Evidence of gene-gene interaction in hidradenitis suppurativa: a nationwide registry study of Danish twins.

BACKGROUND: Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease that, apart from rare causative loss-of-function mutations, has a widely unknown genetic aetiology. OBJECTIVES: To estimate the relative importance of genetic and environmental factors underlying susceptibility to HS. METHODS: Via the Danish Twin Registry and the Danish National Patient Registry we pulled together information on zygosity with that of HS status. Cases of HS were identified by the International Classification of Diseases (ICD)-8 (705·91) and ICD-10 (L73·2). Heritability was assessed by the classic biometric model and the possibility of gene-gene interaction via the multilocus modelling approach. RESULTS: Among 100 044 registered twins, we found 170 twins (from 163 pairs) diagnosed with HS. The seven concordant pairs were all monozygotic. Monozygotic twins had a case-wise concordance rate of 28% [95% confidence interval (CI) 7-49], corresponding to a familial risk of 73 (95% CI 13-133) times that of the background population. The biometrical modelling suggested a heritability of 0·80 (95% CI 0·67-0·93), and the multilocus index estimate was 230 (95% CI 60-400). This is highly indicative of gene-gene interactions, with the possibility of up to six interacting loci. CONCLUSIONS: This twin study was substantially larger and employed a more valid phenotype than previous studies. Genetics account for the majority of HS susceptibility, and HS is most likely caused by gene-gene interactions rather than monogenetic mutations or solely additive genetic factors. New approaches aimed at assessing potential interactions at a single-nucleotide polymorphism (SNP)-SNP level should be implemented in future HS genome-wide association studies.

The temporal association of hyperhidrosis and its comorbidities - a nationwide hospital-based cohort study.

BACKGROUND: Research on hyperhidrosis comorbidities has documented the co-occurrence of diseases but has not provided information about temporal disease associations. OBJECTIVE: To investigate the temporal disease trajectories of individuals with hospital-diagnosed hyperhidrosis. METHODS: This is a hospital-based nationwide cohort study including all patients with a hospital contact in Denmark between 1994 and 2018. International Classification of Diseases version-10 diagnoses assigned to inpatients, outpatients and emergency department patients were collected from the Danish National Patient Register. The main outcome was the temporal disease associations occurring in individuals with hyperhidrosis, which was assessed by identifying morbidities significantly associated with hyperhidrosis and then examining whether there was a significant order of these diagnoses using binomial tests. RESULTS: Overall, 7 191 519 patients were included. Of these, 8758 (0.12%) patients had localized hyperhidrosis (5674 female sex [64.8%]; median age at first diagnosis 26.9 [interquartile range 21.3-36.1]) and 1102 (0.015%) generalized hyperhidrosis (606 female sex [59.9%]; median age at first diagnosis 40.9 [interquartile range 26.4-60.7]). The disease trajectories comprised pain complaints, stress, epilepsy, respiratory and psychiatric diseases. The most diagnosed morbidities for localized hyperhidrosis were abdominal pain (relative risk [RR] = 121.75; 95% Confidence Interval [CI] 121.14-122.35; P < 0.001), soft tissue disorders (RR = 151.19; 95% CI 149.58-152.80; P < 0.001) and dorsalgia (RR = 160.15; 95% CI 158.92-161.38; P < 0.001). The most diagnosed morbidities for generalized hyperhidrosis were dorsalgia (RR = 306.59; 95% CI 302.17-311.02; P < 0.001), angina pectoris (RR = 411.69; 95% CI 402.23-421.16; P < 0.001) and depression (RR = 207.92; 95% CI 202.21-213.62; P < 0.001). All these morbidities were diagnosed before hyperhidrosis. CONCLUSIONS: This paper ascertains which hospital-diagnosed morbidities precede hospital-diagnosed hyperhidrosis. As hyperhidrosis mainly is treated in the primary health care sector, the trajectories suggests that these morbidities may lead to a worse disease course of hyperhidrosis that necessitates treatment in hospitals. Treating these morbidities may improve the disease course of hyperhidrosis.

Incidence and remission rates of self-reported hidradenitis suppurativa - A prospective cohort study conducted in Danish blood donors.

