Ординатура / Офтальмология / Английские материалы / Diabetic Retinopathy_Lang_2007

2004]. The lack of long-term improvement in this study is in accordance with the hypothesis that ILM peeling does not interfere with the mechanism of macular edema.

Currently, a randomized multicenter study is ongoing (TIME, Triamcinolone versus ILM Peeling in Persistent Diabetic Macular Edema), which investigates the benefit of ILM peeling in patients with persistent diabetic macular edema (time-study@uk-aachen.de).

Cataract Surgery

Cataract surgery is the most frequent and most successful surgery in ophthalmology. Improvement in visual acuity after cataract surgery is achieved despite severe non-PDR in 55% of the patients [Chew et al., 1999].

Nevertheless, the postoperative results in diabetic patients are inferior to patients without diabetes. The ETDRS reports a gain of 2 or more lines in 64.5% of eyes with early and 59.3% of eyes with delayed photocoagulation 1 year after cataract surgery. A visual acuity of 0.5 after cataract surgery was only achieved in 46% of eyes with delayed photocoagulation.

In our experience, worsening or development of a macular edema is the main reason for visual deterioration after cataract surgery. Therefore, every eye with increased central retinal thickness, even if according to ETDRS no clinically significant macular edema is apparent, should be treated by focal photocoagulation, if an adequate view of the fundus is present. Vice versa, a potential postoperative worsening of macular edema is no argument against cataract surgery, but should be treated as indicated below. If during the postoperative course the edema progresses to a cystic form that is difficult to approach with photocoagulation, early treatment with intravitreal triamcinolone should be considered. According to our own experience and published reports [Jonas et al., 2005], steroid injection is able to efficiently reduce the postsurgical edema as well as diabetic macular edema. Prospective randomized clinical trials regarding triamcinolone treatment for diabetic macular edema are currently under investigation (for further information, time-study@uk.aachen.de).

In eyes of dense cataract, not only the patient’s visual acuity, but also the fundus view is obscured, and the necessary panretinal photocoagulation is not adequately possible. In some cases, the use of a crypton laser with a wavelength in the range of 600 nm is advantageous in the penetration of a nuclear cataract.

In cases of proliferative retinopathy, a panretinal photocoagulation prior to cataract surgery is urgently advised. If this is rendered impossible, small incision surgery allows for photocoagulation within a short time after cataract extraction.

Cataract surgery itself requires some peculiarities: in order to facilitate later panretinal photocoagulation or vitrectomy, a large capsulorrhexis is required as well as an IOL with a large optic. Acryl is the recommended lens material, as these IOL can be folded and implanted in small incision surgery. Furthermore, the risk of unfavorable interactions with silicone oil, which could become necessary in subsequent vitreous surgery, is reduced if acryl is used as lens material compared with silicone. Silicone oil tends to stick like glue on silicone lenses if close contact occurs.

Without any doubt, phacoemulsification with implantation of a posterior chamber lens into the capsular bag remains the method of choice for the diabetic eye. Nevertheless, there are also selected indications for lens extraction with subsequent aphakia. As indicated previously, coagulation of the ischemic periphery is an essential part of an antiproliferative therapy. The outermost periphery is easiest approached in aphakic eyes, as is the removal of anterior hyaloid proliferation. Lensectomy or removal of the IOL should be considered in eyes with revision surgery and reduced visual prognosis (e.g., rubeosis and persistent tractional detachment of the macula) and, according to our experience, is not associated with a higher complication rate. Previous reports on stimulation of rubeosis following lensectomy in aphakic eyes did not use the possibility of a facilitated peripheral photocoagulation. Combination of cataract removal, vitrectomy and endophotocoagulation was only reported in small case series to be associated with a higher risk of neovascularization of the iris [Blankenship et al., 1989; Kokame et al., 1989]. The inhibition of ischemia and thus of developing or existing rubeosis by a radical peripheral vitrectomy and endophotocoagulation predominates, in our opinion, the stimulation of rubeosis by aphakia.

Conclusion

The project ‘Diabetes 2000’, which was propagated in the 1990s, aimed to reduce the rate of diabetes patients with visual loss through early diagnosis and treatment of complications [Patz and Smith, 1994]. Refined materials and instrumentation, and thus improvement in surgical techniques, allow preventing complications such as severe anterior hyaloidal fibrovascular proliferation and severe fibrinoid syndrome [Ho et al., 1992] which have been frequently seen in the early years of vitrectomy. Nevertheless, even today, patient expectations of visual rehabilitation cannot be satisfied, and a large discrepancy lies between these expectations and the physician’s hope to limit secondary consequences of rubeotic glaucoma with phthisis bulbi.

