[The impact of district nurses in screening visual impairments]. / A védonok szerepe a gyermekkori látásproblémák felismerésében.

INTRODUCTION: The children's physical and mental health is determinative for the whole society. Parents, teachers, district nurses, and doctors share the duty to ensure their uninterrupted visual development. District nurses compose key elements in connecting families and health care providers, since they have the chance to detect any visual anomalies, and to refer the children to a pediatrician, ophthalmologist, or a neurologist. Their team work yields advantages to the whole community as beyond preserving good vision, children get a real chance of right physical and mental development. OBJECTIVE: Our aim was to recollect district nurses' areas of activity and to collect data about their present status in visual screening programs. Furthermore, to assess their screening methods and circumstances, and to reshape their continuous learning programs linked to the universities. METHOD: Questionnaires were sent online anonymously to district nurses in practice, in order to collect data referring to their focuses during the visual screening methods. Administration of online parental tutorials was assessed, and measures of professional support in nurses' education was debated. RESULTS: Visual screening among infants looks for potential strabismus, and among school-age children looks for potential refractive errors. Vision tests and stereo tests are usually available as screening tools, but pen lights are underused. Only a few nurses suggest online tutorials to enhance patient education, but nurses are highly motivated in postgraduate courses about vision screening. CONCLUSION: Our results reflect good adherence to the screening protocols but there is some uncertainty in some fields. In harmony with the results, adequate technical and educational support and specific training were compiled for postgraduate district nurses. Coaching and training in visual screening (in the form of seminars or e-learning) should be available in spring 2023. Orv Hetil. 2023; 164(3): 88-95.

Novel Meibomian Gland and Tarsal Conjunctival Changes Associated with Trastuzumab, Pertuzumab, and Anastrozole Treatment for Metastatic HER2 Positive Breast Cancer: A Case Report and Literature Review.

The aim of the study was to report a case of severe meibomian gland dysfunction (MGD) and conjunctival changes associated with trastuzumab, pertuzumab, and anastrozole therapy in a HER-2 positive breast cancer patient. A 57-year-old white woman was treated with trastuzumab and pertuzumab biological and anastrozole endocrine therapy for metastatic breast cancer for several months. She suffered from intense eye pain and foreign body sensation. On the ocular surface, severe MGD developed without corneal lesions. On the tarsal conjunctiva, circumscribed lesions evolved 6 months after receiving anticancer therapy. After biopsy, the histological assessment excluded metastasis or chalazion. The lesion consisted of subepithelial lymphocytic infiltrates surrounding lipid-laden CD68-positive macrophages. Besides the redundant lipid accumulation, no acute necrotic reaction was seen. Noncontact infrared meibography visualized ductal drop-out in the upper and lower lids, and functional tests confirmed severe MGD. During the 18-month follow-up, the patient received treatment for MGD and no new conjunctival lesions developed, subjective symptoms subsided, and ocular surface morphology remained unchanged. The novel HER2-inhibitor trastuzumab and pertuzumab biological therapy and anastrozole endocrine therapy were associated with the disruption of the ocular surface milieu. The new histological aspect of tarsal conjunctiva changes may give a hint to understand the potential underlying molecular mechanisms of anticancer therapy-associated severe MGD. Since anticancer therapies may substantially interfere with the ocular surface milieu, awareness of this side effect leads to improved care of oncology patients.

Tear film function in patients with seasonal allergic conjunctivitis outside the pollen season.

BACKGROUND: Seasonal allergic conjunctivitis can manifest itself through tear film instability and symptoms of eye discomfort during the pollen season. This study investigated whether seasonal allergic inflammation defines tear film instability outside the season. METHODS: Twenty-three control subjects and 13 ragweed-allergic patients were involved (21 female, 15 male; mean age 26.6 ± 5.4 years). Outside the pollen season, subjective ocular symptoms, non-invasive tear film break-up time, lower tear meniscus height and the tear lipid layer's interference pattern grade were recorded. C3a complement activation level was also measured in collected tear samples. RESULTS: Non-invasive tear film break-up time, lower tear meniscus height, C3a complement activation level and the incidence of the different grades of tear lipid pattern did not differ significantly in the two examined groups (p ≥ 0.223). The mean eye symptom score outside the season was greater in the allergic group, but the difference was not significant (p = 0.062). The C3a complement activation level showed a significant and inverse correlation with the lipid layer grade (r = -0.343, p = 0.017). Among the participants with thinner tear lipid layers, the complement activation in the tear samples was higher than among those patients with normal tear lipid layers. CONCLUSION: Seasonal allergic inflammation did not cause permanent tear film instability and eye symptoms were not observed outside the pollen season.

