M. G. Todorova

Retinal vessel oxygen saturation in patients suffering from inherited diseases of the retina.

PURPOSE The aim of this study was to evaluate the oxygen saturation in patients with inherited diseases of the retina. METHODS Fundus oximetry images were taken using a retinal vessel analyser (IMEDOS Systems UG, Jena, Germany). Retinal vessel oximetry was performed in 53 eyes of 27 patients suffering from inherited retinal diseases and compared to 22 eyes of 11 healthy controls. The oxygen saturation in all four major retinal arterioles (A-SO2) and venules (V-SO2) were measured and their difference (A-V SO2) was calculated. The data were compared within groups and to controls. RESULTS Based on V-SO2 values, the rod-cone dystrophy group (66.46%; SD, ± 5.09) could well be differentiated from controls 54.02% (SD, ± 3.04), from cone-rod dystrophies 57.56% (SD, ± 5.66), as well as from inherited maculopathies 58.42% (SD, ± 4.74). The mean A-SO2 in the rod-cone dystrophy group was increased to 98.96% (SD, ± 6.06, p<0.014), while in the cone-rod group and in the maculopathy group it was 92.75% (SD, ± 3.75), respectively 94.44% (SD ± 4.85), closer to the normal values (92.68%; SD, ± 3.53, p>0.05). The A-V SO2 difference, as an indirect indicator for retinal oxygen use, was reduced in the rod-cone patients, however only when the controls were taken into account (p=0.01). CONCLUSION This is to our knowledge the first study which proposes the retinal vessel oximetry to be a sensitive measure for differentiating rod-cone dystrophy patients not only from controls, but also from patients with other inherited retinal dystrophies.

Unstable Oxygen Supply and Glaucoma

The pathogenesis of the glaucomatous optic neuropathy (GON) is an ongoing bone of contention. While the role of intraocular pressure (IOP) is well known, it is also clear that a variety of other factors, particularly those of a vascular nature, are involved as well. In contrast to other eye diseases, it is an unstable oxygen supply, as opposed to chronic hypoxia, that contributes to GON. The major cause of fluctuations in the local oxygen tension is an unstable ocular blood flow (OBF). OBF, in turn, fluctuates if the IOP spikes, blood pressure drops, or OBF autoregulation is defective. The main reason for disturbed autoregulation is a primary vascular dysregulation (PVD), particularly in the context of the so-called Flammer syndrome. Unstable oxygen tension leads to local oxidative stress with many detrimental effects, such as the activation of glial cells, which alters their morphology and gene expression. As a consequence, the local concentrations of nitric oxide and the metalloproteinases increase. The metalloproteinases digest extracellular matrix and thereby contribute to tissue remodelling. The short-lived nitric oxide easily diffuses into the neighbouring neuronal axons, allowing a fusion with the superoxide anion and thereby generating the cell-damaging peroxynitrite. Both this tissue remodelling and damage of the axons contribute to the development and progression of GON.

Endothelin-1 Plasma Levels in Patients with both Retinitis Pigmentosa and Flammer Syndrome

BACKGROUND Endothelin-1 is a strong endogenous vasoconstrictor and is also an agent reducing the ocular blood flow. Patients with retinitis pigmentosa are known to have reduced ocular blood flow. This can be secondary to retinal atrophy, but may also partially result from an additional condition, such as a Flammer syndrome. The aim of the study was to investigate whether the endothelin-1 plasma levels in retinitis pigmentosa patients with and without Flammer syndrome are different. PATIENTS AND METHODS In the study we included patients with clinical signs and symptoms of retinitis pigmentosa, confirmed by electrophysiological findings. Blood samples were obtained from 6 retinitis pigmentosa patients with and 4 without Flammer syndrome. The results were related to 30 age- and sex-matched control subjects. Endothelin-1 plasma levels were determined by specific radioimmunoassay. RESULTS The endothelin-1 plasma levels in retinitis pigmentosa patients with Flammer syndrome were significantly higher than those without Flammer syndrome. The mean (±SD) endothelin-1 levels (pg/mL) in retinitis pigmentosa patients with Flammer syndrome were 4.95 (±1.74), range: (2.37-6.76), whereas in patients without Flammer syndrome they were 1.10 (±0.08), range: 1.00-1.20. Our own normal values are: 1.56 (±0.30), range: (0.90-2.13). All retinitis pigmentosa patients with increased endothelin-1 plasma levels had signs and symptoms related to a Flammer syndrome, such as cold extremities, low blood pressure, reduced feeling of thirst, increased sensitivity in general, e.g., increased sensitivity to certain drugs, increased pain sensitivity and increased sense of smell. CONCLUSION Endothelin-1 plasma levels were increased in retinitis pigmentosa patients with but not in patients without Flammer syndrome. Many questions remain open: Why so many retinitis pigmentosa patients suffer from Flammer syndrome, why is the endothelin-1 level in such patients higher than in healthy subjects with Flammer syndrome, how much of the ocular blood flow reduction is due to retinal degeneration and how much to the Flammer syndrome? We hypothesise that Flammer syndrome leads to an additional increase of the endothelin-1 level and an additional decrease of ocular blood flow in retinitis pigmentosa patients. Further studies are needed to analyse the causal relationship between retinitis pigmentosa and Flammer syndrome and evaluate potential therapeutic implications.

