Ординатура / Офтальмология / Английские материалы / Current Aspects of Pathogenesis and Treatment in Diabetic Retinopathy_Kroll_2007

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Fig. 1. Vitreous and subhyaloidal hemorrhage. Fibrovascular membranes were visible and tractional detachment of the retina was suspected. Vision was hand movement. Surgery was recommended.

Fig. 2. Long-standing tractional detachment of the macula. The retina was covered by extensive active fibrovascular membranes. The retina itself was barely visible. Vision was light perception. Vitrectomy was performed anatomically successfully, but vision did not improve.

Eyes with iris neovascularizations require immediate retinal coagulation therapy to avoid irreversible obstruction of the chamber angle by progressive growth of fibrovascular membranes. If media opacities make adequate coagulation therapy impossible, surgical removal of the hemorrhage and intense endolaser treatment become necessary.

It is therefore not possible to give general recommendations about how long to wait for surgery in diabetic vitreous hemorrhage. Vitreous hemorrhage is a dramatic event for the patient, but the prognosis for vision in the long term is often dependent on other factors.

Tractional Detachment of the Fovea

Eyes with tractional detachment of the fovea have very poor vision and if left untreated will not improve (fig. 2). Surgery is the only therapeutic option and it is generally assumed that there is little to lose even if surgery fails. The functional results of surgery are usually disappointing, even after anatomically successful surgery. The poor visual outcome is mostly due to advanced ischemia of macula and optic disc. Analysis of risk factors revealed extension of the retinal detachment, dura-

tion of macular detachment and iris neovascularizations being associated with poor visual outcome [17, 25]. In eyes with these risk factors, chances for significant visual improvement are so small that one has to consider not performing any surgery, especially if the fellow eye is good and general health is poor. Even if these eyes have little vision to lose, failed surgery with complications may even accelerate the loss of the remaining function and loss of the globe. If both eyes have reduced vision, surgical attempts will nevertheless have to be performed despite a poor prognosis.

Extrafoveal Tractional Detachment

Tractional retinal detachment usually does not start in the fovea. Fibrovascular membranes mostly grow along the vascular arcades and close to the optic disc, where traction and tractional detachment usually begin. Extrafoveal tractional retinal detachment is not an absolute indication for surgery. In many cases the situation may remain stable (fig. 3) and a detached retina may even spontaneously reattach [26]. It is important, however, that eyes with extrafoveal tractional detachment must be carefully watched, especially after laser treatment. Active

Fig. 3. Tractional retinal detachment nasally to the fovea. The membranes were atrophic after scatter laser treatment and the traction did not threaten the fovea. Vision was 20/25 and no further therapy was performed.

fibrovascular membranes require retinal photocoagulation. Laser treatment induces fibrotic transformation of the neovascularizations and possibly contraction of the membranes, which may eventually lead to progression of the tractional detachment [27]. Before vitreous surgery was available, these eyes had a very poor prognosis and laser treatment was considered to be dangerous in these eyes. Now that we can surgically treat these tractional membranes, scatter laser treatment is recommended if active neovascularizations are present, but a close followup is mandatory. Vitrectomy is recommended if the detachment progresses and threatens the fovea or if significant vitreous hemorrhage develops.

Tractional Rhegmatogenous Retinal Detachment

Traction by diabetic fibrovascular membranes may create retinal tears and a rhegmatogenous retinal detachment may develop (fig. 4). This combined tractional and rhegmatogenous retinal detachment is relatively rare and shows both features of a tractional detachment with membranes tightly adhering to the retina and a retinal tear. The retinal tear itself may be difficult to identify, but the shape of the retinal detachment is quite different. A pure tractional detachment is usually concave, tent-like shaped and the retina is not mobile. The appearance of rhegmatogenous detachment is convex, bullous and mobile. While a tractional detachment progresses slowly and does not require emergency surgery, a tractional-rhegmatogenous detachment usually progresses rapidly and has to be operated without delay. The prognosis of tractional rhegmatogenous retinal detachment is less favorable than for pure tractional detachments. Intraoperatively it is more difficult to separate the membranes from a mobile retina than from a fixed and relatively stable retina. Perfluorcarbon should not be used until the membranes are removed from the posterior pole. Intraoperative complications are relatively common in this type of surgery [28]. In addition, we occasionally observe reproliferations in the postoperative course which represent a combination of diabetic fibrovascular membranes and the typical proliferative vitreoretinopathy. These proliferations are surgically very difficult to manage.

