We have demonstrated that moderate alcohol consumption  for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. We now report on the relationships between serum estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) levels after 4 weeks of moderate alcohol supplementation, and compare the results to the 8 weeks data to elucidate time-to-effect differences.Postmenopausal women (n = 51) consumed 0 (placebo), 15 (1 drink), and 30 (2 drinks) g alcohol (ethanol)/ day for 8 weeks as part of a controlled diet in a randomized crossover design. Blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Changes in estrone sulfate and DHEAS levels from placebo to 15 g and 30 g alcohol per day were estimated using linear mixed models.At week 4, compared to the placebo, estrone sulfate increased an average 6.9% (P = 0.24) when the women consumed 15 g of alcohol per day, and 22.2% (P = 0.0006) when they consumed 30 g alcohol per day. DHEAS concentrations also increased significantly by an average of 8.0% (P < 0.0001) on 15 g of alcohol per day and 9.2% (P < 0.0001) when 30 g alcohol was consumed per day. Trend tests across doses for both estrone sulfate (P = 0.0006) and DHEAS (P < 0.0001) were significant. We found no significant differences between the absolute levels of serum estrone sulfate at week 4 versus week 8 (P = 0.32) across all doses. However, absolute DHEAS levels increased from week 4 to week 8 (P < 0.0001) at all three dose levels.These data indicate that the hormonal effects due to moderate alcohol consumption are seen early, within 4 weeks of initiation of ingestion. Epidemiological evidence consistently shows a positive association between alcohol, even low to moderate intake, and breast cancer risk . HoweverA reanalysis of nine prospective studies shows that levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women . Clear eDetails of the Women's Alcohol Study (WAS) was previously published . BrieflyBlood for hormone analyses was collected after an overnight fast at weeks 4 and 8. Serum was separated, and aliquots were frozen at -70°C. In the samples taken after 4 weeks of alcohol supplementation, we only measured serum estrone sulfate and DHEAS, as they were the only two hormones that were significantly elevated at 8 weeks [Hormone concentrations were transformed using natural log. Changes in hormone concentrations from placebo to 15 g and 30 g of alcohol per day were estimated at 4 and 8 weeks using linear mixed models including a random intercept and alcohol levels as fixed effects treated as two indicator variables. Separate models used alcohol as a continuous variable to test for trend. Regressions to evaluate the effect of several baseline covariates on the precision of the parameter estimates for alcohol consumption included age, BMI, and years since menopause modeled as continuous fixed effects; assignment order, dietary period, hysterectomy, and race were modeled as indicator variables. Effect modification by race, assignment order, dietary period, age, BMI, and years since menopause were assessed by likelihood ratio tests of improvement in the model fit after addition of cross-product terms to models that included main effects for alcohol and the characteristic being evaluated. All tests of statistical significance were two-sided. Statistical analyses were performed using S-PLUS (S-PLUS version 6.1 for Windows. Seattle (WA): Insightful Corporation; 2002.)Table The effects of alcohol supplementation on serum estrone sulfate and DHEAS levels did not vary with age, BMI, race, or years since menopause. These hormone concentrations also did not differ among the three dietary periods, and the order of the assignment to the treatment regimens did not modify the associations with either of the two hormones.At 8 weeks of alcohol intake, the 15 g dose versus the placebo increased serum estrone sulfate and DHEAS by 7.5% and 5.1% respectively, whereas the 30 g dose compared to the placebo, increased levels of estrone sulfate and DHEAS by 10.7% and 7.5% respectively. When comparisons using linear mixed models are made, after controlling for alcohol intake across all doses, there was no statistically significant difference between the absolute levels of serum estrone sulfate at week 4 versus 8 (P = 0.32). However, controlling for alcohol intake absolute DHEAS levels increased between weeks 4 and 8 (P < 0.0001). The increase in DHEAS between weeks 4 and 8 did not occur in just the 15 or 30 g per day groups, however; the increase was similar in each of the three groups. In the 0 g per day group the geometric mean shifted from 55.3 ng/dL at 4 weeks to 59.4 ng/dL at 8 weeks. In the 15 g per day group the geometric mean shifted from 59.7 ng/dL to 62.5 ng/dL, and in the 30 g per day group the geometric mean shifted from 60.4 ng/dL to 63.9 ng/dL. The models did not suggest an interaction between measurement week and alcohol dose in serum estrone sulfate (P = 0.32) or DHEAS (P = 0.58).In postmenopausal women moderate alcohol consumption for four weeks resulted in statistically significant increased levels of serum estrone sulfate, the most abundant circulating estrogen, and DHEAS, the steroid hormone with the highest concentration in the blood. Compared to the placebo, serum estrone sulfate levels increased 6.9% (P = 0.24) and 22.2% (P = 0.0006) respectively among women who consumed 15 g and 30 g alcohol per day for four weeks. Serum DHEAS concentrations also increased by 8.0% (P < 0.0001) and 9.2% (P < 0.0001) respectively among women who consumed 15 g or 30 g alcohol per day for four weeks. At week 8, serum estrone sulfate levels increased 7.5% and 10.7% respectively among women who consumed 15 g and 30 g alcohol per day whereas DHEAS concentrations increased 5.1% and 7.5% respectively among women who consumed 15 g or 30 g alcohol per day compared to the placebo [For DHEAS, the absolute levels were statistically (P < 0.0001) higher at week 8 compared to week 4 in all the alcohol groups. This increase in DHEAS between weeks 4 and 8 did not differ regardless of 0 g, 15 g, or 30 g per day dose (P = 0.58). Biological reasons may explain the increase in the 15 g and 30 g per day alcohol dose, but the reasons behind the increases in DHEAS for the 0 g dose need further research. We did not find any evidence for an effect modification between measurement week and alcohol supplementation in serum estrone sulfate (P = 0.32) or DHEAS (P = 0.58).These data indicate that the hormonal effects due to moderate consumption of alcohol equivalent to one or two drinks per day are seen early, within 4 weeks of initiation of ingestion. Importantly from a study design perspective, our study also demonstrates that it may be possible to utilize shorter study periods when assessing the effects of alcohol consumption on hormone levels, at least in postmenopausal women. To understand the earliest effects of moderate alcohol intake on hormone levels in postmenopausal women, future studies will have to be designed to assess serum levels earlier than 4 weeks or possibly later than 8 weeks.Postmenopausal women with elevated levels of serum estrone sulfate ,9 and DHAlcohol has many physiologic effects and could influence breast cancer risk through non-hormonal mechanisms as well. Experimental evidence suggests that alcohol interferes with folate absorption, transport, and metabolism, potentially limiting folate stores in the tissues and may interfere with DNA methylation ,13. AlcoIn conclusion, our results provide additional evidence for a mechanism by which moderate alcohol drinking could modify breast cancer risk, indicating that this effect occurs after a short time period (as early as four weeks), and thus provides further support for a causal association.None declared.


The risk factors for recurrence of hemorrhagic or ischemic stroke in patients with intracranial hemorrhage (ICH) are inconclusive. This study was designed to investigate the risk factors for stroke recurrence and the impact of antiplatelet on stroke recurrence in patients with ICH. This population-based case-cohort study analyzed the data obtained from a randomized sample of 2 million subjects in the Taiwan National Health Insurance Research Database. The survival of patients with hemorrhagic stroke from January 1, 2000, to December 31, 2013, was included in the study. During the 5-year follow-up period, the recurrence rate of stroke was 13.1% . The recurrence rate of stroke was 13.3% in the without antiplatelet group and 12.6% in the antiplatelet group. The risk factor for hemorrhagic stroke was hypertension (OR 1.87). The risk factors for ischemic stroke were age (OR 2.99), diabetes mellitus (OR 1.28), hypertension (OR 2.68), atrial fibrillation (OR 1.97), cardiovascular disease (OR 1.42), and ischemic stroke history (OR 1.68). Antiplatelet may decrease risk of hemorrhagic stroke (OR 0.53). The risk of stroke recurrence is high in patients with ICH. Hypertension is a risk factor for ischemic and hemorrhagic stroke recurrence. Antiplatelet therapy does not decrease risk of ischemic stroke recurrence but may reduce recurrence of hemorrhagic stroke. The global burden of hemorrhagic stroke is gradually increasing. Risk factors for ICH included hypertension and warfarin use7. The survival outcomes after hemorrhagic stroke include mortality, functional impairment, quality of life impairment, intracerebral hemorrhage recurrence, ischemic stroke, cognitive impairment, psychiatric diseases, and epilepsy8. The annual rate of stroke recurrence after ICH was approximately 5–10%10. However, the report on the type of recurrent stroke after the patients with ICH is inconclusive. Studies have reported that patients with ICH have a higher risk of hemorrhage recurrence than those with ischemic stroke12. Some studies have reported that patients with deep ICH have a higher risk of ischemic stroke recurrence than those with hemorrhagic stroke and those with lobar hemorrhage have an increased risk of hemorrhagic stroke recurrence10. However, some studies have found that the type of recurrent stroke was not significantly different between patients with lobar hemorrhage and those with deep hemorrhage stroke13. Murthy et al. have found that compared with individuals without ICH, patients with ICH have an increased risk of ischemic stroke with a hazard ratio (HR) of 3.114.Though the incidence and mortality rates of stroke with intracranial hemorrhage (ICH) declined gradually15. In patients with ICH who received antiplatelet drugs, the rate of ICH recurrence and hemorrhage volume did not increase17. In contrast, Biffi et al. have found that the use of antiplatelet drugs may increase the risk of ICH recurrence in patients with lobar hemorrhage15.A study has shown that inadequate blood pressure control increases the probability of ICH recurrenceStroke recurrence may increase mortality and impair daily activity and function. Presently, the risk factors for ischemic and hemorrhagic stroke recurrence remain inconclusive. Therefore, this study was designed to determine and investigate the risk factors for ischemic or hemorrhagic stroke recurrence and the impact of antiplatelet on stroke recurrence in patients with ICH in Taiwan.This population-based case-cohort study used data from the Taiwan National Health Insurance Research Database (NHIRD) that comprises data obtained from 2 million individuals. The National Health Insurance (NHI) program in Taiwan has been operating since 1995. The NHIRD is a research database developed by the NHI