Imaging Vitreomacular Interface Abnormalities in the Coronal Plane by Simultaneous Combined Scanning Laser and Optical Coherence Tomography
A. M. Tammewar; D-U Bartsch; I. Kozak; R. Rosen; I. A. Falkenstein; P. Garcia; W. R. Freeman
Published: 04/14/2009Abstract Aim: To describe vitreoretinal imaging of eyes with vitreomacular abnormalities using high-resolution coronal-plane optical coherence tomography (OCT) scanning combined with simultaneous scanning laser ophthalmoscope (SLO) imaging. Methods: A SLO-OCT (OTI, Canada) was used to scan 835 eyes in 736 patients with vitreomacular interface abnormalities including epiretinal membranes, macular hole, incomplete posterior vitreous detachment, vitreomacular traction syndromes and diabetic and cystoid macular oedema in a retrospective study. The longitudinal-B scan images and the transverse -C scan images in the coronal plane were used to describe vitreomacular interface abnormalities. The SLO-OCT simultaneously produces a confocal image of the retina. Results: The longitudinal "B" scan and en-face "C" scan images allowed identification of tractive forces of epiretinal membrane, contour of the hyaloid membrane and changes in inner retinal surface. A simultaneously obtained OCT scan and SLO image of the fundus offered exact co-localisation of retinal structures and vitreomacular interface abnormalities. Conclusion: Scanning the vitreomacular interface by using combined OCT and SLO enables the visualisation and better understanding of various vitreomacular interface abnormalities, due to the ability to colocalise pathology on OCT with retinal vascular landmarks and the ability to visualise pathology from a new perspective, coronal plane parallel to retinal surface. Introduction Optical coherence tomography (OCT) is now a widely used imaging technique in ophthalmology to diagnose various macular and optic nerve conditions since its first report in 1991.[1] Optical coherence tomography achieves two-dimensional cross-sectional imaging of tissue by measuring the echo delay and intensity of back-reflected infrared light from internal tissue structures.[2] Optical coherence tomography enables the direct real-time imaging of retinal pathology that could not previously be visualised in vivo, and so it is described as a non-invasive optical biopsy of the retina.[3] Since the introduction of commercial OCT in 1996, OCT technology has undergone multiple generations of improvement. OCT has been largely used to create longitudinal images of the eye (analogous to ultrasound B-scan images), which are in-depth measurement through the retina,[4] "i.e. images in the plane (X, Z) or (Y, Z) with the "Z" axis normal to the patient's face." Podoleanu et al, reported an OCT system capable of producing both transverse (en-face) and longitudinal images from the retina in living eye. They developed the combined system of confocal scanning laser ophthalmoscopy to obtain the high-resolution transverse image of retina (fundus view) and OCT to obtain cross-sectional transverse and longitudinal scans.[5,6] This system produces en-face OCT images and a pixel-to-pixel corresponding transverse image of retina provided by the confocal channel simultaneously to compare them directly.[7,8] This is achieved by selective capture of different orientations of OCT images at precise points on the confocal image. The optical source used in this combined system of OCT and confocal scanning laser ophthalmoscopy is similar to that in conventional high-resolution longitudinal OCT (Stratus OCT, Carl Zeiss Meditec, Dublin, California), so the depth resolution obtained is also the same, that is 10-15 µm.[9,10] The recent introduction of several commercial spectral-domain OCT devices has allowed ophthalmologists to obtain three-dimensional high-resolution OCT data.[11-13] In this pilot study, we present the clinical evaluation of various vitreomacular (VM) interface abnormalities by using this novel system of combined scanning laser ophthalmoscope and optical coherence tomography. Our purpose is to show examples of visualisation of VM interface pathology in eyes with epiretinal membrane (ERM), VM traction syndrome, macular hole, incomplete posterior vitreous detachment (PVD) and cystoid macular oedema due to VM interface abnormalities like ERM and diabetic macular oedema in the coronal plane (en-face view).
Patients and Methods We used scanning laser ophthalmoscope optical coherence tomography (SLO-OCT; OTI, Toronto, Ontario, Canada) to scan patients with VM interface abnormalities including epiretinal membrane, macular hole, incomplete (shallow) posterior vitreous detachment, VM traction syndrome, diabetic macular oedema (DME) and cystoid macular oedema (CMO). The SLO-OCT combines optical coherence tomography and confocal ophthalmoscopy. The system uses a super-luminescent diode emitting at a central wavelength of 820 nm with a bandwidth of 20 nm. The light beam is split, directing one part to the patient's eye (sample arm) and the other part to the reference arm (mirror). The returning light beams both from the patient's eye and the reference arm are collected through an interferometer to produce an OCT signal. A fraction of the light returning from the patient's eye is also directed towards another detector to produce a confocal signal, so that both images in the confocal and OCT channels correspond strictly in a pixel-to-pixel manner. The OCT ophthalmoscope produces both transverse and longitudinal scans. The transverse scans or "C" scans are produced in the X-Y plane at a fixed "Z" coordinate. The system produces OCT "C" scans (ie, coronal scans) parallel to the retinal surface by changing the "Z" coordinate. The SLO-OCT also produces longitudinal "B" scan images by making en-face "A" scans along a fixed axis in the X-Y plane and continuously moving the "Z" coordinate. In the current system, both "C" and "B" scans are acquired at a speed of two frames per second. Each scan covers an area of 30 × 20°. Both OCT and confocal images are displayed on a monitor simultaneously as a grey scale image. Within this system, both the depth ("Z" axis) and transverse (X-Y plane) resolutions are 10-15 µm. Both transverse ("C") and longitudinal ("B") scans were obtained through the macular area of all patients with VM interface abnormalities. In the longitudinal "B" scan mode, the images were obtained in both vertical and horizontal lines in the X-Y plane. A total of 835 eyes in 736 patients of various VM interface abnormalities were scanned with the combined SLO-OCT from September 2005 through June 2006 at two university-based retinal practices (Jacobs Retina Center at the Shiley Eye Center, University of California San Diego and New York Eye and Ear Infirmary). Of these patients, 362 were males, and 374 were females. Incomplete PVD patients formed the major group (with 308) followed by diabetic macular oedema, ERM, macular hole, ERM with cystoid macular oedema and VM traction (see Table 1 ). We received approval from the University of California San Diego Human Research Protection Program for the retrospective analysis of these data. Results The following features of each type of