The association between retinal vein ophthalmodynamometric force change and optic disc excavation

Aim: Retinal vein ophthalmodynamometric force (ODF) is predictive of future optic disc excavation in glaucoma, but it is not known if variation in ODF affects prognosis. We aimed to assess whether a change in ODF provides additional prognostic information. Methods: 135 eyes of 75 patients with glaucoma or being glaucoma suspects had intraocular pressure (IOP), visual fields, stereo optic disc photography and ODF measured on an initial visit and a subsequent visit at mean 82 (SD 7.3) months later. Corneal thickness and blood pressure were recorded on the latter visit. When venous pulsation was spontaneous, the ODF was recorded as 0 g. Change in ODF was calculated. Flicker stereochronoscopy was used to determine the occurrence of optic disc excavation, which was modelled against the measured variables using multiple mixed effects logistic regression. Results: Change in ODF (p=0.046) was associated with increased excavation. Average IOP (p=0.66) and other variables were not associated. Odds ratio for increased optic disc excavation of 1.045 per gram ODF change (95% CI 1.001 to 1.090) was calculated. Conclusion: Change in retinal vein ODF may provide additional information to assist with glaucoma prognostication and implies a significant relationship between venous change and glaucoma patho-physiology

An experimental study of VEGF induced changes in vasoactivity in pig retinal arterioles and the influence of an anti-VEGF agent

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in ocular physiology. Anti-VEGF agents are now used for treatment of common retinal diseases. This study characterises the vasoactive properties of VEGF in isolated perfused pig retinal arterioles under normal tone or endothelin-1 (ET-1) pre-contracted conditions and determines the influence of an anti VEGF agent on VEGF induced vasoactivity. METHODS: An isolated perfused retinal arteriole preparation was used. The outer diameter of retinal vessels was monitored at 2 second intervals in response to VEGF and the anti VEGF agent, bevacizumab. The effect of intraluminal delivery of VEGF was determined over a wide concentration range (10(-16) to 10(-7) M) both with and without pre-contraction with ET-1 (3 x 10(-9) M). Bevacizumab (0.35 mg mL(-1)) was applied extraluminally to determine the influence of bevacizumab on VEGF induced vasoactive changes on ET-1 pre-contracted vessels. RESULTS: In retinal arterioles with normal tone, VEGF induced a concentration dependent contraction at low concentrations, reaching 93.5% at 10(-11) M and then contraction was reduced at higher concentrations, recovering to 98.1% at 10(-7) M. VEGF produced a potent concentration dependent vasodilatation in arterioles pre-contracted with ET-1. VEGF induced vasodilatation in arterioles pre-contracted with ET-1 was significantly inhibited by bevacizumab. CONCLUSIONS: VEGF induced vasoactive changes in pig retinal arterioles are dependent on concentration and vascular tone. Bevacizumab inhibits VEGF-induced vasodilatation in pre-contracted arterioles

Laser-Induced Changes in Intraretinal Oxygen Distribution in Pigmented Rabbits

PURPOSE. To make the first measurements of intraretinal oxygen distribution and consumption after laser photocoagulation of the retina and to compare the efficiency of micropulsed (MP) and continuous wave (CW) laser delivery in achieving an oxygen benefit in the treated area. METHODS. Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of retinal depth before and after laser treatment in anesthetized, mechanically ventilated, Dutch Belted rabbits (n ϭ 11). Laser lesions were created by using a range of power levels from an 810-nm diode laser coupled with an operating microscope delivery system. MP duty cycles of 5%, 10%, and 15% were compared with CW delivery in each eye. RESULTS. Sufficient power levels of both the CW and MP laser reduced outer retinal oxygen consumption and increased oxygen level within the retina. At these power levels, which correlated with funduscopically visible lesions, there was histologically visible damage to the RPE and photoreceptors. Retinal damage was energy dependent but short-duty-cycle MP delivery was more selective in terms of retinal cell damage, with a wider safety range in comparison with CW delivery. CONCLUSIONS. The relationship between laser power level and mode of delivery and the resultant changes in oxygen metabolism and oxygen level in the retina was determined. Only partial destruction of RPE and photoreceptors is necessary, to produce a measurable oxygen benefit in the treated area of retina. (Invest Ophthalmol Vis Sci. 2005;46:988 -999

