AMD COMPLICATIONS

What is the optimal approach for treating a patient with macular degeneration who develops a submacular haemorrhage? Jan van Meurs MD, a vitreoretinal surgeon at the Rotterdam Eye Hospital, and colleagues have initiated a prospective clinical trial to compare existing treatments.

Treatment options are generally quite limited and the prognosis is guarded. Intravitreal anti-VEGF agents are the standard of care for exudative AMD. However, they are not effective in restoring or improving visual acuity when a large submacular haemorrhage is present. Further, the haemorrhage causes not only immediate visual loss, it is also retinotoxic, leading to permanent damage. Designed with colleague Elsbeth van Zeeburg MD at the Rotterdam Ophthalmic Institute, the prospective, single-centre, comparative intervention study is randomising patients with a submacular haemorrhage of less than two weeks old to either a more invasive approach - vitrectomy followed by submacular rt-PA, intravitreal C3F8 / air mixture and intravitreal bevacizumab, or a less invasive approach utilising intravitreal (rather than submacular) rt-PA, C3F8 gas tamponade and intravitreal bevacizumab.

In preparation for this ambitious study, the researchers performed a literature review of the procedures. The Submacular Surgery Trial, a randomised, prospective trial published nearly 10 years ago, evaluated the outcomes of observation versus surgery. The trials found that vitrectomy with removal of the (older) subretinal haemorrhage could not improve or stabilise visual acuity compared to observation. However, eyes receiving surgery were more likely to avoid severe vision loss despite a higher complication rate compared with controls.

An alternative technique of more acute hemorrhages involves pneumatic displacement of the blood, to an area inferior in the eye, away from the fovea, where it causes less damage when resorbed. A standard vitrectomy is performed, subretinal tissue plasminogen activator (rt-PA) is delivered via a 41-gauge cannula, and gas is instilled into the eye. Postoperative half-prone (45° anterior headtilt) positioning can result in extramacular displacement of blood. A third technique, intravitreal injection of expansile gas such as SF6 or C3F8, along with the same half-prone positioning, with or without adjunctive intravitreal rt-PA, has also been described.

Despite the various possibilities, many patients have gone untreated because of the lack of proper comparative research to determine the safest and most effective modality or combination thereof. The recent trend has been towards the most invasive combination, namely vitrectomy followed by subretinal rt-PA and gas tamponade. However, whether the primary mechanism for haemorrhage displacement is the pushing or rolling action of a partial tamponade or the effect of gravity or pressure due to a complete tamponade is as yet unclear. Besides their review of the literature, Drs van Meurs and van Zeeburg had prior experience evaluating this procedure, although for another indication. In this case, it was for acute haemorrhages caused by retinal arterial macroaneurysms. In this study, large haemorrhages were completely displaced from the submacular retina of 10 of 11 patients. Mean visual acuity improvement of all patients was 1.3 logMAR, suggesting outcomes better than natural history.

Macular Function

But what about those patients whose macular function has been essentially destroyed in the course of exudative AMD? This includes those patients where anti-VEGF has proven futile; patients with AMD and a tear in the retinal pigment epithelium; or in patients with AMD and massive haemorrhage, too old to be displaced with rtPA (greater than14 days). The macular surgery research team has developed a technique to replace the damaged tissue with healthy autologous tissue. The surgeon removes the damaged choroid and RPE and translocates healthy choroid and RPE from the periphery to the macula. This free transplant is inserted under the retina via a parafoveal retinotomy.

Prof van Meurs, Dr van Zeeburg and Kristel Maaijwee MD, a fellow in vitreoretinal surgery, have made this topic a primary focus of their research work. A prospective study of 133 consecutive patients who underwent the procedure, reported encouraging results. Re-vascularisation and subsequent perfusion of the graft, as visualised on OCT, has been confirmed, with this study published in IOVS (Van Zeeburg et al, 2011, July 29 ; 52(8)). Fixation on the graft, as evaluated by microperimetry, suggests that the graft, and not the removal of the pathology submacular tissue or haemorrhage, was responsible for the preservation of macular function in these patients.

The multicentre, randomised trial comparing RPE-choroid graft surgery with anti-VEGFstarted in 2010 was, unfortunately, aborted because inclusion was as calculated in Rotterdam only, with the consequence that an insufficient number of patients could be recruited. The procedure is apparently not yet sufficiently standardised; a simplification of the technique (with a 180 degree peripheral retinotomy) may meet this failing.