OCT Imaging of lid-parallel conjunctival folds in soft contact lens wearers.

PURPOSE: To visualize, using Fourier-domain optical coherence tomography (FD-OCT), the alterations in lid-parallel conjunctival fold (LIPCOF) morphology in eyes with contact lenses and after their removal. METHODS: One randomly selected eye of each of 24 volunteers with normal ocular surface status was examined using FD-OCT. The study group included 18 female and 6 male subjects, with a mean age of 28.9 years (range, 18-50 years). The presence, height, and number of conjunctival folds and the tear meniscus area were evaluated by FD-OCT, and the difference between "before and after lens removal" were analyzed by the Wilcoxon signed-rank test. To determine the coverage of the folds, the OCT-LIPCOF grading system was applied. Visualization of the folds was compared on linear and raster scans. The Spearman rank test was applied for correlations (SPSS 16.0; SPSS Inc., Chicago, MI). RESULTS: OCT scans were able to visualize and objectively describe the LIPCOF and its relation to the tear film in contact lens wearers. Raster scanning provided more information about the folds, but the measurements were easier to carry out on the single line scans. After removal of the contact lens, the height of the conjunctival folds significantly decreased (p < 0.001), and the tear meniscus area significantly increased (p = 0.017). The number of LIPCOF did not change (p = 0.971), but LIPCOF coverage by the tear film increased after lens' removal and resulted in changes in the OCT-LIPCOF grading (p < 0.001). CONCLUSIONS: FD-OCT could be a quick, non-invasive, quantitative method for the imaging of LIPCOF in contact lens patients. When grading LIPCOF, the mechanical forces of the lens and the tear meniscus changes caused by the lens should be taken into account as these factors influence results. Follow-up of the patients using the same methods is suggested with or without contact lenses.

Imaging lid-parallel conjunctival folds with OCT and comparing its grading with the slit lamp classification in dry eye patients and normal subjects.

PURPOSE: To visualize and describe the morphologic appearance of lid-parallel conjunctival folds (LIPCOFs) by using optical coherence tomography (OCT) and to relate it to dry eye signs and symptoms. METHODS: The LIPCOF grade, noninvasive tear film breakup time (NIBUT), lipid layer interference pattern, and dry eye symptoms were recorded in 17 normal subjects and 33 patients with dry eye. LIPCOFs were evaluated with a slit lamp and visualized by OCT. Three different algorithms for OCT were developed to grade LIPCOFs according to tear meniscus height or the covering tear film on the folds. RESULTS: The three OCT methods showed significant correlation with the slit lamp method (r = 0.470-0.473, P < 0.01). The OCT LIPCOF imaging methods were independent of NIBUT. The Dry Eye Questionnaire (DEQ) scores correlated with the height of the folds and the absence of tear film coverage of the folds (r = 0.574, P < 0.001 and r = -0.527, P < 0.001, respectively). The OCT LIPCOF grades correlated with the DEQ scores (r = 0.494, P < 0.001 and r = 0.310, P = 0.029, respectively). The slit lamp grade did not correlate with the DEQ scores in the whole population, but did in the normal group (r = 0.458, P = 0.024). The OCT LIPCOF grades showed inverse correlation with lipid pattern in the normal group (r = -0.422-0.481, P = 0.05); however, this association disappeared in the dry eye group. CONCLUSIONS: OCT enabled a noninvasive, high-resolution method of imaging, evaluating, and classifying LIPCOFs. These new classifications correlated well with the slit lamp grade and the DEQ scores, promising a new, more objective evaluation of dry eye.

Kinetic analysis of topographical parameters and interference pattern of tear lipid layer in normal subjects.

