Should timing be considered before abandoning convalescent plasma in covid-19? Results from the Turkish experience.

INTRODUCTIONS: Results with convalescent plasma therapy in coronavirus disease 2019 (COVID-19) have been contradictory. Timing seems to be an important factor for COVID-19 convalescent plasma(CCP) to be effective. Aim of this study is to compare disease outcomes in hospitalized COVID-19 patients who were treated with CCP within first three or seven days of symptoms to patients with symptoms longer than seven days. MATERIAL AND METHODS: A multicenter retrospective study was conducted to evaluate disease outcomes in hospitalized COVID-19 patients who received CCP in addition to standard of care (SOC) approach. Patients were subgrouped according to time of CCP administration; within three days of symptoms, seven days of symptoms and after seven days of symptoms. A control group was formed from age, gender and comorbidity matched hospitalized patients who received SOC treatments without CCP. Length of hospital stay, rates of anti-inflammatory treatment initiation, intensive care unit (ICU) admission and mortality was set as outcome measures. RESULTS: A total of 223 patients were enrolled in this study, 113 patients received CCP (38 within three days, 63 within seven days, 50 after seven days of symptom onset). Rate of anti-inflammatory treatment initiation was significantly lower (38.1 % vs 62.7 %, p = 0.002, relative risk, 0.60,73; 95 % confidence interval [CI], 0.42 to 0.85) and length of hospital stay was significantly shorter (median(IQR) 8(4) days vs 9.5(5.25) days, p = 0.0025) in patients who received CCP within seven days of symptom onset when compared to SOC group. CONCLUSION: CCP therapy may provide better outcomes when applied within seven days of symptoms.

Serum defensin levels in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and lung as well as involvement of kidney, gastrointestinal system and heart. Aetiology and exact mechanism of disease is poorly understood. The association between antimicrobial peptides (AMPs) and other diseases such as idiopathic pulmonary fibrosis, diffuse panbronchiolitis, pulmoner alveolar proteinosis and psoriasis have been reported. A small number of studies have examined the role of AMPs on autoimmune diseases which has not been studied in scleroderma yet. We aimed to investigate AMP serum levels and their association with disease characteristics of SSc. METHODS: Forty-two patients (40 female, mean age 42 years) and 38 healthy subjects (32 female, mean age 38 years) were enrolled. For SSc patients, the following data were recorded: disease subset (limited/diffuse), autoantibodies (antinuclear, anti-centromere (ACA), and anti-SCL-70), blood tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), modified Rodnan skin score, presence and history of digital ulcers, kidney, gastrointestinal disease and lung involvement assessed by computed tomography and pulmonary function tests. Association between serum AMPs and disease characteristics were analysed. RESULTS: Twenty-nine of the patients had diffuse (69%) and 13 of the patients had limited (31%) systemic sclerosis. Average disease duration was 5.5 years. Pulmonary involvement was detected in 20 patients (47.6%). Serum concentration of alpha defensin was higher than healthy subjects (563 ± 415 vs 377 ± 269 ng/mL, p = 0.02). However, no difference was observed for beta-1 and beta-2 defensins in SSc patients and healthy controls. In sub-group analysis patients with interstitial lung disease had higher levels of alpha defensin than those without lung involvement (684 ± 473 vs 430 ± 299 ng/ml, p = 0.04). There was also correlation between alfa defensin serum concentrations and CRP (r = 0.34). CONCLUSIONS: Alpha defensin levels are increased in scleroderma patients and correlated with lung involvement indicating a role in the pathogenesis of disease. TRIAL REGISTRATION: This study is not a clinical trial study.

Effectiveness of Canakinumab in Colchicine- and Anakinra-Resistant or -Intolerant Adult Familial Mediterranean Fever Patients: A Single-Center Real-Life Study.

