Ganglion Cell Layer Thinning in Alzheimer's Disease.

The main advantages of optical retinal imaging may allow researchers to achieve deeper analysis of retinal ganglion cells (GC) in vivo using optical coherence tomography (OCT). Using this device to elucidate the impact of Alzheimer's disease (AD) on retinal health with the aim to identify a new AD biomarker, a large amount of studies has analyzed GC in different stages of the disease. Our review highlights recent knowledge into measuring retinal morphology in AD making distinctive between whether those studies included patients with clinical dementia stage or also mild cognitive impairment (MCI), which selection criteria were applied to diagnosed patients included, and which device of OCT was employed. Despite several differences, previous works found a significant thinning of GC layer in patients with AD and MCI. In the long term, an important future direction is to achieve a specific ocular biomarker with enough sensitivity to reveal preclinical AD disorder and to monitor progression.

Bilateral choroidal osteoma: long-term follow-up of secondary choroidal neovascularization in a child using antiangiogenic therapy.

Choroidal osteoma is a rare condition, and its treatment is not well established, especially in the pediatric population, where use of antiangiogenics for choroidal neovascularization is poorly studied. Few studies have reported the long-term follow-up of pediatric patients with bilateral choroidal osteomas. We report the case of a girl who was diagnosed at the age of 3, with the appearance of bilateral secondary choroidal neovascularization, and has been under strict observation for 12 years. The effectiveness of antiangiogenic agents as a long-term therapeutic option for secondary choroidal neovascularization in pediatric patients with symptomatic choroidal osteomas is discussed.

The retinal ganglion cell layer reflects neurodegenerative changes in cognitively unimpaired individuals.

BACKGROUND: To evaluate a wide range of optical coherence tomography (OCT) parameters for possible application as a screening tool for cognitively healthy individuals at risk of Alzheimer's disease (AD), assessing the potential relationship with established cerebrospinal fluid (CSF) core AD biomarkers and magnetic resonance imaging (MRI). METHODS: We studied 99 participants from the Valdecilla Study for Memory and Brain Aging. This is a prospective cohort for multimodal biomarker discovery and validation that includes participants older than 55 years without dementia. Participants received a comprehensive neuropsychological battery and underwent structural 3-T brain MRI, lumbar puncture for CSF biomarkers (phosphorylated-181-Tau (pTau), total Tau (tTau), beta-amyloid 1-42 (Aß 1-42), and beta-amyloid 1-40 (Aß 1-40)). All individuals underwent OCT to measure the retinal ganglion cell layer (GCL), the retinal nerve fiber layer (RFNL), the Bruch's membrane opening-minimum rim width (BMO-MRW), and choroidal thickness (CT). In the first stage, we performed a univariate analysis, using Student's t-test. In the second stage, we performed a multivariate analysis including only those OCT parameters that discriminated at a nominal level, between positive/negative biomarkers in stage 1. RESULTS: We found significant differences between the OCT measurements of pTau- and tTau-positive individuals compared with those who were negative for these markers, most notably that the GCL and the RNFL were thinner in the former. In stage 2, our dependent variables were the quantitative values of CSF markers and the hippocampal volume. The Aß 1-42/40 ratio did not show a significant correlation with OCT measurements while the associations between pTau and tTau with GCL were statistically significant, especially in the temporal region of the macula. Besides, the multivariate analysis showed a significant correlation between hippocampal volume with GCL and RNFL. However, after false discovery rate correction, only the associations with hippocampal volume remained significant. CONCLUSIONS: We found a significant correlation between Tau (pTau) and neurodegeneration biomarkers (tTau and hippocampus volume) with GCL degeneration and, to a lesser degree, with damage in RFNL. OCT analysis constitutes a non-invasive and unexpensive biomarker that allows the detection of neurodegeneration in cognitively asymptomatic individuals.

Different follow-up OCT analyses of traumatic optic neuropathy. A case report.

PURPOSE: Optical coherence tomography (OCT) is established as a promising technology for assessing the optic nerve atrophy progression after trauma. However, reports on the effectiveness and sensitivity of ganglion cell layer (GCL) and Bruch's membrane opening-minimum rim width (BMO-MRW) for studying this damage course over time are still lacking. OBSERVATIONS: A 53-year-old man with severe optic nerve trauma had repeated OCT scans of the retinal nerve fiber layer (RNFL), GCL and BMO-MRW during 12 months after the injury. There was gradual damage in all measurements. Interestingly, BMO-MRW was the first analysis affected whilst GCL showed the greatest damage over time. CONCLUSIONS: Our outcomes suggest that OCT might be able to assess axonal loss after traumatic optic neuropathy. BMO-MRW measurement might be more sensitive than other analyses in the first two weeks after trauma and GCL might better monitor belated damage. Thus, it might be possible to combine all these sets of measurements to increase diagnostic sensitivity an specificity.