Research Institute and contains patient healthcare data from hospitals, outpatient clinics, and community pharmacies. NHI encompasses more than 99% of 23 million individuals and 95% of the hospitals in Taiwan. The NHI Research Institute provides the database to researchers after anonymizing all personal information. This study included data retrieved from the “Longitudinal Health Insurance Database” (LHID 2005) from a random sample of 2 million individuals within the NHIRD, with linked longitudinal data available from 2000 to 2013. The randomized data (LHID 2005) represent all beneficiaries as no significant differences in sex, age, and premium rate are found between individuals in the LHID 2005 and the original NHIRD datasets. The codes of the International Classification of Diseases, Ninth Revision (ICD-9) were used to define diseases. This study was approved by the Institutional Review Board of Ditmanson Medical Foundation Chiayi Christian Hospital, Taiwan (CYCH-IRB: 2020131). Due to the anonymity of the NHIRD, the requirement for informed consent from each patients was waived by the IRB of Ditmanson Medical Foundation Chiayi Christian Hospital.18. All hospitalized patients with the diagnosis of hemorrhagic stroke (ICD-9 codes: 430 and 431) between January 1, 2000 and December 31, 2013 were included in the study. Recurrent hemorrhagic stroke was defined as patient re-hospitalization with a discharge diagnosis of hemorrhagic stroke (ICD-9 codes: 430 and 431). Recurrent ischemic stroke was defined as patient re-hospitalization with a discharge diagnosis of ischemic stroke . Stroke risk factors were defined as the following disease diagnosis during discharge in patients with hemorrhagic stroke: hypertension , diabetes mellitus , atrial fibrillation , cardiovascular disease , congestive heart failure , and dyslipidemia . All patients underwent computed tomography or magnetic resonance imaging to confirm the occurrence of stroke. The exclusion criteria were as follows: (1) patients younger than 20 years; (2) those who had a history of hemorrhagic stroke; (3) those who continue to use antiplatelet drugs for more than 7 days 1 month before the onset of hemorrhagic stroke; (4) those with stroke recurrence within 1 month before hemorrhagic stroke onset; and (5) those who died within 1 month after stroke onset.Hemorrhagic stroke was defined as an episode of rapidly developing neurological deficit attributed to the focal collection of blood within the brain parenchyma or ventricular system (ICH) or due to subarachnoid bleeding (subarachnoid hemorrhage) not caused by traumaIn total, 12,053 patients were hospitalized under the discharge diagnosis of hemorrhagic stroke. Among them, 75 patients were younger than 20 years, 1876 patients used antiplatelet drugs for more than 7 days within 1 month before stroke onset, 127 patients had stroke recurrence within 1 month after stroke onset, and 2386 patients died within 1 month after stroke onset, all of whom were excluded from this study. Finally, 7589 patients were included in the study . The baseline characteristics of the patients as categorical variables were compared using the chi-square test. Continuous variables were compared using the t-test. Cox proportional hazards regression models were used to evaluate the HRs and 95% confidence intervals (CIs) for the recurrence of ischemic and hemorrhagic stroke in each risk factor. All statistical analyses were performed using SAS statistical software . From 2000 to 2013, 7589 patients fulfilled the inclusion criteria for this study. The characteristics of the 7589 patients are shown in Table P < 0.01), while the recurrence rates of ischemic stroke were5.53% (306/5529) and 7.72% (159/2060) (P < 0.01) respectively.During the 5-year follow-up period, stroke in 997 patients recurred; the recurrence rate of stroke was 13.1% (997/7589), of whom 7.01% (532/7589) had hemorrhagic stroke and 6.12% (465/7589) had ischemic stroke. The rate of stroke recurrence was 13.3% (737/5529) in the without antiplatelet group and 12.6% (260/2060) in the antiplatelet group. Moreover, the rate of hemorrhagic stroke recurrence was lower in the antiplatelet group and the rate of ischemic stroke recurrence was higher in the antiplatelet group. The recurrence rates of hemorrhagic stroke were 7.79% (431/5529) and 4.9% (101/2060) in the without antiplatelet and antiplatelet groups  in patients aged between 45 and 59 years and 2.99 (95% CI 1.91–4.68) in patients aged ≥ 60 years. The HR of ischemic stroke was 1.28 (95% CI 1.04–1.57) in patients with diabetes mellitus, 2.68 (95% CI 1.55–4.63) in patients with hypertension, 1.97 (95% CI 1.40–2.76) in patients with atrial fibrillation, 1.42 (95% CI 1.15–1.74) in patients with cardiovascular disease, and 1.69 (95% CI 1.18–2.40) in patients with a history of ischemic stroke. The antiplatelet group did not reduce risk of ischemic stroke with an HR of 0.90 (95% CI 0.74–1.09) (Table The factors for hemorrhagic stroke recurrence included hypertension. The HR of hemorrhagic stroke was 1.87 95% CI 1.32–2.64) in patients with hypertension. After adjusting for possible confounding factors , the use of antiplatelet drugs was found to decrease the risk of hemorrhagic stroke with an HR of 0.53 (95% CI 0.42–0.66) .The risk factors for ischemic stroke recurrence were age, sex, diabetes mellitus, hypertension, atrial fibrillation, cardiovascular disease, and ischemic stroke history. The HR of ischemic stroke was 1.98 (95% CI 1.10–3.57) in patients aged between 45 and 59 years and 2.49 (95% CI 1.38–4.47) in patients aged ≥ 60 years. The HR of ischemic stroke was 2.24 (95% CI 1.27–3.93) in patients with hypertension, 1.87 (95% CI 1.30–2.71) in patients with atrial fibrillation, 1.42 (95% CI 1.15–1.77) in patients with cardiovascular disease, and 1.56 (95% CI 1.06–2.30) in those with a history of ischemic stroke. The antiplatelet group did not reduce the risk of ischemic stroke with an HR of 0.80 (95% CI 0.70–1.05) (Table The factors for hemorrhagic stroke recurrence included hypertension. The HR of hemorrhagic stroke was 1.87 (95% CI 1.32–2.64) in patients with hypertension. The use of antiplatelet drugs was found to decrease the risk of hemorrhagic stroke with an HR of 0.52 (95% CI 0.42–0.66) (Table The main findings of this study include the following: (1) in patients with ICH stroke, the 5-year rate of stroke recurrence was 13.1%; (2) stroke recurrence was more frequent in patients with hemorrhagic stroke than that in patients with ischemic stroke with a ratio of 1.13; (3) antiplatelet therapy cannot decrease the risk of ischemic stroke but may decrease the risk of hemorrhagic stroke recurrence; (4) hypertension may increase the risk of hemorrhagic and ischemic stroke recurrence.10. Bailey et al. reviewed data with a mean follow-up of 3.4 person-year and found that the rate of hemorrhagic stroke recurrence was 8.35% (157/1880) and 2.4% per patient-year11. In a study with a follow-up duration of less than 5 years, Vermeer has reported that the rate of hemorrhagic stroke recurrence was 12% (30/243) and the annual rate of ICH recurrence was 2.1%19. In this study, with a follow-up duration of less than 5 years, the rate of hemorrhagic stroke recurrence was 7.01%, with incidence 1.64–1.95 patient-years in each age group, which is mildly lower than that reported in a previous study. The difference may be due to the stroke type. Studies have shown that patients with lobar hemorrhage have a higher risk of hemorrhage recurrence than those with deep hemorrhage12. Vermeer has reported a higher rate of hemorrhagic stroke recurrence than this study; the difference may be related to the higher proportion (55%) of patients with lobar hemorrhage in Vermeer’s study19.Studies have shown that in patients with ICH stroke who were followed for less than 3–5 years, the rate of hemorrhagic stroke recurrence was between 7 and 12%. In a single-center study, with a mean follow-up period of less than 3.6 years, Hill et al. have found that the rate of hemorrhagic stroke recurrence was 8.72% (15/172)19 but lower than that found in another study13. In a study with a 5-year follow-up period, Casolla et al. have found that the cumulative rate of ischemic stroke recurrence was 9.8%. The difference could be because the patients in this study was younger than those in Casolla et al.’s study , and this study included patients with subarachnoid hemorrhage. Moreover, patients with hemorrhagic stroke have a higher risk of ischemic stroke recurrence than those without stroke history. Murthy et al. have found that patients with a history of hemorrhagic stroke had a higher risk of ischemic stroke recurrence than those without hemorrhagic stroke history, with an HR of 3.114.The rate of ischemic stroke recurrence was 6.12% in patients who did not use antiplatelet drugs. The rate of ischemic stroke recurrence was close to that reported by Vermeer et al.11. However, some studies have found that ischemic stroke is more frequent than hemorrhagic stroke13. Our study found that hemorrhagic stroke was more frequent than ischemic stroke. The difference may be related to patient characteristics and location of ICH. Studies have found that patients with lobar hemorrhage have a higher risk of ICH recurrence, and deep hemorrhage increases the risk of ischemic stroke recurrence20. ICH is also a risk factor for ischemic stroke recurrence.Some studies have found that patients with hemorrhagic stroke have a higher risk of brain hemorrhage than those with ischemic stroke21. The condition may be because most patients with hemorrhagic stroke have many stroke risk factors, which may affect the recurrence of ischemic and hemorrhagic stroke (Table It is reasonable to consider that antiplatelet therapy may increase the risk of hemorrhage and decrease the risk of ischemic stroke. However, this study found that antiplatelet therapy did not decrease the risk of ischemic stroke but may decrease the risk of hemorrhagic stroke. The result agrees with those reported in a previous study. Murthy et al. have found that antiplatelet therapy did not affect mortality and clinical outcomes in patients with ICHThe study found that hypertension may increase the risk of hemorrhagic and ischemic stroke recurrence. Age, atrial fibrillation, cardiovascular disease, and history of ischemic stroke are also risk factors of ischemic stroke recurrence. Intensive control blood pressure may decrease the risk of ischemic and hemorrhagic stroke recurrence.This study has several limitations. First, this was a retrospective study; we did not have data regarding deep hemorrhage or lobar hemorrhage. Second, stroke recurrence was based on the diagnosis of ischemic or hemorrhagic stroke among hospitalized patients, which may have underestimated the rate of stroke recurrence. Third, information on stroke risk control, such as blood pressure, blood sugar, and blood lipid level, was unavailable, which may have affected the rate of stroke recurrence and stroke type. Fourth, this is a retrospective observational study, we cannot rule out the possibility that antiplatelet agent were prescribed to the patient whom less likely to have recurrence of hemorrhagic stroke.In conclusion, the risk of stroke recurrence is high in patients with ICH. Antiplatelet therapy does not decrease risk of ischemic stroke recurrence but may decrease risk of hemorrhagic stroke recurrence. Hypertension is a risk factor of ischemic and hemorrhagic stroke recurrence.Supplementary Information.


