Dissipating the fog: Cognitive trajectories and risk factors 1 year after COVID-19 hospitalization.

INTRODUCTION: Cognitive impairment is common after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, associations between post-hospital discharge risk factors and cognitive trajectories have not been explored. METHODS: A total of 1105 adults (mean age ± SD 64.9 ± 9.9 years, 44% women, 63% White) with severe coronavirus disease 2019 (COVID-19) were evaluated for cognitive function 1 year after hospital discharge. Scores from cognitive tests were harmonized, and clusters of cognitive impairment were defined using sequential analysis. RESULTS: Three groups of cognitive trajectories were observed during the follow-up: no cognitive impairment, initial short-term cognitive impairment, and long-term cognitive impairment. Predictors of cognitive decline after COVID-19 were older age (ß = -0.013, 95% CI = -0.023;-0.003), female sex (ß = -0.230, 95% CI = -0.413;-0.047), previous dementia diagnosis or substantial memory complaints (ß = -0.606, 95% CI = -0.877;-0.335), frailty before hospitalization (ß = -0.191, 95% CI = -0.264;-0.119), higher platelet count (ß = -0.101, 95% CI = -0.185;-0.018), and delirium (ß = -0.483, 95% CI = -0.724;-0.244). Post-discharge predictors included hospital readmissions and frailty. DISCUSSION: Cognitive impairment was common and the patterns of cognitive trajectories depended on sociodemographic, in-hospital, and post-hospitalization predictors. HIGHLIGHTS: Cognitive impairment after coronavirus disease 2019 (COVID-19) hospital discharge was associated with higher age, less education, delirium during hospitalization, a higher number of hospitalizations post discharge, and frailty before and after hospitalization. Frequent cognitive evaluations for 12-month post-COVID-19 hospitalization showed three possible cognitive trajectories: no cognitive impairment, initial short-term impairment, and long-term impairment. This study highlights the importance of frequent cognitive testing to determine patterns of COVID-19 cognitive impairment, given the high frequency of incident cognitive impairment 1 year after hospitalization.

The spatial distribution of ERGs reflecting luminance and L-/M-cone-opponent signals.

PURPOSE: To study the spatial retinal distribution of electroretinographic (ERG) responses that reflect signals in the L-/M-cone-opponent and luminance post-receptoral pathways. METHODS: ERG recordings to heterochromatic stimuli (sinusoidal counter-phase modulation of red and green LED light sources) were performed, while varying fractions of red and green modulation. Two temporal frequencies of the stimuli were employed: 12 Hz to record ERGs that reflect L-/M-cone-opponent signal and 36 Hz for recording ERG signals sensitive to stimulus luminance. Stimuli were about 20° in diameter and projected on various retinal locations: the fovea and four eccentricities (10°, 19°, 28° and 35°), each presented nasally, temporally, inferiorly and superiorly from the fovea. RESULTS: The 36 Hz stimuli elicited responses that strongly varied with red fraction and were minimal at iso-luminance. Moreover, response phases changed abruptly at the minimum by 180°. In contrast, the responses to the 12 Hz stimuli had amplitudes and phases that changed more gradually with red fraction. The 36 Hz response amplitudes were maximal close to the fovea and sharply decreased with increasing distance from the fovea. The responses to 12 Hz stimuli were more broadly distributed across the retina. CONCLUSIONS: In the present study, it was found that retinal eccentricity and direction from the fovea have distinct effects on ERGs reflecting different post-receptoral mechanisms. The results are in accord with previous findings that ERGs to 12 Hz stimuli are predominantly determined by the red-green chromatic content of the stimuli, thus reflecting activation in the L-/M-cone-opponent pathway, while responses to 36 Hz stimuli manifest post-receptoral luminance-dependent activation. We found that the response in the cone-opponent pathway is broadly comparable across the retina; in comparison, response amplitude of the luminance pathway strongly depends on retinal stimulus position.

