order SIRT1/2 Inhibitor IV br Materials and Methods br Results

Materials and Methods

Table 1 summarizes the characteristics of the 48 cases of idiopathic retinal detachment and the 99 controls. Cases were older than controls and had higher mean BMI. As shown in Table 2, all the correlations between the exposure indexes were strong (Spearman’s rank correlation coefficient always > 0.9). Table 3 reports results from the logistic regression models for the three exposure indexes. The measures of relative goodness of fit, AIC and BIC, were almost the same for each of the 3 adjusted logistic regression models. In the multivariate analysis, all 3 indexes were associated with risk of idiopathic retinal detachment. Subjects in the highest categories of exposure showed a three to fourfold increase, compared with unexposed subjects. For all 3 indexes a dose-response relationship was apparent, as well as moderate to strong evidence supporting a trend.

We previously reported an association between cumulative exposure to occupational lifting and the risk of retinal detachment in myopic subjects [8]. In the present analysis we expanded our study order SIRT1/2 Inhibitor IV by including non-myopic cases that were previously excluded due to lack of non-myopic controls and focused exclusively on the possible role of occupational lifting after adjusting for BMI (another implicated risk factor and an important confounder). Given the larger number of available cases, we decided to exclude subjects with history of cataract surgery, coexisting aphakia or onset presenting after external trauma. The rationale for this choice was identification of idiopathic retinal detachment cases, which comprise an ideal population in which to study possible causal associations with occupational exposures.
We only considered occupational lifting of at least 10kg (a cut-off selected to catch the 15-20kg or more loads that have been reported to produce substantial intraocular pressure spikes [15]). To develop suitable exposure measures, we broadly followed examples provided by studies on lumbar disk hernia, for which lifting is a prominent risk factor and in which at least three components are thought to contribute; intensity, frequency and long-term duration of lifting manoeuvres [16]. To allow consideration of the different contributions of these three components, we adopted three different exposure indexes for occupational lifting. For each of these we found evidence of an association with idiopathic retinal detachment. Unfortunately, in our study population the three indexes were strongly correlated, thereby precluding any evaluation of the different contributions of intensity, frequency and duration.
Our main pathophysiological hypothesis is that the observed increase in risk could be a consequence of the frequent and prolonged variation in intraocular pressure caused by the Valsalva manoeuvre. The possibility that this may be linked to retinal detachment has been considered in the context of case reports and a case series [1, 5, 6]. As early as 1921, Edridge-Green [17] noted that “when anyone tries to lift a box which is at the limit of his strength he experiences a great feeling of tension in the eyes.” In 1973, Dambite and Flik [18] presented a case series of 352 myopic workers; the authors highlighted an association between selected comorbidities (i.e., retinal detachment and hemorrhagic retinopathy) and high demand physical work. When Pivovarov et al. [15] measured intraocular pressure in healthy subjects performing static physical efforts associated with various simulated lifting manoeuvres (with or without sudden holding of the breath), it was found that lifting of weights over 15-20kg was generally accompanied by an abrupt rise (~25mmHg) and fall in intraocular pressure, particularly when this exertion was accompanied by a sudden holding of the breath. The authors of this study hypothesized that these hydro-/hemodynamic spikes could eventually cause breaches, triggering retinal detachment. An alternative pathophisiological pathway linking lifting and retinal detachment could be mediated by ciliary muscle spasm; however, an experimental study conducted by Schwab and Gartner [19] suggests that lifting a 25-kg-heavy weight is unlikely to provoke a considerable ciliary spasm.