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Biomedical subjects

H G Lemij

Publications and source records attributed to H G Lemij.

At least 19 recordsLinked to original sources

Baerveldt glaucoma implant in paediatric patients.

AIM: To evaluate the Baerveldt glaucoma implant (BGI) in paediatric glaucoma treatment. METHODS: In a retrospective non-comparative case series 55 eyes of 40 consecutive paediatric patients (< or =16 years) with primary or secondary glaucoma underwent Baerveldt (350 mm2) implantation. Surgical outcome was evaluated by Kaplan-Meier table analysis. RESULTS: The overall success rate was 80% at last follow up, with a mean follow up of 32 (range 2-78) months. Cumulative success was 94% at 12 months and 24 months, 85% at 36 months, 78% at 48 months, and 44% at 60 months. 11 eyes (20%) failed postoperatively because of an IOP >21 mm Hg (eight eyes), persistent hypotony (two eyes), and choroidal haemorrhage following cataract surgery (one eye). The most frequent complication needing surgery was tube related (20%). A new observation was mild to moderate dyscoria in 22% of the eyes, all buphthalmic, caused by entrapment of a tuft of peripheral iris in the tube track. CONCLUSIONS: The BGI is effective and safe in the management of primary and secondary glaucoma. When angle surgery has proved to be unsuccessful or inappropriate in paediatric patients, a BGI is a good treatment option. One must be prepared to deal with the tube related problems.

Adolescent↗

Estimating the clinical usefulness of optic disc biometry for detecting glaucomatous change over time.

PURPOSE: First, to determine the absolute measurement precision of scanning laser ophthalmoscopy (SLO) parameters, by expressing them as 95% limits of agreement (LA(95%)). Second, to propose a method for mathematically estimating the clinical ability of a parameter to monitor disease progression, expressed as the Discriminating Capacity Index (DCI). METHODS: We measured the optic disc of 14 healthy volunteers and 14 glaucoma patients. LA(95%)-values were calculated from the average standard deviation of three measurements on the same day for repeatability, and three measurements on separate days within a 6-week period for reproducibility. We then calculated the DCI by dividing the measurement range by its LA(95%) in healthy subjects and glaucoma patients separately. Thus, the DCI takes into account both the dynamic range of disease progression and the extent of measurement variance, providing an index of the possible clinical usefulness of a parameter. As the DCI is dimensionless it allows comparison across various parameters and across technologies. RESULTS: In the glaucoma group, the SLO parameters with the highest DCIs were 'volume below' (DCI, 9.38) and 'mean contour depth' (DCI, 8.02). In the healthy group, 'Neuroretinal rim area' had the highest index (DCI, 2.15). CONCLUSION: SLO optic disc biometry is uniformly reproducible and may prove a clinically useful method for glaucoma follow-up, due to the high DCI found for several parameters. The capacity to detect conversion from health to glaucoma is less pronounced, possibly due to a larger biological variability found in healthy volunteers.

Biometry↗

Automated detection of wedge-shaped defects in polarimetric images of the retinal nerve fibre layer.

PURPOSE: Automated glaucoma detection in images obtained by scanning laser polarimetry is currently insensitive to local abnormalities, impairing its performance. The purpose of this investigation was to test and validate a recently proposed algorithm for detecting wedge-shaped defects. METHODS: In all, 31 eyes of healthy subjects and 37 eyes of glaucoma patients were imaged with a GDx. Each image was classified by two experts in one of four classes, depending on how clear any wedge could be identified. The detection algorithm itself aimed at detecting and combining the edges of the wedge. The performance of both the experts and the algorithm were evaluated. RESULTS: The interobserver correlation, expressed as ICC(3,1), was 0.77. For the clearest cases, the algorithm yielded a sensitivity of 80% at a specificity of 93%, with an area under the ROC of 0.95. Including less obvious cases by the experts resulted in a sensitivity of 55% at a specificity of 95%, with an area under the ROC of 0.89. CONCLUSIONS: It is possible to automatically detect many wedge-shaped defects at a fairly low rate of false-positives. Any detected wedge defect is presented in a user-friendly way, which may assist the clinician in making a diagnosis.

Algorithms↗

A model based method for retinal blood vessel detection.

