Mesopic and Scotopic Light Sensitivity and Its Microstructural Correlates in Pseudoxanthoma Elasticum
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Mesopic and Scotopic Light Sensitivity and Its Microstructural Correlates in Pseudoxanthoma Elasticum. / Hess, Kristina; Gliem, Martin; Charbel Issa, Peter; Birtel, Johannes; Müller, Philipp L; von der Emde, Leon; Herrmann, Philipp; Holz, Frank G; Pfau, Maximilian.
In: JAMA OPHTHALMOL, Vol. 138, No. 12, 01.12.2020, p. 1272-1279.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Mesopic and Scotopic Light Sensitivity and Its Microstructural Correlates in Pseudoxanthoma Elasticum
AU - Hess, Kristina
AU - Gliem, Martin
AU - Charbel Issa, Peter
AU - Birtel, Johannes
AU - Müller, Philipp L
AU - von der Emde, Leon
AU - Herrmann, Philipp
AU - Holz, Frank G
AU - Pfau, Maximilian
PY - 2020/12/1
Y1 - 2020/12/1
N2 - IMPORTANCE: Correlates for Bruch membrane alterations are needed for interventional trials targeting the Bruch membrane in pseudoxanthoma elasticum (PXE).OBJECTIVES: To quantify mesopic and scotopic light sensitivity and identify its microstructural correlates associated with a diseased Bruch membrane in patients with PXE.DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, cross-sectional case-control study was conducted at a tertiary referral center from January 31, 2018, to February 20, 2020. Twenty-two eyes of 22 patients with PXE and 40 eyes of 40 healthy individuals were included. Data analysis was completed March 15, 2020.EXPOSURES: Mesopic and dark-adapted 2-color fundus-controlled perimetry (microperimetry) and multimodal retinal imaging including spectral-domain optical coherence tomography (SD-OCT) and OCT angiography were performed. Perimetry thresholds were analyzed using mixed models, and structure-function correlation with SD-OCT data was performed using machine learning.MAIN OUTCOMES AND MEASURES: Observed dark-adapted cyan sensitivity loss as measure of rod photoreceptor dysfunction, as well as mean absolute error between predicted and observed retinal sensitivity to assess the accuracy of structure-function correlation.RESULTS: Of the 22 patients with PXE included in this study, 15 were women (68%); median age was 56.5 years (interquartile range, 50.4-61.2). These patients exhibited mesopic (estimate, 5.13 dB; 95% CI, 2.89-7.38 dB), dark-adapted cyan (estimate, 9.08 dB; 95% CI, 6.34-11.82 dB), and dark-adapted red (estimate, 7.05 dB; 95% CI, 4.83-9.27 dB) sensitivity losses. This sensitivity loss was also evident in 9 eyes with nonneovascular PXE (mesopic: estimate, 3.21 dB; 95% CI, 1.28-5.14 dB; dark-adapted cyan: 5.93 dB; 95% CI, 3.59-8.27 dB; and dark-adapted red testing: 4.84 dB; 95% CI, 2.88-6.80 dB), showing a distinct centrifugal pattern of sensitivity loss with preserved function toward the periphery. Retinal function could be predicted from microstructure with high accuracy (mean absolute errors, of 4.91 dB for mesopic, 5.44 dB for dark-adapted cyan, and 4.99 dB for dark-adapted red). The machine learning-based analysis highlighted an association of a thinned inner retina and putative separation of the pigment-epithelium-photoreceptor complex with sensitivity loss.CONCLUSIONS AND RELEVANCE: In this study, among 22 patients with PXE, those with and without choroidal neovascularization exhibited reductions of retinal sensitivity being most pronounced in dark-adapted cyan testing. This finding suggests that pathologic characteristics of this Bruch membrane disease may be dominated by rod photoreceptor degeneration and/or dysfunction. A putative pigment-epithelium-photoreceptor separation may further impair rod function, while inner retinal abnormalities appear to be correlated with overall dysfunction.
AB - IMPORTANCE: Correlates for Bruch membrane alterations are needed for interventional trials targeting the Bruch membrane in pseudoxanthoma elasticum (PXE).OBJECTIVES: To quantify mesopic and scotopic light sensitivity and identify its microstructural correlates associated with a diseased Bruch membrane in patients with PXE.DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, cross-sectional case-control study was conducted at a tertiary referral center from January 31, 2018, to February 20, 2020. Twenty-two eyes of 22 patients with PXE and 40 eyes of 40 healthy individuals were included. Data analysis was completed March 15, 2020.EXPOSURES: Mesopic and dark-adapted 2-color fundus-controlled perimetry (microperimetry) and multimodal retinal imaging including spectral-domain optical coherence tomography (SD-OCT) and OCT angiography were performed. Perimetry thresholds were analyzed using mixed models, and structure-function correlation with SD-OCT data was performed using machine learning.MAIN OUTCOMES AND MEASURES: Observed dark-adapted cyan sensitivity loss as measure of rod photoreceptor dysfunction, as well as mean absolute error between predicted and observed retinal sensitivity to assess the accuracy of structure-function correlation.RESULTS: Of the 22 patients with PXE included in this study, 15 were women (68%); median age was 56.5 years (interquartile range, 50.4-61.2). These patients exhibited mesopic (estimate, 5.13 dB; 95% CI, 2.89-7.38 dB), dark-adapted cyan (estimate, 9.08 dB; 95% CI, 6.34-11.82 dB), and dark-adapted red (estimate, 7.05 dB; 95% CI, 4.83-9.27 dB) sensitivity losses. This sensitivity loss was also evident in 9 eyes with nonneovascular PXE (mesopic: estimate, 3.21 dB; 95% CI, 1.28-5.14 dB; dark-adapted cyan: 5.93 dB; 95% CI, 3.59-8.27 dB; and dark-adapted red testing: 4.84 dB; 95% CI, 2.88-6.80 dB), showing a distinct centrifugal pattern of sensitivity loss with preserved function toward the periphery. Retinal function could be predicted from microstructure with high accuracy (mean absolute errors, of 4.91 dB for mesopic, 5.44 dB for dark-adapted cyan, and 4.99 dB for dark-adapted red). The machine learning-based analysis highlighted an association of a thinned inner retina and putative separation of the pigment-epithelium-photoreceptor complex with sensitivity loss.CONCLUSIONS AND RELEVANCE: In this study, among 22 patients with PXE, those with and without choroidal neovascularization exhibited reductions of retinal sensitivity being most pronounced in dark-adapted cyan testing. This finding suggests that pathologic characteristics of this Bruch membrane disease may be dominated by rod photoreceptor degeneration and/or dysfunction. A putative pigment-epithelium-photoreceptor separation may further impair rod function, while inner retinal abnormalities appear to be correlated with overall dysfunction.
KW - Case-Control Studies
KW - Cross-Sectional Studies
KW - Dark Adaptation/physiology
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Male
KW - Middle Aged
KW - Prospective Studies
KW - Pseudoxanthoma Elasticum/complications
KW - Retina/diagnostic imaging
KW - Retinal Diseases/diagnosis
KW - Tomography, Optical Coherence/methods
KW - Visual Acuity
KW - Visual Field Tests/methods
KW - Visual Fields/physiology
U2 - 10.1001/jamaophthalmol.2020.4335
DO - 10.1001/jamaophthalmol.2020.4335
M3 - SCORING: Journal article
C2 - 33090206
VL - 138
SP - 1272
EP - 1279
JO - JAMA OPHTHALMOL
JF - JAMA OPHTHALMOL
SN - 2168-6165
IS - 12
ER -