Fig. 4. Tractional rhegmatogenous retinal detachment, visual acuity hand movement. The retinal tear is marked with an arrow.

Tractive Macular Edema

In some cases traction on the fovea may cause tractive macular edema, even if the fovea itself is not detached. Traction of diabetic fibrovascular membranes may cause an ophthalmoscopic appearance with typical hard exudates (fig. 5). Atrophic fibrovascular membranes may

also create a picture similar to macular pucker with distortion of the central retina. The best therapy for tractional edema is to remove the traction. Tractional membranes may often be easily visible, but in other cases biomicroscopy only shows minimal changes. In some instances ocular coherence tomography can clearly demonstrate the fine membranous structures exerting tractional forces and creating swelling of the macula [29]. Thus, ocular coherence tomography imaging should be included in the diagnostic workup of diabetic macular edema. In cases without traction, laser treatment is a valuable approach; focal laser treatment is not recommended if mechanical traction is the cause for macular edema. Visual recovery after surgery is mainly dependent on the degree of macular ischemia; therefore preoperative fluorescein angiography is helpful to give a picture of the status of macular microcirculation.

Diffuse Macular Edema

Several recent reports have described an improvement of diffuse diabetic macular edema without visible traction after vitrectomy in eyes with attached vitreous [30]. The pathophysiological basis for this attempt was to improve access of oxygen and nutrients from the vitreous to

the retina, and vice versa, to facilitate diffusion of cytokines from the retinal tissue into the vitreous, avoiding accumulation of factors triggering macular edema within the macular tissue. Despite significant anatomical improvement of the edema after removal of the vitreous, recovery of vision was rather unsatisfactory in many cases. It is still controversial whether this approach with or without removal of the inner limiting membrane significantly improves the long-term course of the disease in eyes with diffuse diabetic macular edema without traction [31, 32].

Surgery for Neovascular Glaucoma

The cause for neovascularizations of the iris and chamber angle is believed to be the ischemic retina, which produces vasoproliferative growth factors. These cytokines may diffuse to the anterior segment of the eye, triggering anterior segment neovascularizations. In aphacic and vitrectomized eyes there is no diffusion barrier between the anterior and posterior segment of the eye. Therefore these eyes are particularly at risk for the development of neovascular glaucoma. Therapy has to be primarily directed to the cause of the neovascular stimulus, the ischemic retina. The most important element of treatment is there-

fore retinal ablation by laser or cryotreatment [33]. Since this treatment can induce fibrotic regression but not complete dissolution of the membranes in the chamber angle, retinal ablation is often not sufficient to regulate intraocular pressure. Therefore additional treatment to lower intraocular pressure is usually necessary. Filtering surgery has a poor prognosis, since the high levels of cytokines in the aqueous humor stimulate fibrosis which is obstructing the fistula. Antimetabolites or glaucoma drainage devices [34] may be used to improve success rates but have an increased risk for complications. Transscleral cryotherapy [35] or transscleral laser treatment to the ciliary body is an alternative to reduce aqueous humor production but has a relatively narrow therapeutic window; overtreatment may induce phthisis of the globe. If other diabetic complications are present, requiring vitreoretinal surgery, direct endolaser treatment to the ciliary processes can be applied to reduce aqueous humor production [36]. In severe cases instillation of liquid silicone can form a diffusion barrier between the retina and the anterior segment of the eye and may contribute to a stabilization of anterior segment neovascularization [37].

