Joseph T. Barr

Biomicroscopic signs and disease severity in keratoconus

The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Survey represents the largest sample of clinic-based keratoconus patients to date. Data were collected at 38 clinical centers on 1,579 keratoconus patients. This article reports demographic variables, ages, self-reported ages at diagnosis, keratometry, slit-lamp findings, systemic disease, family history of keratoconus, and best spectacle-corrected and contact lens-corrected visual acuity of this sample group. The average age of this clinic-based sample group was 37 years (range 10-89 years), with 84% between 20 and 49 years old. Thirteen percent of patients had unilateral keratoconus, defined as unilateral corneal irregularity. More advanced disease (steeper average keratometric reading) was associated with a greater likelihood of Vogts striae, Fleischers ring, and/or corneal scarring. Fifty-eight percent of the eyes in this group of patients had ≥40/40 visual acuity with manifest refraction. Penetrating keratoplasty was reported in 12.3% of eyes. This prospective survey identifies the association between the presence of Vogts striae, Fleischers ring, and/or corneal scarring and increasing steepness, as measured by keratometry.

A New Method for Grading the Severity of Keratoconus: The Keratoconus Severity Score (KSS)

Purpose: To define a new method for grading severity of keratoconus, the Keratoconus Severity Score (KSS). Methods: A rationale for grading keratoconus severity was developed using common clinical markers plus 2 corneal topographic indices, creating a 0 to 5 severity score. An initial test set of 1012 eyes, including normal eyes, eyes with abnormal corneal and topographic findings but not keratoconus, and eyes with keratoconus having a wide range of severity, was used to determine cutpoints for the KSS. Validation set 1, comprising data from 128 eyes, was assigned a KSS and compared with a clinicians ranking of severity termed the “gold standard” to determine if the scale fairly represented how a clinician would grade disease severity. κ statistics, sensitivity, and specificity were calculated. A program was developed to automate the determination of the score. This was tested against a manual assignment of KSS in 2121 (validation set 2) eyes from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study, as well as normal eyes and abnormal eyes without keratoconus. Ten percent of eyes underwent repeat manual assignment of KSS to determine the variability of manual assignment of a score. Results: From initial assessments, the KSS used 2 corneal topography indices: average corneal power and root mean square (RMS) error for higher-order Zernike terms derived from the first corneal surface wavefront. Clinical signs including Vogt striae, Fleischer rings, and corneal scarring were also included. Last, a manual interpretation of the map pattern was included. Validation set 1 yielded a κ statistic of 0.904, with sensitivities ranging from 0.64 to 1.00 and specificities ranging from 0.93 to 0.98. The sensitivity and specificity for determining nonkeratoconus from keratoconus were both 1.00. Validation set 2 showed κ statistics of 0.94 and 0.95 for right and left eyes, respectively. Test-retest analysis yielded κ statistics of 0.84 and 0.83 for right and left eyes, respectively. Conclusion: A simple and reliable grading system for keratoconus was developed that can be largely automated. Such a grading scheme could be useful in genetic studies for a complex trait such as keratoconus requiring a quantitative measure of disease presence and severity.

Overnight orthokeratology: preliminary results of the Lenses and Overnight Orthokeratology (LOOK) study.

Background. The Lenses and Overnight Orthokeratology (LOOK) study is a pilot study designed to learn the procedures of orthokeratology lens fitting in preparation for a planned larger clinical trial and to obtain data with which to calculate a sample size for that larger study. Data are presented for the first 3 months of the LOOK study. Methods. Sixty subjects were enrolled in this multicenter pilot study to evaluate the success and safety of treatment with overnight orthokeratology contact lenses. Refractive error, corneal topography, and biomicroscopic data were collected to determine the amount of refractive error change achieved, corneal changes, and a safety profile of overnight wear of reverse geometry rigid gas permeable lenses for orthokeratology. Results. Of the 60 subjects enrolled, 46 completed the 1-month visit, and 31 completed the 3-month visit. The mean change in spherical equivalent manifest refraction from baseline to the morning 3-month visit was 2.08 ± 1.11 D in the right eye and 2.16 ± 1.05 D in the left eye. At the 3-month morning visit, 74% of right eyes and 61% of left eyes had 20/20 unaided visual acuity. No corneal infiltrates or ulcers were noted in any subjects. Observations of fluorescein staining of the cornea, imprinting, and microcysts were noted in some patients at the 3-month visit. Conclusions. The preliminary results of the LOOK study indicate that improvement in unaided visual acuity can be attained for at least 6 h after lens removal. The short-term safety and efficacy of the procedure appear to be favorable; however, future studies are needed to determine the long-term outcomes of treatment.