PURPOSE: To investigate the post-blink changes of the topographical regularity indices, the corneal wavefront aberrations and the tear lipid layer's interference pattern, and analyze the relationship between these parameters' changes. METHODS: Sequential topographical measurements were recorded on 23 normal participants. The surface regularity index (SRI), surface asymmetry index (SAI), corneal total higher order aberrations (HOA) root mean square (RMS), Coma RMS and Spherical RMS were calculated from the topographical measurement. The incidence of the type 1 (with an initial decrease after blink) alteration trend, and the times to the initial minimum were determined in every parameter. The movement of the tear lipid layer's interference pattern was recorded, and the spreading time of the lipid layer was measured subjectively by three independent observers. RESULTS: The incidence of the type 1 SRI trend (82%) was the most common among those measured. The average time to the type 1 SRI trends' minimum was 4.05 ± 1.46 s. There was no correlation between the time to the minimum of type 1 trends of the topographical indices, the HOA, Coma and Spherical RMS. The mean lipid layer spreading time was 5.09 ± 1.90 s. We found weak but significant correlation between the times to the minimum of type 1 SRI trends and the lipid spreading time (r = 0.540, p = 0.021).The minimum of the SRI index occurred before the stoppage of superficial lipid layer's motion. CONCLUSION: Relatively long lipid layer spreading time was observed suggesting that the tear film build-up process did not finish completely at the end of the initial rapid tear film alteration phase. The detected initial decrease of the SRI after blink related to the post-blink tear film motion. This initial pattern is characteristic of the majority of the normal population in spite of the post-blink alteration pattern of the topographical SAI or corneal aberrations. The SRI seems to be the most useful indirect topographical parameter of the tear film dynamics.

Elevated antibody levels against Chlamydia pneumoniae, human HSP60 and mycobacterial HSP65 are independent risk factors in myocardial infarction and ischaemic heart disease.

The relative significance of traditional risk factors, chronic infections and autoimmune processes in the development of acute myocardial infarction (AMI) has not been fully elucidated. We compared serum IgG antibody titres to various pathogens, i.e. Chlamydia pneumoniae (Cpn), cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1), and to the potential autoantigens human heat shock protein 60 (hHSP60) and mycobacterial heat shock protein 65 (mHSP65), in serum samples obtained from patients 3-48 h after AMI (n = 40) or stable effort angina (SEA, n = 43), and from controls (n = 46). The strongest association was observed between AMI and the elevated level of hHSP60 antibodies. The association between AMI and the level of Cpn antibodies was also significant. High levels of hHSP60 and Cpn antibodies represented independent risk factors for the development of AMI, but the simultaneous presence of high levels of antibodies to Cpn and hHSP60 suggested a joint effect on the relative risk of AMI (OR = 12.0-21.1). The antibody titres to mHSP65 were higher in the SEA group than in the controls, and the simultaneous presence of high levels of Cpn and mHSP65 antibodies meant an increased risk among the SEA patients. The antibody titres to CMV or HSV-1 were similar in the three groups. In conclusion, these results demonstrate associations of AMI with high levels of anti-hHSP60 and anti-Cpn antibodies, and of SEA with the level of anti-mHSP65 antibodies, these being independent risk factors.

Antibodies against the human heat shock protein hsp70 in patients with severe coronary artery disease.

Heat shock proteins (hsps) play complex role in the function of the immune system, they can activate both humoral and cellular immune response, as well the complement system. Although autoimmunity to hsp70 was implicated in certain autoimmune diseases and other conditions, the exact role of anti-hsp70 antibodies is not known. It was demonstrated by our previous work and other's findings that antibodies against the 60 kDa hsps are strongly associated with coronary atherosclerosis and carotis disease. It is also known that there is increased hsp70 expression at different sites of atherosclerosis. Therefore our aim was to study whether level of anti-hsp70 antibodies correlate with the presence of severe coronary artery disease (CAD). We measured and compared anti-hsp70 IgG antibody levels in CAD patients (n = 99) and healthy subjects (n = 99) with ELISA. The frequency of these antibodies was high in both groups and there was no significant difference in the median level of anti-hsp70 antibodies between patients with severe CAD and controls (653 (400-1141) vs. 630 (326-1152) AU/mL, P = 0.337). Adjustment for age, sex, BMI and lipid parameters did not change this result. Furthermore we did not find a correlation between anti-hsp70 antibody levels and certain risk factors of CAD (age, lipid parameters, body mass index, C-reactive protein, gender, smoking, diabetes and anti-hsp60 antibodies). By contrast, in accordance with our previous findings, anti-hsp60 and anti-hsp65 antibody levels were significantly higher in CAD patients, compared to this control group (p < 0.0001 for both variables). We did not find any correlation between the levels of anti-hsp70 and anti-hsp60 or anti-hsp65 antibodies either in the patients or the controls. The exact role of hsp70 in atherosclerosis is controversial, but we suggest that humoral immunity against human hsp70 does not contribute to coronary atherosclerosis in contrast to antibodies against 60kDa hsps.

