Ординатура / Офтальмология / Английские материалы / Diabetic Retinopathy_Lang_2007

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José Cunha-Vaz, MD, PhD AIBILI

Azinhaga Santa Comba, Celas PT–3000-548 Coimbra (Portugal)

Tel. 351 239480100, Fax 351 239480117, E-Mail cunhavaz@aibili.pt

Nerve fiber layer

Inner plexiform layer

Outer plexiform layer

Inner photoreceptor layer

Outer photoreceptor layer

Retinal pigment epithelium

Choroid

Fig. 1. OCT of a normal macula.

Table 1. OCT potentials in image analysis

OCT enables to detect

Morphological changes

Retinal thickness

Retinal volume

Surface area

OCT allows image analysis

Qualitative analysis

Quantitative analysis

Reflectivity

Comparison of images obtained during subsequent examinations

Follow the disease course

Intervention studies

tomographic cross-sections of the retina. OCT measurements are similar to those of ultrasound B-mode examination. OCT can provide important information complementary to clinical examination and fluorescein angiography for certain findings in diabetic retinopathy.

OCT Techniques and Principles

OCT is based on the analysis of the reflections of low coherence radiation from the tissue. The resolution with current clinically used instrumentation is 10 m. It allows images to be obtained for the retinal, retinal pigment epithelial and choriocapillary layers (fig. 1). OCT potentials in image analysis enable to detect morphological changes, quantitative and qualitative analysis (table 1). With OCT qualitative analysis, one can differentiate between hyperreflectivity, hyporeflectivity and shadowing effects (table 2).

The possibility to make repeatable, high-resolution measurements of the retina with good image quality is important for the diagnosis, follow-up and

Table 2. OCT qualitative interpretation

Hyperreflective

Hard exudates

Cotton wool spots

Hyporeflective

Intraretinal edema

Exudative retinal detachment

Cystoid macular edema

Shadow effect

Hemorrhages

Exudates

Retinal vessels

treatment of diabetic retinopathy. OCT of the posterior pole can be performed through a pupil as small as 3 mm in diameter. Mydriasis, however, makes the OCT examination easier. The OCT software, the latest version of Zeiss Stratus OCT is version 4, offers different scanning protocols. For diagnosis of diabetic maculopathy, fast macular thickness allows quantitative and qualitative analysis for the diagnosis and follow-up of diabetic retinopathy. The scans of the macular thickness mode require more time for the scan acquisition, but provide more detailed information of the six 6-mm-long radial scans. If the fixation is bad, an X-line mode can be chosen, because it can be taken in less than 2 s. For proliferative changes, single linear scans are recommended. While the scans are being taken, the position of the signal in the display window can be adjusted either automatically or manually to optimize the signal strength [1].

The images are displayed directly on the monitor in real time using a false color or gray scale that represents the degree of light reflected from tissues at different depths in the retina. The images are then saved and an analysis protocol can be selected. The software can map the thickness and volume of the macular region, based on six 6-mm-long radial scans. The scans are performed with intersections in the foveolar region. Each scan is rotated by 30 in relation to the preceding one. At each of these locations, the signal is sampled longitudinally at 1,024 equal intervals over a depth of 2 mm. The macular retinal map divides the region into a central disc with a radius of 500 microns and 2 concentric rings divided into 4 quadrants. The normal retina in the macular region has a mean thickness of 200–250 microns, and the physiological foveal depression has a mean thickness of 170 microns. In the false color scale, blue is assigned to thickness between 150 and 210 microns, green to 210–270 microns, yellow to 270–320 microns, orange to 320–350 microns, red to 350–470 microns, and

Table 3. Retinal thickness measured by OCT [2]

white to over 470 microns. Panozzo et al. [2] have provided detailed thickness and volume measurements of a normal subject database (table 3). The normal foveal thickness is 150 20 m. Retinal thickness can be classified as normal, borderline and edema [2].

When interpreting the OCT, one should always look at the original scans as well, in addition to the different image processing techniques. The alignment algorithm reduces the artifacts caused by axial movement of the eye during the scan acquisition phase. When using the algorithms, it is very important to take into account that the possibility of interpretation errors exists, because the software cannot always distinguish between the retinal variations resulting from ocular movements and the morphological variations. Consequently, there is always the possibility of misestimation when using the algorithms. The normalization algorithm eliminates the saturation points of the signal, redistributing the acquired values over the entire available range of false colors. This algorithm allows to compare scans with different signal strengths. Gaussian smoothing of the scales allows to evaluate data on a broad scale, at the expense of details. The median smoothing function applies the median value of points in the same 3 3 mm area, thereby eliminating background noise while minimizing the loss of important details. A normal subject database is available for macular retinal thickness [1].

Table 4. OCT findings typical for macular edema

Retinal thickening

Cystoid macular edema

Loss of foveal depression

Detachment of the neurosensory retina

Epiretinal membrane

Pseudohole formation

Vitreomacular and vitreoretinal traction

Preretinal neovascularization

Retinal thinning

Secondary epiretinal membrane

OCT can be difficult or impossible to perform in patients with opacification of the cornea, lens or vitreous and in patients that cannot fixate.

The analysis of the OCT has to be done in two steps, qualitative (morphology, reflectivity) and quantitative, and then results in the synthesis leading to the diagnosis together with the clinical and, if necessary, angiographic correlation. In the normal retina, the nerve fibers and retinal pigment epithelium are highly reflective, the plexiform and nuclear layers are medium reflective and the photoreceptors are low reflective (fig. 1).

