Isolated pigment epithelium detachment: evidence for relation to central serous chorioretinopathy and effect of photodynamic therapy.

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.

Multifocal central serous chorioretinopathy with photoreceptor-retinal pigment epithelium diastasis in heritable pulmonary arterial hypertension.

PURPOSE: To report atypical central serous chorioretinopathy and choroidal thickening in a patient with heritable pulmonary arterial hypertension. METHODS: A 40-year-old man with heritable pulmonary arterial hypertension presented with blurred vision in his left eye and was followed up for 1 year with clinical examination, enhanced depth optical coherence tomography, fluorescein and indocyanine green angiography, and fundus photography. RESULTS: At presentation, atypical central serous chorioretinopathy with multiple retinal pigment epithelial detachments, a thick subfoveal choroid, and dilated choroidal vessels were seen in the patient's symptomatic left eye. After treatment for pulmonary hypertension, the serous detachments disappeared and choroidal thickness gradually decreased over a period of 4 weeks and remained unchanged at 13 months of follow-up. CONCLUSION: Central serous chorioretinopathy and choroidal thickening that responded to treatment of pulmonary arterial hypertension suggest a pathophysiological link between pulmonary arterial hypertension and central serous chorioretinopathy, perhaps mediated by choroidal venous stasis.

Cadherin 5 is regulated by corticosteroids and associated with central serous chorioretinopathy.

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.

Foveal function and thickness after verteporfin photodynamic therapy in central serous chorioretinopathy with hyperautofluorescent subretinal deposits.

PURPOSE: To assess the prognostic effect of subretinal deposits in eyes with central serous chorioretinopathy (CSC). METHODS: The study included 21 eyes with foveal detachment and subretinal deposits at presentation that underwent photodynamic therapy (PDT). No symptoms or signs of CSC were found in the fellow eyes. Microperimetry, autofluorescence imaging, and optical coherence tomography were performed in both eyes before and after PDT. Subgroup analyses included comparison of eyes with an initial episode versus a recurrent episode of CSC. RESULTS: Four months after PDT, foveal sensitivity had improved significantly in both initial episode eyes and recurrent episode eyes, but sensitivity remained at 3.1 dB (SD = 3.06, P = 0.008) and 2.7 dB (SD = 3.55, P = 0.028), respectively, lower than in the fellow eyes. Four months after PDT, foveal thickness was 245 µm (SD = 24.2) in the initial episode eyes versus 285 µm (SD = 22.6) in the fellow eyes (P < 0.001) and 246 µm (SD = 33.7) in the recurrent episode eyes versus 291 µm (SD = 24.8) in the fellow eyes (P = 0.001). CONCLUSION: 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.

Choroidal thickness following extrafoveal photodynamic treatment with verteporfin in patients with central serous chorioretinopathy.

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 (full-dose 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 µm [mean; 95% confidence interval (CI(95) ) 356-458 µm] to 349 µm (mean; CI(95) 300-399 µm; p < 0.0001), and subfoveal choroidal thickness was reduced from 421 µm (mean; CI(95) 352-489 µm) to 346 µm (mean; CI(95) 278-414 µm; p = 0.0001). Initially, subfoveal choroidal thickness was significantly increased in the treated eye compared with the healthy fellow eye (mean 324 µm; CI(95) 273-376 µm; 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.

Apical atrophy of retinal pigment epithelial detachments in central serous chorioretinopathy.

PURPOSE: To describe a presumed precursor stage of central serous chorioretinopathy (CSC). METHODS: Two patients were identified during follow-up study of patients with CSC or CSC-related conditions. Two patients first seen with retinal pigment epithelial detachment subsequently developed findings compatible with CSC. RESULTS: A juxtafoveal retinal pigment epithelial detachment with apical atrophy of the retinal pigment epithelium with corresponding severe attenuation of the pigmentation of the retinal pigment epithelium was observed in both patients. One of the patients presented with a serous neurosensory retinal detachment with smokestack leakage 7 years after first being seen. The other patient was never seen with a neurosensory detachment. CONCLUSION: Isolated pigment epithelial detachment with apical retinal pigment epithelial atrophy may represent a precursor stage of CSC.

Characterization of subretinal fluid leakage in central serous chorioretinopathy.

PURPOSE: The purpose of the study was to determine which category of hydrodynamic phenomena the smokestack in central serous chorioretinopathy (CSC) most likely belongs to: leakage by diffusion or bulk flow. METHODS: Fluorescein angiograms of 13 eyes of 13 patients were reviewed and analyzed quantitatively. Two methods were used to assess the rate of fluid leakage. One was based on observation of the expansion rate of the bubble of stained fluid seen in the earliest phase of the angiogram, and the other one compared the area of the source of the leakage to the remaining area of retinal pigment epithelium (RPE) exposed to subretinal fluid, by using a standard value for RPE fluid resorption capacity per unit surface area and assuming that resorption equals leakage. RESULTS: The mean rates of leakage were 16.2 µL/mm(2)/h (95% CI, 11.9-22.1) with the expanding-bubble method and 16.1 µL/mm(2)/h (95% CI, 12.0-21.7) with the area-of-resorption method (P = 0.95, linear correlation r = 0.94). The repeatability coefficient for both methods was 36.3%. CONCLUSIONS: 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.

Laser Doppler flowmetry is valid for measurement of cerebral blood flow autoregulation lower limit in rats.

Laser Doppler flowmetry (LDF) is a recent technique that is increasingly being used to monitor relative changes in cerebral blood flow whereas the intra-arterial 133xenon 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 CO2 reactivity with the 133xenon injection technique as the gold standard. Simultaneous measurements of cerebral blood flow (CBF) were collected by LDF (CBF(LDF)) and the 133xenon 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 CO2 (P(a,CO2)). 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 133xenon and the LDF techniques: 65 +/- 3.9 mmHg and 60 +/- 5.6 mmHg, respectively. Linear regression analysis yielded CBF(Xe) = (1.02 x CBF(LDF)) + 9.1 and r = 0.90. Even for substantial changes in P(a,CO2), 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 CO2 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.

Cerebral pressure autoregulation and vasoreactivity in the newborn rat.

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-CO2 reactivity was estimated to 13.4% per kPa (95% CI, 2-24.8%), p=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=0.80). CBF pressure autoregulation and reactivity to CO2 operate in the newborn rat. This model may be useful for future investigations concerning perinatal pathophysiology in the immature brain.

[Late sequelae after severe intracranial hemorrhage in 23 premature children. Parental perspectives]. / Senfølger efter alvorlig hjerneblødning hos 23 praemature børn. Foraeldrenes opfattelse.

INTRODUCTION: Cerebral hemorrhage in very premature infants results in high mortality and increases the risk of handicap. The aim of the study was to evaluate: 1) the parental opinion of the child's motor function, 2) their opinion of the child's development compared to their expectations, and 3) how they experienced the information given by nurses and doctors at the time of the diagnosis. MATERIAL AND METHODS: Parents of 23 of 24 premature infants answered a questionnaire. During the neonatal period all infants had suffered from a major cerebral hemorrhage. The children had reached an age between two and seven years. RESULTS: Half of the children had motor deficits (48%), and 22% of the children had severe motor problems. Future development and motor function were reliably estimated by the doctors during the neonatal period. Most of the parents (79%), however, estimated that their child's development was better than expected. The majority of the parents were satisfied with the information that had been given at the time of diagnosis, and they had received adequate support. DISCUSSION: Cerebral hemorrhage in premature infants is still a major problem. Our results, however, do not suggest major change of clinical practice.