Ординатура / Офтальмология / Английские материалы / Macular Degeneration_Penfold, Provis_2005

fectiveness and safety of the procedure (Submacular Surgery Trials Pilot Study 2000a, 2000b; Stone and Sternberg 2002). This recommendation led to the organization of the Submacular Surgery Trials (SST) study group, which has initiated a trio of multicenter, randomized clinical trials with the goal of determining whether surgical removal of subfoveal CNV stabilizes or improves vision more often than observation (NIH clinical research studies

– Protocol number NEI-52). Three groups of patients are under study – Group B (blood), Group N (new CNV), and Group H (histoplasmosis/idiopathic; Stone and Sternberg 2002). The final results are pending. In 2001 the Swedish national survey of surgical excision for submacular CNV was published (Berglin et al. 2001). The study compared visual outcomes after surgical removal of subfoveal CNV between patients younger or older than 50 years of age. It was concluded that surgical removal of submacular CNV does not appear to improve visual acuity in patients older than 50 years of age (i.e., with AMD).

10.2.4.7.2

Macular Translocation

Surgical translocation of the macula is another surgical alternative to laser or drug treatment for wet AMD. In this technique,the neurosensory retina is surgically detached, then shifted away from the underlying subfoveal CNV to overly normal RPE (Au Eong et al. 2001; Fujii et al. 2002). The CNV can then be treated with thermal laser or other techniques. Two techniques have been developed. In the macular translocation surgery 360º (MTS360) technique, the entire retina is detached with 360º retinectomy (segmentation of the retina from its peripheral insertion) allowing macular rotation 5–20° from its original location (Terasaki 2001; Toth and Freedman 2001). The procedure is not without significant risks for intraoperative and postoperative complications such as retinal detachment, macular pucker, increased lens opacity in the phakic eyes, diplopia, and tilted image (Toth and Freedman 2001; Aisenbrey et al. 2002; Fujii et al. 2002). Also, the vitreous cavity is usually filled with silicone oil to

tamponade the retina in place, which often requires surgical removal or can lead to associated toxicity (Kampik and Gandorfer 2000). Subsequent extraocular muscles movement is usually required to realign the eye. However, recent case reports indicate that, in the hands of experienced surgeons, MTS360 can achieve excellent results in selected cases (Toth and Freedman 2001; Aisenbrey et al. 2002).

A less-extensive technique involves limited macular translocation (LMTS; de Juan and Fujii 2001; Fujii et al. 2001b, 2002). It consists of par- tial-thickness scleral resections near the equator at either the superotemporal or the inferotemporal quadrant followed by a near-total retinal detachment (de Juan et al. 1998; de Juan and Vander 1999; de Juan and Fujii 2001). The resected sclera edges are sutured, causing shortening of the sclera with subsequent reattachment of the retina, resulting in translocation of the fovea to an area overlying nonfoveal RPE and choroid. Preliminary case reports indicate the technique seems to be effective in selected cases (de Juan and Vander 1999; Ho 2000; Fujii et al. 2001a; Ohji et al. 2001; Sullivan et al. 2002; Chang et al. 2003). Currently a phase I/II clinical trial is under way comparing this surgical technique with PDT in eyes with subfoveal CNV secondary to AMD.

10.2.5

Future Research

10.2.5.1

Basic Scientific and Preclinical Research

As outlined above, many recent, exciting developments are occurring in clinical trials for the treatment of wet AMD. To a great extent, this progress is the result of outstanding basic scientific and preclinical research. In particular, excellent research data are available that address the paradigm of angiogenesis for neovascular AMD with in vitro systems and various animal models. However, less well developed are data supporting the potential contributions for the other paradigms. As described above, ongoing work from our and other laboratories suggests how research in these other paradigms

of CNV pathogenesis may result in improved knowledge and new therapeutic ideas.

10.2.5.2

Prevention of Vision Loss

CNV causes the most severe cases of vision loss in AMD (Green 1999), but minimal research is available to define the specific mechanism for retinal dysfunction. At least three possibilities explain vision loss: permanent retinal dysfunction due to death of photoreceptors (Young 1987; Curcio et al. 1996); retinal dysfunction due to leakage (Donati et al. 1999; Bressler 2001; Lim 2002); or dysfunction due to some other property, such as disruption of the bipolar-photore- ceptor synapse (Caicedo et al. 2003). The latter two are potentially reversible. In fact,the phaseII trials with Lucentis described above indicate that blockade of VEGF and improvement of retinal leakage results in improved vision in some

patients, proving reversible vision loss.

Recent work in our laboratory has suggested another mechanism for preventable or reversible vision loss in CNV. We hypothesize that the following sequences of events are induced in the retina overlying CNV. First, blood-de- rived macrophages invade the retina at onset of CNV, which infiltrate into the plexiform layers and co-localize with Muller cells (Fig. 10.14). Then, Muller cells become activated by mediators produced by infiltrating macrophages. Muller cell activation results in subsequent loss of neurotrophic factor production and other changes in function. Finally, the changes in the activated Muller cells result in disruption of the bipolar photoreceptor synapse (Fig. 10.15; Caicedo 2003; Caicedo et al. 2003). Much more work needs to be done in order to clarify and fully understand the pathogenesis that leads to vision loss in AMD.

Fig. 10.14. Fluorescent microscope photograph of a vertical section of a choroidal neovascular (CNV) lesion and retina under CNV. Left: Macrophages (green) invade the retina under CNV and predominantly localize to the outer and inner borders of the inner nuclear layer were they can be seen in close association with glial cells, such as Müller cells. Adjacent regions of the retina

away from CNV are practically devoid of macrophages. Right: Confocal microscope photograph of a vertical section of a retina under a CNV lesion showing activated Muller cells (white asterisks) in relation to a recruited circulating macrophage (white arrow). (CC choriocapillaris, ONL outer nuclear layer, OPL outer plexiform layer, INL inner nuclear layer, IPL inner plexiform layer)

Fig. 10.15. Fluorescent microscope photograph of a vertical section of a retina under a choroidal neovascular (CNV) membrane. Left: Control retina showing a normal distribution of a synaptic marker (vGluT, red). Right: Retina under CNV 4 weeks after experimental induction of CNV lesion. There is an abnormal redistribu-

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