Retinal blood vessels are important structures in ophthalmological images. Many detection methods are available, but the results are not always satisfactory. In this paper, we present a novel model based method for blood vessel detection in retinal images. It is based on a Laplace and thresholding segmentation step, followed by a classification step to improve performance. The last step assures incorporation of the inner part of large vessels with specular reflection. The method gives a sensitivity of 92% with a specificity of 91%. The method can be optimized for the specific properties of the blood vessels in the image and it allows for detection of vessels that appear to be split due to specular reflection.

Algorithms↗

Detecting glaucomatous wedge shaped defects in polarimetric images.

Wedge shaped defects of the retinal nerve fiber layer (RNFL) may occur in glaucoma. Currently, automatic detection of wedge shaped defects in Scanning Laser Polarimetry (SLP) images of the RNFL is not available. An automatic classification is currently based only on global parameters, thereby ignoring important local information. Our method works by a modified dynamic programming technique that searches for locally strong edges with a preference for straight edges. These edges are initially classified based on their strength and next combined into wedge shaped defects. Our method yields a sensitivity of 73% and a specificity of 90% on a limited set of 65 images.

Diagnosis, Computer-Assisted↗

Surgical revision of filtration blebs: a follow-up study.

PURPOSE: To assess the clinical outcome of one technique for surgical revision of filtration blebs in terms of bleb function and intraocular pressure control. METHODS: Retrospective analysis of 36 consecutive cases of leaking, overfiltrating, or oversized blebs treated with bleb excision and conjunctiva and Tenon advancement in a glaucoma referral center between January 1991 and December 1999. Surgical success was defined as a final intraocular pressure between 6 and 22 mm Hg with or without topical antiglaucoma medication, resolution of the bleb leak, hypotony maculopathy and symptoms, and no need for repeat glaucoma surgery. RESULTS: With a minimum of 12 months and an average of 29.5 months of follow-up, the overall success rate was 86.1%, with 51.6% of patients not requiring medication. In the success group, mean (SD) intraocular pressure was 23.7 (5.9) mm Hg before the original trabeculectomy, 4.3 (3.7) mm Hg prior to revision surgery, and 13.5 (SD 3.8) mm Hg at the last follow-up visit after the revision surgery. Mean number of antiglaucoma medications was 2.1 (range, 1-4) before the original trabeculectomy, none before the revision surgery, and 0.8 (range, 0-3) at the last follow-up visit. CONCLUSIONS: The surgical revision technique offers a definitive solution for most of these bleb complications and a satisfactory intraocular pressure control in the majority of patients.

Adult↗

Scanning laser polarimetry in a selected group of patients with glaucoma and normal controls.

PURPOSE: To evaluate the ability of scanning laser polarimetry to discriminate between subjects with glaucoma with specific patterns of visual field defect and normal controls. METHODS: This cross-sectional, prospective study in a glaucoma practice, focused on subjects with glaucoma with predefined types of visual field defect, including advanced (group A, n = 14), localized (group L, n = 46), or mixed (diffuse and localized) defects (group M, n = 22) and normal controls (n = 32). Scanning laser polarimetry was performed in one study eye per subject. Two methods of analysis were used: a subjective analysis, in which examination printouts with the image of the optic disk manually blocked were classified by two observers masked to the diagnosis, and a logistic regression analysis of the retardation parameters included in the printouts. RESULTS: The observers correctly identified 97% of the controls and 68% of subjects with glaucoma (overall correct classification of 77%), with 93%, 70%, and 47% of patients from groups A, L, and M, respectively, being correctly identified. The best discrimination obtained with the logistic regression correctly identified 69% of controls and 94% of glaucoma subjects (overall correct classification of 87%). The performance was only slightly better for cases from group A compared with L and M. CONCLUSIONS: Subjective assessment of the scanning laser polarimetry standard printout of single eyes might not be sensitive enough to detect cases of glaucoma with localized or milder mixed types of visual field defect. The discriminating ability of scanning laser polarimetry improves slightly when logistic regression analysis is employed.

Cross-Sectional Studies↗

Prevalence of split nerve fiber layer bundles in healthy eyes imaged with scanning laser polarimetry.

