Reproducibility of high-resolution optical coherence tomography measurements of the nerve fibre layer with the new Heidelberg Spectralis optical coherence tomography.

AIM: Conventional time-domain OCT technology for detection of retinal nerve fibre layer (RNFL) neurodegeneration suffers from technical inaccuracy owing to a lack of exact scan centring around the optic disc as well as a true follow-up possibility. In this study, the authors evaluated a novel high-resolution spectral-domain OCT device (SD-OCT) with an incorporated eye-tracking feature in its ability to objectively measure the RNFL thickness (RNFLT) by testing intraobserver reproducibility in a series of healthy volunteers. METHODS: Triplicate circumferential RNFL scans of six peripapillary sectors were obtained from both eyes of all 31 participants. The authors compared the measurements of RNFLT during three separate examination days under miotic (Mi) and mydriatic (My) pupil conditions using a high-speed (HS) and high-resolution (HR) scan-acquisition mode. To examine the intersession reproducibility of the SD-OCT measurements, the mean, SD and coefficient of variation (COV) were calculated. RESULTS: No significant differences were found in all groups, independent of the mode of image acquisition and examination day (p always >0,05). Under all conditions, low COVs between 0.545% and 3.97% (intrasession COV on baseline) were found. The intersession COV with activated follow-up mode ranged between 0.29% and 1.07%. In both settings, the temporal sector showed the highest COV values. CONCLUSIONS: True follow-up measurement of identical peripapillary regions may enable clinicians to detect discrete levels of retinal thickness change over time. This constitutes a crucial prerequisite for a reliable monitoring of subtle RNFL changes in neurodegenerative disorders.

Effects of high-dose prednisolone on optic nerve head blood flow in patients with acute optic neuritis.

BACKGROUND: In this study, patients with optic neuritis were treated with high-dose prednisolone. Little information is available about the effects of this treatment on ocular blood flow. We set out to investigate the effects of high-dose prednisolone on optic nerve head (ONH) blood flow in patients with acute optic neuritis. METHODS: Thirteen patients with acute optic neuritis were included in the study. 1000 mg of prednisolone was infused intravenously over 30 minutes on 3 consecutive days. On each study day, ONH blood flow was measured using laser Doppler flowmetry. The ocular hemodynamic measurements were performed on the unaffected eye of the patients with unilateral acute optic neuritis before and immediately after cessation of the infusion. Intraocular pressure (IOP) and systemic blood pressure was measured before and after the infusion on each study day. Data was analyzed using a repeated measures ANOVA model. RESULTS: Prednisolone increased ONH blood flow in the patients under study (p = 0.04), although the effects were in generally small. No significant change in mean arterial pressure (p = 0.70) or IOP (p = 0.20) could be detected in the patients treated with high-dose prednisolone. CONCLUSIONS: A small but significant increase in ONH blood flow resulted from infusion of high-dose prednisolone. Further studies are required to investigate whether this effect contributes to the therapeutic efficacy of cortisone in patients with optic neuritis.

Respiratory chain complex-I defect mimicking myasthenia.

In a 67-year-old woman with ptosis, double vision, dysphagia, ambiguous Tensilon tests, normal acetylcholine-receptor antibodies, normal thymus, and repeatedly abnormal responses to low-frequency repetitive stimulation, ocular myasthenia was suspected. Pyridostigmin was ineffective, but corticosteroids improved the abnormalities. Despite this therapy, lower-limb weakness developed. Reevaluation disclosed abnormal increase of serum lactate during slight exercise, myogenic electromyography, ragged-red fibers, reduced oxidative enzyme staining and abnormally shaped and structured mitochondria on muscle biopsy, and a respiratory chain complex-I defect on biochemical investigation of the muscle homogenate. Respiratory chain disorder due to complex-I defect with abnormal decremental response to low-frequency repetitive stimulation was diagnosed. It is concluded that respiratory chain disorders due to a complex-I defect may mimic ocular myasthenia clinically, electrophysiologically, and even therapeutically.

A new colour vision arrangement test to detect functional changes in diabetic macular oedema.

