Measuring patient activation: the utility of the Patient Activation Measure administered in an interview setting.

BACKGROUND: Patient activation is an emerging field in healthcare research concerning knowledge, skills, and confidence of patients in managing their health. This is particularly important for patients with chronic diseases, who often require more complex care management and self-care skills. However, due to temporary or longer-lasting visual impairments, certain patient groups cannot answer a questionnaire independently. The main objective is to investigate the psychometric properties of the German Patient Activation Measure® (PAM) survey in an everyday clinical setting where it has to be read aloud. METHODS: Outpatients with macular edema participated in this questionnaire-based cross-sectional study. The study assessed patient activation by the PAM® survey, self-rated health, self-efficacy, quality of life, and general mood. Interviewers read questionnaires aloud to patients. Psychometric properties of the PAM® survey were investigated by item response theory (IRT), Cronbach's α and trait-trait correlations. RESULTS: The analysis included N = 554 patients. Median age was 69 (IQR 62.0-76.0) years and mean overall activation score 74.1 (SD 13.7). All items showed ceiling effects. Empirical reliability from the IRT model and Cronbach's α were 0.75. The PAM® survey showed a Spearman correlation of 0.54 with self-efficacy, 0.51 with quality of life and 0.34 with general mood. CONCLUSION: The read-aloud PAM® survey has been shown to provide to adequate measurement precision and convergent validity to be used as a screening tool in an everyday clinical setting. Objective assessment in an interview setting with the PAM® survey is possible. PAM® items are good in distinguishing lower to middle activated patients, but not patients with high activation. Further, issues with structural validity need more investigation.

ENDOTHELIN-1 AS A RISK FACTOR IN RETINAL VEIN OCCLUSION.

PURPOSE: Retinal vein occlusion (RVO) risk factors largely coincide with cardiovascular risk factors. Endothelin-1 (ET-1), the most potent vasoconstrictor with proinflammatory properties, is a known cardiovascular risk factor. In this study, we explore the role of serum ET-1 as a potential risk factor for RVO. METHODS: Endothelin-1 serum levels were measured in patients with RVO and control subjects. Samples were measured using the sandwich enzyme-linked immunosorbent assay for the quantitative determination of human big endothelin-1 (Biomedica Group, Austria). RESULTS: The study consisted of 147 RVO patients and 150 control subjects. Median serum ET-1 was significantly higher in RVO patients (0.26 pmol/L; range, 0.19-0.37 pmol/L) compared with control subjects (0.10 pmol/L; range, 0.05-0.22 pmol/L) (P < 0.0001) independent of the occlusion site. The difference remained significant after adjusting for arterial hypertension, diabetes mellitus, history of stroke, history of myocardial infarction, history of venous thromboembolism, glomerular filtration rate, and c-reactive protein. CONCLUSION: In conclusion, our results suggest that ET-1 is a potential risk factor for all types of RVO.

Role of the ABO blood groups as a risk factor for retinal vein occlusion.

Introduction A recent study suggested that non-O blood groups had an increased risk for the presence of RVO. In this study we investigated (i) an association between blood group and the presence of RVO and (ii) whether this association correlated to other RVO risk factors. Methods We included 485 RVO patients and 295 control subjects who were recruited in this case-control study. We determined ABO genotypes rs8176719 as a marker for the O allele and rs8176746 for the B allele by polymerase chain reaction. Results We did not find an association between ABO blood group and the presence of RVO. In detail, the proportion of ABO blood groups was similar among RVO patients and control subjects (p=0.527). In a logistic regression, non-O blood group was associated with 1.06-fold higher odds of being a RVO patient (95%CI: 0.78-1.45, p=0.693), and this lack of association prevailed upon multivariable adjustment for age, gender, history of stroke and venous thromboembolism and co-medication with lipid-lowering agents. Discussion Although non-O blood groups are a known risk factor for thrombotic and cardiovascular disease, they do not seem to be a major risk factor for the development of RVO.

Cotinine and cytokine levels in the vitreous body and blood serum of smokers and non-smokers - A pilot study.