VM interface abnormality were identified and are illustrated here. Epiretinal Membrane In all eyes with epiretinal membrane (113 eyes), "B" scan images showed a hyper-reflective membranous structure (band) on the surface of retina with a serrated or folded internal retinal surface. At some places, it showed points of cleavage with the internal retinal surface (see fig 1A arrow and fig 1B). The en-face "C" scan of ERM showed a radiating pattern with retinal folds and the membrane's extensions (see fig 1C,D). The surface of the membrane was visible when the plane of the "C" scan was superficial at the level of vitreous-retina interface. As the plane of the "C" scan had travelled deeper (changing the "Z" coordinate), the ERM appeared less visible, and the retinal layers started appearing as concentric rings in en-face imaging. The en-face imaging of ERM showed the complete structure of the membrane along with the traction's epicentre. Figure 1. (A,B) Epiretinal membrane with the traditional transverse B-scan image on top of both images. The position of the B-scan in correspondence to the scanning laser ophthalmoscope (SLO) fundus image (bottom right of A and B) is indicated by the grey line. The B-scan is located at the macula showing a hyper-reflective membrane on the retinal surface with folds of internal limiting membrane (arrow). The small image on the bottom left of A and B allows us to judge eye movement during the B-scan. (C,D) Image pair showing the SLO fundus view (left) and the en-face "C" scan (right) of the same patient's macular area showing the epicentre of the membrane with its radiating transverse extensions. VM Traction Syndrome VM Traction with Retinal Surface Abnormalities. Figure 2A,B shows the longitudinal scan ("B" scan) showing vitreous attachment to the retinal surface and elevated areas of it indicating the transverse as well as axial traction on the retina. The firm adherence of the posterior hyaloid to the retina is seen clearly (fig 2B, arrow). The en-face scan ("C" scan) showed the vitreous as a moderate hyper-reflective circular structure surrounded by concentric layers of retina when the "C" scan depth was anterior to the retinal surface. Figure 2C shows a circular hyper-reflective structure indicating the posterior hyaloid (arrow). Since the scan is slightly tilted, the bottom of this circular structure shows its point of adhesion to the retinal surface (arrow head) with different retinal layers seen within the same scan. The bottom of the scan showing the retinal layers is scanning deeper in the retina than the top of the scan, which shows the ERM (curved arrow). Figure 2D is a "C" scan of the same eye at a deeper level in the retina showing ERM (arrow). Figure 2. Vitreomacular traction with retinal surface abnormality. (A) Scanning laser ophthalmoscope image (bottom right) and transverse "B" scan of macular area showing epiretinal membrane (ERM) (arrowhead) with vitreomacular traction (arrow). (B) "B" scan of the same eye nasal to fovea. Note the attachment of posterior hyaloid to the retina with traction induced retinal oedema (arrow). (C) En-face "C" scan of the same patient's epiretinal membrane with vitreomacular traction showing circular hyper-reflective posterior hyaloid (arrow) with its attachment with retinal surface at the base (arrowhead). The curved arrow shows the ERM in the same scan. (D) "C" scan of the same eye at a deeper level than in C, showing the ERM (arrow). Diabetic Macular Oedema with VM Traction. The second category of the patients with VM traction were diabetic macular oedema with axial traction on the macula. Figure 3A depicts horizontal cross-sectional high-resolution OCT image (longitudinal "B" scan) through the foveal region of right eye showing an attachment of a hyper-reflective membranous shadow in the vitreous (posterior hyaloid) with the fovea (arrow). The inner retinal layer at the attachment is elevated indicating the VM traction at the fovea. The foveal region shows a large hypo-reflective area below the elevated superficial retinal layers indicating the traction induced cystoid macular oedema and disrupted photoreceptor layer below it (arrowhead). Figure 3B is an image of the same eye by conventional (stratus) OCT, which did not show posterior hyaloid and its traction on fovea. The StratusOCT image appears horizontally stretched due to the difference in lateral scan length between both instruments. We do not know why the SLO-OCT has a better visualisation of the VM traction. We speculate that differences in wavelength or detector design may contribute to the better visualisation. Figure 3. Vitreomacular traction in diabetic macular oedema. (A) Horizontal cross-sectional high resolution optical coherence tomography (OCT) image (longitudinal "B" scan) through the foveal region of the right eye with scanning laser ophthalmoscope (SLO) image of the fundus in a 63-year-old diabetic male, showing an attachment of a hyper-reflective membranous shadow in the vitreous (posterior hyaloid) with the fovea (arrow). Note the cystoid change in the fovea and disrupted photoreceptor layer (inner and outer segment junction) (arrowhead) due to axial vitreofoveal traction. (B) Image of the same eye (on the same day and same location) with conventional OCT showing vitreomacular traction (arrowhead) less clearly compared with that seen in A with SLO-OCT. (C) En-face "C" scan of the same eye anterior to retinal surface showing a hyper-reflective ring shadow (arrow) of vitreous cone (coronal cut) anterior to the fovea with concentric retinal layers seen at the periphery. (D) En-face "C" scan of the same eye very close to the fovea, showing a small ring of the shadow of the posterior hyaloid in continuation with the retinal layers (short arrow). Figure 3C,Ddepicts the en-face "C" scan (transverse scan) of the same eye in the macular region at different depths. When the "Z" axis coordinate was superficial, that is, anterior to the retinal surface, the posterior hyaloid was seen as a hyper-reflective ring shadow in the centre (fig 3C, arrow), and when the "Z" axis coordinate was deeper, that is, very close to the retinal surface, the "C" scan showed a small hyper-reflective ring in continuation with concentric shadows of retinal layers (fig 3D short arrow) indicating the adherent posterior hyaloid in the foveal area. Macular Hole The longitudinal "B" scan of the full-thickness macular hole (fig 4A) showed typical OCT features in the form of a full-thickness gap in retinal layers with the exception of the hyper-reflective RPE layer with cystic spaces at the edges of the hole (fig 4A, arrow). The "C" scan (fig 4B) images showed a unique feature. When the depth of the "C" scan was at the level of vitreoretinal interface and superficial retinal layers, the hole was seen as a black central circular area surrounded by small circular hyper-reflective cystic images (fig 4B, arrow). As the scan travelled deeper at the level of RPE, the floor of the macular hole appeared as a white hyper-reflective circular area surrounded by a dense reflective shadow of RPE (fig 4C, black arrowhead). The "B" scan (fig 4D) of lamellar macular hole