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.

Physiology of vitreous surgery.

Optical coherence tomography (OCT) is a technique that is used to peer inside a body noninvasively. Tissue structure defined by tissue absorption and scattering coefficients, and the speed of blood flow, are derived from the characteristics of light remitted by the body. Singly backscattered light detected by partial coherence interferometry (PCI) is used to synthesize the tomographic image coded in false colors. A prerequisite of this technique is a low time-coherent but high space-coherent light source, for example, a superluminescent diode or a supercontinuum source. Alternatively, the imaging technique can be realized by using ultrafast wavelength scanning light sources. For tissue imaging, the light source wavelengths are restricted to the red and near-infrared (NIR) region from about 600 to 1300 nm, the so-called therapeutic window, where absorption (μa ≈ 0.01 mm−1) is small enough. Transverse resolution in OCT is diffraction limited, as in conventional imaging; depth resolution is limited by the coherence length of the light. Both figures are of the order of micrometers. Velocity resolution is of the order of 0.1 mm s−1. Several instruments are commercially available. At present, OCT is mainly used in the medical field, in particular, in ophthalmology. Owing to the high transmissivity of ocular media, the depth penetration is considerable. Corresponding applications in dermatology are somewhat hindered by the strong scattering of epidermic tissue (μs ≈ 102 mm−1). As OCT provides images with a resolution comparable to conventional histology, but in real time, it can be used as a biopsy technique in a wide range of biological systems to detect diseases. These include the tomographic imaging of the internal microstructure of in vivo atherosclerotic plaques, the tomographic real-time diagnostics for intraoperative monitoring, and in microsurgical intervention. Optical biopsy based on OCT also provides diagnostic information by differentiating the architectural morphology of urological tissue, gastrointestinal tissue, and respiratory tissue.

Optical Coherence Tomography

Despite treatment advances, diabetic eye disease remains a leading cause of visual acuity (VA) loss worldwide. No methods to prospectively determine which patients will gain or lose vision exist, limiting individualized risk assessment and management. We investigated whether noninvasive, readily obtainable spectral domain optical coherence tomography parameters were correlated with VA in eyes with current or resolved center-involved diabetic macular edema (DME). Images were evaluated for disorganization of the retinal inner layers (DRIL), cysts, epiretinal membranes, microaneurysms, subretinal fluid, and outer layer disruption/reflectivity. DRIL affecting ≥50% of the 1-mm central retinal zone was associated with worse VA in all eyes, eyes with current edema, and eyes with resolved edema. Furthermore, early 4-month change in DRIL extent predicted VA change from baseline to 1 year. These data suggest that DRIL is a robust predictor of VA in eyes with present or previous DME and more highly correlated with VA than other widely used measures, such as retinal thickness. If further studies confirm DRIL as a predictive biomarker of future VA, physicians would gain a new tool of substantial clinical and investigative importance that could significantly change the approach to ophthalmic counseling and therapeutic management in patients with diabetes.

https://diabetes.diabetesjournals.org/content/diabetes/64/7/2560.full.pdf

Neural Retinal Disorganization as a Robust Marker of Visual Acuity in Current and Resolved Diabetic Macular Edema

Background:Intravitreal ranibizumab and pegaptanib are registered for neovascular age-related macular degeneration. No formal safety study has been conducted for intravitreal bevacizumab. These anti-vascular endothelial growth factor (anti-VEGF) drugs are being used on a large scale in daily practic

A systematic review of the adverse events of intravitreal anti-vascular endothelial growth factor injections

Bevacizumab (Avastin) for the treatment of ocular disease.

