Central serous chorioretinopathy (CSC) is characterized by leakage of fluid from the choroid into the subretinal space and, consequently, loss of central vision. The disease is triggered by endogenous and exogenous corticosteroid imbalance and psychosocial stress and is much more prevalent in men. We studied the association of genetic variation in 44 genes from stress response and corticosteroid metabolism pathways with the CSC phenotype in two independent cohorts of 400 CSC cases and 1,400 matched controls. The expression of cadherin 5 (CDH5), the major cell–cell adhesion molecule in vascular endothelium, was downregulated by corticosteroids which may increase permeability of choroidal vasculature, leading to fluid leakage under the retina. We found a significant association of four common CDH5 SNPs with CSC in male patients in both cohorts. Two common intronic variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant associations with CSC; P = 0.00012; odds ratio (OR) = 1.5; 95%CI [1.2;1.8], and P = 0.0014; OR = 0.70; 95%CI [0.57;0.87], respectively. A common haplotype was present in 25.4% male CSC cases and in 35.8% controls (P = 0.0002; OR = 0.61, 95% CI [0.47–0.79]). We propose that genetically predetermined variation in CDH5, when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population.
Laser Doppler flowmetry (LDF) is a recent technique that is increasingly being used to monitor relative changes in cerebral blood flow whereas the intra-arterial133 xenon injection technique is a well-established method for repeated absolute measurements of cerebral blood flow. The aim of this study was to validate LDF for assessment of cerebral autoregulation and CO 2 reactivity with the 133 xenon injection technique as the gold standard. Simultaneous measurements of cerebral blood flow (CBF) were collected by LDF (CBF LDF ) and the 133 xenon method (CBF Xe ) while (1) cerebral autoregulation was challenged by controlled systemic haemorrhage, or (2) cerebral blood flow was varied by manipulating the arterial partial pressure of CO 2 (P a,CO 2 ). LDF slightly overestimated CBF under conditions of haemorrhagic shock and haemodilution caused by controlled haemorrhage (paired t test, P < 0.05). However for pooled data, the autoregulation lower limit was similar when determined with the 133 xenon and the LDF techniques: 65 ± 3.9 mmHg and 60 ± 5.6 mmHg, respectively. Linear regression analysis yielded CBF Xe = (1.02 × CBF LDF ) + 9.1 and r = 0.90. Even for substantial changes in P a,CO 2 , the two methods resulted in similar results. We conclude that even though LDF overestimated CBF during haemorrhagic shock caused by controlled haemorrhage, the lower limit autoregulation was correctly identified. The laser Doppler technique provides a reliable method for detection of a wide range of cerebral blood flow changes under CO 2 challenge. Haemodilution influences the two methods differently causing relative overestimation of blood flow by the laser Doppler technique compared to the 1 33 xenon method.
Perinatal brain injury has been associated with impaired cerebral blood flow (CBF) pressure autoregulation. The brain of 3-to 5-d-old rat pups is immature and similar to that of a preterm infant, and therefore we tested cerebral vasoreactivity in that animal. CBF pressure autoregulation was tested in 20 Wistar pups during normocapnia and hypercapnia, respectively. Hypotension was induced by hemorrhage and cerebral perfusion was monitored with laser Doppler flowmetry and near-infrared spectroscopy. Systolic blood pressure was measured noninvasively from the tail. During normocapnia, the autoregulatory plateau was narrow. Resting systolic blood pressure (SBP) was 39.2 mm Hg and CBF remained constant until SBP decreased below 36.0 mm Hg (SE 0.8). Below the lower limit, CBF declined by a mean of 2.7% per mm Hg [95% confidence interval (CI), 2.4 -3.0%], and hemoglobin difference (HbD) and total hemoglobin (HbT) changed proportionally to CBF. After inhalation of carbon dioxide, CBF increased significantly by a mean of 17.7% (95% CI, 13.7-22.8%). The CBF-CO 2 reactivity was estimated to 13.4% per kPa (95% CI, 2-24.8%), p ϭ 0.026. Over the range of SBP (6 -54 mm Hg), a linear relationship between CBF and SBP was found during hypercapnia, indicating abolished pressure autoregulation. A linear correlation between CBF and HbD was found (r ϭ 0.80). CBF pressure autoregulation and reactivity to CO 2 operate in the newborn rat. This model may be useful for future investigations concerning perinatal pathophysiology in the immature brain. In very preterm infants, brain injury has been associated with impaired pressure autoregulation of CBF. Accordingly, periventricular hemorrhage may result from abrupt hyperperfusion whereas periventricular leukomalacia has been related to ischemia (1-9).Cerebral pressure autoregulation refers to vascular mechanisms whereby CBF is held within constant levels during variations in perfusion pressure. Perfusion is thus maintained over a range of pressures by appropriate alterations in the diameter of precapillary arterioles. However, the lower limit of autoregulation is reached when the vessels become fully dilated and, beyond that point, any further decrease in pressure results in proportional drops in CBF. Several conditions may affect the autoregulatory plateau and increased CBF as well as complete pressure passiveness secondary to vasodilatation is observed during hypercapnia, hypoglycaemia, hypoxia, and seizure (10 -13).Cerebral pressure autoregulation has been documented in several newborn animals such as piglets, lambs, and puppies (14 -19). Most of these animals have rather mature brains at birth, and to compare vascular physiology with that of a preterm infant, the newborn rat pup served as a model (20,21). Because we could not control ventilation in this immature animal, we evaluated the cerebrovascular response to hemorrhagic hypotension during normocapnia and carbon dioxide inhalation. The hypothesis was that pressure autoregulation operates normally in the healthy immature brain. METH...
