Rapid Responses to:

EDITORIALS: Usha Chakravarthy Age related macular degeneration BMJ 2006; 333: 869-870 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Age-related macular degeneration: better tools are available to measure quality of life and visual outcomes

Clare Bradley, and Jan Mitchell   (27 October 2006)

Monoclonal antibodies to vascular endothelial growth factor (VEGF) provide vision for the future

Amit Patel   (30 October 2006)

The role of generic measures of health status in ARMD

John E Brazier, Carolyn Czoski-Murray, Jill Carlton   (14 November 2006)

Health status tools do not measure the impact of macular degeneration (AMD) on QoL: A reply to Professor Brazier and colleagues.

Jan Mitchell, Clare Bradley, Professor of Health Psychology, Royal Holloway, University of London.   (23 November 2006)

Age-related macular degeneration: better tools are available to measure quality of life and visual outcomes 27 October 2006
Clare Bradley, Professor of Health Psychology Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK, and Jan Mitchell Send response to journal: Re: Age-related macular degeneration: better tools are available to measure quality of life and visual outcomes	Editor We appreciate Professor Chakravarthy’s editorial 1 on our review of the literature on quality of life in macular degeneration (AMD) which was commissioned as a ‘White Paper’ by the AMD Alliance International to help raise awareness of the impact of AMD 2. We are pleased that Professor Chakravarthy has endorsed our key points including the view that widely used measures of health status and health utility do not capture the effects of AMD on quality of life. We comment on three issues: 1. Professor Chakravarthy wrote ‘The authors of the review recommend their own instrument the MacDQoL 3, which measures the impact of age- related macular degeneration on quality of life and can discriminate between mild and moderate disease’. Her further comment ‘The usefulness of this tool is difficult to assess, however, as what constitutes mild or moderate age related macular degeneration is not defined’ is an error. Definitions were given in the original paper 3 and in the White Paper (p12: severe, moderate and mild AMD were categorised by UK registration status: blind, partially-sighted or not registered) 2. It is possible that Professor Chakravarthy sought a definition in terms of clinical vision assessments unavailable in the first MacDQoL study 3 but included in a later study 5, longitudinal data from which are soon to be reported. Recent work has also indicated that the MacDQoL is likely to be more sensitive to visual acuity than the widely used measure of visual function, the National Eye Institute visual functioning questionnaire (NEI -VFQ) 4. 2. Professor Chakravarthy suggested that we were unduly harsh in criticising visual function measures for lacking sensitivity to disease severity of disease. She offered several very good reasons for the lack of sensitivity including the fact that people with AMD often develop adaptive strategies over time. We recognise that such factors as adaptation and rehabilitation will diminish the relationship between disease severity and visual function. We might expect even less relationship between disease severity and the impact of AMD on quality of life though the MacDQoL related sensibly to disease severity in our relatively small cross- sectional study 3. 3. In her final paragraph, Professor Chakravarthy suggested that an ideal instrument for use in wet AMD would be responsive to changes in visual function and quality of life as well as measuring satisfaction with treatment. It is not necessary, or even advisable, to have a single instrument to do all these things as they need different response options, question formats etc. We are currently completing qualitative research to design a measure of AMD treatment satisfaction, the MacTSQ. The MacTSQ is similar to the RetTSQ 6, designed to measure treatment satisfaction for diabetic retinopathy. Thus we will soon be able to supply the MacTSQ measure of treatment satisfaction for use along with our existing MacDQoL measure of the impact of AMD on quality of life and good measures of visual function, such as the NEI-VFQ 7, are also available. Together these instruments provide the tools needed to measure quality of life, treatment satisfaction and visual outcomes associated with age-related macular degeneration. References 1. Chakravarthy U. Age related macular degeneration. BMJ 2006;333:869 -870. 2. Mitchell J, Bradley C. Quality of life in age-related macular degeneration: A review of the literature: Royal Holloway, University of London/AMD Alliance International, 2006:http://amdalliance.org/documents/White%20paper%20amended%20final%20fcr%201909061.pdf. 3. Mitchell J, Bradley C. Design of an individualised measure of the impact of macular disease on quality of life (the MacDQoL). Qual Life Res 2004;13(6):1163-75. 4. Berdeaux GH, Mesbah M, Bradley C. Metric properties of the MacDQol in French, German, Italian and American populations: an individualised QOL instrument specific to macular disease. Value in Health 2006;in press. 5. Mitchell J, Wolffsohn JS, Woodcock A, Anderson SJ, McMillan CV, ffytche T, et al. Psychometric evaluation of the MacDQoL individualised measure of the impact of macular degeneration on quality of life. Health Qual Life Outcomes 2005;3(1):25. 6. Woodcock A, Plowright R, Kennedy-Martin T, Hirsch A, ffytche T, Bradley C. Development of the new Retinopathy Treatment Satisfaction Questionnaire (RetTSQ). Proceedings of Vision 2005; International Congress Series 2005;1282:342-346. 7. Mangione C, Lee P, Pitts J, Guierrez P, Berry S, Hays R. Psychometric Properties of the National Eye Institute Visual Function Questionnaire (NEI-VFQ). Arch Ophthalmol 1998;116:1496-1504. Competing interests: Clare Bradley and Jan Mitchell worked on the design and development of the MacDQoL and the design of the MacTSQ. Clare Bradley is the copyright holder and director of Health Psychology Research Ltd (HPRcontracts@aol.com)which licences questionnaires for others to use.