PURPOSE: The GDx (Laser Diagnostic Technologies, San Diego, CA) is a scanning laser polarimeter designed to assess the peripapillary nerve fiber layer in vivo. On the GDx, a nerve fiber bundle can appear as a single or as a split bundle. The aim of our study was to determine the prevalence of split nerve fiber layer bundles and to demonstrate their clinical relevance. DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred fifty-four healthy volunteers participated. METHODS: We imaged 454 eyes of 254 healthy white persons with the GDx. All eyes had intraocular pressure of 21 mmHg or less, normal appearance of the optic nerve head, and normal visual fields (Humphrey Field Analyzer 24-2 full threshold program). According to our working definition, a bundle appeared 'split' when the color-coded pixels corresponding to areas of higher retardation were clearly divided into two more-or-less symmetrical parts not resembling a wedge defect. The classification was performed by two independent observers who used an identical set of reference examples to standardize the classification. MAIN OUTCOME MEASURES: The presence of a split nerve fiber layer bundle. RESULTS: Interobserver agreement was very good (kappa = 0.83), and a consensus was reached in all cases. In 419 eyes (92.3%) there was no split bundle. A split superior bundle was seen in 29 eyes (6.4%). A split inferior bundle was observed in five eyes (1.1%), and in one eye (0.2%) a split bundle was seen superiorly and inferiorly. When considering subjects, a split superior bundle (either in the right eye, or in the left eye, or in both eyes) occurred in 12.0% of normal subjects. The 'superior maximum' parameter was significantly lower in eyes with a split superior bundle than in eyes with a single superior bundle (67.2 microm vs. 89.9 microm; P<0.001). The same was observed for the 'symmetry' parameter (0.88 microm vs. 0.98 microm; P<0.001). CONCLUSIONS: Split nerve fiber layer bundles are a common finding in healthy eyes when imaged with the GDx. A split superior bundle is the most frequent variation, in which cases an abnormal superior maximum or symmetry parameter, otherwise potential indicators of glaucoma, should not readily be interpreted as abnormal.

Adult↗

The value of polarimetry in the evaluation of the optic nerve in glaucoma.

Scanning laser polarimetry (SLP) is a technology used to measure the thickness of the human retinal nerve fiber layer (NFL) in vivo. SLP has been demonstrated to well differentiate between glaucomatous, ocular hypertensive, and normal eyes, despite overlapping data. Recently increased interest is seen in the polarizing properties of the cornea and crystalline lens that may lead to spurious measurements. Although the instruments that use SLP compensate for these anterior segment polarizing properties, recent interest has focused on the extent and effects of incomplete compensation. If well compensated in all, SLP may better separate diseased from normal eyes. Its promising role in the follow-up of glaucoma is still under investigation.

Disease Progression↗

Upper eyelid motility in blepharoptosis and in the aging eyelid.

PURPOSE: To study the metrics of lid saccades in blepharoptosis and to distinguish any differences in the dynamics of eyelid movements that are related to the cause of blepharoptosis and to aging. METHODS: The lid and vertical eye saccades of 7 patients with congenital blepharoptosis and those of 18 patients with aponeurogenic blepharoptosis, either involutional or rigid-contact-lens-induced, were recorded with electromagnetic search coils. For each saccade, two parameters were assessed: amplitude and peak velocity. Two age-matched control groups were assessed in the same manner. Repeated measures analysis of variance was used to investigate any observed differences between the included groups. RESULTS: Congenital and rigid-contact-lens-induced blepharoptosis were readily distinguishable from one another, as well as from the age-matched control group, in both lid saccadic amplitude and peak velocity. For example, 40 degrees downward lid saccades in the congenital blepharoptosis group averaged 22.9 degrees +/- 4.0 degrees (SD), whereas 30.0 degrees +/- 4.7 degrees lid saccades were made by the age-matched control group. The subjects in the two groups with aponeurogenic blepharoptosis also made lid saccades that were distinctive for their group (P: < 0.02), in both amplitude and peak velocity. For 40 degrees downward saccades in involutional and rigid-contact-lens-induced blepharoptosis, lid saccadic amplitude averaged 32.7 degrees +/- 4.3 degrees and 40.3 degrees +/- 3.5 degrees, respectively. Lid saccadic peak velocity declined significantly with age. Lid saccadic peak velocity for 40 degrees upward saccades in the younger control group averaged 401.7 +/- 11.4 deg/sec, whereas the older control group achieved an average peak velocity of 360.7 +/- 60.4 deg/sec. The lid saccadic dynamics in the involutional blepharoptosis group proved to be similar (P: > 0.05) in saccadic amplitude and peak velocity to those of age-matched controls. CONCLUSIONS: In different forms of blepharoptosis, distinctive metrics of lid saccades occur. The current data suggest that involutional blepharoptosis is not a consequence of normal age-related changes in eyelid function.

