Transpupillary thermotherapy for age-related macular degeneration: Principles and techniques

Transpupillary thermotherapy (TTT) is a subthreshold, low irradiance, long exposure duration, large spot size, infrared diode laser protocol. Retinal temperature increases in TTT for choroidal neovascularization (CNV) are substantially lower than those in conventional short-pulse photocoagulation, but they are maintained for 60 seconds to achieve therapeutic results. Treatment power is adjusted for retinal lesion size, chorioretinal pigmentation, macular elevation and media clarity. TTT uses 810-nm diode laser infrared radiation, which has no significant retinal phototoxicity. A parfocal laser delivery system is required to assure uniformity of irradiance across large diameter treatment spots. Relative contraindications for TTT include dense subretinal hemorrhage, prior focal photocoagulation and serous RPE detachment. Adverse events are rare, and include decreased vision and retinal arteriole occlusion. Randomized, prospective multi-center trials are underway to compare the results of TTT for occult CNV in age-related macular degeneration to the natural history of the disorder. Imaging, electrophysiologic or thermometric techniques may ultimately provide intra-operative or post-operative monitoring to assure the adequacy of TTT for CNV, despite the absence of ophthalmoscopically visible lesions.     

Transpupillary thermotherapy (TTT) for age-related macular degeneration

PURPOSE: To review the results of transpupillary thermotherapy (TTT) on choroidal neovascular membranes associated with age-related macular degeneration (AMD). MATERIALS AND METHODS: 35 eyes of 35 patients with AMD and choroidal neovascularization and exudation were treated with TTT and had fundus photographs and fluorescein angiography (FA) before and at least six months after TTT. 28 eyes had predominantly occult lesions as seen on FA, while 7 demonstrated primarily classic lesions. All were treated with 650mw power or less using the 810 nm diode laser (3000 micron spot, duration of 60 seconds). Visual acuity, lesion size, and amount of subretinal fluid were determined by results of examination and review of photographs and fluorescein angiograms. RESULTS: A 50% reduction in subretinal fluid was achieved in 67% of treated eyes overall, with stabilization of vision (less than three lines of visual acuity lost) in 86%. Complications from treatment were infrequent (9%) and involved hemorrhage noted in the region of treatment upon follow-up. CONCLUSION: TTT promotes resolution of subretinal fluid and appears to stabilize visual acuity in patients with exudative AMD.     

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity

Background: To examine the contribution of mutations within the Norrie disease (NDP) gene to the clinically similar retinal diseases Norrie disease, X‐linked familial exudative vitreoretinopathy (FEVR), Coat’s disease and retinopathy of prematurity (ROP). Methods: A dataset comprising 13 Norrie‐FEVR, one Coat’s disease, 31 ROP patients and 90 ex‐premature babies of <32 weeks’ gestation underwent an ophthalmologic examination and were screened for mutations within the NDP gene by direct DNA sequencing, denaturing high‐performance liquid chromatography or gel electrophoresis. Controls were only screened using denaturing high‐performance liquid chromatography and gel electrophoresis. Confirmation of mutations identified was obtained by DNA sequencing. Results: Evidence for two novel mutations in the NDP gene was presented: Leu103Val in one FEVR patient and His43Arg in monozygotic twin Norrie disease patients. Furthermore, a previously described 14‐bp deletion located in the 5′ unstranslated region of the NDP gene was detected in three cases of regressed ROP. A second heterozygotic 14‐bp deletion was detected in an unaffected ex‐premature girl. Only two of the 13 Norrie‐FEVR index cases had the full features of Norrie disease with deafness and mental retardation. Conclusion: Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non‐coding region was associated with only mild‐regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full‐term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long‐term outcome.     

