Comparison of visual acuity measurements and Purkinje's vessel shadow perception for prediction of postoperative visual acuity in different ophthalmological diseases

PURPOSE: Prediction of postoperative visual acuity (VA) is extremely important to the patient and highly relevant to the surgeon. However, objective evaluation of the macula is frequently impossible in cases such as mature cataract, cataract in high myopia or vitreous haemorrhage. This study compares different preoperative examination techniques used to predict postoperative VA. METHODS: We retrospectively evaluated the charts of all patients who underwent any of the following procedures at our hospital in 2004: phacoemulsification for mature cataract or cataract in high myopia; vitrectomy for diabetic vitreous haemorrhage; macular pucker, and macular hole. The following methods were evaluated: preoperative distance and reading VA; laser interferential VA; Purkinje's vessel shadow perception, and postoperative distance VA. RESULTS: Complete documentation was available for 136 patients (29 mature cataracts, 25 immature cataracts in high myopia, 42 vitreous haemorrhages, 19 macular puckers, 21 macular holes). In cases of preoperative mature cataract, a positive Purkinje's vessel shadow perception predicted a postoperative VA >or= 20/50 (odds ratio 11.2). In cases of high myopia, interferential VA correlated best with visual outcome (p < 0.05). In macular surgery laser interferential VA predicted postoperative VA to be better and preoperative reading VA predicted it to be worse than it actually turned out after surgery. Laser interferential VA and last known VA prior to vitreous haemorrhage (mean of 20 months previously) correlated best with postoperative VA (p < 0.05) in cases of vitreous haemorrhage. Purkinje's vessel shadow perception--if positive--predicted a postoperative VA >or= 20/300 in these cases (odds ratio 15.0). CONCLUSIONS: Postoperative VA after vitrectomy for macular pucker or macular hole and in cases of cataract in high myopia is best predicted by laser interferential VA. Postoperative VA after vitrectomy for diabetic vitreous haemorrhage is best predicted by prehaemorrhage VA or laser interferential VA, especially when prehaemorrhage VA is unknown. Positive Purkinje's vessel shadow perception is an excellent method of predicting postoperative VA >or= 20/300 in cases of vitreous haemorrhage and VA = 20/50 in mature cataract.     

Autoantibodies to bullous pemphigoid antigen 180 induce dermal-epidermal separation in cryosections of human skin

Bullous pemphigoid is a subepidermal autoimmune blistering disease associated with autoantibodies to the hemidesmosomal bullous pemphigoid antigens 180 and 230. Most sera from bullous pemphigoid patients recognize epitopes within the N-terminal NC16A portion of the bullous pemphigoid 180 ectodomain. Using cryosections of human skin, patients' sera were shown to generate dermal-epidermal separation when coincubated with leukocytes and complement from healthy volunteers; however, the specificity of pathogenic autoantibodies in bullous pemphigoid patients has not yet been elucidated. In this study, by the use of a modified version of the cryosection model, we show that sera from all of 13 bullous pemphigoid patients and from two rabbits, immunized against bullous pemphigoid 180 NC16A, induced dermal-epidermal separation. This finding was confirmed with the use of IgG purified from patients' sera, whereas sera and purified IgG from healthy controls were not pathogenic. The induction of subepidermal splits in this experimental model was shown to be dependent on the presence of neutrophils, but not complement. Interestingly, patients' autoantibodies affinity purified against a recombinant form of bullous pemphigoid 180 NC16A retained their blister-inducing capacity, whereas patients' IgG depleted of reactivity to NC16A lost this ability. F(ab')2 fragments of antibodies specific to NC16A, lacking the Fc portion, did not induce splits. In addition, patients' autoantibodies purified against a recombinant fragment of the C-terminus of bullous pemphigoid 180 as well as rabbit antibodies to the intracellular portion of bullous pemphigoid 180 and to bullous pemphigoid 230 did not cause dermal-epidermal separation. Our in vitro results support the idea that autoantibodies to bullous pemphigoid 180 from patients with bullous pemphigoid are of pathogenic relevance.     

Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses

The tyrosine kinase inhibitors sorafenib and sunitinib are approved for the treatment of patients with malignant diseases. To analyze the possible use of these compounds in combination with immunotherapeutic approaches, we analyzed the effects of both inhibitors on the immunostimulatory capacity of human dendritic cells (DCs) and the induction of primary immune responses in vivo. Sorafenib, but not sunitinib, inhibits function of DCs, characterized by reduced secretion of cytokines and expression of CD1a, major histocompatibility complex, and costimulatory molecules in response to TLR ligands as well as by their impaired ability to migrate and stimulate T-cell responses. These inhibitory effects are mediated by inhibition of PI3 and MAP kinases and NFB signaling. In contrast, sorafenib had no influence on the phenotype and proliferation of T cells. To analyze the effects of both TKIs on cytotoxic T-cell induction in vivo, C57BL/6 mice were pretreated with sorafenib or sunitinib and immunized with OVA_257-264 peptide. Sorafenib, but not sunitinib, application significantly reduced the induction of antigen-specific T cells. Numbers of regulatory T cells were reduced in peripheral blood mononuclear cells from mice treated with sunitinib. These results indicate that sunitinib, but not sorafenib, is suitable for combination with immunotherapeutic approaches for treatment of cancer patients.     

Obsessive–Compulsive Disorder is Characterized by a Lack of Adaptive Coping Rather than an Excess of Maladaptive Coping

The present study aimed to elucidate the profile of coping in patients with obsessive–compulsive disorder (OCD) in order to discern whether the disorder is characterized by an excess of maladaptive coping skills and/or a lack of adaptive coping skills. Sixty individuals with OCD were compared with 110 individuals with depression and 1050 nonclinical controls on the Maladaptive and Adaptive Coping Styles Questionnaire (MAX). Psychopathology was assessed with the Obsessive–Compulsive Inventory-Revised (OCI-R), the Yale-Brown Obsessive–Compulsive Scale (Y-BOCS), and the Patient Health Questionnaire-9 for depression (PHQ-9). Individuals with OCD and depression displayed more maladaptive coping and avoidance as well as less adaptive coping than nonclinical controls. Importantly, adaptive coping was significantly lower in individuals with OCD than in those with depression at a medium effect size, whereas the clinical groups were indistinguishable on maladaptive coping and avoidance. Lack of adaptive coping was strongly correlated with resistance to symptoms and poor insight in OCD (Y-BOCS), even after controlling for depression. Lack of adaptive coping skills may represent a specific pathogenetic factor in OCD. Longitudinal studies need to clarify whether strengthening adaptive skills during childhood and adolescence may help to prevent the progression from subclinical to manifest OCD.     

Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1)

Large clonal expansions of peripheral CD8+ T cells carrying receptors for single epitopes of CMV and EBV are common in the elderly and may be associated with an immune risk phenotype predicting mortality. Here we show that the frequency of CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1), a marker of cells unable to undergo further clonal expansion, was markedly elevated in CD8+ T cells from old donors. Moreover, tetramer staining revealed that the elevated frequency of CMV-specific CD8+ T cells in the elderly was due to an accumulation of cells bearing this dominant negative receptor. The fraction of CMV-specific T cells able to secrete interferon-gamma after specific antigenic stimulation was significantly lower in the elderly than in the young, although the total number of functional cells was comparable. Therefore, the majority of the clonally expanded virus-specific CD8+ cells in the elderly was dysfunctional. Thus, T cell responses are altered in the aged by an accumulation of replicatively senescent dysfunctional T cells carrying receptors for persistent herpes viruses. The presence of clonal expansions of such virus-specific cells may shrink the available repertoire for other antigens and contribute to the increased incidence of infectious disease in the elderly.