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Biomedical Optics Express Sep 2023The use of optical attenuation coefficients (OAC) in optical coherence tomography (OCT) imaging of the retina has improved the segmentation of anatomic layers compared...
The use of optical attenuation coefficients (OAC) in optical coherence tomography (OCT) imaging of the retina has improved the segmentation of anatomic layers compared with traditional intensity-based algorithms. Optical attenuation correction has improved our ability to measure the choroidal thickness and choroidal vascularity index using dense volume scans. Algorithms that combine conventional intensity-based segmentation with depth-resolved OAC OCT imaging have been used to detect elevations of the retinal pigment epithelium (RPE) due to drusen and basal laminar deposits, the location of hyperpigmentation within the retina and along the RPE, the identification of macular atrophy, the thickness of the outer retinal (photoreceptor) layer, and the presence of calcified drusen. OAC OCT algorithms can identify the risk-factors that predict disease progression in age-related macular degeneration.
PubMed: 37791280
DOI: 10.1364/BOE.496080 -
Investigative Ophthalmology & Visual... Sep 2023Choroidal vascular changes occur with normal aging and age-related macular degeneration (AMD). Here, we evaluate choroidal thickness and vascularity in aged rhesus...
PURPOSE
Choroidal vascular changes occur with normal aging and age-related macular degeneration (AMD). Here, we evaluate choroidal thickness and vascularity in aged rhesus macaques to better understand the choroid's role in this nonhuman primate model of AMD.
METHODS
We analyzed optical coherence tomography (OCT) images of 244 eyes from 122 rhesus macaques (aged 4-32 years) to measure choroidal thickness (CT) and choroidal vascularity index (CVI). Drusen number, size, and volume were measured by semiautomated annotation and segmentation of OCT images. We performed regression analyses to determine any association of CT or CVI with age, sex, and axial length and to determine if the presence and volume of soft drusen impacted these choroidal parameters.
RESULTS
In rhesus macaques, subfoveal CT decreased with age at 3.2 µm/y (R2 = 0.481, P < 0.001), while CVI decreased at 0.66% per year (R2 = 0.257, P < 0.001). Eyes with soft drusen exhibited thicker choroid (179.9 ± 17.5 µm vs. 162.0 ± 27.9 µm, P < 0.001) and higher CVI (0.612 ± 0.051 vs. 0.577 ± 0.093, P = 0.005) than age-matched control animals. Neither CT or CVI appeared to be associated with drusen number, size, or volume in this cohort. However, some drusen in macaques were associated with underlying choroidal vessel enlargement resembling pachydrusen in human patients with AMD.
CONCLUSIONS
Changes in the choroidal vasculature in rhesus macaques resemble choroidal changes in human aging, but eyes with drusen exhibit choroidal thickening, increased vascularity, and phenotypic characteristics of pachydrusen observed in some patients with AMD.
Topics: Humans; Animals; Macaca mulatta; Retrospective Studies; Retina; Choroid; Aging; Macular Degeneration; Retinal Drusen; Tomography, Optical Coherence
PubMed: 37773500
DOI: 10.1167/iovs.64.12.44 -
Ophthalmology and Therapy Dec 2023Age-related macular degeneration (AMD) is a leading cause of severe vision loss worldwide, with a global prevalence that is predicted to substantially increase.... (Review)
Review
Age-related macular degeneration (AMD) is a leading cause of severe vision loss worldwide, with a global prevalence that is predicted to substantially increase. Identifying early biomarkers indicative of progression risk will improve our ability to assess which patients are at greatest risk of progressing from intermediate AMD (iAMD) to vision-threatening late-stage AMD. This is key to ensuring individualized management and timely intervention before substantial structural damage. Some structural biomarkers suggestive of AMD progression risk are well established, such as changes seen on color fundus photography and more recently optical coherence tomography (drusen volume, pigmentary abnormalities). Emerging biomarkers identified through multimodal imaging, including reticular pseudodrusen, hyperreflective foci, and drusen sub-phenotypes, are being intensively explored as risk factors for progression towards late-stage disease. Other structural biomarkers merit further research, such as ellipsoid zone reflectivity and choriocapillaris flow features. The measures of visual function that best detect change in iAMD and correlate with risk of progression remain under intense investigation, with tests such as dark adaptometry and cone-specific contrast tests being explored. Evidence on blood and plasma markers is preliminary, but there are indications that changes in levels of C-reactive protein and high-density lipoprotein cholesterol may be used to stratify patients and predict risk. With further research, some of these biomarkers may be used to monitor progression. Emerging artificial intelligence methods may help evaluate and validate these biomarkers; however, until we have large and well-curated longitudinal data sets, using artificial intelligence effectively to inform clinical trial design and detect outcomes will remain challenging. This is an exciting area of intense research, and further work is needed to establish the most promising biomarkers for disease progression and their use in clinical care and future trials. Ultimately, a multimodal approach may yield the most accurate means of monitoring and predicting future progression towards vision-threatening, late-stage AMD.
