Ординатура / Офтальмология / Английские материалы / Diabetic Retinopathy_Lang_2007

Fig. 5. a Clinically significant macular edema with focal area of retinal thickening with hard exudates. b The same eye after focal laser treatment.

In patients with diabetic macular edema, blood glucose and blood pressure control, serum lipids and proteinuria should be checked and treated adequately.

Diabetic macular edema has to be differentiated from ischemic maculopathy, which is caused by capillary dropout in the center of the macula leading to an enlargement of the foveal acvascular zone. Isolated ischemic maculopathy is not treated with laser. However, if ischemic maculopathy is associated with clinically significant macular edema, laser treatment is indicated.

Laser treatment reduced the risk of vision loss due to diabetic macular edema by 50–70%. About 17% of laser-treated eyes will experience a three-line improvement in visual acuity in 5 years [3]. Ohkoshi [31] found that visual acuity after grid laser photocoagulation in diffuse diabetic macular edema improved more than 0.2 levels in 41% of eyes, as well as in 60% of eyes in which preoperative visual acuity had been less than 0.5. Average visual acuity reached a plateau within 3 months after surgery.

After argon laser treatment, Wei et al. [22] found an improvement in visual acuity by at least one line on the visual acuity chart in 35%, no change in 55%, and deterioration in 19% of eyes. Retinal edema and fluorescein leakage were reduced in 89% of eyes, with the rest requiring additional treatment.

In focal diabetic macular edema, only the area of retinal thickening is treated (fig. 5). In circinate rings of hard exudates, the leaking microaneurysms that need to be treated are usually located in the center of the ring. Successfully treated leaking microaneurysms change the color to either white or dark red. Spots of 50 m have a higher risk of Bruch’s membrane perforation and should be avoided. Initial treatment must not be applied close to the center of the foveal avascular zone, because it results in central scotomas. Laser burns are not applied within 500 m of the center of the fovea [21]. For the patient, the most disturbing

Table 9. Laser lenses and spot magnification

scars are located at 3 and 9 o’clock. If the clinically macular edema persists after 3–6 months, leaking microaneurysms up to 300 m from the center of the fovea can be treated. Often mild intensity burns are as effective as more intense burns in reaching an improvement or resolution of the macular edema and they also allow more retreatment sessions if necessary. In diabetic macular edema, no confluent burns should be used in the macular area. It is important to retreat the patients in 3-month intervals, in areas where the macular edema persists.

Focal macular edema is treated only in the area of leaking microaneurysms and retinal thickening between 500 and 3,000 m from the center of the macula. Individual microaneurysms are treated with a spot size of 50 or preferably 100 m. Minimal power should be used to get a color change (whitening or darkening) of the microaneurysms.

Grid laser treatment is recommended for diffuse macular edema and is still the gold standard for treatment of diffuse macular edema. Prompt photocoagulation is indicated in eyes with center involvement of the macula. Light to moderate intensity of 100to 200- m burns are placed 1 burn apart, producing a grid of equally spaced burns (tables 9–10; fig. 6). The patients should be

Fig. 6. a Diffuse macular edema with hard exudates in the center of the macula after laser retreatment. b The same patient after complete resorption of the macular edema and hard exudates.

examined at 3-month intervals and considered for additional treatment if clinically significant macular edema persists.

Bandello et al. [32] studied light versus classic laser treatment for clinically significant macular edema. In light laser treatment, the energy employed was the lowest capable to produce barely visible burns at the level of the retinal pigment epithelium. It was as effective in decreasing the foveal retinal thickness on OCT and visual improvement or loss.

Vitreomacular traction is very difficult to detect on clinical grounds but is easily visible on OCT. If it is combined with clinically significant macular edema, we perform a grid laser treatment first, if possible. Sometimes, there is a spontaneous complete vitreous detachment and resolution of the vitreomacular traction after laser treatment. If vitreomacular traction persists, vitrectomy is performed. Often after vitrectomy, further macular laser treatment is necessary because of persistent clinically significant macular edema. Epiretinal membranes also have to be treated by vitrectomy and membrane peeling, combined with laser treatment. However, they tend to recur after some time.