showed a gap in the superficial layers of retina. The absence of cystic changes surrounding the hole is notable in the "C" scan (fig 4E). The visualisation of PVD, gap or discontinuity in the retinal layers on "B" scan differentiates it from the pseudo-hole. Figure 4. Macular hole. (A) Scanning laser ophthalmoscope image and longitudinal "B" scan of the macular area showing the full- thickness macular hole with cystic spaces in the retina at the edges (arrow). (B) En-face "C" scan of the macular hole from the same patient showing centrally the hole (circular black area within the retinal layer mage) with radially arranged cystic spaces (flower petal appearance) (arrow). (C) "C" scan of the same patient of the macular hole for a deeper layer of the retina showing the floor of the hole as a white (hyper-reflective) circular shadow (black arrowhead). (D) Longitudinal "B" scan of the macula showing a lamellar macular hole and hyper-reflective posterior hyaloid. (E) En-face view ("C" scan) of the same lamellar macular hole. Shallow Posterior Vitreous Detachment In the longitudinal "B" scan done at the level of the superior arcade, a linear hyper-reflective shadow was seen anterior to the surface of the retina with its attachment to the retinal surface in the macular area indicating incomplete PVD (fig 5A, arrow). The "C" scan showed the posterior hyaloid as a hazy white concentric shadow when the depth of the "C" scan was anterior to the retinal surface, that is, prior to the appearance of image of the retinal layers (fig 5B, arrows). Retinal layers were seen at the periphery of the scan, since the depth of the "C" scan was more tangential due to the normal curvature of the eye (fig 5B). Figure 5. Shallow posterior vitreous detachment. (A) Longitudinal "B" scan showing posterior hyaloid (arrow) separated from retina with its attachments at two places (incomplete posterior vitreous detachment). (B) En-face "C" scan with corresponding scanning laser ophthalmoscope image showing posterior hyaloid in the optically translucent space anterior to retinal layers as concentric hazy white shadow (arrowheads). The shape is curved because the "C" scan is tangential to the curved retinal surface. CMO with VM Interface Abnormality The imaging of CMO secondary to the VM interface abnormalities in 59 patients showed a classic appearance on the "C" scan. The longitudinal scan ("B" scan) showed vertical cystic spaces involving retinal layers in macular area (fig 6A). It also showed the disrupted photoreceptor outer segment band due to oedema and traction (arrow in fig 6A). Figure 6B,C shows an en-face image of typical CMO in the form of multiple circular hyper-reflective shadows, variable in size, representing the intra-retinal cysts (arrow in fig 6C). The macular image appeared anterior to the rest of retinal layers due to its swelling (fig 6B). Figure 6. Cystoid macular oedema with VM interface abnormality. (A) Longitudinal "B" scan of macular area showing cystic spaces (axial view) in the retinal layers with the epiretinal membrane. Note the disrupted photoreceptor outer segment band anterior to the retinal pigment epithelial layer (arrow) due to oedema. (B) En-face "C" scan of elevated macula of same patient showing cystic spaces and oedema. Note that the macular image appears anterior to the rest of the retinal layers due to its elevated position (oedema). (C) "C" scan of same patient at a deeper retinal level showing an en-face view of cystoid macular oedema with multiple cysts of variable sizes arranged radially (arrow). Diabetic Macular Oedema In patients with diabetic macular oedema, SLO-OCT images of macula not only showed typical cystoid or non-cystoid oedema but also revealed the VM interface relations. Figure 7A depicts the vertical cross-sectional longitudinal "B" scan image with SLO-OCT in an eye with diabetic macular oedema showing partial vitreous detachment with attachment of posterior hyaloid to the macula (arrow) and cystoid oedema of retinal layers in the macular region. Figure 7B shows a vertical cross-sectional image of the macular region of the same eye with conventional (stratus OCT, Carl Zeiss) OCT, which is not showing the posterior hyaloid and its attachment at the macular region. Figure 7C shows the enface "C" scan image of the macular area of the same eye showing small bubble-like clear areas with hyper-reflective margins in the retinal tissue, which was a coronal section of multiple cystic spaces in the retinal layers (white arrowhead). In all these eyes, the "B" scan showed a very clear, thin, hyper-reflective band in front of the hyper-reflective RPE band representing the junction of the outer and inner segments of the photoreceptors. Figure 7. Diabetic macular oedema with incomplete posterior vitreous detachment. (A) Vertical cross-sectional longitudinal "B" scan image with scanning laser ophthalmoscope-optical coherence tomography (SLO-OCT) in an eye with diabetic macular oedema in a 62-year-old male showing partial vitreous detachment with attachment of posterior hyaloid to the macula (arrow) and cystoid oedema of retinal layers in the macular region. (B) Vertical cross-sectional image of the macular region of the same eye with conventional (stratus) OCT in the location (close to the location in A), not showing the posterior hyaloid and its attachment to the macular area. Multiple stratus images were obtained which did not show this attachment. None of the six StratusOCT images corresponded exactly with the SLO-OCT image. (C) En-face "C" scan image of macular area of the same eye showing the coronal section of multiple cystic spaces in the retinal layers (arrowhead).
Discussion Interpretation of images obtained by scanning the retina in the coronal plane by combined scanning laser and optical coherence tomography is different from the conventional longitudinal "B" scan. En-face imaging gives a top (surface) view of retinal layers obtained at different depths by changing the "Z" axis coordinate. This gives images the appearance as if one is slicing the retina parallel to its surface or histological sections taken through the retina perpendicular to the optical axis. The images are cross-sectional cuts through the retinal tissue. However, since the optical axis of the OCT scanner and the optical axis of the eye do not always coincide, different parts of one image can be recorded from different optical depths. Thus, several structures of different depths are simultaneously imaged. In en-face "C" scans, retinal layers are seen as concentric rings. The deeper structures appear further away from the centre of the rings. The exact position of each of these concentric rings within the image depends on the depth of the scan along the "Z" axis. Although the precise location of the scan along "Z" axis (depth) cannot be predicted accurately, it can be judged by the appearance of the retinal vessels in the "C" scan. As the "C" scan depth progresses deeper into the retinal layers, the retinal vessels appear as dark lines, due to the shadow cast on the deeper layers. As the "C" scan images are obtained at a superficial level (near the retinal surface), the retinal vessels