Monoclonal antibodies to vascular endothelial growth factor (VEGF) provide vision for the future 30 October 2006
Amit Patel, Senior House Officer in Cardiology The Heart Hospital, UCLH NHS Foundation Trust, 16-18 Westmoreland Street, London, W1G 8PH, UK Send response to journal: Re: Monoclonal antibodies to vascular endothelial growth factor (VEGF) provide vision for the future	Chakravarthy’s[1] discussion on the paucity of available validated tools for measuring quality of life, treatment satisfaction and visual outcomes in patients with neovascular age-related macular degeneration understates the recent advances in therapy for these patients, using visual acuity as the primary outcome measure. The advent of ranibizumab and bevacizumab, monoclonal antibodies to vascular endothelial growth factor (VEGF) A, represent the first therapy to improve visual acuity in most patients, regardless of lesion size and angiographic subtype. Monthly intravitreous ranibizumab, in a randomised placebo controlled double-blind study[2] and in a randomised double-blind study comparing it to verteporfin,[3] demonstrated a dose dependent (0.3 mg and 0.5 mg) improvement in visual acuity. These large studies reported a low incidence of serious adverse effects; endophthalmitis (1-1.4%) and serious uveitis (0.7-1.3%) [2, 3] Limited non-randomised data demonstrate both intravenous[4] and intravitreous[5] bevacizumab improves visual acuity. This drug is used to treat metastatic colorectal carcinoma but represents a cheaper option for the large numbers of mainly elderly patients afflicted with this devastating disease, and is currently being utilised by some ophthalmologists, awaiting a direct comparison between these two agents, if one occurs. [1] Chakravarthy U. Age related macular degeneration. BMJ 2006;333:869-70. [2] Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419-31. [3] Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432- 44. [4] Michels S, Rosenfeld PJ, Puliafito CA, Marcus EN, Venkatraman AS. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration twelve-week results of an uncontrolled open-label clinical study. Ophthalmology 2005;112:1035-47. [5] Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 2006;113:363-372. Competing interests: None declared
The role of generic measures of health status in ARMD 14 November 2006
John E Brazier, Professor of Health Economics School of Health and Related Research, University of Sheffield, Regent COurt, 30 Regent Street, Shef, Carolyn Czoski-Murray, Jill Carlton Send response to journal: Re: The role of generic measures of health status in ARMD	We were impressed to see such a broad ranging review of measures of health status and quality of life in ARMD by Professor Chakravathy. We agree with her conclusion that there is insufficient evidence about the validity of existing measures in this field, but we do not agree that existing measures should be so readily dismissed. Specifically, we felt that her review may have benefited from the results of a study we recently published that support earlier work of Brown and others. We undertook a study of 209 patients with unilateral or bilateral AMD at the Royal Hallmashire hospital in Sheffield (Espallargues et al, 2005, Bansback et al, 2006). Patients underwent visual tests (near and distant visual acuity (VA) and contrast sensitivity (CS)) and completed health status questionnaires including the VF-14 (vision specific) and three generic preference-based measures (HUI-3, EQ-5D, SF-6D) and time trade-off for own current state. The sample was predominantly elderly, the very population Professor Chakravathy was rightly concerned about. Our findings support her conclusion that the commonly used generic measures of EQ-5D and SF-6D failed to reflect differences in VA or CS. However VF-14, HUI-3, TTO (supporting the findings of Brown et al, 2 refs) were all found to be significantly related to VA and CS. Furthermore, we were able to achieve excellent levels of completion (over 97.5%). The HUI3 is a generic measure that contains a visual function dimension, and whilst it does not specifically address ARMD our findings suggest that it and TTO show promise in this condition. We accept that ultimately a specific measure may prove to be better, but what is needed is better psychometric evidence on the performance of these measures in terms of the conventional psychometric criteria of reliability, validity and responsiveness (Fitzpatrick et al, 1991). It should be borne in mind that condition specific measures are not always found to be more sensitive than generic measures (Fitzpatrick et al, 1999). Furthermore, some of the existing measures carry other advantages. The HUI3, for example, has been weighted using the values of the general population rather than largely arbitrary scoring systems used by many measures in this field and is suitable for use in cost effectiveness studies. The more widely used generic measures and measures of vision are also better able to capture side-effects of treatment and the consequences of co-morbities. References