AIM: A study was undertaken to investigate the correlation between colour discrimination tests and the presence of macular oedema in patients with type I diabetes to find a sensitive diagnostic tool for the detection of early functional changes. METHODS: The study was performed in 39 type I diabetic patients, 10 with and 29 without macular oedema. The examination included biomicroscopy, fundus photography of the macula, videofluorescein angiography, the LogMAR visual acuity chart, Farnsworth-Lanthony desaturated D-15 test, and the new Mollon-Reffin "Minimalist" test for colour vision deficiencies version 6.0. RESULTS: A highly significant correlation was found between the tritan value of the Mollon test and the presence of clinically significant macular oedema (p<0.0015), with a high sensitivity (88.9%) and specificity (93.3%). The DD-15 test was not significant (p=0.345) and showed low sensitivity for the presence of macular oedema (36%). All variables concerning the grading of macular oedema showed a highly significant association with the tritan values of the Mollon test (p<0.0001). CONCLUSION: The results suggest that the Mollon-Reffin "Minimalist" test version 6.0 is the best colour discrimination test for detecting macular oedema, with higher specificity and sensitivity than the other methods used in the study.

Apoplexy of a pituitary macroadenoma with reversible third, fourth and sixth cranial nerve palsies following administration of hypothalamic releasing hormones: MR features.

Pituitary apoplexy in patients with pituitary macroadenomas can occur either spontaneously or following various interventions. We present a case of a 71-year-old woman who developed third, fourth, and sixth cranial nerve palsies following administration of the four hypothalamic releasing hormones for routine preoperative testing of pituitary function. The MR examination showed interval tumor growth with impression of the floor of the third ventricle. There were also changes in signal intensity characteristics of the mass, suggestive of intratumoral bleeding. A transsphenoidal surgery with subtotal resection of the pituitary adenoma was performed. Microscopical examination revealed large areas of necrosis and blood surrounded by adenomatous tissue. Third, fourth, and sixth cranial nerve palsies completely resolved within 4 months. We conclude that MR imaging is useful in the demonstration of pituitary apoplexy following preoperative stimulation tests, but we suggest that these tests should be abandoned in patients with pituitary macroadenomas.

Growth hormone replacement therapy is not associated with retinal changes.

GH and/or growth factors are thought to play a role in the pathogenesis of diabetic retinopathy. In addition, the occurence of retinal changes mimicking diabetic retinopathy in two GH-deficient (GHD) patients receiving GH replacement therapy (GHRT) has recently been reported. The present study was performed to evaluate whether this was a coincidence or whether GHRT might regularly induce retinal changes. Sixty-one GHD patients on GHRT with a mean age of 42.5 +/-17.3 yr were examined by one ophthalmologist (AR). The mean duration of GHRT was 8.4 +/- 3.7 yr in childhood onset and 3.5 +/- 2.1yr in adult onset patients. Plasma insulin-like growth factor I concentrations were 76.4 +/- 49.6 ng/mL before GHRT and 244.3 +/- 119.2 ng/mL while receiving GHRT with a dose of 1.7 +/- 0.7 IU/day. After pupil dilatation with tropicamide, fundus examinations of both eyes were performed using a Volk 90 diopter fundus lens with a slit lamp (Haag Streit, Bern, Switzerland). In none of the patients were vascular or retinal changes like macular edema, microaneurysms, hemorrhages, hard exsudates, cotton wool spots, preproliferative signs, or proliferations found. The optic discs were also normal in all patients. We conclude, therefore, that long-term GHRT can be administered safely in GHD patients without an increased risk of retinal changes.

Delayed visual deterioration after surgery for pituitary adenoma.

