Peripapillary retinal nerve fibre layer thinning rate as a biomarker discriminating stable and progressing relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Peripapillary retinal nerve fibre layer (pRNFL) thickness is a strong candidate as a biomarker of axonal degeneration in multiple sclerosis (MS). The aim was to determine a cut-off value of pRNFL thinning rates in relapsing-remitting MS (RRMS) to discriminate between stable and progressing patients. METHODS: In this 3-year prospective longitudinal study on 141 RRMS patients, annual pRNFL thinning rates (aLpRNFL) were determined by individual linear regression models. The best possible cut-off value discriminating clinically progressing (physical progression or cognitive decline) and stable patients was defined by receiver operating characteristic analysis. Cut-off values were validated using a multivariate logistic regression model. RESULTS: Average aLpRNFL in progressing patients (2.4 µm, SD 2.1) was significantly higher compared to stable patients (0.5 µm, SD 1.2, P < 0.001). At a predefined specificity of 90%, aLpRNFL >1.5 µm was able to distinguish between stable and progressing RRMS with a sensitivity of 76.1%. aLpRNFL >1.5 µm was associated with a 15-fold increased risk of clinically progressing MS (P < 0.001). CONCLUSIONS: A cut-off of aLpRNFL discriminating clinically progressing and stable RRMS was identified. After validation in independent cohorts, this cut-off could be used as a biomarker of axonal degeneration supporting disease monitoring in daily clinical routine.

The effect of streptozotocin-induced diabetes mellitus on substance P and calcitonin gene-related peptide expression in the rat trigeminal ganglion.

Substance P (SP) and calcitonin gene-related peptide (CGRP) constitute the main sensory peptides in the trigeminal ganglion (TG). The objective of this study was to characterize peptidergic changes in the streptozotocin-induced diabetes mellitus rat model both quantitatively and qualitatively. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) and the levels of SP and CGRP were measured by means of radioimmunoassay (RIA) in a time-dependent manner. Peptide immunoreactivities were characterized by high pressure liquid chromatography (HPLC). The expression of both neuropeptides was examined 5 weeks after streptozotocin injection using in situ hybridization with 35S-labelled oligonucleotides. Saline-injected rats served as controls. SP was significantly decreased in the diabetic rat TG, i.e. , a 44.6% (+/-10.9) decrease after 1 week, 40.2% (+/-11.8) after 3 weeks and 72.3% (+/-14.6) after 5 weeks. CGRP was decreased only after 5 weeks (19.6% decrease +/-3.9), whereas at later stages, both peptide levels returned to normal values. HPLC revealed one major peak coeluting with the synthetic peptides. By using in situ hybridization, a significantly increased signal of both peptide-encoding mRNAs was found (43.8%), which seems to act to restore a diabetes-associated depletion of neuropeptides in the diabetic rat TG. The decreased SP- and CGRP levels in the diabetic rat TG reflect a diabetes-associated deficit which may be clinically relevant. Diabetes mellitus is associated with a variety of ocular complications, even corneal complications, including decreased corneal sensitivity, which in many ways resemble those after interruption of the normal trophic innervation of the eye. Our results point to reduced availability of neuropeptides for corneal innervation and may thus support the idea of a partial loss of trophic influences from the trigeminal nerve in diabetics.

Inhibitory effect of certain neuropeptides on the proliferation of human retinal pigment epithelial cells.

