The relation between disease asymmetry and severity in keratoconus.

BACKGROUND/AIM: Keratoconus is described as a bilateral, asymmetric, non-inflammatory corneal ectasia. The purpose of the study was to examine the relation between disease asymmetry and severity in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study cohort. METHODS: Analyses included 1037 keratoconus patients from the CLEK Study baseline examination visit, none of whom had undergone corneal surgery in either eye. Disease asymmetry was determined by taking the difference between eyes for continuous variables. For categorical variables, asymmetry was categorised by whether the variable was present in neither, one, or both eyes. Disease severity was defined using the first definite apical clearance lens (FDACL) technique (a rigid contact lens to measure corneal curvature) from the worse (steeper) eye. Statistical analyses included Pearson's correlation coefficients (continuous variables) and analysis of variance (categorical variables). RESULTS: There were generally weak correlations between asymmetry and severity for low contrast habitual visual acuity (r = 0.12, p = 0.0003), high contrast habitual visual acuity (r = 0.14, p<0.0001), low contrast best corrected visual acuity (r = 0.21, p<0.0001), and high contrast best corrected visual acuity (r = 0.29, p<0.0001). Asymmetry in refractive error was more moderately correlated with disease severity (r = 0.41, p<0.0001), as was asymmetry in the flat (r = 0.61, p<0.0001) and steep keratometric readings (r = 0.54, p<0.0001). The average FDACL was significantly steeper in patients who had one eye with Vogt's striae, Fleischer's ring, or corneal scarring compared with the average FDACL when neither eye had these findings. CONCLUSION: Keratoconus patients with more severe disease are also more asymmetric in their disease status.

A comparison of two methods of evaluating cornea-to-contact lens base curve fluorescein patterns in keratoconus.

PURPOSE: The purposes of the study were as follows: (1) to compare the apical fitting relationship of habitual contact lens fluorescein patterns in keratoconus as determined by clinician assessment of on-eye patterns to those determined by photograph readers looking at slides of fluorescein patterns and (2) to determine the validity of the techniques used in assessing the apical fitting relationships of rigid corneal contact lenses on keratoconic corneas. METHODS: Central fluorescein patterns of rigid contact lens-wearing keratoconus patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study were graded as "definite touch," "touch," "clearance," or "definite clearance" by certified clinicians. Photographs of these patterns were evaluated independently by certified, masked photograph readers using the same grading scale. RESULTS: Agreement between "re-reads" of the same fluorescein pattern slides by the photograph readers was substantial (weighted kappa = 0.751). Agreement between assessments of habitual fit fluorescein patterns at the baseline vs. the repeat visits was poor for the photograph readers (weighted kappa = 0.254) and moderate for the clinicians (kappa = 0.480). Agreement between clinicians' and photograph readers' assessment of the habitual contact lens fluorescein pattern at the baseline visit was fair (weighted kappa = 0.382). CONCLUSIONS: Repeatability and validity of this technique were fair to excellent. Many factors influence fluorescein pattern interpretation, and improvement of the objective method of fluorescein pattern assessment by photograph readers will require improved methodology that takes these factors into consideration.

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.

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, Vogt's striae, Fleischer's 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), Fleischer's 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, Fleischer's 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.

Rigid contact lens fitting relationships in keratoconus. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group.

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 clinician's fluorescein pattern interpretation. The remainder (88%) was wearing lenses fitted with apical touch. For mild (steep keratometric reading <45 D) keratoconus corneas, the mean estimate of the base curve to cornea-fitting relationship was 1.18 D flat (SD +/- 1.84 D); moderate (steep keratometric reading: 45 to 52 D) corneas were fitted on average 2.38 D flat (SD +/- 2.56 D); and severe (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.

Discordance for keratoconus in two pairs of monozygotic twins.

