Sheryl S. Wizov

Importance of Visual Acuity and Contrast Sensitivity in Patients With Glaucoma

OBJECTIVE To determine which aspects of vision most influence the ability of patients with glaucoma to function. METHODS A total of 192 patients with a full range of glaucomatous visual loss were selected from the Glaucoma Service of Wills Eye Institute. Patients were evaluated clinically with standard visual assessments: visual acuity, contrast sensitivity, visual field, stereopsis, the Disc Damage Likelihood Scale, and intraocular pressure. Patients were evaluated objectively using a comprehensive performance-based measure of visual function, the Assessment of Disability Related to Vision (ADREV), and subjectively with the 25-item National Eye Institute Visual Function Questionnaire. Statistical analyses, including Spearman correlation coefficients and regression analysis, were performed on the data. RESULTS Performance on the ADREV was most strongly associated with binocular visual acuity (r = -0.79; P < .001) and binocular contrast sensitivity (r = 0.80; P < .001). Monocular and binocular visual field test results correlated well with the ability to perform the ADREV tasks, but there was a significantly weaker association (P < .05) compared with visual acuity and contrast sensitivity. CONCLUSION The aspects of visual function that best predict the ability of a patient with glaucoma to perform activities of daily living are binocular visual acuity and contrast sensitivity.

Congenital periodic alternating nystagmus: Diagnosis and management

PURPOSE The purpose of the study is to investigate diagnostic criteria and treatment methods for patients with congenital periodic alternating nystagmus (PAN). METHODS A retrospective analysis was performed of clinical findings and serial eye movement recordings of patients with congenital PAN. Eighteen patients observed from 1983 through 1996 and diagnosed with congenital PAN are included. Five of these have ocular or oculocutaneous albinism. Nine of the 18 patients were treated. Three had Kestenbaum operations before referral to the authors, one was treated with baclofen, and five had large recessions of the four horizontal recti. The studied parameters included visual acuity (VA) and abnormal head posture (AHP); temporal aspects of PAN cycle, nystagmus waveforms, frequency, amplitude, and velocity; as well as mean foveation fraction, a mean percentage of the nystagmus cycle spent at retinal slip velocities less than 10 degrees per second. RESULTS The authors diagnosed PAN in 9% of patients with congenital nystagmus, although most had not been diagnosed with PAN before referral, despite changing nystagmus. Sixteen patients had AHP, typically shifting. The PAN cycle was of variable duration, often with asymmetric right- and left-beating components. Although horizontal jerk nystagmus with accelerating slow phase was predominant, other waveforms were encountered in the active phase of PAN. In the quiet phase (close to null zone), similar, but less intense, oscillations than those in the active phase were characteristic. Half of the patients showed a combination of waveforms in both phases. Baclofen treatment was unsuccessful. Patients who had Kestenbaum procedures remained with AHP in the original or opposite direction, without change in nystagmus or VA. Large recessions of four horizontal recti proved uncomplicated. This treatment improved, at least for several years, AHP and VA and caused favorable changes in nystagmus parameters in all patients. Mean foveation fractions increased significantly after surgery. CONCLUSIONS Congenital PAN often is underdiagnosed. Differing waveforms may indicate PAN. Evaluation of nystagmus, especially before surgery, for at least 3 minutes, preferably with eye movement recordings, is necessary to diagnose PAN and perhaps prevent Kestenbaum procedures, which seem inappropriate. Large horizontal recti recessions seem to provide safe and promising treatment.