CORNEAL SCARRING IN THE COLLABORATIVE LONGITUDINAL EVALUATION OF KERATOCONUS (CLEK) STUDY : BASELINE PREVALENCE AND REPEATABILITY OF DETECTION

PurposeThe multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the prevalence of corneal scarring in these patients. We also report on the test-retest repeatability of corneal scar documentati

The effect of overnight contact lens corneal reshaping on higher-order aberrations and best-corrected visual acuity.

Purpose. The purpose of this study is to determine the effect of higher-order aberrations after Corneal Refractive Therapy (CRT) on best-corrected visual acuity (BCVA) and the impact of pupil size on BCVA. Methods. High-contrast (HC) and low-contrast (LC) Bailey-Lovie BCVA was measured in the morning before and after pupil dilation on 20 myopes (mean spherical equivalent -3.11 D ± 0.96 D) under age 40. BCVA was measured again in the afternoon after dilation. Dilated am and pm aberrations were measured using the Complete Ophthalmic Analysis System (WaveFront Sciences). Patients were fit with CRT lenses in each eye. One month after finalizing the lens fit, BCVA and aberration testing were repeated. Average higher-order RMS error (third to sixth order), spherical aberration, third-, fourth-, fifth-, and sixth-order RMS error were calculated at each visit for a 3-mm and 5-mm pupil. BCVA and aberration data were analyzed using a repeated measures analysis of variance. Linear regression was used to describe the relationship between aberrations and BCVA reductions after CRT. Results. Mean refractive error changed by +3.33 D ± 0.96 D. No clinically significant changes were found in HC BCVA post-CRT, whereas LC BCVA reductions of 0.07 logarithm of the minimum angle of resolution (logMAR) (nondilated, p = 0.002) and 0.12 logMAR (dilated, p < 0.001) were found. No additional decrease in HC BCVA was found after pupil dilation, whereas a mean additional decrease of 0.08 logMAR in LC BCVA was found with dilation post-CRT (p = 0.013). Higher-order RMS error increased for both 3-mm and 5-mm pupils (p < 0.0001) and remained stable between measurements. Spherical aberration increased for 5-mm pupils after CRT (p < 0.0001). For a 5-mm pupil, a 0.1-&mgr;m increase in spherical aberration was associated with an additional decrease in LC BCVA after pupil dilation post-CRT of 0.056 logMAR (R2 = 0.382, p = 0.004). Conclusions. CRT results in reduced low-contrast BCVA as a result of increased higher-order aberrations. Higher-order aberrations appear to be relatively stable after CRT. Spherical aberration appears to drive additional low-contrast BCVA losses as pupil size increases.

Characteristics of corneal staining in hydrogel contact lens wearers

Corneal fluorescein staining is widely used in clinical practice and research, but little information exists on the distribution of staining in a large group of asymptomatic contact lens wearers. This cross-sectional study took place at 3 centers, and investigated the pattern of corneal fluorescein staining in both eyes of 98 hydrogel contact lens wearers. We also investigated the strategies used by three experienced clinicians to grade corneal staining. Overall corneal staining was graded using a scale from 0 to 4 in one-half steps, and five corneal zones, superior, inferior, nasal, temporal, and central, were also graded. The average overall staining grade for both eyes of our subjects was 0.50, with an average of 0.57 for the right eye and 0.44 for the left. This difference between the eyes was statistically significant (p = 0.011). In addition, a comparison of the zones within each eye showed a significant difference (p = 0.0001) among the zones. Corneal staining between the two eyes was also positively and significantly correlated (r = 0.58; p = 0.0001). Grading strategies among clinical investigators were significantly different (p = 0.0001), indicating a potential source of bias in multi-centered studies. The difference in corneal staining between the eyes may represent a source of systematic bias, and could be due to grading the right eye before the left. The correlation in corneal staining between the eyes indicates that the two eyes of a subject cannot serve as independent data points. One-third of the subjects who participated in this study had notable corneal staining. This finding underlines the importance of regularly checking corneal staining in clinical practice.

