Age-related macular degeneration (AMD) has become one of the leading causes of irreversible blindness worldwide. With the advancement of stem cell technology, tissue engineering and biomaterials, cell-based therapy has been inspiring for many degenerative diseases. For its unique advantages, AMD has become one of the most promising fields for cell-based therapy, which involve retinal pigment epithelium (RPE) cells, induced differentiation of neural retina cells and related cytokine regulations. RPE cells can be derived from human embryonic stem cells (hESC) or Induced pluripotent stem cells (iPS). Recently hESC-derived RPE cells have been applied to patients with dry AMD with initial success in clinical trials. In terms of tissue engineering, studies are focused on factors affecting the long-term survival of transplanted cells, including tissue scaffolds, soluble hybrid materials and scaffold anchoring. This article briefly reviews the RPE differentiation, neural retina differentiation and related cytokines of cell-based therapy and scaffolds, materials, and cell-scaffolds interactions of tissue engineering in AMD treatment.
Replacement of diseased retinal pigment epithelium (RPE) cells with healthy RPE cells by transplantation is one option to treat several retinal degenerative diseases including age-related macular degeneration, which are caused by RPE loss and dysfunction. A cellular scaffold as a carrier for transplanted cells, may hold immense promise for facilitating cell migration and promoting the integration of RPE cells into the host environment. Scaffolds can be prepared from a variety of natural and synthetic materials. Strategies, such as surface modification and structure adjustment, can improve the biomimetic properties of the scaffolds, optimize cell attachment and cellular function following transplantation and lay a foundation of clinical application in the future.
Objective To investigate the therapeutic efficacy of transpupillary thermal therapy (TTT) for age-related macular degeneration (AMD) accompanied with subfoveal choroidal neovascularization (CNV). Methods Fifty-one eyes of 47 patients whose illness had been diagnosed as AMD by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were treated with diode 810 laser. There are 42 eyes of 39 patients had occult CNV and 9 eyes of 8 patients had classic CNV, and the average visual acuity in their fist diagnosis was 0.12. According to the focus size, the diameters of beam spot varied from 0.8, 1.2, 2.0, and 3.0 mm; and the power was 120, 160, 260 and 360mW correspondingly, with the duration of 60 seconds. The follow-up examination was performed once a month after the treatment, and repetitious treatment would be taken once to thrice if necessary. The follow-up period was 3~33 months with the mean of 10 months. Visual acuity, haemorrhage in ocular fundus, absorption of exudation, and the closure of CNV were examined in the follow-up examination. Results No immediate decrement of visual acuity or any other discomforts were found in all of the treated eyes soon after the treatment. The average visual acuity of 51 eyes was 0.16 in the last diagnosis, which remained no change in 68.62%; increased in 23.53% and decreased in 7.84% compared with that in the first diagnosis. The results of FFA and ICCG demonstrated that at the 3rd months after the treatment, the closure rate was 42.86% in occult CNV and 22.22% in classic CNV; and at the 6th month, the closure rate was 73.81% in occult CNV and 66.67% in classic CNV. The results of ophthalmoscopy showed that at the 3rd month after the treatment, partial or complete absorption of hemorrhage and/or exudates with various thickness of organized scarring tissue was found in 42 eyes with occult CNV; decrement of hemorrhage and exudates was observed in 7 out of 9 eyes with classic CNV; and new hemorrhage occurred in 1 eye. At the 6th month, in 27 eyes with occult CNV, new hemorrhage occurred in 3 including 2 eyes with occult CNV, new hemorrhage occurred in 3 including 2 eyes with faster absorption and remaining unchanged for 12 months; in 5 eyes with classic C NV, new hemorrhage occurred in 2, which was absorbed after treated again and remained stable in the 16-month followed-up. In 19 eyes with occult CNV which had been followed up for more than 6 months, hemorrhage disappeared in 5 and new hemorrhage occurred in 5. In the followed-up over 6 months, new hemorrhage occurred in 8 eyes with the recurrent rate of 15.6%. Conclusion TTT is effective for AMD with either classic or occult CNV. In the long-term followed-up, CNV recurs in 15.6% of the treated eyes which may be improved after the further treatment. (Chin J Ocul Fundus Dis,2004,20:280-284)