BACKGROUND: A large discrepancy between physician-diagnosed and self-reported Hidradenitis suppurativa (HS) exists. Knowledge regarding incidence and remission rates of self-reported HS is missing, but may help bridge the gap in understanding between these two phenotypes. OBJECTIVES: To determine the incidence and remission rates of self-reported HS, and to what degree these are affected by sex, smoking and BMI. METHODS: A prospective cohort of 23 930 Danish blood donors. Information on self-reported HS, symptom-localisation, sex, age, BMI and smoking status was collected at baseline and study termination. Self-reported HS fulfilled clinical obligatory diagnostic criteria. Cox proportional hazards regression analyses were conducted for both incidence and remission rates providing a hazard ratio (HR) of risk for each variable in the regression. RESULTS: Incidence rate of self-reported HS was 10.8/1000 person-years (95% confidence interval (CI): 9.9-11.7), decreasing as a function of numbers of areas affected. Female BMI points above 25 (HR = 1.11, 95% CI: 1.09-1.13), male BMI points above 25 (HR = 1.07, 95% CI: 1.04-1.11), active smoking (HR = 1.72, 95% CI: 1.15-2.57), male sex (HR = 0.55, 95% CI: 0.45-0.67) and years of age above 25 (HR = 0.97, 95% CI: 0.96-0.97) were all statistically associated with the development of self-reported HS. Remission rate of self-reported HS was 256.7/1000 person-years (95% CI: 223.9-292.6), decreasing as a function of numbers of affected areas. Symptoms in ≥3 areas (HR = 0.54, 95% CI: 0.34-0.85), active smoking (HR = 0.49, 95% CI: 0.32-0.76) and female weight loss (every percentage drop in BMI: HR = 1.07, 95% CI: 1.05-1.11) all significantly affected the remission rate. CONCLUSIONS: Both incidence and remission rates of self-reported HS are high, indicating that many with self-reported HS are unlikely to be diagnosed, as they to a higher degree experience mild transient HS symptoms.

Convergent Validity of Suffering and Quality of Life as Measured by The Hidradenitis Suppurativa Quality of Life.

BACKGROUND: Hidradenitis suppurativa (HS) is a painful chronic, recurrent inflammatory skin disease with great impact on health-related quality of life (HRQOL). Recently, Hidradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) established HRQOL as a core domain set for HS clinical trials and developed the Hidradenitis Suppurativa Quality of Life (HiSQOL) as a validated outcome measurement instrument. OBJECTIVES: To provide further convergent validity of HiSQOL by comparing it to Dermatology Life Quality Index (DLQI) and Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2). METHODS: In this cross-sectional study, 103 participants completed HiSQOL, PRISM-R2 and DLQI. PRISM-R2 is an instrument designed to measure suffering and reports the two measures, Illness Perception Measure (IPM) and Self-Illness Separation (SIS). Correlation analyses were performed including a sub-analysis for a subgroup of patients with high scores in the HS-specific domains of HiSQOL. RESULTS: A very strong correlation was found between HiSQOL and DLQI (ρ = 0.93, P < 2.2 × 10-16 , (95% CI: 0.89;0.95)), and moderately strong correlations were found between HiSQOL and SIS (ρ = -0.73, P < 2.2 × 10-16 , (95% CI: -0.81; -0.62)) and DLQI and SIS (ρ = -0.70, P < 2.2 × 10-16 , (95% CI: -0.79; -0.59)). IPM was positively associated with HiSQOL and DLQI and negatively with SIS. CONCLUSIONS: HiSQOL is a valid measure of quality of life for HS patients, and we suggest that HiSQOL can be used as a measure of suffering as well.

Full exome sequencing of 11 families with Hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is not a well-studied or easily treated disease. Genetic information is essential for advances in the understanding and treatment of HS. This study aims to examine mutations in the gamma-secretase complex, the Notch signalling pathway and to perform a Mendelian analysis of genetic variants that segregated with disease in a full exome sequencing of 11 families with HS. METHOD: Whole-exome sequencing and Mendelian analysis of 11 families with HS from Denmark. Patients with a clinical diagnosis of active HS and a positive family history of HS were recruited. Consenting family members were enrolled and examined for HS as well. We included 11 families, with a total of 51 participants, 24 with HS and 27 without. Whole-exome sequencing using HiSeq platform as paired-end 2 × 150 bases was used. RESULTS: We found mutations in the Notch pathway for all families. We found mutations in the PSENEN and APH1B of the gamma-secretase genes. We also report 161 variants of unknown significance that segregated with the disease within these families. CONCLUSIONS: We did not find causative mutation for each family in this study, supporting the theory that HS is rarely caused by single-gene mutations. We suggest that future genetic studies should be focused on genome-wide association with thousands of cases, as this technique is better suited for suspected polygenic diseases.

