneal fibroblasts, mitigated epithelial-mesenchymal-transition (EMT), as well as enhanced fibrinolysis and impaired angiogenesis. Thus, this study identifies prevention of postsurgical peritoneal adhesions as a novel and promising field for the application of HIF inhibitors in clinical practice.