Course of pattern-reversed visual evoked cortical potentials in 30 eyes after bony orbital decompression in dysthyroid optic neuropathy.

AIM: To investigate optic nerve function using the pattern-reversed visual evoked cortical potentials (VECP) before and after bony orbital decompression in dysthyroid optic neuropathy (DON) due to Graves' disease. METHODS: A total of 30 eyes of 15 patients (n=14 female) were observed over 30 ± 13 months after bony three-wall orbital decompression. We examined visual acuity (VA), VECP P100 amplitudes and latencies, as well as proptosis using Hertel's exophthalmometry. RESULTS: Mean logarithm of the minimum angle of resolution (logMAR) VA increased, statistically significantly, by 2.4 lines during 30 ± 13 months (from 0.38 ± 0.25 before surgery to 0.14 ± 0.1 at the end of observation, p=0.0001). All eyes maintained or improved vision by at least one line. Mean postoperative reduction of proptosis was 6.4 ± 3 mm. While VECP P100 amplitudes improved significantly, P100 latencies remained abnormal in 18 eyes (60%) during follow-up of 10 ± 7 months. Nine eyes (30%) with previous latency defects improved in at least one check test, five of which normalised completely. Worsening was evident in seven eyes (23%), and three previously normal eyes developed new pathological latencies. P100 latencies in 14 eyes (47%) remained unchanged. CONCLUSION: After decompression surgery, DON remission was observed in all patients regarding vision and VECP amplitudes. New or persistent P100 latency defects were seen in 60% of eyes after surgery. DON is considered to be caused by compressive ischaemic damage, which further underlines the importance of early decompression surgery.

[Different indications of photodynamic therapy in ophthalmology]. / Verschiedene Indikationen der photodynamischen Therapie in der Augenheilkunde.

BACKGROUND: Photodynamic therapy (PDT) in eye disease was approved 10 years ago for age-related macular degeneration (AMD). Thereafter it was approved for choroidal neovascularisation (CNV) in pathological myopia. The treatment regimen is based on two prospective, multicentre trials (TAP and VIP studies). MATERIAL AND METHODS: In the meantime PDT has been successfully used also in several other ocular diseases. PDT is minimally invasive and has an excellent side effect profile. Different diseases and their treatment with PDT are discussed. RESULTS: The treatments of idiopathic CNV, secondary CNV in inflammatory diseases of the retina and choroid, choroidal haemangioma, vasoproliferative tumours, malignant melanoma of the choroid, and central serous chorioretinopathy with PDT are described. In most patients the disease progression can be stopped and in some the PDT treatment results in visual improvement. The prognosis is better in patients with early disease detection and small lesions. CONCLUSION: Several retinal and choroidal diseases can be treated successfully with PDT. Except for AMD and pathological myopia, PDT is an off label treatment.

[Endoresection of large uveal melanomas after pretreatment by single-dose stereotactic convergence irradiation with the leksell gamma knife--first experience on 46 cases]. / Endoresektion grosser Melanome der Uvea nach stereotaktischer Single-dose-Vorbestrahlung mit dem Leksell Gamma-Knife -- Erste Erfahrungen an 46 Fällen.

BACKGROUND: The aim of this non-comparative, consecutive case series is to evaluate the short-term results after endoresection of large uveal melanomas in combination with pretreatment with stereotactic gamma knife radiosurgery. METHODS: Between March 2000 and November 2002, forty-six patients with large uveal melanomas underwent stereotactic radiosurgery followed by endoresection of the tumour via a standard three-port vitrectomy including laser photocoagulation and silicone oil tamponade. The average tumour height was 9.5 mm. The minimum dose delivered to the tumour volume was 25 Gy. RESULTS: The median follow-up time was 410 days. In 40 cases (87 %), the eye was retained with a VA of 20/200 or better in 30 cases (65.2 %) and 20/63 or better in ten cases (21.7 %). In 12 eyes with a follow-up of >/= 0.5 years, the median VA was 20/80 after silicone oil removal and cataract surgery had been performed. Six eyes (13 %) were enucleated due to serious complications caused by the radiosurgery (3 cases) or endoresection (3 cases). In 13 patients (28.2 %), additional major surgery was required. Seven patients developed liver metastases during follow-up and six patients died. No local tumour recurrences were observed. CONCLUSIONS: Eyes with large uveal melanomas can be salvaged by stereotactic radiotherapy followed by endoresection.

Ruthenium-106 plaque brachytherapy for symptomatic vasoproliferative tumours of the retina.