ABSTRACT.Purpose: To evaluate the effect of verteporfin photodynamic treatment (PDT) on choroidal thickness in patients with central serous chorioretinopathy (CSC). Methods: Choroidal thickness was measured with enhanced depth imaging-optical coherence tomography (EDI-OCT) before and after verteporfin PDT (fulldose verteporfin, half-light dose) in 16 eyes in 16 patients with serous detachment of the fovea secondary to extrafoveal angiographic fluorescein leakage. Treatment was confined to the area of leakage, whereas choroidal thickness before and after treatment was assessed over a larger area of the fundus using OCT. Results: Complete resolution of the serous detachment was seen in all 16 eyes within 1 month of extrafoveal PDT, while choroidal thickness in the area where PDT was applied decreased from 407 lm [mean; 95% confidence interval (CI 95 ) 356-458 lm] to 349 lm (mean; CI 95 300-399 lm; p < 0.0001), and subfoveal choroidal thickness was reduced from 421 lm (mean; CI 95 352-489 lm) to 346 lm (mean; CI 95 278-414 lm; p = 0.0001). Initially, subfoveal choroidal thickness was significantly increased in the treated eye compared with the healthy fellow eye (mean 324 lm; CI 95 273-376 lm; p = 0.0003), but after treatment, the difference was not significant. Discussion: Photodynamic therapy of active CSC was followed by choroidal thickness reduction, not only locally but also at considerable distance from the treated area. Thus, the process that causes choroidal thickening in CSC appears to spread laterally within the choroid.
The study demonstrated sufficient overall agreement between the two methods of assessing leakage rates in smokestack CSC, with adequate repeatability. Leakage rates of the RPE lesions in smokestack CSC occurred at rates consistent with bulk fluid flow, rather than secretion and diffusion, indicating that the primary source of leaking fluid was not the RPE, but a segment of underlying choroidal vasculature.
Purpose: To describe clinical characteristics and response to verteporfin therapy (PDT) in eyes with retinal pigment epithelium detachment (PED) in the absence of primary disease other than characteristics compatible with central serous chorioretinopathy (CSC). Methods: Retrospective review of 634 consecutive patients diagnosed with isolated PED or CSC in one or both eyes in the period from 2007 to 2014 at a single institution. Results: Pigment epithelium detachment (PED) in the absence of primary pathology other than angiographic choroidal hyperpermeability in the incident or fellow eye or manifest CSC in the fellow eye was found in 22 eyes in 19 patients. Follow-up ranged from 4 to 61 months. Five of 19 patients (26%) had classic CSC in the fellow eye. Transition from isolated PED to manifest CSC in the eye with PED was observed in seven eyes (33%) over a median untreated period of observation of 11 months (range, 1-32 months). A single session of PDT followed up 1-6 months later showed full resolution of the PED in seven (78%) of nine eyes. Of the 13 untreated eyes, five eyes (38%) underwent spontaneous resolution of the PED. Conclusion: Fellow-eye findings, conversion to CSC, resolution of PED after PDT or, less commonly, spontaneously support that isolated PED is a manifestation of CSC that represents an intermediate stage between pachychoroid and classic CSC. The chance of experiencing resolution of the PED was roughly twice as high with PDT as with untreated observation.
Eyes with foveal detachment and subretinal deposits that underwent PDT for CSC did not recover to the functional and structural level of the asymptomatic fellow eyes, irrespective of the number of episodes of CSC. The study indicates that subretinal deposits are associated with irreversible foveal damage in CSC.
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