Development and Validation of Quality-of-Life Questionnaires for Birdshot Chorioretinopathy
Authors: John A. Barry, Annie Folkard, Alastair K. Denniston, Eileen Moran, William Ayliffe
Journal: Ophthalmology (2014)

Birdshot chorioretinopathy (BCR) is a rare form of chronic posterior uveitis, usually requiring long-term, systemic immunosuppression.1Rothova A. Berendschot T.T. Probst K. et al.Birdshot chorioretinopathy: long-term manifestations and visual prognosis.Ophthalmology. 2004; 111: 954-959Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar The severe impact of the disease on acuity, visual field, color discrimination, and electrodiagnostics is well-documented,1Rothova A. Berendschot T.T. Probst K. et al.Birdshot chorioretinopathy: long-term manifestations and visual prognosis.Ophthalmology. 2004; 111: 954-959Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar, 2Holland G.N. Shah K.H. Monnet D. et al.Longitudinal cohort study of patients with birdshot chorioretinopathy II: color vision at baseline.Am J Ophthalmol. 2006; 142: 1013-1018Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar but studies on quality of life (QoL) have been limited. Furthermore, existing QoL tools fail to capture the unique and wide range of symptoms associated with BCR and BCR medications. Ethical approval was granted by the Royal Free London Hospital. All procedures, such as prior informed consent, were conducted in accordance with the Declaration of Helsinki. Item development was via face-to-face meetings of the Item Generation Group (composed of 2 patients with BCR, a consultant ophthalmologist, and a psychologist). From this bank, 3 questionnaires were derived: the Birdshot Disease & Medication Symptoms Questionnaire (BD&MSQ) with 43 items, the QoL impact of BCR (QoL BCR) with 25 items, and the QoL impact of BCR medication (QoL Meds) with 25 items. The content of the 2 QoL questionnaires was similar, except that the QoL BCR focused on the daily impact of experiences attributable to the disease and the QoL Meds focused on the daily impact of experiences attributable to medication. Four-point Likert scales were used, with lower scores indicating worse QoL. The 3 questionnaires were then administered to a second group—8 volunteers with BCR and 1 person with no eyesight problems—as an on-line survey. Participants and Item Generation Group members were selected in accordance with the usual standards for survey methodology.3De Vaus D.A. Surveys in Social Research.5th ed. Allen & Unwin, London2002: 94-119Google Scholar A factor analysis of the questionnaires was conducted to refine their structure. The thresholds for acceptability were: Kaiser-Meyer-Olkin ≥ 0.6; Cronbach's α ≥ 0.7, and the factor loading threshold of >0.6.4Tabachnick B.G. Fidell L.S. Using Multivariate Statistics. Allyn and Bacon, 2001: 619-646Google Scholar All statistical analyses were done using SPSS 21 (IBM Corp, Armonk, NY). Members of BCR support groups and a community control group were invited by email to participate in an online questionnaire. Out of 292 support group members with BCR, 152 responded, a response rate of 52%. Seventy-three percent (111 of 152) were women. The age range was 29 to 76 years old, with a mean (± SD) of 53.12±9.63 SD. Of the 33 healthy community controls, it was possible to closely match 18 of them with the BCR group for age and sex. The matched controls had healthy eyesight apart from corrected refractive error. In the development of the BD&MSQ, after incomplete responses were eliminated, there were 141 BCR participants. Factor analysis found 21 items forming 8 factors, 2 factors representing a Birdshot disease symptoms domain, and 6 representing a medication symptoms domain. Together, these accounted for 57.75% of the variance in scoring after extraction. In the development of the QoL BCR, after incomplete responses were eliminated, there were 150 participants. Factor analysis revealed 20 items forming four factors, accounting for 71.98% of the total variance. In the development of the QoL Meds, after incomplete responses were eliminated, there were 126 participants. (This number is lower than the other 2 questionnaires because fewer participants reported medication use). Three factors were found, consisting of 12 items, accounting for 70.1% of the total variance. For all 3 questionnaires, the thresholds for acceptability for Kaiser-Meyer-Olkin, Cronbach's α, and factor loadings were met or exceeded. The subscales for the 3 questionnaires that resulted from the factor analyses are shown in Table 1 (available at www.aaojournal.org). Construct validity was assessed by comparing the BCR group and control group using Wilcoxon's tests. Table 2 (available at www.aaojournal.org) shows that the BCR group scored significantly lower than controls on the BD&MSQ and QoL BCR scales and subscales, at a minimum P < 0.01. The profile of non-BCR medication was similar in both groups. Figure 1 (available at www.aaojournal.org) shows box-and-whisker plots for the total scores for the 2 scales. (Comparison