appear as white lines (fig 3A, red arrowhead), and as the depth of "C" scan increases, the retinal blood vessels appear as black lines (green arrowhead in fig 3A). Van Velthoven et al [14] documented a similar observation. We describe this new imaging device, combined coronal OCT and SLO. This imaging technique involves en-face scanning in the X-Y plane and combines the high-resolution tomographic images with the surface imaging ability of the scanning laser ophthalmoscope. It has two advantages. The first advantage is that the "C" scan of the retina shows pathology parallel to RPE and shows tractional forces, retinal surface and inner retina in a way not usually seen with a commercially available OCT system. Second, combined SLO gives a simultaneous fundus image with OCT. The fundus image is taken simultaneously with the OCT that allows co-localisation of the structures and pathology visible with conventional imaging or ophthalmoscopy with the OCT image of the exact same area of the fundus. Thus, the confocal image is used for general orientation and localisation of the pathology on the retina. It is also used for better and more reliable positioning of the OCT "B" scan and to detect the eye movements so that images with eye movements can be discarded. This freedom of imaging and precise co-localisation of retinal pathology with the fundus image were not available previously with the StratusOCT (OCT-3), since OCT-3 uses a scan orientation fundus photograph taken after completion of all of the OCT "B" scans. Another advantage of the simultaneous confocal image is that, given that the images in confocal and OCT channel are correspond pixel-to-pixel, transformed angiographic images can be directly superimposed over the OCT image, since angiography images are also displayed in the transverse plane.[15] The rapid technological advances in spectral-domain (SD) or Fourier-domain OCT have allowed ophthalmologists to choose from seven different vendors with seven different types of instruments in addition to several laboratory devices with advanced capabilities. A recent review by Drexler and Fujimoto gives an excellent overview of the advances in this field.[13] SD-OCT technology has achieved an improvement of axial scan rates from 400 A-scans per second in the time-domain OCT technology to 236 000 A-scans per second in laboratory devices, while commercially available devices top out at 40 000 A-scans per second.[16] However, even at the highest scan rate of 236 000/s, it takes more than 1 s to image an area of 512 by 512 pixels. In contrast, simultaneous acquisition of the SLO image as demonstrated in this device allows the co-localisation of the OCT B-scan with the SLO fundus image. Coronal scans or C-scans can be calculated from SD-OCT image stacks by projection of the data into the coronal plane. However, in the absence of eye-motion correction,[17] the coronal scan calculation can be complicated, or incomplete. OCT images have been proved to be very helpful in evaluating VM interface abnormalities. VM interface abnormality may exert traction in the axial direction and as well as in the transverse direction, and lead to the distortion of retinal layers and loss of the foveal depression, also exemplified here in the images of ERM and VM traction syndromes. Delineation of all these transverse tractional forces is much clearer by scanning the retina in the coronal plane and obtaining the en-face "C" scan images with this combined SLO-OCT. In this report, we have documented the en-face "C" scan (coronal scan) and the longitudinal "B" scan features of VM interface abnormalities including ERM, macular hole, VM traction syndrome and incomplete or shallow PVD by combined scanning laser ophthalmoscope and optical coherence tomography. The "C" scan of ERM showed the complete structure of the membrane in the form of radial lines extending from the traction's epicentre with all its extensions in a radiating pattern along with retinal folds; this was not possible with the conventional "B" scan mode of OCT. ERM in the longitudinal "B" scan mode showed several points of cleavage with the internal retinal surface. It indicates that traction is formed between the hyper-reflective band (epiretinal membrane) and the surface of the retina (transverse traction forces). Since there is pixel-to-pixel correspondence between the OCT image and confocal image, a particular area can be localised within the X-Y plane of the confocal image of the retina, and a parallel can be directly drawn with its location on the OCT image. Thus, one can determine the areas of ERM where there is some space between it and the retinal surface. This may aid in the planning of dissection sites for surgical removal of ERM. On "C" scan imaging of macular holes, we found similar features to those reported by van Velthoven et al.[14] In full-thickness macular holes, the "C" scan showed a typical central black space surrounded by small circles of adjacent retinal oedema. In the cases of CMO en-face "C" scanning, small intraretinal cysts were found in the form of circular structures arranged in radial pattern around the fovea. The coronal view of the macular hole provides a unique opportunity to assess the state of the tissue around the hole and to determine the dimensions of the hole more precisely. Combining the vertical diameter calculated from "B" scan images, it is possible to get the exact dimensions of the macular hole. Various studies have reported the size of the hole as one of the strong prognostic factors for surgical outcome of the macular hole.[18-21] In VM traction syndrome, the "B" scan showed points of adhesion and traction at the retinal surface very distinctly, these areas of vitreoretinal traction could be colocalised with simultaneously produced confocal image of the retina as previously described. Specifically, imaging the macular area in suspected VM traction cases on SLO-OCT with en-face scanning mode is very useful to identify the VM traction areas which are otherwise missed by conventional OCT imaging systems, as exemplified in fig 3A,B in a diabetic macular oedema case. This can be useful in managing the cases of VM traction syndromes. In incomplete PVD cases, the "B" scan showed the posterior hyaloid distinctly as a highly reflective band at a distance from the retina within the vitreous cavity. This enables ophthalmologists to identify the contour of the hyaloid membrane. This band was absent in vitrectomised eyes and eyes with no clinical signs of PVD. Identification of this perifoveal vitreous detachment, as probably the important pathogenic event in idiopathic macular hole formation,[22] is reported as stage 0 macular hole. The presence of a stage 0 hole was associated with an almost sixfold increase in risk of macular hole formation.