The spectrum of indications for surgical interventions in diabetic retinopathy did not change during the past decade. Helbig et al. [1997, 1998a,

b, 2002] report on 389 eyes which underwent surgery between 1990 and 1994. In this series, indications for vitrectomy included 39% vitreous hemorrhages, 13% tractional detachments of the macula, 12% tractional rhegmatogenous detachment, and 36% severe progressing proliferative retinopathy. A retrospective analysis of the patients at the department in Cologne from 2000 to 2004, which analyzed 361 patients, demonstrated 54% vitreous hemorrhages, 9% tractional detachment including the macula, 4% tractional detachment without the macula, 7% rubeotic secondary glaucoma, 2% macular edema, and 1% others.

At present, the major discussion about the value of vitrectomy in the treatment of diabetic retinopathy refers to the optimal time point for intervention [Helbig et al., 1996]. According to the DRVS, early vitrectomy in cases of severe vitreous hemorrhage without tractional detachment improves the longterm prognosis in type 1 diabetics despite the immediate risk of the surgical procedure [DRVS Research Group, 1990]. Earlier in this review, risk factors for progression have been discussed extensively, e.g., lack of previous panretinal photocoagulation or tractional detachment of the fellow eye in young diabetics with insufficient adjustment of blood glucose levels. Without risk profile, in patients with vitreous hemorrhages, it is allowed to wait until the hemorrhage clears up (for a maximum of 3 months) and photocoagulation is possible. Among several exceptions, single eyes, which require quick visual rehabilitation, should be reminded of.

However, the frequency of iatrogenic holes and the risk of reproliferation can be reduced with the improved surgical techniques. Helbig et al. [1998a, b] found postoperative detachments in 18% of all vitrectomies. Selecting patients with pure vitreous hemorrhage reduces the proportion to 5%. Certainly only a small part of the detachments are induced by iatrogenic retinal holes. Reproliferation is a major reason [Messmer et al., 1992]. Thus, more recent publications report on a lower redetachment rate [Helbig et al., 1997, 1998a, b; Joussen, unpubl.].

The indication for revision surgery in cases with combined rhegmatogenous tractional detachment and cases of ‘ghost cell glaucoma’ after vitreous hemorrhage should be generously handled.

In general, combined cataract and vitreoretinal surgery is possible in diabetic patients. If possible, we would prefer two separate procedures. In any case, it is important to perform a sufficient panretinal photocoagulation for reduction in ischemia and the proliferative stimulus.

Only few years back, silicone oil tamponade was controversially discussed, but is now an integral component of surgical treatment in diabetic retinopathy. Silicone oil was described to increase the risk of progression of maculopathy, damage to the optic disc, and reproliferation [Messmer et al., 1992; Helbig et al.,

1997]. Whether the differences reported here have any clinical relevance still remains questionable. Silicone oil tamponade, performed in cases of severe angiopathy, is not necessarily causally linked to disease progression. Similarly, reproliferation under oil is more likely attributable to incomplete membrane removal. Thus, ‘perisilicone proliferation’ [Lewis et al., 1988] should rather be ‘proliferation following incomplete peeling’. In fact, severe postoperative bleeding can lead to formation of epiretinal membranes requiring revision surgery. We suggest to perform the revision surgery after an interval of 8–12 weeks following primary surgery to avoid repeated bleeding and to lower the proliferative vitreoretinopathy rate. In general, silicone oil removal should be attempted after 3 months to prevent formation of secondary glaucoma or cataract formation [Messmer et al., 1992; Karel and Kalvodova, 1994; Sima and Zoran, 1994].

Summary

•Despite anatomically satisfying results, vitreoretinal surgery can only partially meet the patient’s expectations of visual rehabilitation.

•A complete panretinal photocoagulation and thus reduction in the ischemic proliferation is key to surgery in eyes with active neovascularization and its complications. Even in prognostic unfavorable situations with preexisting rubeosis or persistent tractional detachment involving the macula, surgical treatment is worthwhile to prevent phthisis or neovascular glaucoma.

•There are only small case series regarding the effectiveness of pars plana vitrectomy in diabetic macular edema. The results of large, randomized clinical investigations are being awaited.

•Besides surgical therapy, a long-term optimization of the blood glucose levels is inevitable [Diabetes Control and Complications Trial Research Group, 1993; Davidson, 1994; UK Prospective Diabetes Study Group, 1998].

