Functional Correlates of Outer Retina Remodeling in Intermediate Age-Related Macular Degeneration Using Microperimetry

Abstract

Purpose To assess the effect of drusen morphometric changes and choroidal vascular modifications on retinal sensitivity (RS) evaluated through microperimetry in intermediate age-related macular degeneration (iAMD). Methods A retrospective review of 18 iAMD patients (18 eyes) with a 12-month follow-up was performed. Eye-tracked spectral-domain optical coherence tomography was obtained, with automatic segmentation of the outer retinal layer (ORL) delineating the drusen area from the external limiting membrane to Bruch's membrane and outer nuclear layer (ONL) thickness maps adjusted manually, as needed. Advanced retinal pigment epithelium analysis was also performed with a ZEISS PLEX Elite 900. Microperimetry obtained under mesopic conditions was overlaid with the corresponding thickness maps with Fiji software. The choroidal vascularity index (CVI) was calculated in the subfoveal b-scan and volumetric in the central 1-mm subfield. Results A reduced central ONL thickness was strongly associated with RS decline at the same region ( r = 0.69, P = 0.002) and globally ( r = 0.80, P < 0.001) at baseline, but also at 1 year in the central subfield (central: r = 0.70, P = 0.001). One-year subfoveal CVI variation, differently from volumetric CVI, directly influenced the central ( r = 0.64, P = 0.004) and global RS ( r = 0.59, P = 0.009), indicating that a CVI reduction negatively affected RS. A greater volumetric CVI within central 1-mm was associated with ORL thickening at 1 year ( r = 0.61, P = 0.008). Conclusions Progressive degeneration of the ONL is related to irreversible photoreceptor dysfunction in iAMD. Likewise, choroidal vascular modifications are associated with a significant functional decline in the central region and diffusely.

Choroidal Vasculature Changes in Age-Related Macular Degeneration: From a Molecular to a Clinical Perspective

“…AMD is a multifactorial and complex disease that includes several possible mechanisms: genetic risk factors encoding for the complement system such as complement factor H, CFHR, C2, C3, CFI and SERPING1, inflammatory, oxidative, lipidic, mitochondrial, and microvascular factors [ 17 , 43 ]. Evidence of CC impairment in AMD emerged from several studies with different approaches, including prolonged choroidal filling on both indocyanine green and fluorescein angiography in early AMD, Doppler flow studies, a proteomic analysis that found the loss of CC protein (CA4 and HLA-A) with the preservation of RPE proteins (CRALBP and RPE 65), histopathological studies, and more recently, with the advancements in multimodal imaging [ 43 , 44 , 45 , 46 , 47 , 48 , 49 ].…”

“…The post-processing method is usually applied on a single subfoveal OCT B-scan with optimal visualization of the choroid–scleral junction. However, a volumetric CVI estimation calculating several consecutive B-scans can also be obtained [ 44 , 112 , 113 , 114 ].…”

Biomarkers for the Progression of Intermediate Age-Related Macular Degeneration

“…One strategy to improve the ability to show change over time could be to individualize the test grid and so gain information in specific regions identified as being at risk of progression, such as areas showing early OCT signs of atrophy. Although time intensive to perform, scotopic microperimetry may be of particular use in iAMD cohorts [ 116 ]. In eyes with earlier stages of AMD, scotopic retinal sensitivity is more decreased than photopic or mesopic sensitivity compared to healthy controls [ 117 , 118 ].…”

Choroidal vascularity index in different types of central serous chorioretinopathy: A meta-analysis

“…In contrast to Sonoda’s method, which selects the choroidal area before binarization, in 2016, Agrawal [ 19 ] modified this method by proceeding with binarization before selecting the choroidal area, and they calculated the ratio of the LA to the total choroidal area and called it CVI. In recent years, more studies have used CVI as an indicator to evaluate the choroid in healthy or diseased eyes [ 20 , 21 ].…”