To determine vision-related quality of life (QoL) measured with the National Eye Institute Visual Function Questionnaire (NEI-VFQ) in keratoconus (KCN) patients who have undergone penetrating keratoplasty (PK) in 1 or both eyes and to compare the results of our study to those of historical controls.
Clinical-based, cross-sectional study.
setting: Wills Eye Institute, Cornea Service, Thomas Jefferson University, Philadelphia, Pennsylvania. study population: This study included 149 consecutive patients who had undergone PK for KCN. intervention: Between June 1, 2008 and December 31, 2008, the NEI-VFQ was administered to 149 patients. The relationship between demographic and clinical factors and NEI-VFQ subscale scores was evaluated. main outcome measure: Vision-related quality of life.
Eighty-three of 149 patients (55.7%) were male. Approximately half of the patients (76/149; 51.0%) had PK in both eyes. Visual acuity with current correction in the better eye was better than 20/40 in 80% of patients (119/149). Our sample had significantly lower (worse) NEI-VFQ scores compared to Collaborative Longitudinal Evaluation of Keratoconus (CLEK) historical control group for the subscales of role difficulties, dependency, driving, and peripheral vision. In general, scores of our sample were between scores of patients with age-related macular degeneration (AMD) category 3 and 4. Patients with visual acuity better than 20/40 (in the better eye) showed significantly higher scores in all subscales except color vision. There was a significant relationship between minimum time since the graft of 5 years or greater and NEI-VFQ overall score better than AMD category 3 ( P = .004).
Despite satisfactory results on visual outcome measures obtained after PK, vision-related QoL in KCN patients remains impaired.
Keratoconus (KCN) is a progressive, asymmetric, noninflammatory condition of the cornea associated with corneal steepening and apical thinning that leads to decrease in vision secondary to progressive irregular astigmatism. KCN mainly affects young adults. A mean age of 39.2 years at the time of enrollment was reported in the large series of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study patients. Although 77.9% of these patients had a best-corrected visual acuity (VA) of 20/40 or better in both eyes, significant impairment in vision-related quality of life (QoL), with average scores comparable to category 3 and category 4 age-related macular degeneration (AMD), has been shown by the CLEK study group. Given that most KCN patients are young adults in their prime earning and child-rearing years who usually maintain good VA despite the chronicity of KCN, this was an unexpected result.
Penetrating keratoplasty (PK) is a well-accepted treatment for advanced KCN. Overall, 12% to 20% of patients with KCN eventually require PK at a relatively young age. The long-term success rate of PK for KCN has been well described in terms of the visual acuity and graft clarity, with a 25-year graft survival rate of 85% and 20/40 or better vision in 66% to 91% of patients followed more than 15 years.
The National Eye Institute-Visual Function Questionnaire (NEI-VFQ) is a vision-targeted survey that assesses the impact of visual impairment on the quality of life. The purpose of this report is to determine vision-related QoL based on self-reported results from the NEI-VFQ in KCN patients who have undergone PK in 1 or both eyes and to compare the QoL in KCN patients after PK to those without PK as reported in the CLEK study. The relationship between subscale scores of NEI-VFQ and clinical measures of outcomes after PK was also evaluated.
Material and Methods
The research protocol and informed consent were approved by the Wills Eye Institute Institutional Review Board; all study patients provided written informed consent, and the study was in accordance with Health Insurance Portability and Accountability Act (HIPAA) regulations.
Consecutive patients were enrolled from July 1, 2008 to December 31, 2008 when they came for ophthalmic examination on the Cornea Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. Primary inclusion criterion was PK in either 1 eye or both eyes attributable to KCN. We excluded patients with less than 1 year follow-up after PK, because stable visual outcomes are not usually achieved by the first year after PK. If a patient had PKs in both eyes or had a repeat PK in either eye, at least 1 year of follow-up after the most recent PK was required. We did not exclude patients who had intraoperative or postoperative complications (eg, cataract, wound dehiscence, secondary glaucoma) to avoid bias toward patients with uneventful postoperative courses.
The questionnaires were completed before the ophthalmic examination to reduce the influence of the clinical encounter on patient responses and were returned to the investigator (E.H.Y.) and not seen by the treating physician. The 25-item NEI-VFQ, the short-form version of the 51-item NEI-VFQ, was used to assess the vision-related QoL. A 14-item appendix was also administered to all patients to enhance the reliability of various subscales of the 25-item NEI-VFQ. Thus the NEI-VFQ used in this study contained 39 items and 12 domains or subscales including general health, general vision, pain or discomfort in or around the eyes, difficulty with near activities, difficulty with distance activities, limitations in social functioning, mental health symptoms related to vision, role difficulties, dependency, driving difficulties, and limitations with color vision and peripheral vision. The subscale scores, ranging from 0 (worst) to 100 (best), were calculated according to the published algorithm.