Adult↗

Axonal loss in a patient with anterior ischemic optic neuropathy as measured with scanning laser polarimetry.

PURPOSE: To report Nerve Fiber Analyzer (NFA/GDx; Laser Diagnostic Technologies, San Diego, California) measurements in a patient during the early phase of an anterior ischemic optic neuropathy. METHODS: Case report. A 58-year old man with acute anterior ischemic optic neuropathy had repeated NFA/GDx scans of the nerve fiber layer adjacent to the optic nerve head of the involved eye, as well as repeated HFA 30.2 (Humphrey Field Analyzer; Humphrey Systems, San Leandro, California) visual field examinations. RESULTS: At presentation (day 0), he had a normal superior nerve fiber bundle on the NFA/GDx, with a deep inferior hemifield scotoma. By day 21 and day 36, the superior nerve fiber bundle thinned on the NFA/GDx, whereas the scotoma remained practically unchanged. CONCLUSION: These findings suggest that after the onset of an anterior ischemic optic neuropathy, acute loss of axonal function results in scotoma, presumably from ischemia. This is followed by a gradual disappearance of nerve fiber tissue, as measured with the NFA/GDx, within several weeks.

Axons↗

Comparison of artificial eye amplitudes with acrylic and hydroxyapatite spherical enucleation implants.

PURPOSE: To compare artificial eye amplitudes in patients who randomly received either a hydroxyapatite or an acrylic, scleral-covered spherical implant after enucleation. DESIGN: Randomized, controlled trial. PARTICIPANTS: Thirty-four consecutive patients who underwent enucleation because of an intraocular melanoma and 21 healthy control participants from the hospital staff. METHODS: Eligible patients randomly received a hydroxyapatite or an acrylic, scleral-covered spherical orbital implant. Fourteen patients were fitted with a hydroxyapatite implant, and 16 were fitted with an acrylic implant. We measured horizontal and vertical saccadic amplitudes of both the artificial eye and the healthy eye. Measurements were performed with the magnetic search coils technique. Saccadic amplitudes of the artificial eye were compared with the healthy eye of the patient. The amplitudes of the healthy eyes were compared with saccadic amplitudes of control participants. The interval from surgery to measurements was at least 3 months in all patients. Saccadic gain (artificial eye and eye amplitude divided by target amplitude) and saccadic symmetry (artificial eye amplitude divided by healthy eye amplitude) were calculated. MAIN OUTCOME MEASURES: Saccadic gain and saccadic symmetry. RESULTS: The gain in the healthy eyes of the patients was comparable with the gain of the control eyes. Saccadic symmetry was 1.0 in control participants. In patients, it was 0.334 in horizontal saccades and 0.577 in vertical saccades. However, saccadic symmetry did not differ significantly between the acrylic group and the hydroxyapatite group (P: > 0.1 for any saccadic direction). Equivalence was detectable with a power more than 90% for horizontal saccades and more than 80% for vertical saccades. Curvilinearity was rejected for both patient groups and for all saccadic directions (P: > 0.5). CONCLUSIONS: When no motility peg is placed, acrylic and hydroxyapatite spherical implants yield comparable saccadic amplitudes of the artificial eye. Artificial eye amplitudes were markedly more restricted horizontally than vertically. In all saccadic directions, the relation between target amplitude and artificial eye amplitude was linear.

Acrylic Resins↗

Reproducibility of measurements with the nerve fiber analyzer (NfA/GDx).