Relationships in Glaucoma Patients Between Standard Vision Tests, Quality of Life, and Ability to Perform Daily Activities

Purpose: To determine the relationships among three methods of assessing visual loss caused by glaucoma: (1) standard clinical tests of vision, (2) self-reported quality of life, and (3) the ability to perform activities of daily living. Methods: One hundred and ninety two glaucoma patients with a full range of glaucomatous visual loss were selected from the Glaucoma Service of Wills Eye Institute. Subjects were evaluated clinically by visual acuity, contrast sensitivity, visual field, stereopsis, the Disc Damage Likelihood Scale, and intraocular pressure. Subjects were evaluated subjectively by the 25-item National Eye Institute’s Visual Functioning Questionnaire (NEI-VFQ-25) and objectively by a performance-based measure of visual function, the Assessment of Disability Related to Vision (ADREV). Statistical analysis, including Spearman coefficients, was performed on the data from the clinical measures, NEI-VFQ-25, and ADREV. Results: The clinical tests had higher correlations with ADREV than with the NEI-VFQ-25. There was a moderate, but not strong, connection between how patients rated their own visual ability with how they performed when objectively tested. Conclusions: ADREV provides valid estimates of how visual loss due to glaucoma affects the ability to perform activities of daily living. Performance-based testing and quality of life evaluations are both independently important measures of health, which are related, but by no means the same.

Evidence for widespread structural brain changes in glaucoma: a preliminary voxel-based MRI study.

PURPOSE To investigate structural brain changes in patients with glaucoma. METHODS High-resolution T1-weighted anatomical brain magnetic resonance images (MRI) were collected in 15 patients with glaucoma of varying severity and in 15 age-, race-, and sex-matched controls. Exclusion criteria included neurological disease, another disorder which could affect the visual field, and a score of less than 25 on the mini-mental status examination. The scans were analyzed with an automatic volumetric MRI technique to measure the volumes of 93 structures in each brain. Analyses of covariance with age as a covariate were carried out to identify structures that differed significantly between the two groups (i.e., glaucoma versus normal control). The volumes of all brain structures in the group of 15 glaucoma patients were also correlated with clinical measures of disease severity. Linear multivariate regression analyses were conducted to determine the significance of these relationships. RESULTS Five structures differed significantly between the two groups (P < 0.05). These structures included the right and left inferior occipital gyri and the right middle occipital gyrus, right inferior temporal gyrus, and right occipital lobe white matter. Interestingly, all of these structures were larger in the glaucoma group than in the control group. Within the group of glaucoma patients, 38% of all brain structures had independent associations between decreasing volume and more severe disease in multivariate regression analysis. CONCLUSIONS These results suggest that patients with glaucoma undergo widespread and complex changes in cortical brain structure and that the extent of these changes correlates with disease severity.

Comparison of Human Ocular Distribution of Bimatoprost and Latanoprost

PURPOSE This study investigated the ocular distribution of bimatoprost, latanoprost, and their acid hydrolysis products in the aqueous humor, cornea, sclera, iris, and ciliary body of patients treated with a single topical dose of 0.03% bimatoprost or 0.005% latanoprost for understanding concentration-activity relationships. METHODS Thirty-one patients undergoing enucleation for an intraocular tumor not affecting the anterior part of the globe were randomized to treatment with bimatoprost or latanoprost at 1, 3, 6 or 12 h prior to surgery. Concentrations of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid in the human aqueous and ocular tissues were measured using liquid chromatography tandem mass spectrometry. RESULTS Following topical administration, intact bimatoprost was distributed in human eyes with a rank order of cornea/sclera >iris/ciliary body >aqueous humor. Bimatoprost acid was also detected in these tissues, where its low levels in the cornea relative to that of latanoprost acid indicated that bimatoprost hydrolysis was limited. Latanoprost behaved as a prodrug that entered eyes predominantly via the corneal route. Levels of latanoprost acid were distributed as cornea >>aqueous humor>iris>sclera>ciliary body. CONCLUSIONS Our study provided experimental evidence that levels of bimatoprost in relevant ocular tissues, and not only aqueous humor, are needed to understand the mechanisms by which bimatoprost lowers intraocular pressure (IOP) in human subjects. The data suggest that bimatoprost reached the target tissues favoring the conjunctival/scleral absorption route. Findings of intact bimatoprost in the target ciliary body indicated its direct involvement in reducing IOP. However, bimatoprost acid may have only a limited contribution on the basis that bimatoprost has greater/similar IOP-lowering efficacy than latanoprost, yet bimatoprost acid levels were a fraction of latanoprost acid levels in the aqueous humor and cornea and only sporadically detectable in the ciliary body. In this report, human ocular tissues were examined concurrently with aqueous humor for the in vivo distribution of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid.