Tobacco smoking is a risk factor for many ocular diseases. Of the multiple tobacco smoke compounds nicotine and its main metabolite cotinine are likely agents in disease modulation. The interaction of these compounds with exposed tissue is complex and ranges from proinflammatory to potentially neuroprotective properties. We aimed to determine cotinine and cytokines in the vitreous in smokers and non-smokers in this prospective, cross-sectional study at the Department of Ophthalmology, Medical University Graz, Austria. We included 10 smokers and 10 non-smokers. Vitreous and serum samples were analyzed for cotinine and cytokines. The cytokine analysis was performed with multiplex assay and cotinine was quantified with enzyme-linked immunosorbent assay. Cotinine was detectable in smokers only with a mean of 154.0 ng/ml ± 107.3 ng/ml in the vitreous and of 194.1 ng/ml ± 121.3 ng/ml in the serum. The difference between intraocular and systemic levels was statistically significant. There were no statistically significant differences between the cytokine levels of smokers and non-smokers. However, intravitreal VEGF-A was by trend elevated in smokers and correlated positively with intravitreal cotinine (r = 0.59, p = 0.073). In conclusion cotinine is detectable in the vitreous of smokers and is lower than the serum. There is a trend towards elevation of VEGF-A in the vitreous of smokers.

SERUM LEVELS OF ANTIBODIES AGAINST OXIDATION-SPECIFIC EPITOPES ARE DECREASED IN PATIENTS WITH RETINAL VEIN OCCLUSION.

PURPOSE: Oxidative stress and inflammation have been implicated in the development of retinal vein occlusion (RVO). Oxidation-specific epitopes (OSEs) represent products of oxidative stress that can trigger vascular inflammation and thrombosis. Natural occurring antibodies have been shown to bind oxidation-specific epitopes thereby inhibiting their inflammatory potential and promoting their removal. METHODS: This prospective cross-sectional study included 270 patients with RVO and 81 in-hospital control patients. We measured three types of serum levels of oxidation-specific epitope-specific immunoglobulin M and immunoglobulin G antibodies (anti-copper-oxidized LDL [CuOx-LDL], antiphosphocholine [PC], anti-malondialdehyde-modified LDL [MDA-LDL]). History of arterial hypertension, hyperlipidemia, myocardial infarction, diabetes mellitus, stroke, smoking status, and several laboratory parameters were determined to control for potential confounders. RESULTS: Compared with controls, patients with RVO had significantly lower levels of immunoglobulin M and immunoglobulin G antibodies against CuOx-LDL and PC, and significantly lower levels of immunoglobulin G but not immunoglobulin M antibodies against MDA-LDL. The association between RVO patients and lower levels of these antibodies prevailed upon multivariable adjustment. CONCLUSION: These prospective data show that antibodies against oxidation-specific epitope are lower in patients with RVO compared with control patients and support the concept that oxidative stress and inflammation play key roles in the development and subsequent complications in RVO.

Vitrectomy for diabetic macular edema and the relevance of external limiting membrane.

PURPOSE: To evaluate the relevance of external limiting membrane (ELM) on the visual and morphological results in eyes with diabetic macular edema (DME) that underwent pars plana vitrectomy (PPV) with epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling. METHODS: Medical records of patients with DME who underwent PPV at our unit between January 2017 and December 2019 were reviewed. We assessed preoperative and postoperative best-corrected visual acuity (BCVA), central macular thickness (CMT) using spectral domain OCT (optical coherence tomography). Exclusion criteria were previous PPV; incomplete data; concomitant diseases including retinal vein occlusion, age-related macular degeneration, uveitis; and a follow-up of less than 12 months. The surgeries were performed using 23- or 27-gauge vitrectomy. The ELM was graded depending on its configuration (grade 0 = intact, grade 1 to 3: disruption of varying extent). RESULTS: Ninety-nine eyes were enrolled. The postoperative follow up averaged 23.7 months. The preoperative and final BCVA averaged 0.71 ± 0.28 and 0.52 ± 0.3 logMAR, respectively (p = 0.002). The CMT averaged 515.2 ± 209.1 µm preoperatively and 327 ± 66.1 µm postoperatively (p = 0.001). Eyes with intact ELM (n = 8) had a significantly better BCVA compared to those with ELM disruption (0.28 ± 0.14 vs. 0.7 ± 0.25 logMAR, p = 0.01). The final CMT was similar among the groups (intact ELM: 317 ± 54.6 µm; ELM disruption: 334 ± 75.2, p = 0.31). CONCLUSIONS: PPV with ERM and ILM peeling is an effective treatment of DME. Eyes with intact ELM preoperatively had a significantly better final visual outcome. To maximize the benefit for patients with DME we recommend early PPV as long as ELM is intact.

Vitreous albumin redox state in open-angle glaucoma patients and controls: a pilot study.