Interprofessional education on complex patients in nursing homes: a focus group study.

BACKGROUND: An ageing population leads up to increasing multi-morbidity and polypharmacy. This demands a comprehensive and interprofessional approach in meeting patients' complex needs. This study describes graduate students' experiences of working practice based in interprofessional teams with complex patients' care needs in nursing homes. METHOD: Students from advanced geriatric nursing, clinical nutrition, dentistry, medicine and pharmacy at the University of Oslo in Norway were assigned to groups to examine and develop a care plan for a nursing home patient during a course. Focus groups were used, 21 graduate students participating in four groups. Data were collected during spring 2018, were inductively analysed according to a thematic analysis method (Systematic Text Condensation). An analytical framework of co-ordination practices was applied to get an in-depth understanding of the data. RESULTS: Three themes were identified: 1) Complex patients as learning opportunities- an eye-opener for future interprofessional collaboration 2) A cobweb of relations, and 3) Structural facilitators for new collective knowledge. Graduate university students experienced interprofessional education (IPE) on complex patients in nursing homes as a comprehensive learning arena. Overall, different co-ordination practices for work organization among the students were identified. CONCLUSIONS: IPE in nursing homes facilitated the students' scope from a fragmented approach of the patients towards a relational and collaborative practice that can improve patient care and strengthen understanding of IPE. The study also demonstrated the need for preparatory teamwork training to gain maximum benefit from the experience. Something that can be organized by the education institutions in the form of a stepwise learning module and as an online pre-training course in interprofessional teamwork. Further, focusing on the need for well thought through processes of the activity by the institutions and the timing the practice component in students' curricula. This could ensure that IPE is experienced more efficient by the students.

Bis-cyclooctatetraenyl Thulium(II): Highly Reducing Lanthanide Sandwich Single Molecule Magnets.

Divalent lanthanide organometallics are well-known highly reducing compounds usually used for single electron transfer reactivity and small molecule activation. Thus, their very reactive nature prevented for many years the study of their physical properties, such as magnetic studies on a reliable basis. In this article, the access to rare organometallic sandwich compounds of TmII with the cyclooctatetraenyl (Cot) ligand impacts on the use of divalent organolanthanide compounds as an additional strategy for the design of performing Single Molecule Magnets (SMM). Herein, the first divalent thulium sandwich complex with f13 configuration behaving as a Single Molecule Magnet in absence of DC field is highlighted.

Surgical repair of parastomal bulging: a retrospective register-based study on prospectively collected data.

AIM: The aim of this work was to examine (1) the incidence of primary repair, (2) the incidence of recurrent repair and (3) the types of repair performed in patients with parastomal bulging. METHOD: Prospectively collected data on parastomal bulging from the Danish Stoma Database were linked to surgical data on repair of parastomal bulging from the Danish National Patient Register. Survival statistics provided cumulative incidences and time until primary and recurrent repair. RESULTS: In the study sample of 1016 patients with a permanent stoma and a parastomal bulge, 180 (18%) underwent surgical repair. The cumulative incidence of a primary repair was 9% [95% CI (8%; 11%)] within 1 year and 19% [95% CI (17%; 22%)] within 5 years after the occurrence of a parastomal bulge. We found a similar probability of undergoing primary repair in patients with ileostomy and colostomy. For recurrent repair, the 5-year cumulative incidence was 5% [95% CI (3%; 7%)]. In patients undergoing repair, the probability was 33% [95% CI (21%; 46%)] of having a recurrence requiring repair within 5 years. The main primary repair was open or laparoscopic repair with mesh (43%) followed by stoma revision (39%). Stoma revision and repair with mesh could precede or follow one another as primary and recurrent repair. Stoma reversal was performed in 17% of patients. CONCLUSION: Five years after the occurrence of a parastomal bulge the estimated probability of undergoing a repair was 19%. Having undergone a primary repair, the probability of recurrent repair was high. Stoma reversal was more common than expected.

T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression.