Retinal Vessel Oxygen Saturation in Giant Cell Arteritis Patients without Ocular Symptoms

BACKGROUND The aim of this study was to determine subclinical ocular ischemia related to giant cell arteritis (GCA) by means of retinal oximetry (RO) measurements. PATIENTS AND METHODS Four test-retest RO images per eye were taken with the retinal vessel analyser (IMEDOS Systems UG, Jena). RO measurements in arterial (A-SO2) and venous (V-SO2) retinal vessels and their difference (A-V SO2) were calculated in GCA patients and compared to those of age-matched controls. RESULTS GCA biopsy and duplex sonography positive patients (n=8, 13 eyes) from the Basler Riesenzellarteriitis Kohorte study (BARK) were recruited. In controls (n=6, 10 eyes), the mean (± SD) A-SO2 and V-SO2 were measured at 93.89% (± 3.0) and at 55.60% (± 3.4), respectively. In the GCAs, a reduction in the A-SO2 to 93.37% (± 3.3) and an increase in V-SO2 to 61.13% (± 3.6) were found. The A-V SO2 difference was reduced in the GCAs to 32.24% (± 3.8) whereas in the controls the difference was 38.31% (± 2.8). CONCLUSIONS Oxygen metabolism is affected in cases with GCA. Thus, RO may provide additional data in the diagnosis of GCA, even when no ophthalmic symptoms have been reported.

Unexpected Effect of Calcium Channel Blockers on the Optic Nerve Compartment Syndrome.

BACKGROUND The optic nerve compartment syndrome is a pathological condition in which cerebrospinal fluid of the subarachnoid space surrounding the optic nerve is partly or totally segregated from the cerebrospinal fluid of the intracranial subarachnoid space, leading - inter alia - to an increase in the diameter of the optic nerve sheath. The pathogenesis of this condition remains unclear. We have observed clinically that optic nerve compartment syndrome often occurs in normal tension glaucoma patients with Flammer syndrome. To treat Flammer syndrome, some glaucoma patients received a low dose of a calcium channel blocker and we analysed whether this treatment also had an effect on the optic nerve compartment syndrome. PATIENTS AND METHODS We retrospectively analysed the data of 10 eyes of seven patients suffering from a combination of primary open angle glaucoma, optic nerve compartment syndrome, and Flammer syndrome. We included subjects who had eye socket echography before and after a few months of therapy with a calcium channel blocker. THERAPY AND RESULTS All patients received a low dose of a calcium channel blocker (nifedipine or amlodipine) to treat Flammer syndrome. As expected, the symptoms of Flammer syndrome were mitigated. To our surprise, the optic nerve compartment syndrome also improved in eight of the 10 eyes (80 %), but remained unchanged in the remainder. CONCLUSIONS To some extent, the optic nerve compartment syndrome is related to the combination of primary open angle glaucoma and Flammer syndrome. On the basis of our results, we hypothesise that treatment of Flammer syndrome may also improve the optic nerve compartment syndrome.

Comparing Short-Duration Electro-Oculograms with and without Mydriasis in Healthy Subjects.

BACKGROUND In order to obtain artifact-free electro-oculogram recordings the subjects cooperation is necessary. The aim of our study is to evaluate the recording characteristics of short-duration EOG and to compare the effect of mydriasis on electro-oculogram recordings in a cohort of controls. PATIENTS AND METHODS Electro-oculogram recordings were performed on a light-emitting diode stimulus screen using a RETI-port gamma plus2 system (RETIscan™, Roland Consult). Fast oscillations were set at 1.5 sec (6 cycles; total duration 75 sec).The dark phase included: pre-adaptation (6 min), alternate fixation (4 min), fixation-rest (20 sec), 100 sweeps. The light phase included: light adaptation (4 min), alternate fixation (10 min), fixation-rest (20 sec), 250 sweeps. The amplifier band pass was filtered at 0.1÷50 Hz. The background illumination in mydriasis was 100 cd/m2 and in miosis--450 cd/m2. RESULTS A total of 55 controls participated and were divided into three age groups [number; mean (years, y); ±SD]: group 1: 18-20 years (19; 19.49 years; ±0.89); group 2: 20-40 years (18; 27.91 years; ±5.39) and group 3: 40-60 years (18; 48.66 years; ±4.00). The Arden ratio, dark-trough and light-peak did not differ between recordings with or without mydriasis (p=0.914; p=0.880; p=0.680, linear mixed-effects model). The age did not influence the Arden ratio, dark-trough, light-peak (p=0.206; p=0.112; p=0.155). Arden ratio, dark-trough, light-peak were comparable between tested eyes (p=0.934; p=0.193; p=0.270). CONCLUSIONS Short-duration electro-oculograms allow successful recording, furthermore, the application of mydriasis does not influence the quality of the recording.