Cataract Surgery

Second to age, diabetes is the main epidemiological risk factor for the development of cataracts. Cataract surgery in eyes with diabetic retinopathy is performed to improve vision for the patient, but it also allows a clear view to the fundus for diagnosis and treatment of the retinopathy. However, cataract surgery may worsen retinopathy [38]. Neovascularizations and macular edema may be stimulated to grow after cataract surgery [39, 40]. Nevertheless, conventional cataract surgery with phacoemulsification and implantation of an intraocular lens can be safely performed in most eyes with diabetic retinopathy [41, 42]. Intracapsular surgery is associated with an increased risk for neovascular glaucoma [43] and should be avoided in diabetic eyes. Several other aspects should be taken into account. Whenever possible retinopathy should be treated and stabilized before surgery using adequate laser photocoagulation. Especially eyes with iris neovascularizations require intense preoperative laser coagulation or transscleral cryotreatment of the retina. If this is not possible before surgery or not sufficient, a combined procedure with cataract and vitreous surgery including endolaser treatment of the retina should be considered. Fibrinous reaction after cataract surgery alone may render postoperative laser treatment in eyes with iris rubeosis difficult.

If macular edema is present, preoperative focal laser treatment should be used. If it is not possible to have a completely dry macula at the time of cataract surgery, there is a high risk for worsening of macular edema and visual loss. If cataract surgery has to be performed in the presence of diabetic macular edema, it may be recommended to combine cataract surgery with an intravitreal injection of triamcinolone [44–46]. Intravitreal triamcinolone has been shown to successfully improve vision and retinal thickening in diabetic macular edema [47].

Other specific aspects for cataract surgery in eyes with diabetic retinopathy include a large capsulorhexis and an intraocular lens with large optics to facilitate possible subsequent diagnosis and laser treatment of the retina. Silicone intraocular lenses should be avoided because they interact with liquid silicone which possibly has to be used for endotamponade in the later course of diabetic eye disease. Diabetic eyes have an increased risk for postoperative fibrin exudation and formation of synechiae between the lens capsule and the iris due to an impaired blood retinal barrier [48–50].

Complications of Surgery for Diabetic Retinopathy

Cataract

Opacification of the lens is a mandatory consequence of vitrectomy independently of the cause for vitrectomy. Generally, development of cataracts appears to occur faster in diabetic eyes after vitrectomy than after vitrectomy in nondiabetic eyes. Silicone tamponade leads to an acceleration of cataract formation. Gas tamponade induces an immediate posterior subcapsular opacification occurring a few hours after surgery, which is mostly reversible. Later nuclear sclerosis develops, which does not appear to be much faster after gas tamponade than after vitrectomy with Ringer’s solution [48]. In young patients cataract formation occurs more slowly, and the lens may remain clear for many years or decades before surgery becomes necessary [51]. In older patients significant cataracts may form within a few months after vitrectomy.

The rapid development of cataract after vitrectomy especially in older diabetics has led some surgeons to perform combined viteoretinal and cataract surgery even for eyes with primarily clear lenses. This approach has been shown to be successful and saves the patient a second surgery [52, 53]. Combined surgery however appears to be associated with a higher rate of inflammatory responses with fibrin in the anterior chamber and the formation of synechiae compared to a 2-step procedure [50]. It may

Helbig

therefore be safer to operate on the lens in a second surgery if possible. Combined cataract and vitreoretinal procedure may only be performed if lens opacities are disturbing intraoperative visualization of the posterior segment.