Background: Almost half of the patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing following CPI treatment was able to generate functional tumor-specific immune responses. Materials and methods: Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which progressed during or after anti-programmed cell death protein 1 (PD)-1 and anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) treatment. Tumor-specific immune responses were assessed with co-culture assays of TILs and autologous tumor cells. Results: TILs from 23 metastases of individual patients could be assessed for T cells recognition of autologous tumor cells. All metastases were progressive on or following anti-PD-1 (23/23, 100%), and the majority also after anti-CTLA-4 (17/23, 74%). Functional antitumor immune responses were detected in 19/23 patients (83%). Both CD8+ (in 18/23 patients, 78%) and CD4+ (in 16/23 patients, 70%) TILs were able to recognize autologous tumors. A large fraction of CD8+ TILs (median 23%, range 1.0%-84%) recognized tumor cells. This is similar to the cohorts of unselected patient populations with metastatic melanoma presented in previous studies. The localization of intratumoral immune infiltrates was heterogeneous among samples. In a phase I/II clinical trial, TILs were administered with lymphodepleting chemotherapy, pegIFNα2b and interleukin-2 to 12 patients with CPI-resistant melanoma. Out of 12 patients who previously failed CPI therapy, treatment with TILs resulted in two partial responses, of which one is ongoing. Conclusions: Tumor-reactive T cells appear to heavily infiltrate the tumor microenvironment of patients who failed previous CPI treatment. These patients can still respond to an infusion of unselected autologous TILs. Our results warrant further testing of novel immune re-activation strategies in melanoma patients who failed multiple CPI therapy.

Incidence and risk factors for parastomal bulging in patients with ileostomy or colostomy: a register-based study using data from the Danish Stoma Database Capital Region.

AIM: The aim was to investigate the incidence and risk factors for parastomal bulging, a clinically important complication, in patients with an ileostomy or colostomy. METHOD: The Danish Stoma Database Capital Region prospectively collects data on patients with a stoma up to a year after surgery. Stoma care nurses clinically assessed the main outcome, parastomal bulging. We linked data from the Stoma Database to data from the Danish Anaesthesia Database. Cumulative incidence of parastomal bulging over the first year was calculated with death and stoma reversal as competing risks. Risk factors were investigated using an exploratory approach. RESULTS: In a study population of 5019, the cumulative incidence (with competing risks) of parastomal bulging was 36.2% at 400 days after surgery. Age, colostomy, male gender, alcohol consumption and laparoscopy were associated with an increased risk of parastomal bulging. Compared with cancer, inflammatory bowel disease was associated with a lower risk of parastomal bulging, and diverticulitis was associated with a higher risk. Peristomal mesh and stomas placed through a separate incision were associated with a reduction in risk. There was neither increased nor decreased risk of parastomal bulging for body mass index, American Society of Anesthesiologists score, smoking status, emergency surgery and preoperative stoma site marking. CONCLUSION: Parastomal bulging is a common complication affecting one in three patients within 1 year of surgery. Along with previous findings, there is now considerable evidence for age and colostomy as being risk factors for parastomal bulging.

Self-reported minor infections in patients with hidradenitis suppurativa and healthy controls.

BACKGROUND: Patients with hidradenitis suppurativa (HS) often report opportunistic infections such as herpes and urinary tract infections. AIM: To compare opportunistic infections in patients with HS against a group of healthy controls (HCs). METHODS: In total, 99 patients with HS and 109 HCs were recruited at random to this retrospective case-control study. We devised a questionnaire to explore the frequency of minor infections, general practitioner (GP) visits and sick days experienced during the past 6 months. Additionally, participants were asked if they felt unwell more often compared with their peers. RESULTS: Patients with HS felt unwell more often than did HCs (26.3% vs. 7.3%, P < 0.001). Although there was no difference between the groups in five of the seven diseases studied, patients with HS had a higher frequency of the common cold (P < 0.01) and genital herpes (P < 0.01). Number of pack-years of smoking did not affect risk of infections (Pearson correlation, P = 0.51). Subgroup analysis of nonsmokers found the same differences in frequency of minor infections, common cold and genital herpes between patients with HS and controls. CONCLUSIONS: Patients with HS appear to experience more frequently symptoms compatible with minor infections in general, and the common cold and genital herpes specifically. This results in more GP visits and more sick days. Further research is needed to determine if this is caused by an immunological hyper-reactive state in these patients or a reduced threshold for minor infections.

Eccentric exercise induces spatial changes in the mechanomyographic activity of the upper trapezius muscle.