Neuropeptides, Trophic Factors, and Other Substances Providing Morphofunctional and Metabolic Protection in Experimental Models of Diabetic Retinopathy

Vision is the most important sensory modality for many species, including humans. Damage to the retina results in vision loss or even blindness. One of the most serious complications of diabetes, a disease that has seen a worldwide increase in prevalence, is diabetic retinopathy. This condition stems from consequences of pathological metabolism and develops in 75% of patients with type 1 and 50% with type 2 diabetes. The development of novel protective drugs is essential. In this review we provide a description of the disease and conclude that type 1 diabetes and type 2 diabetes lead to the same retinopathy. We evaluate existing experimental models and recent developments in finding effective compounds against this disorder. In our opinion, the best models are the long-term streptozotocin-induced diabetes and Otsuka Long-Evans Tokushima Fatty and spontaneously diabetic Torii rats, while the most promising substances are topically administered somatostatin and pigment epithelium-derived factor analogs, antivasculogenic substances, and systemic antioxidants. Future drug development should focus on these

Protective role of endothelial nitric oxide synthase following pressure-induced insult to the optic nerve

Although intracranial pressure (ICP) elevation can induce significant structural and functional changes within the central nervous system (CNS), almost complete neuronal recovery is possible if ICP and associated pathogenic factors are restored in the acute phase of the disease process. Nitric oxide synthase (NOS) isoforms have been implicated in the pathogenesis of many CNS diseases and may play an important role in the development of neuronal tolerance in the early stages of pressure elevation. In this paper we use the pig optic nerve, a typical central white matter tract, to study the time-dependent sequence of NOS isoform change following pressure elevation. The timing of NOS isoform change in relationship to structural and functional changes to axons and glial cells is also discussed. This study demonstrates that endothelial cell nitric oxide synthase (ecNOS), an enzyme that plays a protective role in the CNS, is up-regulated in a time-dependent manner after pressure elevation. ecNOS levels increase after axonal and astrocyte injury, suggesting that it might be a compensatory response that is initiated in an effort to preserve CNS function. Inducible NOS (iNOS) and neuronal NOS (nNOS), which are known to have a deleterious effect on the CNS, were not detected in this study. The increase in ecNOS demonstrated in this study is significantly different to the increase in iNOS and nNOS previously demonstrated following traumatic brain injury. Changes in ecNOS levels may therefore be important in the development of neuronal tolerance in the early stages of CNS diseases such as hydrocephalus

An Explanation of the "Supernormal" B-Wave In Vitro

The isolated arterially perfused eye preparation has proven to be comparable to the in vivo model in many respects. However, the existence of "supernormal" b-wave amplitudes in the perfused eyes has remained an unexplained functional difference between the two preparations. The term "supernormal" reflected the observation that at high perfusate flow rates the amplitude of the b-wave from the perfused eyes was frequently larger than that recorded in vivo under the same stimulus and adaptation conditions. Recent investigations in this laboratory have demonstrated that the position of the scleral electrode on the isolated eye greatly influences the amplitude of the b-wave obtained. The simple comparison of b-wave amplitudes in vivo and in vitro was therefore not appropriate, due to the different electrode locations used in the two situations. In addition, the relationship between perfusate flow rate and b-wave amplitude at a fixed location has been reinvestigated. In our perfusion system the b-wave amplitude has been shown to saturate at moderate flow rates (1.5 ml/min), considerably lower than those required to maximize the b-wave amplitude in earlier studies. This difference is due to the higher oxygen tension of our perfusate at the entry point to the eye. It is concluded that b-wave stability with increasing perfusate flow can be achieved in vitro, and that the apparently supernormal b-wave amplitudes observed under these conditions can be explained in terms of the different electrode environment in the in vivo and in vitro preparations. The implications of these findings with regard to autoregulation of the retinal circulation are discussed. Invest Ophthalmol Vis Sci 29: [1044][1045][1046][1047][1048][1049]1988 Following the first use of the isolated arterially perfused eye technique, 4 - 6 This description resulted from the observation that increasing the perfusate flow rate, or the oxygen con