Alterations of color vision and pupillary light responses in age-related macular degeneration.

Introduction: Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries and one of the leading causes of blindness. In this work, we evaluated color vision and the pupil light reflex (PLR) to assess visual function in patients with early and neovascular AMD (NVAMD) compared with the control group. Methods: We recruited 34 early patients with dry AMD and classified them into two groups following AREDS: 13 patients with NVAMD and 24 healthy controls. Controls and patients with early dry AMD had visual acuity (VA) best or equal to 20/25 (0.098 logMAR). Color vision was assessed in controls and patients with early dry AMD using the Cambridge Color Test (CCT) 2.0 through the Trivector protocol. The PLR was evaluated using a Ganzfeld, controlled by the RETI-port system. The stimuli consisted of 1s blue (470 nm) and red (631 nm) light flashes presented alternately at 2-min intervals. To assess the cone contribution, we used a red flash at 2.4 log cd.m-2, with a blue background at 0.78 log cd.m-2. For rods, we used 470-nm flashes at -3 log cd.m-2, and for the melanopsin function of ipRGCs, we used 470 nm at 2.4 log cd.m-2. Results: Patients with early dry AMD had reduced color discrimination in all three axes: protan (p = 0.0087), deutan (p = 0.0180), and tritan (p = 0.0095) when compared with the control group. The PLR has also been affected in patients with early dry AMD and patients with NVAMD. The amplitude for the melanopsin-driven response was smaller in patients with early dry AMD (p = 0.0485) and NVAMD (p = 0.0035) than in the control group. The melanopsin function was lower in patients with NVAMD (p = 0.0290) than the control group. For the rod-driven response, the latency was lower in the NVAMD group (p = 0.0041) than in the control group. No changes were found in cone-driven responses between the control and AMD groups. Conclusion: Patients with early dry AMD present diffusely acquired color vision alteration detected by CCT. Rods and melanopsin contributions for PLR are affected in NVAMD. The CCT and the PLR may be considered sensitive tests to evaluate and monitor functional changes in patients with AMD.

The Association Between Acquired Color Deficiency and PET Imaging of Neurodegeneration in Mild Cognitive Impairment and Alzheimer Disease.

Purpose: To evaluate color vision changes and retinal processing of chromatic and luminance pathways in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI) compared with a matched control group and whether such changes are associated with impaired brain glucose metabolism and ß-amyloid deposition in the brain. Methods: We evaluated 13 patients with AD (72.4 ± 7.7 years), 23 patients with MCI (72.5 ± 5.5 years), and 18 controls of comparable age (P = 0.44) using Cambridge color test and the heterochromatic flicker ERG (HF-ERG). The Cambridge color test was performed using the trivector protocol to estimate the protan, deutan and tritan color confusion axes. HF-ERG responses were measured at a frequency of 12 Hz, which ERGs reflect chromatic activity, and at 36 Hz, reflecting luminance pathway. A study subsample was performed using neuropsychological assessments and positron emission tomography. Results: Patients with AD presented higher mean values indicating poorer color discrimination for protan (P = 0.04) and deutan (P = 0.001) axes compared with the controls. Along the tritan axis, both patients with AD and patients with MCI showed decreased color vision (P = 0.001 and P = 0.001) compared with controls. The analyses from the HF-ERG protocol revealed no differences between the groups (P = 0.31 and P = 0.41). Diffuse color vision loss was found in individuals with signs of neurodegeneration (protan P = 0.002, deutan P = 0.003 and tritan P = 0.01), but not in individuals with signs of ß-amyloid deposition only (protan P = 0.39, deutan P = 0.48, tritan P = 0.63), regardless of their clinical classification. Conclusions: Here, patients with AD and patients with MCI present acquired color vision deficiency that may be linked with impaired brain metabolism.

Correlations Between Dark-Adapted Rod Threshold Elevations and ERG Response Deficits in Duchenne Muscular Dystrophy.

