Surgical Therapy

Core Messages

›The term “maculoplasty” is a future vision.

›So far, “surgical therapy” stands for the autologous replacement of affected retinal pigment epithelium by a hybrid of functioning retinal pigment epithelium and choroid.

›Macular translocation and relocation of a free pigment epithelium choroid transplant are currently practised simultaneously.

›Rupture of pigment epithelium, anti-VEGF nonresponder and massive submacular bleeding are potential indications for surgical therapy.

›Transplantation is technically possible in dry age-related macular degeneration and macular dystrophy. The chances of success are currently being investigated.

18.1Maculoplasty

The term “maculoplasty” goes back to Del Priore [1]. “Maculoplasty” signalizes a reconstruction of the atrophic macula. In Germany, nine-tenths of

B. Kirchhof

Department of Ophthalmology, University of Cologne, Cologne, Germany

e-mail: bekirchhof@googlemail.com

affected people with age-related macular degeneration (AMD) are in the end-stage of the disease (450,000 patients) [2]. This means that the macula, and in particular the photoreceptors, are atrophied. Since retinal tissue, like the whole central nervous system, does not regenerate, the restoration of the macular function needs a replacement not only of the retinal pigment epithelium (RPE), but especially of the photoreceptors. However, recent experiments with fetal allogenic retinal full thickness grafts failed because the nerve cells do not cultivate synapses with donor retina and gradually atrophy in the subretinal space. On the other hand, stem cells do not develop to photoreceptors underneath the atrophied macula. Efforts are currently being made to cultivate stem cells already in vitro to more or less mature photoreceptors and to put them into the subretinal space in their differentiated phase. This way, they will keep their differentiation, survive and may be able to develop synapses with local tissue. In an animal experiment, a first photoreceptor transplantation has been successful [3]. Admittedly, the receiving retina was not degenerated and still not mature.

Until we succeed in building up an atrophied macula neuronally, we will have to depend on operating in the early stage of the illness. Currently, “maculoplasty” can only mean the replacement of the affected retinal pigment epithelium and the choroid. However, the replacement is a precondition to at least maintain the functioning of the macula. The degradation of macular tissue cannot be stopped without pigment epithelium. This is generally accepted as a result of

the “Submacular Surgery Trial” [4]. Inthe“Submacular Surgery Trial” only choroidal neovascularizations were extracted from underneath the macula. An improvement of vision, or at least a delay in vision loss, could not be achieved. Basically, the exudative macular degeneration was merely transferred into dry progression. Therefore, in clinical application “surgery of macular degeneration” currently means to provide macula at an early stage of AMD with intact or only marginally affected retinal pigment epithelium and choroid.

18.2Macular Translocation

Macular translocation is known as the displacement of the macula on less affected RPE. For this, the complete retina has to be lifted from the pigment epithelium and separated from the ora serrata. However, by pivoting the retina around the optic nerve head, one gains just as much mobility to relocate the macula into the former position of the temporal vessel arcades [5]. The correct position of the retina (retinotopy) remains unchanged after displacement. Consequently, the patient sees a vertically offset, tilted and more or less twisted environmental picture. Within surgery of proliferative vitreoretinopathy (PVR), the retinal surgeon is familiar with complete retinal detachment and its treatment by means of 360° retinotomy. He knows the psychological strain of patients with double image perception when the macula cannot be put back exactly into its former position. The experts were all the more astonished when Robert Machemer suggested in 1998 to displace the macula deliberately in order to avoid the affected RPE area [6]. The reward was that for the first time it was possible to slow down the degeneration of the macula and in particular cases (submacular hemorrhage) to achieve a visual improvement. Meanwhile, there are medical histories with stable reading visual acuity for over more than 10 years!

Retinal surgeons have had to learn how to detach the retina as non-traumatically as possible (dark adaptation, calcium depletion, submacular BSS injection). Only a few retinal surgeons (more in Europe than in the USA) are making an effort to develop the surgical technique further. They combine the displacement of

Table 18.1 Comparison of advantages and disadvantages of macula translocation (left column) with free transplant (patch, right column)

the macula with a corresponding displacement of the ocular muscles in order to achieve a compensatory counter rotation of the eyeball. Thus, the position of the macula can be more or less maintained in the same location, while the RPE, choroid and sclera underneath the retina are moved away by rotation. The tilt of the visual impression cannot be completely compensated. Vast efforts of the surgeons and willingness of the patients to comply reflect the psychological strain of macular degeneration. Preservation of macular function is gained through loss of vision in both eyes and impairs spatial orientation. Typically patients orientate themselves (walking, catching) with the “bad” eye (not operated on), while they read with the operated eye. In spite of all efforts, 10% of patients have permanent diplopia (Table 18.1). Only the remaining functional eye should be treated applying this technique.

