[Value of non-IOP lowering therapy for glaucoma]. / Stellenwert der "nicht Augendruck senkenden Glaukomtherapie"

It is well established that an IOP reduction improves, on average, the prognosis of all types of glaucoma. It is also known, however, that even an ideal IOP does not stop progression in all patients. The insight into the pathogenesis of glaucomatous damage leads to new therapeutic approaches. Whilst most of these new avenues of treatment are still in the experimental phase, others, such as magnesium, Ginkgo, salt and fludrocortisone are already used by some physicians. Blood pressure dips can be avoided by intake of salt or fludrocortisone. Vascular regulation can be improved either locally by carbonic anhydrase inhibitors or systemically with magnesium or with low doses of calcium channel blockers. A number of other food ingredients such as polyphenolic flavonoids occurring in tea, coffee, dark chocolate or red wine and anthocyanosides found in bilberries have potential antioxidative effects. The oxidative stress at the level of the mitochondria can be reduced by Ginkgo biloba. Experimentally, glaucomatous optic neuropathy can be prevented by inhibition of astrocyte activation, either by blockage of epidermal growth factor receptor or by counteracting endothelin. Glaucomatous optic neuropathy can also be prevented by nitric oxide-2 synthase inhibition. Inhibition of matrix metalloproteinase-9 inhibits apoptosis of retinal ganglion cells and tissue remodelling. Up-regulation of heat shock proteins protects the retinal ganglion cells and the optic nerve head.

Ginkgo biloba: an adjuvant therapy for progressive normal and high tension glaucoma.

Gingko biloba has been used for hundreds of years to treat various disorders such as asthma, vertigo, fatigue and, tinnitus or circulatory problems. Two of the main extracts are EGb761 and LI 1370. Most pharmacological, toxicological and clinical studies have focused on the neuroprotective value of these two main extracts. Neuroprotection is a rapidly expanding area of research. This area is of particular interest due to the fact that it represents a new avenue of therapy for a frustrating disease that may progress despite optimal treatment. One such disease is glaucoma.Glaucoma leads to the loss of retinal ganglion cells and their axons but also to tissue remodelling which involves both the optic nerve head and the retina. In the retina the astrocytes get activated. In addition, the optic nerve gets thinner and the cells of the lateral geniculate ganglion disappear partially. On average, ocular blood flow (OBF) is reduced in glaucoma patients in various tissues of the eye. Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage. Nevertheless, there is little doubt that other risk factors besides IOP are involved. One such risk factor is a primary vascular dysregulation (PVD) occurring in patients with a disturbed autoregulation, another risk factor is oxidative stress.

The effect of ranibizumab versus photodynamic therapy on DNA damage in patients with exudative macular degeneration.

PURPOSE: To compare the effect of ranibizumab treatment versus photodynamic therapy (PDT) on single-stranded DNA damage in circulating leukocytes in patients with exudative age-related macular degeneration (AMD). METHODS: A comparative quantification of single-stranded DNA breaks was performed in circulating leukocytes of AMD patients before and 30 min, 45 min, 60 min, and 24 h after two different modes of therapy: a) PDT; and b) intravitreal ranibizumab injection. DNA breaks lead to smaller pieces of DNA, which in an electrical field, migrate out of the nucleus forming a tail. Damage of an individual cell was quantified as a comet tail moment. The proportion of non-zero values compared to the total number of observations was referred to as "amount of DNA damage" expressed in arbitrary units (AU). Comparisons between time points and study groups were assessed using a linear mixed-effect model. RESULTS: PDT induced an increase in the amount of single-stranded DNA damage in the circulating leukocytes from 0.2 AU (before treatment) to 0.53 AU (30 min after treatment). This increase was significant (p=0.004). In contrast, after ranibizumab treatment, the DNA damage in the circulating leukocytes remained unchanged. CONCLUSIONS: PDT purposely induces a local oxidative stress to damage the newly formed vessels. Our results indicate an additional systemic oxidative stress, apparent as amount of single-stranded DNA damage in the circulating leukocytes, for at least 30 min after treatment.

Adrenaline-induced chronic ocular hypertension in adult rabbits.