Improvement in Visual Function in Patients with Inherited Diseases of the Retina Following Acupuncture Treatment

BACKGROUND The aim of this pilot study was to examine the short-term effect on visual function of acupuncture treatment in a cohort of patients with inherited diseases of the retina. PATIENTS AND METHODS A prospective pilot study was performed on 14 patients (10 ♀, 4 ♂; mean age: 43.43 y (± 19.72 y)), with the clinically and electrophysiologically confirmed diagnosis of inherited disease of the retina. Acupuncture treatment consisted of needle application to the body and ears and was performed following a standardized protocol. The treatment was scheduled for 10 half-hour sessions over five weeks. Visual function was measured before acupuncture, between acupuncture treatments and after the end of treatment. Objective measurements included best corrected visual acuity (ETDRS charts), contrast vision (CSV-1000, Vector Vision) and Goldmann perimetry (isopters 3IIIe; Haag-Streit). Subjective evaluation was based on evaluation questionnaires. To exclude the effect of variability on the psychophysical tests, a non-acupuncture control group (Nr: 8; 5 ♀, 3 ♂; mean age: 38.56 y (± 9.08 y)) was taken for comparison. RESULTS All patients with inherited diseases of the retina showed general improvement in objective visual functions, with post-/pre- acupuncture improvement in: visual acuity (p = 0.031, left eyes), contrast vision (p = 0.015 and p = 0.041; both eyes) and widening of the temporal radius of the visual field (0.013; left eyes). Subjectively, all patients reported better daytime, color and contrast vision, better visual focus and less visual tiredness. In addition, some general symptoms, such as longer sleep-onset time, feeling cold, and migraine/headache attacks were significantly reduced. CONCLUSIONS The acupuncture protocol improved visual function in our patients with inherited diseases of the retina and was well tolerated. Nevertheless, the long-term effect of this complementary therapy remains to be evaluated.

Ocular Manifestation of Non-Parenchymal Neuro-Behçet Syndrome

Behçetʼs disease (BD) has been first described by Hippocrates, while it has been brought back to attention by Hulusi Behçet. Its classical triad includes recurrent, usually painful oral and genital ulcers and uveitis [1]. BD is a chronic relapsing primary vasculitis disorder, which may involve small, medium and large-sized blood vessels [2]. Neurological involvement has been found to occur in 9.4% of 387 subjects with BD over twenty-year follow-up [3]. With the increasing availability of neuroimaging, subclinical Neuro-Behçet Syndrome (NBS) can also be diagnosed. Parenchymal NBS is more common and presents as meningoencephalitis, affecting the brainstem, basal ganglia, the spinal cord and/or the hemispheres. The

Tendinous muscle insertions (scleromuscular junctions of the recti muscles) in patients with ocular alignment problems.

BACKGROUND The purpose of this study was to prove the hypothesis whether the scleromuscular junction of extraocular recti muscle is tendinous. PATIENTS AND METHODS Muscle samples of the 41 extraocular recti muscles of 33 patients and 4 muscle-/eye-matched samples from 2 postmortem eyes, were processed for light/electron microscopy and immunohistochemistry with antibodies against desmin, smooth-muscle actin and muscle regulating proteins like myf3 and myf4 (myogenin), tenascin C and for 8 samples against collagens I to IV. RESULTS Histological examination of the muscle samples confirmed a thick collagen-structured tissue, specific for muscle tendon; without appearance of muscle tissue. This was confirmed by immunohistochemistry with antibodies against desmin, smooth-muscle actin, myf3 and myf4 (myogenin) and for eight samples with collagens I to IV. Anti-tenascin C marker was only strongly positive in the connective tissue of the blood vessel walls. Electron microscopy demonstrated collagen bundles composed of parallel oriented fibrils with a moderate amount of ground substance. CONCLUSIONS The absence of contractile fibers at the sclerotendinous junction is an entirely normal finding in humans and cannot be related to ocular alignment pathogenesis.