Despite its description in the literature there remains uncertainty about the incidence, the pathophysiological basis and the best management of a delayed visual deterioration in the presence of an empty sella after surgery for pituitary adenomas. Out of a series of 501 patients with pituitary adenomas operated on at our institution between 1984 and 1996, four patients (0.8%) developed a worsening of their visual function 3 to 37 months after surgery in the absence of tumour recurrence. None of the patients had received radiotherapy. Magnetic resonance imaging (MRI) ruled out compression by tumour and showed herniation of suprasellar structures into an empty sella. In three cases re-operation by a subfrontal approach with freeing of the optic structures from tethering scar tissue led to an improvement of visual deficits. In one case a spontaneous recovery was initiated by a minor head injury. Although apparently a rare event, our cases provide evidence for the occurrence of a potentially reversible delayed deterioration of visual function after surgery for pituitary adenomas. Based on our operative findings and our outcome we recommend re-operation by a transcranial approach in patients in whom repeated ophthalmological testing does not show spontaneous improvement within a short period of time.

Red, green, and red-green hybrid pigments in the human retina: correlations between deduced protein sequences and psychophysically measured spectral sensitivities.

To analyze the human red, green, and red-green hybrid cone pigments in vivo, we studied 41 male dichromats, each of whose X chromosome carries only a single visual pigment gene (single-gene dichromats). This simplified arrangement avoids the difficulties of complex opsin gene arrays and overlapping cone spectral sensitivities present in trichromats and of multiple genes encoding identical or nearly identical cone pigments in many dichromats. It thus allows for a straightforward correlation between each observer's spectral sensitivity measured at the cornea and the amino acid sequence of his visual pigment. For each of the 41 single-gene dichromats we determined the amino acid sequences of the X-linked cone pigment as deduced from its gene sequence. To correlate these sequences with spectral sensitivities in vivo, we determined the Rayleigh matches to different red/green ratios for 29 single-gene dichromats and measured psychophysically the spectral sensitivity of the remaining green (middle wavelength) or red (long wavelength) cones in 37 single-gene dichromats. Cone spectral sensitivity maxima obtained from subjects with identical visual pigment amino acid sequences show up to a approximately 3 nm variation from subject to subject, presumably because of a combination of inexact (or no) corrections for variation in preretinal absorption, variation in photopigment optical density, optical effects within the photoreceptor, and measurement error. This variation implies that spectral sensitivities must be averaged over multiple subjects with the same genotype to obtain representative values for a given pigment. The principal results of this study are that (1) approximately 54% of the single-gene protanopes (and approximately 19% of all protanopes) possess any one of several 5'red-3'green hybrid genes that encode anomalous pigments and that would be predicted to produce protanomaly if present in anomalous trichromats; (2) the alanine/serine polymorphism at position 180 in the red pigment gene produces a spectral shift of approximately 2.7 nm; (3) for each exon the set of amino acids normally associated with the red pigment produces spectral shifts to longer wavelengths, and the set of amino acids normally associated with the green pigment produces spectral shifts to shorter wavelengths; and (4) changes in exons 2, 3, 4, and 5 from green to red are associated with average spectral shifts to long wavelengths of approximately 1 nm (range, -0.5 to 2.5 nm), approximately 3.3 nm (range, -0.5 to 7 nm), approximately 2.8 nm (range, -0.5 to 6 nm), and approximately 24.9 nm (range, 22.2-27.6 nm).

[Color duplex of retrobulbar arteries in normal pressure and open angle glaucoma]. / Farbduplex der retrobulbären Arterien bei Normaldruck- und Offenwinkelglaukom.

BACKGROUND: Various authors report that the glaucomatous loss of function is due to a chronic anterior ischemic optic neuropathy, being caused by a disturbed relationship between intraocular pressure and perfusion pressure in the posterior short ciliary arteries, which possibly leads to increased resistance in the ciliary vascular system. The authors attempt to test this hypothesis by measuring the vascular resistance (Resistance Index) in the ciliary vessel system by means of color Doppler sonography. PATIENTS AND METHODS: 35 eyes of 35 patients, suffering from open angle glaucoma (OAG), with a mean age of 65.3 years, were examined as well as 35 eyes of 35 patients with normal tension glaucoma (NTG), whose mean age was 65.8 years. Both glaucoma groups were compared to an age- and sex-matched control group of healthy volunteers. The color-Doppler measurements were performed with an Acuson 128 XP/10, which allows imaging of all retrobulbar arteries, the ophthalmic artery, the central retinal artery and the short posterior ciliary arteries, and also guarantees the precise calculation of blood flow velocity and resistive index (RI). The RI was statistically evaluated. RESULTS: The resistance index of all retrobulbar arteries showed a statistically significant increase (p < 0.05) according to Wilcoxon's test in the OAG group as well as the NTG group. CONCLUSIONS: Increased vascular resistance was found in all retrobulbar arteries in OAG and in NTG. These findings point out the pathognomonic importance of perfusion disturbance in glaucoma.