Data Collection and Statistical Analysis
The patients’ records were reviewed for the following data: demographics (age, sex, and ethnicity), number of PKs (unilateral, bilateral, or repeat PK), age of graft (calculated by subtracting the enrollment date from the date of surgery), use of contact lenses, and actual visual acuity (Snellen visual acuity with their usual correction) in each eye. The eye with better actual visual acuity was defined as the better eye. Steep keratometric values by topography (Zeiss Corneal Topography System Model 995; Carl Zeiss Meditec Inc, Dublin, California, USA) were recorded for the better and worse eyes.
The mean and standard deviation for each of the NEI-VFQ subscale scores was computed for the current sample, and a z-score was used to determine whether the mean for the current sample was significantly different from the mean of both historical controls reported for KCN and AMD patients. Effect sizes (computed as the mean difference divided by the average standard deviation) were used to illustrate the relative magnitude of the differences in means (effect sizes are: small = 0.20, medium = 0.50, large = 0.80).
A series of analyses of general linear models were used to compare differences in the mean NEI-VFQ scale scores, for baseline clinical and demographic variables. For ordinal and interval predictor variables (eg, age, VA), the initial regression modeled the predictor as a continuous covariate. Subsequent analysis-of-variance models used clinically important cutoff points for continuous covariates. Stratification variables included sex (female, male), ethnicity (Caucasian, African American, Hispanic, Asian), age at the time of enrollment (<30 years, 30–50 years, >50 years), PK (unilateral PK vs bilateral PK), age of graft (<5 vs ≥5, <10 vs ≥10, <15 vs ≥15 years), visual acuity in the better eye (≥20/40 vs <20/40, ≥20/25 vs <20/25), visual acuity in the worse eye (≥20/40 vs <20/40 and ≥20/25 vs <20/25), steep keratometric (steep K) values in both eyes (<45 diopters [D], 45-52 D, >52 D), and contact lens wear in at least 1 eye.
In order to account for the inclusion of both unilateral and bilateral grafts in the present sample, 3 graft age variables were computed for each cutoff point: mean, minimum, and maximum age of graft. Since graft age is taken as the average age for bilateral grafts, repeating the analysis using the minimum and maximum graft age serves to pick up possible differences by graft age that may be masked by taking the average for bilateral PKs. Differences in the mean steep K values by graft age group (<5 years, 5-10 years, >10 years) were also analyzed. Tukey-adjusted post hoc contrasts were used for multiple comparisons involving stratification variables with more than 2 levels. Finally, the Fisher exact test was used to assess the relationship between 2 categorical variables.
A total of 149 consecutive KCN patients were enrolled during the study period. Table 1 summarizes the baseline demographic and clinical variables for the patients. The mean age (± SD) at the time of enrollment was 53.9 ± 13.5 years (range, 24 to 87). There were slightly more male patients in the sample (83/149, 55.7%), and the majority of patients (122/149, 81.9%) were Caucasian. About half of the patients (76/149, 51.0%) had PKs in both eyes. Almost 80% of patients (119/149) had a VA better than 20/40 and 60% (90/149) had a VA 20/25 or better in the better eye. A majority of better eyes (124/149, 83.2%) had undergone PK.
|Number of Patients (n)||%|
|Hispanic or Latino||3||2.0%|
|Contact lens wear|
|One eye only||35||23.5%|
|Any rigid gas-permeable CL use in PK eye||68||45.6%|
|Corneal scarring present (either eye)||21||14.1%|
|Steep keratometric reading (better eye)|
|Steep keratometric reading (worse eye)|
|Visual acuity (better eye)|
|Better than 20/40||119||79.9%|
|20/40 or worse||30||20.1%|
|Visual acuity (worse eye)|
|Better than 20/40||55||36.9%|
|20/40 or worse||94||63.1%|
|Visual acuity (better eye)|
|20/25 or better||90||60.4%|
|Worse than 20/25||59||39.6%|
|Visual acuity (worse eye)|
|20/25 or better||29||19.5%|
|Worse than 20/25||120||80.5%|
|Mean ± SD (range)|
|Age at enrollment (y) (N = 149)||53.9 ± 13.5 (24 to 87)|
|Age of graft (better eye) (N = 120)||15.6 ± 10.1 (1 to 54)|
|Age of graft (worse eye) (N = 105)||13.9 ± 9.9 (1 to 52)|
Comparison of NEI-VFQ Scale Scores with Historical Controls
Results indicated that the current sample had significantly lower (worse) scores compared to the cross-sectional CLEK QoL study for the subscales of role difficulties, dependency, driving, and peripheral vision. The effect sizes were small (ranging from 0.21 to 0.33) for the CLEK historical control group.
