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

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 30 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 "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 process.

Photodynamic therapy of experimental choroidal neovascularization in the mouse.

PURPOSE: To evaluate the qualitative and quantitative effects of verteporfin photodynamic therapy (PDT) on laser-induced choroidal neovascularization (CNV) in the mouse. METHODS: PDT was applied to the normal mouse fundus using light doses of 32, 64, and 83 s, and histological analysis of the treated areas was performed. CNV was induced using krypton laser photocoagulation of the fundus, and the CNV lesions were subsequently treated with PDT using light doses of 32, 64, and 83 s. Enucleated eyes were analyzed with light and transmission electron microscopies, and measurements of CNV size were done on histologic sections and on isolectin B4-stained choroidal flat mounts. RESULTS: PDT induced a light dose-dependent damage to the surrounding neural retina in normal eyes. At a light dose of 32 s, minimal damage was detected in the neural retina, whereas higher light doses caused distortion and disruption of the outer and inner nuclear layers and of the retinal pigment epithelium. When PDT was applied over laser-induced CNV lesions, the relative height of the lesions was significantly reduced (p < 0.05) using all light doses. Transmission electron microscopy 1 day after PDT treatment revealed occlusion of many of the CNV vessels. One week after PDT treatment, the CNV lesions contained patent vessels irrespective of light dose applied. Accordingly, PDT treatment inhibited (p < 0.05) but did not halt CNV lesion growth. CONCLUSIONS: PDT treatment of laser-induced CNV may create an acute occlusion of neovessels and an inhibition of CNV lesion growth without apparent injury to the surrounding neural retina. However, PDT-treated areas will remain vascularized with continued growth of the CNV lesion, which in turn may explain the often limited effect of PDT in patients with neovascular age-related macular degeneration. Elevating the PDT light dose will not increase the treatment effect substantially but may lead to increased collateral injury.

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 laser-induced CNV lesions, the height of lesions was significantly reduced (P < 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 +/- 0.89 in untreated mice, whereas in TTT-treated mice it was 1.69 +/- 0.35, 1.69 +/- 0.41 and 1.70 +/- 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.

Vision-related function after low-dose transpupillary thermotherapy versus photodynamic therapy for neovascular age-related macular degeneration.

PURPOSE: To compare the effects of low-dose transpupillary thermotherapy (TTT) and verteporfin photodynamic therapy (PDT) on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) in patients with occult neovascular age-related macular degeneration (AMD). METHODS: Patients were randomized to receive either low-dose TTT (and sham PDT) (n = 52) or PDT (and sham TTT) (n = 46). Patients were followed for 12 months with retreatment according to clinical assessment. The clinical outcome of this study has been recently reported. The NEI VFQ-25 questionnaire was administered at baseline and at 12 months. RESULTS: Forty-two patients (80.1%) in the TTT group and 37 patients (80.0%) in the PDT group completed the questionnaire at the 12-month follow-up. The mean change in the NEI VFQ-25 composite score was +1.2 for the TTT group (p > 0.05) and +0.7 for PDT group (p > 0.05). None of the subscale categories showed significant changes between treatment groups at 12 months. Subgroup analysis showed that NEI VFQ-25 scores were lower in patients treated in their better-seeing eye. CONCLUSION: In this randomized study on patients with occult neovascular AMD, low-dose TTT and PDT appeared to be equally potent at stabilizing patient-reported visual function. However, the study was underpowered for this conclusion to be made firmly. Also, given the impressive results obtained with ranibizumab for all types of neovascular AMD, neither PDT nor low-dose TTT should be considered as first-line treatments.