OBJECTIVE: We aimed to present our single-center real-life experience of canakinumab use in adult patients with familial Mediterranean fever (FMF). METHODS: Data were derived from the Gazi FMF cohort, which was established in 2010. From that year, all patients with FMF were registered. The impact of FMF on their lives was tracked by either an FMF diary or mobile phone application (FMF-AIDD, free to download in App Store and Google Play). The records of patients who were treated with canakinumab were reviewed. RESULTS: Twenty-three adult patients with FMF (65% female) were enrolled in this study. The median age was 32 years (min-max, 24-58 years), and the disease duration was 26 years (14-59 years). A total of 86% of patients harbored homozygous or compound heterozygous exon 10 MEFV mutations. Indications for interleukin 1 inhibitor use were colchicine resistance (n = 12) or intolerance (n = 2), amyloidosis (n = 7), and chronic manifestations of the disease (n = 2). All patients used anakinra before. The median duration of canakinumab use was 7 months (min-max, 1-44 months). Pre- and post-canakinumab periods were compared. Attack severity, duration, frequency, C-reactive protein level, and erythrocyte sedimentation rate were significantly improved (p ≤ 0.01), whereas serum creatinine and alanine aminotransferase levels remained the same (p = 0.27 and p = 0.74, respectively). Canakinumab achieved complete disease remission in 14 patients (60%). Canakinumab was discontinued in 7 patients. The reasons for discontinuation were pregnancy (n = 2), dominance of axial spondyloarthropathy (n = 2), inflammatory bowel disease, patient's refusal, and weight gain. CONCLUSIONS: Canakinumab is effective in the prevention of FMF bouts without severe adverse effects. Treatment with canakinumab in an individualized dose and interval may be a reasonable choice for colchicine- and anakinra-resistant or -intolerant adult patients with FMF and those with chronic manifestations of disease.

Platelet/lymphocyte ratio and mean platelet volume in patients with granulomatosis with polyangiitis

Abstract Background: Granulomatosis with polyangiitis (GPA) is a granulomatous necrotizing vasculitis with high morbidity and mortality. Anti-neutrophil cytoplasmic antibody is a valuable diagnostic marker, however its titer lacks predictive value for the severity of organ involvement. Platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) has been regarded as a potential marker in assessing systemic inflammation. We aimed to explore the value of PLR and MPV in the assessment of disease activity and manifestations of disease in GPA. Methods: 56 newly diagnosed GPA patients and 53 age-sex matched healthy controls were included in this retrospective and cross-sectional study with comparative group. Complete blood count was performed with Backman Coulter automatic analyzer, erythrocyte sedimentation rate (ESR) with Westergen method and C-reactive protein (CRP) levels with nephelometry. The PLR was calculated as the ratio of platelet and lymphocyte counts. Result: Compared to control group, ESR, CRP and PLR were significantly higher and MPV significantly lower in GPA patients. In patients group, PLR was positively correlated with ESR and CRP (r = 0.39, p = 0.005 and r = 0.51, p < 0.001, respectively). MPV was negatively correlated with ESR and CRP (r = - 0.31, p = 0.028 and r = - 0.34 p = 0.014, respectively). Patients with renal involvement had significantly higher PLR than patients without renal involvement (median:265.98, IQR:208.79 vs median:180.34 IQR:129.37, p = 0.02). PLR was negatively correlated with glomerular filtration rate (r = - 0.27, p = 0.009). A cut-off level of 204 for PLR had 65.6% sensitivity and 62.5 specificity to predict renal involvement. Conclusion: PLR exhibit favorable diagnostic performance in predicting renal involvement in patients with GPA.(AU)