The analysis considered differences between the current sample and the 2 historical controls based on AMD cutoff values (using mean cutoff values for AMD category 3 and 4 for the historical controls). Results showed that, in general, our sample group had lower (worse) scores compared to AMD category 3 scores for all NEI-VFQ scores, except color vision. Effect sizes ranged from a “small” decrement for general vision to a “large” decrement for mental health, role difficulties, and driving. When compared to cutoff scores for AMD category 4, the current sample generally showed higher (better) scores for all subscales except ocular pain (where our sample group had significantly worse scores) and peripheral vision (no significant difference) ( Table 2 ).
|Current Study||CLEK Study||ARED Study AMD Category 3||ARED Study AMD Category 4|
|Scale||Mean||SD||Mean||SD||P Value a||ES||Mean||P Value a||ES||Mean||P Value a||ES|
Differences in NEI-VFQ Subscale Scores by Demographics and Clinical Variables
Mean NEI-VFQ subscale scores by gender, age, and clinical variables are reported in Supplemental Table 1 ( Supplemental material at AJO.com ) and Table 3 . There were differences on a number of subscales by gender. In general, male patients had significantly higher (better) scores compared to female, including scores for general health, ocular pain, distance activities, mental health, role difficulties, dependency, driving, peripheral vision, and overall score. There were no statistically significant differences in the mean subscale scores between different age groups and between patients with bilateral or unilateral PKs.
|Better Eye VA||Worse Eye VA||Contact Lens Wear|
|20/40 Cutoff Point||20/25 Cutoff Point||20/40 Cutoff Point||20/25 Cutoff Point||Either Eye||PK Eye|
|Scale||>20/40 n = 119||≤20/40 n = 30||≥20/25 n = 90||<20/25 n = 59||>20/40 n = 55||≤20/40 n = 94||≥20/25 n = 29||<20/25 n = 120||Yes n = 84||No n = 65||Yes n = 68||No n = 81|
|General health||76.3 a||68.3||78.4 a||68.9||78.5 a||72.4||81.1 a||73.1||77.4 a||71.1||76.1||73.5|
|General vision||76.1 a||63.9||77.1 a||68.3||81.7 a||68.9||84.6 a||71.0||76.7 a||69.7||78.0 a||70.0|
|Ocular pain||78.0 a||67.1||77.4||73.5||80.7 a||73.0||83.6 a||74.0||78.0||73.1||78.1||73.9|
|Near activities||81.2 a||69.0||82.5 a||73.1||84.9 a||75.2||82.8||77.8||80.6||76.4||80.5||77.3|
|Distance activities||79.8 a||61.2||80.8 a||68.8||83.4 a||71.7||84.8 a||73.9||78.9 a||72.4||80.4 a||72.4|
|Social function||93.7 a||79.9||93.6 a||86.9||96.8 a||87.5||96.0 a||89.7||92.9||88.4||94.0 a||88.4|
|Mental health||77.9 a||62.5||77.3||70.9||81.9 a||70.6||84.3 a||72.5||76.2||73.0||77.5||72.6|
|Role difficulties||79.5 a||60.8||80.2 a||68.9||81.9 a||72.1||82.8 a||74.0||76.1||75.2||77.4||74.3|
|Dependency||92.3 a||73.6||93.1 a||81.6||92.5||86.2||94.4||87.1||91.2||85.0||92.7 a||85.0|
|Driving||73.1 a||46.2||76.8 a||54.2||77.0 a||62.7||77.0||66.1||72.1||62.9||73.0||64.1|
|Peripheral vision||84.7 a||65.8||84.7 a||75.0||89.5 a||75.8||90.5 a||78.5||83.6||77.3||85.3 a||77.1|
|VFQ-39 overall||81.8 a||66.5||82.5 a||73.0||84.8 a||75.2||85.7 a||77.1||80.8||76.0||81.7 a||76.2|
Patients with visual acuity (in the better eye) that was better than 20/40 showed significantly higher scores in all subscales except for color vision, compared to patients with visual acuity of 20/40 or worse (effect sizes ranged from a low ½ standard deviation to 1 standard deviation difference). Similar results were found for 20/40 visual acuity in the worse eye, although effect sizes were generally smaller (there were no significant differences for dependency or color vision).
Patients with visual acuity (in the better eye) that was 20/25 or better showed significantly higher overall and subscale scores except for ocular pain, mental health, and color vision, compared to patients with vision worse than 20/25. The effect sizes were about ½ standard deviation. A slightly different pattern of results was found for visual acuity of 20/25 or better in the worse eye with significant differences except for near activities, dependency, driving, and color vision. Effect sizes were approximately ½ standard deviation, except for general vision, which had a 1 standard deviation difference in means.
Use of rigid gas-permeable (RGP) lenses in either eye showed higher (better) scores on general health, general vision, and distance activities, and use of RGP lens in an eye with PK showed higher (better) scores on measures of general vision, distance activities, social function, dependency, peripheral vision, and overall score (effect sizes ranged from 0.35 to 0.53).
The results of the analysis-of-variance models on graft age using cutoff points of 5, 10, and 15 years are summarized in Table 4 . Patients had higher scores for mental health, dependency, and overall scores for a mean age of graft ≥5 years compared to <5 years. There were no statistically significant effects when using mean age of graft at 10- and 15-year cutoff points. However, there were significant differences for near activities, distance activities, social function, mental health, role difficulties, dependency, peripheral vision, and overall score when stratified by minimum graft age ≥5 years versus <5 years (better scores with minimum graft age ≥5 years), and effect sizes ranged from 0.37 to 0.70. When using a cutoff of 10 years, significant effects were found only for distance activities and peripheral vision. A cutoff of 15 years yielded significant differences only for distance activities and driving (better scores with minimum graft age <15 years).