Transpupillary thermotherapy and Photodynamic therapy for neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among elderly in industrialized nations, and promises to extract an even greater toll with the imminent demographic shift. Neovascular AMD (wet AMD) often develops quickly and involves the growth of new blood vessels under the retina (choroidal neovascularization, CNV). These new blood vessels tend to be fragile and often leak blood and fluid. The blood and fluid elevates the macula, the central part of the retina, causing rapid visual loss. Without treatment the prognosis is poor with profound impact on an individual s ability to perform daily tasks. Photodynamic therapy (PDT) has been the most common treatment for neovascular AMD. PDT uses a cold laser to seal the leaking blood vessels. This involves injecting a lightsensitive drug that reaches and coats the abnormal blood vessels via the blood stream. The drug is then activated by light leading to a local occlusion of new vessels. Transpupillary thermotherapy (TTT) is technique in which a laser-induced subretinal vascular occlusion can be created through a small temperature elevation but without any photosensitive drugHowever, there has been a controversy about the optimal TTT laser intensity and controlled clinical trails demonstrating efficacy in neovascular AMD have been lacking. The first two studies of the thesis demonstrate that PDT as well as TTT can reduce experimental CNV, without causing damage to the surrounding tissue. A cellular damage in surroundning tissues was however seen at higher dosage. The therapeutic window is thus narrow for both treatments underscoring the importance minimizing treatment doses. We also found that both TTT and PDT induce an immediate thrombosis and cessation of perfusion in CNV areas, but after PDT some areas remained vascularised while after TTT the closure of the abnormal vessels proceeded for at least one week. The third and fourth studies of the thesis were on a prospective clinical study, randomizing 98 patients with neovascular AMD (occult CNV) to either low-dose TTT or PDT. During a follow-up of 12 months, no significant differences between the two groups emerged. The proportion of patients with stabilized visual acuity was approximately 75% in both groups and the two treatments were equally potent at stabilizing patient-reported visual function. Recently intravitreal anti-VEGF has become the first line treatment for neovascular AMD demonstrating superior efficacy for all forms of neovascular AMD. However, anti-VEGF is expensive and requires repeated injections. The use of PDT as an adjuvant to anti-VEGF therapy has been suggested to decrease both the cost and the need for repeated injections. Also this combination may prove beneficial regarding control of lesion growth. The results of this thesis, showing that low dose TTT may be equipotent to PDT, suggests that TTT may be a cost-effective adjuvant to intravitreal anti-VEGF treatment

Subthreshold transpupillary thermotherapy reduces experimental choroidal neovascularization in the mouse without collateral damage to the neural retina

PURPOSE. Transpupillary thermotherapy (TTT) is currently being evaluated for treatment of choroidal neovascularization (CNV) in age-related macular degeneration. To optimize TTT for CNV, the effect was analyzed of invisible (subthreshold) or visible (threshold) doses of TTT on the normal mouse retina and on experimental CNV. METHODS. TTT was delivered to the normal retina of 42 mice with a diode laser at increasing power settings (50, 60, 70, or 80 mW), to obtain thermal lesions ranging from invisible (subthreshold) to visible (threshold) burns. CNV was induced in 53 mice by krypton laser photocoagulation of the fundus, after which the CNV lesions were treated with TTT (50, 60, or 80 mW). Eyes were enucleated 7 days after TTT and prepared for histology, and the CNV complex was evaluated on hematoxylin-eosin stained serial sections by measuring the maximum height of the CNV lesions. Ultrastructural changes were examined by transmission electron microscopy. RESULTS. Increasing the TTT laser power yielded gradually more visible effects. At 50 mW, which induced subthreshold burns, no damage was seen in the neural retina, retinal pigment epithelium (RPE), or choroid at any time point. By contrast, eyes treated with higher power exhibited progressively more damage to the neural retina, including a complete disruption of the outer nuclear layer. When TTT was applied to the laserinduced CNV lesions, the height of lesions was significantly reduced (P Ͻ 0.001) in response to all three power settings at 7 days after treatment. The mean relative thickness of the CNV lesion was 3.29 Ϯ 0.89 in untreated mice, whereas in TTTtreated mice it was 1.69 Ϯ 0.35, 1.69 Ϯ 0.41 and 1.70 Ϯ 0.17 at power settings of 50, 60, and 80 mW, respectively. The overlying neural retina showed no apparent damage with the 50-or 60-mW settings, whereas outer nuclear layer disruption occurred with a power of 80 mW. Electron microscopy confirmed the presence of vascular occlusion at 1 day and a fibrotic scar at 7 days after TTT. CONCLUSIONS. Subthreshold TTT can effectively occlude newly formed vessels and cause regression of the experimental CNV complex without damaging the neural retina. The results demonstrate the importance of using subthreshold laser power in experimental and clinical evaluation of TTT. (Invest Ophthalmol Vis Sci. 2004;45:1969 -1974) DOI:10.1167/iovs.03-1329 I n the Western world, age-related macular degeneration (AMD) is a leading cause of central vision loss in patients older than 60 years. AMD can be subgrouped into exudative and nonexudative forms, depending on the formation of choroidal neovascularization (CNV). Despite a lower prevalence of exudative AMD compared with nonexudative AMD, approximately 80% of severe vision loss occurs secondary to the formation of CNV. 1 Although laser photocoagulation for some forms of CNV reduces the incidence of severe visual loss, photocoagulation damages the overlying neural retina, resulting in an immediate decline of visual function corresponding to the laser-treated area. A new therapeutic era in photodynamic therapy (PDT) was started by the use of a photosensitizing dye (verteporfin) and a low laser power setting. PDT can close newly formed subretinal vessels without substantial damage to the neural retina, and its efficacy of occluding subfoveal (predominantly classic) CNV is well documented. 2 Transpupillary thermotherapy (TTT) is a technique in which vascular occlusion can be induced without the use of photosensitive dye, by delivering radiation at near infrared intensity (810 nm) to the target tissue through the pupil. TTT is successfully used as an adjunctive treatment for choroidal melanoma. 3 However, TTT in this setting usually causes localized retinal destruction, retinal vascular occlusions, and nerve fiber bundle defects. 10 In TTT, a low increase in temperature (10°C), maintained for 60 seconds, is used to treat CNV. However, there is controversy about the clinical safety of TTT for CNV. This limits the possibility of applying an optimal dose of TTT, making under-and overtreatment a potential problem. Consequently, reports of neuroretinal and RPE damage after TTT for CNV have been published. In the present study, we analyzed the effect of TTT on the normal mouse retina and on experimental CNV in response t

