Early detection of cone photoreceptor cell loss in retinitis pigmentosa using adaptive optics scanning laser ophthalmoscopy

Nakatake, Shunji; Murakami, Yusuke; Funatsu, Jun; Koyanagi, Yoshito; Akiyama, Masato; Momozawa, Yukihide; Ishibashi, Tatsuro; Sonoda, Koh Hei; Ikeda, Yasuhiro

doi:10.1007/s00417-019-04307-0

Cited by 20 publications

(10 citation statements)

References 45 publications

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“…Although this region was characterized by intact ellipsoid band, recent data showed reduced cone cell density in this zone using adaptive optics scanning laser ophthalmoscopy. 34 Although we did not examine the cone density in our study, the finding of widespread relative scotoma by using an age-and loci-specific cutoff is consistent with previous studies showing structural changes. In the case of the patient with a large cumulative dose of hydroxychloroquine, the use of an age-and loci-specific cutoff leads to the conclusion that there was no progression of suspected toxicity.…”

Section: Discussionsupporting

confidence: 88%

Interpreting MAIA Microperimetry Using Age- and Retinal Loci-Specific Reference Thresholds

Charng

Sanfilippo

Attia

et al. 2020

Trans. Vis. Sci. Tech.

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Macular Integrity Assessment (MAIA) microperimetry is used widely in clinical trials and routine practice to assess paracentral scotoma. Current interpretation of MAIA is based on an assumed uniform 25 decibel (dB) cutoff for normal function irrespective of subject age and retinal location. We examined this convention by establishing an ageand loci-specific reference in healthy eyes and comparing this to the <25 dB cutoff. Methods: Retrospective MAIA results from healthy eyes were analyzed for prevalence of loci with <25 dB. At each locus, a new reference cutoff was derived from quantile regression of sensitivity against age at the 2.5th percentile. Two clinical cases of serial MAIA testing were analyzed using the new approach and compared to the <25 dB cutoff. Results: Fifty-four and 56 age-matched (range: 16-75 years) healthy eyes underwent small (37 loci) and large (68 loci) grid testing, respectively. Retinal sensitivity <25 dB was found in 5% of the small grid (1998 data points) and 10% of the large grid (3808 data points). These were found predominantly in older subjects and at the central point or in the perifoveal region. Quantile regression at each individual locus showed age-related decline with a median gradient of 0.6 dB/decade. Conclusions: We caution against using <25 dB cutoff in MAIA interpretation and advocate an age-and loci-specific cutoff criterion. Translational Relevance: Our study suggests that MAIA interpretation is influenced by the criterion used for defining abnormal pointwise measurement.

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Section: Discussionsupporting

confidence: 88%

Interpreting MAIA Microperimetry Using Age- and Retinal Loci-Specific Reference Thresholds

Charng

Sanfilippo

Attia

et al. 2020

Trans. Vis. Sci. Tech.

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“…The authors suggested that the rod system dysfunction in RCD patients may lead to a consequent cone dysfunction and thus to progressive visual field constriction and central vision impairment. In agreement with this, studies using adaptive optics scanning laser en-face images in RCD patients have shown reduced cone photoreceptor density and a strong correlation with retinal eccentricity [59,65]. Since using antioxidants in RCD models supposedly decreases the oxidative damage and prevents the death of cone photoreceptors, it is inferred that oxidative damage is a major contributor to cone photoreceptor apoptosis [66].…”