Bansback N, Espallargues M, Murray C, Lewis G, Carlton J, Hughes L, Brand C, Brazier J. Determinants of Health-Related Quality of Life and Health-State Utility in Patients with Age-Related Macular Degeneration: the Association of Contrast Sensitivity and Visual Acuity. Quality of Life Research 2006 (in press) Brown GC, Sharma S, Brown MM, Kistler J. Utility values and age- related macular degeneration. Arch Ophthalmol 2000; 118(1):47-51. Brown MM, Brown GC, Sharma S, Landy J, Bakal J. Quality of life with visual acuity loss from diabetic retinopathy and age-related macular degeneration. Arch Ophthalmol 2002; 120(4):481-4. Espallargues M, Czoski-Murray C, Bansback N, Carlton J ,Lewis G, Hughes L, Brand C, Brazier J. (2005) The impact of Age Related Macular Degeneration on health state utility values. Investigative Ophthalmology and Visual Science 46:4016-4023. Fitzpatrick R, Zeibland S, Jenkinson C, Mowat A (1993). A comparison of the sensitivity to change of several health status measures in rheumatoid arthritis. Journal of Rheumatology 20:429-36. Fitzpatrick R, DFavey C, Buxton M, Jones DR. Evaluating patient- based outcome measures for use in clinical trials. Health Technology Assessment 1998, 2(14). Competing interests: None declared
Health status tools do not measure the impact of macular degeneration (AMD) on QoL: A reply to Professor Brazier and colleagues. 23 November 2006
Jan Mitchell, Research Psychologist Royal Holloway, University of London, Egham, Surrey, TW20 0EX., Clare Bradley, Professor of Health Psychology, Royal Holloway, University of London. Send response to journal: Re: Health status tools do not measure the impact of macular degeneration (AMD) on QoL: A reply to Professor Brazier and colleagues.	At first reading, Professor Brazier and colleagues’ recent letter to the BMJ [1] suggests that they may have been confused at the time of writing. They refer to a ‘broad ranging review of measures of health status and quality of life in ARMD’ written by Professor Chakravarthy but, in fact, the review (commissioned as a ‘White Paper’ by the AMD Alliance International) was written by ourselves [2] and it was discussed in an editorial by Professor Chakravarthy [3]. Neither the White Paper nor the editorial was referenced by Brazier et al so the letter was misleading to those who had not read the editorial and the review to which it referred. Professor Brazier and colleagues go on to describe results published by Brazier’s team [4] and earlier work of Brown et al [5,6] which they suggest would have benefited Professor Chakravarthy’s review. In fact all three articles were referred to in our review and they helped to inform our conclusions including the view that widely used measures of health status and health utility do not capture the effects of AMD on quality of life. The papers by Brazier’s and Brown’s teams refer to and encourage the use of utility instruments such as the HUI-3 and time-trade off (TTO) as measures of quality of life in the AMD population. We have made the point that, regardless of whether these measures are sensitive to clinical outcomes such as visual acuity and contrast sensitivity they are not measures of quality of life. Indeed our work suggests that TTO is not a valid measure of either health status or quality of life [7]. Health economists may regard measures such as the HUI-3 and TTO as expedient instruments for calculating the cost effectiveness of interventions but this is not to say that they reflect patients’ experiences of AMD and its impact on their quality of life or, in the case of TTO, that they offer a fair assessment of disease severity. We feel that Professor Brazier and colleagues have been remiss in apparently criticizing Professor Chakravarthy’s editorial when it would have been more appropriate to refer directly to our review. What is needed is open discussion about these important measurement issues that, in the hands of NICE (National Institute for Health and Clinical Excellence), have such important implications for people at risk of severe vision loss from macular degeneration . References [1] Brazier J, Czoski-Murray CJ, Carlton J. The role of generic measures of health status in ARMD. BMJ. 2006;http://www.bmj.com/cgi/eletters/333/7574/869. [2] Mitchell J, Bradley C. Quality of life in macular degeneration: a review of the literature: Royal Holloway, University of London/AMD Alliance International, 2006: http://amdalliance.org/documents/White%20paper%20amended%20final%20fcr%201909061.pdf. [3] Chakravarthy U. Age related macular degeneration. BMJ 2006;333(7574):869-70. [4] Espallargues M, Czoski-Murray CJ, Bansback NJ, Carlton J, Lewis GM, Hughes LA, Brand CS, Brazier JE. The impact of age-related macular degeneration on health status utility values. Invest Ophthalmol Vis Sci 2005;46(11):4016-23. [5] Brown GC, Sharma S, Brown MM, Kistler J. Utility values and age- related macular degeneration. Arch Ophthalmol 2000;118(1):47-51. [6] Brown MM, Brown GC, Sharma S, Landy J, Bakal J. Quality of life with visual acuity loss from diabetic retinopathy and age-related macular degeneration. Arch Ophthalmol 2002;120(4):481-4. [7] Mitchell J, Bradley C. Measuring quality of life in macular disease: What use are utilities? Proceedings of Vision 2005; International Congress Series 2005;1282:654-658. Competing interests: Jan Mitchell and Clare Bradley worked on the design and development of macular disease-specific quality of life and related measures. Clare Bradley is the copyright holder and director of Health Psychology Research Ltd which licences questionnaires for others to use.