Relationship of anti-60 kDa heat shock protein and anti-cholesterol antibodies to cardiovascular events.

BACKGROUND: Several recent studies have indicated an association between key inflammatory mediators and atherosclerotic diseases. We evaluated whether high levels of antibodies against heat shock proteins and cholesterol (ACHA) predicted cardiovascular (CV) events. METHODS AND RESULTS: We used blood samples from the Heart Outcomes Prevention Evaluation (HOPE) study to conduct a nested case-control study of 386 cases with CV events and 386 age- and sex-matched HOPE study controls without events. We explored the relationship between anti-hsp antibodies, ACHA, and subsequent outcomes (incident myocardial infarction, stroke, or CV death) during a mean follow-up of 4.5 years using conditional logistic regression. High levels of anti-hsp65 antibodies (> or =90th percentile) predicted CV events (OR, 2.1; 95% CI, 1.2 to 3.9, P=0.01). Anti-hsp60 antibodies did not predict any event type, whereas incident stroke developed significantly less frequently in patients with high ACHA levels. Anti-hsp antibodies and ACHA did not correlate with inflammatory (fibrinogen, C-reactive protein, interleukin-6, intracellular adhesion molecule-1) or infectious markers (C pneumoniae or cytomegalovirus antibodies). Anti-hsp65 antibodies (> or =90th percentile) and fibrinogen (highest tertile) had a strong joint effect: patients with high concentrations of both had more CV events (OR, 5.5; 95% CI, 1.8 to 17.5, P=0.004) than patients with low levels of both. A similar joint effect (OR, 2.7; 95% CI, 1.3 to 5.7, P=0.01) was found for high levels of anti-hsp65 and presence of cytomegalovirus antibodies. CONCLUSIONS: Serum antibodies to hsp65 were associated with subsequent CV events in this study of high-risk patients, independent of conventional cardiovascular risk factors and other inflammatory markers.

Helicobacter pylori infection in connective tissue disorders is associated with high levels of antibodies to mycobacterial hsp65 but not to human hsp60.

BACKGROUND: To investigate whether the Helicobacter pylori status influences levels of antibodies against mycobacterial heat shock protein (hsp) 65 and human hsp60 in systemic autoimmune diseases and to study the concentration of anti-H. pylori antibodies in autoimmune patients and healthy controls. MATERIALS AND METHODS: Antibodies against human heat-shock protein hsp60, mycobacterial heat-shock protein hsp65 were analyzed by ELISA. Anti-Helicobacter antibodies were determined by enzyme immunoassay. RESULTS: There was a markedly higher prevalence of H. pylori infection in undifferentiated connective tissue disease (82%) (n = 33) and systemic sclerosis (78%) (n = 55) but not in systemic lupus erythematosus (n = 49), polymyositis/dermatomyositis (n = 14), rheumatoid arthritis (n = 21) or primary Raynaud's syndrome (n = 26) compared with controls (59%) (n = 349). In autoimmune diseases H. pylori infection was associated with elevated levels of antihsp65 (p =.008) but not of antihsp60. Anti-hsp65 levels were significantly higher in H. pylori-infected (n = 129) than in uninfected patients (n = 69) (p =.0007). CONCLUSIONS: These findings indicate that in autoimmune diseases the infection with the H. pylori bacterium is associated with increased concentration of antimycobacterial hsp65.

C1r-C1s-C1inhibitor (C1rs-C1inh) complex measurements in tears of patients before and after penetrating keratoplasty.

