Ординатура / Офтальмология / Английские материалы / Diabetic Retinopathy_Lang_2007

including type 3A, without vitreofoveal traction, and type 3B, with vitreofoveal traction. They found that the prevalence of OCT type 1 was higher in diabetic macular edema with focal leakage type and in the diffuse type than in the diffuse cystoid leakage type of fluorescein angiography. The prevalence of OCT types 2 and 3A was higher in the diffuse cystoid leakage type than in the focal type or diffuse leakage type. OCT type 1 and the focal leakage type of fluorescein angiography showed the least foveal thickness and the best visual acuity [7]. Types 2 and 3A increased with the existence of retinal vascular hyperpermeability. The external limiting membrane is not impermeable to fluid and albumin. With the disruption of the blood-retinal barrier, the excessive fluid might reach the subretinal space in large amounts, which cannot be removed by retinal pigment epithelium and may result in subvofeal detachment. Foveal detachment may lead to cystoid foveal changes. The proportion of diffuse leakage and diffuse cystoid leakage type of macular edema increases with proliferative diabetic retinopathy in comparison with nonproliferative diabetic retinopathy. This suggests that the large extent of ischemia in the eyes with proliferative diabetic retinopathy releases endogenous growth factors like vascular endothelial growth factor, which results in the breakdown of the blood-retinal barrier, and causes diffuse leakage from damaged capillaries [4].

Significant differences in retinal thickness between patients with diabetic retinopathy without clinically significant macular edema and controls can be detected by OCT, most likely in the superior nasal quadrant [12].

An excellent agreement between OCT and contact lens examination for the absence or presence of foveal edema is found when OCT thickness is normal ( 200 m) or moderately to severely increased ( 300 m). However, agreement is poor when foveal thickness is mildly increased on OCT (201–300 m) [13]. This suggests that OCT is more sensitive to the detection of mild foveal thickening than slit-lamp biomicroscopy.

Lattanzio et al. [5] found that macular thickness was greater in diabetics than in controls and tended to increase with diabetic retinopathy and macular edema severity.

OCT is also a sensitive technique for quantifying treatment effects like reduction in macular thickness after laser photocoagulation. The change in macular profile and the internal retinal structure after laser photocoagulation of surgical treatment are well visible with OCT [14]. Diabetic macular edema can be accurately and prospectively measured with OCT [15]. In a multivariate logistic regression model, foveal thickness is a strong and independent predictor of clinically significant macular edema [16] suggesting that foveal thickness180 m measured by OCT may be useful for the early detection of macular thickening and may be an indicator for a closer follow-up of the patients with diabetes mellitus.

Fig. 6. a Retinal thickness of the macular thickness mode of a patient with diabetes mellitus. b Retinal thickness of the fast macular mode of the same patient showing a thickened macula in the parafoveal area (normal thickness, gray area). c Retinal thickness of the macular thickness mode of a patient with cystoid macular edema showing markedly thickened macula and loss of foveal depression. d Retinal thickness of the fast macular mode of the same patient.

OCT allows to quantify retinal thickness in diabetic retinopathy with excellent reproducibility and is able to detect sight-threatening macular edema with great reliability [17]. Retinal thickness can be obtained either by the macular thickness mode or by the fast macular mode, which provides an agematched normal subject database (fig. 6). For fast-scan retinal thickness, measurements are taken at 128 points in each scan, for a total of 78 transverse points, 6 of which intersect at the fovea. Thus, the measurements are more precise at the center than at the periphery of the map. For macular thickness map scan, the retinal thickness measurements are taken at 512 points in each scan by default, but this number can be adjusted to 256 or 128 per scan line. The mean

a

b

Cotton wool spots are ischemic infarctions of the nerve fiber layer. On ophthalmoscopy, they are white and located superficially. On OCT, they appear as hyperreflective, nodular or elongated lesions in the nerve fiber layer, which can cast a shadow on the posterior layers (fig. 2).

Hemorrhages can be located pre-, intraor subretinally. On ophthalmoscopy, they are flame shaped when located in the nerve fiber layer, and they are rounded or irregular when located in the deep retinal layers. They are hyperreflective on OCT and can produce a shadow cone on the posterior layer, especially if they are located preretinally (fig. 8a–e).

OCT Findings in Proliferative Diabetic Retinopathy,

Vitreoretinal Traction and ERMs

Proliferative diabetic retinopathy is characterized by either neovascularization on the disc or elsewhere [19]. Preretinal neovascularization can be detected by OCT when a certain amount of fibroglial tissue is present, showing medium reflective preretinal structures shadowing the posterior layers (fig. 8a, c, d). Vitreous hemorrhage, when it is not too severe, shows preretinal high reflective structures shadowing the retinal layers. If vitreous hemorrhage is more severe, no good reflection can be obtained from retinal structures.