The recurrence of bipolar disorder due to poor treatment adherence can be explained by different factors.The poor awareness of the disorder seems to be the major cause.To evaluate insight in patients followed for euthymic bipolar disorders and determine the factors correlated with it,mainly the self-esteem.A cross-sectional descriptive and analytical study of 33 euthymic subjects with bipolar I and II disorders (DSM 5) and followed up at the psychiatric consultation in Hédi Chaker university Hospital of Sfax.Data collection was performed using a sheet exploring socio-demographic and clinical data. We used Birchwood insight scale to assess the quality of insight and Rosenberg’s Self-Esteem scale.The average age of our patients was 44,52±12,99 years old.The sex ratio =0.32.Patients were followed for bipolar I disorder(60.6%).The first episode of the disease was depressive in(51.5%) of cases.The average number of depressive episodes was1.97±1.87.The last episode was depressive in(57.6%) or manic in(42.4%).There were no psychotic characteristics in(42.4%) of cases.The patients had good insight in(54.5%).The average of self-esteem score was27±7.85and it was low in 51.5% of cases.Factors correlated with good insight were bipolar II disorder(p=0.001), high number of depressive episodes(p=0.013) and absence of psychotic characteristics(p=0.003) during the last episode.In addition,good insight was significantly associated with low self-esteem(p=0.023).Our study shows that a poor insight depends mainly on the clinical characteristics of bipolar disorders. Moreover,low self-esteem seems to be linked to it. For this reason, our attention should be focused on psychoeducation to improve insight, especially during episodes, in order to facilitate integration and increase patients’ self-esteem.


This open-label multicentre trial evaluated the efficacy and safety of oral dimethyl fumarate (DMF) in patients with moderate-to-severe plaque psoriasis in real-life clinical practice over 52 weeks. Disease severity and improvement were assessed using the psoriasis area severity index (PASI), body surface area (BSA) affected, and Physician Global Assessment (PGA). Quality of life (QoL) was assessed using the Dermatology Life Quality Index (DLQI) questionnaire. The visual analogue scale (VAS) was used to quantify pruritus and measure treatment satisfaction. A total of 141 patients were included, being 66.7% male, aged 49.1 ± 14.7 years and with disease duration of 16 ± 12.1 years. After 52 weeks, mean PASI decreased from 15.9 ± 6.8 to 1.5 ± 2 and 87.7%, 56.9% and 24.6% of patients achieved PASI 75/90/100 response, respectively. BSA decreased from 26.5 ± 14.8% to 2.7 ± 3.5% at 52 weeks, and 81.5% of patients had a PGA 0-1. DLQI scores decreased from 9.4 ± 6.4 to 2.1 ± 3.3, and VAS of pruritus decreased from 53 ± 28.4 to 19.1 ± 26.2 at Week 52. VAS for treatment satisfaction was 79.4 ± 29.4 at Week 52. A total of 34.2% of patients had an AE leading to permanent discontinuation. These findings show that DMF can significantly improve indices of disease severity, pruritus and QoL, with high levels of patient satisfaction and similar safety profile to other fumarates. Plaque psoriasis is a chronic, inflammatory, immune-mediated skin disease affecting 2–3% of the population worldwide  and haviBiological therapies such as tumour necrosis factor (TNF), interleukin (IL) 12/23 and IL-17 and IL-23 inhibitors have revolutionised the treatment of moderate-to-severe psoriasis allowing many patients to achieve complete remission ,5,6. HowFumaric acid esters (FAEs) are a type of systemic treatment based on small molecules that have demonstrated a good tolerability and efficacy profile in patients with moderate to severe plaque psoriasis ,11,12,13®; Biogen Idec GmbH, Munich, Germany) as an active comparator [®, showing a PASI75 score at 16 weeks of 37.5%, compared with 15.3% for placebo- and 40.3% of Fumaderm®-treated patients. In recent years, DMF has been evaluated in the real-life setting, but these studies are frequently limited by a small number of patients or a short follow-up period [The main clinical evidence evaluating the efficacy of DMF to date is based on the BRIDGE study, a double-blind, randomised, placebo-controlled trial, where DMF was evaluated after 16 weeks’ treatment using fumaric acid esters  treatment in adults with moderate to severe chronic plaque psoriasis up to 52 weeks. This study was conducted by 36 investigators at 36 sites across Italy from May 2018 to November 2020.DIMESKIN-2 was a multicentre, open-label study to evaluate the efficacy and long-term tolerability of DMF  was approved by the local Ethical Committee and registered under EudraCT identifier: 2017-003818-11). All patients provided written informed consent before inclusion in the study, in compliance with Italian Legislative Decree (L. 675/1996).Patients underwent a baseline visit and visits during treatment on week 4, 8, 12, 24, 36, 48 and 52. For each visit, a time frame of 3 days before and after the scheduled date was allowed. Oral DMF treatment was administered as indicated in the summary of product information (SmPC) . In the At any time and in case of significant intolerance based on their perception, patients restored the last tolerated dosage of DMF. Patients were also instructed to inform the Investigator immediately, including communication by telephone. The Investigator was responsible for taking the final decision on the restoration of the dosage or on the possibility of treatment interruption (temporarily or permanently). However, changes in the dosage could be necessary in case of alteration of the laboratory parameters: these changes were implemented by the Investigator based on the indications given in the SmPC of the drug or according to their own medical judgment. From Week 24, if a significant improvement in skin lesions was observed  and if the Investigator deemed it appropriate, the daily dose of DMF was gradually reduced—to the extent of one tablet less a day every two months—until the maintenance dose required by the patient’s condition was reached. From Week 24, the use of anti-H1 antihistamines, emollients without salicylic acid and emollients containing less than 10% urea was allowed.The primary objective of this study was to evaluate the efficacy of DMF in adult patients affected by moderate-to-severe chronic plaque psoriasis in terms of the proportion of patients achieving a ≥75% reduction from baseline of the Psoriasis Area and Severity Index (PASI) index after one year of treatment. Secondary objectives included the evaluation of the evolution of psoriasis at each visit over the 52 weeks using the PASI, Physician’s Global Assessment (PGA) and Body Surface Area (BSA). The PGA provides an evaluation of treatment efficacy by means of a score ranging from 0 (no sign of psoriasis) to 5 (severe psoriasis) .Quality of life was assessed using the Dermatology Life Quality Index (DLQI) at each visit over the treatment period. The DLQI questionnaire is based on 10 questions and provides an evaluation of a patient’s QoL by means of a score ranging from 0 (no disease impact) to 30 (maximum disease impact) . The higPruritus/itching and grade of satisfaction were evaluated at each visit by means of the visual analogic scale (VAS). Pruritus VAS is a visual method to assess the intensity of itching. The patient was asked to place a single mark along a 100 mm line; the left extremity represents the absence of itching  and the right one unbearable itching . VAS was also used to assess satisfaction of treatment over the 52 weeks, where a VAS of 0 represents complete lack of satisfaction and a VAS of 100 represents complete satisfaction.The following safety parameters were monitored/collected during the study: treatment exposure and dosage, concomitant medications, adverse events, safety laboratory tests including haematology, clinical chemistry and urinalysis locally assessed at each participating site, vital signs, physical examination, and pregnancy test.p-value of <0.05 was considered statistically significant. Statistical analysis was performed using SAS®  for Windows release 9.4 (64-bit) or later.Three hundred patients were planned to be enrolled in the present study. Defining as success the achievement of a ≥75% reduction from baseline in the PASI index at Week 52 (primary endpoint of the study), the sample size was determined in order to calculate the 95% confidence interval (CI), two-tailed, for the expected success rate of 50%. In order to obtain an accuracy of the estimate of the proportion of patients less than or equal to ±6.9%, 200 patients were to be enrolled in the present study. Considering a 35% expected dropout rate, the sample size was adjusted to 300 patients according to the Friedman formula: n’ = 100 × n/100 − x, where x is the expected dropout rate . Data arn = 75; 53.2%), and topical creams were the most frequent treatments  followed by systemic treatment in 28 (19%) patients. Among the 75 patients with at least one prior psoriasis treatment, the mean time from the end of the last prior psoriasis treatment to the start of the study treatment was 71.2 ± 43.7 days. Abnormal physical examinations were reported in a small proportion of patients at baseline visit .In this multicentre single-arm phase IIIb study, a total of 141 patients with moderate-to-severe psoriasis were treated with DMF for a period of 1 year. Of the 141 patients who initiated treatment, 66 (46.8%) completed the study. Baseline characteristics of patients are presented in p < 0.0001 for each visit) (n = 141). This result was also confirmed following the LOCF approach, showing a PASI75 at Week 52 of 81.1% .Mean PASI total score decreased from 15.9 ± 6.8 at baseline to 1.5 ± 2. after 52 weeks, equating to an absolute change from baseline of −13.1  A. This dh visit) A. At 52 h visit) B. For thp < 0.0001) according to respective linear mixed effects models for repeated measures by visit.The mean PGA index decreased from 3.4 ± 0.65 at baseline to 0.95 ± 0.78 after 52 weeks, resulting in a mean absolute change of −2.3 ± 0.87 A. PGA inp < 0.0001) according to the linear mixed effects model for repeated measures.Mean DQLI total score decreased from 9.4 ± 6.4 at baseline to 2.1 ± 3.3 after 52 weeks, resulting in a mean absolute change from baseline equal to −6.63  A. This dp < 0.0001) according to linear mixed effects model for repeated measures. We also assessed patient satisfaction with regard to study treatment evaluated by the satisfaction VAS score, and it was observed to be similar at Week 24 and Week 52, being 79.9 ± 23 and 79.4 ± 29.4, respectively.Mean pruritus VAS score decreased from 53 ± 28.4 at baseline to 19.1 ± 26.2 at Week 52, resulting in a mean absolute change from baseline equal to −31.3  B. This dMean duration of exposure was 6.9 ± 5 months. All patients took 30 mg as the initial daily dosage, except for one patient who started the study treatment with 600 mg for three days. The patient interrupted treatment due to an AE and re-started with a daily dosage of 30 mg as per protocol. Mean daily dose of DMF increased over the first 9 weeks of treatment according to indication and as indicated in the SmPC  and was Four patients (2.53%) permanently discontinued treatment due to severe treatment-emergent serious adverse events: three patients (1.9%) due to lymphopenia and one patient (0.63%) due to generalised exfoliative dermatitis. The most commonly occurring AEs were related to ‘Gastrointestinal disorders’ reported by 59.5% of patients, ‘Skin and subcutaneous tissue disorders’ reported by 36.7% of patients, ‘Blood and lymphatic system disorders’ reported by 25.9% of patients, ‘Infections and infestations’ reported by 20.9% of patients and ‘Nervous system disorders’ reported by 17.19% of patients. The analysed haematology, biochemistry and urinalysis parameters were normal at each visit with the exception of white blood cells and absolute lymphocytes, which slightly decreased from screening to Week 52.