Serum defensin levels in patients with systemic sclerosis

Abstract Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and lung as well as involvement of kidney, gastrointestinal system and heart. Aetiology and exact mechanism of disease is poorly understood. The association between antimicrobial peptides (AMPs) and other diseases such as idiopathic pulmonary fibrosis, diffuse panbronchiolitis, pulmoner alveolar proteinosis and psoriasis have been reported. A small number of studies have examined the role of AMPs on autoimmune diseases which has not been studied in scleroderma yet. We aimed to investigate AMP serum levels and their association with disease characteristics of SSc. Methods: Forty-two patients (40 female, mean age 42 years) and 38 healthy subjects (32 female, mean age 38 years) were enrolled. For SSc patients, the following data were recorded: disease subset (limited/diffuse), autoantibodies (antinuclear, anti-centromere (ACA), and anti-SCL-70), blood tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), modified Rodnan skin score, presence and history of digital ulcers, kidney, gastrointestinal disease and lung involvement assessed by computed tomography and pulmonary function tests. Association between serum AMPs and disease characteristics were analysed. Results: Twenty-nine of the patients had diffuse (69%) and 13 of the patients had limited (31%) systemic sclerosis. Average disease duration was 5.5 years. Pulmonary involvement was detected in 20 patients (47.6%). Serum concentration of alpha defensin was higher than healthy subjects (563 ± 415 vs 377 ± 269 ng/mL, p = 0.02). However, no difference was observed for beta-1 and beta-2 defensins in SSc patients and healthy controls. In sub-group analysis patients with interstitial lung disease had higher levels of alpha defensin than those without lung involvement (684 ± 473 vs 430 ± 299 ng/ml, p = 0.04). There was also correlation between alfa defensin serum concentrations and CRP (r = 0.34). Conclusions: Alpha defensin levels are increased in scleroderma patients and correlated with lung involvement indicating a role in the pathogenesis of disease. Trial registration: This study is not a clinical trial study.(AU)

Certolizumab Pegol Treatment in Three Patients With Takayasu Arteritis.

Although glucocorticoids are the mainstay of treatment in Takayasu arteritis (TA), anti-tumor necrosis factor agents are other treatment options in refractory disease. The onset of TA is generally observed in females of reproductive age. Certolizumab pegol (CZP) lacks a fragment crystallizable region and this gives advantage of minimal transfer through the placenta, which makes CZP a safer option in pregnancy. Although there are case reports and trials about use of infliximab, etanercept, and adalimumab in TA, there are scarce data about use of CZP. In this article, we present three TA cases treated with CZP. While two patients benefited from CZP, one patient was refractory to CZP.

Validity of the Patient-Rated Wrist Evaluation questionnaire in rheumatoid arthritis.

BACKGROUND: The Patient-Rated Wrist Evaluation (PRWE) is a patient-reported questionnaire focusing on symptoms and function in wrist pathologies. It consists of 15 questions regarding pain and functional activities of the wrist. Rheumatoid arthritis (RA) is a multi-systemic disease characterized by inflammation of the wrist and hand joints in almost all patients. This study aims to test the validity of PRWE in patients with RA. METHOD: Seventy-five patients with RA from a single outpatient clinic participated in the study. Patients filled out the Michigan Hand Outcomes Questionnaire (MHOQ) and grip strength of both hands were measured. Patients filled out the PRWE questionnaire consecutively once for the dominant and once for the non-dominant hand. Correlations between PRWE and MHOQ and grip strength scores were analyzed by Spearman's correlation method. RESULTS: Our results demonstrated that there was a very strong correlation between the PRWE and the MHOQ and a moderate correlation between the PRWE and grip strength (P < .001). PRWE also showed negative and fair correlation with grip strength of both hands (P < .001). CONCLUSIONS: The Patient-Rated Wrist Evaluation is a valid tool for evaluating wrist involvement in patients with RA. PRWE may be preferred in the busy clinical setting since it has simple and short questions. Additionally, it may provide a sensitive follow-up tool for patients separately using its subscales of pain and function.

Detection of Familial Mediterranean Fever attacks by using a connected activity tracker and assessment of impact of attacks to daily physical activities: a pilot study.

OBJECTIVE: The objective of this study was to assess the impact of Familial Mediterranean Fever (FMF) attacks on daily physical activity and detect FMF attacks using a connected activity tracker. METHODS: Patients with FMF according to the Tel-Hashomer criteria were included in this prospective observational study. Attack-related data were collected weekly via phone call to avoid memory bias. Median steps in attack and attack-free days were calculated and compared using the Wilcoxon rank test. Sensitivity and specificity threshold for capturing attacks was set to two thirds of median steps per day in the whole observation period. RESULTS: Twelve patients participated in the study. The median age of patients was 26 (18-32) years, and 7 (58.3%) of them were male. Patients with attacks (n = 10) walked a median of 6990 (4552-11,531) steps per day in attack-free days, whereas this number decreased to a median of 1841 (590-4783) steps in attack days (p = 0.005). The activity tracker captured 42 of 45 attack days and 312 of 361 attack-free days. The cutoff value had 93% sensitivity and 86% specificity for capturing attacks. CONCLUSIONS: FMF attacks significantly impair the physical activity of patients. Activity tracking may be a reasonable method to document FMF attacks. This might prevent errors due to memory bias and help accurately identify and treat patients with FMF.

