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Reliability of Mesopic Measures of Visual Acuity and Contrast Sensitivity and Their Correlation with Rod and Cone Function in Retinitis Pigmentosa

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Reliability of Mesopic Measures of Visual Acuity and Contrast Sensitivity and Their Correlation with Rod and Cone Function in Retinitis Pigmentosa UCLA UCLA Previously Published Works Title Reliability of Mesopic Measures of Visual Acuity and Contrast Sensitivity and Their Correlation with Rod and Cone Function in Retinitis Pigmentosa. Permalink https://escholarship.org/uc/item/0hf8f1q5 Journal Ophthalmic research, 63(2) ISSN 0030-3747 Authors Bittner, Ava K Ferraz, Mariana C Publication Date 2020 DOI 10.1159/000503931 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Research Article Ophthalmic Res Received: July 20, 2019 DOI: 10.1159/000503931 Accepted after revision: October 6, 2019 Published online: December 5, 2019 Reliability of Mesopic Measures of Visual Acuity and Contrast Sensitivity and Their Correlation with Rod and Cone Function in Retinitis Pigmentosa a, b b Ava K. Bittner Mariana C. Ferraz a Department of Ophthalmology, Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA, USA; b College of Optometry, Nova Southeastern University, Fort Lauderdale, FL, USA Keywords photopic conditions were significantly related to reduced Retinitis pigmentosa · Scotopic · Visual acuity · Contrast cone-mediated scotopic sensitivity (p = 0.038). Significant sensitivity · Cone sensitivity · Rod function predictors of the CCT ratio of S-cone to M- and L-cone sensi- tivity were mesopic VA (p = 0.038) and absence of AdaptDx rod function (p = 0.008). Test-retest 95% coefficients of re- Abstract peatability were not significantly different when comparing Background: Mesopic conditions elicit both rod and cone between photopic and mesopic tests of VA (0.16 and 0.12 responses, and they are more commonly encountered in logMAR, respectively) or CS (0.21 and 0.24 logCS, respective- daily life than are scotopic conditions; yet visual function ly). Conclusions: Perifoveal scotopic rod and cone function outcome measures of mesopic visual acuity (VA) or contrast measured with the AdaptDx was significantly correlated sensitivity (CS) are rarely evaluated. Objective: In retinitis with mesopic CS and VA, respectively, which had good, ac- pigmentosa (RP), we explored whether visual reductions in ceptable test-retest repeatability; thus, they appear to be mesopic versus photopic conditions were correlated with suitable outcome measures to monitor mesopic visual func- cone or rod function, as well as the between-visit test-retest tion in clinical practice or trials. RP subjects with reduced me- variability in mesopic measures. Methods: At each of two sopic VA and no perifoveal rod function had a greater loss of visits, 22 RP subjects completed mesopic and photopic sensitivity for S-cones than for L-/M-cones. ETDRS VA and Pelli-Robson chart CS tests obtained with and © 2019 S. Karger AG, Basel without a U23 NoIR 4% transmission filter; testing of perifo- veal scotopic cone or rod sensitivity with the AdaptDx; and the Rabin Cone Contrast Test (CCT). Results: A greater CS Introduction reduction in mesopic versus photopic conditions was sig- nificantly related to absence of scotopic rod function (p = Retinitis pigmentosa (RP) primarily affects rod photo- 0.038) or longer self-reported duration of night vision loss receptor function, but it is also characterized by concur- (p = 0.044). VA reductions > 0.2 logMAR in mesopic versus rent or subsequent progressive loss of cone function [1]. © 2019 S. Karger AG, Basel Ava K. Bittner Department of Ophthalmology, Stein Eye Institute University of California, Los Angeles E-Mail [email protected] 200 Stein Plaza Driveway, Los Angeles, CA 90095 (USA) www.karger.com/ore E-Mail abittne1 @ jhmi.edu Downloaded by: UCLA Biomedical Library 149.142.103.136 - 12/6/2019 8:02:17 PM Some RP patients present with normal rod and cone and the large test-retest variability for mesopic VA and function in the central retina, while others have loss of CS previously documented in RP subjects with moderate both to the same extent, or rod sensitivity loss that pre- vision loss, it remains unclear whether it should be rec- cedes cone sensitivity loss throughout the retina in other ommended that mesopic VA be included as an addition- individuals, while some have only cone function [2, 3]. al outcome measure. It is also currently unknown how These various patterns of rod and cone function loss rep- measures of mesopic VA and CS are related to loss of rod resent different stages of disease progression for some pa- or cone function in RP. tients and/or different mechanisms or subtypes of RP, Over 40 years ago, it was initially reported that RP pa- which has been previously documented to be a geneti- tients had greater loss of sensitivity for blue cones than for cally and phenotypically heterogeneous retinal degenera- green cones [9]. Subsequently, further studies published tive disease [2, 3]. Responses from both rods and cones about 30 years