[23] In all cases, while imaging on the combined scanning laser ophthalmoscope and OCT system, the double structure of the "outer retinal band" is generally seen quite clearly. The interior of the two represents the photoreceptor inner and outer segment junction, and the outer represents the retinal pigment epithelium. By documenting these features of VM interface abnormalities on a combined scanning laser and OCT system, we report that it can provide additional information, which is not possible by conventional OCT. An excellent understanding of these VM interface abnormalities can be acquired by mentally combining the several "C" scans obtained at different depths and "B" scans at different positions along the X-Y axis with simultaneously obtained confocal images of the retina. This technique can be applied to a variety of clinical conditions in the macular area and enables us to understand them in a broader sense within the confines of a non-invasive modality of imaging. Further work with image-processing algorithms to "flatten" the images and therefore allow "C" scans in the plane parallel to the retinal surface, will allow coronal sections of the tissue and aid in three-dimensional reconstruction, retinal topography and thickness analysis. Newer spectral OCT technology using high-resolution and high-speed spectral scan technology is under way to improve the resolution by a factor of three to five. This technology will allow visualisation of pathology in the same plane as retinal photographs and allows for visualisation of traction forces and intraretinal structures in a manner that is useful for surgical planning and understanding the pathology. Three-dimensional OCT will incorporate coronal views with "B" scan information in the future and allow visualisation of pathology from multiple aspects.
References 1.Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography. Science 1991;254:1178-81. 2.Puliafito CA, Hee MR, Lin CP, et al. Imaging of macular diseases with optical coherence tomography. Ophthalmology 1995;102:217-29. 3.Fujimoto JG, Brezinski ME, Tearney GJ, et al. Optical biopsy and imaging using optical coherence tomography. Nat Med 1995;1:970-2. 4.Chauhan DS, Marshall J. The interpretation of optical coherence tomography images of the retina. Invest Ophthalmol Vis Sci 1999;40:2332-42. 5.Podoleanu A, Dobre GM, Webb DJ, et al. Simultaneous en-face imaging of two layers in the human retina by low-coherence reflectometry. Optics Letters 1997;22:1039-41. 6.Podoleanu A, Rogers JA, Jackson DA. OCT En-face images from the retina with adjustable depth resolution in real time. IEEE Journal of selected topics in quantum electronics 1999;5:1176-84. 7.Cucu RG, Podoleanu AG, Rogers JA, et al. Combined confocal/en face T-scan-based ultrahigh-resolution optical coherence tomography in vivo retinal imaging. Opt Lett 2006;31:1684-6. 8.Podoleanu AG, Dobre GM, Cucu RG, et al. Combined multiplanar optical coherence tomography and confocal scanning ophthalmoscopy. J Biomed Opt 2004;9:86-93. 9.Schuman JS, Puliafito CA, Fujimoto JG. Optical coherence tomography of ocular diseases. 2nd edn. Thorofare: SLACK 2004:xii;714. 10.Rogers JA, Podoleanu AG, Dobre GM, et al. Topography and volume measurements of the optic nerve using en-face optical coherence tomography. Optics Express 2001;V9:533-45. 11.Chang LK, Fine HF, Spaide RF, et al. Ultrastructural correlation of spectral-domain optical coherence tomographic findings in vitreomacular traction syndrome. Am J Ophthalmol 2008;146:121-7. 12.van Velthoven ME, Faber DJ, Verbraak FD, et al. Recent developments in optical coherence tomography for imaging the retina. Prog Retin Eye Res 2007;26:57-77. 13.Drexler W, Fujimoto JG. State-of-the-art retinal optical coherence tomography. Prog Retin Eye Res 2008;27:45-88. 14.van Velthoven ME, Verbraak FD, Yannuzzi LA, et al. Imaging the retina by en face optical coherence tomography. Retina 2006;26:129-36. 15.van Velthoven ME, de Vos K, Verbraak FD, et al. Overlay of conventional angiographic and en-face OCT images enhances their interpretation. BMC Ophthalmol 2005;5:12. 16.Huber R, Adler DC, Srinivasan VJ, et al. Fourier domain mode locking at 1050 nm for ultra-high-speed optical coherence tomography of the human retina at 236,000 axial scans per second. Opt Lett 2007;32:2049-51. 17.Wolf-Schnurrbusch UE, Enzmann V, Brinkmann CK, et al. Morphological changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination. Invest Ophthalmol Vis Sci. In press. 18.Freeman WR, Azen SP, Kim JW, et al. Vitrectomy for the treatment of full-thickness stage 3 or 4 macular holes. Results of a multicentered randomized clinical trial. The Vitrectomy for Treatment of Macular Hole Study Group [see comments; published erratum appears in Arch Ophthalmol 1997;115:636]. Arch Ophthalmol 1997;115:11-21. 19.Ullrich S, Haritoglou C, Gass C, et al. Macular hole size as a prognostic factor in macular hole surgery. Br J Ophthalmol 2002;86:390-3. 20.Kusuhara S, Teraoka Escano MF, Fujii S, et al. Prediction of postoperative visual outcome based on hole configuration by optical coherence tomography in eyes with idiopathic macular holes. Am J Ophthalmol 2004;138:709-16. 21.Ip MS, Baker BJ, Duker JS, et al. Anatomical outcomes of surgery for idiopathic macular hole as determined by optical coherence tomography. Arch Ophthalmol 2002;120:29-35. 22.Johnson MW, Van Newkirk MR, Meyer KA. Perifoveal vitreous detachment is the primary pathogenic event in idiopathic macular hole formation. Arch Ophthalmol 2001;119:215-22. 23.Chan A, Duker JS, Schuman JS, et al. Stage 0 macular holes: observations by optical coherence tomography. Ophthalmology 2004;111:2027-32. |
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السبت، أبريل ٢٥، ٢٠٠٩
Imaging Vitreomacular Interface Abnormalities in the Coronal Plane by Simultaneous Combined Scanning Laser and Optical Coherence Tomography
السبت، أبريل ٠٤، ٢٠٠٩
[MeDiCiNe_DoCtOrS] فصائل الدم
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إذا أردت معرفة نوعية فصيلة الدم التي تستطيع أخذها أو العكس فيمكنك معرفة ذلك من خلال الجدول
معلومات من ذهب فصائل الدم الغذاء المناسب لكل منها
فصيلة الدم A : أنت ستصبح أكثر رشاقة على نظام فصيلة الدم A إذا تعودت على أكل الأطعمة المسموح لك بأكلها و حذف ما هو محظور أكله , فصيلة الدم A عكس الفصيلة O تماماً في نظام الأكل والتمثيل الغذائي للطعام الذي يأكله الأشخاص المنتمون للفصيلة O , فنجد أن أكل اللحوم الحيوانية تسرع من عملية التمثيل الغذائي ويصبح أكثر فعالية , بعكس تأثيرها على الأشخاص المنتمون إلى فصيلةA , حيث أن أكل اللحوم يجعل الشخص من فصيلة A متعب وأقل حركة وطاقة عن ما يأكله من البروتينات النباتية . ففصيلة الدم A تحتفظ بالماء في أجسام أصحابها عندما تبطء عملية التمثيل الغذائي , بينما فصيلة O تحرق جميع اللحوم كالوقود بدون أي أضرار في أجسادها . في حين أن فصيلة الدم A تخزن اللحوم الموجودة في الطعام كدهون في الجسم , لذلك اللحوم الحيوانية تسبب السمنة بالنسبة للأشخاص من فصيلة الدم A , بينما هي غذاء جيد لـ O , و السبب في ذلك هو حموضة المعدة في O , بحيث نجد أن نسبة الحموضة في المعدة عالية جداً عندما يهضم اللحم بسهولة بدون أي مشاكل . أما في فصيلة A فنسبة الحموضة منخفضة جداً .. و للتكيف مع هذا النوع يجب الإعتماد على المحاصيل الزراعية ( أي التحول إلى شخص نباتي ) . منتجات الألبان : تهضم بضعف وبطء شديد مع A لذا فهي مزعجة وسيئة بسبب تفاعلات الأنسولين لأن منتجات الألبان مشبعة بالدهون لذا تسبب أضراراً بالقلب وتسبب مرض السكر والسمنة . القمح : يعتبر من العناصر المختلطة في A يمكن لهذه الفصيلة أكل القمح ولكن ليس بكثرة لأن كثرته تسبب حموضة في عضلات وأنسجة الجسم وذلك بعكس O الذي ينمو بقوة على الأنسجة الحمضية فالقمح قاعدي لمن له فصيلة O بينما