There is no significant difference in foveal thickness concerning age and right and left eye. However, men have a greater thickness than women (central area for men, 178 17 m; central area for women, 165 17 m) [3]. The retina is thinner in the temporal areas in comparison with the nasal, superior and inferior areas because of the arciform bunching of the optic nerve fibers.

The information provided by OCT has markedly improved our understanding of diabetic retinopathy. OCT allows to detect macular edema, cystoid maculopathy, hard exudates, intraand preretinal hemorrhages, cotton wool spots, epiretinal membranes (ERMs), and vitreomacular traction.

OCT Findings in Macular Edema

OCT makes it possible to detect, quantify and classify diabetic macular edema (table 4) and get additional important information to ophthalmoscopy and fluorescein angiography.

Macular edema is a common cause of decreased vision in patients with diabetic retinopathy and can occur in any stage of the disease.

The pathogenesis of diabetic macular edema is still not fully understood. Cytotoxic macular edema is initiated by intracytoplasmic swelling of Müller

cells due to ischemia. It may progress to a vasogenic edema with the release of permeability factors such as prostaglandins and vascular endothelial growth factor [4]. The liquefaction necrosis of the Müller cells and adjacent neural cells due to persisting edema and ischemia leads to cystoid cavity formation predominantly in the outer retinal layer. The breakdown of the blood-retinal barrier leads to accumulation of fluid in the retinal cystoid spaces. Some edema may also result from abnormalities in the retinal pigment epithelium, which allows increased fluid from the choriocapillaris to pass through into the sensory retina. Vitreous traction can also play a role in the development of diabetic macular edema in some patients.

Edema within 1 disc diameter of the center of the macula is found in about 9% of the diabetic population, 40% of whom have central macular involvement [5]. The proportion of patients with macular edema increases with the severity of overall retinopathy: 3% in mild nonproliferative diabetic retinopathy, 38% in moderate to severe nonproliferative diabetic retinopathy, and 71% in proliferative diabetic retinopathy. Older-onset diabetic patients are more likely to have visual impairment due to macular edema: 50% of older-onset compared with 20% of younger-onset diabetics [6].

Macular edema can be divided into focal and diffuse edema and cystoid maculopathy. In focal edema, OCT scans detect areas of thickened and hyporeflective retina (fig. 2). The edema can be located in the single scans and by retinal mapping and quantified by retinal thickness and volume mode. The map allows to locate the edema with great precision. OCT has been demonstrated to be more sensitive than biomicroscopy in detecting small changes in retinal thickness and morphology, especially in cases of mild cystoid macular edema [7].

Otani et al. [8] suggested three OCT patterns of diffuse diabetic macular edema: sponge-like swelling, cystoid macular edema and serous retinal detachment. In diffuse macular edema, the retina is becoming thicker and less reflective, with numerous small, irregular cavities reminiscent of spongy fabric (fig. 3). When the retina becomes thicker, the foveal depression finally disappears (fig. 4). If retinal edema persists, necrosis of the Müller cells occurs, leading to cystoid cavities in the retina also visible on OCT. The cavities often start in the external plexiform layer (fig. 3b). When cystoid maculopathy progresses, the walls of the pseudocysts disappear forming larger confluent cystoid cavities. Finally, cystoid maculopathy can involve the full thickness of the retina with atrophy of the retinal tissues, showing hyporeflective cavities on OCT (fig. 5).

However, diabetic macular edema can also be caused by serous fluid that accumulates under the neurosensory retina leading to a serous detachment of the macula which usually does not show on biomicroscopy and fluorescein angiography [9]. It can be detected by OCT showing a hyporeflective area under the macula elevating the neurosensory retina. Serous foveolar

a

b

Fig. 2. a Nonproliferative diabetic retinopathy with numerous cotton wool spots and clinically significant diabetic macular edema with hard exudates. Arrow indicates scanline. b Diffuse diabetic macular edema with hyporeflective serous detachment of the neurosensory retina (arrows), high reflective hard exudates (arrowhead) in the deeper retinal layers shadowing the posterior layers, and hyperreflective cotton wool spot (asterisk).

retinal detachment is reported in up to 15% of diabetic patients [6]. The visual acuity significantly correlates with central foveal thickness measured by OCT [10].

Patients with fovea-involving macular edema show an overnight increase in retinal thickness of about 20 m accompanied by a reduction in visual acuity

a

b

Fig. 3. a Cystoid diabetic macular edema with hard exudates. Arrow indicates scanline. b OCT shows cystoid diabetic macular edema with hyporeflective cystoid cavities (arrows) and high reflective hard exudates (arrowhead) in the deeper retinal layers shadowing the posterior layers.

being directly related to the nocturnal change in blood pressure, indicating a deficient regulation of retinal capillary filling pressure that promotes edema [11].

Yang et al. [7] found a significant correlation between OCT and fluorescein angiography in clinically significant macular edema. They suggested to categorize clinically significant macular edema into four types: type 1, thickening of the fovea with homogenous optical reflectivity throughout the whole layer of the retina; type 2, thickening of the fovea with markedly decreased optical reflectivity in the outer retinal layer; type 3, thickening of the fovea with subfoveal fluid accumulation and distinct outer border of detached retina,

Fig. 4. a Macular edema in diabetic retinopathy. b OCT showing diffuse macular edema with hyporeflective retina, loss of foveal depression and some cystoid cavities. c Early frame of the fluorescein angiography shows microaneurysms, hemorrhages and ischemic maculopathy with enlarged foveal avascular zone. d Late frame shows ischemic and cystoid maculopathy.

a b

Fig. 5. a Cystoid macular edema in diabetic retinopathy. b OCT shows large and small hyporeflective cystoid cavities.