Increased incidence of spondyloarthropathies in patients with Takayasu arteritis: a systematic clinical survey.

OBJECTIVES: Takayasu arteritis and Spondyloarthritis are two distinct inflammatory diseases that affect the same age periods. Increasing number of reports on co-incident Takayasu arteritis-spondyloarthritis cases in literature raised the hypotheses about their association. The purpose of this study is to evaluate the incidence of spondyloarthropathy spectrum diseases in Takayasu arteritis patients. METHODS: Detailed clinical and demographic features of Takayasu arteritis patients were recorded and all were screened meticulously for the presence of spondyloarthropathy features following recommendations of Assessment of SpondyloArthritis international Society. Patients were questioned for inflammatory back pain, enthesitis, uveitis, inflammatory bowel disease, peripheral arthritis, and investigated accordingly with HLA-B27, plain X-rays and sacroiliac magnetic resonance imaging. RESULTS: A total of 69 Takayasu arteritis patients (65 female, 94.2%) were enrolled. After detailed investigation, 14 (20.3%) Takayasu arteritis patients fulfilled the Assessment of SpondyloArthritis international Society criteria for Spondyloarthropathy. Two of 14 (14.2%) spondyloarthropathy patients were positive for HLA-B27. Type 1 and type 2 Takayasu arteritis were more common in patients with diagnosis of both Takayasu arteritis and spondyloarthropathy than those without spondyloarthropathy. Most of patients with diagnosis of both these diseases required biologic therapies than patients with diagnosis of Takayasu arteritis alone (64.3% vs 29.1%, P = 0.014) due to refractory Takayasu arteritis. CONCLUSION: Our results suggest a significant association between Takayasu arteritis and spondyloarthropathy. Possible shared genetic or immunopathogenic processes may explain this association, which merits further investigations.

Effect of interleukin-1 antagonists on the quality of life in familial Mediterranean fever patients.

BACKGROUND: Familial Mediterranean fever (FMF) patients suffer from chronic complications of disease such as AA amyloidosis, chronic arthritis, and spondylitis. Reduced quality of life (QoL) is a feature of chronic diseases but it is also impaired in patients with FMF. Despite the regular use of colchicine at a maximal dose, about 10% of patients do not respond well or resistant to colchicine (crFMF). IL-1 inhibitors have been shown to be effective in controlling attacks in crFMF patients. Herein, we aimed to investigate QoL changes of crFMF patients with IL-1 inhibitors. METHODS: All patients were prospectively monitored for the frequency, duration, severity of attacks, patient global assessments (Visual Analog Scale; VAS), and laboratory features. Either anakinra or canakinumab was used as IL-1 antagonist treatments. Demographic information, MEFV gene mutations, attack characteristics, and previous treatments were registered. Short form-36 (SF-36) quality of life scale was implemented by the interviewer for evaluating the QoL before and 3 months after the treatment. RESULTS: A total of 44 patients were included in this study. Striking improvements were detected in frequency, duration, and VAS severity of attacks (p < 0.001). In the comparison of pre- and post-treatment, SF-36 sub-components significant improvements were observed on physical function, role limitation due to physical difficulty, role limitation due to emotional problem, energy, emotional well-being, social function, pain, general health, and health change. CONCLUSIONS: In conclusion, IL-1 antagonists prevent attacks and improve QoL of crFMF.

Efficacy and safety of interleukin-1 inhibitors in familial Mediterranean fever patients complicated with amyloidosis.

