Clinical review of retinotopy

Two observations made 29 years apart are the cornerstones of this review on the contributions of Dr Gordon T. Plant to understanding pathology affecting the optic nerve. The first observation laid the anatomical basis in 1990 for the interpretation of optical coherence tomography (OCT) findings in 2009. Retinal OCT offers clinicians detailed in vivo structural imaging of individual retinal layers. This has led to novel observations which were impossible to make using ophthalmoscopy. The technique also helps to re-introduce the anatomically grounded concept of retinotopy to clinical practise. This review employs illustrations of the anatomical basis for retinotopy through detailed translational histological studies and multimodal brain-eye imaging studies. The paths of the prelaminar and postlaminar axons forming the optic nerve and their postsynaptic path from the dorsal lateral geniculate nucleus to the primary visual cortex in humans are described. With the mapped neuroanatomy in mind we use OCT-MRI pairings to discuss the patterns of neurodegeneration in eye and brain that are a consequence of the hard wired retinotopy: anterograde and retrograde axonal degeneration which can, within the visual system, propagate trans-synaptically. The technical advances of OCT and MRI for the first time enable us to trace axonal degeneration through the entire visual system at spectacular resolution. In conclusion, the neuroanatomical insights provided by the combination of OCT and MRI allows us to separate incidental findings from sinister pathology and provides new opportunities to tailor and monitor novel neuroprotective strategies

What an endoscopist should know about immunoglobulin-G4-associated disease of the pancreas and biliary tree

Autoimmune pancreatitis (AIP) and IgG4-associated cholangitis (IAC) are the recently recognized pancreatobiliary manifestations of IgG4-associated systemic disease (ISD). Clinically, ISD of the pancreas and/or biliary tree may mimic pancreatic cancer, sclerosing cholangitis, or cholangiocarcinoma. Patients often present with abdominal pain, weight loss, jaundice, itch, and biochemical signs of pancreatitis and cholestasis. Tomography may reveal enlargement of the pancreas or may mimic malignant pancreatic lesions, and cholangiopancreatography may disclose irregularities of the pancreatic duct and stenoses of the distal and/or proximal common bile duct and intrahepatic bile ductules. Serum immunoglobu-lin G4 (IgG4) is elevated in most patients but, unlike tissue IgG4-loaded plasma cell infiltrates, is not diagnostic of the disease. The application of consensus diagnostic criteria for laboratory investigations, imaging, and histologic findings can identify patients who qualify for corticosteroid treatment. The excellent response to immunosuppressive therapy suggests an immune-mediated etiology of the disease, but the exact pathophysiological mechanisms are still under investigation. Relapse may occur after tapering down of corticosteroids, which supports the rationale of maintenance immunosuppression after remission has been induce

Exposure to occupational antigens might predispose to IgG4-related disease

Evidence is mounting that the immune system of patients with IgG4-related disease (IgG4-RD) shows indications of chronic antigenic stimulation. Hypothesizing a possible role for occupational antigenic exposure, we observed in two independent cohorts of patients with IgG4-RD that the majority had had a career in blue collar occupations with prolonged exposures to potentially hazardous occupational antigens. We postulate that the chronic antigenic load associated with 'dirty' jobs could be one of the factors contributing to the development of IgG4-related disease. (Hepatology 2014;

Molecular Targets for the Treatment of Fibrosing Cholangiopathies

Emerging pathophysiologic insights are leading to novel approaches to treating fibrosing cholangiopathies. The current treatment, using ursodeoxycholic acid (UDCA), may slow the progression of some chronic cholangiopathies but cannot heal them. Apart from immunosuppressive interventions aimed at minimizing immune-mediated damage, the use of specific modifiers of hepatobiliary secretory and cytoprotective mechanisms may eventually give rise to a new class of disease-modifying anticholangiofibrotic drug

Sarcoidosis of the liver: to treat or not to treat?

