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Alzheimer's disease (AD) is a neurodegenerative disorder, which is likely to start as mild cognitive impairment (MCI) several years before the its full-blown clinical manifestation. Optical coherence tomography (OCT) has been used to detect a loss in peripapillary retina nerve fiber layer (RNFL) and a reduction in macular thickness and volume of people affected by MCI or AD. Here, we performed an aggregate meta-analysis combining results from different studies. Data sources were case-control studies published between January 2001 and August 2014 (identified through PubMed and Google Scholar databases) that examined the RNFL thickness by means of OCT in AD and MCI patients compared with cognitively healthy controls. 11 studies were identified, including 380 patients with AD, 68 with MCI and 293 healthy controls (HC). The studies suggest that the mean RNFL thickness is reduced in MCI (weighted mean differences in μm, WMD = -13.39, 95% CI: -17.34 to -9.45, p = 0.031) and, even more so, in AD (WMD = -15.95, 95% CI: -21.65 to -10.21, p<0.0001) patients compared to HC. RNFL in the 4 quadrants were all significantly thinner in AD superior (superior WMD = -24.0, 95% CI: -34.9 to -13.1, p<0.0001; inferior WMD = -20.8, 95% CI: -32.0 to -9.7, p<0.0001; nasal WMD = -14.7, 95% CI: -23.9 to -5.5, p<0.0001; and temporal WMD = -10.7, 95% CI: -19.9 to -1.4, p<0.0001); the same significant reduction in quadrant RNFL was observed in MCI patients compared with HC (Inferior WMD = -20.22, 95% CI: -30.41 to -10.03, p = 0.0001; nasal WMD = -7.4, 95% CI: -10.08 to -4.7, p = 0.0000; and temporal WMD = -6.88, 95% CI: -12.62 to -1.13, p = 0.01), with the exception of superior quadrant (WMD = -19.45, 95% CI: -40.23 to 1.32, p = 0.06). Results from the meta-analysis support the important role of OCT for RNFL analysis in monitoring the progression of AD and in assessing the effectiveness of purported AD treatments.

Background/Objectives: This study investigates adaptive changes in long-lasting pattern electroretinogram (PERG) responses in ocular hypertension (OHT) and open-angle glaucoma (OAG) patients, and in healthy subjects. Methods: Sixty consecutive individuals were recruited, including 20 OHT, 20 OAG, and 20 normal subjects. All participants underwent comprehensive ophthalmologic examination, 30–2 perimetry, and retinal nerve fiber layer imaging. Steady-state (7.5 Hz) PERGs were recorded over approximately 2 min, in response to 90% contrast alternating gratings within a large field size. The recordings were acquired into a sequence of 10 averages (packets), lasting 10 s each, following a standardized adaptation paradigm (Next Generation PERG, PERGx). Key outcome measures included PERGx parameters reflecting response amplitude and phase changes over time. Results: The PERGx grand average scalar amplitude, a surrogate of ordinary PERG, was significantly reduced in both OHT and OAG groups compared to normal subjects (p < 0.01). In contrast, minimal adaptation changes were noted in PERGx amplitude among all groups. The PERGx phase exhibited a progressive decline over time, with consistent delays of approximately 20 degrees across all groups. Angular dispersion of the PERGx phase increased significantly in OHT patients compared to normal subjects (p < 0.05). An inverse relationship was observed between PERGx angular dispersion and treated intraocular pressure, specifically in OHT patients. Conclusions: The findings suggest that both OHT and OAG eyes may exhibit temporal abnormalities in PERG adaptation, potentially indicating early dysfunction in retinal ganglion cell activity. Translational Relevance: PERGx phase changes may have significant implications for glaucoma early detection and management.

Doc number: A23

Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract retinal oxidative damage, inflammation and protect retinal cells from apoptosis. This pilot study aimed to evaluate central retinal function following saffron supplementation in STG/FF patients carrying ABCA4 mutations. Methods: in a randomized, double-blind, placebo-controlled study (clinicaltrials.gov: NCT01278277), 31 patients with ABCA4-related STG/FF and a visual acuity >0.25 were randomly assigned to assume oral saffron (20 mg) or placebo over a six month period and then reverted to P or S for a further six month period. Full ophthalmic examinations, as well as central 18° focal electroretinogram (fERG) recordings, were performed at baseline and after six months of either saffron or placebo. The fERG fundamental harmonic component was isolated by Fourier analysis. Main outcome measures were fERG amplitude (in µV) and phase (in degrees). The secondary outcome measure was visual acuity. Results: supplement was well tolerated by all patients throughout follow-up. After saffron, fERG amplitude was unchanged; after placebo, amplitude tended to decrease from baseline (mean change: −0.18 log µV, p < 0.05). Reverting the treatments, amplitude did not change significantly. fERG phase and visual acuity were unchanged throughout follow-up. Conclusions: short-term saffron supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina and visual acuity. The current findings warrant further long-term clinical trials to assess the efficacy of saffron supplementation in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF.