PubMed: 37773477
DOI: 10.1007/s40123-023-00807-9 -
Ophthalmology and Therapy Dec 2023Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis.... (Review)
Review
BACKGROUND
Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis. Preclinical and clinical studies have shown promising results in treating intermediate age-related macular degeneration (AMD), since PBM can produce photochemical reactions in endogenous retinal chromophores. Currently, PBM is approved by the Food and Drug Administration and by the European Medicines Agency for the treatment of intermediate AMD. This narrative review aimed to evaluate the available evidence on the effectiveness and safety of PBM in treating intermediate AMD.
METHODS
A comprehensive search was conducted using the PubMed database, employing the keywords "photobiomodulation" and "age-related macular degeneration." All English-language studies published up to June 2023 were reviewed, and the search was expanded to include relevant references from selected articles. The included publications were analyzed for this review.
RESULTS
The available studies on PBM in AMD demonstrated promising but inconsistent results. PBM showed potential in improving best-corrected visual acuity (BCVA) and contrast sensitivity (CS) in patients with AMD. Some studies also suggested a reduction in AMD lesions, such as drusen volume. However, the long-term efficacy and optimal treatment parameters of PBM in AMD remained to be fully determined due to the limitations of the available studies. These included variations in irradiation techniques, wavelengths, exposure times, and treatment sessions, making it challenging to generalize the effectiveness of PBM. Furthermore, the lack of accurate classification of AMD phenotypes in the available studies hindered the understanding of which phenotypes could truly benefit from this treatment. Finally, the strength of evidence varied among studies, with limited sample sizes, unpublished results, and only three randomized sham-controlled trials.
CONCLUSIONS
Currently, the effectiveness of PBM in promoting drusen resorption or preventing progression to advanced forms of AMD, as observed in the cited studies, remains uncertain.
PubMed: 37768527
DOI: 10.1007/s40123-023-00812-y -
Investigative Ophthalmology & Visual... Sep 2023Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris...
PURPOSE
Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris flow signal deficits (FD%) and visual function in eyes of individuals aged ≥60 years, with and without AMD.
METHODS
One eye of each participant in the baseline visit of the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2; NCT04112667) was studied. AMD presence and severity was determined using the Age-Related Eye Disease Study (AREDS) grading system. FD% was quantified using macular spectral domain optical coherence tomography angiography (OCTA) scans. Vision tests included rod-mediated dark adaptation (RMDA), best-corrected visual acuity, and contrast sensitivity (photopic and mesopic), and microperimetric light sensitivity (scotopic, mesopic, and photopic). Presence of subretinal drusenoid deposits (SDD) was determined using multimodal imaging.
RESULTS
In 410 study eyes of 410 participants (mean [SD] age = 71.7 years [5.9]), FD% was higher in early AMD (mean [SD] = 54.0% [5.5], N = 122) and intermediate AMD (59.8% [7.4], N = 92), compared to normal (52.1% [5.3], N = 196) eyes. Among visual functions evaluated, RMDA showed the strongest association with FD% (r = 0.35, P < 0.0001), followed by contrast sensitivity (r = -0.22, P < 0.0001). Eyes with SDD had worse FD% (58.3% [7.4], N = 87), compared to eyes without SDD (53.4% [6.0], N = 323, P = < 0.0001).
CONCLUSIONS
Choriocapillaris FD% were associated with AMD severity and with impaired vision, especially RMDA. Reduced metabolic transport and exchange across the choriocapillaris-Bruch's membrane retinal pigment epithelium (RPE) complex, a causal factor for high-risk soft drusen formation, also may impair photoreceptor sustenance from the circulation. This includes retinoid resupply, essential to dynamic rod function.
Topics: Humans; Dark Adaptation; Macular Degeneration; Retina; Retinal Drusen; Tomography, Optical Coherence; Choroid
PubMed: 37768273
DOI: 10.1167/iovs.64.12.41 -
Diagnostics (Basel, Switzerland) Sep 2023The present study was conducted to investigate the potential of radiomics to develop an explainable AI-based system to be applied to ultra-widefield fundus...