The mydriatic effect of tropicamide and its diagnostic use in Alzheimer's disease.

The mydriatic effect of topically administered tropicamide was investigated as a possible diagnostic indicator for Alzheimer's disease. Although an initial series seemed to show a correlation between hypersensitivity to tropicamide and intellectual impairment, subsequent testing showed a greater inter- and intra-individual variation than that between the normal group and the group of patients with intellectual impairment. This procedure seems, therefore, to lack sufficient specificity to be useful for such a diagnostic purpose.

The efficient use of perimetry for neuro-ophthalmic diagnosis.

AIMS/BACKGROUND: Automated perimetry is both one of the most important diagnostic procedures in ophthalmology and the most difficult for the patient who is required to comply with strict and tiring conditions. This paper examines the use of a moving fixation target and a strategy for full threshold determination only in those data points found to be abnormal. METHODS: 142 eyes in 71 patients were subjected to two types of visual field tests: the Dicon TKS 4000 Autoperimeter program 5 and the Humphrey field analyser program 30/2. The first procedure was compared with a commonly used instrument and strategy that is usually employed for the management of glaucoma patients. RESULTS: Such a strategy was used in patients presenting with neuro-ophthalmic problems taking an average testing time of 14.9 minutes. The alternative test described here took an average of 3.9 minutes, without loss of diagnostic value. CONCLUSION: The shorter testing time results in greater patient acceptance, fewer fatigue induced artefacts, and the possibility of completing a perimetry test with patients whose ability might seriously be challenged by a longer test. The reduced time required and the more natural condition of not having to fixate on an unmoving position were found not to reduce the diagnostic value of the data produced in patients presenting for various reasons at a neuro-ophthalmology clinic.

Oral zinc and the second eye in age-related macular degeneration.

PURPOSE: To investigate the short-term effect of oral zinc substitution on the development of age-related macular degeneration in the second eye of patients with an exudative form of the disease in the first eye. METHODS: A 2-year, double-masked, randomized, placebo-controlled study including 112 white patients with age-related macular degeneration and exudative lesions (choroidal neovascularization, pigment epithelial detachment, or both) in one eye and a visual acuity of better than 20/40 and macular degeneration without any exudative lesion in the second eye was performed. Patients received either 200 mg of oral zinc sulfate or placebo once daily for 24 months. The main outcome parameters were visual acuity, contrast sensitivity, color discrimination, and retinal grating acuity, as well as serum levels of zinc and copper, red blood cell count, hemoglobin, and morphologic changes detected by grading of monochrome fundus photographs and fluorescein angiograms. RESULTS: In the treatment group, the mean zinc serum level increased significantly (P < 0.0001) from 79 +/- 10 micrograms/dl to 108 +/- 26 micrograms/dl compared to no change (82 +/- 16 micrograms/dl to 85 +/- 10 micrograms/dl) in the placebo group. Serum levels of copper, hemoglobin, and red blood cell count did not change significantly in either group. A choroidal neovascular membrane (CNV) was detected in 14 patients during the treatment period (nine in the treatment group, five in the placebo group). Seven additional patients (three in the treatment group, four in the placebo group) experienced visual loss caused by CNV, and in two patients (one in each group), serous pigment epithelial detachment developed without angiographic evidence of CNV after the end of treatment, during a mean additional follow-up time of 20.8 +/- 8.2 months. In eyes in which exudative lesions did not develop, there was no significant change in any of the functional parameters during the 24-month treatment period, but there was a significant increase in the nonexudative alterations (drusen size, drusen confluence, hyperpigmentation, and focal degeneration of the retinal pigment epithelium) in both groups. CONCLUSIONS: Oral zinc substitution has no short-term effect on the course of age-related macular degeneration in patients who have an exudative form of the disease in one eye.