On clinical grounds, it is often difficult to detect vitreomacular or vitreoretinal traction, when caused by partial vitreous detachment. The posterior hyaloid surface is visible as mid-reflective band inserted in the retina creating traction and resulting in retinal edema. In vitreomacular traction, a thin slightly hyperreflective band is visible adhering to the retina, sometimes at several points to the retinal surface, which is often elevated (fig. 9a, b).

OCT can also detect traction-induced retinal detachment, which can occur in proliferative diabetic vitreoretinopathy. OCT accurately reveals the fibrovascular tissue, the points of traction and the detached retina.

In patients with diabetic retinopathy, secondary ERMs can develop because of epimacular proliferating fibrocellular tissue, which grows across the inner retinal surface causing a cellophane maculopathy or a macular pucker (fig. 9a, b). It can cause a macular distortion. In the beginning, the ERMs often show a global retinal adherence. ERMs with tractional forces show focal adherence. The ERM is characterized by a slightly hyperreflective band on the inner surface of the retina. The ERMs can also detach from the retinal surface. ERMs can lead to pseudohole formation, loss of foveal depression or cystoid maculopathy. OCT is helpful in monitoring postoperative follow-up after pars plana vitrectomy and membrane peeling (fig. 9c).

c

a

e

Fig. 8. a Proliferative diabetic retinopathy with neovascularization on the disc and elsewhere, vitreous hemorrhage and clinically significant macular edema. b OCT shows macular edema with hyporeflective subretinal edema and hyporeflective cystoid cavities. c Medium reflective preretinal neovascular tuft at the superior vascular arcade shadowing the posterior layers. d Medium reflective epipapillar neovascularization shadowing the posterior layers. e High reflective vitreous hemorrhage completely shadowing the posterior layers.

Conclusion

OCT can provide major contributions to the understanding of diabetic macular edema and diabetic retinopathy. It can help monitor treatment results objectively. This is important because new treatment concepts for diabetic retinopathy are under investigation and might be approved within the near future. New OCT developments are high-speed, high-resolution devices and three-dimensional data.

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b

c

Fig. 9. a Cystoid diabetic macular edema with epiretinal macular membrane. b OCT shows vitreomacular traction (arrowhead), epiretinal membrane (arrow), hyporeflective cystoid cavities (asterisks), and serous macular detachment before surgery. c OCT of the same patient after pars plana vitrectomy and membrane peeling.

References

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2Panozzo G, Parolini B, Gusson E, Mercanti A, Pinackatt S, Bertoldo G, Pignatto S: Diabetic macular edema: an OCT-based classification. Semin Ophthalmol 2004;19:13–20.

3Massin P, Erignay A, Haouchine B, Mehidi AB, Paques M, Gaudric A: Retinal thickness in healthy and diabetic subjects measured using optical coherence tomography mapping software. Eur J Ophthalmol 2002;12:102–108.

4Kang SW, Park CY, Ham DI: The correlation between fluorescein angiographic and optical coher-

ence tomographic features in clinically significant diabetic macular edema. Am J Ophthalmol 2004;137:313–322.

5Lattanzio R, Brancato R, Pierro L, Bandello F, Iaccheri B, Fiore T, Maestranzi G: Macular thickness measured by optical coherence tomography (OCT) in diabetic patients. Eur J Ophthalmol 2002;12:482–487.

6Bresnick GH: Diabetic macular edema: a review. Ophthalmology 1986;93:989–992.

7Yang CS, Cheng CY, Lee FL, Hsu WM, Liu JH: Quantitative assessment of retinal thickness in diabetic patients with and without clinically significant macular edema using optical coherence tomography. Acta Ophthalmol Scand 2001;79:266–270.

8Otani T, Kishi S, Mauyama Y: Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol 1999;127:688–693.

9Özdek SC, Erdinc MA, Gürelik G, Aydin B: Optical coherence tomography assessment of diabetic macular edema: comparison with fluorescein angiographic and clinical findings. Ophthalmologica 2005;219:86–92.

10Hee MR, Puliafito CA, Duker JS, Reichel E, Coker JG, Wilkins JR, Schuma JS, Swanson EA, Fujimoto JG: Topography of diabetic macular edema with optical coherence tomography. Opthalmology 1998;105:360–370.

11Larsen M, Wang M, Sander B: Overnight thickness variation in diabetic macular edema. Invest Ophthalmol Vis Sci 2005;47:2313–2316.

12Schaudig UH, Glaefke C, Scholz F, Richard G: Optical coherence tomography for retinal thickness measurement in diabetic patients without clinically significant macular edema. Ophthalmic Surg Lasers 2000;31:182–186.

13Brown JC, Solomon SD, Bressler SB, Schachat AP, Di Bernardo C, Bressler N: Detection of diabetic foveal edema. Arch Ophthalmol 2004;122:330–335.

14Panozzo G, Gusson E, Parolini B, Mercanti A: Role of OCT in the diagnosis and follow up of diabetic macular edema. Semin Ophthalmol 2003;18:74–81.

