[Combination of Intravitreal rTPA, gas and ranibizumab for extensive subfoveal haemorrhages secondary to neovascular age-related macular degeneration]. / Kombinierte intravitreale Injektion von rTPA, Gas und Ranibizumab zur Behandlung grossflächiger subfovealer Blutungen bei neovaskulärer altersbedingter Makuladegeneration.

BACKGROUND: The aim of this study was to evaluate the clinical outcomes of the combination therapy with intravitreal recombinant tissue plasminogen activator (rTPA), gas and lucentis for patients with extensive subfoveal haemorrhages secondary to neovascular age-related macular degeneration (AMD). METHODS: In this retrospective clinical study 10 eyes with extensive subfoveal haemorrhages secondary to neovascular AMD were included and treated with intravitreal rTPA (0.05 mL; 0.025 mg/0.1 mL in 0.9% NaCl), 100% sulphur hexafluoride (SF(6)) gas (0.5 mL) and lucentis (0.05 mL, 10 mg/mL) within two weeks after the onset of the subretinal haemorrhage. Retreatments with lucentis were performed at 4-week intervals if there were persistent submacular haemorrhages or signs of active choroideal neovascularisation (CNV). The treatment effect was evaluated using best-corrected visual acuity (VA, Snellen), complete ophthalmic examination, fluorescein angiography (FLA) and optical coherence tomography (OCT). RESULTS: Mean observation period was 6.4 A+/- 3.7 months (range: 3 - 13 months). With regard to VA, in 7 eyes there was an increase in VA (> or = 1 Snellen lines), in 1 eye a stabilisation and in 2 eyes a decrease in VA (> or = 1 Snellen lines). At the end of follow-up time, with regard to VA no significant difference was observed compared to baseline (p = 0.41). In 1 patient an intra-operative transient central arterial occlusion and in another patient a corneal erosion and an increase of intraocular pressure up to 27 mmHg were observed after initial combination treatment. On average there were 1.9 A+/- 1.3 retreatments indicated after initial treatment. CONCLUSION: The combination of rTPA, gas and lucentis is a valuable therapy for extensive subfoveal haemorrhages secondary to neovascular AMD resulting in stabilisation of both VA and morphologic parameters.

[The role of Stratus OCT in anti-VEGF therapy. Qualitative and quantitative assessment of neovascular AMD]. / Die Rolle des Stratus-OCT bei der Anti-VEGF-Therapie : Qualitative und quantitative Beurteilung bei neovaskulärer AMD.

BACKGROUND: The evaluation of OCT3 during anti-VEGF therapy. METHODS: A total of 29 patients with choroidal neovascularization secondary to AMD received 3 intravitreal injections of ranibizumab. OCT examination and visual acuity testing (ETDRS) were performed before therapy onset, after 1 week and after 1, 2 and 3 months. RESULTS: The central retinal thickness (CRT) was assessed correctly by OCT in 128 out of 145 measurements. There was a distinct (84%) but not significant correlation between decrease in central retinal thickness and increase in visual acuity. Incorrect retinal layer segmentation and inadequate CRT measurements were a significant technical limitation. CONCLUSION: During anti-VEGF therapy, OCT allows documentation and quantification of morphologic retinal changes and in most cases also for an estimation of functional improvement.

Quantification of optic nerve blood flow changes using magnetic resonance imaging.

PURPOSE: To evaluate the possibilities of magnetic resonance imaging (MRI) for quantification of pharmacologically induced changes in optic nerve microcirculation. METHOD: T2-weighted MRI sequences were used to image the eye, optic nerve, and frontal cortex in rats. Two sets of control images before and one set during Gd (DTPA) infusion were recorded. Blood flow values for two regions of the optic nerve (an anterior part, including the optic nerve head, and a more posterior part) and the frontal cortex were calculated by image analysis from the change in signal intensity, as already reported for cerebral blood flow. For each rat, a control experiment before drug administration and a second experiment 30 minutes after subcutaneous injection of either placebo (n = 7), timolol (n = 7), or SDZ GLC-756, a dopamine D-1 antagonist and D-2 agonist (n = 7), were carried out in a double-blind fashion. RESULTS: Mean basal blood flow values were found between 29.4 and 45.6 ml/100 g per minute in the anterior part of the optic nerve, 38.3 and 42.9 ml/100 g per minute in the posterior part of the optic nerve, and 68.0 and 75.0 ml/100 g per minute in the frontal cortex. Placebo and timolol did not cause significant changes. SDZ GLC-756 significantly increased blood flow by 238% +/- 65% in the anterior part and by 87% +/- 40% in the posterior part of the optic nerve. CONCLUSIONS: These results suggest that MRI provides quantification of optic nerve blood flow and that dopaminergic substances increase optic nerve blood flow.