Retinal Artery Contraction After Phenylephrine as a Cardiovascular Risk Biomarker.

BACKGROUND AND AIM: We investigated the in vivo changes of artery diameter (AD) and vein diameter (VD) after topical phenylephrine 2.5% instillation, and its relationship with the Systematic Coronary Risk Evaluation (SCORE). METHODS: This is a cross-sectional study. Healthy control patients were included. All of the participants underwent enhanced depth imaging by spectral-domain optical coherence tomography before and 30 minutes after phenylephrine instillation, using eye-tracking and follow-up software. Changes in AD and VD were assessed. RESULTS: The study included 45 eyes of 45 patients (14 males and 31 females). The mean age was 58.6 ± 15.1 years (26-88 years). Mean SCORE risk estimation value was 2.0 (0-14). No significant correlation was found between pre-phenylephrine AD or VD with age (p=0.237 and p=0.821, respectively), SCORE (p=0.545 and p=0.723, respectively). AD significant thinned after phenylephrine (p<0.001), whereas no significant changes could be depicted in VD (p=0.474). Changes in AD after phenylephrine were significantly related with SCORE risk estimation (p=0.035). Discordantly, changes in VD after phenylephrine were not significantly related with SCORE (p=0.505). CONCLUSION: As a significant thinning of AD occurred following phenylephrine instillation, and as the magnitude of this thinning is related with SCORE, it is useful to test the retinal artery contraction to infer the cardiovascular health status.

Outer Nuclear Layer Damage for Detection of Early Retinal Toxicity of Hydroxychloroquine.

In hydroxychloroquine (HCQ) retinopathy, early detection of asymptomatic retinal changes and the interruption of the drug are essential to prevent permanent vision loss. Our purpose was to investigate the roles of ganglion cell layer (GCL) and outer nuclear layer (ONL) thicknesses measured by optical coherence tomography (OCT) in the early diagnosis of retinopathy. One hundred and fourteen eyes of 76 individuals with HCQ treatment were enrolled in the study (42 eyes with impaired visual field (VF) and 72 eyes with nondamaged VF). We found that ONL was significantly decreased in the HCQ retinopathy group compared with the control group in the nasal macula (p = 0.032) as well as in four sectors (p < 0.044), whereas no significant differences were found comparing GCL in both groups. If VF were altered superiorly or temporarily, ONL was significantly thinned inferiorly (p = 0.029) and nasally (p = 0.008), respectively. Duration of HCQ treatment was significantly related with ONL in seven sectors of ONL (p < 0.047). We suggest that ONL measured with OCT might be used to assess early HCQ retinal toxicity.

Evaluation of choroidal thickness in prodromal Alzheimer's disease defined by amyloid PET.

OBJECTIVE: To assess and compare the involvement of choroidal thickness (CT) in patients with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD) defined by amyloid PET and healthy controls (HC). METHODS: Sixty-three eyes from 34 AD patients [12 eyes (19.0%) with dementia and 51 eyes (80.9%) with MCI], positive to 11C-labelled Pittsburgh Compound-B with positron emission tomography (11C-PiB PET/CT), and the same number of sex- and age-paired HC were recruited. All participants underwent enhanced depth imaging optical coherence tomography (EDI-OCT) assessing CT at 14 measurements from 2 B-scans. Paired Student t-test was used to compare CT measurements between MCI, dementia and sex- and age-paired HC. A univariate generalized estimating equations model (GEE) test was performed to compare MCI and dementia individually with all HC included. RESULTS: Compared with HC, eyes from patients with positive 11C-PiB PET/CT showed a significant CT thinning in 5 selected locations (in foveal thickness in vertical scan, in temporal scan at 1500µm, in superior scan at 500µm and in inferior scan at 1000µm and 1500µm, p = 0.020-0.045) whilst few significant CT reduction data was reported in MCI or dementia individually versus HC. However, the GEE test identified significant CT thinning in AD compared with all HC included (p = 0.015-0.046). CONCLUSIONS: To our knowledge, the present study is the first measuring CT in eyes from MCI and dementia eyes positive to 11C-PiB PET/CT reporting a significant trend towards CT thinning in MCI patients which became more pronounced in dementia stage. We support further investigation involving larger and prospective OCT studies in AD population characterized with available biomarkers to describe whether choroidal vascular damage occurs specifically in prodromal stages of AD.

Peripapillary and macular choroidal thickness before and after phenylephrine instillation.