BACKGROUND: The aim of this study was to develop a new animal model to enhance our understanding of the biological pathomechanisms involved in glaucoma. MATERIALS AND METHODS: Forty white giant rabbits were divided into a treated (N = 30) and a control group (N = 10). Boli of adrenaline hydrochloride (0.1 mL 0.1% solution) were repeatedly injected into the veins of the ears of the rabbits and physiological saline in the control group, respectively, for three months. Intraocular pressure (IOP) and outflow facility of the aqueous humour were measured prior to, during and after treatment (4-6 months, 7-9 months, 10-12 months). RESULTS: In comparison to the control group, the adrenaline-treated group showed a significant increase in IOP both during treatment (25%) and 12 months after treatment (57%). Comparative analysis further showed that the aqueous humour outflow facility of the treated group increased by 16.5% during the treatment, and showed a continuous decrease of 60 % after treatment. CONCLUSION: This rabbit model could be useful for further investigations of the pathomechanisms involved in glaucoma.

The potential value of natural antioxidative treatment in glaucoma.

Glaucomatous optic neuropathy implies loss of retinal ganglion cells, including their axons, and a major tissue remodeling, especially in the optic nerve head. Although increased intraocular pressure is a major risk factor for glaucomatous optic neuropathy, there is little doubt that other factors such as ocular blood flow play a role as well. Mechanisms leading to glaucomatous optic neuropathy are not yet clearly understood. There is, however, increasing evidence that both an activation of glial cells and an oxidative stress in the axons play an important role. Glial cells may be activated by mechanical stress via activation of the epidermal growth-factor-receptor, or by ischemic stress via an increase in endothelin. Several factors can systemically or locally increase oxidative stress. In glaucoma, an unstable ocular blood flow leading to repeated mild reperfusion seems to be most relevant in inducing oxidative stress. The simultaneous production of nitric oxide in the astrocytes and of superoxide in the mitochondria of the axons leads to the production of the damaging peroxynitrite. Therapeutically, we need to reduce intraocular pressure, stabilize ocular blood flow, and reduce oxidative stress. Various natural compounds possess potential antioxidative value. Reduction of oxidative stress at the level of mitochondria can be achieved by gingko biloba. Polyphenolic compounds, such as tea, red wine, dark chocolate, or coffee have antioxidative properties. Coffee contains 3-methyl-1,2-cyclopentanedione (MCP), capable of scavenging peroxynitirite. Red wine-polyphenols (e.g., resveratrol), exert vasoprotective effects by inhibiting the synthesis of endothelin-1. Dark chocolate decreases blood pressure and improves endothelium-dependant vasorelaxation. Anthocyanosides (bilberries) owe their antioxidant effects to their particular chemical structure. Other antioxidants include ubiquinone and melatonin.

Comet assay analysis of single-stranded DNA breaks in circulating leukocytes of glaucoma patients.

PURPOSE: To investigate the amount of single-stranded DNA breaks in circulating leukocytes of primary open-angle glaucoma (POAG) patients. METHODS: A comparative quantification of DNA breaks was performed in circulating leukocytes of POAG patients and healthy controls. The following groups of subjects were compared: (1) POAG patients having primary vascular dysregulation (PVD), (2) POAG patients without PVD, (3) healthy controls with PVD, and (4) healthy controls without PVD. The damage to DNA resulting in single-stranded breaks was assessed by means of the alkaline comet assay in which the damaged DNA migrates out of the nucleus forming a tail, which can be quantified using image analysis. Damage was quantified as the comet tail moment, which represents the extent of DNA damage in individual cells. RESULTS: Leukocytes of POAG patients exerted a significantly higher amount of comet tails, which are indicative of DNA damage, in comparison to control leukocytes (p<0.001). DNA breaks occurred particularly in the subgroup of POAG patients with PVD in comparison to glaucoma patients without PVD (p=0.002). In the control group, there was no significant difference between controls with PVD and controls without PVD (p=0.86). CONCLUSIONS: POAG patients with PVD have a significantly higher rate of DNA breaks than both POAG patients without PVD and healthy controls with and without PVD.

Malpractice in ophthalmology: guidelines for preventing pitfalls.

PURPOSE: To provide ophthamologists with guidelines with which to prevent common errors of malpractice and suggest ways to reduce the risk of liability claims by improving the quality of care. METHODS: Interview of a vitreoretinal surgeon (AW) and search of the current relevant literature. RESULTS: Some of the most common errors leading to ophthalmic malpractice litigation are: 1) failed diagnosis or progression of disease, 2) missing pathology, 3) failed surgery, 4) inadequate patient care, 5) lack of communication, 6) holding back information, 7) no signed informed consent, 8) lack of correct documentation/poor records, 9) poor doctor-patient relationship, 10) no ethical responsibilities, 11) no professional liability insurance coverage, 12) highly pressured hospital set-up, 13) insufficient understanding of law. CONCLUSION: The risk for malpractice litigation for ophthalmologists may be reduced by preventing common causes of malpractice and improving the quality of care.