Mapping standard ophthalmic outcome sets to metrics currently reported in eight eye hospitals

To determine alignment of proposed international standard outcomes sets for ophthalmic conditions to metrics currently reported by eye hospitals. Mixed methods comparative benchmark study, including eight eye hospitals in Australia, India, Singapore, Sweden, U.K., and U.S. All are major international tertiary care and training centers in ophthalmology. Main outcome measure is consistency of ophthalmic outcomes measures reported. International agreed standard outcomes (ICHOM) sets are available for cataract surgery (10 metrics) and macular degeneration (7 metrics). The eight hospitals reported 22 different metrics for cataract surgery and 2 for macular degeneration, which showed only limited overlap with the proposed ICHOM metrics. None of the hospitals reported patient reported visual functioning or vision-related quality of life outcomes measures (PROMs). Three hospitals (38%) reported rates for uncomplicated cataract surgeries only. There was marked variation in how and at what point postoperatively visual outcomes following cataract, cornea, glaucoma, strabismus and oculoplastics procedures were reported. Seven (87.5%) measured post-operative infections and four (50%) measured 30 day unplanned reoperation rates. Outcomes reporting for ophthalmic conditions currently widely varies across hospitals internationally and does not include patient-reported outcomes. Reaching consensus on measures and consistency in data collection will allow meaningful comparisons and provide an evidence base enabling improved sharing of "best practices" to improve eye care globally. Implementation of international standards is still a major challenge and practice-based knowledge on measures should be one of the inputs of the international standardization proces

Die sammlung Eduard Gans : Otto Helbing

[Vente. Numismatique. 1928-12-11. Munich]Avec mode text

Mapping standard ophthalmic outcome sets to metrics currently reported in eight eye hospitals

Abstract Background To determine alignment of proposed international standard outcomes sets for ophthalmic conditions to metrics currently reported by eye hospitals. Methods Mixed methods comparative benchmark study, including eight eye hospitals in Australia, India, Singapore, Sweden, U.K., and U.S. All are major international tertiary care and training centers in ophthalmology. Main outcome measure is consistency of ophthalmic outcomes measures reported. Results International agreed standard outcomes (ICHOM) sets are available for cataract surgery (10 metrics) and macular degeneration (7 metrics). The eight hospitals reported 22 different metrics for cataract surgery and 2 for macular degeneration, which showed only limited overlap with the proposed ICHOM metrics. None of the hospitals reported patient reported visual functioning or vision-related quality of life outcomes measures (PROMs). Three hospitals (38%) reported rates for uncomplicated cataract surgeries only. There was marked variation in how and at what point postoperatively visual outcomes following cataract, cornea, glaucoma, strabismus and oculoplastics procedures were reported. Seven (87.5%) measured post-operative infections and four (50%) measured 30Â day unplanned reoperation rates. Conclusions Outcomes reporting for ophthalmic conditions currently widely varies across hospitals internationally and does not include patient-reported outcomes. Reaching consensus on measures and consistency in data collection will allow meaningful comparisons and provide an evidence base enabling improved sharing of â best practicesâ to improve eye care globally. Implementation of international standards is still a major challenge and practice-based knowledge on measures should be one of the inputs of the international standardization process