®) in patients suffering from moderate-to-severe chronic plaque psoriasis.This multicentre, single-arm, phase IIIb study investigated the efficacy and tolerability of DMF treatment  at 52 weeks of treatment. According to the multiple imputation (MI) approach, the percentage of patients achieving PASI75 at 52 weeks was found to be 86.67% in the ITT population. Similar results were observed following the last observation carried forward (LOCF) approach, while the analysis of the PP population further corroborated these findings. The LOCF approach gave a PASI75 of 81.08%, which is confirmatory of the results obtained through the MI approach.®) as an active comparator [®, showing a PASI75 score at 16 weeks of 37.5%, compared with 15.3% for placebo- and 40.3% of Fumaderm®-treated patients. In the current study, a higher PASI75 value was reported at 52 weeks (87.7%), suggesting a sustained clinical efficacy for DMF in reducing psoriasis severity. Previous studies have shown similar results regarding short- and long-term efficacy of oral FAEs. One retrospective study demonstrated a PASI75 of 76% after 1 year of FAEs treatment [The main clinical evidence regarding the efficacy of DMF so far has been established in a double-blind, randomised, placebo-controlled trial (BRIDGE), where DMF was evaluated after 16 weeks’ treatment, using fumaric acid esters  is considerably affected by dermatological diseases, including psoriasis . The DLQA statistically significant decrease by visit in itching was also recorded based on the pruritus VAS scale (0–100), resulting in a mean absolute change from baseline equal to −31.27  after 52 weeks of treatment. Pruritus is considered one of the most bothersome symptoms in psoriasis, with a prevalence of 60–93% of patients . This stImportantly, treatment satisfaction was high, as reported by patients in a VAS (0–100) scale, being 79.9 ± 23 and 79.4 ± 29.39, at 24 and 52 weeks of treatment, respectively. High treatment satisfaction contributes to improved adherence to treatment, affecting treatment effectiveness in clinical practice .The safety population of this study comprised 158 patients who took at least one dose of the study treatment. Overall, mean exposure time was 6.9 months. Given that most AEs first occur and are most frequent during the first few months of treatment, exposure time in this study is considered adequate to evaluate the safety profile of DMF . Due to The mean daily dose increased as expected during the first weeks of treatment; however, it was lower than expected after Week 4. A mean daily dose of 350.6 ± 201.5 mg was reached at Week 52. In another multicentre study performed in Italy, Corazza and colleagues used a mean daily dose of 262.1 ± 190.9 mg and just over 40% of patients achieved a PASI 75 response by 26 weeks, suggesting that the lower dose may have limited the efficacy observed . Interes®, while 23 serious TEAEs were reported in 3.2%, 2.8% and 3.6% of patients in the DMF, Fumaderm®, and placebo groups, respectively [Based on the observation of AEs, 89.24% of patients reported at least one treatment-emergent adverse event (TEAE), and 4.43% reported at least one serious TEAE. One serious TEAE  lead to one patient’s death, which was assessed as ‘unrelated’ to treatment. Most common adverse events were gastrointestinal disorders, reported mainly as cases of diarrhoea, nausea and abdominal pain, and other skin disorders, mostly erythema. Previous observations from other studies also point towards a similar safety profile regarding DMF and FAE treatment. Overall incidence of AEs in the BRIDGE study was demonstrated to be approximately 84%, both for DMF and Fumadermectively . In the ectively , 86% of ®-treated patients discontinued the study, with the main reason being occurrence of adverse events, observed in 23% and 24% of patients, respectively [Permanent treatment interruption due to TEAEs was reported for 54 patients (34.2%), primarily due to gastrointestinal disorders  with similar rates observed by Pezzolo et al. recently in a real-world study . High diectively . Gastroiectively . In geneectively .® group reported lymphopenia [Leukopenia and lymphopenia may occur under treatment with FAEs and are reported as ‘very common’ side effects in the study product’s SmPC . In thisphopenia . After lphopenia . FAE-indphopenia . Followiphopenia .®, the European expert consensus recommends monitoring visits to be scheduled every 3 months and a complete blood count with differential to be performed [Here, laboratory data evaluation revealed that white blood cell and lymphocyte count slightly decreased from baseline visit to Week 52. The European S3 guidelines recommend measuring full blood count, liver enzymes, serum creatinine, urine sediment, and performing a pregnancy test before starting FAEs and every four weeks during treatment. If leucocytes drop below 3000/μL and lymphocytes below 500/μL, the dose must be reduced, or the treatment should be discontinued . For Skierformed .Given that a high proportion of psoriasis patients (particularly those with moderate-severe disease) are burdened with co-morbidities as well as psoriasis lesions in difficult-to-treat areas , recent evidence suggests that DMF can also be effective in these cases ,43, alloThere were some limitations in this study that should be mentioned. The planned number of participants in the study was not reached and discontinuation rate was high, as out of the 165 patients enrolled, 99 (60%) discontinued the study. Of these, 54% discontinued due to AEs. Due to the high discontinuation rate, the LOCF approach may have ameliorated the reported treatment effect. Additionally, the MI approach implemented the Missing At Random (MAR) assumption in order to adjust the analysis with regard to the missing data. However, the primary challenge was that the MAR assumption cannot be evaluated since there is no knowledge of missing data, therefore it was impossible to make comparisons of observed and missing data to check for any systematic differences. Although similar results were observed for the primary efficacy measure (PASI 75 response) for the available case, LOCF and MI approaches used, the non-responder imputation approach may have produced more conservative results ,45.Current treatment guidelines on psoriasis include the use of biologics that have demonstrated high efficacy for patients with moderate-to-severe psoriasis. Biologic agents for psoriasis treatment include tumour necrosis factor α (TNF-α) inhibitors, interleukin (IL)-23 inhibitors, IL-12/23 inhibitors, or IL-17 inhibitors . It is r®. In addition, the long-term safety profile of DMF in this study was demonstrated to be similar to the previously described safety profile of Skliarence® and FAEs. Due to known gastrointestinal side effects and the effect of FAEs on white blood cells, caution should be applied in individualised dose titration, lymphocyte count should be monitored, and patient expectations should be managed in order to ensure treatment compliance with minimal side effects. This study confirmed the efficacy and safety of DMF for the treatment of moderate-to-severe psoriasis in the Italian population over a period of 52 weeks. As the efficacy of FAEs has been shown to increase over several months of treatment , the lon


Mean LogMAR BCVA at baseline was 0.23 ± 0.44; it remained stable at 12 and 24 months. At baseline, 64% of patients were treated with oral corticosteroids, this decreased to 29.5% at 12 months (p = 0.001) and to 21.9% at 24 months (p < 0.001). Mean time to prednisone dose of ≤0.2 mg/kg/day was 8.1 ± 2.02 months after baseline. A total of 40.5% of eyes were treated with topical steroids at baseline and this significantly decreased to 5.8% at 12 months. Multiple linear regression model was calculated to predict moderate and severe visual loss; only presenting visual acuity accounted for a unique variance in the model. In conclusion, TNF-α inhibitors achieved rapid disease control while enabling a remarkable steroid-sparing effect in children suffering from chronic uveitis. Presenting visual acuity was the sole predictor of moderate to severe visual loss.We aimed to determine medium and long-term effects of TNF-α inhibitors in patients with pediatric uveitis. This was a retrospective review of medical charts. Included were 50 patients (84 eyes). Mean age at diagnosis was 7.22 ± 4.04 years. At baseline (time of initiation of biologic therapy), all patients had active uveitis. Complete control of uveitis was achieved in 84.52% ( Uveitis in children is less common than in adults and it is usually characterized by being chronic . The smoBiological agents have revolutionized the treatment of systemic and ocular inflammatory conditions. In the Sycamore study  adalimumThe aim of the present study was to examine the medium and long-term effects of TNF-α inhibitors in children with chronic uveitis unresponsive to conventional immunomodulatory treatment (IMT). In addition, we aimed to study the visual outcome among patients with anterior vs. non-anterior uveitis and JIA-related vs. non-JIA-related uveitis. This was a retrospective longitudinal study of a consecutive group of patients suffering from chronic refractory noninfectious uveitis and treated with TNF-α inhibitors. The study included children ≤18 years of age, who failed to respond to treatment with corticosteroids and a conventional IMT with at least 3 months of follow-up after baseline. Baseline was defined as the time when anti-TNF-α therapy was started. Adalimumab , was instituted at a dose of 40 mg subcutaneously and repeated every other week in patients weighing ≥30 kg. In children weighing ˂30 kg, adalimumab was instituted at a dose of 20 mg subcutaneously and repeated every other week. Infliximab  (5 mg/kg intravenously) was administered at baseline, at weeks 2 and 6, and every 4–6 weeks afterwards . All the patients were on a stable dose of steroid-sparing agents for at least 12 weeks before baseline. The study was approved by the institutional review board and included waived informed consent for the chart review. The study was conducted in adherence to the tenets of the declaration of Helsinki.Complete blood counts, liver and kidney function tests, serological tests for hepatitis B and hepatitis C, Mantoux tests ± QuantiFERON tests and chest radiographs were obtained before baseline. Brain magnetic resonance imaging was performed to rule out demyelinating disease in patients with intermediate uveitis.Demographic and clinical data that were collected included gender, age at diagnosis of uveitis, anatomical diagnosis according to the Standardization of Uveitis Nomenclature (SUN) group criteria , associaSnellen’s best-corrected visual acuity (BCVA) was recorded at baseline and at 3, 6, 9, 12 and 24 months after baseline. LogMAR (logarithm of the minimum angle of resolution) notation was used to compute the change in VA. Moderate vision loss was defined as BCVA of ≤20/50 and >20/200 and severe vision loss was defined as BCVA ≤20/200. Ocular complications causing moderate and severe vision loss were collected. Response to treatment, time to first flare, rate of flares in the year preceding baseline and in the first year following baseline, the dose of systemic corticosteroids before and after baseline, and time lapse to prednisone dose of ≤0.2 mg/kg/day were documented.Disease control was defined as the time to first flare after baseline being more than 6 months . Flare wp-value < 0.05.Statistical analyses were performed using SPSS Statistics, version 25.0 . Frequency counts and percentages were generated where appropriate. Tests of normality were performed on the data, and parametric and non-parametric tests were applied as needed. Linear regression was used to model the probability of the occurrence of binary dependent variables . A multiple linear regression model was calculated in order to predict the risk factors for moderate and severe visual loss based on significant factors seen in univariate analysis. Statistical significance was defined as a Included were 50 patients (84 eyes), of whom 35 were females (70%). Mean age at time of diagnosis of uveitis was 7.22 ± 4.04 years (range 2–18). At baseline, all patients had active uveitis. It was anterior in 51 eyes (60.71%), intermediate in 19 eyes (22.61%), and posterior and panuveitis in 7 eyes each (8.33%). Ocular disease was bilateral in 34 (68%) patients. Mean total follow-up time was 4.86 ± 2.82 years (range 1–11 years) and mean follow-up time after baseline was 38.62 ± 31.29 months (range 3–120 months). Twenty-five (50%) patients had follow-up longer than 30 months .Thirty-one patients (62%) had an associated systemic disease; of those, JIA was disclosed in 28 patients (90.32%), whereas psoriasis, sarcoidosis and Behçet disease were diagnosed in one patient each (3.22%).The indication to start biological treatments was active ocular disease due to partial or no response to IMT. Three patients (6%) had additionally active systemic diseases which necessitated the initiation of biological agents. No child was found not to qualify for biological therapy because of abnormal results of blood tests or imaging studies.Complete control of uveitis was achieved with the first biological agent in 71 eyes (84.52%) of 41 patients, after a median of 3 months (IQR 2 months).Adalimumab was used in 45 patients (90%) and infliximab in 5 patients (10%). Median time to introduction of biological agents after institution of conventional IMT was 10 months (IQR 12 months).p < 0.0001).The median number of flares/eye in the year preceding the institution of anti-TNF-α therapy was one flare/year (IQR 1 flare/year) and it decreased to 0 flares/year (IQR 0 flares/year) in the first year after baseline (Twenty eyes (23.8%) experienced flares after a mean of 10.07 ± 11.72 months (range 5 to 24 months); 15 eyes were being treated with adalimumab and 5 eyes with infliximab.p < 0.0001) and 2.84 ± 2.81 mg/day (mean 0.05 ± 0.06 mg/kg) (p < 0.0001 compared to baseline) at 12 and 24 months, respectively. At baseline, 32 patients (64%) were dependent on oral corticosteroids, this decreased to 13 patients (29.5%) at 12 months (p = 0.001) and to 7 patients (21.9%) at 24 months (p < 0.001 compared to baseline)  and it decreased to 3.82 ± 3.02 mg/day (mean 0.19 ± 0.24 mg/kg) (aseline) . Mean tip < 0.0001) and remained stable at 24 months . Median dose of topical steroids decreased from 1.5 drops/day (IQR 1.25) at baseline to a median dose of 0.0 drops/day (IQR 0) at month 12 and remained stable at 24 months (p < 0.0001 in each case)  eyes were treated with topical steroids. This decreased to 4 eyes (5.8%) at 12 months (ch case) .n = 34), five eyes (14.7%) used topical corticosteroids >3 drops daily. No eyes received topical corticosteroids >3 drops daily at 12 and 24 months (p = 0.053).Of all eyes that used topical steroids at baseline  used one IMT drug, of those 42 (89.37%) used MTX and 5 (10.63%) used azathioprine. At 12 and 24 months, 38 (out of 44) patients (82.60%) and 29 patients (out of 32) (90.62%) still used one type of second-line IMT, respectively.p = 0.63) and 0.18 ± 0.41 (p = 0.610) at 12 and 24 months, respectively . The rate of severe visual loss (BCVA ≤ 20/200) remained stable at all time points: (2/69 eyes) (2.9%) at 12 months and 2/66 eyes (3.03%) at 24 months .At baseline, 74 eyes (88.10%) had BCVA ≥20/40, 6 eyes (7.14%) had moderate vision loss and 4 eyes (4.76%) showed severe vision loss. The percentage of eyes with BCVA ≥20/40 remained stable at 12 and 24 months after baseline (60/69 eyes) (86.95%) and 57/66 eyes (86.36%), respectively) (Treatment failure occurred in six patients (12%): two were treated with adalimumab and four with infliximab. The two patients who were treated with adalimumab failed treatment at 7 and 60 months after baseline and the four patients who were treated with infliximab failed treatment at 12, 28, 60 and 72 months after baseline. Cataract and band keratopathy were the most common complications at baseline, each was diagnosed in 14 eyes (16.7%). Cystoid macular edema (CME) was the second most common complication, diagnosed in 11 eyes (13%). CME resolved at a mean of 3.81 ± 1.89 months following the institution of TNF-α inhibitors. Additional infrequent complications at baseline included glaucoma in 3 eyes, vitreous hemorrhage in 2 eyes, and optic disc neovascularization in 1 eye. At 24 months after baseline, 9 eyes of 9 patients had BCVA <20/40, all of which suffered from anterior uveitis which was JIA-related in 8 patients and secondary to sarcoid-related uveitis in the 9th patient. At the last follow-up, the complications that resulted in severe visual loss were macular atrophy and optic atrophy, coexisting in 2 eyes.Surgical intervention for the management of ocular complications was required in 7 eyes of 6 patients: one patient underwent pars plana vitrectomy for non-resolving vitreous hemorrhage (1 eye); 5 patients underwent lensectomy and vitrectomy due to dense cataract impeding fundus visualization (6 eyes).p = 0.279 and p = 0.077, respectively). However, better visual acuity at presentation and the use of adalimumab as first-line biological drug correlated inversely with the occurrence of moderate and severe visual loss . In addition, there was an inverse correlation between the disease duration before biologics and the occurrence of moderate to severe visual loss, .Presenting visual acuity, duration of the disease before starting anti-TNF-α therapy, type of anti-TNF-α drug, anatomical type of uveitis and etiological type of uveitis were the variables included in univariate analysis of predictors of moderate to severe visual loss. Neither anatomical type of uveitis (anterior vs. non-anterior) nor etiological type of uveitis (JIA-associated vs. non JIA-associated) were associated with moderate to severe visual loss . However, only presenting visual acuity accounted for a unique variance in the model (p < 0.001), while duration of the disease before starting anti-TNF-α therapy and type of anti-TNF-α drug used as first-line did not significantly account for a unique variance in the model . Therefore, presenting visual acuity was the sole predictor of moderate to severe visual loss, amongst the variables analyzed.Hence, a multiple linear regression model was calculated to predict moderate and severe visual loss based on presenting visual acuity, duration of the disease before starting anti-TNF-α therapy and type of anti-TNF-α drug used as first-line. The overall regression model was significant :8.56, RThe results of the present study demonstrated that TNF-α inhibitors achieved rapid control of pediatric uveitis while enabling a remarkable systemic and topical corticosteroid-sparing effect. Presenting visual acuity was the sole predictor of moderate to severe visual loss.TNF-α inhibitors enabled complete control of uveitis after a median of 3 months. Similarly, Kouwenberg et al.  reportedThis quick control of inflammation subsequently resulted in rapid steroid taper. The percentage of patients using systemic corticosteroids dropped by more than half in the first year after the introduction of the biological agents. This persistent steroid-sparing effect allowed more patients to discontinue systemic corticosteroids in the second year. Despite the multitude of corticosteroid-related side-effects, clinicians prescribe them in cases where the potential benefits outweigh the potential risks. Additionally, corticosteroid bursts  used to Kouwenberg et al.  reportedAiming to decrease and discontinue systemic steroids is an important milestone because of the plethora of side-effects which may negatively affect the child’s physical and psychological well-being. The disease itself in children exerts academic, interpersonal, psychological and developmental challenges . Both thAlthough we used topical steroids less frequently than Kouwenberg et al.  in theirOphthalmologists aim to withhold the use of topical steroids in children with chronic uveitis because of the potential ocular complications that may ensue. Cataract was the most common complication at presentation in the current study. Additionally, it was reported to be a common complication of pediatric uveitis in other studies ,13. KouwChildren are especially susceptible to an IOP increase with steroid use . Gupta eKouwenberg et al.  reportedAs presenting visual acuity was the sole predictor of moderate to severe visual loss and because many children with uveitis are asymptomatic ,17, perfp = 0.002). The authors however did not elaborate on the reason that could account for this positive association between male gender and inactivity of uveitis. Furthermore, during early rheumatoid arthritis (RA), several cohort studies revealed that remission rates were lower for females than males treated with TNF-inhibitor therapies [Kouwenberg et al.  discloseherapies ,21,22,23herapies . To dateThis study was limited by its retrospective design and the variability of the follow-up schedules. Nonetheless, all data were structurally noted in the electronic patient files thus allowing a uniform way of registration and data collection. This cohort represents additional evidence on the role that biologic therapy plays in the context of pediatric uveitis. We have to keep in mind that children treated with TNF-α inhibitors remain at a greater risk of adverse events than patients treated with conventional IMT. The sycamore study  showed that patients who received adalimumab had a much higher incidence of adverse events and serious adverse events than those who received placebos. The most common adverse events in the adalimumab group were minor infections, respiratory disorders and gastrointestinal disorders .In conclusion, the present study further enhances our knowledge on the usefulness of TNF-α blockers in children with chronic refractory uveitis. It presents evidence on the effectivity of biological therapy, on the prompt control of uveitis and on the steroid-sparing effect while preserving vision.


