How do you know?

H ow do you know if your patient improves with any particular therapy? In the treatment of patients with vision threatening uveitis, the primary goal of therapy is far from universally accepted. Should the end point be improvement in visual acuity? An obvious choice but flawed since many patients benefit without a discernable change in acuity measurements. Cataract and macular scars can limit the improvement in acuity even as inflammation is controlled. In addition, acuity measurements do not reflect lighting, effort, or the sporadic variability that some patients observe with uveitis. Should the goal be reduced inflammation as judged by examination? How about improved visual function as judged by patient questionnaire or by physician assessment? Can a drug be deemed efficacious if it results solely in the reduction in a potentially toxic medication such as corticosteroid? Is stabilisation of acuity an adequate goal? If judging benefit is so complex, is there a way to use a single instrument to accommodate multiple potential end points? As we enter an era of trying to base medical decision making on evidence, we need to decide what evidence to accept. Rheumatologists have long faced a similar dilemma in judging the efficacy of treatments for autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. The solution has been to rely on expert panels that have tested composite scores which combine objective measures of disease activity with functional outcomes. These disease indices include the ACR20, ACR50, ACR70, ACR-N, ACR-AUC, and DAS. 2 For example, the ACR20 is defined as 20% improvement in tender and swollen joint scores plus 20% improvement in three out of the following five parameters: patient’s global assessment, physician’s global assessment, level of pain on a visual analogue scale, health assessment questionnaire measuring function, and sedimentation rate. This instrument has been widely employed in judging benefit in clinical trials for rheumatoid arthritis. The randomised controlled trial (RCT) is generally considered the gold standard for assessing clinical efficacy. RCTs are frequent in some medical fields such as oncology and they are increasingly common in the treatment of rheumatological diseases. RCTs in ophthalmology such as the ONTT, COMS, OHTS, and the ETDRS have provided insights that now guide many therapeutic decisions. RCTs have only rarely been undertaken for ocular inflammatory disease, in part because of the relative rarity of these diseases. But RCTs for uveitis are also challenging because judging efficacy is not a straightforward task. Thus, some trials begin with inflammation that is quiescent and ascribe efficacy if other systemic immunosuppressive therapy is reduced. Other trials judge efficacy based on the more conventional improvement in visual acuity. A measure of efficacy that could accommodate patients with active disease who are failing conventional therapy, patients with controlled disease who are receiving potentially toxic therapy, and patients whose visual function improves even without a measurable change in visual acuity would be a major boon to encouraging clinical trials.