Relationships among visual acuity demands, convergence, and nystagmus in patients with manifest/latent nystagmus

BACKGROUND We investigated the role convergence plays in nystagmus dampening, in particular, relationships among visual acuity demands, convergence, and nystagmus. Previously we showed that subjects with idiopathic infantile nystagmus exhibit a range of responses to acuity targets, one of which is nystagmus blockage syndrome. We report herein eye movement responses to acuity targets of patients with manifest/latent nystagmus. METHODS Fourteen patients, 11 with latent or manifest latent nystagmus and 3 with combined manifest latent with infantile nystagmus, were asked to indicate the direction of the gap in Landolt C optotypes while their eye movements were recorded. RESULTS The tested patients exhibited various responses to acuity demands: (1) dampening of nystagmus with convergence (i.e., nystagmus blockage syndrome) (5/14 patients), (2) changes in vergence without nystagmus dampening (2 patients), (3) decrease of nystagmus without convergence (2 patients), and (4) little change in nystagmus or vergence (5 patients). In nystagmus blockage syndrome the amount of convergence increased with acuity demands in two of five patients and the convergence duration in four of five patients; nystagmus dampening increased with acuity demands in one of five patients and the blockage duration in four of five patients. CONCLUSIONS Many, but not all, patients with manifest/latent nystagmus, similar to those with infantile nystagmus, used convergence to dampen their nystagmus. The convergence response tended to increase with acuity demands, but the amount of dampening was idiosyncratic and not predictably related to the measured convergence across patients.

The Impact of Visual Field Clusters on Performance-based Measures and Vision-Related Quality of Life in Patients With Glaucoma

PURPOSE To investigate how visual field (VF) clusters affect performance-based measures of the ability to perform activities of daily living and subjective measures of vision-related quality of life (QoL) in patients with glaucoma. DESIGN Prospective, cross-sectional study. METHODS setting: Institutional - Wills Eye Hospital. STUDY POPULATION 322 eyes of 161 patients with moderate-stage glaucoma. OBSERVATION VF tests were conducted using the Humphrey 24-2 Swedish Interactive Thresholding Algorithm standard perimeter. The VFs of each patient were divided into 5 clusters: nasal, temporal, central, paracentral, and peripheral. The score for each cluster was the averaged total deviation scores of all tested points within the cluster. Each cluster score was correlated with performance-based measures of visual function and subjective assessment of vision-related QoL. MAIN OUTCOME MEASURES The Compressed Assessment of Ability Related to Vision, the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25), and the Modified Glaucoma Symptom Scale. RESULTS The central VF cluster in the better eye was positively correlated with all Compressed Assessment of Ability Related to Vision (performance-based measure) subscales. The strongest correlation for the better eye was between the central VF cluster and total Compressed Assessment of Ability Related to Vision score (0.39, P < .001). The inferior VF hemisphere in both eyes was positively correlated with most Compressed Assessment of Ability Related to Vision subscales. Central VF clusters in the better eye were positively correlated with a majority of the NEI VFQ-25 subscales. There were no significant correlations between VF clusters and Modified Glaucoma Symptom Scale subscales. CONCLUSIONS Scores of central VF defects in the better eye and inferior hemisphere defects in both eyes were positively correlated with performance-based measures of the ability to perform activities of daily living. Glaucoma patients with central defects in the better eye were more likely to have reduced scores on assessments of vision-related QoL.

A clinical method to assess the effect of visual loss on the ability to perform activities of daily living.