was not possible for the QoL Meds because controls did not take BCR medication). Construct validity was further assessed by comparing outcomes in BCR patients taking different amounts of prednisolone daily. Using analysis of covariance to control for any effect of the duration of time since diagnosis, patients with BCR taking >10 mg of prednisolone daily had significantly worse BD&MSQ (P < 0.01) and QoL BCR (P < 0.05), and non-significantly worse QoL Meds scores, compared with patients with BCR taking a lower dose or no dose of prednisolone daily. Concurrent validity was also assessed. For the BCR participants, there was a strong negative correlation between the Visual Function Questionnaire Utility Index health state classification5Kowalski J.W. Rentz A.M. Walt J.G. et al.Rasch analysis in the development of a simplified version of the national eye institute visual-function questionnaire-25 for utility estimation.Qual Life Res. 2012; 21: 323-334Crossref PubMed Scopus (30) Google Scholar and each of the new measures at a minimum of r = −0.546, P < 0.000001, indicating acceptable concurrent validity. In this study, we describe the development of 3 novel patient-reported outcome measures (PROMs) for BCR, directed toward capturing (a) key symptoms of BCR and symptoms of medication for BCR (BD&MSQ), (b) QoL (QoL BCR), and (c) the impact of BCR medication on QoL (QoL Meds), in this rare but debilitating condition. In addition to providing the first disease-specific PROMs for use in BCR, this study provides an example of how PROMs can be developed for even rare conditions. These new instruments (available from the authors) may be of value in clinical trials for this condition, with a view to assessing change in symptoms and QoL arising from either disease or medication. When using the BD&MSQ, we suggest that the 2 domains—disease symptoms and medication symptoms—be scored separately, because each provide important independent information. The medians shown in Table 2 (available at www.aaojournal.org) for each domain and subscale can act as a guide to the severity of QoL problems at baseline. For example, a BCR patient who scores an average of 2.67 on the Birdshot disease domain of the BD&MSQ can be considered to be experiencing a typical level of QoL difficulty for BCR patients. Validity and reliability measures indicate that these tools have excellent psychometric properties and so can be used with confidence for patient reporting of symptoms and QoL in BCR. Table 1Items for the final versions of the Birdshot Disease & Medication Symptoms Questionnaire (BD&MSQ), QoL impact of BCR (QoL BCR), and QoL impact of BCR medication (QoL Meds).SubscaleBD&MSQSubscaleQoL BCRSubscaleQoL MedsLights VisionFluttering lightsMood and relationshipsAngerMood and relationships VisionUnreasonable behaviorFlashing lightsDepressionPersonal relationshipsSimple repeat patternIrritabilityBeing a good family memberLoss of night visionAbility to socializeAngerSkinPoor light-dark adaptTearfulnessIrritabilityLoss of colorFrustrationUsing a computerLack of contrastAnxietyReadingSkin lesionsPersonal relationshipsDrivingSkin discolorationProfessional and work relationshipsWatching TVLumps under skinAbility to focusLow moodDepressionAnxietyBody painPainful musclesDaily activitiesWatching TVTearfulnessPain in legsUsing a computerAching jointsReadingWorkingBreathless & ShakyShakingBreathing difficultyUnhappy FamiliesFeeling violentMoodImpending doomUnreasonable behaviorDepressionBeing a good family memberSleepDisturbed sleepConstantly tiredFeeling unwellNauseaHair lossLoss of eyebrowsHeadacheLoss of hairUnwellOver-consuming alcohol Open table in a new tab Table 2Differences between the Groups of 18 Birdshot Chorioretinopathy (BCR) and Healthy Controls Matched for Age and Sex, for Birdshot Disease & Medication Symptoms Questionnaire (BD&MSQ) and QoL Impact of BCR (QoL BCR) ScoresOutcome MeasureGroupMedianInterquartile Range (Range)Wilcoxon's ZBD&MSQ visionBCR2.671.50 (1.1–3.8)−3.623***Control4.000.33 (2.8–4.0)BD&MSQ lightsBCR2.671.00 (1.0–3.7)−3.735***Control4.000.00 (3.7–4.0)BD&MSQ moodBCR3.001.50 (1.0–4.0)−3.091**Control4.000.50 (2.5–4.0)BD&MSQ body painBCR2.671.00 (1.0–4.0)−2.642**Control4.000.67 (2.3–4.0)BD&MSQ hair lossBCR3.001.50 (1.5–4.0)−3.015**Control4.000.00 (2.0–4.0)BD&MSQ skinBCR3.001.33 (2.0–4.0)−3.226**Control4.000.00 (3.3–4.0)BD&MSQ sleepBCR2.001.50 (1.0–4.0)−2.166*Control3.002.00 (1.0–4.0)BD&MSQ total scoreBCR2.760.56 (1.9–3.9)−3.363***Control3.760.48 (3.29–4.0)QoL BCR mood and relationshipsBCR2.401.30 (1.7–4.0)−3.416***Control3.900.10 (2.8–4.0)QoL BCR daily activitiesBCR2.501.75 (1.0–4.0)−3.250**Control3.750.50 (2.5–4.0)QoL BCR unhappy familiesBCR3.670.67 (2.3–4.0)−2.966**Control4.000.00 (4.0–4.0)QoL BCR feeling unwellBCR3.251.50 (2.0–4.0)−3.300***Control4.000.00 (3.8–4.0)QoL BCR total scoreBCR2.930.95 (2.2–4.0)−3.461***Control3.910.18 (3.3–4.0)*P < 0.05;**P < 0.01;***P < 0.001. Significance values are 2-tailed. Open table in a new tab *P < 0.05; **P < 0.01; ***P < 0.001. Significance values are 2-tailed.