Rigid contact lens fitting relationships in keratoconus

PURPOSE Although the influence of flat-fitting contact lenses on corneal scarring in keratoconus is frequently debated, the current standard of care with regard to the apical fitting relationship in keratoconus remains undocumented. METHODS Patients were examined at baseline in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study (N = 1209). Patients wearing a rigid contact lens in one or both eyes (N = 808) had their habitual rigid contact lenses analyzed, and the fluorescein patterns and base curves were compared to the first definite apical clearance lens (FDACL). The FDACL is the flattest lens in the CLEK Study trial lens set that exhibits an apical clearance fluorescein pattern. For patients wearing a rigid contact lens in both eyes, one eye was selected randomly for analysis. RESULTS Twelve percent of the rigid contact lens-wearing eyes were wearing lenses fitted with apical clearance based upon the clinicians fluorescein pattern interpretation. The remainder (88%) was wearing lenses fitted with apical touch. For mild (steep keratometric reading 52 D) corneas were fitted an average of 4.01 D flat (SD +/- 4.11 D). CONCLUSIONS Despite the potential risk for corneal scarring imposed by flat-fitting rigid contact lenses, most CLEK Study patients wear flat-fitting lenses. Overall, rigid lenses were fitted an average of 2.86 D (SD +/- 3.31 D) flatter than the FDACL.

Factors Associated with Corneal Scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study

Purpose. The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the factors associated with corneal scarring at baseline. Methods. We defined corneal scarring as scars that had been detected both by the clinician examining the patient with the slit-lamp biomicroscope and by masked readers of corneal photographs at the CLEK Photography Reading Center. We investigated associations between corneal scarring and patient variables including gender, ethnicity, a family history of keratoconus, a history of ocular trauma, eye rubbing, contact lens wear, rigid contact lens fitting relationships, and corneal findings (such as curvature, Vogts striae, Fleischers ring, and central/apical staining). Multiple logistic regression analysis using generalized estimating equations to adjust for the correlation between eyes was used for analysis. Results. The following factors were found to increase the odds of corneal scarring at baseline in the CLEK Study: corneal staining (odds ratios (OR) = 3.40, 95% confidence interval 2.53–4.59), contact lens wear (OR = 3.51, 95% confidence interval 2.27–5.45), Fleischers ring (OR = 1.63, 95% confidence interval 1.11–2.40), steeper first definite apical clearance lens base curve radius (per diopter, OR = 1.29, 95% confidence interval 1.25–1.33), and age (per decade, OR = 1.54, 95% confidence interval 1.35–1.75). Conclusions. These baseline data suggest that corneal scarring in keratoconus is associated with corneal staining, contact lens wear, Fleischers ring, a steeper cornea, and increasing age. The factors that imply added risk for corneal scarring that may be affected by practitioner intervention are staining of the cornea, contact lens wear, and the contact lens fitting relationship.

Corneal Scarring and Vision in Keratoconus A Baseline Report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study

Purpose. The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the correlation of corneal scarring with clinical and patient-reported variables at the baseline visit. Methods. Patients completed a questionnaire on their vision, effect of glare, contact lens wear, and work-related issues. Clinical examination included high-and low-contrast visual acuity, refraction, assessment of corneal scarring by the clinician and by photography, and measurement of corneal curvature. The correlation of central corneal scarring with visual acuity and patient-reported variables was analyzed using multiple regression analysis and generalized estimating equations. Results. High-and low-contrast visual acuity with habitual and optimal correction is reduced in scarred eyes. Multiple regression analyses controlling for age, contact lens wear, and disease severity show that central scarring is associated with poorer visual acuity and increased patient-reported symptoms of glare. Restrictions on day-to-day activities do not appear to be associated with corneal scarring above and beyond the effects of keratoconus alone. Conclusions. Corneal scarring in keratoconus is significantly associated with decreased high-and low-contrast visual acuity.

Central and peripheral corneal thickness in keratoconus and normal patient groups

Central and peripheral (superior, inferior, nasal, and temporal) corneal thickness was measured in patients with and without keratoconus using ultrasonic pachometry. In 28 normal eyes (14 patients) mean central corneal thickness (CCT) was 0.56 ± 0.02 mm and the mean difference in thickness between the mean peripheral corneal thickness (PCT) and CCT was 0.24 mm. In 28 keratoconic eyes (14 patients) CCT was 0.52 ± 0.04 mm, and PCT - CCT was 0.29 mm. For keratoconic right eyes, CCT and PCT-CCT were significantly different from normals (p = 0.01). Additional studies within the normal patient group showed no diurnal or day-to-day variations in CCT; they also confirmed the repeatability of the measurements.