Abstract
Chapter 1: Neovascular age-related macular degeneration (AMD) is a common eye disease in the Western countries among people over 60 years old. It causes a central scotoma, resulting in difficulties with daily life activities. The gold standard treatment consists of intraocular injections with anti-vascular endothelial growth factor (anti-VEGF). Submacular surgery, i.e. full macular translocation (FMT) and retinal pigment epithelium (RPE-) choroid transplantation, is reserved for cases that do not benefit from standard treatment.
Chapter 2: A retrospective study regarding FMT including 158 patients with a mean follow-up of 45 months showed a significant postoperative visual gain. Median best-corrected visual acuity (BCVA) improved from 20/160 Snellen to 20/100 Snellen one year after surgery. A ≥3 line gain was observed in 47% and 45% of the patients after one year and at last visit, respectively. The number of legally blind patients was significantly reduced. A subanalysis of patients with a ≥5 year follow-up still had a median significant visual improvement 5 years after FMT compared to baseline. Patients with proliferative vitreoretinopathy (PVR) (4%), recurrent choroidal neovascularization (CNV) (30%), and RPE atrophy (47%) had a worse outcome in the long term.
Chapter 3: Morphological change after FMT was evaluated in 51 patients with a mean follow-up of 30 months. Subretinal tissue complex and subretinal fluid disappeared in all patients except in case of recurrence (4%). The visibility of the external limiting membrane (ELM) decreased in 20%, remained stable in 51%, and increased in 29%. An increase of ELM visibility was correlated with an increased visual acuity. The foveal centre thickness was significantly correlated with the presence of the ELM. Predictive factors for a favourable surgical outcome were presence of ELM and mixed type CNV (type 1 + 2). Patients with intraretinal fluid, fibrotic lesions and non-responders to anti-VEGF had an unfavourable outcome.
Chapter 4: We studied the outcome of 81 patients that underwent RPE-choroid transplantation using a peripheral retinotomy. The mean follow-up was 38 months. There was a significant visual improvement from median 20/400 Snellen to 20/100 Snellen one year after surgery. A ≥3 line improvement was achieved in 53% of the patients after one year, and in 46% at last visit. Reading ability without low vision aids improved significantly. Out of 4 patients with an 8-year follow-up, 3 patients had a ≥6-line gain at last visit. Severe complications were submacular hemorrhage (10%), macular hole (7%) and PVR (4%). Nonperfusion of the graft was successfully treated with scraping of the Bruch’s membrane in six patients. Our results are favourable compared to previous literature reporting results of RPEchoroid transplantation using a parafoveal retinotomy.
Chapter 5: Five patients had a destructive inflammatory reaction after uncomplicated RPE-choroid transplantation. There was diffuse RPE atrophy, subretinal fluid and hyperreflective spots in the retina. In one patient the graft was replaced by a second graft because of a large hemorrhage. Histopathology of the explanted graft showed an increased number of B-cell lymphocytes in the choroid and T-cell lymphocyte infiltration. When testing for RPE-antibodies in these five patients and several control groups, we found no evidence for an auto-immune origin. Also human leukocyte antigen typing did not give the suggestion of autoimmune response. Negative results may be due to the study limitations, or because the inflammation was local or nonspecific.
Chapter 6: In this chapter we reflect on the abovementioned studies. After submacular surgery in AMD patients, some of the macular morphology and function can be restored. Extrafoveal RPE seems to be able to sustain the fovea, also in the long term. The most important predictive factor for surgical outcome is the integrity of the ELM. We observed five cases of inflammatory destructive reaction after RPE-choroid transplantation, even though the graft was autologous. Possibly, the graft was regarded as ‘dangerous’. However, we were unable to pinpoint what elicited this reaction. New treatments including stem cell replacement, prosthesis and gene therapy are emerging. Even though there are obstacles such as high costs, limited market size and technological limitations, these are promising techniques. Hopefully the results from our studies can contribute to these new developments.
Chapter 2: A retrospective study regarding FMT including 158 patients with a mean follow-up of 45 months showed a significant postoperative visual gain. Median best-corrected visual acuity (BCVA) improved from 20/160 Snellen to 20/100 Snellen one year after surgery. A ≥3 line gain was observed in 47% and 45% of the patients after one year and at last visit, respectively. The number of legally blind patients was significantly reduced. A subanalysis of patients with a ≥5 year follow-up still had a median significant visual improvement 5 years after FMT compared to baseline. Patients with proliferative vitreoretinopathy (PVR) (4%), recurrent choroidal neovascularization (CNV) (30%), and RPE atrophy (47%) had a worse outcome in the long term.
Chapter 3: Morphological change after FMT was evaluated in 51 patients with a mean follow-up of 30 months. Subretinal tissue complex and subretinal fluid disappeared in all patients except in case of recurrence (4%). The visibility of the external limiting membrane (ELM) decreased in 20%, remained stable in 51%, and increased in 29%. An increase of ELM visibility was correlated with an increased visual acuity. The foveal centre thickness was significantly correlated with the presence of the ELM. Predictive factors for a favourable surgical outcome were presence of ELM and mixed type CNV (type 1 + 2). Patients with intraretinal fluid, fibrotic lesions and non-responders to anti-VEGF had an unfavourable outcome.
Chapter 4: We studied the outcome of 81 patients that underwent RPE-choroid transplantation using a peripheral retinotomy. The mean follow-up was 38 months. There was a significant visual improvement from median 20/400 Snellen to 20/100 Snellen one year after surgery. A ≥3 line improvement was achieved in 53% of the patients after one year, and in 46% at last visit. Reading ability without low vision aids improved significantly. Out of 4 patients with an 8-year follow-up, 3 patients had a ≥6-line gain at last visit. Severe complications were submacular hemorrhage (10%), macular hole (7%) and PVR (4%). Nonperfusion of the graft was successfully treated with scraping of the Bruch’s membrane in six patients. Our results are favourable compared to previous literature reporting results of RPEchoroid transplantation using a parafoveal retinotomy.
Chapter 5: Five patients had a destructive inflammatory reaction after uncomplicated RPE-choroid transplantation. There was diffuse RPE atrophy, subretinal fluid and hyperreflective spots in the retina. In one patient the graft was replaced by a second graft because of a large hemorrhage. Histopathology of the explanted graft showed an increased number of B-cell lymphocytes in the choroid and T-cell lymphocyte infiltration. When testing for RPE-antibodies in these five patients and several control groups, we found no evidence for an auto-immune origin. Also human leukocyte antigen typing did not give the suggestion of autoimmune response. Negative results may be due to the study limitations, or because the inflammation was local or nonspecific.
Chapter 6: In this chapter we reflect on the abovementioned studies. After submacular surgery in AMD patients, some of the macular morphology and function can be restored. Extrafoveal RPE seems to be able to sustain the fovea, also in the long term. The most important predictive factor for surgical outcome is the integrity of the ELM. We observed five cases of inflammatory destructive reaction after RPE-choroid transplantation, even though the graft was autologous. Possibly, the graft was regarded as ‘dangerous’. However, we were unable to pinpoint what elicited this reaction. New treatments including stem cell replacement, prosthesis and gene therapy are emerging. Even though there are obstacles such as high costs, limited market size and technological limitations, these are promising techniques. Hopefully the results from our studies can contribute to these new developments.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 26 Jan 2023 |
| Place of Publication | Rotterdam |
| Publication status | Published - 2023 |