Background/aims To develop a clinically applicable, performance-based measure of the ability to perform visually related activities. Methods 99 patients with glaucoma and 21 subjects with a normal ocular examination completed a nine-item performance-based test (the Assessment of Ability Related to Vision (AARV)), received a standard ophthalmic clinical examination and answered the questions on the National Eye Institutes Visual Functioning Questionnaire (NEI-VFQ-25). All combinations of two, three or four items of the full nine-item AARV test were analysed, and their scores were compared with the full AARV scores and with clinical measures. Results The correlation of four items (detecting motion, reading signs, finding objects and navigating an obstacle course) reduced test time from 60±5 min to 14±4 min and yielded results highly related to the nine-item test, including maintaining the relationship with clinical measures and with the NEI-VFQ-25. Conclusion A compressed AARV correlates highly with the full test, with a method of evaluating quality of life, and with clinical measures, yet takes on average 14 min to perform. As such, it may provide a clinically useful method of evaluating the worsening effects of illness and the benefits of treatments that affect visual loss on the ability to perform visually related activities.

EVALUATING CONTRAST SENSITIVITY IN AGE-RELATED MACULAR DEGENERATION USING A NOVEL COMPUTER-BASED TEST, THE SPAETH/RICHMAN CONTRAST SENSITIVITY TEST.

Background: Contrast sensitivity (CS) is a valuable measure of visual function in patients with age-related macular degeneration (AMD). The authors aimed to compare a novel computer-based test (the Spaeth/Richman Contrast Sensitivity test) with Pelli–Robson test for evaluating CS in patients with AMD. Methods: In this prospective cross-sectional study, CS was evaluated in patients with various stages of AMD and healthy controls using Spaeth/Richman Contrast Sensitivity test and Pelli–Robson test. Spaeth/Richman Contrast Sensitivity test determined CS scores for 5 areas of vision for each eye (central, superonasal, superotemporal, inferonasal, and inferotemporal) and the total score. Test scores between the two methods were compared using mixed-effects linear regression. Spearmans rank correlation coefficient was used to determine correlations. Test–retest reliability was determined using the intraclass correlation coefficient. Results: Of 35 participants with AMD (54 eyes) and 34 controls (66 eyes), 51% were female and 93% were of European descent. The mean Spaeth/Richman Contrast Sensitivity test score for the central area and each of the 4 peripheral quadrants was significantly lower for patients with AMD versus controls (P < 0.001 for all). The mean Pelli–Robson score was also significantly lower in patients with AMD versus controls (P < 0.001). The intraclass correlation coefficient for Spaeth/Richman Contrast Sensitivity test total score and Pelli–Robson score was 0.87 and 0.92, respectively. Conclusion: Spaeth/Richman Contrast Sensitivity test, a novel Internet-based method of testing CS, had significantly lower scores for patients with AMD compared with controls for central and peripheral vision. This test is a valuable tool for assessing CS in AMD.

Assessing age-related macular degeneration with the ADREV performance-based measure.

Purpose: To validate a new third-generation performance-based measure titled the “assessment of disability related to vision” (ADREV) in a study population of individuals with age-related macular degeneration. Methods: Patients with either exudative or nonexudative age-related macular degeneration, but without ocular comorbidity, completed the ADREV, the 25-item National Eye Institute’s visual functioning questionnaire, and a range of clinical assessments. Correlations were calculated between the data provided by the ADREV, visual functioning questionnaire, and clinical ophthalmic measures. Regression and bootstrap analysis were preformed to determine the relative relationship between specific clinical measures and ADREV performance, while controlling for a range of potentially confounding factors. Results: One hundred twelve patients completed the study and correlative analysis showed that ADREV total and subscale scores were more related to nearly all measures of clinical ophthalmic status in comparison with the data provided by the visual functioning questionnaire. Significant correlative relationships between ADREV and visual functioning questionnaire scores showed moderate to high correlation. Central visual acuity and contrast sensitivity shared the strongest association with performance of activities. Conclusions: The ADREV is a valid instrument for the assessment of visual disability in patients with age-related macular degeneration. Furthermore, the data provided by this performance measure had stronger relationships with clinical indicators of visual impairment in comparison with self-report.