PURPOSE: To assess the effect of intravitreal bevacizumab on diabetic macular oedema (DMO) and retinal vessel calibres. METHODS: We performed a consecutive case series study in which 10 consecutive eyes with diffuse DMO, two of which had not previously been treated, received an intravitreal injection of bevacizumab 1 mg, which was followed by two more injections at 6-week intervals. Fundus photography and optical coherence tomography (OCT) were carried out at baseline immediately before injection and at 1, 2.5 and 4 months after the first injection. Outcome measures were best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters, macular volume, foveal subfield thickness and vessel diameter measurement. RESULTS: Intravitreal administration of bevacizumab was followed by a mean increase in BCVA of 7.3 +/- 17 (mean +/- standard deviation) letters between baseline and month 4, which was 1 month after the last injection (p < 0.0001). This was accompanied by a reduction in mean macular volume from 9.90 +/- 1.9 mm(3) to 8.96 +/- 2.4 mm(3) (p = 0.002) and in foveal subfield thickness from 447 +/- 117 microm to 388 +/- 117 microm (p = 0.03). Two eyes with early proliferative diabetic retinopathy lost all signs of proliferation without any evidence of fibrosis. Although there was a trend towards vasoconstriction, the changes in vessel diameters (arteries and veins) after 4 months of intravitreal Avastin injection were not statistically significant (p = 0.9 and p = 0.17, respectively). Foveal thickness in non-injected fellow eyes with DMO changed from 428 +/- 153 microm at baseline to 383 +/- 151 microm at 4 months (p = 0.1), which did not reach statistical significance. CONCLUSIONS: Intravitreal bevacizumab 1 mg every 6 weeks was followed by a moderate reduction in DMO without normalization of foveal and macular thickness. Our observations suggest that a larger study where patients are examined sooner after injection is needed to elucidate the potential relationship between changes in retinal vessel diameters and thickness changes in DMO.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0420.2007.01057.x

Optical coherence tomography and vessel diameter changes after intravitreal bevacizumab in diabetic macular oedema.

Purpose: To assess the predictive value of optical coherence tomography (OCT) mapping of retinal thickness and intraretinal morphological changes after macular grid for diffuse diabetic macular oedema (DMO). Methods: We carried out a prospective, non-controlled, case series study, in which 28 consecutive eyes with previously untreated diffuse DMO underwent fundus photography and OCT at baseline and at 1, 3 and 6 months after treatment. Results: Macular photocoagulation was followed by a significant reduction in retinal thickness in the foveal centre () 80 lm) and in the foveal subfield () 65 lm) from baseline to 6 months (p 0.05). The relative decrease in retinal thickness at 6 months was highest in the foveal centre () 22%), followed by the foveal region () 18%), the inner parafoveal region () 8%), and the outer parafoveal region () 2%). Thus, the effect of photocoagulation on retinal thickness decreased with increasing eccentricity (p < 0.025). Overall, there was no statistically significant change in best corrected visual acuity (BCVA) between baseline and follow-up (p < 0.05), but changes in foveal subfield thickness and changes in VA were highly correlated (r = 0.66, p < 0.0001). Visual outcome (final BCVA) and final foveal subfield thickness at 6 months were correlated with the pattern of intraretinal morphological changes at baseline (Spearman’s correlation coefficient r = ) 0.41, p = 0.03 and r = 0.45, p = 0.02, respectively). In addition, visual outcome (final BCVA) and final foveal subfield thickness at 6 months were correlated with baseline foveal thickness (Spearman’s correlation coefficient (r = ) 0.37, p = 0.05 and r = 0.5, p = 0.01, respectively). Conclusions: It seems that the 1-month time-point after macular laser treatment is a critical point for establishing the outcome of this modality of management of DMO. Baseline OCT mapping of intraretinal fluid accumulation patterns and foveal thickness can help to predict the final visual outcome and final foveal thickness, but not the absolute change in either of these parameters after macular laser therapy.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0420.2007.01048.x

Sameer Yehya

Papers

Optical coherence tomography and vessel diameter changes after intravitreal bevacizumab in diabetic macular oedema.

The predictive value of optical coherence tomography after grid laser photocoagulation for diffuse diabetic macular oedema