Sarcoidosis is a non-caseating, granulomatous disease of incompletely understood aetiology that can affect nearly all organs including the liver. Hepatic involvement is thought to occur in 50-90% of patients but may remain undiagnosed in many cases. Evidence-based guidelines for the treatment of sarcoidosis of the liver are lacking. Patients usually receive no treatment or are treated pragmatically with corticosteroids. However, treatment with systemic corticosteroids has had mixed results. The use of ursodeoxycholic acid (UDCA) in the treatment of sarcoidosis-associated cholestasis has been reported by several groups, and is empirically prescribed to sarcoidosis patients with hepatic involvement. The effect of UDCA on symptoms and serum liver tests was investigated in a retrospective cohort study in which hepatic sarcoidosis patients had received either no treatment, prednisolone treatment or UDCA treatment. For all patients, laboratory results on ASAT, ALAT, AP and GGT were collected. Patients described the severity of their symptoms before and after treatment on a numerical scale. A total of 17 patients participated in the study. Serum liver tests in the group treated with UDCA had improved as compared with the other groups. Also, symptomatic improvement of pruritus and fatigue was reported in the group treated with UDCA. This retrospective cohort study supports the empirical first-line use of UDCA in the treatment of sarcoidosis of the liver, especially in symptomatic patients. Prospective randomised trials are needed to adequately support this concep

The eye as a window to inborn errors of metabolism

Ocular manifestations in inborn errors of metabolism occur in many diseases and may be associated with any part of all eye components. In a minority of diseases it is possible to attribute the eye symptoms to a single hereditary pathogenetic mechanism. More often the aetiological relationship of the ocular defects to the metabolic disease is unknown. Diverse pathogenetic mechanisms may act via a common pathological pathway inducing ocular damage. The occurrence of eye abnormalities in metabolic disorders suggests that they are associated with direct toxic actions, errors of synthetic pathways or deficient energy metabolism. In this review, metabolic disorders with major abnormalities in the cornea, lens, retina and optic nerve are presented. In all cases, an appropriate combined approach by the ophthalmologist, paediatrician/neurologist, geneticist and clinical biochemist is the only way to diagnostic succes

Superior oblique luxation and trochlear luxation as new concepts in superior oblique muscle weakening surgery

We used superior oblique luxation and trochlear luxation as new surgical procedures to treat acquired Brown's syndrome and superior oblique muscle overaction. We studied nine patients (11 eyes) who underwent trochlear surgery between 1988 and 1993. Four patients had acquired Brown's syndrome and five had superior oblique muscle overaction. In five patients (six eyes) the trochlea was incised to luxate the superior oblique tendon out of the trochlea. In four patients (five eyes) the trochlea was luxated out of its fossa via a periosteal approach without opening the trochlea itself. The mean follow-up was 18 months (range, nine to 33 months). Postoperatively, eight patients showed subjective and objective improvement. One patient with painful traumatic acquired Brown's syndrome had no objective improvement but obtained relief of pain. These new techniques are a successful alternative in the treatment of acquired Brown's syndrome and superior oblique muscle overactio

The biliary HCO(3) (-) umbrella: A unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies

This review focuses on the hypothesis that biliary HCO(3) (-) secretion in humans serves to maintain an alkaline pH near the apical surface of hepatocytes and cholangiocytes to prevent the uncontrolled membrane permeation of protonated glycine-conjugated bile acids. Functional impairment of this biliary HCO(3) (-) umbrella or its regulation may lead to enhanced vulnerability of cholangiocytes and periportal hepatocytes toward the attack of apolar hydrophobic bile acids. An intact interplay of hepatocellular and cholangiocellular adenosine triphosphate (ATP) secretion, ATP/P2Y- and bile salt/TGR5-mediated Cl(-)/ HCO(3) (-) exchange and HCO(3) (-) secretion, and alkaline phosphatase-mediated ATP breakdown may guarantee a stable biliary HCO(3) (-) umbrella under physiological conditions. Genetic and acquired functional defects leading to destabilization of the biliary HCO(3) (-) umbrella may contribute to development and progression of various forms of fibrosing/sclerosing cholangitis. (HEPATOLOGY 2010;