Effects of Photocoagulation on Intraretinal P<scp>o</scp><sub>2</sub>in Cat

Budzynski, Ewa; Smith, Jean B.; Bryar, Paul; Bírol, Gülnur; Linsenmeier, Robert A.

doi:10.1167/iovs.07-0065

Cited by 51 publications

(44 citation statements)

References 43 publications

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“…Anterior segment hypoxia and additional VEGF from the retina will stimulate neovascularisation on the iris. The practice of endophotocoagulation during vitreous surgery helped reduce this threat, as the photocoagulation reduced retinal hypoxia (17,22,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50) and VEGF production, thus decreasing concentration gradients and transport of both oxygen and VEGF between anterior and posterior segments.…”

Section: Iris Neovascularizationmentioning

confidence: 99%

“…4). Naturally, laser photocoagulation will contribute to this by also relieving hypoxia of remaining retinal cells and thus reducing VEGF production (8,17,22,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50) Understanding the physiological principles makes it possible to combine treatment modalities in a sensible way (Fig. 5).…”

Section: Retinal Neovascularisationmentioning

confidence: 99%

“…Photocoagulation improves retinal oxygenation (17,22,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50), reduces VEGF production and constricts retinal arterioles to influence both the osmotic and hydrodynamic arms of Starling's law (8,(71)(72)(73)(74). Vascular endothelial growth factor (VEGF) is a major stimulus for retinal neovascularization.…”

Section: Diabetic Macular Edemamentioning

confidence: 99%

“…This may be done simply by breathing oxygen-enriched air which has been shown to constrict retinal blood vessels and reduce diabetic macular edema (111)(112)(113)(114). Retinal oxygenation may also be improved by scattered laser treatment, which destroys a part of the retina and thereby reduces its oxygen consumption (17,22,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50). Retinal laser treatment destroys some of the photoreceptors, and allows oxygen to diffuse from the choroid through the laser scars into the inner retina, where it improves retinal oxygen tension (17, 38-46, 48-50, 115, 116) and leads to constriction of retinal blood vessels (71)(72)(73)(74).…”

Section: How Do We Treat Edema?mentioning

confidence: 99%

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Physiology of vitreous surgery

Stefánsson

2008

Graefes Arch Clin Exp Ophthalmol

251

198

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Vitreous surgery has various physiological and clinical consequences, both beneficial and harmful. Vitrectomy reduces the risk of retinal neovascularization, while increasing the risk of iris neovascularization, reduces macular edema and stimulates cataract formation. These clinical consequences may be understood with the help of classical laws of physics and physiology. The laws of Fick, Stokes-Einstein and Hagen-Poiseuille state that molecular transport by diffusion or convection is inversely related to the viscosity of the medium. When the vitreous gel is replaced with less viscous saline, the transport of all molecules, including oxygen and cytokines, is facilitated. Oxygen transport to ischemic retinal areas is improved, as is clearance of VEGF and other cytokines from these areas, thus reducing edema and neovascularization. At the same time, oxygen is transported faster down a concentration gradient from the anterior to the posterior segment, while VEGF moves in the opposite direction, making the anterior segment less oxygenated and with more VEGF, stimulating iris neovascularization. Silicone oil is the exception that proves the rule: it is more viscous than vitreous humour, re-establishes the transport barrier to oxygen and VEGF, and reduces the risk for iris neovascularization in the vitrectomized-lentectomized eye. Modern vitreous surgery involves a variety of treatment options in addition to vitrectomy itself, such as photocoagulation, anti-VEGF drugs, intravitreal steroids and release of vitreoretinal traction. A full understanding of these treatment modalities allows sensible combination of treatment options. Retinal photocoagulation has repeatedly been shown to improve retinal oxygenation, as does vitrectomy. Oxygen naturally reduces VEGF production and improves retinal hemodynamics. The VEGF-lowering effect of photocoagulation and vitrectomy can be augmented with anti-VEGF drugs and the permeability effect of VEGF reduced with corticosteroids. Starling's law explains vasogenic edema, which is controlled by osmotic and hydrostatic gradients between vessel and tissue. It explains the effect of VEGF-induced vascular permeability changes on plasma protein leakage and the osmotic gradient between vessel and tissue. At the same time, it takes into account hemodynamic changes that affect the hydrostatic gradient. This includes the influence of arterial blood pressure, and the effect oxygen (laser treatment) has in constricting retinal arterioles, increasing their resistance, and thus reducing the hydrostatic pressure in the microcirculation. Reduced capillary hydrostatic pressure and increased osmotic gradient reduce water fluxes from vessel to tissue and reduce edema. Finally, Newton's third law explains that vitreoretinal traction decreases hydrostatic tissue pressure in the retina, increases the pressure gradient between vessel and tissue, and stimulates water fluxes from vessel into tissue, leading to edema.