15Strom C, Sander B, Laresen N, Larsen M, Lund-Andersen H: Diabetic macular edema assessed with optical coherence tomography and stereo fundus photography. Invest Ophthalmol Vis Sci 2002;43:241–245.

16Sanchez-Tocino H, Alvarez-Vidal A, Maldonado MJ, Moreno-Montanes J, Garcia-Layana A: Retinal thickness study with optical coherence tomography in patients with diabetes. Invest Ophthamol Vis Sci 2002;43:1588–1594.

17Goebel W, Kretzchmar-Gross T: Retinal thickness in diabetic retinopathy. A study using optical coherence tomography (OCT). Retina 2002;22:759–767.

18Browning DJ, Mc Owen MD, Bowen RM, O Marah TL: Comparison of the clinical diagnosis of diabetic macular edema with diagnosis by optical coherence tomography. Ophthalmology 2004;111: 712–715.

19Lang GE: Diabetische Retinopathie – Stadieneinteilung und Laserbehandlung. Klin Monatsbl Augenheilkd 2005;222:R1–R18.

Prof. Dr. Gabriele E. Lang Universitätsklinikum Ulm, Augenklinik Prittwitzstrasse 43

DE–89075 Ulm (Germany)

Tel. 49 731 500 59001, Fax 49 731 500 59002, E-Mail gabriele.lang@uniklinik-ulm.de

Fig. 1. Fluorescein angiography of mild NPDR with hyperfluorescent dots representing microaneurysms.

Retinal capillary microaneurysms are the first definite sign and a hallmark of diabetic retinopathy. They are most common on the posterior pole. Sometimes, they can only be diagnosed and differentiated from punctate hemorrhages with fluorescein angiography (fig. 1). Microaneurysms exhibit bright hyperfluorescent dots in the early frames, whereas hemorrhages block fluorescence. Microaneurysms are 15–60 m in size. Histologically, microaneurysms are hypercellular outpouchings of the capillary wall, subsequent also to a loss of intramural pericytes. Typical for early changes of diabetic retinopathy is the thickening of the basement membrane of retinal capillaries.

Hemorrhages can also occur, but they disappear within 3 months so that they are not considered as diabetic retinopathy changes without accompanying microaneurysms [1].

Microaneurysms alone have no clinical significance concerning risk of vision loss or progression of diabetic retinopathy. However, they are associated with an increased risk of cardiovascular complications.

Altered vascular permeability results in macular edema and deposits of hard exudates. Vascular permeability of the retinal capillaries can already occur in the early stages of diabetic retinopathy caused by increased expression of vascular endothelial growth factor (VEGF). This leads to extravasation of fluid and plasma constituents. Lipoproteins accumulate most often in the macular area. When the macular edema involves the center, this leads to visual loss. Macular edema can be detected with dilated pupil and slit-lamp biomicroscopy, stereoscopic fundus photography and optical coherence tomography. Fluorescein angiography can identify leaking microaneurysms and leakage from

Fig. 2. a PDR with neovascularization on the disc and elsewhere and vitreous hemorrhage. b Fluorescein angiography of the same patient showing dye leakage from preretinal neovascularizations, ischemic maculopathy and blockage of fluorescence caused by vitreous hemorrhage.

retinal capillaries. Fluorescein leakage alone does not always indicate the presence of macular edema, and in patients with significant macular edema, sometimes only mild leakage is found. Hard exudates, that often accompany macular edema, make it much easier to diagnose diabetic macular edema. They are lipid deposits located in the outer plexiform or Henle layer of the retina. Clinically hard exudates are yellow-white, well-defined, intraretinal deposits. On optical coherence tomography (OCT), they are visible as hyperreflective nodular lesions. The deposit of the hard exudates is associated with the damage of the inner blood-retinal barrier, i.e. the breakdown of the endothelial tight junctions in the capillaries and microaneurysms. The extent of the lipid deposits in the retina is associated with the degree of serum lipid elevation [2].

One serious consequence of diabetic retinopathy is the closure of retinal capillaries leading to areas of nonperfused retina. Findings associated with areas of nonperfusion and thus retinal ischemia are large intraretinal hemorrhages, intraretinal microvascular anomalies (IRMA) and venous beading (VB). The ischemia triggers the production of growth factors like VEGF and insulin-like growth factor 1. Increasing areas of nonperfusion result in PDR with preretinal neovascularization and vitreous hemorrhage (fig. 2).

The NPDR is categorized into five levels of severity: very mild, mild, moderate, severe, very severe (table 1). The extent of intraretinal hemorrhages and microaneurysms, IRMA and VB in the 4 midperipheral quadrants (fig. 3, fields 4–7) are the factors that predict the level of NPDR (table 1).

One problem of classification is the difficulty in recognizing IRMA and VB on clinical examination. They can be more easily diagnosed on fluorescein angiography.