Over 7 years, CLEK participants, on average, reported a decline in their V-QoL as measured by most NEI-VFQ scales. On scales for which a decline was seen, the decline was modest (see ), ranging from less than 1 point over 7 years (General Vision) to almost 2 points (Near Activities). The exceptions to this were Dependency, which declined considerably, and Mental Health and Ocular Pain, which improved. In both cases, we suspect that these were examples of changes in extreme attitudes of participants. As previously noted, we found in our baseline report that the average Mental Health score of CLEK participants with normal visual acuity was comparable to people with advanced blinding disease.11
Adaptation to their disease could possibly occur over time, resulting in reduced anxiety. This may explain the otherwise counterintuitive finding of a positive slope on the Mental Health scale in this cohort. Of note, although the mean Mental Health score increased, almost 17% of participants had a slope coefficient that, when extrapolated over 7 years, resulted in a 10-point decline in their scale score (see ). In contrast, at baseline the Dependency scale score was the highest. Not surprisingly, this scale exhibits the most severe response to disease progression because this scale had the greatest opportunity to decline.
Odds Ratios for a 10-point Decline in NEI-VFQ Scale Score Over Seven Years After Adjustment for Race, Education Baseline NEI-VFQ Scale Score, Incident Scarring Baseline VA and Curvature, and Changes in VA and Curvaturea
In our cross-sectional study, we found that the clinical indicators with the strongest association with lower V-QoL at baseline were visual acuity worse than 20/40 and corneal curvature ≥52 D. These baseline measures were not found to be significantly associated with changes in V-QoL on any scale except Dependency, for which a baseline corneal curvature of ≥52 D was associated with a decline in the scale score (see ). On the other hand, a 10-point change in visual acuity was found to be significantly associated with declines in all NEI-VFQ scale scores, except Ocular Pain. A 3.00 D or greater increase in curvature was associated with a decline in all scales except Ocular Pain, Social Function, and Color Vision. For the clinician, this may indicate that positive clinical measures at a single visit are not indicative of a good prognosis for a patient’s quality of life. It is the change in these clinical measures over time has the strongest influence on the patient’s attitude toward his or her disease and perception of its impact on visual function.
This relation was found to be robust in multivariate analyses in which we adjusted for race, education, baseline VFQ scale score, and clinical factors (see ). We found that a substantial minority of CLEK participants had a decline in V-QoL that, when extrapolated over 8 years, was ≥10 points. In the multivariate analysis, a decrease in binocular high-contrast visual acuity of more than 10 letters was associated with increased probability of a 10-point decline in scale scores on all scales except Ocular Pain and Driving, whereas an increase in corneal curvature greater than 3.00 D was associated with increased risk of a 10-point decline on all scales except General Vision, Social Function, and Color Vision. The significance of these findings becomes more apparent considering that the CLEK Study recently reported that over 7 years 19% of participants had a 10-letter loss in high-contrast, best-corrected visual acuity15
and that 25% of participants had a 3.00 D increase in first definite apical clearance lens.16
Clearly, a substantial plurality of people with keratoconus are at risk of substantial declines in their already low-perceived V-QoL.
The AREDS investigators previously reported the responsiveness of the NEI-VFQ to changes in clinical status (i.e., loss of 15 letters and/or change in lens opacity) of elderly people with chronic disease.12
They found that the NEI-VFQ was responsive to changes in visual acuity on most scales but less responsive to changes in lens opacity. In our study of younger adults with keratoconus we found that the NEI-VFQ was responsive to less-severe changes in clinical status. When considered alongside the results reported by the AREDS investigators, our findings provide compelling evidence of the responsiveness of the NEI-VFQ to clinically significant change in visual acuity for study participants across a range of ages and types of ocular disease.
We also report that the NEI-VFQ is responsive to clinically significant changes in corneal curvature in people with keratoconus. This is of particular interest given that corneal curvature (or keratoconus) was not considered a clinical factor by the team that designed the NEI-VFQ.9
In univariate analysis (see ) we found that change in corneal curvature was significantly associated with change on all scales except Ocular Pain, Social Function, and Color Vision. We also found that people with the 3.00 D increase in corneal curvature were at significantly increased risk of a 10-point decline in V-QoL on all scales except General Vision, Social Function, and Color Vision. Importantly, change in curvature was associated with substantially increased risk of a large decline on the ocular pain (odds ratio, 1.92) and mental health (odds ratio, 3.49) scales and on both scales was the most potent predictor of a 10-point decline for that scale. As previously noted, these two scales had very low scores at baseline and showed a mean increase in the scores over 7 years of follow-up. This provided further evidence of the responsiveness of the NEI-VFQ to a clinically significant change in a subgroup of patients.
Our exclusion of people with penetrating keratoplasty at baseline, as well as censoring all observations at PK, limits the generalizability of our findings to people who have not had PK or to people who may be contemplating the procedure. PK is a preferred method to manage keratoconus in people who become contact lens intolerant.17
The CLEK investigators have shown that lower scores on the NEI-VFQ Ocular Pain and Distance Vision scores are modestly predictive of PK after adjustment for other clinical factors.18
Our group has also shown in preliminary analyses that PK patients report substantially improved V-QoL, particularly after transplantation of the fellow eye (Kymes SM, et al. IOVS 2004;45:ARVO E-Abstract 1376). However, our intention in this investigation was to demonstrate the influence on changes in commonly measured clinical factors (visual acuity, corneal curvature, corneal characteristics, etc.) on V-QoL for the “average” person with keratoconus. More complete consideration of PK on V-QoL will have to be the subject of future investigations.
We characterized change in V-QoL as a slope of responses given at a minimum of three CLEK examination visits. The purpose of this method was to minimize the influence of extreme reports on the change in V-QoL. In taking this approach, we may have understated or overstated changes in quality of life. If that is the case, the result may be a biased estimation of the reported associations. However, because the trend seen in most scales is negative (indicating a decline in V-QoL), our smoothing technique more likely resulted in an underestimation of the change in V-QoL rather than an overestimation. This being the case the associations reported here likely represents a conservative estimate of the relation between changes in clinical factors and self-reported quality of life.
Clinical examination of people with keratoconus typically reveals normal entrance and best-corrected visual acuity as well as modest ocular comorbidity. As a consequence, the common clinical wisdom is to assume keratoconus to be a disease of modest consequence to those who bear its burden. Combining the results here with our previous report, we have shown that its impact on patients, from their perspective, highly significant, and gets worse with time. We hope with these findings we have lain to rest the concept that keratoconus is a disease of modest consequence, and that policymakers will be inspired to ensure that clinicians and researchers have the resources necessary to address the needs of those who suffer the consequences of keratoconus.