Retinal layer thicknesses and neurodegeneration in early age-related macular degeneration: insights from the Coimbra Eye Study

Farinha, Cláudia; Silva, Ana Luísa; Coimbra, Rita; Nunes, Sandrina; Cachulo, Maria Luz; Marques, João Pedro; Pires, Isabel; Cunha-Vaz, Josè; Silva, Rufino

doi:10.1007/s00417-021-05140-0

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…Our group previously reported that in early AMD patients from the CES the presence of SDD was associated with both thinner neuroretinal layers and thinner choroids. 31 Subretinal drusenoid deposits are a distinct feature of AMD and a known risk factor for advanced disease. However, their pathophysiological mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Quantification in the macula of the total retinal thickness and volume, and layer-by-layer including the RPE/Bruch's membrane layer (which is an indirect measurement of the drusen load), was performed in patients with early AMD (stages 2 and 3) through semi-automatic segmentation as reported previously. 31 Eyes in stage 4 were excluded from retinal thickness and volume measurements because of the inherent retinal layer distortion caused by GA or MNV. In brief, the Heidelberg segmentation software displays seven distinct retinal layers (retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, and RPE/Bruch's membrane layer), and also provides information on two additional “combination” layers: (1) the inner retinal layers, extending from the inner limiting membrane to the external limiting membrane; and (2) the outer retinal layers, from external limiting membrane to Bruch's membrane.…”

Section: Methodsmentioning

confidence: 99%

“…The subfoveal choroidal thickness was measured manually in both early and late AMD patients with the in-built caliper tool available in the software. 31 …”

Section: Methodsmentioning

confidence: 99%

“…The SDD total area was measured by using the manual Heidelberg Eye Explorer region overlay tool to draw the borders of the area of interest, and GA was measured by using the semi-automated RegionFinder software. 31 , 32 …”

Section: Methodsmentioning

confidence: 99%

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Phenotypic Expression of CFH Rare Variants in Age-Related Macular Degeneration Patients in the Coimbra Eye Study

Farinha

Barreto

Coimbra

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To determine the association between rare genetic variants in complement factor H ( CFH ) and phenotypic features in age-related macular degeneration (AMD) patients from the Coimbra Eye Study (CES). Methods AMD patients from the Incidence CES (NCT02748824) underwent ophthalmologic examination and color fundus photography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, and near-infrared imaging. Multimodal phenotypic characterization was carried out in a centralized reading center. The coding and splice-site regions of the CFH gene were sequenced through single-molecule molecular inversion probe–based next-generation sequencing in association with the EYE-RISK consortium. Variants with minor allele frequency <0.05 resulting in splice-site or protein change were selected. Differences in phenotypic features between carriers and noncarriers were analyzed using generalized estimated equations logistic regression models, considering intereye correlations. Results We included 39 eyes of 23 patients carrying rare CFH variants and 284 eyes of 188 noncarriers. Carrier status was associated with having higher drusen burden in the macula in the inner Early Treatment Diabetic Retinopathy Study circle (odds ratio [OR], 5.44 [95% confidence interval {CI}, 1.61–18.37]; P = 0.006), outer circle (OR, 4.37 [95% CI, 1.07–17.77]; P = 0.04), and full grid (OR, 4.82 [95% CI, 1.13–20.52]; P = 0.033). In SD-OCT, a lower total macular volume and lower inner retinal layers’ volume (OR, 0.449 [95% CI, 0.226–0.894]; P = 0.023; OR, 0.496 [95% CI, 0.252–0.979]; P = 0.043) and pigment epithelial detachments (PEDs) (OR, 5.24 [95% CI, 1.08–25.44]; P = 0.04) were associated with carrying a rare CFH variant. Carriers with subretinal drusenoid deposits (SDD) had the rare variant P258L in all cases except one. Conclusions We identified in our cohort phenotypic differences between carriers and noncarriers of rare variants in the CFH gene. Carriers had more severe disease, namely superior drusen burden, PEDs, and thinner retinas. The rare variant P258L may be associated with SDD. Carriers are probably at increased risk of progression.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The subfoveal choroidal thickness was measured manually in both early and late AMD patients with the in-built caliper tool available in the software. 31 …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Phenotypic Expression of CFH Rare Variants in Age-Related Macular Degeneration Patients in the Coimbra Eye Study

Farinha

Barreto

Coimbra

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…Thinning of the OPL may precede development of drusen 23 . The changes in OPL may occur due to early and progressive neurodegeneration in addition to neuronal migration and peripheral (extramacular proliferation) in AMD 18 , 19 . Similar mechanisms of OPL remodeling may occur in TB SLC, resulting in thinning of the OPL layer and formation of the MLM.…”

Section: Discussionmentioning

confidence: 99%

Semi-automated quantitative analysis of the middle limiting membrane in tubercular serpiginous-like choroiditis using swept-source optical coherence tomography

Agarwal

Kalra

Agrawal

et al. 2021

Sci Rep

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To analyze the longitudinal changes in the outer plexiform layer (OPL) in patients with tubercular serpiginous-like choroiditis (TB SLC) and compare it to the healthy control population. Clinical and imaging data of subjects with TB SLC (minimum 6-month follow-up) and healthy control subjects were reviewed. Optical coherence tomography (OCT) imaging obtained using swept-source device (DRI Triton, Topcon, Japan) from three visits (baseline, 3 months, and 6 months) were analyzed. Three OCT scans were chosen—one passing through the center of the fovea, one line above, and one line below. After random indexing to anonymize the images, they were pre-processed and fed into an automated pipeline to identify, crop, and measure the area of the OPL in the line scan. Longitudinal comparisons of OPL within the patient group were performed. The study included 32 eyes (16 patients; 11 males; mean age: 32.9 ± 7.8 years) with TB SLC. Twenty-eight eyes (14 subjects; 10 males: mean age: 31.1 ± 6.2 years) of healthy control subjects (age- and gender-matched) were also selected. The area of OPL was significantly different between the baseline and month 6 visit (6288 ± 1803 versus 5487 ± 1461; p = 0.0002) at the central scan passing through the fovea. For the scans above and below the fovea, the reduction in OPL area was significant at each visit (p < 0.0001). In comparison with healthy control subjects, OPL area values in patients with TB SLC were significantly lower at the month-3 (6116 ± 1441 versus 7136 ± 2539; p = 0.04) and the 6-month visit (5487 ± 1461 versus 7136 ± 2539; p < 0.001). The atrophied OPL at month 6 has been referred to as the “middle limiting membrane” (MLM). Subjects with TB SLC may develop progressive atrophy of the OPL resulting in formation of MLM, which is seen as a hyper-reflective line replacing the OPL. The analysis of longitudinal changes in the OPL may be useful in predicting anatomical and functional outcomes in these patients.

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Imaging characterization of the fellow eye in patients with unilateral polypoidal choroidal vasculopathy

Pereira,

Simão,

Silva

et al. 2024

Int Ophthalmol

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Retinal layer thicknesses and neurodegeneration in early age-related macular degeneration: insights from the Coimbra Eye Study

Cited by 7 publications

References 30 publications

Phenotypic Expression of CFH Rare Variants in Age-Related Macular Degeneration Patients in the Coimbra Eye Study

Phenotypic Expression of CFH Rare Variants in Age-Related Macular Degeneration Patients in the Coimbra Eye Study

Semi-automated quantitative analysis of the middle limiting membrane in tubercular serpiginous-like choroiditis using swept-source optical coherence tomography

Imaging characterization of the fellow eye in patients with unilateral polypoidal choroidal vasculopathy

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