In this study, we hypothesized that the recordings of multichannel mechanomyography (MMG) of the upper trapezius muscle would reveal spatially dependent manifestations in the presence of delayed onset muscle soreness occurring 24 hours after eccentric exercise (ECC). Sixteen participants performed high-intensity eccentric exercises (5 sets of 10 eccentric contractions at 100% of max elevation force) targeting the upper trapezius on their dominant side. Twelve accelerometers were attached to record MMG activity during submaximal exercise consisting of static and dynamic arm flexion and abduction. Measurements were taken before and 24 hours after ECC. Average rectified value (ARV), percentage of determinism (% DET), and recurrence (% REC) of the MMG signals were computed to estimate the level of muscular activity and the magnitude of regularity of the MMG. The ARV, % REC, and % DET maps revealed heterogeneous MMG activity of the upper trapezius 24 hours after ECC when compared with before. Increased ARV, % REC, and % DET were found 24 hours after ECC when compared with before. The study provides new key information on how a single muscle responds to ECC. Our findings suggest that multichannel MMG and nonlinear analyses may detect muscular and musculo-tendinous alterations due to ECC.

Factors predicting the self-evaluated health of hidradenitis suppurativa patients recruited from an outpatient clinic.

OBJECTIVES: In recent years, Hidradenitis suppurativa has received increased attention but still lack well-defined, robust patient-reported outcome measures. Such measures are likely to be influenced by contextual factors. We, therefore, aim to describe the association of biological and other factors with HS patient's self-evaluated health as reflected by the EQ5D VAS score. METHODS: This cross-sectional study measured basic information, Dermatology Life Quality Index, Major Depression Inventory and Euro-QoL-5D. Information obtained through questionnaires was used to create a model showing the relation between biological factors, questionnaire results and self-evaluated health using the stepwise method for linear regression. Patients with HS (n = 805) registered at our department were invited to participate. A total of 503 (62.5%) patients replied to this survey. There was no difference in basic demographics between responders and non-responders. RESULTS: Possible predictors for this study were DLQI, MDI, BMI, smoking, gender. A final model for correlation with self-evaluated health was obtained. Significant predictors for the model were DLQI (P < 0.05), BMI points above 25 and active smoking (both: P < 0.01) and MDI (P < 0.001). CONCLUSION: As this is a cross-sectional study, it reveals several clinically relevant correlations. Smoking appears to correlate with the highest change in VAS score, but an MDI of 10 (lower than study average) or a BMI of 40 influences the results more. This study provides an assessment of how much BMI and smoking, in relation to other factors, correlate to the self-evaluated health state of patients with HS. These may, therefore, be relevant contextual factors to the construction and interpretation of specific patient-reported outcome measures. To improve QoL, we advocate smoking cessation and weight loss, and advice active screening for depression as over 10% of our patients qualify for a depressive diagnosis according to ICD-10.

Mutation analysis in Norwegian families with hereditary hemorrhagic telangiectasia: founder mutations in ACVRL1.

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is an autosomal dominant inherited disease defined by the presence of epistaxis and mucocutaneous telangiectasias and arteriovenous malformations (AVMs) in internal organs. In most families (~85%), HHT is caused by mutations in the ENG (HHT1) or the ACVRL1 (HHT2) genes. Here, we report the results of genetic testing of 113 Norwegian families with suspected or definite HHT. Variants in ENG and ACVRL1 were found in 105 families (42 ENG, 63 ACVRL1), including six novel variants of uncertain pathogenic significance. Mutation types were similar to previous reports with more missense variants in ACVRL1 and more nonsense, frameshift and splice-site mutations in ENG. Thirty-two variants were novel in this study. The preponderance of ACVRL1 mutations was due to founder mutations, specifically, c.830C>A (p.Thr277Lys), which was found in 24 families from the same geographical area of Norway. We discuss the importance of founder mutations and present a thorough evaluation of missense and splice-site variants.

Qualitative vs. quantitative atopic dermatitis criteria - in historical and present perspectives.