PURPOSE: Numerous studies suggest that reactive oxygen species play a crucial role in the development of glaucoma. Since glaucoma patients exhibit posterior vitreous detachment earlier than controls, it has been suggested that reactive oxygen species-increased in glaucoma-also affect the vitreous. In the present study we evaluated the influence of open-angle glaucoma oxidative stress on the redox state of vitreous albumin. METHODS: Albumin redox states of the vitreous and plasma were evaluated in 22 subjects-11 open-angle glaucoma patients and 11 controls-matched for age, gender, and vitreous state. According to the redox state of cysteine-34, albumin can be separated into: human mercaptalbumin (the thiol form), human nonmercaptalbumin1 (a reversible modification due to mild oxidation), and human nonmercaptalbumin2 (an irreversible modification due to severe oxidation). RESULTS: Albumin of both, the open-angle glaucoma group and the control group, was more oxidized in the vitreous compared to plasma. Furthermore, significantly higher human nonmercaptalbumin1 fractions were found in the vitreous of open-angle glaucoma patients compared to controls. No significant differences were found in the plasma albumin fractions between the groups. CONCLUSION: Our results support the hypothesis that oxidative stress plays a crucial role in open-angle glaucoma and that reactive oxygen species in glaucomatous eyes may also affect the vitreous.

CHANGE OF CHOROIDAL VOLUME IN UNTREATED CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: Choroidal hyperpermeability plays a central role in the pathophysiology of central serous chorioretinopathy (CSC). In active CSC undergoing treatment, choroidal thickness decreases if subretinal fluid (SRF) resolves. This study aimed to investigate the change in choroidal thickness and volume in eyes with untreated CSC. METHODS: The authors retrospectively analyzed 27 eyes with treatment-naïve CSC (25 patients), who had a follow-up of 4 to 6 weeks. Retinal and choroidal volume and SRF were segmented manually and calculated using the Spectralis OCT built-in software (Spectralis; Heidelberg Engineering). RESULTS: In treatment-naïve eyes with CSC, an increase in SRF was significantly associated with an increase in choroidal thickness and volume (rho = 0.93, P < 0.01). Eyes with greater baseline choroidal volume showed a significantly greater decrease in SRF during follow-up (rho = -0.47, P = 0.03). CONCLUSION: In this study, an increase in SRF was associated with an increase in both choroidal thickness and volume in eyes with treatment-naïve CSC. Eyes with thicker baseline choroidal volume showed a greater reduction in SRF.

MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. METHODS: The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. RESULTS: Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P < 0.001). Similarly, subfoveal choroidal thickness had decreased from 157.0 µm (interquartile range 116.0-244.5) at baseline to 139.0 µm (interquartile range 102.5-212.0) at the final examination (P < 0.001). Both parameters macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. CONCLUSION: The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

Assessment of vision-related quality of life in patients with central retinal artery occlusion.

BACKGROUND: Central retinal artery occlusion (CRAO) is a major cause for severe visual impairment. Its effect on vision-related quality of life has not yet been determined. The purpose of the present study was thus to assess vision-related quality of life in patients with CRAO using the 39-item National Eye Institute Visual Function Questionnaire. METHODS: The case-control study comprised 26 patients with unilateral CRAO and a control group consisting of 26 control subjects, matched for age and sex. Vision-related quality of life was measured using the 39-item National Eye Institute Visual Function Questionnaire. RESULTS: After Bonferroni correction, the median 39-item National Eye Institute Visual Function Questionnaire composite score was significantly lower in patients with CRAO than in those in the control group (P(corr) < 0.001). Patients with CRAO showed significantly lower median scores in 9 of 12 subscales: general vision (P(corr) < 0.001), peripheral vision (P(corr) < 0.001), difficulties with near-vision activities (P(corr) < 0.001), difficulties with distance-vision activities (P(corr) < 0.001), role difficulties as a result of vision problems (P(corr) < 0.001), dependency on others because of vision problems (P(corr) < 0.001), limitations in social functioning because of vision problems (P(corr) < 0.001), mental health symptoms because of vision problems (P(corr) < 0.001), and general health (P(corr) = 0.008). CONCLUSION: Our data suggest that vision-related quality of life is reduced in patients with CRAO.

Evaluation of intravitreal injections as a risk factor for capsular rupture during cataract surgery.