If macular edema is combined with ischemic maculopathy, laser treatment should be performed if dye leakage is found on fluorescein angiography or retinal thickening is present on biomicroscopy or OCT examination. However, laser burns should spare about 500 m of the still perfused capillaries on the boarder to the foveal avascular zone. If the laser burns are placed right at the edge of the avascular foveal area, immediate visual loss often occurs because the capillaries are further compromised, leading to more ischemia.

Subthreshold diode micropulse photocoagulation was introduced for the treatment of clinically significant macular edema. Visual acuity was stable or

improved in 85% of treated eyes, with a mean follow-up of 12.2 months. Macular edema decreased in 96% and resolved in 79% of treated eyes. No adverse laser events occurred. No laser lesions were detectable on ophthalmoscopy or angiography after treatment, and no scarring occurred during the follow-up period. Subthreshold diode micropulse laser photocoagulation minimizes chorioretinal damage in the management of clinically significant macular edema and demonstrates a beneficial effect on visual acuity and edema resolution [33].

In a small study, Patel et al. [34] found no visual benefit for standard pars plana vitrectomy and removal of the posterior hyaloid compared with macular grid photocoagulation alone in eyes that showed persistent clinically significant macular edema despite previous macular photocoagulation.

VEGF inhibitors were beneficial in diabetic macular edema in a phase II study. A combination therapy of laser and VEGF inhibitors might result in a better outcome and needs to be further investigated.

Wavelengths

The most commonly used wavelengths are double-frequency Nd:YAG (532 nm) or argon green (514 nm). Krypton red and dye lasers are equally effective, but they may be more painful. Gupta et al. [35] examined the efficacy of various wavelengths in the treatment of clinically significant macular edema. Reduction or elimination of macular edema was found in 93.3% of argon-, 88.5% of krypton-, 92.9% of frequency-doubled Nd:YAG-, and 84.8% of diode laser-treated eyes. Although there was no statistically significant difference between the groups, frequency-doubled Nd:YAG-treated eyes appeared to have the advantage of requiring fewer retreatment sessions.

Rules to Bear in Mind

The therapeutic effect of the laser occurs through absorption of the laser energy in the retinal pigment epithelium. Laser burns should not be directed on vitreous hemorrhage or larger intraretinal hemorrhages because the hemoglobin would absorb the laser energy and the vitreous traction, or nerve fiber damage would result. Hard exudates should not be treated directly either, because they do not absorb the laser energy. Major retinal vessels should not be treated directly because of the risk of vessel rupture or closure; however, this is very rare. Areas with proliferative vitreoretinopathy should not be

treated directly because of the risk of shrinkage of the membrane, which then causes retinal traction and detachment. Chorioretinal scars should be avoided because the risk of visual field loss and secondary choroidal neovascularization increases.

In unsatisfactory laser treatment results, one should always consider undertreatment as reason for failure of improvement in macular edema or proliferative changes. Either the treated area was too small, the number of applied burns not sufficient or there was no adequate retreatment.

Side Effects

The most common side effects of panretinal laser treatment are pain during the treatment, moderate visual loss, restriction of the visual fields and nyctalopia. Visual field loss occurs in 5% of argon laser-treated eyes [36]. Permanent visual loss of two or more lines is experienced in 3% of treated eyes. Other side effects are glare, exudative retinal detachment, ciliochoroidal effusion, elevated intraocular pressure, angle-closure glaucoma and subretinal or epiretinal fibrosis. The risk of ciliochoroidal effusion depends on burn intensity, burn size and number and axial length representing the percentage of the retinal surface area. Some degree of cilioretinal effusion occurs in up to 59–90% of patients, resolving within 2 weeks. Those side effects are less common when scatter treatment is carried out in two or more sessions [37]. Macular edema may exacerbate by panretinal laser treatment. Visual loss can be reduced by treating the macular edema prior to initiating panretinal photocoagulation, avoiding intense panretinal photocoagulation burns and dividing panretinal photocoagulation in several treatment sessions. Rare side effects are damage of the cornea, iris or lens (especially in wide field laser lenses). Transient myopia, accomodative pareses, retinal or choroidal hemorrhages, and uveitis are rare. After panretinal laser treatment, a breakdown of the blood-aqueous barrier is found. More pigmented irides showed a greater breakdown than blue irides [38].