BACKGROUND: Colchicine is the mainstay of the treatment of familial Mediterranean fever (FMF). However, 10% of FMF patients do not respond well to colchicine. Efficacy of interleukin (IL)-1 inhibitors in reducing attacks have been demonstrated in colchicine-resistant FMF (crFMF) patients recently. Colchicine is still the only approved drug for the prevention of amyloidosis in FMF and utility of IL-1 inhibitors in crFMF cases who already has amyloidosis remain to be elucidated. Herein, we evaluated efficacy and safety of IL-1 inhibitors in patients with crFMF-associated AA amyloidosis in a relatively large single center study. METHODS: Medical records of FMF patients complicated with AA amyloidosis in our dedicated FMF center were retrospectively reviewed and those patients who ever treated with IL-1 inhibitors were enrolled into the study. Patient global, physician global assessments (on 0-10 cm visual analog scale), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatinine and 24-h urinary protein excretion values for each visit were recruited from computer-based hospital records. Treatment response of patients were assessed with clinical symptoms, serum albumin, CRP and ESR values. Renal outcome parameters were analyzed on those not receiving renal replacement therapy. RESULTS: Seventeen patients were identified with crFMF-amyloidosis that ever treated with IL-1 inhibitors. Background colchicine therapy was continued in all patients in maximal-tolerated dose along with IL-1 inhibitors. All patients benefit from IL-1 antagonists assessed by patient and physician global assessments. Inflammatory markers, CRP and ESR, were significantly reduced in all and normalized in 12 out of 17 patients. More importantly, the amount of proteinuria was remarkably improved following IL-1 inhibitor therapy (1606 mg/day to 519 mg/day, p = .008). Both anakinra and canakinumab were well-tolerated without severe side effects. All patients were initially treated with anakinra but switched to canakinumab in seven patients (one leukopenia, four injection site reaction, two inefficacy). CONCLUSION: We evaluated the clinical and laboratory responses to IL-1 inhibitors in crFMF-associated amyloidosis patients. We found significant decreases in CRP, ESR and proteinuria after IL-1 inhibitor therapy. This study confirmed that IL-1 inhibitors are effective for controlling attacks and inflammatory activity in FMF patients complicated with AA amyloidosis. Moreover, they reduce or stabilize amount of proteinuria and preserve renal function in short-term follow-up. Prolonged prospective clinical trials are warranted to assess their long-term efficacy in this particular patient group.

On demand use of anakinra for attacks of familial Mediterranean fever (FMF).

To evaluate the efficacy of on-demand use of anakinra in patients with crFMF. The Gazi FMF cohort was established in the year 2010, and from that date, 689 patients with FMF diagnosed according to the Tel Hashomer criteria were registered. Attack type, duration, severity, and their impact on life were collected either by disease diaries or a mobile phone application (FMF AIDD, AppStore, and Playstore). A retrospective cohort analysis was made from records of patients who have ever been treated with IL-1 inhibitors. A total of 78 patients were treated with IL-1 inhibitors in our cohort. Among these, 15 patients were identified who received on-demand anakinra. Rationale for on-demand use was prominent prodrome or trigger for attacks and patient's personal claim. Six patients were switched from regular use and nine were directly started as on-demand use. All were using background colchicine in maximum tolerated doses. None of the patients had evidence of persistently elevated acute phase reactants or proteinuria. The median duration of on-demand anakinra use was 6 (3-36) months. Pre- and post- on-demand anakinra periods were compared. Patient reported attack severity (p = 0.002), duration (p = 0.001), frequency (p = 0.001), absenteeism (p = 0.002), and presenteeism (p = 0.002) were significantly improved. On-demand anakinra prevented progression of prodromes to full-blown attacks which was demonstrated by decrease in the rate of attack/prodrome ratio (p = 0.02). On-demand anakinra can be continued in ten subjects on long-term. On-demand anakinra significantly improved FMF attacks in certain patients which suggest this approach would be of benefit in daily practice in selected patients.

Clinical characteristics of avascular necrosis in patients with Behçet disease: a case series and literature review.

Avascular necrosis (AVN), also known as osteonecrosis, is characterized by death of the osteocytes due to inadequate blood supply caused by various mechanisms. The hip is the most common affected joint followed by knee. Incidence of AVN in rheumatic diseases is variable and high corticosteroid (CS) therapy is a known major risk factor for development of AVN. Data on the AVN in Behçet disease (BD) are limited. The purpose of this study is to examine the clinical and treatment characteristics of BD patients with diagnosis of AVN. Retrospective medical records of 337 BD patients were reviewed. Nine BD patients with AVN were detected. The clinical data of these patients with AVN have been reviewed. All patients had MRI of the symptomatic joints compatible with AVN. All of the nine patients who were diagnosed with AVN were male. Median duration of BD was 7 years. Median time between diagnosis of BD and detection of AVN was 3 years (1-16 years). Multiple joints were involved in seven patients. Six patients had bilateral knee AVN. Six patients had vascular BD. The median time interval between initial CS dose and AVN development was 24 months (range = 2-100). The median highest daily CS dose was 64 mg/day (range = 32-80) and median cumulative CS dose prior to AVN was 18 g. All of patients had intravenous pulse steroids. CS treatment, smoking and vascular involvement may predispose to AVN in patients with BD. According to this cohort, AVN in BD frequently tended to be in the knee joint and bilateral.