PURPOSE: The aim of this pilot study was to determine the presence of complement activation products in tears from pre- and postkeratoplasty eyes and the fellow eyes in order to investigate the activation of the classical and alternative pathways of the complement system in the early postkeratoplasty period. METHODS: Tear samples from both eyes of 19 prekeratoplasty patients were tested. From 10 patients, samples were taken before operation, one week and 3 weeks after penetrating keratoplasty. Only baseline and 1 weak samples, and baseline and 3 week samples were available from 5 and 2 patients, respectively, while only baseline tear samples were collected from 2 patients. Tear concentration of two complement activation products, C1rs-C1inh and C3bBbP were determined by enzyme-linked immunosorbent assay. RESULTS: There was no difference (p = 0.339) between baseline samples of the eyes waiting for operation (0.93 +/- 0.51 AU/ml, mean +/- SEM) and the fellow eyes (0.33 +/- 0.33 AU/ml) in respect of mean C1rs-C1inh complex concentration. The one-week samples of the operated eyes revealed significantly (p = 0.006) elevated levels of C1rs-C1inh complexes (18.8. +/- 6.37 AU/ml), compared to their baseline samples (1.18 +/- 0.64 AU/ml), whereas the one-week values of the fellow eyes did not differ from the baseline values. Compared to the increased one-week values, the three-week values decreased to the baseline values in the operated eyes. C3bBbP could be detected in 3/68 tear samples. CONCLUSIONS: In our study we demonstrated the increased concentration of C1rs-C1inh complex in several tear samples taken early after human penetrating keratoplasty. These findings provide direct evidence that the classical pathway of complement may be activated in the early postoperative period after penetrating keratoplasty.

Impaired humoral immune response against mycobacterial 65-kDa heat shock protein (HSP65) in patients with inflammatory bowel disease.

Since only scarce data are available on the immune response against heat shock proteins (HSP) in inflammatory bowel disease (IBD), we have measured with an ELISA method serum levels of IgG, IgA, and IgM antibodies to mycobacterial HSP65 and human HSP60 in 66 patients with Crohn's disease (CD), 42 patients with ulceratiVe colitis (UC), and 126 age-and gender-matched healthy controls. Serum concentration [median (25th-75th percentiles) of IgG anti-HSP65 antibodies was substantially lower in patients with either CD (P < 0.01) or UC (P < 0.001) than in healthy controls, while no difference was found in the levels of anti-HSP60 antibodies. Low anti-HSP65 antibody levels were measured in patients with active CD and in both active and inactive UC, and only in IBD patients with no extraintestinal manifestations. In conclusion, our present findings indicate that an abnormal immune response to bacterial HSP65 or some epitopes of the protein may contribute to the dysregulation of host defenses against certain intestinal bacteria.

The promoter polymorphism of the IL-6 gene is associated with levels of antibodies to 60-kDa heat-shock proteins.

Elevated levels of antibodies to 60 kDa heat shock proteins are associated with severe coronary heart disease and carotid atherosclerosis. The presence of self hsp60-reacting antibodies can only be partially explained by microbial infections and induction by bacterial hsp65 proteins, since important differences (including the epitope specificity and complement activating ability) between hsp60 and hsp65 reacting antibodies have been shown. The aim of this study was to investigate the possible effects of genetic polymorphisms of different genes of proinflammatory cytokines on anti-hsp60 autoantibody levels. One hundred and seventy-six male blood donors were recruited and antibody levels to human hsp60 and Mycobacterium bovis hsp65 were determined by ELISA. Also in these donors, polymorphisms of the promoter of the IL-6 gene at position -174, the biallelic base exchange of the IL-1 beta gene at the -511 position and the IL-1 alpha gene at position -889 were investigated by PCR. A strong association between IL-6 -174 polymorphism and anti-hsp60 antibody levels was seen; the effect on anti-hsp65 antibody was less marked. Carriers of allele C at this position had significantly lower levels of anti-hsp60 and anti-hsp65 antibodies. A lack of associations between IL-1 beta and IL-1 alpha gene polymorphisms and antibody levels was detected. This is the first study in which associations between genetic polymorphisms and autoantibody levels have been described in healthy subjects. Further studies are needed to gain insight into the detailed mechanism of how the IL-6 gene polymorphism at position -174 influences anti-hsp60 autoantibody levels.