Karla Zadnik

The Repeatability of Clinical Measurements of Dry Eye

Purpose: The repeatability of individual dry eye diagnostic tests has been reported in the literature on normal samples of patients and to a lesser degree in dry eye patients. In this study, the repeatability of a battery of clinical diagnostic tests for dry eye was assessed on mild to moderate dry eye patients. Methods: A dry eye examination was performed on 75 patients on two occasions by a single examiner. The battery of dry eye tests included symptom assessment, contact lens and medical history, slit-lamp biomicroscopic evaluation of the eyelids, evaluation of Meibomian glands, assessment of tear film quality, tear meniscus height, assessment of blink quality, fluorescein tear breakup time (TBUT), fluorescein and rose bengal staining of the cornea and conjunctiva, phenol red thread test, and Schirmer test. Results: The repeatability of subjective report of dryness (κw = 0.62) and grittiness (κw = 0.73) was moderate to high. In contrast, the repeatability of Meibomian gland disease classification (κw = 0.20), presence or absence of inferior corneal fluorescein staining (κ = 0.25), and inferior conjunctival rose bengal staining (κ = 0.21) was poor. When a summed staining score of corneal and conjunctival regions was evaluated, weighted κ reliability was fair. The repeatability of tear breakup time was substantial [95% limits of agreement −5.71 to 5.83 seconds; intraclass coefficient coefficient (ICC) 0.65], and improved when the two timed readings were averaged. Repeatability of the Schirmer test is more variable as wetting scores increase. When the average Schirmer scores ≤10 mm were evaluated, moderate repeatability was demonstrated, indicating that the test performs better with more advanced disease. Conclusion: Although patient-reported symptoms are moderately repeatable from visit to visit, many of the procedures clinically used to diagnose and monitor dry eye syndromes are largely unrepeatable.

Ocular component data in schoolchildren as a function of age and gender.

Purpose. To describe the refractive error and ocular components of a large group of school-aged children as a function of age and gender. Methods. In this report, we describe the refractive error and ocular components of 2583 school-aged children (49.3% girls, overall mean [±SD] age 10.0 ± 2.3). Measurement methods included cycloplegic autorefraction, autokeratometry, videophakometry, and A-scan ultrasonography. For statistical comparisons across gender and age, a critical point of &agr; = 0.005 was used to assess significance because of the large sample size and the large number of comparisons made. Results. Of these 2583 children, 10.1% were myopic (−0.75 D or more myopia in both meridians), and 8.6% were hyperopic (+1.25 D or more hyperopia in both meridians). As would be expected, there was a significant effect of age on refractive error (spherical equivalent, p < 0.0001), toward less hyperopia/more myopia. There was no significant difference in the average refractive error between girls and boys (p = 0.0192). Girls had steeper corneas than boys (0.74 D steeper in the vertical meridian and 0.63 D steeper in the horizontal meridian, p < 0.0001). There were no significant differences in corneal power with age (p = 0.16). Both older age and male gender were significantly associated with deeper anterior chambers (p < 0.0001 for both). The crystalline lens showed significant thinning with age (p < 0.0001), however, there was no significant difference in the lens thickness between girls and boys (p = 0.66). Both Gullstrand lens power and calculated lens power showed significant effects of age and gender (p < 0.0001 for both). Girls, on average, had Gullstrand lens powers that were 0.28 D steeper and calculated lens powers that were 0.80 D more powerful than boys. Axial length also showed significant effects of age and gender (p < 0.0001 for both). Girls’ eyes were, on average, 0.32 mm shorter than those of boys. Conclusions. These cross-sectional data show a general pattern of ocular growth, no change in corneal power, and crystalline lens thinning and flattening between the ages of 6 and 14 years. Girls tended to have steeper corneas, stronger crystalline lenses, and shorter eyes compared with boys.

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.

Initial cross-sectional results from the Orinda Longitudinal Study of Myopia.