Macular translocation is not suited for treatment of dry AMD since sufficient intact pigment epithelium is often only found outside the temporal vessel arcade. The few experiments carried out to help patients with dry AMD by means of macular translocation were unsuccessful. Underneath the displaced macula a new pigment epithelium atrophy develops [7]. Even so, macular translocation has been an important improvement

in the therapy of AMD. It proves the significance of the pigment epithelium in the prognosis of AMD. In isolated cases the functional results permit reading acuity over many years, so that some surgeons still adhere to this practice today.

18.3Single Cell Suspensions

At about the same time as the macular translocation trial, an experiment transplanting isolated pigment epithelium cells suspended in a culture medium took place for the first time (single cell suspension). This intervention is only a minor expansion of the already established technique of submacular membrane extraction. There are far less surgical complications with this method than in macular translocation as the macula is not displaced and the retina only has to be detached by infusion into the subretinal space at the posterior pole [8]. The surgical complication rate is approximately that of submacular membrane extraction or macular pucker peeling. Available cell types are RPE and iris pigment epithelium (IPE). It had previously been shown that the IPE could adopt functions of the RPE. Unfortunately, the functional results with IPE as a single cell suspension are not significantly better than after membrane extraction without pigment epithelium replacement. Also, no considerably better results were achieved with autologous RPE as a single cell suspension. The most probable reason for this failure is that in order to survive and function, RPE and IPE need a suitable base to which they can affix themselves. The conditions underneath the affected macula do not offer any or only insufficient possibilities for cell adhesion. On the one hand, Bruch’s basal membrane is often removed together with the choroidal neovascularization; on the other hand, age-related changes of Bruch’s membrane are in conflict with cell adhesion. The question as to which is the most suitable cell type is not as important as the question as to which might be the most suitable substrate for anchorage and survival of the cells. All the same, the search is still going on for a suitable RPE replacement that can be cultivated outside the eye and then probably be moved into the subretinal space as a cell composite on an artificial basal membrane. These experiments are in the preclinical trial phase at present.

18.4Pigment Epithelium-Choroid Translocation (Patch)

The free transplant of pigment epithelium and choroid evades the problem of cell anchorage. The cells are not detached, but removed together with the Bruch’s membrane and choroid [9]. Fortunately, within a short time the transplant can attach itself to the choroidal vessels at the new location. After just 4 weeks, Barbara Parolini (2010) [10] was able to prove transplant perfusion by means of ICG angiography. The vessel anastomoses succeeded to the edge of the transplant. A second lucky incident is that the pigment epithelium is not generally prone to fibrotic overgrowth. There are many free fibroblasts in the choroid of the transplant as well as in the receiving choroidal bed. However, fibrotic encapsulations are mostly observed when the pigment epithelium area of the transplant is small or when wound healing is stimulated by blood (secondary bleeding).

Up to now, autologous transplantations have been performed. The advantage is that immune reactions can be avoided. The en bloc tissue is obtained from the vitreous cavity and does not have to be moved into the eye ab externo by means of sclerotomy. The disadvantage of this is that the cells will have aged. A therapeutic success is only to be expected when the peripheral RPE can cope with the metabolic requirements underneath the macula. Thus, a race between life expectancy of the patient and age-related changes of the transplant begins. From long-term experiences (over more than 7 years) one can expect that autologous peripheral RPE functions sufficiently long underneath the macula so that it is not necessary to substitute it with younger allogenic RPE cells from a source outside the eye. Particularly, as technical difficulties during the insertion of the transplant into the eye and the danger of immune reaction would have to be coped with. Functional long-term results, as reported by Jan van Meurs, are comparable to those of macular translocation. Reading acuity has been proven to be stable over more than 5 years. To give up macula translocation in favor of the free transplant is also supported by many other benefits (Table 18.1). The patch method is also applicable to “first eyes.” There are no double images. However, the PVR risk could not be reduced significantly.