Sensitive and robust outcome measures of retinal function are pivotal for clinical trials in age-related macular degeneration (AMD). A recent development is the implementation of artificial ...intelligence (AI) to infer results of psychophysical examinations based on findings derived from multimodal imaging. We conducted a review of the current literature referenced in PubMed and Web of Science among others with the keywords 'artificial intelligence' and 'machine learning' in combination with 'perimetry', 'best-corrected visual acuity (BCVA)', 'retinal function' and 'age-related macular degeneration'. So far AI-based structure-function correlations have been applied to infer conventional visual field, fundus-controlled perimetry, and electroretinography data, as well as BCVA, and patient-reported outcome measures (PROM). In neovascular AMD, inference of BCVA (hereafter termed inferred BCVA) can estimate BCVA results with a root mean squared error of ~7-11 letters, which is comparable to the accuracy of actual visual acuity assessment. Further, AI-based structure-function correlation can successfully infer fundus-controlled perimetry (FCP) results both for mesopic as well as dark-adapted (DA) cyan and red testing (hereafter termed inferred sensitivity). Accuracy of inferred sensitivity can be augmented by adding short FCP examinations and reach mean absolute errors (MAE) of ~3-5 dB for mesopic, DA cyan and DA red testing. Inferred BCVA, and inferred retinal sensitivity, based on multimodal imaging, may be considered as a quasi-functional surrogate endpoint for future interventional clinical trials in the future.
Preservation of photoreceptors beyond areas of retinal pigment epithelium atrophy is a critical treatment goal in eyes with geographic atrophy (GA) to prevent vision loss. Thus, we assessed the ...association of treatment with the complement C3 inhibitor pegcetacoplan with optical coherence tomography (OCT)-based photoreceptor laminae thicknesses in this post hoc analysis of the FILLY trial (NCT02503332). Retinal layers in OCT were segmented using a deep-learning-based pipeline and extracted along evenly spaced contour-lines surrounding areas of GA. The primary outcome measure was change from baseline in (standardized) outer nuclear layer (ONL) thickness at the 5.16°-contour-line at month 12. Participants treated with pegcetacoplan monthly had a thicker ONL along the 5.16° contour-line compared to the pooled sham arm (mean difference 95% CI + 0.29 z-score units 0.16, 0.42, P < 0.001). The same was evident for eyes treated with pegcetacoplan every other month (+ 0.26 z-score units 0.13, 0.4, P < 0.001). Additionally, eyes treated with pegcetacoplan exhibited a thicker photoreceptor inner segment layer along the 5.16°-contour-line at month 12. These findings suggest that pegcetacoplan could slow GA progression and lead to reduced thinning of photoreceptor layers beyond the GA boundary. Future trials in earlier disease stages, i.e., intermediate AMD, aiming to slow photoreceptor degeneration warrant consideration.
To assess the clinical application of multicolor imaging by confocal scanning laser ophthalmoscopy (cSLO).
Retinal imaging was performed in 76 patients including cSLO multicolor imaging (SPECTRALIS ...SD-OCT, Heidelberg Engineering, Heidelberg, Germany) and color fundus photography (CFP).
The use of confocal optics, reduced light scatter and automated eye tracking enable high-resolution cSLO reflectance images. Compared to CFP, the appearance of pigment alterations and hemorrhages were some of the differences observed. Various artifacts including those derived from optical media alterations need to be considered when interpreting images. Specific pathological findings including epiretinal membranes, fibrovascular proliferations, and reticular pseudodrusen may be better visualized on multicolor images.
When using multicolor imaging, ophthalmologists need to be mindful about differences in the appearance of pathological changes and artifacts. Multicolor imaging may offer information over and above conventional CFP; it can be performed through undilated pupils and is less affected by media opacities.
Here, we investigate the extent to which re-implementing a previously published algorithm for OCT-based drusen quantification permits replicating the reported accuracy on an independent dataset. We ...refined that algorithm so that its accuracy is increased. Following a systematic literature search, an algorithm was selected based on its reported excellent results. Several steps were added to improve its accuracy. The replicated and refined algorithms were evaluated on an independent dataset with the same metrics as in the original publication. Accuracy of the refined algorithm (overlap ratio 36-52%) was significantly greater than the replicated one (overlap ratio 25-39%). In particular, separation of the retinal pigment epithelium and the ellipsoid zone could be improved by the refinement. However, accuracy was still lower than reported previously on different data (overlap ratio 67-76%). This is the first replication study of an algorithm for OCT image analysis. Its results indicate that current standards for algorithm validation do not provide a reliable estimate of algorithm performance on images that differ with respect to patient selection and image quality. In order to contribute to an improved reproducibility in this field, we publish both our replication and the refinement, as well as an exemplary dataset.