PURPOSE: To determine the reproducibility of measurements with the Nerve Fiber Analyzer, a scanning laser polarimeter designed for quantifying glaucoma in healthy patients and patients with glaucoma. The authors also assessed the variance of measurements between instruments. METHODS: Measurements were made with the third generation Nerve Fiber Analyzer, the GDx. The study consisted of three parts. In the first part, the authors measured the right eyes of 10 healthy volunteers on 5 consecutive days. In the second part, 45 patients with glaucoma underwent Nerve Fiber Analyzer measurements of one randomly selected eye on two separate days in a 5-week period. For all 14 available parameters, reproducibility of measurements was expressed in terms of 95% limits of agreement and as the intraclass correlation coefficient. The Nerve Fiber Analyzer software has an option of creating a mean image from a selection of single images; for both parts of the study, the reproducibility of measurements was calculated for a "single image," and a "mean-of-three" image. In the third part of the study, 17 volunteers underwent repeated Nerve Fiber Analyzer measurement sessions on each of three different instruments. Using multivariate analysis of variance, the authors determined the variance of measurements between instruments. RESULTS: The reproducibility of measurements varied considerably across parameters. Limits of agreement in mean images for superior maximum and inferior maximum were 7.2 microm and 7.7 microm, respectively in the healthy volunteers, and 8.7 microm and 7.9 microm, respectively in the patients with glaucoma. For healthy patients, the intraclass correlation coefficient was greater than 90% in 10 of 14 parameters. In patients with glaucoma, the intraclass correlation coefficient was greater than 90% in 13 of 14 parameters. Some parameters reproduced better in a mean than in a single image; these differences, however, were small and generally not statistically significant. The between-instruments component also varied across parameters and was highest in ratio-based parameters. CONCLUSIONS: The reproducibility of measurements varied across parameters. In general, the reproducibility of measurements with the Nerve Fiber Analyzer was high. The reproducibility of measurements was similar between healthy patients and patients with glaucoma. Any measured change in nerve fiber layer thickness would be statistically significant if it exceeded approximately 7 or 8 microm in the superior maximum or inferior maximum parameter in healthy patients. Reproducibility of measurements hardly differed between single images and mean images. The reproducibility of measurements among the three instruments we used was highest for straight parameters.

Adult↗

Retinal nerve fiber layer thickness in human strabismic amblyopia.

BACKGROUND AND PURPOSE: Amblyopia is characterized by histopathological changes in the visual cortex and lateral geniculate nucleus. In the retina, however, no abnormalities have yet been reported. The purpose of this study was to compare the nerve fiber layer (NFL) thickness in the amblyopic eye with that in the sound eye of patients with strabismic amblyopia. As a practical implication, we investigated the validity of comparing Nerve Fiber Analyzer (NFA) measurements obtained in amblyopic eyes to the normative database built into the NFA. METHODS: NFL thickness was measured with a third generation NFA, the GDx (Laser Diagnostic Technologies, San Diego, CA). This is a scanning laser polarimeter, designed for monitoring glaucoma. The following NFL thickness parameters (all in microns) were compared: average thickness, superior maximum, inferior maximum, superior average, inferior average, nasal median and temporal median. Twenty patients with strabismic amblyopia were imaged with the NFA. Patients had no nystagmus, neurological disease or glaucoma. Nine patients had amblyopia in the right eye, and 11 patients in the left eye. RESULTS: In general, the sound eyes yielded higher thickness measures than the amblyopic eyes. These differences, however, were small, averaging only 1.5%, p = 0.6, and therefore not "statistically significant" at the p&le 0.05 level. CONCLUSIONS: Using the standard of "Statistical Significance = p< or =0.05", when amblyopic eyes are measured with the NFA, the built-in normative database may serve as the reference data

Adolescent↗

Retinal nerve fiber layer measurements in normal black subjects as determined with scanning laser polarimetry.

PURPOSE: This study aimed to obtain normal nerve fiber layer (NFL) measurements by means of scanning laser polarimetry in black subjects and to compare these measurements with those in normal white subjects. METHODS: Polarimetric NFL measurements were obtained in 1 eye of 133 normal black subjects and 133 age- and gender-matched white subjects. Ratios were determined for the superior and inferior NFL, each relative to the nasal value (S/N and I/N, respectively). Results of black and white subjects were compared by means of the Student's t test. The effect of age on NFL measurements was determined with linear regression analysis. RESULTS: The mean S/N was statistically significantly lower in black subjects (1.7) when compared with that of white subjects (2.5). Similar values were obtained for I/N. In this cross-sectionally performed study, a negative, albeit not significant relation (-0.003) was recognized between NFL measurements and age for both S/N and I/N in black subjects. In the white subjects, there was a statistically significant relation of -0.012 between age and NFL measurements. CONCLUSIONS: The NFL retardation is less in black than in white subjects. Compared with white subjects, the decrease in NFL measurements of black subjects over time, cross sectionally, appears less.