PURPOSE: We present two pairs of monozygotic twins discordant for keratoconus. METHODS: Two pairs of twins, each with one twin with keratoconus, and available family members were examined clinically and with computer-assisted videokeratography. Polymerase chain reaction-based zygosity assays using between nine and 11 unique, anonymous DNA markers were performed on blood obtained from the twins and surviving parents to assess the probability of genetic monozygosity. RESULTS: DNA probes showed a >99% probability that each of the two sets of twins was monozygotic. One twin from each pair had clinically diagnosed keratoconus. The remaining twins were normal by clinical examination and corneal topography. Clinical results for all family members examined were normal except that five of 13 from one family and one of six from the other family demonstrated "suspicious" corneal topography. CONCLUSION: Recent advances in knowledge and understanding of the twinning process suggest that monozygotic twins discordant for keratoconus does not preclude the possibility of a significant genetic component.

The incidence of glassy corneal striae.

Glassy corneal striae (GCS) are fine colorless lines that run parallel to each other in a vertical or near-vertical orientation in the central cornea near the level of Descemet's membrane. It is postulated that GCS "brace" the stroma, thus adding stability to the cornea. The purpose of this study was to determine the incidence of GCS in patients with "normal" corneas and to determine whether a correlation exists between the presence of GCS and gender, age, iris color, or corneal astigmatism (toricity). Modified marginal retro-illumination biomicroscopy was used to evaluate the cornea for the presence of GCS. One hundred thirteen "normal" right corneas were evaluated for the presence of GCS. A total of 85.8% (97/113) of subjects in our study sample exhibited GCS. However, we were unable to establish a statistically significant correlation between the presence of GCS and gender, age, iris color, or corneal toricity.

Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.

PURPOSE: To describe the baseline findings in patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. METHODS: This is a longitudinal observational study of 1209 patients with keratoconus enrolled at 16 clinical centers. Its main outcome measures are corneal scarring, visual acuity, keratometry, and quality of life. RESULTS: The CLEK Study patients had a mean age of 39.29+/-10.90 years with moderate to severe disease, assessed by a keratometric-based criterion (95.4% of patients had steep keratometric readings of at least 45 D) and relatively good visual acuity (77.9% had best corrected visual acuity of at least 20/40 in both eyes). Sixty-five percent of the patients wore rigid gas-permeable contact lens, and most of those (73%) reported that their lenses were comfortable. Only 13.5% of patients reported a family history of keratoconus. None reported serious systemic diseases that had been previously reported to be associated with keratoconus. Many (53%) reported a history of atopy. Fifty-three percent had corneal scarring in one or both eyes. CONCLUSIONS: Baseline findings suggest that keratoconus is not associated with increased risk of connective tissue disease and that most patients in the CLEK Study sample represent mild to moderate keratoconus. Additional follow-up of at least 3 years will provide new information about the progression of keratoconus, identify factors associated with progression, and assess its impact on quality of life.

Repeatability and agreement of two corneal-curvature assessments in keratoconus: keratometry and the first definite apical clearance lens (FDACL). CLEK Study Group. Collaborative Longitudinal Evaluation of Keratoconus.

PURPOSE: This study was conducted to determine the agreement and test-retest repeatability of two methods for measuring corneal curvature in keratoconus: keratometry and the First Definite Apical Clearance Lens (FDACL). Our interest in the FDACL procedure stems from the important contact lens-fitting information and documentation of disease progression provided by the FDACL trial lenses and observation of fluorescein patterns. METHODS: The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is an observational study that has enrolled 1,209 keratoconus patients to characterize the progression of keratoconus, to determine factors associated with its progression, and to assess its impact on quality of life. Ten percent of the patients were randomly selected at baseline for a retest examination. The baseline examination, which included keratometry and FDACL, was repeated in this sample. The FDACL is the flattest lens in the standardized CLEK trial lens set that vaults the apex of the cone. FDACL provides an estimate of the sagittal height of the cone. RESULTS: The correlation of FDACL with the steep keratometric reading (r = 0.89; p = 0.0001) and the flat keratometric reading (r = 0.83; p = 0.0001) were high. Test-retest repeatability as measured by the intraclass correlation coefficient (ICC) was high: FDACL ICC, 0.97; steep keratometric reading ICC, 0.96; and flat keratometric reading ICC, 0.95. Test-retest repeatability of FDACL remained high in advanced disease. CONCLUSION: FDACL provides a repeatable new procedure for determining disease severity in keratoconus.

