Balancing risk in ophthalmic prescribing: assessing the safety of anti-VEGF therapies and the risks associated with unlicensed medicines.

Vascular endothelial growth factor (VEGF) inhibitor medications such as ranibizumab, pegaptanib and bevacizumab are in use for the treatment of neovascular age-related macular degeneration (AMD) and other retinal conditions, although only ranibizumab and pegaptanib are approved for these conditions. In contrast, bevacizumab was developed for the intravenous systemic treatment of colorectal cancer and is not formulated for intravitreal use, but is commonly used off-label in ophthalmology. European Union legislation permits the use of drugs outside the terms of their licence ('off-label') only under certain circumstances, such as during clinical trials, compassionate/named patient use in the absence of a licensed alternative, emergency scenarios (e.g., pandemics) or at the discretion of a treating physician. In such cases, patients should be fully informed regarding their treatment and any potential risks involved. Off-label drug use can be an important tool to provide patients with treatment in cases of unmet medical need. However, the use of an unlicensed medicinal product, when a suitable licensed alternative is available, puts prescribing physicians at risk of liability if safety issues arise. Emerging clinical evidence suggests safety differences exist between ranibizumab and bevacizumab

The letter contrast sensitivity test: Clinical evaluation of a new design

PURPOSE. To compare the reliability, validity, and responsiveness of the Mars Letter Contrast Sensitivity (CS) Test to the Pelli-Robson CS Chart.METHODS. One eye of 47 normal control subjects, 27 patients with open-angle glaucoma, and 17 with age-related macular degeneration (AMD) was tested twice with the Mars test and twice with the Pelli-Robson test, in random order on separate days. In addition, 17 patients undergoing cataract surgery were tested, once before and once after surgery.RESULTS. The mean Mars CS was 1.62 log CS (0.06 SD) for normal subjects aged 22 to 77 years, with significantly lower values in patients with glaucoma or AMD (P &lt; 0.001). Mars test-retest 95% limits of agreement (LOA) were &plusmn;0.13, &plusmn;0.19, and &plusmn;0.24 log CS for normal, glaucoma, and AMD, respectively. In comparison, Pelli-Robson test-retest 95% LOA were &plusmn;0.18, &plusmn;0.19, and &plusmn;0.33 log CS. The Spearman correlation between the Mars and Pelli-Robson tests was 0.83 (P &lt; 0.001). However, systematic differences were observed, particularly at the upper-normal end of the range, where Mars CS was lower than Pelli-Robson CS. After cataract surgery, Mars and Pelli-Robson effect size statistics were 0.92 and 0.88, respectively.CONCLUSIONS. The results indicate the Mars test has test-retest reliability equal to or better than the Pelli-Robson test and comparable responsiveness. The strong correlation between the tests provides evidence the Mars test is valid. However, systematic differences indicate normative values are likely to be different for each test. The Mars Letter CS Test is a useful and practical alternative to the Pelli-Robson CS Chart.<br /

Regression of Posterior Uveal Melanomas Following Cobalt-60 Plaque Radiotherapy

A method has been devised for evaluating the rate and extent of regression of the first 100 consecutive patients with a posterior uveal melanoma that we had managed by Cobalt-60 plaque radiotherapy at Wills Eye Hospital. It was found that the "average" posterior uveal melanoma in the series did not regress rapidly to a flat, depigmented scar but shrank slowly and persisted as a residual mass approximately 50% of the thickness of the original tumor at 54 months following Cobalt-60 plaque radiotherapy. We also found that the rate and extent of regression of the tumors in patients who subsequently developed metastatic melanoma were not appreciably different than the rate and extent of regression of the tumors in patients who remained well systemically. These observations indicate that the rate and extent of regression of posterior uveal melanomas following Cobalt-60 plaque radiotherapy are poor indicators of the prognosis of the affected patients for subsequent development of clinical metastatic disease

Economic Burden of Bilateral Neovascular Age-Related Macular Degeneration: Multi-Country Observational Study

Background: There is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD. Objective: To document the economic burden of bilateral NV-AMD, the late stage of AMD, in elderly patients, from a societal perspective. Study design, setting and participants: A cross-sectional, observational study surveyed 401 patients with bilateral NV-AMD and 471 non-AMD subjects in Canada, France, Germany, Spain and the UK. Physicians' records and subjects' standardized telephone interviews were used to record medical resource utilization, assistance with daily living and social benefits. Annual bilateral NV-AMD-related socioeconomic costs were calculated in _, year 2005 values. Main outcome measures: Societal costs including direct vision-related medical costs (e.g. treatment of AMD and vision-related equipment), direct non-vision-related medical costs (e.g. medications) and direct non-medical-related costs (e.g. home healthcare and social services) were the main outcome measures. Results: The demographic profile of NV-AMD patients was similar across countries; however, co-morbid condition profiles varied. NV-AMD patients reported substantial health-related problems and associated health resource utilization (HRU). In the previous 12 months, 12-22% of patients fell, and half of these patients required medical treatments. More than 20% (range 21-59%) of patients were prescribed vision-enhancing equipment. More than half of the patients (54-81%) were living with a spouse or family member and 19-41% reported receiving assistance for activities of daily living. The average annual societal cost per bilateral NV-AMD patient treated was estimated to be _7879 in Canada, _7349 in France, _12 445 in Germany, _5732 in Spain and _5300 in the UK, and direct vision-related medical costs accounted for 23-63% of the total cost. Half of the patients were diagnosed with bilateral NV-AMD for =1 year. Estimated annual societal costs of bilateral NV-AMD patients in these countries ranged from _268 to _1311 million. Estimated annual societal costs of all NV-AMD patients in these countries ranged from _671 to _3278 million. Conclusions: Bilateral NV-AMD imposes significant functional impairment on patients, leading to increased HRU and a high societal cost burden. Differences in national healthcare systems and NV-AMD treatment patterns were reflected in the wide variation of NV-AMD costs across the five surveyed countries. Even though the prevalence rates and per-patient costs varied by country, the societal costs of NV-AMD patients were substantial in each country. Earlier intervention with effective therapies is expected to reduce disease burden and disability associated with NV-AMD and, thus, decrease the overall societal cost.Age-related-macular-degeneration, Cost-of-illness, Elderly