Adult↗

Eyeball position in Graves orbitopathy and its significance for eyelid surgery.

The goal of this article is to investigate the effect of Graves orbitopathy and orbital decompression on the position of the eyeball, and to relate this to a straight upper eyelid contour, observed in several patients after correction of upper eyelid retraction. The positions of the pupil center and the upper and lower eyelid margin were measured in relation to a reference line through the medial canthi, on slides obtained from 120 eyelids before and after correction of upper eyelid retraction, and on similar slides obtained from 90 control eyelids. In control subjects, the distance between the reference line and the pupil center was, on average, 4.5 mm (SD 1.2 mm). In decompressed patients, the pupil center was, on average, 2.2 mm lower (SD 1.3 mm), and in nondecompressed patients it was, on average 1.0 mm lower (SD 1.2 mm). A relatively straight upper eyelid contour after otherwise satisfactory correction of upper eyelid retraction was observed in 14 eyelids of 8 patients. All cases occurred in decompressed patients with a distance between the pupil center and the reference line of 2 mm or less. No significant difference was found in the position of the lateral canthal angle between the three groups. Many patients with Graves orbitopathy show a downward shift of the pupil center in relation to a reference line through the medial canthi. This is partially caused by orbital decompression, but also by other factors discussed by the authors. If the distance between this reference line and the pupil center is 2 mm or less, otherwise satisfactory correction of upper eyelid retraction may cause visible straightening of the upper eyelid contour.

Adult↗

Saccadic eye movements in Graves' disease.

PURPOSE: To describe the saccades made by patients with Graves' disease (GD) and to attempt to distinguish these objectively and quantitatively from the saccades in control subjects. METHODS: In 12 euthyroid patients with GD, the saccades of both eyes were recorded simultaneously with electromagnetic search coils. Subjects were asked to alternate their gazes between two fixed targets that were 10 degrees, 20 degrees, 30 degrees, or 40 degrees apart along each horizontal or vertical meridian. The data from the patients with GD and those from the similarly recorded group of 12 control subjects were examined in two ways. First, the difference in saccadic sizes between the two eyes was assessed. Second, the saccadic dynamics--that is, the maximum velocity and the saturation constant of the main sequence--were determined for each eye. Repeated measurement analysis of variance was used to test observed differences between the two groups. Finally, through exact logistic regression analysis, classification of the saccades as those of a patient with GD or of a control subject was carried out. RESULTS: The saccades of patients with GD were generally less conjugate than those of control subjects (P < 0.05). On average, the maximum main sequence velocities in patients with GD were lower than in control subjects (P < 0.05). The saccades of patients with GD were well differentiated from those of control subjects. CONCLUSIONS: The saccades in GD may differ markedly from normal saccades, and the two can be reliably distinguished.

Adult↗

The sensitivity and specificity of nerve fiber layer measurements in glaucoma as determined with scanning laser polarimetry.

PURPOSE: To determine the sensitivity and specificity for detecting glaucoma by scanning laser polarimetry and to assess the relation between nerve fiber layer (NFL) measurements and visual field indices. METHODS: The peripapillary NFL was divided into four segments: superior, inferior, temporal, and nasal. The mean polarimetric NFL for each segment was calculated out of six selected areas of 256 pixels each. Ratios relative to the nasal segment were determined for the superior and inferior segments. With the use of previously obtained normograms for polarimetric NFL readings, the sensitivity of scanning laser polarimetry was assessed in 200 glaucomatous eyes (155 subjects). The specificity was assessed in a normal population of 150 eyes (150 subjects). The relation between hemifield polarimetric NFL and visual field indices was assessed by linear regression analysis. RESULTS: The sensitivity of scanning laser polarimetry was 96% and the specificity was 93%. The correlation between NFL parameters and visual field indices ranged from -0.18 to +0.26. The amount of variation by the linear regression model ranged from 3% to 6%. CONCLUSIONS: Although quantitative measurements of the NFL with scanning laser polarimetry relate poorly to visual field indices, the technique seems to be promising for screening populations for glaucoma. Whether measurements of the NFL with scanning laser polarimetry are also sensitive enough to detect change over time requires further study.

Adult↗