Reliability and Repeatability of Cone Density Measurements in Patients With Stargardt Disease and RPGR-Associated Retinopathy

Abstract

PurposeTo assess reliability and repeatability of cone density measurements by using confocal and (nonconfocal) split-detector adaptive optics scanning light ophthalmoscopy (AOSLO) imaging. It will be determined whether cone density values are significantly different between modalities in Stargardt disease (STGD) and retinitis pigmentosa GTPase regulator (RPGR)–associated retinopathy.MethodsTwelve patients with STGD (aged 9–52 years) and eight with RPGR-associated retinopathy (aged 11–31 years) were imaged using both confocal and split-detector AOSLO simultaneously. Four graders manually identified cone locations in each image that were used to calculate local densities. Each imaging modality was evaluated independently. The data set consisted of 1584 assessments of 99 STGD images (each image in two modalities and four graders who graded each image twice) and 928 RPGR assessments of 58 images (each image in two modalities and four graders who graded each image twice).ResultsFor STGD assessments the reliability for confocal and split-detector AOSLO was 67.9% and 95.9%, respectively, and the repeatability was 71.2% and 97.3%, respectively. The differences in the measured cone density values between modalities were statistically significant for one grader. For RPGR assessments the reliability for confocal and split-detector AOSLO was 22.1% and 88.5%, respectively, and repeatability was 63.2% and 94.5%, respectively. The differences in cone density between modalities were statistically significant for all graders.ConclusionsSplit-detector AOSLO greatly improved the reliability and repeatability of cone density measurements in both disorders and will be valuable for natural history studies and clinical trials using AOSLO. However, it appears that these indices may be disease dependent, implying the need for similar investigations in other conditions.

Hereditäre Netzhautdystrophien: Kombination ophthalmologischer Methoden zur Optimierung des Readout

“…Allerdings ist zu berücksichtigen, das bisher nur wenige IRD (z. B. assoziiert mit ABCA4, RPGR) detailliert untersucht wurden und die Aussagekraft einzelner Parameter krankheitsspezifisch variieren kann [20], sodass die Übertragbarkeit auf IRD anderer genetischer Ursache sorgfältig überprüft werden muss. Der Vergleich verschiedener Biomarker zwischen verschiedenen NIRB-Methoden und IRD ist wesentlich, um pathogenetische Abläufe zu analysieren und krankheits-, gen-oder ggf.…”

Cellular imaging of inherited retinal diseases using adaptive optics

“…Cone density is the most commonly used mosaic metric, with good reliability and repeatability established in healthy controls [91][92][93]. However, the comparative difficulty of cone identification in retinal degenerations has rendered this metric variable when applied to patients with Stargardt disease [94], RPGR-associated retinopathy [94], and achromatopsia [79]. In addition to inter-disease variances, several studies demonstrate inter-imaging modality differences in cone density reliability, with split-detector AOSLO conferring the best results [94,95].…”

“…However, the comparative difficulty of cone identification in retinal degenerations has rendered this metric variable when applied to patients with Stargardt disease [94], RPGR-associated retinopathy [94], and achromatopsia [79]. In addition to inter-disease variances, several studies demonstrate inter-imaging modality differences in cone density reliability, with split-detector AOSLO conferring the best results [94,95]. Limitations in reliability and repeatability are similarly reported for cone spacing metrics in IRDs [96], largely due to differences in mosaic sampling window size and areas with increased cone reflectivity loss.…”

An update on ocular complications of Ebola virus disease

“…Preliminary results have demonstrated that survivors who test negative for EBOV RT-PCR may undergo manual small incision cataract surgery with significant improvements in visual acuity [19,22]. The EVICT study will provide evidence that can guide the ophthalmic community related to invasive eye procedures in EVD survivors.…”