贝伐单抗治疗老年性黄斑变性临床观察

目的：评价玻璃体腔内注射贝伐单抗（阿瓦斯汀）治疗老年性黄斑变性（age-related macular degeneration,AMD）的临床效果与安全性。方法：对48例50眼接受玻璃体腔注射bevacizumab（1.75mg）治疗的AMD患者进行回顾分析,通过常规眼科检查方法、光学相干断层扫描（OCT）、眼底荧光血管造影（FFA）和/或吲哚青绿血管造影（ICGA）等方法,观察治疗后1,3,7d; 1,6mo 最佳矫正视力（best corrected visual acuity,BCVA）、眼压、晶状体、玻璃体、黄斑中心凹厚度（central foveal thickness,CFT）和黄斑容积（total macular volume,TMV）变化,与治疗前对比分析。对注射后渗漏无明显改善或病情反复者进行眼内重复注射,所有病例都完成至少3mo的观察随访。玻璃体腔内注射avastin 1.75mg,每6wk注射一次。结果：在48例50眼患者中,平均年龄58±20.46岁。治疗前患者的基线平均对数BCVA为0.82±0.53,CFT为364.97±151.83μm,注药后1wk虽然平均CFT和TMV没有显著改善,但BCVA有显著提高,经平均9.7mo的随访,BCVA,CFT和TMV3项指标均较基线有显著改善,终末随访时BCVA提高至少两行者为32眼（64%）,稳定者为18眼（36%）。本组患者共接受了98次玻璃体腔内注射,平均注射次数为1.98次/眼,有50%患者再注射能在术后1wk使视力提高两行或两行以上。治疗过程中未发现严重不良反应。结论：玻璃体腔内注射bevacizumab治疗湿性AMD引起的CNV安全、副作用少,可改善患者的视功能（VA）,减轻黄斑水肿,减少CNV渗漏。但长期治疗效果需要进一步观察。     

Intravitreal bevacizumab (Avastin) in combination with verteporfin photodynamic therapy for choroidal neovascularization associated with age-related macular degeneration (IBeVe Study)

Background A novel alternative for combined treatment using verteporfin photodynamic therapy (PDT) has emerged as preliminary safety and efficacy data of the intravitreal use of the anti-angiogenic bevacizumab became available. In the current study we investigate the feasibility of intravitreal bevacizumab combined with verteporfin PDT for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Methods A single-centre, prospective, open-label study of 11 patients with documented CNV progression after PDT treatment who underwent combined PDT and intravitreal injection of 1.5 mg of bevacizumab was undertaken. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 2, 12 and 24. Clinical evidence of complications and changes in logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts and in fluorescein leakage from CNV were evaluated. Results The mean (±SD) age of the 11 patients was 74 (±5) years. Seven eyes had been treated with one previous PDT session and four eyes had two previous PDT sessions. The mean baseline logMAR ETDRS BCVA was 1.031 (Snellen equivalent, 20/200⁻²). At follow-up weeks 1, 2, 12 and 24, the mean logMAR ETDRS BCVA (Snellen equivalent) was 0.944 (20/160⁻²), 0.924 (20/160⁻¹), 0.882 (20/160⁺¹), and 0.933 (20/160⁻²), respectively. The change in BCVA from baseline was significant at each study follow-up interval (P ≤ 0.001); at 12 and 24 weeks, the mean change in BCVA from baseline was an improvement of 1.49 and of 0.98 ETDRS line, respectively. Fluorescein leakage from CNV was absent in all eyes at week 12. One additional treatment session was required in seven (63.6%) eyes at week 24 due to recurrent fluorescein leakage from CNV (“minimum” [<50% of the leaking area noted at baseline], n = 4; and “moderate” [>50% of the leaking area noted at baseline], n = 3). No progression of the neovascular lesion was observed at week 24. No safety issues were identified throughout the period of the study. Conclusions The overall changes in vision and fluorescein leakage from CNV throughout the study suggest that a possible synergistic effect may arise from the combination of intravitreal bevacizumab with verteporfin PDT for the treatment of neovascular AMD. In terms of funding, this was an investigator’s driven study.