Efficacy of hand washing procedures on bacterial contamination of hydrogel contact lenses.

The effect of various hand washing regimens on transfer of bacterial contaminants from the hands to a hydrogel contact lenses was evaluated. Each of 47 subjects performed 5 different hand washing procedures, and then handled a new, sterile hydrogel contact lens. The lenses were cultured to determine colony-forming units (CFUs) and microbial identity. Median CFUs on lenses handled after washing with water, soap and water, or soap and water followed by towel drying were higher than the median CFU for lenses handled after no hand washing. The median CFU for lenses handled after soap and water washing followed by an alcohol wipe was not different from the no washing group. The majority of the contaminants were identified as Staphylococcus epidermidis. These results show that ordinary hand washing alone does not decrease, and may even increase, the amount of contaminants transferred from the hands to a hydrogel lens. Use of an alcoholic wipe after hand washing reverses this effect. Hand washing is still recommended in contact lens hygiene for removal of more pathogenic contaminants.

Feasibility of fitting contact lenses with apical clearance in keratoconus.

Despite the wide variety of rigid contact lens fitting philosophies for the visual correction of keratoconus, questions remain, including which approach-flat, divided support, or steep-contributes the most toward the preservation of a clear cornea. One goal of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Pilot Study was to determine the feasibility of managing early keratoconus patients with apical clearance rigid contact lenses. Of 30 keratoconus patients identified with at least 1 nonscarred cornea, 17 patients (30 eyes) were randomly assigned to a steep lens fitting protocol. After trial fitting with a standardized lens design demonstrating minimum apical clearance, lenses were dispensed whose base curve was 0.2 mm steeper than the minimum apical clearance lens. Patients were re-evaluated on a quarterly schedule concluding at 12 months. Changes in keratometry between baseline and 12 months identified unequal steepening of the flat and steep corneal curvatures, suggestive of corneal molding. Best corrected rigid lens visual acuity measures illustrated no significant changes over the course of the study. Clinically significant corneal compromise was transiently observed in some patients. Only 1 of 22 eyes completing the pilot study and fitted with apical clearance developed mild corneal scarring.

Standardized rigid contact lens fitting protocol for keratoconus.

Keratoconus is typically managed by a variety of rigid contact lens fitting techniques and lens designs. The two most fundamental fitting techniques are apical corneal touch (including divided or three-point touch) and apical clearance. In the course of designing a multi-center study of keratoconus patients, a standardized keratoconus fitting protocol was developed. All contact lens parameter options are uniform except for base curve and secondary curve radii, which are determined by interpretation of fluorescein patterns using the CLEK Study trial lens set and protocol. The initial trial lens's base curve is the average keratometric reading; sequentially steeper lenses are applied until definite apical clearance is observed. We have evaluated the feasibility of this standardized fitting protocol on 30 keratoconus patients. Our results suggest that we have developed a standardized contact lens fitting set and fitting protocol to simplify contact lens management in patients with mild to moderate keratoconus.

Photodocumentation of corneal scarring. Collaborative Longitudinal Evaluation of Keratoconus Study Group.

PURPOSE: A standardized system for photodocumenting corneal scars and for evaluating these photographs does not exist and is essential for clinical research. To address this need, we developed a system for photographing and evaluating corneal scars. METHODS: In the "Development Phase," we tested several procedures in small samples totaling 40 eyes of 20 keratoconus patients. In the "Test Phase," we used an independent sample of 150 eyes of 82 keratoconus patients. Fifty-nine of these 150 eyes had corneal scars, and 91 of the eyes did not as determined by the clinician. RESULTS: The photography protocol requires four central parallelepiped and two whole cornea oblique photographs after pupil dilation. With the clinician as gold standard, this technique yielded sensitivity of 96% and specificity of 83%. Evaluation of the corneal photographs as to the presence or absence of corneal scarring was performed independently by two masked readers. Agreement between clinicians on the presence of corneal scarring was 0.99 (kappa); agreement between readers for the presence of scarring was 0.80 (kappa). CONCLUSIONS: The corneal photography protocol we describe is recommended for use in clinical investigations of cicatricizing corneal disease and appears robust enough to be used in multicenter studies.