ago found that some patients with the au- would be elicited in conditions with mesopic illumination tosomal recessive form of RP, as well as patients with (i.e., dim or low light levels) if both photoreceptors are glaucoma or diabetic retinopathy, initially lose short- functional. Mesopic conditions are more often encoun- wavelength cone sensitivity or function (i.e., S-cones) pri- tered during typical activities of daily living than are sco- or to cones that respond to longer wavelengths (i.e., L- topic conditions; yet mesopic visual acuity (VA) or con- and M-cones) [10–12]. Around that time, it was hypoth- trast sensitivity (CS) tests are rarely included as outcome esized that this may be related to changes in the optical measures in clinical or research settings. Given the inter- density of the macular pigment [13], or a mechanism est in documenting visual changes that may impact the might affect a shared biochemical pathway vulnerability performance of typical daily activities, there is a need to found in both rods and S-cones selectively but not in oth- validate testing performed in simulated mesopic illumi- er cones [10]. However, rod function was not measured nation as a means of evaluating visual function in dim in the previous studies, and our recent search of PubMed light conditions among individuals with RP. and similar databases revealed no further research on the Previous research has reported mesopic measures of possible relationship between loss of S-cone and rod retinal sensitivity obtained with the microperimeter in RP function in RP. S-cones may be more susceptible to [4–7]. However, microperimetry is time-consuming and changes in the retinal pigment epithelium due to mor- its test-retest reliability in RP is unknown. A more effi- phologic differences from L- and M-cones. S-cones are cient measure of mesopic central visual function could smaller, and they have a longer and larger intersegment entail the use of a U23 NoIR 4% transmission filter while and deeper innervation projecting further into the sub- obtaining VA and CS measures, such as with the standard retinal space towards the retinal pigment epithelium [14]. ETDRS and Pelli-Robson letter charts. The use of the U23 S-cones also have more permeable membranes than L- NoIR 4% transmission filter for mesopic VA and CS test- and M-cones [10]. Rods and S-cones are more similar ing would be low-cost and straightforward to implement than L- and M-cones as far as calcium metabolism and across various sites. To validate the use of mesopic mea- proteins, as well as early saturation during psychophysi- sures of VA and CS for the evaluation of individuals with cal responses, are concerned [10]. Another potential ex- RP, it is important to consider their test-retest reliability. planation for the loss of S-cone sensitivity may be the fact A previous study in which one of the coauthors was in- that S-cones are the least numerous, representing only volved had reported the 95% coefficient of repeatability 10% of all cones; therefore, a loss of a few S-cone cells (CR.95) for mesopic VA with the U23 NoIR 4% transmis- would have a greater impact on visual function. However, sion filter as very similar to that for photopic VA, i.e., previous research has found greater support for metabol- 0.12–0.13 logMAR for 4 RP subjects with a VA > 0.3 log- ic damage as a source of loss of S-cone sensitivity than for MAR, but the CR.95 for mesopic VA measured in 12 RP postreceptoral causes within the visual system [15]. subjects with a VA of 0.3–1.0 logMAR in this study was The aims of the current study were to examine the re- much higher, i.e., 0.41 logMAR [8]. Similarly, the 95% lationships between scotopic visual function and: (1) VA coefficients of repeatability determined for mesopic CS or CS in mesopic versus photopic conditions in RP, and with the Pelli-Robson chart were much higher (0.51 (2) S-cone sensitivity among individuals with presumed logCS) than those for photopic CS (0.31 logCS) for RP autosomal recessive RP. We anticipated that mesopic subjects with a VA of 0.3–1.0 logMAR in that previous measures of VA and CS would be correlated with both study [8]. Given the relatively small number of RP sub- photopic and scotopic visual status. Based on previous jects with mild-to-moderate vision loss in that past study work in this field, we hypothesized that S-cone sensitivity 2 Ophthalmic Res Bittner/Ferraz DOI: 10.1159/000503931 Downloaded by: UCLA Biomedical Library 149.142.103.136 - 12/6/2019 8:02:17 PM would be correlated with rod function in those with pre- occurs at 3 log units below the brightest stimulus that is presented sumed autosomal recessive RP. Furthermore, we were in- by the AdaptDx. We administered this test with a 76% initial flash for bleaching and evaluated the most sensitive perifoveal retinal terested in determining and comparing the between-visit area located eccentrically at 5° from central fixation either superi- test-retest reliability for mesopic and photopic measures orly, inferiorly, nasally, or temporally, as was determined by results of VA and CS.
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