Surgical Options for Macular Degeneration
Numerous surgical approaches have been attempted to treat the exudative form of age related macular degeneration, such as surgical removal of subfoveal CNV, removal of subfoveal hemorrhage, macular translocation, and transplantation of the pigment epithelium. Removal of the CNV together with extensive hemorrhage in age related macular degeneration was first described by de Juan in 1988. The first visual results of membrane excision were disappointing with visual improvement in only 0 to 33% of the cases. Evaluation of the removal of subfoveal CNV compared with observation has been conducted between 1997 and 2003 by the Submacular Surgery Trials (SST). The SST showed that this surgical alternative therapy did not improve vision. A retrospective meta-analysis evaluating 647 cases of subretinal membrane excision in age related macular degeneration subjects showed that improvement was achieved in about 33% and deterioration occurred in 27%. Moreover, the recurrence rate of CNV was approximately 25%, and the progression of the atrophic scar size led to further visual loss. In a patient with recent macular hematoma secondary to CNV, different surgical options may be considered. The pneumatic displacement of the submacular hemorrhage with SF6 or C3F8 may allow an improvement of the visual acuity. More aggressive options including three-port vitrectomy, eventual TPA injection, hematoma removal, CNV excision, and gas tamponade have been proposed with variable functional and anatomical results. Despite these limited results, there are still some indications for submacular surgery, such as for patients with low preoperative visual acuity due to large hemorrhagic or fibrotic membranes.
The first retinal translocation surgery for age related macular degeneration was done by Machemer in 1993. The development of a partial retinal rotation combined with a scleral shortening has been tested for several years. Because of the very small angle of rotation, the high rate of recurrence (approximately 50%), and the availability of other therapies (vPDT), this technique is no longer implemented. A complete 360-degree retinotomy, which allows a higher rotation angle of the retina, has been proposed in the second eye-affected patients. Long term reports have shown favorable visual results with 52% of the subjects having one or more lines of improvement, specifically reading vision and contrast sensitivity after one year. A high rate of PVR (approximately 30% of the cases in inexperienced hands and between 8% to 18% in experienced hands) limits the use of this surgical technique. However, retinal rotation with 360-degree retinotomy may be an alternative in a very large CNV, when it does not respond to new therapies or when it is associated with large hematomas.
The disappointing visual results after CNV excision were explained by the simultaneous mechanical removal of the RPE layer and the transplantation of the RPE seemed to be a logical solution to restore vision. Currently, different techniques of autologous transplantation of the RPE are under evaluation. The iris pigment epithelial transplantation has been proposed, but this tissue is incapable of expressing crucial enzymes of the retinoid visual cycle. Investigators proposed the use of RPE suspension cells harvested through a nasal retinotomy at the beginning of the surgery and transplanted in the sub-retinal macular space after the excision of the CNV. A prospective trial was conducted with autologous suspension cell transplantation after membrane excision compared to membrane excision alone. At 12 months, visual improvement of two or more lines was achieved in 52.5% of the transplantation group (21.5% in the excision alone group), 32.5% remained the same, and 15% had a decrease of vision (21.5% in the excision alone group). The statistical analysis of far visual acuity showed just a trend in favor of the transplanted group, but the statistical analysis of the multifocal ERGs showed a significant difference between the two groups, with better results in the transplanted group. Another transplantation technique using a full thickness RPE-choroid sheet has been proposed by some researchers with interesting results regarding the long-term survival and the revascularization of the transplanted tissue . This technique uses a RPE-choroid flap taken in the superior mid-periphery, which is directly introduced through the macular retinotomy into the subretinal space. This particular technique, however, seems to be traumatic and presents a high rate of PVR.
The two main limitations of “one-time” autologous transplantation techniques are the graft size and the quality of the RPE and the Bruch’s membrane. Culturing prior to transplantation may offer the potential to at least partially influence or reverse aging and the lipofuscin load per cell might be reduced by dilution during cell division. This “rejuvenation” process may also be combined with a potential gene defect correction. Unfortunately, the right surgical technique (with a prosthetic Bruch’s membrane) and a viable method of culturing are not yet available. RPE-like cells generated from embryonic stem cells, neural stem cells, or bone marrow derived cells, however, may represent the future of the RPE transplantation in age related macular degeneration.