Background. Although investigations of human refractive error development and normal ocular growth have been conducted for the last 50 years, no previous study of refractive error and the ocular components has measured all the ocular components. Methods. The Orinda Longitudinal Study of Myopia was initiated to characterize the development of refractive error and normal eye growth in a sample of predominantly Caucasian children ages 6 to 14 years. Results. Crosssectional results from 530 children ages 5 to 12 years in the 1st, 3rd, and 6th grades are presented. Conclusions. This samples refractive error decreased toward emmetropia with age from an average of +0.73 D at age 6 years to an average of +0.50 D by age 12 years. Between the ages of 6 and 12 years, the vitreous chamber elongated (by 0.52 mm) and the crystalline lens power decreased (by 1.35 D); surprisingly, the crystalline lens thinned by 0.14 mm during this same time period

Myopia development in childhood

Purpose. The Orinda Longitudinal Study of Myopia is a 12-year project examining predictive factors for the onset of myopia, the underlying etiologies of myopia, and normal eye growth in school children. Methods. This paper reports on all measurements made of the ocular components (cycloplegic refractive error, corneal curvature, crystalline lens power, and axial ocular dimensions), parental history of myopia, and near work activity in children participating in the Orinda Longitudinal Study of Myopia between 1989 and 1993. An analysis of the interaction between parental history of myopia and childrens near work is conducted on the cross-sectional study data from 1993. Results. The cross-sectional and longitudinal data show a gradual decrease in refractive error from low hyperopia toward emmetropia, no shift in corneal curvature, a gradual decrease in crystalline lens power, thinning of the crystalline lens, and elongation of the eye between the ages of 6 and 14 years. Parental history is more contributory to a statistical model predicting myopia than is near work, but near work is a significant factor as well. We can find no evidence of statistical interaction between parental history and near work in explaining the presence or absence of myopia. Conclusions The emmetropization process is evident in the gradual decrease in refractive error toward emmetropia, the axial elongation of the eye, and the compensating decrease in crystalline lens power. Both nature and nurture play a role in the etiology of myopia, although the predominant role appears to belong to a positive parental history of myopia. This role does not appear to be through an interaction between parental myopia status and childrens near work activity.

Frequency of dry eye diagnostic test procedures used in various modes of ophthalmic practice.

Purpose. There are many suggested dry eye diagnostic test batteries in the literature. However, clinicians use a wide variety of dry eye diagnostic tests in clinical practice due to a number of factors, including time constraints. In addition, there has been no systematic description of the standard of care in diagnosing dry eye in the literature. The purpose of this study is to determine the type and frequency of dry eye diagnostic tests used in various modes of ophthalmic practice across a spectrum of dry eye severity. Methods. A total of 467 patient charts (patients with a previous dry eye diagnosis) were reviewed retrospectively to determine diagnostic test frequency. In reviewing patient charts, the following tests were identified as performed or not performed: symptom assessment, fluorescein staining, tear break-up time (TBUT), Schirmer test, rose bengal staining, and “tear assessment” (including quantity and quality of the tear meniscus). Results. Dry eye diagnostic tests were used in the following frequencies across all modes of practice: symptom assessment (82.8%), fluorescein staining (55.5%), TBUT (40.7%), tear assessment (22.2%), Schirmer test (8.5%), and rose bengal staining (4.9%). When the clinics are pooled, two test procedures were used with the highest frequency (38.9%). The most commonly performed two-test procedure combination was a symptom assessment combined with fluorescein staining of the cornea (43.7%). Conclusions. Symptom assessment plays a large role in the diagnosis of dry eye. The current clinical standard of care for dry eye diagnosis includes the performance of at least one test procedure in addition to a symptom assessment.

Between-Eye Asymmetry in Keratoconus

Purpose. To report baseline differences between eyes on key variables in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study cohort compared with a retrospectively assembled group of myopic contact lens wearers without ocular disease. Methods. A total of 1,079 keratoconus patients who had not undergone a penetrating keratoplasty in either eye before their baseline visit were enrolled and examined at baseline. Records from 330 contact lens-wearing myopes were reviewed. Corneal curvature (keratometry), visual acuity, refractive error (manifest refraction), and corneal scarring were measured. Results. The mean differences between keratoconic eyes are as follows (better eye–worse eye for each variable, separately). Flat keratometry: −3.59 ±4.46 D and steep keratometry: −4.35 ±4.41 D; high-contrast best-corrected visual acuity: 7.30 ±6.83 letters; low-contrast best-corrected visual acuity: 8.53 ±7.51 letters; high-contrast entrance visual acuity: 9.03 ±8.40 letters; low-contrast entrance visual acuity: 9.43 ±7.88 letters; spherical equivalent refractive error: 3.15 ±3.84 D; and refractive cylinder power 1.55 ±1.42 D. Twenty-one percent of the keratoconus patients had corneal scarring in only one eye. There is an association between patient-reported unilateral eye rubbing and greater asymmetry in corneal curvature, and between a history of unilateral eye trauma and greater asymmetry in corneal curvature and refractive error, with the rubbed/traumatized eye being the steeper eye most of the time. Conclusions. Keratoconus is asymmetric in the CLEK Study sample.