Purpose: The purpose of this study was to characterize changes in the full-field flash electroretinogram (ERG) in association with psychophysical dark-adapted visual thresholds in patients with genetically characterized Duchenne muscular dystrophy (DMD) either lacking Dp427 (Up 30) or at least Dp260 in addition to Dp427 (Down 30). Methods: Twenty-one patients with DMD and 27 age-similar controls participated in this study. Dark-adapted (0.01, 3.0, and 10 cd.s/m² flashes) and light-adapted (3.0 cd.s/m² flash) ERGs were recorded following International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. Visual detection thresholds to 625-nm (cone function) and 527-nm (rod function) light-emitting diode (LED) flashes (2 degree diameter) were measured during a dark adaptation period after a 1-minute exposure to a bleaching light (3000 cd/m²). Initially, 8 minutes of interleaved 625-nm and 527-nm thresholds were measured. After an additional 5 minutes of dark-adaptation, a second set of threshold measurements to 527-nm stimuli was performed during the subsequent 6 minutes. Results: Dark-adapted b-wave amplitude was significantly reduced to all strengths of flash and a-wave in response to the strong flash stimulus was delayed (15.6 vs. 14.7 ms, P < 0.05) in patients with Down 30 compared with controls. Dark-adapted cone thresholds did not differ among the groups (-2.0, -1.8, and -1.7 log cd/m² for Down 30, Up 30, and controls, respectively, P = 0.21). In contrast, dark-adapted rod thresholds were elevated (F(2,36) = 8.537, P = 0.001) in patients with Down 30 (mean = -3.2 ± 1.1 log cd/m²) relative to controls (mean = -4.2 ± 0.3 log cd/m²). Dark-adapted b-wave amplitudes were correlated with dark-adapted rod sensitivity in patients with DMD (Spearman Rho = 0.943, P = 0.005). The changes were much smaller or absent in patients with intact Dp260. Conclusions: Dp260 is particularly required for normal rod-system function in dark adaptation.

Longitudinal visual acuity development in ZIKV-exposed children.

PURPOSE: To follow the visual acuity development of children exposed to or infected with the Zika virus (ZIKV) during gestation and to relate potential visual acuity deficits to their clinical condition. METHODS: In this prospective study, visual acuity was measured via Teller Acuity Cards in three groups of children: (1) those with confirmed ZIKV exposure (ZE) through the mother only, (2) those with confirmed infection (ZI), and (3) unaffected controls. Visual acuity was measured 2-4 times in each child during the first 30 months of age. RESULTS: The study included 22 children in the ZE group, 11 in the ZI group, and 27 controls. Visual acuity developed normally in both patient groups, including infected patients (ZI) that did not manifest clinical symptoms. In a small subgroup of patients with characteristics consistent with congenital Zika syndrome (CZS), visual acuity was within normative values, with the exception of single child with chorioretinal atrophy. CONCLUSIONS: In this southeastern Brazil study cohort, visual acuity development seemed to progress normally in infected children without CZS symptoms.

Melanopsin System Dysfunction in Smith-Magenis Syndrome Patients.

Purpose: Smith-Magenis syndrome (SMS) causes sleep disturbance that is related to an abnormal melatonin profile. It is not clear how the genomic disorder leads to a disturbed synchronization of the sleep/wake rhythm in SMS patients. To evaluate the integrity of the intrinsically photosensitive retinal ganglion cell (ipRGC)/melanopsin system, the transducers of the light-inhibitory effect on pineal melatonin synthesis, we recorded pupillary light responses (PLR) in SMS patients. Methods: Subjects were SMS patients (n = 5), with molecular diagnosis and melatonin levels measured for 24 hours and healthy controls (n = 4). Visual stimuli were 1-second red light flashes (640 nm; insignificant direct ipRGC activation), followed by a 470-nm blue light, near the melanopsin peak absorption region (direct ipRGC activation). Blue flashes produce a sustained pupillary constriction (ipRGC driven) followed by baseline return, while red flashes produce faster recovery. Results: Pupillary light responses to 640-nm red flash were normal in SMS patients. In response to 470-nm blue flash, SMS patients had altered sustained responses shown by faster recovery to baseline. SMS patients showed impairment in the expected melatonin production suppression during the day, confirming previous reports. Conclusions: SMS patients show dysfunction in the sustained component of the PLR to blue light. It could explain their well-known abnormal melatonin profile and elevated circulating melatonin levels during the day. Synchronization of daily melatonin profile and its photoinhibition are dependent on the activation of melanopsin. This retinal dysfunction might be related to a deficit in melanopsin-based photoreception, but a deficit in rod function is also possible.

