The Value of Static Perimetry in the Diagnosis and Follow-up of Negative Dysphotopsia.

SIGNIFICANCE: There is a clinical need for a quantitative test to objectively diagnose negative dysphotopsia, especially because the diagnosis is generally assessed using patients' subjective descriptions. In the search of a clinical test to objectify the shadow experienced in negative dysphotopsia, this study excludes static perimetry as suitable evaluation method. PURPOSE: This study aimed to evaluate the value of static perimetry in the objective assessment and follow-up of negative dysphotopsia. METHODS: Peripheral 60-4 full-threshold visual field tests were performed in 27 patients with negative dysphotopsia and 33 pseudophakic controls. In addition, 11 patients with negative dysphotopsia repeated the test after an intraocular lens exchange. Both the total peripheral visual field and the averaged peripheral visual field from 50 to 60° eccentricity were compared between patients and controls, and pre-operatively and post-operatively in patients who had an intraocular lens exchange. RESULTS: The peripheral visual fields from 30 to 60° did not show significant differences between patients with negative dysphotopsia and pseudophakic controls. Analysis of the peripheral visual field from 50 to 60° showed a median [Q1, Q3] of 20.0 [17.1, 22.5] dB in the negative dysphotopsia group compared with 20.1 [15.5, 21.3] dB in the control group (P = .43). Although 82% of patients treated with an intraocular lens exchange subjectively reported improvement of their negative dysphotopsia complaints post-operatively, there were no significant differences in their total peripheral visual field or averaged peripheral visual field from 50 to 60° (P = .92). CONCLUSIONS: Full-threshold static perimetry with a Goldmann size III stimulus up to 60° eccentricity does not show significant differences between patients with negative dysphotopsia and pseudophakic controls or between measurements before and after intraocular lens exchange. Therefore, this type of static perimetry cannot be used as a quantitative objective test for diagnosis or follow-up of patients with negative dysphotopsia.

The feasibility of quantitative MRI of extra-ocular muscles in myasthenia gravis and Graves' orbitopathy.

Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra-ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye-motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2water ) of EOM in healthy controls (HC), myasthenia gravis (MG) and Graves' orbitopathy (GO) patients. FF, EOM volumes and T2water values were determined in 12 HC (aged 22-65 years), 11 MG (aged 28-71 years) and six GO (aged 28-64 years) patients at 7 T using Dixon and multi-echo spin-echo sequences. The EOM were semi-automatically 3D-segmented by two independent observers. MANOVA and t-tests were used to assess differences in FF, T2water and volume of EOM between groups (P < .05). Bland-Altman limits of agreement (LoA) were used to assess the reproducibility of segmentations and Dixon scans. The scans were well tolerated by all subjects. The bias in FF between the repeated Dixon scans was -0.7% (LoA: ±2.1%) for the different observers; the bias in FF was -0.3% (LoA: ±2.8%) and 0.03 cm3 (LoA: ± 0.36 cm3 ) for volume. Mean FF of EOM in MG (14.1% ± 1.6%) was higher than in HC (10.4% ± 2.5%). Mean muscle volume was higher in both GO (1.2 ± 0.4 cm3 ) and MG (0.8 ± 0.2 cm3 ) compared with HC (0.6 ± 0.2 cm3 ). The average T2water for all EOM was 24.6 ± 4.0 ms for HC, 24.0 ± 4.7 ms for MG patients and 27.4 ± 4.2 ms for the GO patient. Quantitative MRI at 7 T is feasible for measuring FF and muscle volumes of EOM in HC, MG and GO patients. The measured T2water was on average comparable with skeletal muscle, although with higher variation between subjects. The increased FF in the EOM in MG patients suggests that EOM involvement in MG is accompanied by fat replacement. The unexpected EOM volume increase in MG may provide novel insights into underlying pathophysiological processes.

Correction Method for Optical Scaling of Fundoscopy Images: Development, Validation, and First Implementation.