ObjectiveTo summarize the clinical results and safety of photodynamic therapy (PDT) through 4 years after single and multi-treatments of patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration(AMD). MethodsClinical data of 73 AMD cases (95 eyes) diagnosed through fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optic coherence tomography (OCT), treated with PDT were reviewed and analyzed in this hospital from June 2000 to June 2004. The changes of best corrected visual acuity (BCVA), fundus pictures, FFA, ICGA and OCT were compared before and after PDT. Follow-up time varied from 3 months to 4 years (mean, 2 years). ResultsThe mean age of 73 patients was 67.8 years old. The BCVA was from CF/10 cm to 1.0. At the final follow up, the BCVA was improved (increase≥2 lines) in 39 eyes (41.1%), stabilized (±1 line) in 51 eyes (53.7 %) and decreased 2 lines in 5 eyes (5.3%). Fundus hemorrhage and exudation reduced after PDT. FFA and ICGA showed CNV complete closure in 58 eyes (61.05%), partial closure in 6 eyes (6.32%), CNV incomplete closure in 22 eyes (23.16% ) and recurrence in 9 eyes (9.47%). After once PDT of 12 eyes with early-stage AMD, the BCVA improved (from 0.6 to 1.5), CNV completely closed, and the OCT showed disappearance of macular edema and neursensory retinal deta chment. No CN V recurred in our four years follow-up observation and the BCVA of the patients remained stable. The mean number of PDT treatment was 1.8 per eye in 95 cases. No serious local or systemic complications were encountered. ConclusionsSingle or multiple sessions of PDT can acheive long-term safety and efficacy. For early-stage AMD patients with minimally classic CNV, PDT can completely make CNV closed and reduce the risk of visual loss.(Chin J Ocul Fundus Dis,2004,20:275-279)
Atrophic age-related macular degeneration (AMD) does not show obvious loss of visual function in the early stage, so it is not easy to be taken seriously. In the advanced stage, most of the patients suffered from macular area retinal map atrophy, which affected night vision and central vision. Drugs currently used in clinical or clinical trials to treat atrophic AMD include drugs for improving choroidal perfusion, reducing the accumulation of harmful substances, preventing oxidative stress injury, inhibiting inflammatory reactions, as well as neuroprotectants and lipid metabolism drugs. Stem cell transplantation for atrophic AMD is currently the most promising treatment. In theory, it is feasible to replace atrophic AMD with retinal photoreceptor cells and RPE cells derived from human stem cell differentiation. However, there are still many problems to be solved, such as how to improve the efficiency of directional differentiation of seed cells and how to ensure the safe and effective RPE cell transplantation and survival after transplantation. At present, several studies have found that multiple locus mutations are associated with atrophic AMD, so gene therapy also plays an important role in the development of the disease.
The diagnosis and treatment of age-related macular degeneration (AMD) is an international hotspot of eye research. Successful clinical applications of antiVEGF drugs promoted both basic research and clinical practice of AMD. A number of countries and professional societies have established clinical guidelines for AMD management, including the epidemiology, risk factors, diagnosis, classification, and treatment process. These AMD guidelines are mostly based on recently published results of clinical trials, provided good model of evidence based medicine. It is urgent and necessary to have our own guideline which is suitable for Chinese patients. Reviewing and learning existed guidelines will help us to improve the clinical practice of AMD in China.
Objective To evaluate short-term effects of a single photodynamic therapy (PDT) treatment with visudyne (CIBA Vision Corp.) for choroidal neovascularization (CNV) in age-ralated macular degeneration (AMD). Methods Thirty cases (35 eyes) diagnosed as AMD patients with classic CNV were treated with PDT. The data of visual acuity testing, fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optic coherence tomography (OCT) were used to evaluate the effects of a single treatment of PDT before and 1 week, 1 ,3 month after treatment. Results The visual acuity of 34 eyes were stable or improved in 3 months follow-up;and the visual acuity of 1 eye was decreased. Decrease or dispearance of fluorescein leakage from CNV was noted in 19 eyes. No serious complication occurred. Conclusion Single treatment of PDT for CNV in AMD can achieve short-term decrease or cessation of fluorescein leakage from CNV without loss of visual acuity. (Chin J Ocul Fundus Dis, 2002, 18: 171-174)