Section: Altered Central Structure and Metabolic Function In Irdsmentioning

confidence: 66%

Retinal Oxygenation in Inherited Diseases of the Retina

Türksever

Torres

Valmaggia

et al. 2021

Genes

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(1) Background: The aim of our study was to investigate the relationship between retinal metabolic alterations (retinal vessel oximetry, RO) and structural findings (retinal vessel diameter, central retinal thickness and retinal nerve fiber layer thickness, RNFL) in patients with inherited retinal diseases (IRDs). (2) Methods: A total of 181 eyes of 92 subjects were examined: 121 eyes of 62 patients with IRDs were compared to 60 eyes of 30 healthy age-matched controls. The retinal vessel oximetry was performed with the oxygen saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The oxygen saturation in all four major peripapillary retinal arterioles (A-SO2; %) and venules (V-SO2; %) were measured and their difference (A-V SO2; %) was calculated. Additionally, retinal vessel diameters of the corresponding arterioles (D-A; µm) and venules (D-V; µm) were determined. The peripapillary central retinal thickness and the RNFL thickness were measured using spectral domain optical coherence tomography (SD-OCT) (Carl Zeiss Meditec, Dublin, CA, USA). Moreover, we calculated the mean central retinal oxygen exposure (cO2-E; %/µm) and the mean peripapillary oxygen exposure (pO2-E; %/µm) per micron of central retinal thickness and nerve fiber layer thickness by dividing the mean central retinal thickness (CRT) and the RNFL thickness with the mean A-V SO2. (3) Results: Rod-cone dystrophy patients had the highest V-SO2 and A-SO2, the lowest A-V SO2, the narrowest D-A and D-V and the thickest RNFL, when compared not only to controls (p ≤ 0.040), but also to patients with other IRDs. Furthermore, in rod-cone dystrophies the cO2-E and the pO2-E were higher in comparison to controls and to patients with other IRDs (p ≤ 0.005). Cone-rod dystrophy patients had the lowest cO2-E compared to controls and patients with other IRDs (p ≤ 0.035). Evaluated in central zones, the cO2-E was significantly different when comparing cone-rod dystrophy (CRD) against rod-cone dystrophy (RCD) patients in all zones (p < 0.001), whereas compared with controls and patients with inherited macular dystrophy this was observed only in zones 1 and 2 (p ≤ 0.018). The oxygen exposure was also the highest in the RCD group for both the nasal and the temporal peripapillary area, among all the evaluated groups (p ≤ 0.025). (4) Conclusions: The presented metabolic-structural approach enhances our understanding of inherited photoreceptor degenerations. Clearly demonstrated through the O2-E comparisons, the central and the peripapillary retina in rod-cone dystrophy eyes consume less oxygen than the control-eyes and eyes with other IRDs. Rod-cone dystrophy eyes seem to be proportionally more exposed to oxygen, the later presumably leading to more pronounced oxidative damage-related remodeling.

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“…2,3 Main advantages of AO ophthalmoscopy include the ability to observe single cells in vivo and to track those same cells over time. Indeed, AO ophthalmoscopy has been used to describe the degeneration of cone photoreceptor structure using metrics, such as cone density or spacing, in numerous inherited retinal diseases, including retinitis pigmentosa, [4][5][6][7] Stargardt's, [8][9][10] achromatopsia, [11][12][13][14] and choroideremia (CHM), [15][16][17] among others. 2,3 In addition, investigators have demonstrated longitudinal imaging of the same photoreceptors over time.…”

Section: Introductionmentioning

confidence: 99%

Cone Identification in Choroideremia: Repeatability, Reliability, and Automation Through Use of a Convolutional Neural Network

Morgan

Chen

Huang

et al. 2020

Trans. Vis. Sci. Tech.

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Adaptive optics imaging has enabled the visualization of photoreceptors both in health and disease. However, there remains a need for automated accurate cone photoreceptor identification in images of disease. Here, we apply an open-source convolutional neural network (CNN) to automatically identify cones in images of choroideremia (CHM). We further compare the results to the repeatability and reliability of manual cone identifications in CHM. Methods: We used split-detection adaptive optics scanning laser ophthalmoscopy to image the inner segment cone mosaic of 17 patients with CHM. Cones were manually identified twice by one experienced grader and once by two additional experienced graders in 204 regions of interest (ROIs). An open-source CNN either pre-trained on normal images or trained on CHM images automatically identified cones in the ROIs. True and false positive rates and Dice's coefficient were used to determine the agreement in cone locations between data sets. Interclass correlation coefficient was used to assess agreement in bound cone density. Results: Intra-and intergrader agreement for cone density is high in CHM. CNN performance increased when it was trained on CHM images in comparison to normal, but had lower agreement than manual grading. Conclusions: Manual cone identifications and cone density measurements are repeatable and reliable for images of CHM. CNNs show promise for automated cone selections, although additional improvements are needed to equal the accuracy of manual measurements. Translational Relevance: These results are important for designing and interpreting longitudinal studies of cone mosaic metrics in disease progression or treatment intervention in CHM.

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Early detection of cone photoreceptor cell loss in retinitis pigmentosa using adaptive optics scanning laser ophthalmoscopy

Cited by 20 publications

References 45 publications

Interpreting MAIA Microperimetry Using Age- and Retinal Loci-Specific Reference Thresholds

Interpreting MAIA Microperimetry Using Age- and Retinal Loci-Specific Reference Thresholds

Retinal Oxygenation in Inherited Diseases of the Retina

Cone Identification in Choroideremia: Repeatability, Reliability, and Automation Through Use of a Convolutional Neural Network

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