OBJECTIVES: We investigated the effects of topical phenylephrine 2.5% instillation on choroidal thickness (CT), peripapillary choroidal thickness (pCT) and retinal nerve fibre layer (RNFL). METHODS: Healthy control patients underwent enhanced depth imaging (EDI) by spectral-domain optical coherence tomography (OCT) before and 30 min after phenylephrine instillation, using eye-tracking and follow-up software. Changes in 14 different locations of CT, 2 locations of pCT and RNFL were assessed. RESULTS: The study included 119 eyes of 62 patients (19 males and 43 females), with a mean age of 59.8 ± 15.3 years (range: 26-88 years). Within 30 min after instillation, the mean subfoveal CT both in vertical and horizontal scan were significantly thinned (p = 0.005 and p = 0.018, respectively). In total, 1500, 1000 and 500 µm temporal CT measurements showed also a significant thinning (p = 0.021, p = 0.037 and p = 0.020, respectively), as well as 500 µm both superior (p = 0.045) and inferior (p = 0.009). 1500, 1000 and 500 µm nasal CT, and 1500 and 1000 µm CT superior and inferior measurements showed no significant thinning after phenylephrine instillation. pCT was significantly thinned after phenylephrine in both superior (p = 0.016) and inferior (p = 0.050) measurements. RNFL analysis did not significantly change after phenylephrine instillation (p = 0.209). CONCLUSIONS: A significant thinning of CT and pCT occurred following phenylephrine instillation. Future studies analysing CT and pCT should detail if this mydriatic agent was used or not.

Topographic correlation and asymmetry analysis of ganglion cell layer thinning and the retinal nerve fiber layer with localized visual field defects.

PURPOSE: To evaluate the accuracy of the measurement of the ganglion cell layer (GCL) of the posterior pole analysis (PPA) software of the Spectralis spectral-domain (SD) optical coherence tomography (OCT) device (Heidelberg Engineering, Inc., Heidelberg, Germany), the asymmetry of paired GCL sectors, the total retinal thickness asymmetry (RTA), and the peripapillary retinal nerve fiber layer (pRNFL) test to discriminate between healthy, early and advanced glaucoma eyes. METHODS: Three hundred eighteen eyes of 161 individuals with reliable visual fields (VF) were enrolled in this study. All participants were examined using the standard posterior pole and the pRNFL protocols of the Spectralis OCT device. VF impairment was graded in hemifields, and the GCL sectors were correlated with this damage. Thicknesses of each GCL, the GCL map deviation asymmetry and the pRNFL were compared between control and glaucomatous eyes. The area under the receiver operating characteristic curve (AUC) of these analyses was assessed. RESULTS: Fourteen of the 16 sectors of the GCL and pRNFL were significantly thinner in eyes with glaucoma than in control eyes (p<0.006). Similarly, the GCL map deviation showed a significant difference between these eyes and both the control eyes as well as the eyes with early glaucoma (p = 0.001 and p = 0.039, respectively). The highest values of AUC to diagnose both early and advanced glaucoma corresponded to the average pRNFL analysis and the GCL map deviation (AUC>0.823, p<0.040 and AUC>0.708, p<0.188, respectively). CONCLUSIONS: Although 16 central sectors of the GCL observed with PPA showed good correlation with VF damage, the pRNFL and the GCL map deviation were more effective for discrimination of glaucomatous damage.

Ganglion cell layer thinning in prodromal Alzheimer's disease defined by amyloid PET.

INTRODUCTION: The objective of this study was to investigate and compare optic nerve and retinal layers in eyes of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) with paired control eyes using optical coherence tomography. METHODS: Sixty-three eyes of 34 subjects, 12 eyes with AD and 51 eyes with MCI, positive to 11C-labeled Pittsburgh Compound-B with positron emission tomography (11C-PiB PET/CT), and the same number of sex- and age-paired control eyes underwent optical coherence tomography scanning analyzing retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), Bruch's membrane opening-minimum rim width (BMO-MRW), inner plexiform layer (IPL), outer nuclear layer, and lamina cribrosa (LC). RESULTS: Compared with healthy controls, eyes of patients with positive 11C-PiB PET/CT showed a significant thinning of RNFL (P < .028) and GCL (P < .014). IPL and outer nuclear layer also showed significant thinning in two (P < .025) and one location (P < .010), respectively. No significant differences were found when optic nerve measurements BMO-MRW and LC were compared (P > .131 and P > .721, respectively). Temporal sector GCL, average RNFL, and temporal sector RNFL also exhibited significant thinning when MCI and control eyes were compared (P = .015, P = .005 and P = .050, respectively), and also the greatest area under the curve values (0.689, 0.647, and 0.659, respectively). GCL, IPL, and RNFL tend to be thinner in the AD group compared with healthy controls. DISCUSSION: Our study suggests that RNFL and GCL are useful for potential screening in the early diagnosis of AD. LC and BMO-MRW appear not to be affected by AD.