Background Patients suffering from migraine with aura can have either pure visual auras or complex auras with sensory disturbances and dysphasia, or both. Few studies have searched for possible pathophysiological differences between these two subgroups of patients. Methods Methods - Forty-seven migraine with aura patients were subdivided in a subgroup with exclusively visual auras (MA, N =  27) and another with complex neurological auras (MA+, N =  20). We recorded pattern-reversal visual evoked potentials (VEP: 15 min of arc cheques, 3.1 reversal per second, 600 sweeps) and measured amplitude and habituation (slope of the linear regression line of amplitude changes from the 1st to 6th block of 100 sweeps) for the N1-P1 and P1-N2 components in patients and, for comparison, in 30 healthy volunteers (HV) of similar age and gender distribution. Results VEP N1-P1 habituation, i.e. amplitude decrement between 1st and 6th block, which was obvious in most HV (mean slope −0.50), was deficient in both MA (slope +0.01, p =  0.0001) and MA+ (−0.0049, p =  0.001) patients. However, VEP N1-P1 amplitudes across blocks were normal in MA patients, while they were significantly greater in MA+ patients than in HVs. Conclusions Our findings suggest that in migraine with aura patients different aura phenotypes may be underpinned by different pathophysiological mechanisms. Pre-activation cortical excitability could be higher in patients with complex neurological auras than in those having pure visual auras or in healthy volunteers.

Background To determine whether the functional effects of oral supplementation with Saffron, a natural compound that proved to be neuroprotective in early age-related macular degeneration, are influenced by complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk genotypes. Methods Thirty-three early AMD patients, screened for CFH (rs1061170) and ARMS2 (rs10490924) polymorphisms and receiving Saffron oral supplementation (20 mg/day) over an average period of treatment of 11 months (range, 6–12), were longitudinally evaluated by clinical examination and focal electroretinogram (fERG)-derived macular (18°) flicker sensitivity estimate. fERG amplitude and macular sensitivity, the reciprocal value of the estimated fERG amplitude threshold, were the main outcome measures. Results After three months of supplementation, mean fERG amplitude and fERG sensitivity improved significantly when compared to baseline values (p < 0.01). These changes were stable throughout the follow-up period. No significant differences in clinical and fERG improvements were observed across different CFH or ARMS2 genotypes. Conclusions The present results indicate that the functional effect of Saffron supplementation in individual AMD patients is not related to the major risk genotypes of disease.

Background Alzheimer's disease (AD) is a neurodegenerative disorder, which is likely to start as mild cognitive impairment (MCI) several years before the its full-blown clinical manifestation. Optical coherence tomography (OCT) has been used to detect a loss in peripapillary retina nerve fiber layer (RNFL) and a reduction in macular thickness and volume of people affected by MCI or AD. Here, we performed an aggregate meta-analysis combining results from different studies. Methods and Findings Data sources were case-control studies published between January 2001 and August 2014 (identified through PubMed and Google Scholar databases) that examined the RNFL thickness by means of OCT in AD and MCI patients compared with cognitively healthy controls. Results 11 studies were identified, including 380 patients with AD, 68 with MCI and 293 healthy controls (HC). The studies suggest that the mean RNFL thickness is reduced in MCI (weighted mean differences in mu m, WMD = -13.39, 95% CI: -17.34 to -9.45, p = 0.031) and, even more so, in AD (WMD = -15.95, 95% CI: -21.65 to -10.21, p<0.0001) patients compared to HC. RNFL in the 4 quadrants were all significantly thinner in AD superior (superior WMD = -24.0, 95% CI: -34.9 to -13.1, p<0.0001; inferior WMD = -20.8, 95% CI: -32.0 to -9.7, p<0.0001; nasal WMD = -14.7, 95% CI: -23.9 to -5.5, p<0.0001; and temporal WMD = -10.7, 95% CI: -19.9 to -1.4, p<0.0001); the same significant reduction in quadrant RNFL was observed in MCI patients compared with HC (Inferior WMD = -20.22, 95% CI: -30.41 to -10.03, p = 0.0001; nasal WMD = -7.4, 95% CI: -10.08 to -4.7, p = 0.0000; and temporal WMD = -6.88, 95% CI: -12.62 to -1.13, p = 0.01), with the exception of superior quadrant (WMD = -19.45, 95% CI: -40.23 to 1.32, p = 0.06). Conclusion Results from the meta-analysis support the important role of OCT for RNFL analysis in monitoring the progression of AD and in assessing the effectiveness of purported AD treatments.

Purpose: To assess regional cone-mediated function in age-related maculopathy (ARM) by focal electroretinograms (FERGs), and to compare FERGs with morphologic changes and perimetric sensitivity at corresponding locations. Methods: Twenty-six ARM patients and 12 age-matched controls were evaluated. FERGs were elicited by either a central (0–2.25°, C) or a paracentral annular (2.25–9°, PC) flickering (41 Hz) field, presented on a light-adapting background. Morphological changes (soft drusen and/or retinal pigment epithelium defects) at matched locations were assessed by fundus photography and fluorescein angiography. Perimetric sensitivity was measured by Octopus 10° program (tM2). Results: When compared to controls, mean C and PC FERG amplitudes of patients were reduced (p < 0.01), and the mean PC FERG phase was delayed (p < 0.01). Both FERG delays and morphologic lesions tended to involve to a greater extent the PC compared to the C region. In the C region, perimetric losses were correlated with the extent of morphologic lesions (p < 0.05). In the PC region, perimetric losses were correlated with FERG amplitudes (p < 0.05). Conclusions: In ARM, FERG losses are eccentricity-dependent, not quantitatively linked to retinal morphology, and correlated with perimetric losses, suggesting a heterogeneous dysfunction with loss of both C and PC perimetric sensitivities.