AIMS: To define the effect of the neuropeptides substance P, calcitonin gene related peptide, vasoactive intestinal polypeptide, neuropeptide Y, and secretoneurin on the proliferation of human retinal pigment epithelial (RPE) cells. METHODS: ARPE-19 cells were used. The cells were cultured in Dulbecco's modified Eagle's medium. 1000 and 2000 cells were incubated with the peptides for 3 and 5 days, and the effect of the peptides was evaluated by an ATP lite assay dose dependently. Furthermore, specific antagonists at 10(-6) M were used to find out whether the effect would be reversed. RESULTS: In brief, each of the peptides tested had an inhibiting effect. This inhibiting effect was weak but highly significant, averaging 10% to 15%, and was most pronouncedly seen at concentrations between 10(-10) M and 10(-14) M. Each antagonist reversed the inhibiting effect fully. CONCLUSIONS: These results clearly indicate that RPE cells are under neural control and the low effective concentration of the peptides may be the one physiologically acting on these cells. The results are of important relevance both physiologically and pathophysiologically: physiologically, the inhibitory effect may mean that these peptides cause the cells to remain in a differentiated condition. Pathophysiologically, the findings are relevant in proliferative vitreoretinopathy where RPE cells proliferate in excess. The authors hypothesise that the inhibiting effect diminishes when these cells are swept out and actively migrate from their physiological location and thus, dedifferentiate and begin to proliferate. This hypothesis improves the knowledge of the initial processes in the pathogenesis of the disease as there seems to be a discrepancy between facilitatory and inhibitory influences favouring the former in proliferative vitreoretinopathy. Furthermore, these neuropeptides constitute the first endogenous inhibitors of RPE cell proliferation.

Iris transillumination defects in patients with primary open angle glaucoma.

PURPOSE: To examine the incidence and pattern of iris transillumination defects in patients with primary open angle glaucoma (POAG) with and without vascular dysregulation, in comparison to controls. METHODS: We prospectively examined 24 patients with POAG (M/F 10:14; mean age 59 +/- 14, range 21-76 years) and 23 controls (M/F 10:13; mean age 52 +/- 15, range 25-86 years). Vascular dysregulation was presumed if patients had a typical medical history of vasospasm and a pathological result in nailfold capillaroscopy. Iris transillumination defects were visualized by video-taped, digitized diaphanoscopy and assessed by two blinded observers. RESULTS: We found significantly more iris transillumination defects in POAG than in controls (54.2% vs. 8.7%; chi2 = 8.85; df = 1; p = 0.002). The defects in POAG showed a characteristic radially-streaked pattern different from those described, for instance, in pigment dispersion syndrome, pseudoexfoliation syndrome, and acute glaucoma. Glaucoma patients with vascular dysregulation had a tendency to a higher incidence of transillumination defects than non-vasospastic patients, though this finding was not significant. CONCLUSIONS: Patients with POAG have a higher incidence of iris transillumination defects than controls. The underlying mechanisms are not yet clear and call for further investigation.

Intraocular pressure during lumbar disc surgery in the knee-elbow position.

Increased intraocular pressure is often implicated in the aetiology of postoperative visual impairment. Such an increase in intraocular pressure has been demonstrated in the prone position. We investigated intraocular pressure in seven patients undergoing lumbar disc surgery in the knee-elbow position with the head resting on a cushion and turned to the side. Measurements were performed in the supine position before induction of anaesthesia and in the knee-elbow position after surgery with the patient still anaesthetised. After a mean (SD) duration of prone positioning of 121 (18) min, mean (SD) intraocular pressure in the nondependent eye was unchanged when compared to the awake state (17.7 (2.4) mmHg vs 18.9 (5.5) mmHg), whereas the intraocular pressure in the dependent eye had significantly decreased (17.0 (3.6) mmHg vs 8.1 (1.8) mmHg; p < 0.01). These results may be important for choosing the optimal position for spinal surgery when an increase in intraocular pressure should be avoided.

Tolerance of N-chlorotaurine, a new antimicrobial agent, in infectious conjunctivitis - a phase II pilot study.

N-Chlorotaurine (NCT) is an endogenous microbicidal oxidant. This open pilot study (phase IIa) with 9 patients was done to gain first knowledge on the tolerance of NCT in infectious conjunctivitis. By application of 1% NCT 5 times a day, no adverse effects could be observed. All 6 subjects with bacterial conjunctivitis were cured within 3-5 days. Two subjects with epidemic keratoconjunctivitis were treated for 7-10 days and 1 subject with herpes simplex blepharitis for 3 days with no rapid improvement but probable mitigation of inflammation. Therefore, NCT seems to be useful in the treatment of infectious conjunctivitis, and further investigation on its therapeutic efficacy is suggested.