حمضي لمن له فصيلة A . وبالإضافة إلى أكل الأطعمة الصحية وقليلة الدهن والخضار والحبوب المتوازنة فإن فصيلة الدم A تحتاج للأكل الخفيف للحصول على الفائدة العامة والتأثيرات الجيدة 0 ولذلك سنعطي دليل سريع لأهم وأفضل الأطعمة التي تفيد أو تضر بالجسم . فمن الأطعمة التي تساعد على زيادة الوزن : لأصحاب الفصيله A اللحوم : بطيئة الهضم وتخزن في الجسم كدهون وتزيد سموم الهضم . مشتقات الألبان : تبطيء عملية التمثيل الغذائي . الفاصوليا القلوية : تتداخل مع إنزيمات الهضم وتبطيء عملية التمثيل الغذائي . القمح : يوقف ويثبط الأنسولين . زيت الخضار : يساعد على الهضم الجيد ويمنع حفظ الماء في الجسم . الأطعمة التي تساعد على إنزال الوزن : أطعمة الصويا : تساعد على الهضم وتمثيل الغذاء بسرعة . الخضار : تساعد على التمثيل الغذائي الصحيح وتسرع من حركة الأمعاء . :الأناناس : يساعد على سرعة حركة الأمعاء . للحصول على أفضـل نتائج فصيلة A يجب عليها الإمتناع عن تـناول اللحوم في نظام أكلها ، فمن المفروض أن هذه الفصيلة أشخاصها معرضين للإصابة بأمراض القلب والسكر وسرطان المعدة ، لذا يجب الإمتناع عن المحظورات و أكل كل ما هو مفيد للجسم . تكملة الأغذيه الممنوعه والمفيده للفصيله A نكمل ما يخص الفصيله A من حيث الأغذيه الممنوعه والمفيده والمحايده : المحظورات : اللحوم الحمراء بصفة عامة - الكبد - القلب – الأرنب – الخنزير – البط – الوز – البقر- الماعز . المحايد : الدجاج – الديك الرومي ( التركي ) – الفروج ( صغار الدجاج ) الأسماك : المفيد منها : السارديـن – السالمون – الماكريل – الكود – السمك الأبيـض – الرد سنابر ( الحمراء ) – القرش – التونة – سمك السيف . المحظورات من الأسماك : الكافيار – الجمبري – الضفادع – الكلامب ( CLAMP ) - المحار – الأستاكوزا – السلاحف – الأخطبوط – السمك الأزرق – قط البحر – الأصداف يمكن للأشخاص من فصيلة الدم A إستخدام منتجات الألبان ولكن يجب الإمتناع عن الأشياء المصنعة من الحليب الكامل الدسم – وتحدد كمية البيض المستهلك . كما يمكن استخدام حليب الصويا واللبن الرائب والزبادي الكريمة الغير مدهنة و حليب الماعز كبديل جيد للحليب الكامل – جبن الصويا – معظم مشتقات الألبان أو الحليب غير مهضومة جيداً عند الأشخاص من هذه الفصيلة , وذلك لأن هذه الفصيلة تنتج مضادات حيوية للسكر الموجود في الحليب الكامل الدسم مع الفيوكوز FUCOSE يمثل TYPE BANTIGEN أي يمثل بروتين يسمى BANTIGEN وهذه الفصيلة ترفض أي شيء من هذا المركب التي تسبب المناعة الطبيعية لهذه الفصيلة , فالمضادات الحيوية التي تكونها هذه الفصيلة ترفض كل مشتقات الحليب الكامل الدسم ، فإذا كنت تعاني من حساسية من الحليب الكامل الدسم هذا يعني أن إفرازات الصدر تكون كثيرة مما يؤدي إلى مشاكل في الجهاز التنفسي نتيجة إفراز كمية كبيرة من الإفرازات المخاطية التي تضر بالصدر وعادة هذا النوع يفرز أكثر من غيره من فصائل الدم بالنسبة للإفرازات المخاطية . مشتقات الحليب المفيدة : جبن الصويا – وحليب الصويا . مشتقات الحليب الغير ضارة ( المحايده ) : جبن الغنم – حليب الغنم – المازولا – اللبن الزبادي – واللبن المثلج – اللبن الزبادي بالفواكه - جبن الفيتا الغنمي . المحظورات : الجبن الأمريكي – الجبن الأزرق – الزبدة – زبدة الحليب – جبن الشيدر – الكوتينج – جبن الكريم ( الكاسات ) – الآيس كريم – جبن البارميسان السويسري – الحليب الكامل الدسم الزيوت والدهون : الدهون والزيوت غير مرغوبة لهذه الفصيلة إلا زيت الكتان و زيت الزيتون حيث يمكن استخدام ملعقة يومياً من زيت الزيتون للطبخ أو للسلطة لأنه يساعد على خفض نسبة الكوليسترول . المفيد جداً : زيت الزيتون – زيت الكتان المحظورات : زيت الذرة – زيت القطن – زيت اللوز – زيت دوار الشمس . المكسرات والبذور : بما أن هذه الفصيلة مسموح لها بقليل من البروتين الحيواني لذلك فإن البروتينات النباتية الموجودة في المكسرات مفيدة لهذه الفصيلة كبذور دوار الشمس وبذور القرع ( الفصفص الدبة ) واللوز البجلي واللوز السوداني مفيد جداً لهذه الفصيلة , يجب أكل اللوز دائماً لأن فيه مواد مضادة للسرطان ( Cancer Fighting Lectin ) . ويجب أكل قشر اللوز إذا كنت تعاني من مشاكل في المرارة , ويجب أكل زبدة اللوز بكمية بسيطة بدلاً من أكل اللوز بأكمله . المفيد والمسموح : اللوز السوداني – زبدة اللوز – بندق – بذر القرع ( الفصفص الدبة ) المسموح والمحايد : زبدة اللوز – الماكاديميا – القعقع ( الجوز ، عين جمل ) اللوز البجلي – زبدة دوار الشمس بذور السمسم – زبدة السمسم ( الطحينة ) . المحظورات : المكسرات البرازيلية – الكاجو – الفستق . البقول : تعمل بقوة عظيمة بالنسبة لفصيلة A , ولكن هناك أنواع ضارة لإحتوائها على الـ Lectin الذي يخفض نسبة الأنسولين في الإنتاج مما يؤدي للسمنة أو مرض السكري . المفيد منها : الفاصوليا بأنواعها الخضراء والسوداء والحمراء – العدس المحلي والأخضر والأحمر واللوبـيا. المحايد والممكن استخدامه بدون ضرر : البازلاء الخضراء وأنواع من الفاصوليا المحظورات : نحاس الفاصوليا – الفاصوليا على شكل الكلى . الرقاق ( CEREALS ) : يستحب استخدام الحبوب الكاملة وليست التي مرت بعملية التصنيع , كما يجب الحذر من إكثار القمح لأنه يساعد على الإفرازات المخاطية في الصدر المفيد من الحبوب : الحبوب المكونة من الذرة - والشعير - والأرز . المحظورات :كريمة القمح وكثرة الأشياء المصنوعة من القمح الخبز : بالنسبة للخبز فإن الناس الذين يعانون من إفرازات مخاطية في الصدر نتيجة لحساسية الصدر يجب الامتناع أو الابتعاد عن القمح الكامل وأخذ دقيق الصويا أو دقيق الرز كبديل لـها. المفيد والمسموح للاستخدام : دقيق الصويا – الكيك المصنوع من دقيق الرز – خبز القمح ( النخالة ) . المحايد : خبز الشعير والذرة . المحظور : خبز القمح الكامل والخبز البروتيني المكرونات : للمكرونة اختيارات وافرة وتحتوي على مصادر جيدة للبروتين النباتي ويمكن الحصول على مواد غذائية ضرورية لا يمكن الحصول عليها من اللحوم الحيوانية الابتعاد عن الوجبات المثلجة والمكرونة المحضرة من الصلصات أو خليط من الرز مع الخضار الجاهزة , ويحبذ صنع الغذاء في المنزل وعدم استخدام المأكولات الجاهزة . المفيد والمسموح به : دقيق الرز – الباستا – الشعير ودقيقه . المحظورات : الدقيق الأبيض – المكرونة المصنوعة من السبانخ والسميد والدقيق الكامل . الخضروات : الخضروات ضرورية لاحتوائها على المعادن والإنزيمات ومواد ضد الأكسدة , وتؤكل نية أو بالبخار ، فمعظم الخضروات مسموحة ولكن هناك بعض المحظورات كالفلفل والباذنجان والطماطم والبطاطس والجزر اليماني ومن الخضار المفيدة جداً والتي تمنع أو تحمي الخلايا الغير طبيعية من الانقسام بسبب الأكسدة هو : البروكلي و الثوم و الجزر و القرع والسبانخ واللفت والخضار الحديدية والورقية والبصل الأصفر وكذلك التوفو ( TOFO ) فهو من أفضل الخضار لهذه الفصيلة .. الخضار المفيدة جداً : الأرضي الشوكي – أوراق البنجر – البروكلي – الجزر – الخضار الورقية – الهدرباء البرية – البصل بأنواعه – السبانخ – الباميا – الخس – اللفت – الفجل – الثوم – البقدونس – القرع المحايد والممكن استخدامه : البنجر – الأفوكادو – القرنبيط – الكرفس – الذرة – الخيار - الخس – الفجل الأحمر . المحظورات ( الممنوعات ) : الكرنب الأحمر والأبيض – الباذنجان الأسود – المشروم ( عش الغراب – الفطر ) - الزيتون الأسود ( اليوناني – الأسباني ) – الفلفل بأنواعه ( الأحمر والأخضر والأصفر ) – البطاطس – والجزر اليماني – الطماطم . الفواكه : يجب أكل الفاكهة يومياً على الأقل ثلاث مرات في اليوم لتعادل الحموضة المتكونة من الحبوب ، فبعض الفواكه تكون ضارة كالبرتقال والبطيخ والخربز والفواكه الاستوائية كالمانجو والبابايا والموز , حيث أن بعضها يكون مفيد كالليمون والعنب والخوخ والتين . الفواكه المفيدة : الخوخ – التوت الأسود والأزرق – الكرز- التين – العنب – الليمون – الأناناس – البرقوق - الزبيب – المشمش 0 الفواكه المحايدة : التفاح – البلح الأسود والأحمر الطازج – العنب بأنواعه – الجوافة – الكيوي – الحبحب – الخوخ – الكمثرى – الفراولة , والمربى من الفواكه المقبولة " بدون سكر " , وكذلك الجيلي 0 المحظورات من الفواكه : الموز – النارجــين – المانجو – الخربز ( الشمـام ) – الهنـدول – البرتقــال – البابايا – اليوسف أفندي . العصيرات والسوائل يجب أخذ كأس من الماء الفاتر كل يوم في الصباح مع نصف ليمونه ( عصير ) للتخلص من الإفرازات المخاطية في الصدر . | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
الجمعة، مارس ٢٠، ٢٠٠٩