This review summarizes historical aspects, clinical expression and pathophysiology leading to coining of the terms atopy and atopic dermatitis, current diagnostic criteria and further explore the possibility of developing quantitative diagnostic criteria of atopic dermatitis (AD) based on the importance of atopic features - subjective, objective, and those derived from laboratory tests - the new partly promising AD biomarkers. 'Atopy', introduced in 1923, denoted 'the sense of a strange disease without a precise place in the body'. A decade later, Sulzberger and Hill, first defined 'atopic dermatitis'. The pioneering well-recognized criteria, 'Hanifin & Rajka' (Acta Derm Venereol, 92, 1980, 44), were developed empirically on 'clinical experience' and expert consensus. As opposed to the widely used, rather anamnestic 'UK Criteria' (1994), they have few formal validation studies, but appear to well embrace various atopic phenotypes. Pruritus, xerosis, typical morphology/distribution of dermatitis and tendency to a relapsing/chronic course are common basic features in AD criteria, whereas skin sensitivity, heredity and various ill-defined atopic stigmata also seem to comprise the atopic phenomenon. Specific pheno- and endotypes are now emerging potentially enabling us to better classify patients with AD, but the influence of these on the diagnosis of AD is so far unclear. Few diagnostic models use quantitative scoring systems to establish AD cases from normal population, which, however, may be useful to better study and manage this disease. Long-term prospective observational studies, from which few are available at this point, along with interventional studies, are a perquisite and will provide the best option to improve our understanding of its complex characteristics and etiology.

Development, validation and implementation of a quantitative food frequency questionnaire to assess habitual vitamin D intake.

BACKGROUND: A well-designed, validated quantitative food frequency questionnaire (FFQ) could offer an efficient and cost-effective method for assessing habitual vitamin D intake. The present study aimed to describe the development, validation and implementation of a vitamin D FFQ. METHODS: National food consumption survey data obtained from Irish adults (18-64 years) were used to identify foods that contribute 95% of vitamin D intake. A winter-based validation study was carried out for the resulting FFQ in 120 females, including 98 women [mean (SD) 65.0 (7.3) years] and 22 girls [12.2 (0.8) years], using a 14-day diet history (DH) as a comparator. Serum 25(OH)D concentrations were analysed. Validity coefficients were calculated using the method of triads. Cross-classification and Bland-Altman analysis were also performed. RESULTS: Median (interquartile range) vitamin D intakes (including the contribution from nutritional supplements) were 5.4 (3.7) and 3.7 (5.9) µg day(-1) from the FFQ and DH, respectively and intakes of vitamin D from food sources were 3.6 (3.1) and 2.4 (2.2) µg day(-1) . The FFQ and DH classified 86% and 87% of individuals into the same and adjacent thirds of wintertime serum 25(OH)D status, respectively. There was a strong association (r = 0.71, P < 0.0001) and no significant systematic or proportional bias observed for the difference between estimates from the FFQ and DH. The validity coefficient for the FFQ was 0.92 (95% confidence interval = 0.80-0.97). Repeatability analysis (n = 56) performed 6-12 months later showed no significant difference in estimates of vitamin D between administrations. CONCLUSIONS: The data obtained in the present study indicate high validity and good reproducibility of a short, interviewer-administered FFQ for vitamin D.

Trends of barriers to eye care among adults with diagnosed diabetes in Germany, 1997-2012.

BACKGROUND AND AIMS: To study trends of barriers to receiving recommended eye care among subjects with diabetes aged 20-81 years in northeast Germany. METHODS AND RESULTS: We analyzed population-based data from two repeated cross-sectional surveys conducted in 1997-2001 and 2008-2012 (Ns of 4308 and 4402). Andersen's Behavioral Model of Health Services Utilization was used to identify individual-level demographic, financial and health-related barriers to annual eye-care utilization in subjects with a self-reported physician's diabetes and to examine population trends in these barriers. The prevalence of diabetes increased from 6.5% to 11.4%. The prevalence of annual eye-care utilization among persons with diabetes decreased from 69.4% to 56.0% (adjusted relative risk = 0.77, p < 0.001). The decline of eye care utilization over the past decade in eye-care use was more pronounced in groups at risk for diabetes-related complications (i.e., lower socio-economic status, >5 years since diagnosis of diabetes, poor glycemic control, obesity, smoking, lack of physical activity, co-existing diseases). We identified relevant predictors of missed annual eye-care use among diabetics. CONCLUSION: The increase of diabetes prevalence and downward trend of eye-care visits at the recommended level call for development, implementation and evaluation of continued efforts to improve access to eye specialists, particularly among those with poor diabetic control, co-existing diabetic complications, and comorbidities.