Pupillary dilatation test and Fourier analysis of pupillary oscillations in patients with multiple sclerosis.

Recently we investigated 29 patients aged between 31 and 60 years with multiple sclerosis by means of two new techniques. The first technique was based on pupillary dilatation response to the topical application of the cholinergic antagonist tropicamide. The second technique was the Fourier analysis of pupillary oscillations for measurement of central activation, carried out without and under the influence of a cognitive task. The multiple sclerosis group had a pupillary dilatation of 31.9% after 40 min. Under the influence of a cognitive task the patient group revealed lower amplitudes of pupillary oscillations reflecting a decreased capacity for cognitive activation.

Wavelength discrimination as a function of field intensity, duration and size.

Wavelength discrimination was measured in 8 normal observers as a function of test field intensity (2.5-63 td), duration (0.5-5 sec) and dia (0.5-2 degrees) to determine the conditions under which the just noticeable difference (JND) is smallest. The wavelengths of the standard and comparison hemifields were always equated for the observer's sensation luminance. For field intensity and duration, the wavelength JND was found to decrease until these parameters were increased beyond a certain value--25 td and 1.0 sec, respectively--and to remain constant thereafter. For field diameter, however, the JND was smallest only within a very limited range of values--between 1.0 and 1.5 degrees--and increased sharply with smaller and larger values.

Is colour vision possible with only rods and blue-sensitive cones?

At night all cats are grey, but with the approach of dawn they take on colour. By starlight, a single class of photoreceptors, the rods, function, whereas by daylight, three classes, the blue-, green- and red-sensitive cones, are active and provide colour vision. Only by comparing the rates of quantal absorption in more than one photoreceptor class is colour vision possible. Although the comparisons generally take place between the cones, they can involve the rods as well. Here we investigate the wavelength discrimination of an extremely rare group of individuals, blue-cone monochromats, who have only rods and one class of cones. We find that these individuals can distinguish wavelengths (440 to 500 nm) in the twilight region where the rods and blue-sensitive cones are simultaneously active.

[Nyctometry and flicker discrimination in diabetic retinopathy]. / Nyktometrie und Flackerdiskrimination bei diabetischer Retinopathie.

98 diabetics and 34 healthy probands were recruited for ophthalmoscopic evaluation of the retina with a fundus camera, and for functional tests of the retina using a flicker frequency analyzer and a nyctometer. One year later, funduscopic evaluation of the ocular fundal state was carried out, and the results compared with the original baseline set of functional parameters. In the control group of healthy probands, a result only partially duplicated in the group of diabetics. An age-corrected comparison of the two groups revealed no difference between the diabetics and the healthy probands. Attempts were made to identify groups displaying significant differences in retinal performance as evaluated by the procedures mentioned above, but neither taking duration of diabetes as a criterion, nor selecting for differences in the course of diabetic retinopathy enabled the identification of such groups. A decrease in retinal performance was seen in very severe stages of diabetic retinopathy. These functional tests are not suitable in the early stages of diabetic retinopathy for defining that group of high-risk patients in which rapid progression of diabetic retinopathy is to be expected.

The correlation of the results of vitreous fluorophotometry and fluorescein angiography in nonproliferative diabetic retinopathy.

The authors examined 103 eyes of 53 patients with insulin-dependent diabetes mellitus simultaneously by fluorescein angiography and vitreous fluorophotometry and correlated the stage of diabetic retinopathy with the posterior vitreous leakage (PVL) level, calculated from the preinjection-, bolus-, and measurement scans. There was a significant correlation between stage of retinopathy and PVL level, but there was a large variation of PVL readings within each group of retinopathy stages. All eyes were reexamined after a mean period of 11.84 months. In 15 of 16 eyes with progressive retinopathy the first PVL readings were within the distribution range of the respective retinopathy level. A progression of retinopathy was not accompanied by a significant change of the PVL. It was concluded that vitreous fluorophotometry alone is not sufficient for the grading of diabetic retinopathy and has only little prognostic value for the course of the disease.