OBJECTIVE: To determine whether previous intravitreal injections are an independent risk factor for posterior capsular rupture (PCR) during cataract surgery after adjusting for known risk factors. DESIGN: Single-centre medical records analysis of a population-based cohort at a university-based referral centre. A retrospective cohort study has been conducted with inclusion of cataract surgeries done from January 1, 2005 to December 31, 2020 at the Department of Ophthalmology, Medical University of Graz, Austria. PARTICIPANTS: All consecutive cataract surgeries done in patients of at least 18 years of age from January 1, 2005 to December 31, 2020 have been included. METHODS: Association between previous intravitreal injections and PCR rates has been analysed through univariable and multivariable generalized estimating equations (GEE). Other investigated risk factors were age, combined surgery, pseudoexfoliation, surgeon's experience, and type of cataract surgery. RESULTS: A statistically significant higher rate of posterior capsular rupture during cataract surgery has been found in patients with previous intravitreal therapy compared with patients with no history of intravitreal therapy (OR 1.27, 95% CI 1.10-1.46, p = 0.008). However, after adjusting for confounding risk factors, no statistically significant effect was seen (OR 1.04, 95% CI 0.89-1.21, p = 0.664). CONCLUSION: We found no association between history of intravitreal injections and PCR during cataract surgery after adjusting for known risk factors. Further studies upon interactions between history of intravitreal injections and known risk factors for PCR, especially pseudoexfoliation, are needed.

Measurement of tumor necrosis factor-alpha, interleukin-6, Fas ligand, interleukin-1α, and interleukin-1ß in the aqueous humor of patients with open angle glaucoma using multiplex bead analysis.

PURPOSE: Various cytokines, including tumor necrosis factor-alpha (TNF-α), Fas ligand (FasL), interleukin-1α (IL-1α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), contribute to the pathogenesis of primary open angle glaucoma (POAG). The present study was set to measure these cytokines in the aqueous humor of patients with POAG and in control subjects using multiplex bead analysis. METHODS: Twenty-five patients with POAG and 29 control subjects were enrolled in this case-control study. Aqueous humor concentrations of the cytokines (IL-1 α, IL-1 ß, IL-6, FasL, and TNF- α) were measured using multiplex bead analysis. RESULTS: Mean aqueous humor levels of IL-6 were significantly lower in patients with POAG compared to the control subjects (9.3±23.7 versus 55.3±94.4 pg/ml; p=0.002). No significant difference in the aqueous humor concentration of IL-1ß was found between patients with POAG and control subjects (0.5±0.8 versus 0.4±0.8 pg/ml; p=0.85.) Concentrations of IL-1α, TNF-α, and FasL were below limits of detection. No significant correlation was found between IL-6 concentration and age, duration of disease, cup/disc ratio, or mean deviation. CONCLUSIONS: In the present study, we found significantly lower concentrations of IL-6 in the aqueous humor of patients with POAG.

Risk assessment of idiopathic macular holes undergoing vitrectomy with dye-assisted internal limiting membrane peeling.

BACKGROUND: The purpose of this study was to investigate and identify predictors for idiopathic macular hole persistence after pars plana vitrectomy with dye-assisted internal limiting membrane peeling. METHODS: In a retrospective case series, 160 eyes underwent identical vitreoretinal procedures performed by the same surgeon. Baseline characteristics and preoperative optical coherence tomography were evaluated regarding the postoperative anatomical outcome. RESULTS: n overall closure rate of 86.3% (138/160) was achieved. According to the Gass classification system, the closure rates were 100.0% (11/11) in Stage 2, 95.0% (57/60) in Stage 3, and 78.7% (70/89) in Stage 4. Thereby, a significant influence of preoperative best-corrected visual acuity and basal hole diameter was observed. Especially, idiopathic macular hole with a basal hole diameter of ≥800 µm and a best-corrected visual acuity of ≤20/100 had a 4 and 6 times higher risk to persist, respectively. On the other hand, age, gender, bilateral occurrence, symptom duration, and lens status did not have an effect on the surgical outcome. Furthermore, perifoveal pseudocysts were associated with a higher closure rate in Stage 4 idiopathic macular hole. CONCLUSION: Simple clinical parameters such as best-corrected visual acuity, basal diameter, and perifoveal pseudocysts are efficient predictors and might be used to expand the validity of the Gass classification.

Role of vascular endothelial growth factor polymorphisms in the treatment success in patients with wet age-related macular degeneration.

PURPOSE: Along with environmental risk factors such as smoking, hypertension, and atherosclerosis, genetic susceptibility is a primary contributor to the development and progression of exudative age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a central angiogenic regulator and there has been general agreement now that it is an important trigger for the progression of exudative AMD. In the present study, we tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with exudative AMD. DESIGN: Prospective cohort study. PARTICIPANTS: We included 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally administered bevacizumab in this trial. METHODS: All patients were aged >50 years and had angiographically verified exudative AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs833061, rs699947, rs3024997, and rs1005230. At each follow-up visit, visual acuity was reassessed and an ophthalmic examination was carried out. Visual acuity outcome, number of retreatments, and overall time of treatment were analyzed in dependence of the VEGF polymorphisms. MAIN OUTCOME MEASURES: Mean change in visual acuity at the end of the treatment period. RESULTS: The included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment period of 42 to 1182 days. In univariate analysis only the G/G genotypes of rs3024997 and rs2010963 compared with all other 5 single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a significant correlation. CONCLUSIONS: The current study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD.

Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.

To identify the disease-causing gene responsible for an autosomal dominantly inherited Charcot-Marie-Tooth neuropathy subtype in a family excluded for mutations in the common Charcot-Marie-Tooth genes, we used array-based sequence capture to simultaneously analyse the disease-linked protein coding exome at chromosome 14q32. A missense mutation in fibulin-5, encoding a widely expressed constituent of the extracellular matrix that has an essential role in elastic fibre assembly and has been shown to cause cutis laxa, was detected as the only novel non-synonymous sequence variant within the disease interval. Screening of 112 index probands with unclassified Charcot-Marie-Tooth neuropathies detected two further fibulin-5 missense mutations in two families with Charcot-Marie-Tooth disease and hyperextensible skin. Since fibulin-5 mutations have been described in patients with age-related macular degeneration, an additional 300 probands with exudative age-related macular degeneration were included in this study. Two further fibulin-5 missense mutations were identified in six patients. A mild to severe peripheral neuropathy was detected in the majority of patients with age-related macular degeneration carrying mutations in fibulin-5. This study identifies fibulin-5 as a gene involved in Charcot-Marie-Tooth neuropathies and reveals heterozygous fibulin-5 mutations in 2% of our patients with age-related macular degeneration. Furthermore, it adumbrates a new syndrome by linking concurrent pathologic alterations affecting peripheral nerves, eyes and skin to mutations in the fibulin-5 gene.

Heme oxygenase-1 gene rs2071746 polymorphism in retinal vein occlusion.

BACKGROUND: Heme oxygenase-1 (HO-1) is an important cytoprotective enzyme due to its ability to degrade pro-inflammatory heme. The common single nucleotide polymorphism (SNP) rs2071746 on the HMOX1 gene has been associated with HO-1 activity and a variety of cardiovascular diseases. This study was performed to investigate the association between the rs2071746 SNP and retinal vein occlusion (RVO). METHODS: We included 496 RVO patients and 297 control subjects in this case-control study. Genotypes of the rs2071746 polymorphism were determined by TaqMan assays. RESULTS: There was no association between the rs2071746 genotype and the presence of RVO (p = .443). The lack of association was found in all three logistic regression models, namely the dominant (p = .560), the recessive (p = .373) and the co-dominant model (p = .444). The distribution of the rs2071746 genotype was 30% (AA), 51% (AT), and 19% (TT). Baseline characteristics were similar between these genotypes, except for diabetes mellitus, which was less prevalent in the AA genotype (p < .001). CONCLUSION: The rs2071746 polymorphism does not seem to be a major risk factor for the presence of RVO.

Ultrasound-detected inflammation is more common in clinically manifest hand osteoarthritis than in painless bony enlarged finger joints: subanalysis of the population-based Bruneck study.

Purpose: The aim of this article is to examine the extent of structural and inflammatory lesions by ultrasound in elderly subjects with hand osteoarthritis (HOA) fulfilling the ACR classification criteria (Group A), in subjects with painless enlarged finger joints (Group B), and in individuals without clinical abnormalities at hands (Group C). Methods: This study was nested within the population-based, prospective Bruneck study; 293 subjects of ⩾65 years of age were assessed. Clinical and ultrasound assessment was conducted at wrists and finger joints. Gray scale synovitis (GSS), Power Doppler (PD), osteophytes, and erosions were scored semiquantitatively (0-3). The Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH), the Health Assessment Questionnaire (HAQ), and the Functional Index for Hand Osteoarthritis (FIHOA) were retrieved. Results: Most subjects had ⩾1 ultrasound abnormality, of which osteophytes were the most prevalent finding in all groups (Group A: 100%, Group B: 99.4%, and Group C: 93.9%). GSS and PD-signals were more common in Group A than in Group B (94% versus 67% and 33% versus 13%, respectively). In Group C, GSS was observed in 39.4% of subjects. In subjects with HOA, the SF-SACRAH correlated with osteophyte scores (corrcoeff = 0.48), and the FIHOA correlated with the osteophyte (corrcoeff = 0.42) and PD scores (corrcoeff = 0.33). Conclusion: GSS and PD were more frequent in patients with symptomatic HOA than in cases with painless bony enlargements and subjects without clinical joint abnormalities. Functional restriction in HOA is associated with structural and inflammatory ultrasound changes.