AIM: To investigate the safety and efficacy of beta ray brachytherapy in treatment of vasoproliferative tumours of the retina (VTR). METHODS: 35 consecutive patients with symptomatic VTR were treated with a ruthenium-106 ((106)Ru) plaque. Three tumours had been treated previously (two with cryotherapy; one with transpupillary thermotherapy). 32 VTR (91.4%) were located in the lower half of the retina and all of them were found between the mid-periphery and the ora serrata. The mean tumour thickness was 2.8 mm. An exudative retinal detachment was present in 25 eyes (71.4%) and in 15 cases (42.9%) hard exudates were found in the macula. The major symptom was loss of vision (77.1%). RESULTS: Brachytherapy was well tolerated by every patient. The mean applied dose was 416 Gy at the sclera and 108 Gy at the tumour apex. In all but four eyes (88.6%), it was possible to control the VTR activity. The median follow up time was 24 months. Three of the above mentioned four eyes with treatment failure had had secondary glaucoma before therapy. There was no case of radiation induced neuropathy or retinopathy. Cataract surgery was necessary for five patients. The development of epiretinal gliosis was the most common event during follow up (n = 10, 28.6%). The mean visual acuity decreased slightly (0.33 before and 0.29 after brachytherapy). Multivariate analysis showed that the presence of macular pathology before treatment was associated with a 6.1-fold risk of vision of 0.25 or better (p = 0.03). CONCLUSIONS: beta ray brachytherapy with (1106)Ru plaques was able to control the activity of VTR and retain vision. Cases with secondary glaucoma before treatment had a very poor prognosis.

Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma.

AIM: To investigate the safety and efficacy of photodynamic therapy with verteporfin in patients with choroidal haemangioma. METHODS: A non-randomised, prospective clinical investigation of 19 patients with symptomatic circumscribed choroidal haemangioma was performed. Unsuccessful pretreatment (external beam irradiation, laser photocoagulation) was performed in four patients. Patients were included when (1) subretinal exudation involving the fovea, (2) a decrease in visual function, and (3) additional symptoms (for example, metamorphopsia) were present. Photodynamic therapy (PDT) was performed with verteporfin at a concentration of 6 mg/m(2) body surface area and a light dose of 100 J/cm(2) at 692 nm. RESULTS: The mean follow up time was 10.6 months (2-24 months). The mean number of treatment sessions was 2.15 (range 1-5). Visual acuity improved by at least one line in 73.3%, by at least two lines in 42.1%, was stable in 21.1%, and decreased by one line in 5.2% of the patients. Exudation was completely resolved in 94.8% of the cases. Regression of tumour height was documented in all 19 tumours. Patients receiving any pretreatment before PDT, a visual acuity of 0.1 and less, a history of more than 30 months, and no significant response after the first PDT session, did not show any significant improvement. Cox regression analysis revealed that the number of PDT treatment sessions was inversely associated with the improvement in visual acuity of at least two lines. No recurrences and no local or systemic side effects were observed during the follow up time. CONCLUSION: PDT using verteporfin is a safe and effective therapy for the treatment of symptomatic choroidal haemangioma even in tumours located beneath the fovea.

[Clinical findings in autosomal recessive syndrome of blue cone hypersensitivity]. / Klinische Befunde bei autosomal-rezessivem Syndrom der Blauzapfenhypersensitivität.

BACKGROUND: Intrafamilial variability of the syndrome of night blindness, maculopathy, and enhanced S-cone hypersensitivity was examined. PATIENTS AND METHODS: Siblings with a history of night blindness and reduced visual acuity were examined clinically, psychophysically, electroretinographically (ERG), and electro-oculographically (EOG). RESULTS: The siblings had had night blindness since early childhood and reduced visual acuity since the age of 20 years. Ophthalmoscopy showed degenerative, pigmented changes and subretinal spots, while one sibling had cystic lesions in the fovea. Scotopic ERG showed no rod-driven responses, while large, slow waveforms were detected in response to bright flashes. Photopic ERG induced responses similar in time, amplitude, and configuration to those of the dark-adapted ERG. The b-wave configuration was unchanged in response to chromatic stimuli. However, photopic ERG was more sensitive to blue and white than to red stimuli. The light peak on EOG was reduced. CONCLUSIONS: The enhanced S-cone sensitivity syndrome was expressed to a different degree of severity and probably inherited in an autosomal recessive mode. These unusual ERG findings may be due to a depressed rod system and an increased number of S-cone photoreceptors, postreceptoral circuits, and S-cone sensitive ganglion cells.

[Effect of retinal coagulation status on oxidative metabolite and VEGF in 208 patients with proliferative diabetic retinopathy]. / Einfluss des retinalen Koagulationsstatus auf oxidative Metabolite und VEGF bei 208 Patienten mit proliferativer diabetischer Retinopathie.