The present study was conducted to investigate the potential of radiomics to develop an explainable AI-based system to be applied to ultra-widefield fundus retinographies (UWF-FRTs) with the objective of predicting the presence of the early signs of Age-related Macular Degeneration (AMD) and stratifying subjects with low- versus high-risk of AMD. The ultimate aim was to provide clinicians with an automatic classifier and a signature of objective quantitative image biomarkers of AMD. The use of Machine Learning (ML) and radiomics was based on intensity and texture analysis in the macular region, detected by a Deep Learning (DL)-based macular detector. Two-hundred and twenty six UWF-FRTs were retrospectively collected from two centres and manually annotated to train and test the algorithms. Notably, the combination of the ML-based radiomics model and the DL-based macular detector reported 93% sensitivity and 74% specificity when applied to the data of the centre used for external testing, capturing explainable features associated with drusen or pigmentary abnormalities. In comparison to the human operator's annotations, the system yielded a 0.79 Cohen , demonstrating substantial concordance. To our knowledge, these results are the first provided by a radiomic approach for AMD supporting the suitability of an explainable feature extraction method combined with ML for UWF-FRT.
PubMed: 37761333
DOI: 10.3390/diagnostics13182965 -
American Journal of Ophthalmology Jan 2024Retinal drusen have been described in people with IgA nephropathy. We examined the frequency of drusen in IgA nephropathy and compared their location and composition...
PURPOSE
Retinal drusen have been described in people with IgA nephropathy. We examined the frequency of drusen in IgA nephropathy and compared their location and composition with those for drusen in age-related macular degeneration.
DESIGN
Immunohistological case series of eyes of patients with IgA nephropathy, and a comparison eye with age-related macular degeneration.
METHODS
Donor eyes from 4 individuals (3 male, 1 female, aged 40-80 years) with biopsy-proven IgA nephropathy and kidney failure were examined for the presence of drusen, and location and composition using antibodies for vitronectin, IgA, IgM, IgG, C3, and C1q. Results were compared with those for drusen in macular degeneration without IgA nephropathy.
RESULTS
All 4 donors had sparse, subretinal pigment epithelium drusen of 55-65 mm diameter that stained for vitronectin but not for IgA or complement. All donors had retinal capillaries and choriocapillaris staining for IgA. The youngest donor (female, 40) had rare deposits in the outer nuclear layer that stained for IgA, but not for vitronectin. The oldest donor (male, 82) had large cystlike spaces in the inner nuclear and plexiform layers, and smaller cysts in the outer nuclear layer, with no staining for IgA or complement.
CONCLUSIONS
Retinal drusen are uncommon in IgA nephropathy, even with kidney failure. Drusen in IgA nephropathy resemble drusen found in age-related macular degeneration. IgA-staining deposits in the outer nuclear layer were likely due to systemic deposition of IgA and complement activation. The nature of cystic spaces is unknown. Further analysis of the retinas of people with glomerulonephritis is recommended.
Topics: Humans; Male; Female; Retinal Drusen; Glomerulonephritis, IGA; Vitronectin; Macular Degeneration; Renal Insufficiency; Immunoglobulin A
PubMed: 37757996
DOI: 10.1016/j.ajo.2023.09.019 -
BMC Ophthalmology Sep 2023Microophthalmos or 'dwarf eye' is characterized by an axial length 2 standard deviation less than age-matched controls. It is classified into nanophthalmos, relative...
BACKGROUND
Microophthalmos or 'dwarf eye' is characterized by an axial length 2 standard deviation less than age-matched controls. It is classified into nanophthalmos, relative anterior microphthalmos, and posterior microphthalmos based on the anterior segment: posterior segment ratio. Nanophthalmos can occur in association with optic disc drusen, foveoschisis, and retinitis pigmentosa, as an autosomal recessive syndrome linked to mutations in the MFRP gene. We report a case of bilateral nanophthalmos and pigmentary retinopathy with angle closure glaucoma and optic disc pit in one eye. We believe this to be the first case presenting with optic disc pit in association with nanophthalmos.
CASE PRESENTATION
A 56-year-old female presented with bilateral small eyes, high hypermetropia, shallow anterior chamber depth, increased lens thickness, mid-peripheral retinal flecks, and macular edema. She also had high intraocular pressure in the right eye, with a disc cupping of 0.9 with an Optic disc pit. The macular edema in the right eye was found to occur in association with the Optic disc pit, whereas, in the left eye, it was associated with intra-retinal hemorrhages and diagnosed as macular branch retinal vein occlusion secondary to hypertension. She was started on anti-glaucoma medications in both eyes and planned for Anti-VEGF injection in the left eye.
CONCLUSION
This case report is unique as it reports an association of Nanophthalmos with Optic Disc pit, with an associated angle closure glaucoma in the same eye, an association which has never been previously reported in the literature.