Purpose: Although fundus photography is extensively used in ophthalmology, refraction prevents accurate distance measurement on fundus images, as the resulting scaling differs between subjects due to varying ocular anatomy. We propose a PARaxial Optical fundus Scaling (PAROS) method to correct for this variation using commonly available clinical data. Methods: The complete optics of the eye and fundus camera were modeled using ray transfer matrix formalism to obtain fundus image magnification. The subject's ocular geometry was personalized using biometry, spherical equivalent of refraction (RSE), keratometry, and/or corneal topography data. The PAROS method was validated using 41 different eye phantoms and subsequently evaluated in 44 healthy phakic subjects (of whom 11 had phakic intraocular lenses [pIOLs]), 29 pseudophakic subjects, and 21 patients with uveal melanoma. Results: Validation of the PAROS method showed small differences between model and actual image magnification (maximum 3.3%). Relative to the average eye, large differences in fundus magnification were observed, ranging from 0.79 to 1.48. Magnification was strongly inversely related to RSE (R2 = 0.67). In phakic subjects, magnification was directly proportional to axial length (R2 = 0.34). The inverse relation was seen in pIOL (R2 = 0.79) and pseudophakic (R2 = 0.12) subjects. RSE was a strong contributor to magnification differences (1%-83%). As this effect is not considered in the commonly used Bennett-Littmann method, statistically significant differences up to 40% (mean absolute 9%) were observed compared to the PAROS method (P < 0.001). Conclusions: The significant differences in fundus image scaling observed among subjects can be accurately accounted for with the PAROS method, enabling more accurate quantitative assessment of fundus photography.

Peripheral visual field shifts after intraocular lens implantation.

PURPOSE: To assess whether intraocular lens (IOL) implantation induces shifts in the peripheral visual field. SETTING: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. DESIGN: Ray-tracing study. METHODS: Nonsequential ray-tracing simulations were performed with phakic and pseudophakic versions of the same eye model to assess potential shifts in the visual field after IOL implantation. 2 different IOL designs were evaluated and for each design 5 different axial positions and 7 different intrinsic powers were tested. The relation between the physical position of the light source and the location where the retina was illuminated was determined for each eye model. Subsequently, these relations were used to calculate whether the visual field shifts in pseudophakic eyes. RESULTS: The pseudophakic visual field shift was below 1 degree for central vision in all evaluated models. For peripheral vision, the light rays in the pseudophakic eyes were refracted to a more central retinal location compared with phakic eyes, resulting in a central shift of the peripheral visual field. The magnitude of the shift depended on the IOL design and its axial position, but could be as high as 5.4 degrees towards central vision. CONCLUSIONS: IOL implantation tends to have little effect on the central visual field but can induce an over 5 degrees shift in the peripheral visual field. Such a shift can affect the perception of peripheral visual complaints.

Measuring quality of vision including negative dysphotopsia.

PURPOSE: To adapt the Quality of Vision Questionnaire (QoV) for measuring negative dysphotopsia and to validate the original and modified versions in the Dutch population. METHODS: The QoV was translated into Dutch according to standardized methodology. Negative dysphotopsia items were constructed based on focus group interviews, literature review and clinical data. The questionnaire was completed by 404 subjects, including contact lens wearers, patients with cataract and after cataract surgery (95.5% with a monofocal, 4.5% with a multifocal intraocular lens). Rasch analysis was applied for evaluation of reliability and validity of the original QoV and modified version, Negative Dysphotopsia QoV (ND-QoV). RESULTS: The frequency, severity and bothersome scales of the QoV and ND-QoV demonstrated good measurement precision, good fit statistics for all but one item, but significant mistargeting of more than one logit. Item estimations were stable across the study groups and scales were unidimensional with more than 50% of variance explained by the measurements. There was a positive correlation between questionnaire scores and best corrected visual acuity (r = 0.3, p < 0.01). The quality of vision measured by all three scales was significantly poorer (p < 0.01) in patients with negative dysphotopsia compared to asymptomatic pseudophakic patients. CONCLUSION: The Dutch version of the QoV questionnaire has shown good psychometric properties comparable to the native version as well as good reliability and validity. The addition of negative dysphotopsia items is a valuable modification for the reliable assessment of quality of vision in pseudophakic patients.

Comparison of Magnetic Resonance Imaging-Based and Conventional Measurements for Proton Beam Therapy of Uveal Melanoma.

