Objective lt;brgt;To evaluated the effect of transpupillary thermotherapy (TTT) on age-related macular degeneration (AMD). lt;brgt; lt;brgt;Methods lt;brgt;Sixty-two cases (62 eyes) of exudative AMD were managed with TTT. Before treatment, 58 cases underwent fundus fluorescein angiography(FFA),42 cases underwent simultaneous indocyanine green angiography (ICGA), and 56 cases underwent optic coherence tomography (OCT).TTT was delivered using a 810 nm diode laser with variable spot sizes 0.5-3.0 mm and power range 60-40 mW,60 seconds duration. Sixty-two cases were followed up for 1-10 months with 4.8 months average. lt;brgt; lt;brgt;Results lt;brgt;The visual acuities of last visit were compared with those before the treatment. The visual acuity was unchanged in 43 cases (69.3%), improved in 15 cases (24.2%), and declined in 4 cases (6.5%). OCT was re-done in 51 cases and compared with OCT images before TTT treatment. The height of macular edema was unchanged in 29 cases (56.9%), decreased in 18 cases (35.3%), and increased in 4 cases (7.8%). The amelioration of visual acuity was compatible with that of macular configuration in the majority of cases (74.5%). Only in 13 cases (25.5%) the amelioration of visual acuity lagged behind that of macular configuration. The re-treatment was performed in 18 cases (29.1%), probably due to insufficiency of laser power. No side-effect was found. lt;brgt; lt;brgt;Conclusion lt;brgt;TTT makes most of the cases of exudative AMD retaining or improving their visual acuity. The employment is secured. Further exploration is needed in order to obtain the parameters of the laser treatment. (Chin J Ocul Fundus Dis, 2002, 18: 180-183)
Optogenetics is a novel technique which combines optics with genetics. Using genetic means, a selected opsin protein is ectopically expressed in target neurons, which are then stimulated by light to moderate the neuronal circuit, as a consequence to regulate the animal's behaviors. Retinal degeneration like retinitis pigmentosa and aged macular degeneration causes visual impairment and eventual blindness. Optogenetics techniques have opened the door to creating artificial photoreceptors in the remaining retinal circuits of retinal degeneration retinas via gene therapy. However, there are still limitations in optogenetics technique, for example, potential risk in virus infection, the choice of target cells and the low visual resolution of the experiment animal. It has been reported that vision was successfully restored to a certain extent in animal model using optogenetics technique. With higher photosensitivity of opsin protein, longer activation kinetics and higher transfection efficiency of virus vector, optogenetics techniques' application in ophthalmology will be improved.
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.
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.
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.
Exudative or wet age-related macular degeneration (AMD) is characterized by the progressive growth of choroidal neovascularization (CNV). Anti-vascular endothelial growth factor (VEGF) drugs have been used in the control of the development of CNV and vision improvement, but there are still defects like frequent injections, drug resistance and so on. Radiotherapy can deactivate local inflammatory cell populations, and make CNV unstable in the absence of pericytes and VEGF stimulation, which induce apoptosis of the vascular endothelial cells. Therefore, radiotherapy is considered as a potential adjuvant treatment of anti-VEGF therapy. The current clinical approaches include epimacular brachytherapy (EMBT) and long-range stereotactic radiotherapy (SRT). SRT may be a preferred adjuvant treatment for patients receiving anti-VEGF therapy. Knowing the progress of radiotherapy for the treatment of exudative AMD may help us to fully understand the pathogenesis of wAMD in China
Vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and complements play key roles in the pathogenesis of age-related macular degeneration (AMD). Pegaptanib, the first therapeutic aptamer against VEGF165, has been approved by the Food and Drug Administration (FDA) of US for the treatment of exudative AMD. Another two aptamers E10030 and ARC1905, each target PDGF-B and complement C5 respectively, are undergoing clinical trials. Recent trends to treat AMD are combined therapies targeting multiple key molecules in the pathogenesis of AMD; aptamers against multiple targets may become the preferred drug for AMD.
Based on the pathogenic mechanisms of age-related macular degeneration (AMD), tremendous preclinical and clinical trials have demonstrated that cell transplantation which aim to replace impaired retinal pigment epithelium (RPE) with healthy RPE cells is a promising approach to treat AMD. So far, choices of cell sources mainly are autologous RPE, iris pigment epithelium, fetal RPE, human embryonic stem cell-derived RPE and human induced pluripotent stem cell-derived RPE, and some of them are undergoing clinical researches. Grafting manners in cell-based therapies are various including RPE sheet or RPE-choroid complex transplantation, RPE cell suspension injection, and RPE sheet transplantation with scaffolds. This review is limited to cell-based therapies for RPE that damaged first in the progress of AMD and focus on recent advances in cell sources, transplantation methods, preclinical and clinical trials, and the obstacles that must be overcome.
Objective lt;brgt;To study the clinical results and safty of photodynamic therapy (PDT) after single and multi-treatments of patients with subfoveal choroidal neovascularization (CNV) caused by wet agerelated macular degeneration (AMD). lt;brgt; lt;brgt;Methods lt;brgt;From July, 2000 to July, 2001, 20 wet AMD patients (31 eyes) 4788 years old (mean 68.2 years old) with best-corrected visual acuity from FC/10 cm to 0.6 diagnosed through optic coherence tomography (OCT), fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were treated with PDT. All cases were assigned to benzoporphyrin derivative mono acid (BPD) (6 mg per square meter of body surface area), administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm (Zeiss company, German) delivered 50 J/cm2 at an intensity of 600 mW/cm2 over 83 seconds on CNV. Visual acuity, photochrome of ocular fundus, OCT, FFA, ICGA were used to evaluate the effects of photodynamic therapy with BPD. Follow-up of these patients was planned 1-2 week and every 3 month after PDT. Once the lesion area progressed, PDT was applied again. Tweenty cases (31 eyes) were followed up from 3 to 18 months (average 12 month).In 1 affected eye, PDT was applied fow 4 times, 4 eye for 2 times, and the other 26 eyes for 1 time. lt;brgt;Results lt;brgt;The visual acuity in 13 (41.9%) eyes was improved (increase≥2 lines) after PDT. Stabilized (±1 line) in 17 (54.8%) eyes and decreased 2 lines（attributed to the recur of CNV ）in 1 (3.2%) eye. After PDT, the fundus haemorrhage and fluid leakage reduced. FFA and ICGA showed. cessation and obvious reduction of fluorescein leakage from CNV in all patients 2 weeks after photodynamic therapy, and retreatment decreased the leakage step by step. Fluorescein leakage from at least a portion of the CNV reappeared by 1-3 month after treatment in some cases. OCT also showed the reduction of the size of CNV, moreover, the edema of surrounding retina and choriodal and serous neural epithelial detachment recovered obviously. No side affect during and after PDT was noticed. lt;brgt;Conclusions lt;brgt;PDT with BPD can achieve short-term effect on part or total cessation of fluorescein leakage from CNV without loss of vision or growth of classic CNV in patients with age-related macular degeneration, retreatment of PDT was also effective. lt;brgt; lt;brgt;(Chin J Ocul Fundus Dis, 2002, 18: 175-179)