Purpose: Describe the cognitive and behavioral symptomatology of patients with chronic ocular rubbing in keratoconus (KC) and Ocular Surface Disease (OSD) using a self-questionnaire. Methods: A prospective study was conducted in a tertiary ophthalmology center between May and July 2021. We consecutively included all patients presenting with one of the following conditions: KC and OSD. A questionnaire including the evaluation of Goodman and CAGE-modified criteria for eye rubbing was given to patients in consultation to evaluate their ocular symptoms and medical background. Results: We included 153 patients in the study. Of these, 125 (81.7%) patients reported eye rubbing. The average Goodman score was 5.8 ± 3.1 and was ≥ 5 in 63.2% of cases. The CAGE score was ≥ 2 in 74.4% of patients. Addiction (p = 0.045) and psychiatric family history (p = 0.03) were more frequent in patients with higher scores. Ocular symptoms and eye rubbing were significantly more frequent and intense in patients with higher scores; Conclusion: Eye rubbing presents addictive-like cognitive and behavioral characteristics in patients with KC or OSD. The eye rubbing cycle could play an essential role in the onset and progression of keratoconus and could be a factor in the maintenance of dry eye. Pruritus is clinically defined as the subjective and unpleasant sensation of a desire to scratch . Many opEye rubbing is a frequent behavioral manifestation. It occurs in most cases in response to the sensation of ocular pruritus or irritation to relieve an unpleasant sensory stimulus. It can also occur spontaneously, particularly at bedtime or upon awakening, during ocular fatigue or even be psychogenic . The preThe pathophysiology of pruritus and ocular rubbing is already a subject of research . HoweverThe aim of this non-interventional study was to describe, using a self-questionnaire, the cognitive and behavioral symptomatology of patients with chronic eye rubbing in a population of keratoconus and OSD.We conducted this single-center prospective study in a tertiary ophthalmology center  between May 2021 and July 2021. We included over two consecutive months all patients presenting to ophthalmology consultations in two specialized consultations and presenting with one of the following pathologies: keratoconus (KC group) and Ocular Surface Disease (OSD group). The exclusion criteria were as follows: age younger than 18 years, history of recent eye surgery (<3 months) and presence of a language barrier preventing reliable responses. Patients who incorrectly completed the questionnaire  were excluded retrospectively. The questionnaire was given to patients in consultation on a voluntary basis. Informed consent was obtained from the subjects after explanation of the nature of the study. The research followed the tenets of the Declaration of Helsinki.The first part of the questionnaire included an interrogation concerning the patient’s ophthalmological, dermatological and psychiatric background and a self-evaluation of ophthalmological symptoms. The following data were collected: age, sex, working conditions, medical and surgical ophthalmological history, ophthalmological treatments, use of glasses and contact lenses. Next, we assessed the ocular symptoms experienced by the patients using an open-ended question. Symptomatology was then evaluated in terms of frequency and intensity using the SANDE (Symptom Assessment In Dry Eye) questionnaire, which estimates the frequency of occurrence of symptoms and their intensity . PsychiaThe second part of the questionnaire dealt with eye rubbing. As for the ocular symptoms, we used the SANDE scale to evaluate the frequency and intensity of eye rubbing. We looked for daily or occasional occurrences as well as the period of day. We used the Goodman and DSM-5 diagnostic criteria for addiction to obtain a 16-item cognitive–behavioral assessment of eye rubbing . We consAn ophthalmologic examination by a specialist was performed on the same day for each patient. The following data were collected for all patients: best corrected distance visual acuity (CDVA), intraocular pressure (IOP), presence of follicles, papillae or blepharitis, break-up time (BUT) and Oxford grading score (Oxf). For keratoconus, we evaluated the presence of Vogt’s striae and corneal opacities, the maximum keratometry (Kmax) and the thinnest pachymetry .® software v20.218 . Chi-square test, Student t-test, ANOVA test, and logistic regression were used. Variables were first studied in univariate analysis and then analyzed in multivariate regression. Regression analysis was performed using Spearman’s correlation coefficient. The threshold for statistical significance was set at p < 0.05 for the entire study. We separated patients into two groups: patients with (group R) and without (group NR) eye rubbing. Statistical analysis of the data was performed with MedCalcBetween May and July 2021, 153 patients were included in the study: 69 keratoconus (45.1%) and 84 chronic ocular surface pathologies (54.9%). Of these patients, 125 (81.7%) reported rubbing their eyes. The average age was 39 ± 17 years and 61.4% of patients were female. Of the patients surveyed, 18 patients (11.8%) reported an addiction disorder and 38 patients (24.8%) reported a psychiatric disorder, mainly depression and anxiety. The characteristics of the study population are described in The KC group had a corrected distance visual acuity (CDVA) of 0.1 (±1.7 lines) LogMAR, a Kmax of 58.57D (±10.14) and a thinnest pachymetry of 431 μm (±49). On clinical examination, nine patients (13%) had corneal opacities and 32 patients (46.4%) had Vogt’s striae.The OSD group included 77 Dry Eye Diseases (DED) (91.7%), 19 blepharitis (22.6%) and 14 chronic allergic conjunctivitis (16.7%). The CDVA was 0.02 (±0.6 line) LogMAR. Average BUT was 5.9 (±2.39) seconds and mean Oxf score was 0.81 (±1.04). Meibomian gland dysfunction (MGD) was found in 58.3% of patients.p < 0.001). Of the patients surveyed, 17.4% of KC and 38.1% of OSD reported a dermatological history (p = 0.005), 26.1% and 47.6%, respectively, experienced skin pruritus (p = 0.04), while 18.8% and 38.1%, respectively, reported skin scratching (p = 0.009).Several significant differences were found between the KC and OSD groups . Mean agp = 0.03). The modified SANDE score was higher for OSD, with a significant difference for frequency (p < 0.001) and intensity (p < 0.001) of symptoms experienced by patients. Finally, 62 (89.9%) KC and 63 (75%) OSD reported eye rubbing (p = 0.02). Ophthalmological examination found significantly more papillae in KC (p = 0.0007) and more MGD in OSD (p < 0.0001).Ocular pruritus was more frequent in KC, affecting 58% of patients, compared with 40.5% of OSD (p = 0.01). In the NR group, seven patients (25%) presented a keratoconus versus 62 (49.6%) in the R group (p = 0.02). In addition, 20 patients (71.4%) in the NR group had DED versus 61 (48.8%) in the R group (p = 0.03). The two groups showed no difference for anti-allergic treatment. Patients in the NR group were significantly more treated with anti-inflammatory eyedrops (p = 0.049). Dermatologically, 17.9% of NR patients experienced skin pruritus compared to 38.4% of R patients (p = 0.04), while 14.3% of NR patients reported scratching their skin compared to 32.8% of R patients (p = 0.052). Allergy was reported by seven NR patients (25%) and 65 R patients (52%) (p = 0.01). No significant difference was found for psychiatric and addictive history.We compared patients with (group R) and without eye rubbing (NR group) . The meap = 0.006). Ocular pruritus was reported by 7.1% of NR patients and 57.6% of R patients (p < 0.0001). Slit lamp examination found papillae in six (21.4%) NR patients and 82 (65.6%) R patients (p < 0.0001). Mean BUT was 7.27 (±2.80) in NR and 6.14 (±2.68) in R (p = 0.047). Mean Oxford grade was 0.34 (±0.58) in NR and 0.59 (±0.95) in R (p = 0.011). Subpopulation analyses of KC with and without ocular rubbing showed no significant difference for clinical severity.Among the patients interviewed, 75% of NR patients reported ocular symptoms compared to 92.8% of R patients (p = 0.005), while 40.3% of KC patients and 71.4% of OSD patients reported rubbing their eyes regardless of the time of day (p < 0.002). Daily occurrence of eye rubbing was 32.3% for KC versus 55.6% for OSD (p = 0.009). Daily frequency was higher for OSD (p = 0.002).Characteristics of eye rubbing were studied in 125 patients . NighttiRegarding Goodman criteria, the average score obtained for eye rubbers was 5.8 ± 3.1. Among these patients, 79 (63.2%) had a Goodman score of 5 and above. The CAGE questionnaire reported a mean score of 2.2 ± 1.2 for the rubbing population. The CAGE score greater than or equal to 2 was found in 93 patients (74.4%). KC and OSD subgroups did not differ significantly for Goodman criteria or CAGE score.p = 0.045). Psychiatric family history was reported by 17.7% of positive patients and 4.3% of negative patients (p = 0.03). There was no significant difference in personal psychiatric history between the two groups. Patients with a positive score had significantly more ocular symptoms (p = 0.008) and itching (p = 0.001) than those with a negative score. Similarly, the frequency and intensity of symptoms were higher in the positive population . Finally, eye rubbing’s frequency and intensity were higher in the positive score population (p < 0.001). On clinical examination, 58 (70.7%) of the positive patients and 21 (48.8%) of the negative patients had papillae (p = 0.02). Mean BUT was significantly shorter in patients with a positive score (p = 0.03).We compared patients with Goodman scores of 5 and above (positive score) and those below 5 (negative score) . Age wasp = 0.0001). This rate was not different between patients with a positive and negative Goodman score.Of the 125 eye rubbers interrogated, 87 patients (69.6%) declared they would be willing to stop eye rubbing after completing the questionnaire. The positive responses rate was 85.5% for KC versus 54% for OSD , in KC (89.9%) and in OSD 75%). In comparison, a study found 29.5% eye rubbing in a population visiting an eye center in the United States . This im%. In comThe severity of DED was higher in patients with eye rubbing . Eye rubbing could act on ocular surface inflammation and cell apoptosis, which are essential elements of DED’s vicious cycle described by Baudouin et al. ,18.Ophthalmological symptoms reported were more intense and frequent for patients with higher Goodman score. Similarly, frequency and duration of eye rubbing were greater for these patients. This could be secondary to peripheral and central sensitization, which are phenomena well described in skin pruritus .No significant difference was found between KC and OSD for diagnostic and predictive criteria of addiction. Eye rubbing was more frequent in KC but OSD had higher daily frequency. These results suggest that it is not the cognitive–behavioral characteristics of eye rubbing that are responsible for the occurrence of KC but rather its mechanical characteristics combined with corneal susceptibility to ectasia.Conjunctival papillae seem to play an important role in eye rubbing. First, their presence was more frequent in KC as well as in patients rubbing their eyes. Second, in the eye rubbing population, papillae were significantly more frequent in patients with high addiction criteria scores. Papillae could not only be an essential element in the pathophysiology of eye rubbing but could also be an essential element in the eye rubbing cycle. Papillae could be part of the peripheral sensitization phenomenon in ocular pruritus. Further studies are needed to investigate this hypothesis.Patients without eye rubbing were significantly more treated with anti-inflammatory eye drops (cyclosporine and corticosteroids) than eye rubbers, whereas there was no difference for antihistamine and mast cell stabilizer drops. These results support the hypothesis that chronic ocular pruritus, similar to skin pruritus, is primarily mediated by non-histaminergic pathways and is supported by local inflammatory mechanisms .After answering the questionnaire, patients with KC were more likely to stop rubbing their eyes than those with OSD. These positive responses may be secondary to patients’ awareness of eye rubbing’s role in the pathophysiology of KC . On the In our study, patients with higher Goodman criteria scores reported more addictions and family psychiatric history. These results are consistent with data reporting the existence of psychiatric and addictive comorbidities concerning up to 50% of patients with addictive disorders ,23.The findings of this study have to be seen in light of some limitations. First, there was a selection bias related to recruiting patients from a tertiary care center, selecting more severe KC and OSD. In addition, the inclusion of KC or OSD in this study limits the extrapolation of the results to the general population. A controlled study with healthy eye rubbers and less severe patients would provide additional data. Second, there was an assessment bias inherent to answering a self-questionnaire with psychiatric questions. This could result in an underestimation of psychiatric and addictive disorders as a result of negative responses ,25. TherFinally, an important bias of this study is the lack of validated specific diagnostic criteria. Indeed, specific diagnostic criteria exist for substance addictions and some behavioral addictions, but no generic questionnaire is validated for behavioral addictions . In thisThe parallel between eye rubbing and addiction allows us to consider new clinical and therapeutic approaches. Patient management should include information on ocular pruritus, eye rubbing and their potential consequences. Evaluation of ocular pruritus and rubbing in KC and OSD could allow a more appropriate management by involving patients and allowing better understanding of their symptoms, behavior and resulting disorders. As suggested by McMonnies, an informative document can be given to eye rubbers to limit the apparition and progression of corneal ectasia . When thDermatologists studied the central and peripheral mechanisms of skin pruritus and scratching, describing the “itch–scratch cycle” ,13. FollIn conclusion, eye rubbing is a behavior with addictive-like cognitive–behavioral characteristics in patients with KC or OSD. Eye rubbing is part of a vicious cycle with peripheral and central sensitization. This cycle plays an essential role in the occurrence and progression of keratoconus. Moreover, it could constitute an important element of maintenance and aggravation of DED, explaining the high prevalence of rubbing found in our OSD population.