Abstract Fundus autofluorescence imaging is an imaging method that provides additional information compared to conventional imaging techniques. It permits to topographically map lipofuscin ...distribution of the retinal pigment epithelial cell monolayer. Excessive accumulation of lipofuscin granules in the lysosomal compartment of retinal pigment epithelium cells represents a common downstream pathogenetic pathway in various hereditary and complex retinal diseases including age-related macular degeneration (AMD). This comprehensive review contains an introduction in fundus autofluorescence imaging, including basic considerations, the origin of the signal, different imaging methods, and a brief overview of fundus autofluorescence findings in normal subjects. Furthermore, it summarizes cross-sectional and longitudinal fundus autofluorescence findings in patients with AMD, addresses the pathophysiological significance of increased fundus autofluorescence, and characterizes different fundus autofluorescence phenotypes as well as fundus autofluorescence alterations with disease progression.
Age-Related Macular Degeneration: A Review Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Chakravarthy, Usha
JAMA : the journal of the American Medical Association,
01/2024, Volume:
331, Issue:
2
Journal Article
Peer reviewed
IMPORTANCE: Age-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older ...people and is expected to affect approximately 288 million people worldwide by 2040. OBSERVATIONS: Older age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD. AMD occurs when extracellular deposits accumulate in the outer retina, ultimately leading to photoreceptor degeneration and loss of central vision. The late stages of AMD are characterized by outer retinal atrophy, termed geographic atrophy, or neovascularization associated with subretinal and/or intraretinal exudation, termed exudative neovascular AMD. The annual incidence of AMD ranges from 0.3 per 1000 in people who are aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older. The estimated heritability of late-stage AMD is approximately 71% (95% CI, 18%-88%). Long-term prospective cohort studies show a significantly higher AMD incidence in people who smoke more than 20 cigarettes per day compared with people who never smoked. AMD is diagnosed primarily with clinical examination that includes a special lens that focuses light of the slit lamp through the pupil. Exudative neovascular AMD is best identified using angiography and by optical coherence tomography. Individuals with AMD who take nutritional supplements consisting of high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability to progress to late-stage AMD at 5 years vs a 28% probability for those taking a placebo. In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal anti–vascular endothelial growth factor (anti-VEGF) injections experience less than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving sham treatment. CONCLUSIONS AND RELEVANCE: The prevalence of AMD is anticipated to increase worldwide to 288 million individuals by 2040. Intravitreally administered anti-VEGF treatment is first-line therapy for exudative neovascular AMD.
To report prevalence, clinical characteristics, and prognostic significance of refractile drusen in eyes with intermediate age-related macular degeneration (AMD).
Presence of refractile drusen by ...color fundus photography (CFP), corresponding findings by multimodal imaging, and longitudinal changes with annual examinations for up to 4 years were analyzed within a prospective natural history study of 98 eyes with non-late AMD of 98 patients (Age-Related Eye Disease Study AREDS stages 3 and 4).
A total of 115 refractile drusen were detected at baseline in 20 eyes (20.4%). Refractile drusen typically showed hyperreflectivity by infrared (80.9%) and blue (93.9%) reflectance imaging, appearing more distinct when compared to CFP. Laminar intense hyperreflectivity of Bruch's membrane was detected in 31 lesions by spectral-domain optical coherence tomography and was strongly related to atrophy development (23 out of 31 lesions). Presence of refractile drusen at baseline was overall associated with later development of geographic atrophy (GA) (9/20 eyes versus 6/78 eyes, P < 0.001). Spontaneous regression without evident atrophy occurred in seven lesions.
Refractile drusen are a relative common phenotype in intermediate AMD and appear to confer risk for the development of late AMD. While not all lesions develop late AMD and regression may also occur, distinct subphenotypes as identified by multimodal imaging may not only be visible earlier but also be topographically associated with the risk for GA development. Recognizing the characteristic pattern on multimodal imaging would inform physicians for identification of the lesion and its clinical history.
To analyze focal hyperreflective morphologic alterations in outer retinal layers in patients with type 2 idiopathic macular telangiectasia (MacTel type 2) using spectral-domain optical coherence ...tomography (SD OCT).
Cross-sectional case-control study.
Forty-one patients with MacTel type 2.
Anatomic layers were evaluated and compared with those of controls of similar age. Simultaneous SD OCT scans were obtained with a combined confocal scanning laser ophthalmoscope for simultaneous tomographic and topographic in vivo imaging (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany).
Morphologic alterations in the retinal layers secondary to MacTel type 2.