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Section: Iris Neovascularizationmentioning

confidence: 99%

Section: Retinal Neovascularisationmentioning

confidence: 99%

Section: Diabetic Macular Edemamentioning

confidence: 99%

Section: How Do We Treat Edema?mentioning

confidence: 99%

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Physiology of vitreous surgery

Stefánsson

2008

Graefes Arch Clin Exp Ophthalmol

251

198

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“…20,21 In spite of the fact that laser panretinal photocoagulation for diabetic retinopathy has been used since it was first suggested by Meyer-Schwickerath almost 50 years ago, 22 and that grid laser treatment in the management of macular oedema has been used for some 40 years, 23 some aspects of the mode of action of laser in these and similar conditions remain incompletely explained. Thus, although it has been established both experimentally [24][25][26][27] and clinically [28][29][30][31] that laser treatment results in an increase in oxygen availability in the inner retina, explanations for this finding have varied between an increased inward diffusion of oxygen from the choroid through laser-disrupted tight junctions in the retinal pigment epithelium (RPE), 32 and a reduced oxygen demand in the outer retina (and a consequent increased availability of oxygen in the inner retina) resulting from laser destruction of highly energydemanding photoreceptors 26,33 or from destruction of other retinal neural elements, 34 or from a combination of these factors, including diffusion of oxygen from the anterior chamber in eyes undergoing concomitant vitrectomy and laser treatment. 35 Originally it was suggested that laser panretinal photocoagulation obtained its effect from destruction of ischaemic retina, but in diabetes and after ischaemic retinal vein occlusion, retinal capillary closure leading to retinal ischaemia and hypoxia affects the inner retina while laser is preferentially absorbed, and produces its effects in the RPE and outer retina.…”

Section: Introductionmentioning

confidence: 99%

A role for photoreceptors in retinal oedema and angiogenesis: an additional explanation for laser treatment?

Foulds

Kaur

Luu

et al. 2009

Eye

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Purpose To investigate the possible roles of retinal photoreceptors in macular oedema and retinal angiogenesis with particular reference to the mode of action of laser therapy. Methods (i) Studies in rats made hypoxic for 2 h by administering an oxygen/nitrogen mixture of reduced oxygen content, and growth factors determined by RT-PCR, western blotting, and immunohistochemistry. Assessment of blood-retinal barrier integrity using fluorescent and electron-dense tracers.(ii) Studies in pigs with one retina made hypoxic by selective embolisation of the retinal capillary circulation with fluorescent microspheres. (iii) Assessment of laser therapy in selected cases of retinal neovascularisation indicating a role for photoreceptors. Results In the hypoxic retina, angiogenic and vascular permeability factors such as vascular endothelial growth factor (VEGF), nitric oxide synthases (NOSs), and insulin-like growth factor-1 are upregulated in retinal astrocytes and Mü ller cells but are also present in large amount in the photoreceptors. Hypoxiainducible factor-1 (HIF-1) is upregulated in retinal glial cells but not in the photoreceptors, suggesting that growth factors in the photoreceptors may not have been generated there. The tracer dye, rhodium isothiocyanate, leaking from an abnormally permeable inner blood-retinal barrier in the hypoxic retina accumulates in the photoreceptors. Conclusions The results indicate that laser treatment of macular oedema or retinal neovascularisation may obtain its effect not only by improving oxygen availability in the inner retina, but also by reducing the load of angiogenic/permeability factors that accumulate in the photoreceptors in hypoxic/ ischaemic conditions.

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