For these 229 miRNAs, the F1-score, sensitivity, specificity, and AUC ranged from 0–88.2%, 0–99.4%, 4.3–100%, and 41.5–68%, respectively. Utilizing the combined bioinformatic and NGS approach, a specific and broad panel of miRNAs was detected as being potentially suitable for building a blood signature of endometriosis.The aim of our study was to describe the bioinformatics approach to analyze miRNome with Next Generation Sequencing (NGS) of 200 plasma samples from patients with and without endometriosis. Patients were prospectively included in the ENDO-miRNA study that selected patients with pelvic pain suggestive of endometriosis. miRNA sequencing was performed using an Novaseq6000 sequencer . Small RNA-seq of 200 plasma samples yielded ~4228 M raw sequencing reads. A total of 2633 miRNAs were found differentially expressed. Among them, 8.6% ( The mammalian genome contains sequences for RNAs coding for messenger RNA (mRNA) proteins and non-coding RNAs (ncRNA). ncRNAs represent 98% of the transcriptome . The knoApproximately 70% of studies evaluated exosomes as the source of choice for ncRNAs . The RNAEndometriosis, defined by the presence of endometrium-like tissue outside the uterus, affects 2–10% of the female population, i.e., around 190 million women worldwide . It is wTherefore, the goal of the present study was to describe using NGS and bioinformatics systematic approach the miRNome sequencing of 200 plasma samples based on the prospective data from the ENDO-miRNA study.We used data from the prospective “ENDO-miRNA” study  . Data cog (3000 rpm) for 10 min, followed by 13,000–14,000× g for 10 min to remove all cell debris) then aliquoted, labeled, and stored at −80 °C until analysis, as previously published [Blood samples (4 mL) were collected in EDTA tubes . Plasma was isolated from whole blood within 2 h after blood sampling by two successive centrifugations at 4 °C  according to the manufacturer’s protocol. Libraries for small RNA sequencing were prepared using the QIAseq miRNA Library Kit for Illumina . The resulting small RNA libraries were concentrated by ethanol precipitation and quantified using a Qubit 2.0 Fluorometer . Samples were indexed in batches of 96, with a targeted sequencing depth of 17 million reads per sample. Sequencing was performed using 100 base single-end reads, using an Novaseq6000 sequencer  [RNA was extracted from 500 μL of plasma on a Maxwell 48CA, USA) ,36.https://www.ncbi.nlm.nih.gov/genome/guide/human/ 10 March 2022 and miRBase21) (miRNAs) using the MirDeep2 v0.1.0 package. The raw sequencing data quality was assessed using FastQC software v0.11.7 [Sequencing reads were processed after adaptation using the bioinformatics and processing pipeline according to Potla et al., review ,38. Fast v0.11.7 ,35,39,40p value adjusted for multiple testing was <0.05 [miRNA expression was quantified using miRDeep2 . Differeas <0.05 .2 test as appropriate for categorical variables. Values of p < 0.05 were considered to denote significant differences. Data were managed with an Excel database  and analyzed using R 2.15 software, available online .To evaluate the accuracy of each miRNA biomarker, sensitivity, specificity, and ROC analysis was performed, and the ROC AUC was calculated ,44. Addin = 153) were diagnosed with endometriosis and 23.5% (n = 47) without. In the endometriosis group, 52% (80) had rASRM stages I–II and 48% (73) had stages III–IV. The control group was mainly composed of complex patients defined by patients sharing symptoms of endometriosis but without clinical or imaging features of endometriosis, and patients with other gynecologic disorders but with symptoms suggestive of endometriosis.The clinical characteristics of the endometriosis and control patients are presented in Small RNA-seq of 200 plasma samples yielded ~4228 M raw sequencing reads (from ~11.7 M to ~34.98 M reads/sample). Pre-filtering and filtering steps retained 39% (~1639 M) of initial raw reads. The majority of filtered reads were of 20–23 nt length which corresponds to the range of mature miRNA sequences. Quantification of filtered reads and identification of known miRNAs yielded ~2588 M sequences to be mapped to 2633 known miRNAs from miRBase v22. The number of expressed miRNAs ranged from 666 to 1274 per sample. The distribution of expressed miRNAs in the 200 plasma samples and according to the overall composition of processed reads is shown in n = 229) were up- or downregulated. Respectively, 66% (152) and 34% (77) of the 229 miRNAs were up- and down regulated  are reported in The diagnostic metrics for endometriosis for all the regulated plasma miRNAs  and 3.1% (7) had a value ranging between 41.5–59% and ≥60%, respectively.n = 153) and 33.2% (n = 76) had a value ranging between 0–79%, and ≥80%, respectively.For the F1-scores, 66.8% (n = 160) and 30.1% (n = 69) had a value ranging between 0–79%, and ≥80%, respectively.For sensitivity, 69.8% (n = 96) and 58% (n = 133) had a value ranging between 0–79%, and ≥80%, respectively.For specificity, 42% (Among the 229 regulated miRNAs, 69 had a sensitivity over 0.80 and 100 had a specificity over 0.80 but none had both sensitivity and specificity over 0.80 .To our knowledge this is the first report which describes a sequencing and systematic bioinformatics approach for plasma miRNome of patients with endometriosis. The current study demonstrates that using an NGS technique allows the display of a specific and broad panel of miRNAs potentially suitable for statistical analysis as potential biomarker in endometriosis.The recent literature review by Monnaka et al. of miRNA expression in endometriosis found that 30 miRNAs were deregulated in the blood; 27 in the serum, and 18 in the plasma of women with endometriosis compared with control populations. Interestingly, the authors of this critical review concluded that no particular miRNAs or miRNA combination was individually accurate enough to screen and diagnose endometriosis . SimilarAnother issue is the difficulty of simultaneously analyzing hundreds of miRNAs taking into account the diversity of endometriosis phenotypes and the incomplete knowledge of the pathophysiology . PreviouAnother issue is the discrepancy in miRNA expression from one series to another ,15,17,23Some remaining issues for the evaluation of miRNAs in the context of endometriosis should be discussed. Two of the important determinants of miRNA analysis are the phase of the menstrual cycle and the impact of hormonal treatments . AlthougIt is well known that endometriosis, which affects 190 million women worldwide, is a debilitating disorder with a negative impact on quality of life and fertility, and that it represents a major socioeconomic burden . Our res


Aim: To evaluate the visual outcome of penetrating ocular injuries with a retained intraocular foreign body (IOFB) managed by pars plana vitrectomy (PPV) and to describe the risk factors associated with poor visual acuity and retinal detachment (RD) development. Methods: Medical records of 56 patients with IOFB that were removed by PPV over a period of 11 years (1 January 2010–31 December 2020) were reviewed. We extracted the demographic data, initial and final best corrected visual acuity (BCVA) using standard Snellen chart, IOFB characteristics, complications and surgical details. Outcome was evaluated according to the final BCVA: poor <0.1, good 0.1–<0.5 or excellent ≥0.5. Results: The mean age was 36.1 ± 14.1  years and the majority of patients were males . IOFB was retinal in 27 (48.2%) cases and intravitreal in 29 cases (51.8%). IOFB size was ≤3mm in 26 (46.4%) cases and >3mm in 30 (53.6%) cases. Preoperative RD was identified in 12 (21.4%) cases and endophthalmitis in 17 cases (30.4%). IOFBs larger than 3 mm and retinal location were associated with RD development. Poor visual outcome was associated with initial BCVA, retinal location, RD and endophthalmitis. Conclusion: Initial BCVA, retinal foreign body, RD and endophthalmitis were risk factors for poor visual outcome. Intraocular foreign bodies (IOFBs) represent a major cause of vision loss, particularly in the working-age population ,2. They This retrospective study was carried out in the Department of Ophthalmology, “Iuliu Hațieganu”, University of Medicine and Pharmacy, Emergency County Hospital from Cluj-Napoca, Romania, between 1 January 2010 and 31 December 2020. The study was conducted in accordance with the Declaration of Helsinki and was approved by The Ethics Committees belonging to the “Iuliu Hațieganu” University of Medicine and Pharmacy and the Emergency County Hospital Cluj-Napoca and all the patients signed the informed consent.The inclusion criterion was represented by IOFB that was extracted by PPV. During the abovementioned 11-year period, 56 cases fell into this category. Both primary and additional surgery procedures (if needed) were performed by the same surgeon (S.D.N.). We reviewed the medical records of the 56 patients and collected data including age, sex, rural or urban setting, type of accident, initial and final BCVA (Snellen Chart), initial ocular findings, characteristics of the IOFB, the surgeries performed and complications. Information on the location, material and size of the IOFB were collected. In perforating cases where IOFB could not be retrieved, the size was noted according to the measurements provided by computer tomography. The location of the entry lesion was classified according to the Ocular Trauma Classification Group  and diviThe diagnosis of IOFB and associated lesions has been established by clinical examination, B-scan ultrasonography, computer tomography or orbital radiography. Post-traumatic endophthalmitis was diagnosed based on past ocular trauma history, clinical findings and symptoms at presentation. During surgery, no vitreous tap for culture was taken due to economic reasons. Nevertheless, even with negative cultures, we cannot exclude a diagnosis of endophthalmitis in the presence of clinical signs. The vitreous tap would have identified the specific germ involved, but the antibiotics that can be administered intravitreally are limited. The goal of treatment was to remove the IOFB and restore the integrity and function of the eye. Primary suture was carried out in patients with leaking wounds. Three-port PPV was performed in all cases. Following core vitrectomy, any adherence between the IOFB and the vitreous or the retina was eliminated, and the IOFB was released into the vitreous cavity and then removed through one enlarged sclerotomy with the intraocular magnet. Additional surgical gestures were dictated by the specific situation: lensectomy/phacoemulsification, if traumatic cataract was associated; endolaser