Hyperreflective spots in the outer retina of MacTel type 2 patients were detected in all stages of disease using the SD OCT. Their presence was confined to the foveolar and parafoveolar region. The phenomenon also was detected in a monozygotic twin in an eye with no typical angiographic sign of the disease. A hyperreflective haze was detected in the vicinity of a disruption of the hyperreflective OCT line that is assumed to represent the line between the photoreceptor inner and outer segments and interdigitation of the outer segments and the retinal pigment epithelium. No corresponding pathologic features could be identified by biomicroscopy, time-domain OCT, or confocal scanning laser ophthalmoscope imaging. Crystalline deposits and intraretinal migration of pigmented cells were distinguishable because of differences in shape, reflectivity, and location.
Hyperreflective spots were identified in outer retinal layers of patients with MacTel type 2 in all disease stages. It is suggested that this phenomenon represents an early sign of a neurodegenerative process. Secondary assumptions include extravasated deposits or vascular abnormalities. The pathologic features are indicative of an active disease process before the disease manifests by typical fluorescein angiographic signs.
Proprietary or commercial disclosure may be found after the references.
To determine intraobserver and interobserver longitudinal measurement variability of novel semiautomated software for quantification of age-related macular degeneration-associated geographic atrophy ...(GA) based on confocal scanning laser ophthalmoscopy fundus autofluorescence (FAF) imaging.
Three-field FAF (excitation 488 nm, emission 500-700 nm), near-infrared reflectance (820 nm), and blue reflectance (488 nm) images of 30 GA subjects were recorded according to a standardized protocol at baseline after 6 and 12 months. At all visits, the GA area was analyzed on central FAF images by seven independent readers using semiautomated software. The software allows direct export of FAF images from the database and semiautomated detection of atrophic areas by shadow correction, vessel detection, and selection of seed points.
The mean size of atrophy at baseline and the mean progression rate were 5.96 mm² (range, 1.80-15.87) and 1.25 mm²/year (0.42-2.93), respectively. Mean difference of interobserver agreement (Bland-Altman statistics) ranged from -0.25 to 0.30 mm² for the baseline visit and from -0.14 to 0.11 mm²/year for the atrophy progression rate. Corresponding reflectance images were helpful for lesion boundary discrimination, particularly for evaluation of foveal GA involvement and when image quality was poor.
The new image processing software offers an accurate, reproducible, and time-efficient identification and quantification of outer retinal atrophy and its progression over time. It facilitates measurements both in natural history studies and in interventional trials to evaluate new pharmacologic agents designed to limit GA enlargement.
Acta Ophthalmol. 2010: 88: 842–849
.
Purpose: To evaluate the clinical relevance of a new diagnostic modality, simultaneous confocal scanning laser ophthalmoscopy (cSLO) and high‐speed, ...high‐resolution, spectral‐domain optical coherence tomography (OCT), for the visualization of macular pathologies.
Methods: OCT images and simultaneous recording of fluorescein angiography, indocyanine green (ICG) angiography, infrared, and blue reflectance (‘red‐free’) or fundus autofluorecence (FAF) images were obtained with a novel imaging device (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). An optically pumped solid‐state laser generated the excitation wavelength (488 nm) required for blue reflectance, FAF and fluorescein angiography images. For ICG angiography and infrared imaging, diode laser sources at 790 and 815 nm were used. For OCT, 40 000 A‐scans per second were acquired with 7 μm axial and 14 μm lateral optical resolution. The B‐scans covering a transversal range of 30° had a scan width up to 1.536 A‐scans with a digital lateral resolution of 5 μm/pixel, a scan depth of 1.8 mm with 3.5 μm/pixel digital axial resolution and a scan rate of up to 48 B‐scans/second. In addition, volume scans could be obtained at 15, 20 and 30° fields of view. An integrated eye tracking allowed for live averaging of cSLO images as well as OCT B‐scans.
Results: Early, neovascular and atrophic age‐related macular degeneration, macular telangiectasia, retinal arterial, branch vein occlusion and other pathologies were imaged, and cSLO and OCT frames correlated. Fluorescein and ICG angiographic phenomena recorded in cSLO images could be analysed accurately in corresponding OCT cross‐sections. Abnormal FAF signals were correlated to alterations at the outer retinal/retinal pigment epithelial cell layer in high‐resolution OCT scans. Three‐dimensional OCT enabled comprehensive retinal coverage. The imaging software tracked eye movements accurately. Averaging of live B‐scans enhanced image quality considerably.
Conclusion: The combined cSLO/OCT system allowed for simultaneous recordings of topographic and tomographic images with accurate correlation between the confocal angiograms, FAF images as well as other imaging modes with the OCT scans. The instrument thus provides simultaneous multi‐modal imaging of retinal pathologies and disease.
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