Background
Subretinal drusenoid deposits (SDD), also denominated reticular pseudodrusen, are closely associated with age-related macular degeneration (AMD) and have been identified as an independent risk factor for a worse prognosis due to progression to atrophic or neovascular AMD. Recently, it has been shown that the condition is associated with choroidal thinning and thinning of the ganglion cell layer-inner plexiform layer of the retina.However, the etiopathogenesis and implications of SDD are still not completely clarified.
Objectives
The primary purpose of this study is to evaluate blood flow and vascular density of the macular superficial and deep vascular plexus, peripapillary plexus, choriocapillaris, and evaluation of the foveal avascular zone in patients with SDD. Furthermore, ganglion cell complex (GCC) thickness will be evaluated. Analysis of data will be carried out to seek possible correlations of the GCC thickness with macular vascular alterations, and to evaluate the predominance of neuronal and/or vascular component changes using these parameters.
Subjects/Methods
Patients with AMD will be enrolled composed as follows: patients with SDD alone or predominant SDD, patients with conventional (soft) drusen alone or predominant drusen, and a group of healthy, age-matched controls. Visual acuity assessment and comprehensive ophthalmological examination with photographic documentation will be performed. Near infrared reflectance, optical coherence tomography angiography (OCT-A) and standard OCT images will be acquired. Drusen and SDD will be diagnosed based on OCT scans and near infrared reflectance images. GCC thickness maps will be generated with automated segmentation of OCT. OCT-A will include evaluation of the foveal avascular zone, density and flow of the superficial and deep macular vascular plexus, peripapillary plexus, and choriocapillaris.
State of Art
Novel research has identified a possible role of the choroid and choroidal circulation in the etiopathogenetic mechanisms behind AMD, this has been possible with the advent of enhanced depth imaging which enables choroidal thickness/morphology evaluation; previously not possible with OCT systems. The advent of OCT- angiography (OCT-A) in the recent years is providing further information on retinal and choroidal vascularization in numerous subtypes of AMD.
Potential to provide advancement in our knowledge
The presence of SDD carries important implications to consider in the management of patients with AMD as early diagnosis through identification of biomarkers can enable early treatment with a lower economic burden on medical care. Thus, our recent publication on ganglion cell- inner plexiform layer thinning using OCT has potentially opened a window on new etiopathogenetic mechanisms and biomarkers in patients with SDD. The research we are currently proposing continues in this directions but will allow further advances in the existing knowledge of the pathology using the innovative imaging method of OCT angiography. It is not yet clear if GCL-IPL thinning is prevalently due to the neuronal or the vascular components of these layers, and by carrying out both thickness evaluation of the GCC and OCT-A to assess the neural and the macular vascular components we aim to shed further light on this aspect.
This research aims to further clarify the etiopathogenetic mechanism behind SDD and establish biomarkers for AMD associated with SDD in order to enable early diagnosis and evaluation of risk factors in the follow up and management of AMD patients.
Innovation of the research
Recently we published an article in the prestigious journal of the Royal College of Ophthalmologists entitled "Optical coherence tomography evidence of macular ganglion cell-inner plexiform layer thinning in eyes with SDD; Eye (Lond) 2019 Mar 29, doi 10.1038/s41433-019-0405-3" The finding of ganglion cell- inner plexiform layer (GCL-IPL) thinning is potentially a new biomarker of SDD in the context of AMD. Therefore, in the present proposal we aim to study and evaluate vascular density and flow in the superficial and deep retinal vascular plexus together with evaluation of choriocapillaris flow and density with a non- invasive and rapid imaging technique (OCT-A), which we currently possess at the Ophthalmology Unit, Sapienza University of Rome, Ospedale Sant¿Andrea. (Joint research will be carried out at the medical retinal unit directed by Prof. Zweifel) The ganglion cell complex layer thickness will also be assessed with particular regard to possible correlations of GCC and OCT-A alterations. Analysis of data will be carried out to evaluate the predominance of neuronal and/or vascular component alterations using these parameters.
We will be collaborating with Prof. Zweifel who is head of the Medical Retina Unit of the University of Zurich and a leading figure in research on SDD.