Emerging use of Bevacizumab in the Treatment of Posterior Retinopathy of Prematurity(ophthalmic hyperguides)
| Pediatric Ophthalmology Emerging use of Bevacizumab in the Treatment of Posterior Retinopathy of Prematurity Rudolph S. Wagner, MD The Institute of Ophthalmology & Visual Science · University of Medicine and Dentistry of New Jersey · New Jersey Medical School · Newark, New Jersey Aswin Chandrakantan The Institute of Ophthalmology & Visual Science · University of Medicine and Dentistry of New Jersey · New Jersey Medical School · Newark, New Jersey Angiogenesis is the process by which new capillaries are formed from blood vessels. Physiologically, it is a normal process; however, it also can be a cause of significant pathology in retinopathy of prematurity (ROP), diabetic retinopathy and AMD. The process of angiogenesis is regulated by a multitude of both pro- and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic factors in this interplay of regulation.1 VEGF is a category of proteins that increase capillary growth through the use of tyrosine kinase receptors. VEGF uses cascades to promote neovascularization, and pharmacological treatments can focus on inhibiting VEGF directly and indirectly via the modulation of VEGF, as well as its upstream receptors.2 Pharmacologic agents such as pegaptanib, ranibizumab, bevacizumab, VEGF-Trap and Sirna-027 have shown promise in treating pathological ocular neovascularization.3 Of particular interest in recent years is bevacizumab, which is a monoclonal antibody against VEGF-A, a particular subcategory of VEGF. Retinopathy of Prematurity ROP is a leading cause of blindness in children and is caused by an incomplete vascularization of the peripheral retina leading to a subsequent overcompensatory neovascularization. Risk factors include degree of prematurity, birth weight and use of oxygen supplementation in the postdelivery period.4 The Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) - Outcome Study of Cryotherapy for Retinopathy of Prematurity has shown that 44.4% of preterm infants with severe ROP subsequently treated with cryotherapy had a visual acuity of 20/200 at 10 years of age and, of the children whose treated eye had a visual acuity higher than 20/200, only 45.4% had a visual acuity 20/40 or better. In this trial, peripheral retinal ablation was performed when the risk for retinal detachment approached 50%.5 This cut-off deemed "threshold" is defined as at least 5 contiguous zones or 8 cumulative sectors of stage 3 ROP in zone I or I with plus disease. Plus disease is a measurement of dilation and tortuosity of posterior retinal vessels that exceed that of a normal eye. Results of the Early Treatment for Retinopathy of Prematurity (ETROP) study that was funded by the National Institutes of Health demonstrated that peripheral ablation should be considered for any eye with type I ROP defined as (1) zone I, any stage ROP with plus disease; (2) zone 1, stage 3 ROP with or without plus disease; or (3) zone II, stage 2 or 3 ROP with plus disease (Slide 1). Serial examinations are recommended in type II ROP, which is defined as (1) zone I, stage 1 or 2 ROP without plus disease or (2) zone II, stage 3 ROP without plus disease.6 Slide 1. Retinal image showing stage 3, zone II retinopathy of prematurity with plus disease. (Image courtesy of Rudolph S. Wagner, MD) http://www.ophthalmic.hyperguides.com/images/content/tutorials/37514/slide1.jpg Active screening is required in at-risk neonates followed by monitoring of oxygen supplementation and ablating the peripheral retina once "threshold" disease has been reached. Zone I disease, in particular, has been shown to be associated with a poor prognosis as compared to zone II or zone III disease, even after the use of laser photocoagulation or cryotherapy. The CRYO-ROP study found a 77.8% unfavorable outcome rate using cryotherapy and the ETROP study found a 55.2% unfavorable outcome rate using laser photocoagulation in treating patients with zone I ROP disease.5,6 It has been suggested that the frequent failure of ablation therapy in the treatment of zone I ROP can be caused by neovascularization due to VEGF-165 secreted by vitreal macrophages.7 VEGF levels have been shown to be higher in patients with ROP stage III than those with lower stage of disease. Furthermore, it is has been established that patients with zone I ROP, especially aggressive proliferative ROP, have poor clinical outcomes despite proper screening and timely intervention using laser therapy. 8-13 Hence, there is increased attention toward the downregulation of VEGF in patients with ROP, and preliminary studies and case reports have shown the successful clinical use of bevacizumab. Bevacizumab for Treatment of Retinopathy of Prematurity The benefits of using anti-VEGF agents include the elimination of the numerous complications of laser therapy, prevention of retinal atrophy and consequent visual field loss, decreased myopia and reduced strabismus with or without amblyopia. The BLOCK-ROP study, a phase 1 trial that started in fourth quarter 2007, will evaluate the effectiveness of 0.75-mg intravitreal injections of bevacizumab in 22 patients in the potential treatment of ROP. Case reports In previous studies, injections have been performed with continuous cardiorespiratory monitoring under conscious sedation or intubated general anesthesia. The injections are delivered behind the lens by aiming the needle toward the optic nerve, entering the sclera through the conjunctiva 1 mm to 1.5 mm behind the limbus and advancing the needle two thirds of the way and delivering the injection into the central vitreous. Using an indirect ophthalmoscope, the neonate's eye is then examined for signs of lens injury and blood flow through the retinal artery and to identify tears or vitreous hemorrhage that may have inadvertently occurred during the procedure.14,15 There is no consensus on the dosing of bevacizumab in neonates; however, previous studies have reported no serious side effects in doses ranging from 0.75 mg to 2.5 mg. 15-19 The normal adult dose is 1.25 mg and, considering that neonates have smaller vitreous volume, it may be prudent to use lower doses. Four previous case reports have shown that dosages of 0.75 mg may be sufficient to inhibit the production of VEGF and consequently neovascular proliferation.4,14,18,19 These cases received 0.75 mg bevacizumab to successfully treat aggressive posterior ROP with no reported systemic complications. One case reported bilateral anterior segment ischemia, which may have been due to extensive laser ablation rather than the use of bevacizumab.18 A set of case reports from Portugal details how 3 neonates with aggressive posterior ROP were given a 0.75-mg intravitreal injection of bevacizumab and, within 24 hours, showed regression of both tunica vasculosa lentis and iris vessel engorgement with a concurrent disappearance of iris rigidity.19 The most recent trial performed on 11 neonates with severe stage 3 ROP in zone I or posterior zone II were treated bilaterally with 0.625 mg of bevacizumab and had no concurrent laser therapy. The treatment was successful in all eyes and no patients experienced complications.14 