Platelet/lymphocyte ratio and mean platelet volume in patients with granulomatosis with polyangiitis.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a granulomatous necrotizing vasculitis with high morbidity and mortality. Anti-neutrophil cytoplasmic antibody is a valuable diagnostic marker, however its titer lacks predictive value for the severity of organ involvement. Platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) has been regarded as a potential marker in assessing systemic inflammation. We aimed to explore the value of PLR and MPV in the assessment of disease activity and manifestations of disease in GPA. METHODS: 56 newly diagnosed GPA patients and 53 age-sex matched healthy controls were included in this retrospective and cross-sectional study with comparative group. Complete blood count was performed with Backman Coulter automatic analyzer, erythrocyte sedimentation rate (ESR) with Westergen method and C-reactive protein (CRP) levels with nephelometry. The PLR was calculated as the ratio of platelet and lymphocyte counts. RESULT: Compared to control group, ESR, CRP and PLR were significantly higher and MPV significantly lower in GPA patients. In patients group, PLR was positively correlated with ESR and CRP (r = 0.39, p = 0.005 and r = 0.51, p < 0.001, respectively). MPV was negatively correlated with ESR and CRP (r = - 0.31, p = 0.028 and r = - 0.34 p = 0.014, respectively). Patients with renal involvement had significantly higher PLR than patients without renal involvement (median:265.98, IQR:208.79 vs median:180.34 IQR:129.37, p = 0.02). PLR was negatively correlated with glomerular filtration rate (r = - 0.27, p = 0.009). A cut-off level of 204 for PLR had 65.6% sensitivity and 62.5 specificity to predict renal involvement. CONCLUSION: PLR exhibit favorable diagnostic performance in predicting renal involvement in patients with GPA.

Associations between Depressive Disorders and Inflammatory Rheumatic Diseases.

Depressive disorders, are not only common but also among the leading causes of disability worldwide. They are associated with increased incidences of various other diseases. It has been shown that in patients with autoimmune diseases, when depression coexists, the quality of life is worse and medical treatment and management is compromised. Depression-like symptoms, such as fatigue and disinterest are also common in inflammatory rheumatic diseases and often associated with poor quality of life. Medical therapy targeting inflammation results in alleviation of these symptoms in many patients. Interestingly, there is cumulating evidence suggesting potential roles of inflammatory cytokines in the pathogenesis of major depression. Effects of some of the biological agents used in rheumatic diseases have been studied on depressive disorders. Results have been controversial and further studies are needed in this area. These findings suggest associations between depression and inflammatory rheumatic diseases and raise the possibility that treatment of one of them might influence the outcome of the other. We have reviewed the current literature on associations between depression and inflammatory rheumatologic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome and ankylosing spondylitis.

Acute lupus choroidopathy: multimodal imaging and differential diagnosis from central serous chorioretinopathy.

IMPORTANCE: Systemic lupus erythematosus (SLE) is a thoroughly examined multi-organ disease whose common ocular complications are also well documented. However, SLE choroidopathy, being a rare ocular complication, is needed to be better understood, in order to make the differential diagnosis from clinical conditions such as central serous chorioretinopathy and provide adequate prompt treatment. OBJECTIVE: To provide a clear understanding for the clinical course of SLE choroidopathy by the help of enhanced depth imaging optical coherence tomography, fluorescein angiography, and indocyanine angiography. DESIGN: The study is designed as a case presentation, consisting of the physical examination results and the data gathered by the relevant screening methods for each visit, applied by the same ophthalmologists and technicians. SETTING: The visits were organized as same day examinations as needed, in a university hospital which works as a referral center.