Potential role of nitric oxide and endothelin in the pathogenesis of glaucoma.

Glaucoma is an optic nerve head neuropathy in which retinal ganglion cells are lost. A clear association exists between glaucoma and different risk factors, such as high intraocular pressure (IOP) or blood-flow dysregulation. Nitric oxide (NO) and endothelin, two recently identified cellular mediators, appear to be involved in the regulation of IOP as well as in the modulation of ocular blood flow. To some extent, NO is also involved in apoptosis, a mechanism of cell death that can lead to retinal ganglion cell loss in glaucoma. This article provides a short and simplified overview of the biochemistry of NO and endothelin and highlights the potential role of these two mediators in certain important aspects related to the pathogenesis of glaucoma.

Choroidal capillary and venous congestion in central serous chorioretinopathy.

PURPOSE: Abnormalities in choroidal perfusion have been hypothesized to be causative factors in central serous chorioretinopathy. This prospective study was performed to evaluate changes in the choroidal circulation in cases of central serous chorioretinopathy. METHODS: In 32 consecutive patients with acute or chronic recurrent central serous chorioretinopathy, complete clinical ophthalmologic examinations, fluorescein angiography, and indocyanine green angiography with a scanning laser ophthalmoscope and a digital imaging system were performed. RESULTS: All patients with acute and chronic recurrent central serous chorioretinopathy demonstrated a localized delay in arterial filling followed by choroidal hyperperfusion in the area of the damaged retinal pigment epithelium, frequently associated with dilated capillaries and dilated draining venules in one or more choroidal lobules. These changes corresponded to areas with pigment epithelial detachment or focal leakage from the retinal pigment epithelium found in fluorescein angiography. Furthermore, in some patients, localized choroidal ischemia could be observed in additional areas throughout the central fundus in both diseased eyes and normal fellow eyes. CONCLUSIONS: Delayed arterial filling followed by capillary and venous hyperemia, angiographically appearing as capillary and venous congestion, can be observed frequently in eyes with central serous chorioretinopathy. The results suggested that capillary or venous congestion after ischemia in one or more choroidal lobules might be the reason for the choroidal hyperpermeability associated with central serous chorioretinopathy.

Influence of acquisition parameters on hemodynamic measurements with the Heidelberg Retina Flowmeter at the optic disc.

PURPOSE: The Heidelberg Retina Flowmeter (HRF; Heidelberg Engineering GmbH, Heidelberg, Germany) is a new instrument that determines hemodynamic variables at discrete locations of the retina and the optic disc. The objective of this study was to evaluate the influence of various HRF recording settings on the long-term variability of the HRF parameter. "Flow," computed at the optic nerve head in healthy individuals. METHODS: The authors obtained 2 sets of 5 HRF recordings in 10 healthy individuals (age range, 23-60 years). The HRF recordings were obtained within a scan area of 10 degrees x 2.5 degrees (set 1) and 20 degrees x 5 degrees (set 2). For each set, the HRF recordings were obtained on 5 consecutive days. Respective HRF recordings for both sets were obtained on the same days. On these recordings, the HRF parameter, "Flow," was computed at 3 different regions of interest (temporal superior, temporal inferior, and temporal rim of the optic disc). At all three locations, Flow was computed within windows of measurement of 10 pixels x 10 pixels and 20 pixels x 20 pixels. The effect of larger windows (30 pixels x 30 pixels, 40 pixels x 40 pixels, and 50 pixels x 50 pixels) was tested at the temporal rim of the optic disc. RESULTS: The highest reliability coefficient was reached with a scan area of 20 degrees x 5 degrees at the temporal superior rim of the optic disc (r = 0.93). Within a scan area of 20 degrees x 5 degrees, the size of the user-defined measuring window did not influence the reliability. Two models of analysis of variance disclosed that the only effect on the computed value of Flow that reached statistical significance was that because of the scan area (F = 11.172; p = 0.001). The location of the window of measurement and its size had no statistically significant effect. CONCLUSION: The present results show that the location of the window of measurement has an important effect on the long-term variability of the HRF parameter, Flow. In addition, different scan areas influence significantly the computed values of this parameter.