BACKGROUND: Oxidative metabolites and different cytokines are believed to be involved in the pathogenesis of (proliferative) diabetic retinopathy. It was the aim of this study to analyze vitreous body and proliferations of diabetic patients for oxidative metabolites and VEGF und to correlate these values to the retinal coagulation status. PATIENTS AND METHODS: The study was performed in 208 patients vitrectomized for diabetic retinopathy (Type I: n = 114, Type II: n = 94). Grouping of patients was performed according to retinal coagulations status: (1) no or minimal preoperative coagulation [mean coagulation area, CA: 156 mm2], (2) coagulation (scatter laser coagulation und/oder cryopexy) < 3 months before surgery [CA: 589 mm2]. (3) coagulation > 3 months before surgery [CA: 546 mm2]. In the vitreous body and, if present, in the fibrovascular proliferations (Type I: n = 83; Type II: n = 73) the level of lipid peroxides (LPO, measured with two methods) and VEGF was determined. RESULTS: In the vitreous body LPO in group 1 were significantly (P < 0.01 (Type I und II)) higher as compared to other groups. In group 3 LPO were significantly lower as compared to group 2 (P < 0.01 (Typ I) and P < 0.05 (Typ II)). Similar results were observed in the proliferations. In Type I patients VEGF values were significantly (P < 0.01 for group 1 vs. 2 and groups 1/2 vs. 3) reduced following coagulation and coagulation + 3 months. In Type II patients only group 3 was significantly (P < 0.01) different from group 1. In proliferations groups 2 and 3 were significantly different from group 1 (P < 0.05 for Typ I and Type II patients). CONCLUSIONS: The time course of the values leads to the conclusion that oxidative metabolites are able to directly modulate growth activity and to exert this effect via induction of VEGF. This hypothesis has to be confirmed in vitro and by means of a prospective study.

Effects of adenosinergic agents on the vascular resistance and on the optic nerve response in the perfused cat eye.

The function of A1- and A2a-adenosine receptors in the control of vascular resistance and in the modulation of light-evoked neuronal activity was investigated in the isolated perfused cat eye. The A1 agonist CCPA, the A1 antagonist CPT, the A2a agonist CGS 21680 and the A2 antagonist DMPX were used. The agents were applied intra-arterially at concentrations in the low nanomolar to micromolar range during rod-selective photic stimulation. The flow rate of perfusate, reflecting vascular resistance and the light-evoked optic nerve response (ONR) were recorded. Our results show a vasodilating effect of both A1 and A2 agonists and a vasoconstricting effect of the respective antagonists. The dose-effect relationships are suggestive, however, of an A2a receptor-mediated mechanism. The amplitude of the ONR-ON component was decreased during application of both adenosine-agonists. Analysis of the dose-effect relationships and the blockade of the CCPA-induced decrease by CPT suggests that inhibition is mediated by A1 receptors. However, CGS 21680-mediated inhibition cannot be explained by unspecific binding at A1 receptors alone and suggests the involvement of inhibitory A2a receptors.

Mutation analysis of the ND6 gene in patients with Lebers hereditary optic neuropathy.

DNA sequence analysis of the gene encoding subunit 6 of the NADH-ubiquinone-oxidoreductase complex (ND6) in human mitochondria was performed in 25 independent patients who suffer from Lebers hereditary optic neuropathy (LHON). In 10 cases the well-known LHON mutation at nucleotide position (np) 14484 was detected. Furthermore, silent substitutions at np14167 and np14527 and missense mutations at np14498, np14564, np14568, and np14582 were found in individual patients. The np14498 and np14568 mutations were found in patients who present a typical clinical picture and course of LHON but lack any of the canonical mtDNA mutations. The np14568 mutation, which replaces a moderately conserved glycine by a serine residue, was observed in a single male patient and subsequently excluded in 175 independent controls. The mutation at np14498, which replaces an evolutionarily highly conserved tyrosine with a cysteine, was found in a multigeneration family with four affected members, the eldest carrying a heteroplasmic mixture of mutated and wildtype mtDNA molecules. None of 170 analyzed control subjects carried this mutation. These findings provide evidence that several allelic ND6 gene mutations may be involved in Lebers hereditary optic neuropathy.

Angiotensin II-like immunoreactivity in the retina of some mammalian species.

The decapeptide angiotensin II (AngII) is a circulating hormone and the most important endogenous vasoconstrictor. In the central nervous system (CNS), AngII has been reported to have a transmitter-like function. In the retina angiotensin I (AngI), the precursor protein of AngII, and AngI-converting enzyme (ACE), the rate-limiting enzyme for AngII synthesis, are present. Both ACE inhibition and application of an AngII antagonist affect the b-wave of the electroretinogram. In the present study we used immunocytochemical techniques to identify putative AngII-containing cells in the bovine, cat, and rabbit retina. In the rabbit retina, faintly labeled amacrine cells were visible at the inner border of the inner nuclear layer. Preincubation with protease inhibitors (PI) resulted in an enhanced immunoreaction and in the labeling of ganglion cells and fibers in the inner plexiform layer. In the bovine retina, AngII-like immunoreactivity was detectable only after preincubation with PI. Under these conditions, ganglion cells and amacrine cells as well as cells in more distal parts of the inner nuclear layer were stained. In the cat retina, AngII-like immunoreactivity was detectable only after preincubation with PI and exogenous AngII. Photoreceptor and ganglion cells showed an enhanced AngII-like immunoreaction, and amacrine cells were stained preferably in clusters that were irregularly distributed within the retina. Our results demonstrate that AngII is a putative neurotransmitter in a subpopulation of mammalian amacrine cells.