Relative Peripheral Refractive Error and the Risk of Onset and Progression of Myopia in Children

PURPOSE To investigate whether relative peripheral hyperopia is a risk factor for either the onset of myopia in children or the rate of myopic progression. METHODS The risk of myopia onset was assessed in 2043 nonmyopic third-grade children (mean age ± SD = 8.8 ± 0.52 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study between 1995 and 2007, 324 of whom became myopic by the eighth grade. Progression analyses used data from 774 myopic children in grades 1 to 8. Foveal and relative peripheral refractive error 30° in the nasal visual field was measured annually by using cycloplegic autorefraction. Axial length was measured by A-scan ultrasonography. RESULTS The association between more hyperopic relative peripheral refractive error in the third grade and the risk of the onset of myopia by the eighth grade varied by ethnic group (Asian children odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.06-2.30; African-American children OR = 0.75, 95% CI = 0.58-0.96; Hispanics, Native Americans, and whites showed no significant association). Myopia progression was greater per diopter of more hyperopic relative peripheral refractive error, but only by a small amount (-0.024 D per year; P = 0.02). Axial elongation was unrelated to the average relative peripheral refractive error (P = 0.77), regardless of ethnicity. CONCLUSIONS Relative peripheral hyperopia appears to exert little consistent influence on the risk of the onset of myopic refractive error, on the rate of myopia progression, or on axial elongation.

Two-year multicenter, randomized, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia.

PURPOSE To evaluate if the safety and efficacy of the relatively selective M1-antagonist, pirenzepine, in slowing the progression of myopia in children is sustained over a 2-year period. METHODS This was a multicenter, parallel-group, placebo-controlled, double-masked, randomized clinical trial. Enrolled were children aged 8 to 12 years, with entry spherical equivalent refractive error of -0.75 to -4.00 D and astigmatism </=1.00 D. Patients were randomized in a 2:1 ratio to receive 2% pirenzepine ophthalmic gel or a placebo control (vehicle), twice daily to each eye. The main outcome measure was spherical equivalent refractive error via cycloplegic autorefraction. RESULTS At study entry, spherical equivalent was -2.10 +/- 0.90 D (mean +/- SD) for the pirenzepine group (n = 117) and -1.93 +/- 0.83 D for the placebo group (n = 57; p = 0.22). At 1 year, there was a mean increase in myopia of 0.26 D in the pirenzepine group versus 0.53 D in the placebo group (p < 0.001). Eighty-four patients elected to continue for a second year (pirenzepine = 53, placebo = 31). At 2 years, the mean increase in myopia was 0.58 D for the pirenzepine group and 0.99 D for the placebo group (p = 0.008). Thirteen (11%) pirenzepine patients dropped out due to adverse effects in the first year, and 1 did so in the second year. CONCLUSIONS Pirenzepine ophthalmic gel 2% was effective compared with placebo in slowing the progression of myopia over a 2-year treatment period and demonstrated a clinically acceptable safety profile.

Time outdoors, visual activity, and myopia progression in juvenile-onset myopes.

PURPOSE To investigate the association between myopia progression and time spent outdoors and in various visual activities. METHODS Subjects were 835 myopes (both principal meridians -0.75 diopters [D] or more myopia by cycloplegic autorefraction) in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study with both progression data and at least one measure of activity associated with a progression interval. Activity data were collected by parental survey. Average activity level (mean of the activity at the beginning and the end of a 1-year progression interval) was the primary predictor in a repeated-measures mixed model. The model controlled for age, sex, ethnicity, refractive error at the beginning of the progression interval, clinic site, and type of autorefractor used. Effects were scaled based on performing an additional 10 hours per week of an activity. RESULTS In the multivariate model, the number of hours of reading for pleasure per week was not significantly associated with annual myopia progression at an a priori level of P ≤ 0.01, nor were the other near activities, the near-work composite variable diopter-hours, or outdoor/sports activity. The magnitude of effects was clinically small. For example, the largest multivariate effect was that each additional 10 hours of reading for pleasure per week at the end of a progression interval was associated with an increase in average annual progression by -0.08 D. CONCLUSIONS Despite protective associations previously reported for time outdoors reducing the risk of myopia onset, outdoor/sports activity was not associated with less myopia progression following onset. Near work also had little meaningful effect on the rate of myopia progression.