OBJECTIVE: Conventionally, ocular proton therapy (PT) is planned using measurements obtained by an ophthalmologist using ultrasound, fundoscopy, biometry, and intraoperative assessments. Owing to the recent advances in magnetic resonance imaging (MRI) of uveal melanoma (UM), it is possible to acquire high-resolution 3-dimensional images of the eye, providing the opportunity to incorporate MRI in ocular PT planning. In this study, we described how these measurements can be obtained using MRI, compared the MRI-based measurements with conventional ophthalmic measurements, and identified potential pitfalls for both modalities. DESIGN: Cross-sectional study. SUBJECTS: Data from 23 consecutive patients with UM treated with PT were retrospectively evaluated. METHODS: Magnetic resonance imaging-based measurements of axial length, tumor height and basal diameter, and marker-tumor distances were compared with the conventional ophthalmic measurements, and discrepancies were evaluated in a multidisciplinary setting. MAIN OUTCOME MEASURES: Tumor prominence and basal diameters on MRI and ultrasound, axial length on MRI and biometry, tumor-marker distances on MRI and measured intraoperatively. RESULTS: The mean absolute differences of the tumor height and basal diameter measurements between ultrasound and MRI were 0.57 mm and 1.44 mm, respectively. Larger absolute differences in height and basal diameter were observed when the full tumor extent was not visible on ultrasound (0.92 mm and 1.67 mm, respectively) compared with when the full tumor extent was visible (0.44 mm and 1.15 mm, respectively). When the full tumor was not visible on ultrasound, MRI was considered more reliable. Tumor-marker distances measured using MRI and intraoperative techniques differed < 1 mm in 55% of the markers. For anteriorly located and mushroom-shaped tumors (25% of the markers), MRI provided more accurate measurements. In flat UM (15% of the markers), however, it was difficult to delineate the tumor on MRI. The mean absolute difference in axial length between optical biometry and MRI was 0.50 mm. The presence of the tumor was found to influence optical biometry in 15 of 22 patients; the remaining patients showed a better agreement (0.30 mm). Magnetic resonance imaging-based biometry was considered more reliable in patients with UM. CONCLUSIONS: Magnetic resonance imaging allowed for the 3-dimensional assessment of the tumor and surrounding tissue. In specific patients, it provided a more reliable measurement of axial length, tumor dimensions, and marker-tumor distances and could contribute to a more accurate treatment planning. Nevertheless, a combined evaluation remains advised, especially for flat UM.

Effect of anatomical differences and intraocular lens design on negative dysphotopsia.

PURPOSE: To assess the effect of ocular anatomy and intraocular lens (IOL) design on negative dysphotopsia (ND). SETTING: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. DESIGN: Ray-tracing study based on clinical data. METHODS: Ray-tracing simulations were performed to assess the effect of anatomical differences and differences in IOL design on the peripheral retinal illumination. To that end, eye models that incorporate clinically measured anatomical differences between eyes of patients with ND and eyes of pseudophakic controls were created. The anatomical differences included pupil size, pupil centration, and iris tilt. The simulations were performed with different IOL designs, including a simple biconvex IOL design and a more complex clinical IOL design with a convex-concave anterior surface. Both IOL designs were analyzed using a clear edge and a frosted edge. As ND is generally considered to be caused by a discontinuity in peripheral retinal illumination, this illumination profile was determined for each eye model and the severity of the discontinuity was compared between eye models. RESULTS: The peripheral retinal illumination consistently showed a more severe discontinuity in illumination with ND-specific anatomy. This difference was the least pronounced, 8%, with the frosted edge clinical IOL and the most pronounced, 18%, with the clear edge biconvex IOL. CONCLUSIONS: These results show that small differences in the ocular anatomy or IOL design affect the peripheral retinal illumination. Therewith, they can increase the severity of ND by up to 18%.

Magnetic resonance imaging reveals possible cause of diplopia after Baerveldt glaucoma implantation.

PURPOSE: To assess if ocular motility impairment, and the ensuing diplopia, after Baerveldt Glaucoma device (BGI) implantation, is related to the presence of a large fluid reservoir (bleb), using Magnetic Resonance Imaging (MRI). METHODS: In a masked observational study (CCMO-registry number: NL65633.058.18), the eyes of 30 glaucoma patients with (n = 12) or without diplopia (n = 18) who had previously undergone BGI implantation were scanned with a 7 Tesla MRI-scanner. The substructures of the BGI-complex, including both blebs and plate, were segmented in 3D. Primary outcomes were a comparison of volume and height of the BGI-complex between patients with and without diplopia. Comparisons were performed by using an unpaired t-test, Fisher's Exact or Mann-Whitney test. Correlations were determined by using Spearman correlation. RESULTS: The median volume and height of the BGI-complex was significantly higher in patients with compared to patients without diplopia (p = 0.007 and p = 0.025, respectively). Six patients had an excessively large total bleb volume (median of 1736.5mm3, interquartile range 1486.3-1933.9mm3), four of whom experienced diplopia (33% of the diplopia patients). Fibrotic strands through the BGI plate, intended to limit the height of the bleb, could be visualized but were not related to diplopia (75% versus 88%; p = 0.28). CONCLUSIONS: With MRI, we show that in a significant number of diplopia cases a large bleb is present in the orbit. Given the large volume of these blebs, they are a likely explanation of the development of diplopia in at least some of the patients with diplopia after BGI implantation. Additionally, the MR-images confirm the presence of fibrotic strands. As these strands are also visible in patients with a large bleb, they are apparently not sufficient to restrict the bleb height.

MRI-based 3D retinal shape determination.