Potential risks of therapy With the downregulation of VEGF, theoretically, there is a risk of downregulating both normal and pathological neovascularization, although such effects have not been demonstrated in any studies thus far. Hence, excessive doses of a VEGF-inhibiting pharmacological agent may risk inhibiting physiologically normal angiogenesis and hinder the normal development of the neonate eye. Further studies are warranted to investigate the optimal dosing for neonates and these case reports can serve as a platform for inquiry. Intraocular risks of intravitreally administered bevacizumab in adults have included endophthalmitis, retinal detachment, cataract and uveitis. In adult patients given pegaptinib, endophthalmitis occurred at a rate of 0.16% per injection, retinal detachment occurred at a rate of 0.08% per injection and cataract occurred at 0.07% per injection.20 One case report details acute contraction of the proliferative membrane leading to partial tractional retinal detachment after the injection of 0.4 mg of bevacizumab.21 Studies on the use of bevacizumab in patients with severe proliferative diabetic retinopathy (PDR) also reported the possibility of tractional retinal detachment after the injection. Although these anti-VEGF drugs have not been extensively studied in neonates with ROP, it is important to study the safety profile of this drug within this population. Bevacizumab is indicated for the treatment of patients with metastatic colon cancer. Ranibizumab is an anti-VEGF agent; however, with a molecule size of 48 kilodaltons (kD), it is considerably smaller than bevacizumab (148 kD).14 It has been hypothesized that smaller molecules may infiltrate the peripheral undifferentiated retina and cause local damage. Furthermore, potential exists for diffusion into systemic circulation in amounts that could cause side effects. Studies of the use of bevacizumab in rabbits have found bevacizumab levels of 1:1,000 in the untreated versus treated eye.22 In adults, the intravitreal half-life of bevacizumab is 5.6 days in contrast with a half-life of 3.2 days for ranibizumab, which is hypothesized to be considerably extended in preterm neonates' viscous vitreous fluid.14 Other Potential Treatments Interest in the role of insulin-like growth factor-1(IGF-1) in the development of normal retinal vasculature has grown. Low levels of IGF-1 have been implicated in the development of ROP and hence it is believed that supplementation of IGF-1 in preterm infants could prevent the development of ROP.23 IGF-1 has been associated with gestational age and birth weight and therefore preterm infants have been found to have significant reductions in this important somatic growth factor.24 It is believed that preterm neonates may be unable to normally develop their retinal vasculature leading to retinal hypoxia and having a subsequent rebound in IGF-1 levels that triggers proliferative neovascularization. Further studies are warranted to identify the potential use of IGF-1 supplementation to prevent subsequent neovascular changes, especially in preterm infants. Bevacizumab shows potential in the treatment of patients with ROP; however, no large-scale randomized study has proven its efficacy for the treatment of this condition and it is not yet approved by the FDA for this use. It is hoped that ongoing research will show the potential use of this promising drug in the treatment of retinopathy of prematurity. References Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997; 18:4-25. Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME. Vascular endothelial growth factor in eye disease. Progress in Retinal and Eye Research. 2008; 27:331-371. Andreoli CM, Miller JW. Anti-vascular endothelial growth factor therapy for ocular neovascular disease. Curr Opin Ophthalmol. 2007; 18:502-508. Palmer EA, Hardy RJ, Dobson V, et al. 15-year outcomes following threshold retinopathy of prematurity: Final results from the multicenter trial of cryotherapy for retinopathy of prematurity. Arch Ophthalmol. 2005; 123:311-318. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity: ophthalmological outcomes at 10 years. Arch Ophthalmol. 2001; 119:1110-1118. Good WV, Hardy RJ. The multicenter study of Early Treatment for Retinopathy of Prematurity (ETROP). Ophthalmology. 2001; 108:1013-1014. Naug H, Browning J, Gole G, Gobe G. Vitreal macrophages express VEGF165 in oxygen-induced retinopathy. ClinExp Optom. 2000; 28:48-52. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Three-month outcome. Arch Ophthalmol. 1990; 108:195-204. Early Treatment for Retinopathy of Prematurity Cooperative Group. Revised indication for the treatment of retinopathy of prematurity: Results of early treatment for ROP randomized trial. Arch Ophthalmol. 2003; 121:1684-1696. Flynn JT, Chan-Ling T. Retinopathy of prematurity: Two distinct mechanisms that underlie zone 1 and zone 2 disease. Am J Ophthalmol. 2006; 142:46-59. Katz X, Kychenthal A, Dorta P. Zone I retinopathy of prematurity. J AAPOS 2000; 4:373-376. O'Keefe M, Lanigan B, Long VW. Outcome of zone I retinopathy of prematurity. Acta Ophthalmol Scand. 2003; 81:614-616. Kychenthal A, Dorta P, Katz X. Zone I retinopathy of prematurity: Clinical characteristics and treatment outcomes. Retina. 2006; 26:S11-S15. Mintz-Hittner HA, Kuffel R. Intravitreal injection of bevacizumab (Avastin) for the treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina. 1008; 28:831-838. Chung EJ, Kim JH, Ahn HS, Koh HJ. Combination of laser photocoagulation and intravitreal bevacizumab (Avastin®) for aggressive zone I retinopathy of prematurity. Graefe's Arch Clin Exp Ophthalmol. 2007; 245:1727-1730. Fung AE, Rosenfeld PJ, Reichel E. The International Intravitreal Bevacizumab Safety Survey: Using the internet to assess drug safety worldwide. Br J Ophthalmol. 2006; 90:1344-1349. Lynch SS, Cheng CM.) Bevacizumab for neovascular ocular diseases. Ann Pharmacother. 2007; 41:614-625. Shah PK, Narendran V, Tawansy KA, Raghuram A, Narendran K. Intravitreal bevacizumab (Avastin) for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity. Indian J Ophthalmol. 2007; 55:75-76. Travassos A, Teixeira S, Ferreira P et al. Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging. 2007; 38:233-237. D'Amico DJ, Masonson HN, Patel M, et al. Pegaptanib sodium for neovascular age-related macular degeneration: Two-year safety results of the two prospective, multicenter, controlled clinical trials. Ophthalmology. 2006; 113:992-1001e6. Honda S, Hirabayashi H, Tsukahara Y, Negi A. Acute contraction of the proliferative membrane after an intravitreal injection of bevacizumab for advanced retinopathy of prematurity. Graefe's Arch Clin Exp Ophthalmol. 2008; 246:1061-1063. Bakri SJ, Snyder MR, Reid JM, et al. Pharmacokinetics of intravitreal bevacizumab (Avastin). Ophthalmology. 2007; 114:855-859. Hellstrom A, Perruzzi C, Ju M, et al. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity. Proc Natl Acad Sci. 2001; 98:5804-5808. Simons B D, Flynn J T. Retinopathy of prematurity and associated factors. Int Ophthalmol Clin. 1999; 39:29-48. |
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