Gliosis-like retinal alterations in glaucoma patients.

SUMMARY: Morphological alterations resembling fine epiretinal gliosis in the midperiphery of the retina of glaucoma patients were examined biomicroscopically. Examination with a laser-scanning ophthalmoscope (Zeiss CLSO) incorporating an argon laser confirmed sharply bordered, patchy retinal alterations in the superficial layers. These alterations were predominantly in the Bjerrum area but did not conform to the shape of the nerve fiber bundles. Patchy retinal alterations were found to be absent or rare in nonglaucomatous controls (0 of 15 controls) but to occur quite often in people with glaucoma. Although all glaucoma patients examined had typical optic nerve heads and visual field damage, the prevalence of patchy retinal alterations was especially high in the group with progressive damage despite successfully reduced intraocular pressure (13 of 15; 86.7%); the alterations were only slightly less prevalent in the normal-tension-glaucoma group (11 of 16; 68.8%).

Descriptive information of topographic parameters computed at the optic nerve head with the Heidelberg retina tomograph.

PURPOSE: To analyze the frequency distribution and descriptive information of topometric data obtained with the Heidelberg Retina Tomograph (HRT) in a normal population. METHODS: Topographic measurements of the optic disc were acquired and evaluated using the HRT in 225 subjects between 12 and 90 years of age. After randomly selecting one eye per subject, the frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles were evaluated for topographic parameters computed by the HRT. The influence of age, intraocular pressure (IOP), disc size, and disc shape on optic disc topometric data was analyzed. A principal component analysis of the topometric parameters was performed. The frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles of the interocular difference in topographic parameters were evaluated. RESULTS: All topographic parameters showed a unimodal but not necessarily normal distribution. None of the parameters showed a relevant correlation with age, IOP (in the normal range), and overall shape of the anterior optic nerve, but a few parameters showed a clinically significant correlation with disc size. A principal component analysis identified four relevant factors (optic nerve cup, retinal nerve fiber layer, optic disc size, and optic nerve cup shape) in the entire data set of optic nerve topometric data. The absolute value of all interocular differences in topographic parameters showed an asymmetric but unimodal distribution. CONCLUSION: The mathematical description of the optic nerve cup shape provides information on optic nerve head topography independently from cupping, nerve fiber layer thickness, and disc size. Potentially, quantification of further aspects in optic nerve head topography might improve the discriminatory power of computerized quantitative optic nerve head analysis.

Interocular differences in optic disc topographic parameters in normal subjects.

PURPOSE: To test the interocular differences in optic disc topography in normal subjects by means of confocal scanning laser ophthalmoscopy. METHODS: Topographic measurements of the optic disc were evaluated by means of confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph) in 314 eyes of 157 healthy volunteers. The examination was started randomly either with the right eye or the left eye. Differences between right and left eyes in disc area, cup area, cup volume, cup/disc area ratio, rim area, rim volume, maximum cup depth, cup shape measure, retinal nerve fiber layer thickness, and retinal nerve fiber cross section area for 360 degrees and for the temporal and nasal regions of the optic nerve head were evaluated by means of Student t-test. The same parameters were assessed in a subgroup of 80 elderly (age> 50 years) healthy subjects. Holm's sequentially rejective method was used for significance correction of multiple comparisons. RESULTS: Significant interocular differences in the average retinal nerve fiber layer thickness (p = 0.0010) and retinal nerve fiber layer cross section area (p = 0.0036) were found, with the right eye showing, on the average, lower values. The left eye showed a larger retinal nerve fiber layer thickness in 94 subjects (59.87%) and a larger retinal nerve fiber cross section area in 101 subjects (64. 33%). In the temporal optic disc area there were no statistically significant differences in topometric data (p> 0.05). In the nasal area, significant interocular differences in the retinal nerve fiber layer thickness (p = 0.0002) and retinal nerve fiber layer cross section area (p = 0.0003) were found. Similar results were found when the group of subjects older than 50 years was considered. CONCLUSIONS: This study demonstrates systematic interocular differences in optic disc topometric data. Such a finding, be it due to methodological or biological reasons, should be taken in consideration in clinical trials.

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.