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Antonia M. Joussen Department of Ophthalmology

Heinrich-Heine University Duesseldorf Moorenstraße 5

DE–40225 Duesseldorf

Tel. 49 0211 81 17321, Fax 49 0211 81 16241, E-Mail joussena@googlemail.com

Pathophysiology

Causes of diabetic macular edema include increased vasopermeability and damage to the retinal capillaries and the barrier provided by the retinal pigment epithelium [5]. Alternatively, or additionally, increased vasopermeability resulting in macular edema may be induced by vitreomacular traction [6]. In a subset of eyes with diabetic macular edema, the role of the vitreous and – in particular – the role of the posterior vitreous cortex have become increasingly recognized [7].

Role of the Vitreous and Vitreoschisis

Evidence of a vitreous origin of development and exacerbation of diabetic macular edema arises from several clinical studies. The prevalence of posterior vitreous detachment (PVD) in patients with diabetic macular edema is significantly lower than in diabetic patients without macular edema [8]. Spontaneous vitreomacular separation can cause resolution of diabetic macular edema [9].

In 1993, Kishi and Shimizu [10] reported the clinical manifestations of the premacular vitreous in proliferative diabetic retinopathy. In 94% of their 134 studied eyes with partial PVD, a posterior precortical vitreous pocket was observed in front of the macula. The posterior border of this pocket was formed by the premacular cortical vitreous which remained attached to the macula.

Schwartz et al. [11] identified cortical vitreous remaining attached to the macula (‘vitreoschisis’) during surgery in 145 (81%) of 179 patients with proliferative diabetic retinopathy and traction retinal detachment. By using immunochemical staining, they were able to show that the wall of the vitreoschisis cavity was composed of type II collagen, thus providing direct evidence of the occurrence of splits in the posterior vitreous cortex [11].

Histopathologic studies in patients suffering from proliferative diabetic retinopathy disclosed the growth of newly formed blood vessels into the posterior vitreous cortex [12], thereby providing a possible explanation for the low incidence of progressive diabetic retinopathy in patients with complete PVD and the significantly higher risk of aggressive proliferation of new blood vessels in patients with partial PVD [13].

In a recent clinicopathological series of 61 eyes with diffuse diabetic macular edema, only 11% showed complete PVD, whereas 89% had a partially or completely attached vitreous [14]. There was a higher incidence of complete PVD confirmed intraoperatively in patients with nonproliferative disease (29%) compared with patients with proliferative diabetic retinopathy (8%).

In summary, vitreoschisis and the presence of a thickened posterior cortical vitreous have been considered to play a key role in disease progression – not only in terms of neovascularization but also in terms of diabetic macular edema – and removal of the cortical vitreous has been suggested as one treatment option of diffuse diabetic macular edema [15].

Ultrastructural Findings of the Vitreous Cortex

We investigated the ultrastructure of the vitreomacular interface in a consecutive series of patients with diffuse diabetic macular edema [14]. Our approach was based on en bloc removal of the internal limiting membrane (ILM) together with all epimacular tissue. We found native vitreous collagen covering the ILM in almost all specimens (60/61). Even in the presence of clinically complete PVD and in eyes which had been vitrectomized previously, there were remnants of the cortical vitreous present at the vitreal side of the ILM. These findings emphasize that in diabetic eyes, PVD rarely occurs between the ILM and the vitreous cortex. Splitting of the vitreous cortex is a common finding, leaving a layer of cortical vitreous at the vitreoretinal interface. Our results also show that surgical induction of PVD by suction does not separate the vitreous cortex from the ILM but leaves a layer of collagen attached to the ILM. Native vitreous collagen was also the major ultrastructural component of a clinically prominent premacular cortical vitreous which had previously been called ‘thickened and taut premacular hyaloid’. In these eyes, fibroblasts, fibrous astrocytes and macrophages were embedded in collagen or were localized on a layer of vitreous collagen [14].

Vascular Endothelial Growth Factor and the Cortical Vitreous

It has been hypothesized previously that the presence of factors capable of altering vascular permeability may be a more physiological rather than mechanical cause of macular edema [16]. Vascular endothelial growth factor (VEGF) and its receptors as well as interleukin-6 have been localized to cells of vascular and avascular epiretinal membranes in patients with diabetic retinopathy [17, 18]. The presence of these and other factors altering vasopermeability, which are produced by cells within the cortical vitreous, may promote persistence of macular edema. Antonetti et al. [19] showed that increased levels of VEGF in the vitreous decrease levels of occludin, a membrane spanning tight junction protein, which could alter the structure of the retinal endothelial junction and may account for the increased vasopermeability in patients with diabetic