The most common side effects of macular laser treatment are scotomas in laser burns close to the boarder of the foveal avascular zone. Subretinal fibrosis most likely develops in eyes with severe hard exudate deposition. Secondary choroidal neovascularization can develop in laser scars because of the rupture of Bruch’s membrane. The larger laser burns have a lower risk of breaks in Bruch’s membrane and therefore a lower risk of secondary choriodal neovascularization in the area of laser scars.

If the patient is not cooperative, a foveal burn might occur if the patient moves the eye during laser exposure. Inadvertent foveal burns can be avoided by the laser surgeon if the center of the macula and the patient’s fixation point

are clearly identified before the laser treatment is started. Treatment of macular edema can be challenging if the fovea is obscured by edema, exudates or hemorrhages. It must also be taken into consideration that laser scars expand with time. Maeshima et al. [39] found that 90% of the laser scars gradually increase in size. The mean annual expansion rates were 12.7% in the posterior pole and 7% in the midperiphery. The annual expansion rate (16.5%) more than 4 years after treatment was higher than that (8.8%) within 4 years of treatment. Lasers of a longer wavelength contributed to larger areas of chorioretinal atrophy. Delivery of laser energy using small spot sizes, short durations and high power increases the risk of perforation of Bruch’s membrane and choroidal neovascularization. Blue wavelength should not be used because of the damage of photoreceptors.

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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

Table 1. Indications for vitrectomy in diabetic retinopathy

Ischemia and complications

Active proliferative retinopathy and consequences

Neovascularization of the anterior segment in connection with secondary glaucoma

Media opacities

Persistent vitreous opacities Persistent subhyaloidal fibrosis

Neovascularization of the anterior segment in connection with vitreous opacities Vitreous hemorrhage (e.g., postoperatively) in combination with ‘ghost cell glaucoma’

Traction-related complications

Progressive fibrovascular proliferation

Tractive macular detachment

Combined tractional rhegmatogenous detachment

Macular edema with a ‘taut hyaloid’

Nonvascularized epiretinal membranes (e.g., postoperatively)

•tractional retinal detachment outside the macula, which may remain stable without progression [Smiddy and Flynn, 1999]; exceptions are cases presenting with newly formed active neovascularization, recurrent vitreous bleeding, or progression towards the macula area;

•neovascular glaucoma [Bartz-Schmidt et al., 1999; Joussen et al., 2003]. It is agreed that vitreoretinal traction on the macula is best addressed by vit-

rectomy and membrane peeling, although surgery is unable to heal altered original retinal vessels. However, it may lower the diffusional barrier between the retinal compartment and the vitreous cavity. Vitrectomy alone seems to help with the resolution of exudative macular edema [Lewis et al., 1992; Pendergast et al., 2000; Lewis, 2001; Yamamoto et al., 2001]. A more complete clearing of potential diffusion barriers is achieved by induction of a posterior vitreous detachment and by removal of the inner limiting membrane (ILM) from the posterior pole [Gandorfer et al., 2000; Radetzky et al., 2004; Rosenblatt et al., 2005].

In conclusion, indications for surgery in diabetic eyes can be attributed to three areas: ischemia, media opacities and tractional forces (table 1). This review aims to critically discuss indications and expected results of surgical approaches to diabetic retinopathy and maculopathy.

Surgical Techniques

The 3-port access is standard for vitrectomy in diabetes. Besides the growing miniaturization of intraocular surgery tools, major advances of the past