Retinal Detachment

Rhegmatogenous retinal detachment is a typical complication of vitrectomy [54]. Retinal holes may be created intraoperatively when traction to the vitreous base is exerted. The most common location of iatrogenic holes is close to the sclerotomies where intraocular instruments are introduced into the eye. The more instruments are exchanged during surgery, the higher the risk for creating holes. The risk can be reduced by carefully removing the anterior vitreous next to the sclerotomies with the cutter before instruments like scissors are introduced. In righthanded surgeons the most common location is temporal superior in the right eye and nasal superior in the left eye. Careful inspection of the peripheral retina out to the ora serrata at the end of the surgery under indentation using a wide angle viewing system may identify such retinal tears [55]. Adequate treatment can reduce the risk for postoperative retinal detachment. If postvitrectomy rhegmatogenous retinal detachment occurs, pneumatic retinopexy as a minimum invasive procedure is often the treatment of choice. The tears are anteriorly located and can be reached with transscleral cryotherapy without opening the conjunctiva. The holes are mostly located in the superior quadrants and gas injection in a vitrectomized eye is not associated with a high risk of creating new holes.

Another possible cause for postoperative retinal detachment after vitrectomy for diabetic retinopathy are retinal holes located more posteriorly. These holes may be created during the preparation of membranes tightly adhering to the thin and atrophic retina mostly being located close to the major vascular arcades. If such holes are recognized intraoperatively, all traction surrounding the hole has to be released, the hole should be encircled with laser spots and an adequate internal tamponade, often liquid silicone, should be used.

Tractive redetachment may occur if severe reproliferations develop. The traction of reproliferation may also tear off laser scars and create a combined tractional rhegmatogenous retinal detachment.

Reproliferations

Reproliferation of diabetic fibrovascular membranes is a severe complication after vitrectomy for diabetic ret-

inopathy. Since the ischemic retina is believed to secrete the proliferative stimuli, the ischemic retina has to be adequately treated with laser. Especially in eyes with silicone tamponade growth factors may concentrate in the shallow interface between silicone and retina and provide an intense stimulus for reproliferations [56, 57]. Complete removal of all fibrovascular tissue using various techniques (‘segmentation’ technique [58], ‘delamination’ [59] or ‘en bloc’ [60] technique) eliminates the starting point and the substrate for reproliferations. In rare cases fibrovascular membranes may also develop along the anterior vitreous remnants creating anterior hyaloid fibrovascular membranes. Neovascularizations at the internal side of the sclerotomies may be the source for recurrent hemorrhage, if no neovascularizations are present in the posterior pole. In advanced cases it may be difficult to differentiate between diabetic reproliferations and proliferative vitreoretinopathy reactions, which we also occasionally see after surgery for rhegmatogenous retinal detachment in nondiabetic eyes.

Hemorrhage

Small amounts of blood are found in most eyes after vitreous surgery for diabetic retinopathy and significant rebleeding is not exceptionally rare. Diabetic neovascularizations are cut or torn off during surgery creating opening of the vessel lumen and a potential source for a vitreous hemorrhage. Bleeding vessels may be identified intraoperatively by lowering the intraocular pressure and should be coagulated intraoperatively using endodiathermia. If the source of hemorrhage is a large vessel or the optic disk, this may not be possible. The bleeding often stops spontaneously or after increasing the infusion pressure, but it may cause hemorrhages in the early postoperative phase when the blood pressure increases. Very dense hemorrhages after vitrectomy may be removed by revitrectomy or by fluid-air exchange [61].

Iris Rubeosis and Neovascular Glaucoma

Neovascularizations of the iris and chamber angle may occur if growth factors from the ischemic retina reach the anterior segment of the eye. Obstruction of the trabecular meshwork by fibrovascular membranes and increased intraocular pressure is a severe complication of diabetic retinopathy. Two aspects of vitreous surgery may contribute to the development of postoperative iris rubeosis. First, the removal of preretinal neovascularizations may worsen retinal ischemia and further stimulate the production of growth factors. Second, after removal of the vitreous these cytokines can more easily diffuse to

the anterior segment of the eye. Especially after additional intracapsular cataract surgery there is no diffusion barrier left between iris and retina. To reduce the stimulus for neovascularizations, endolaser treatment should be applied at the end of vitreous surgery whenever possible.

Iris rubeosis is associated with retinal detachment in diabetic eyes. Sudden appearance of rubeosis in the postoperative course should alert the ophthalmologist to carefully inspect the peripheral retina [62].

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