OBJECTIVE: To establish a good method to determine the retinal shape from MRI using three-dimensional (3D) ellipsoids as well as evaluate its reproducibility. METHODS AND ANALYSIS: The left eyes of 31 volunteers were imaged using high-resolution ocular MRI. The 3D MR-images were segmented and ellipsoids were fitted to the resulting contours. The dependency of the resulting ellipsoid parameters on the evaluated fraction of the retinal contour was assessed by fitting ellipsoids to 41 different fractions. Furthermore, the reproducibility of the complete procedure was evaluated in four subjects. Finally, a comparison with conventional two-dimensional (2D) methods was made. RESULTS: The mean distance between the fitted ellipsoids and the segmented retinal contour was 0.03±0.01 mm (mean±SD) for the central retina and 0.13±0.03 mm for the peripheral retina. For the central retina, the resulting ellipsoid radii were 12.9±0.9, 13.7±1.5 and 12.2±1.2 mm along the horizontal, vertical and central axes. For the peripheral retina, these radii decreased to 11.9±0.6, 11.6±0.4 and 10.4±0.7 mm, which was accompanied by a mean 1.8 mm posterior shift of the ellipsoid centre. The reproducibility of the ellipsoid fitting was 0.3±1.2 mm for the central retina and 0.0±0.1 mm for the peripheral retina. When 2D methods were used to fit the peripheral retina, the fitted radii differed a mean 0.1±0.1 mm from the 3D method. CONCLUSION: An accurate and reproducible determination of the 3D retinal shape based on MRI is provided together with 2D alternatives, enabling wider use of this method in the field of ophthalmology.

Evaluation of intraocular lens position and retinal shape in negative dysphotopsia using high-resolution magnetic resonance imaging.

PURPOSE: To assess potential relationships of intraocular lens (IOL) position and retinal shape in negative dysphotopsia (ND). SETTING: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. DESIGN: Case-control study. METHODS: High-resolution ocular magnetic resonance imaging (MRI) scans were performed in patients with ND and pseudophakic controls, and subsequently used to determine the displacement and tilt of the in-the-bag IOL about the pupil and iris. In addition, anterior segment tomography was used to assess the iris-IOL distance. Furthermore, the retinal shape was quantified from the MRI scans by fitting an ellipse to the segmented inner boundary of the retina. Both the IOL position and retinal shape were compared between groups to assess their potential role in the etiology of ND. RESULTS: In total, 37 patients with ND and 26 pseudophakic controls were included in the study. The mean displacement and tilt of the IOL were less than 0.1 mm and 0.5 degrees, respectively, in both groups and all directions. The corresponding mean iris-IOL distance was 1.1 mm in both groups. Neither of these values differed statistically significantly between groups (all P values >.6). The retinal shape showed large variations but was not statistically significantly different between the groups in both the left-right (P = .10) and the anterior-posterior (P = .56) directions. CONCLUSIONS: In this study, the in-the-bag IOL position and retinal shape did not statistically significantly differ between patients with ND and the general pseudophakic population. Given the large variation in retinal shape between subjects, however, it could still be an important factor in a multifactorial origin of ND.

Distinct differences in anterior chamber configuration and peripheral aberrations in negative dysphotopsia.

PURPOSE: To provide insights into the anatomical characteristics associated with negative dysphotopsia using quantitative clinical data. SETTING: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. DESIGN: Case-control study. METHODS: Anterior chamber tomography and peripheral aberrometry were measured in 27 pseudophakic patients with negative dysphotopsia and 30 pseudophakic control subjects. Based on these measurements, the total corneal power, anterior chamber depth, pupil location and diameter, iris tilt, and peripheral ocular wavefront up to 30 degrees eccentricity were compared between both groups. In addition, ray-tracing simulations using pseudophakic eye models were performed to establish a connection between these clinical measurements and current hypotheses on the etiology of negative dysphotopsia. RESULTS: Twenty-seven patients with negative dysphotopsia and 25 pseudophakic controls were included in the analysis. The patients with negative dysphotopsia had a smaller (P = .03/P = <.01) and more decentered (P < .01) pupil than that of the pseudophakic controls. In addition, an increased temporal-tilted iris (P < .01) and an asymmetric peripheral aberration profile were observed in patients with negative dysphotopsia, of which the latter was also apparent in several ray-tracing models. The combination of these in vivo results and ray-tracing simulations indicated that patients with negative dysphotopsia had a temporal-rotated eye, which confirmed the hypothesized relation between negative dysphotopsia and an increased angle κ. CONCLUSIONS: Patients with negative dysphotopsia had a smaller pupil and an increased angle κ, which made them more susceptible to experiencing a shadow in the temporal visual field.