Immune Mediator Profile in Aqueous Humor Differs in Patients with Primary Acquired Ocular Toxoplasmosis and Recurrent Acute Ocular Toxoplasmosis.

PURPOSE: To compare the intraocular cytokine and chemokine profiles in patients with acute primary acquired ocular toxoplasmosis (pOT) or recurrent ocular toxoplasmosis (rOT) and to correlate them with their clinical characteristics. METHODS: Aqueous humor samples were collected from 62 consecutive patients (21 pOT, 30 rOT, and 11 noninfected controls) and analyzed by multiplex assay. Correlations were assessed between cytokine/chemokine levels, type of inflammatory response (Th1, Th2, and Th17), and clinical characteristics. In all OT patients, the clinical diagnosis of either pOT or rOT was confirmed by positive intraocular Goldmann/Witmer-Desmonts coefficient. Correlations were assessed between a preselected panel of immune mediators and the clinical characteristics of OT. RESULTS: In pOT patients, increased levels of IL-2, IFN-γ, TNF-α, IL-15, IL-4, IL-5, IL-9, IL-13, IL-17, IL-1Rα, IL-6, IL-1ß, and chemokines MIP-1α, MIP-1ß, IP-10, Eotaxin, IL-8, RANTES, PDGF-bb, GM-CSF, G-CSF, and MCP-1 were found in comparison to those in controls (p < 0.05). Patients with rOT showed elevated levels of IL-2, IFN-γ, TNF-α, IL-15, IL-4, IL-5, IL-9, IL-17, IL-1Rα, IL-6, IL-1ß, and chemokines MIP-1α, IP-10, Eotaxin, IL-8, RANTES, PDGF-bb, G-CSF, and MCP-1 compared to controls (p < 0.05). In addition, IL-7 (p = 0.028) differed between pOT and rOT; IL-9 (p = 0.054) and IL-13 (p = 0.051) showed a tendency of higher concentration in pOT than in rOT. A negative correlation was found between IL-7 (p = 0.017) as well as IL-9 (p = 0.008) and the number of recurrences. Cytokine ratios showed no difference between pOT and rOT, indicating a dominant Th1-type response in both infectious groups. Moreover, a positive correlation was detected between IL-7, VEGF, IL-13 and age at aqueous humor sampling (p < 0.05). CONCLUSIONS: This study for the first time shows subtle differences between the intraocular cytokine profiles in patients with either acute pOT or rOT.

Therapy Rationale for Mineralocorticoid-Receptor Antagonists, Acetazolamide and a Switch of Therapy in Nonresponders in Central Serous Chorioretinopathy.

PURPOSE: To evaluate the efficacy of mineralocorticoid-receptor antagonists in comparison to acetazolamide and observation in the treatment of central serous chorioretinopathy. METHODS: Retrospective, interventional cohort study on 93 patients with acute or chronic central serous chorioretinopathy (37 patients: acetazolamide group, 20 patients: mineralocorticoid-receptor antagonist group, 8 patients: observation group, and 27 patients with a therapy switch between both medications). Main outcome measures were the change in best-corrected visual acuity, subretinal fluid (SRF) volume, central retinal prominence, and highest retinal prominence (HRP) at 12 weeks. RESULTS: HRP and SRF volume improved with statistical significance (P ≤ 0.05) after mineralocorticoid-receptor antagonist (P = 0.0000003 for the prominence, P = 0.008 for the volume) and acetazolamide (P < 0.0000001 for the prominence, P = 0.0000007 for the volume) treatment. HRP and SRF volume also improved after observation, but without statistical significance (P = 0.08 for the prominence, P = 0.72 for the volume). Corresponding visual acuity improved significantly in acetazolamide (P = 0.002) and mineralocorticoid-receptor antagonist (P = 0.03) treated patients. Interestingly, HRP and SRF volume in acetazolamide nonresponsive patients improved after switch to mineralocorticoid-receptor antagonists, whereas no benefit was seen in patients switching vice versa. CONCLUSIONS: Both medical treatments are effective first-line treatment options for central serous chorioretinopathy. In patients who are nonresponsive to acetazolamide, therapy switch to mineralocorticoid-receptor antagonists could be beneficial.

Baseline retrobulbar blood flow is associated with both functional and structural glaucomatous progression after 4†years.

BACKGROUND/AIMS: Previous studies suggest that vascular abnormalities are involved in the pathogenesis of open-angle glaucoma. This study aims to examine the relationship of baseline retrobulbar blood flow measurements with functional and structural glaucomatous progression in patients with open-angle glaucoma over 4 years. METHODS: In this study, 112 patients with open-angle glaucoma were examined at baseline and 78 with retrobulbar blood flow assessments were followed to 4 years. Colour Doppler imaging was used to evaluate retrobulbar blood flow. Structural disease progression was examined with optical coherence tomography and Heidelberg Retinal Tomography III. Functional disease progression was monitored with automated perimetry using Humphrey visual fields. Mixed-model analysis of covariance was used to test for significance of changes from baseline to 4-year follow-up. Two-sample t tests and χ2 tests were used to test for baseline blood flow differences between patients who progressed and those who did not progress. RESULTS: Patients who progressed structurally had a statistically significant lower baseline mean ophthalmic artery peak systolic velocity (PSV) (p=0.024) and ophthalmic artery end diastolic velocity (EDV) (p=0.012) compared with those who did not progress. Similarly, a lower baseline mean ophthalmic artery PSV (p=0.031) and ophthalmic artery EDV (p=0.005) were associated with patients who progressed functionally compared with those who did not progress after 4 years. CONCLUSIONS: In this study population, lower baseline ophthalmic artery blood flow velocities were associated with simultaneous structural and functional glaucoma progression after 4 years.

Control of head morphogenesis in an invertebrate asexually produced larva-like bud ( Cassiopea andromeda; Cnidaria: Scyphozoa).

Scyphopolyps of Cassiopea andromeda propagate asexually by forming larva-like buds which separate from the parent in a developmentally quiescent state. These buds metamorphose into sessile polyps when exposed to specific biogenic, chemical inducers. Morphogenesis of transversely dissected buds indicates the presence of pattern-determining signals; whereas the basal bud fragments may still form a complete scyphistoma the apical bud fragments develop spontaneously in the absence of an inducer into a polyp head without stalk and foot. Based on these findings Neumann (dissertation, Cologne University, 1980) postulated a head-inhibiting signal which is released at the basal pole and inhibits head formation at the apical end. Contrary to this hypothesis dissection itself might induce the development of head structures. The present study deals with the control of polyp head formation in C. andromeda. It concentrates on two points, namely the postulated head inhibitor and the involvement of compounds known to act during metamorphosis (the enzyme protein kinase C and the specific metamorphosis inducer Z-GPGGPA). We found that compared to intact buds and apical bud fragments transversely incised buds reached an intermediate stage of head development. This confirms Neumann's hypothesis. Consequently we focused on the mode of action and the chemical nature of the head-inhibiting signal in C. andromeda. Our results indicate that the head inhibitor may be included in one of six pooled fractions isolated from bud homogenate via gel filtration on a Sephadex G-50 column. The inhibitor is supposed to be water-soluble and to have a molecular weight of 850-1,500 Da. Furthermore we prove that head formation is not promoted by the metamorphosis-inducer Z-GPGGPA but is prevented by the inhibitors psychosine, chelerythrine and RO-32-0432 showing the involvement of protein kinase C in this process.