Topics: Female; Humans; Middle Aged; Microphthalmos; Optic Disk; Glaucoma, Angle-Closure; Macular Edema; Eye Abnormalities; Retinitis Pigmentosa; Membrane Proteins
PubMed: 37752465
DOI: 10.1186/s12886-023-03132-8 -
Investigative Ophthalmology & Visual... Sep 2023The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD)...
PURPOSE
The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD.
METHODS
In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg), we graded AMD via color fundus images applying two established classification systems (CC and 3CACSS). We calculated the genetic risk score (GRS) across 50 previously identified variants for late AMD, its association via logistic regression, and area under the curve (AUC) for each AMD stage.
RESULTS
We analyzed 2188 persons aged 70 to 95 years. When comparing the two classification systems, we found a distinct pattern: CC "age-related changes" and CC "early AMD" distinguished individuals with 3CACSS "no AMD"; 3CACSS "mild/moderate/severe early AMD" stages, and distinguished CC "intermediate AMD". This suggested a 7-step scale combining the 2 systems: (i) "no AMD", (ii) "age-related changes", (iii) "very early AMD", (i.e. CC "early"), (iv) "mild early AMD", (v) "moderate early AMD", (vi) "severe early AMD", and (vii) "late AMD". GRS association and diagnostic accuracy increased stepwise by increased AMD severity in the 7-step scale and by increased restriction of controls (e.g. for CC "no AMD without age-related changes": AUC = 55.1%, 95% confidence interval [CI] = 51.6, 58.6, AUC = 62.3%, 95% CI = 59.1, 65.6, AUC = 63.8%, 95% CI = 59.3, 68.3, AUC = 78.1%, 95% CI = 73.6, 82.5, AUC = 82.2%, 95% CI = 78.4, 86.0, and AUC = 79.2%, 95% CI = 75.4, 83.0). A stepwise increase was also observed by increased drusen size and area.
CONCLUSIONS
The utility of a 7-step scale is supported by our clinical and GRS data. This harmonization and full data integration provides an immediate simplification over using either CC or 3CACSS and helps to sharpen the control group.
Topics: Humans; Cross-Sectional Studies; Macular Degeneration; Area Under Curve; Fundus Oculi; Risk Factors
PubMed: 37721739
DOI: 10.1167/iovs.64.12.31 -
Translational Vision Science &... Sep 2023To examine spatial patterns of retinal sensitivity loss in the three key features of intermediate age-related macular degeneration (iAMD).
PURPOSE
To examine spatial patterns of retinal sensitivity loss in the three key features of intermediate age-related macular degeneration (iAMD).
METHODS
One-hundred individuals (53 iAMD, 47 normal) underwent 10-2 mesopic microperimetry testing in one eye. Pointwise sensitivities (dB) were corrected for age, sex, iAMD status, and co-presence of co-localized key iAMD features: drusen load, pigmentary abnormalities, and reticular pseudodrusen (RPD). Clusters (labeled by ranks of magnitude C-2, C-1, C0) were derived from pointwise sensitivities and then assessed by quadrants and eccentricity/rings.
RESULTS
Two clusters of decreased sensitivities were evident in iAMD versus normal: C-2, -1.67 dB (95% CI (confidence intervals), -2.36 to -0.98; P < 0.0001); C-1, -0.93 dB (95% CI, -1.5 to -0.36; P < 0.01). One cluster of decreased sensitivity was independently associated each with increased drusen load (13.57 µm increase per -1 dB; P < 0.0001), pigmentary abnormalities (C-1: -2.23 dB; 95% CI, -3.36 to -1.1; P < 0.01), and RPD (C-1: -1.07 dB; 95% CI, -2 to -0.14; P < 0.01). Sensitivity loss in iAMD was biased toward the superior and central macula (P = 0.16 to <0.0001), aligning with structural distributions of features. However, sensitivity loss associated with drusen load also extended to the peripheral macula (P < 0.0001) with paracentral sparing, which was discordant with the central distribution of drusen.
CONCLUSIONS
Drusen load, pigmentary abnormalities, and RPD are associated with patterns of retinal sensitivity loss commonly demonstrating superior and central bias. Results highlighted that a clinical focus on these three key iAMD features using structural measures alone does not capture the complex, spatial extent of vision-related functional impairment in iAMD.
TRANSLATIONAL RELEVANCE
Defining the spatial patterns of retinal sensitivity loss in iAMD can facilitate a targeted visual field protocol for iAMD assessment.
Topics: Humans; Retina; Macular Degeneration; Retinal Drusen; Macula Lutea; Transcription Factors
PubMed: 37676679
DOI: 10.1167/tvst.12.9.6