photocoagulation, if retinal lesions were identified. If RD was present, fluid/air exchange with repair of the lesion and silicon tamponade was performed, and in cases with endophthalmitis, intravitreal vancomycin 1 mg/0.1 mL, ceftazidime 2.2 mg/0.1 mL, amikacin 0.4 mg/0.1 mL and dexamethasone 0.4 mg/0.1 mL were injected. n, %). Outcome was evaluated according to the final BCVA: poor <0.1, good [0.1–0.5) or excellent ≥0.5. A chi-squared test or Fisher test for categorical variables was applied to compare the differences among subjects. Univariate logistics regression was applied to examine the associations between risk factors and final BCVA. A p-value of less than 0.05 was considered statistically significant throughout the study. In case of unequal data distribution, the p-value was obtained by the Kruskal–Wallis test.Statistical analyses were performed using the SPSS Statistics version 20 . All numerical data are expressed either as the median (minimum–maximum) or as the mean ± standard deviation. All categorical variables are expressed as the number and percentage  years. The demographic characteristics of the study population are summarized in p = 0.046). The average IOFB length was 3.54 mm, ranging between 0.5 mm and 8 mm . AccordiThe preoperative and postoperative BCVAs are listed in p < 0.018), the retinal location of the IOFB (p < 0.046), the association of RD at initial examination (p < 0.010) and endophthalmitis (p < 0.040) were risk factors associated with a poor visual outcome. Univariate analyses of the factors associated with final BCVA are summarized in p = 0.046). From the 27 cases with retinal IOFB, only 8 (29.6%) recovered useful vision (BCVA ≥ 0.1), whereas from the 29 cases with intravitreal IOFB, 18 (62.1%) ended up with a good visual outcome (BCVA ≥ 0.1) (p = 0.010). Within the group of 12 patients with RD during follow-up, 5 cases had endophthalmitis upon presentation and in 1 case, the foreign body was in the orbit; 11 patients had final BCVA of CF or less and only 1 maintained BCVA ≥ 0.1. RD was identified in 24 patients (42.85%), of which 12 occurred at the time of presentation and 12 during follow-up. Among the 12 patients with RD at presentation, only 1 (8.0%) achieved final BCVA ≥0.1, whereas from the 44 cases without RD at presentation, 24 (54.6%) recovered final BCVA ≥0.1 (p = 0.040). Endophthalmitis was associated in 17 cases (30.4%) and compromised the visual outcome in 13 of them (76.5%). Only four patients (23.5%) within the endophthalmitis group reached final BCVA ≥0.1. Among the patients without endophthalmitis (39 cases—69.6%), 22 (56.4%) had final BCVA ≥0.1 (p = 0.208), PPV that was performed later carried out a higher risk for poor visual outcome. From the 26 cases in which PPV was performed later than 48 h from injury, 17 (65%) had a final BCVA <0.1. Of the 30 cases where PPV was performed within the first 48 h, 17 (57%) had a final BCVA ≥0.1. In our study, the age, IOFB size, entry site time of extraction and lens injury did not have a statistically significant impact on the final BCVA . The timThe surgical treatment is summarized in The other primary surgical procedures were lensectomy in 25 cases (44.6%), phacoemulsification in 3 cases (5.4%), suture of the globe in 25 cases (44.6%), intravitreal antibiotic injection in 12 cases (21.4%) and laser of the retinal lesion in 24 cases (42.9%). Subsequent surgeries were performed as follows: PPV 21 cases (37.50%), phacoemulsification 5 cases (8.9%), IOL implantation 12 cases (21.4%) and intravitreal antibiotic injection 5 cases (8.9%). Of the 28 eyes that underwent lensectomy or phacoemulsification as part of the first intervention, in 4 of them, IOL was implanted at the end of surgery, and in 12, IOL was planted at a later stage; 12 eyes remained aphakic. Ten of the cases that remained aphakic exhibited extensive ocular damage with low potential for visual improvement. The other two cases presented concurrent endophthalmitis and we made the decision to have a secondary IOL implantation at a later stage but, for unknown reasons, these 2 patients were lost during follow-up. For eight eyes, lensectomy or phacoemulsification was performed at a later stage and was followed by IOL implantation in three eyes. Overall, 17 eyes remained aphakic. Endolaser photocoagulation of the retinal lesion produced by the IOFB was carried out in 24 eyes, of which 6 developed RD at a later stage. Overall, 24 eyes were treated for RD. Of these, 12 (50%) were present at the initial setting, and 12 occurred later (50%); 10 had concurrent endophthalmitis and 3 cases were seen with intraorbital foreign body. In all cases in which visibility was permitted, reattachment of the retina was performed and silicone oil was used for internal tamponade. Among all patients with RD, the final BCVA was ≤ hand motion in 14 cases, CF in 8 cases and >0.1 in 2 cases. Proliferative vitreoretinopathy (PVR) was noted in 9 out of 24 eyes with RD (37.5%). Among the nine PVR cases, eight cases had IOFB ≥ 3mm, four cases had concurrent endophthalmitis and four cases underwent PPV after 48 h. p < 0.001). We also found that the IOFBs larger than >3 mm carried a higher risk for RD compared to smaller ones: of the 30 eyes with IOFB >3 mm, 17 (56.6%) developed RD, whereas of the 26 cases with IOFB ≤ 3mm, 7 (26.9%) developed RD (p = 0.02). In the postoperative RD subgroup, the IOFB size was not correlated with a higher risk of RD (p = 0.29). Endophthalmitis did not represent an indicator for RD development in any subgroup, but it did show an increased predisposition to RD in the whole group; of the 17 cases with endophthalmitis, 10 (58.8%) developed RD, and of the 39 eyes without endophthalmitis, 14 developed RD (35.9%) (p = 0.11).We also analyzed the risk factors for RD, which are summarized in Post-traumatic endophthalmitis was present in 17 eyes, 12 eyes received intravitreal antibiotic injections with vancomycin 1.0 mg/0.1 cc and/or ceftazidime 2.2 mg/0.1 cc at the time of primary repair and for 5 eyes, intravitreal therapy was given at 1 day (one case), 2 days (one case), 3 days (one case), 4 days (one case) and 37 days (one case) after the primary repair. In all cases, systemic moxifloxacin was administered (400 mg/day). Regarding the final BCVA, excellent outcome was seen in 3 cases (17.6%), good outcome in 1 case (5.9%) and poor outcome in 13 cases (76.5%).The indications for undergoing additional PPV were: RD (14 cases), endophthalmitis (3 cases), epiretinal membrane (1 case), cataract (1 case), combined RD and cataract (1 case), combined endophthalmitis, RD and cataract (1 case) and retinal break (1 case). The average number of surgical procedures performed per patient was 2.14 ± 1.25 .Eye trauma is an important and preventable cause of unilateral blindness, with penetrating eye injuries taking first place . In thisIn this retrospective study, we analyzed the data of 56 patients with the aim to outline the prognostic factors and complications associated with final BCVA in penetrating ocular injuries with retained IOFB during an 11-year period. The average age of our patients was 36.1 ± 14.1 years and included a total of 55 males 98.2%), which is similar to the demographic characteristics of other reports ,26. Youn8.2%, whip = 0.270). The explanation for this observation lies in the fact that most of the patients in our series are young, due to the different mechanism by which eye trauma occurs in the elderly compared to the young. More precisely, eye trauma in the geriatric population most often results in globe ruptures due to falls and rarely involves an IOFB, which is in contrast with young males with an occupational-related open globe injury and IOFBs [Several authors ,22 foundnd IOFBs . p = 0.018). Previous research indicated that poor BCVA at presentation is a major risk factor for poor visual outcome, mainly because it reflects a higher degree of ocular damage at presentation [p = 0.208), but a delay in surgery of more than 48 h showed a higher risk for poor visual outcome with 17 cases of 26 (56.7%) ending up with final BCVA <0.1. Timing of surgery (delayed vs. immediate) is a well-discussed, controversial topic and depends on several factors such as patient’s general health condition, presence or absence of endophthalmitis and the availability of well-trained surgeons and personnel. On the one hand, there are authors who pointed out that late PPV and IOFB removal (after 24 h) increases the risk of developing endophthalmitis and PVR [Initial poor BCVA was correlated with a poor prognosis throughout our study  [Regarding the size of IOFBs, some authors indicated that IOFBs ≥3mm are an important independent risk factor for poor visual outcome, suggesting that the larger the IOFB, the greater the kinetic energy that develops when it penetrates the eye, which increases the risk of retinal damage ,18,19,34p = 0.932), which corresponds to previous findings [p = 0.046). It is well-documented in the literature that posterior segment IOFBs are more likely to damage the retina and cause RD and ir-reversible vision loss [The location of the entry site did not prove to be a prognostic factor for the visual outcome in our series . Post-traumatic cataract is a common complication of open globe injuries with IOFB, ranging from 44% to 66% of cases . TraumatThe primary cause of vision loss in penetrating ocular injuries with posterior segment IOFB is the development of RD and PVR. Preoperative and postoperative RD remain a frequent complication associated with high risk of vision-threatening consequences despite all surgical progress made in ocular trauma management ,15,20,26PVR following open globe injuries is much more frequent than in primary RD, occurring in 40–60% of patients . The higp = 0.376). Immediate PPV with IOFB removal has been described to reduce the incidence of endophthalmitis [Traumatic endophthalmitis is a devastating complication of open globe injuries, with an incidence ranging from 0% to 17% in different studies ,10,11,12halmitis ,30,31. HThis study has some limitations, represented by its retrospective nature, with all data being collected from medical charts; the relatively small number of patients; and the lack of long-term information regarding the patients’ visual outcome.Poor visual outcome after posterior segment IOFBs is strongly related to initial BCVA, RD at presentation, endophthalmitis and retinal location of the IOFB. The retinal location of the IOFB is significantly associated with the occurrence of RD. Because the IOFBs represent a cause of potential visual morbidity and blindness among young, working-class men, eye protection during prone activities is crucial and needs more promotion and education.