Biomicroscopic signs and disease severity in keratoconus. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group.

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 variable, 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 Vogt's striae, Fleischer's ring, and/or corneal scarring. Fifty-eight percent of the eyes in this group of patients had > or = 20/40 visual acuity with manifest refraction. Penetrating keratoplasty was reported in 12.3% of eyes. This prospective survey identifies the associates between the presence of Vogt's striae, Fleischer's ring, and/or corneal scarring and increasing steepness, as measured by keratometry.

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.

The relationship between corneal eccentricity and improvement in visual acuity with orthokeratology.

BACKGROUND: Due to the renewed attention given to reduction of myopia, interest in orthokeratology has dramatically increased. This study was performed to determine whether or not a predictor for orthokeratologic changes can be identified. METHODS: Fifteen subjects enrolled in the study. For each subject, corneal eccentricity (e) was measured, subjective refraction and autorefraction were performed, and intraocular pressures were taken. Each subject was then fitted with a rigid contact lens for orthokeratology and followed for a minimum of 16 weeks. Eleven subjects completed the study. RESULTS: No correlation between corneal eccentricity and improvement in visual acuity was found. Correlations were found between e and changes in subjective refraction, and between e and changes in autorefraction. There was also correlation between lower intraocular pressure and changes in subjective refraction, and between lower intraocular pressure and changes in autorefraction. CONCLUSIONS: These findings suggest that corneal eccentricity and lower intraocular pressures may be predictors of orthokeratologic changes. A longitudinal study with a larger subject size will be needed to conclusively determine if these two measurements are predictors of orthokeratologic changes.

Keratoconus.

Keratoconus is characterized by the presence of corneal distortion (secondary to thinning of the apex) and either Fleischer's ring (found in 57% of patients) or Vogt's striae (found in 44% of patients). Often the only presenting symptom is decreased visual acuity. Steep keratometric readings are not usually diagnostic; 18% of patients with keratoconus have readings flatter than 45.00 D. Treatment requires correction of acuity with spectacles or contact lenses. More advanced cases are generally managed with rigid gas-permeable contact lenses. Corneal scarring occurs in approximately 43% of cases; 10% to 20% of patients require penetrating keratoplasty to restore acuity.

A comparative study of techniques for decreasing contact lens storage case contamination.

BACKGROUND: Contact lens storage cases may harbor a variety of pathogenic organisms, and are a potential source of ocular infection. In this study, we evaluated the anti-microbial efficacy of several methods of rinsing of contact lens storage cases. METHODS: Lens cases were inoculated with Pseudomonas aeruginosa and then 1) rinsed with hot tap water and closed without drying, 2) rinsed with hot tap water followed by air drying, 3) rinsed with 3% hydrogen peroxide followed by air drying, or 4) left closed and undisturbed (control condition). After 24 hours, the cases were cultured to determine the rate of disinfection. RESULTS: The hydrogen peroxide rinse was the most effective (99.5 percent of cases disinfected), followed by hot water with air drying (94.7 percent) and hot water without drying (51.1 percent). Significant residual hydrogen peroxide was detected in the cases rinsed with peroxide. CONCLUSIONS: Therefore, we recommend that patients be instructed to rinse their cases with hot water and allow them to air dry after use, as well as replace their cases on a regular basis.

Soft contact lens and corneal changes associated with Visine use.

Sixteen subjects were fit with Cibasoft clear daily wear contact lenses and were asked to use two drops of tetrahydrozoline (Visine) twice a day for 4 months on one eye. Visual acuity, lens coloration, and slit lamp results were compared to baseline data between the test and control eye of each subject. Visual acuity and lens coloration results showed statistically insignificant changes from baseline. However, clinically important changes in corneal integrity were noted in 26.7% of the subjects.