Nerve fiber layer in glaucomatous hemifield loss: a case-control study with time- and spectral-domain optical coherence tomography.

PURPOSE: To evaluate the retinal nerve fiber layer measurements with time-domain (TD) and spectral-domain (SD) optical coherence tomography (OCT), and to test the diagnostic ability of both technologies in glaucomatous patients with asymmetric visual hemifield loss. METHODS: 36 patients with primary open-angle glaucoma with visual field loss in one hemifield (affected) and absent loss in the other (non-affected), and 36 age-matched healthy controls had the study eye imaged with Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, California, USA) and 3 D OCT-1000 (Topcon, Tokyo, Japan). Peripapillary retinal nerve fiber layer measurements and normative classification were recorded. Total deviation values were averaged in each hemifield (hemifield mean deviation) for each subject. Visual field and retinal nerve fiber layer "asymmetry indexes" were calculated as the ratio between affected versus non-affected hemifields and corresponding hemiretinas. RESULTS: Retinal nerve fiber layer measurements in non-affected hemifields (mean [SD] 87.0 [17.1] µm and 84.3 [20.2] µm, for TD and SD-OCT, respectively) were thinner than in controls (119.0 [12.2] µm and 117.0 [17.7] µm, P<0.001). The optical coherence tomography normative database classified 42% and 67% of hemiretinas corresponding to non-affected hemifields as abnormal in TD and SD-OCT, respectively (P=0.01). Retinal nerve fiber layer measurements were consistently thicker with TD compared to SD-OCT. Retinal nerve fiber layer thickness asymmetry index was similar in TD (0.76 [0.17]) and SD-OCT (0.79 [0.12]) and significantly greater than the visual field asymmetry index (0.36 [0.20], P<0.001). CONCLUSIONS: Normal hemifields of glaucoma patients had thinner retinal nerve fiber layer than healthy eyes, as measured by TD and SD-OCT. Retinal nerve fiber layer measurements were thicker with TD than SD-OCT. SD-OCT detected abnormal retinal nerve fiber layer thickness more often than TD-OCT.

A comparison of bimatoprost 0.03% versus the fixed-combination of latanoprost 0.005% and timolol 0.5% in adult patients with elevated intraocular pressure: an eight-week, randomized, open-label trial.

INTRODUCTION AND PURPOSE: Bimatoprost and the fixed combination of latanoprost with timolol maleate are 2 medications widely used to treat glaucoma and ocular hypertension (OHT). The aim of the study is to compare the efficacy of these 2 drugs in reducing intraocular pressure (IOP) after 8 weeks of treatment in patients with primary open angle glaucoma (POAG) or OHT. METHODS: In this randomized, open-label trial, 44 patients with POAG or OHT were allocated to receive either bimatoprost (1 drop QD) or latanoprost/timolol (1 drop QD). Primary outcome was the mean diurnal IOP measurement at the 8th week, calculated as the mean IOP measurements taken at 8:00 am, 10:00 am, and 12:00 pm Secondary outcomes included the baseline change in IOP measured 3 times a day, after the water-drinking test (performed after the last IOP measurement), and the assessment of side effects of each therapy. RESULTS: The mean IOP levels of latanoprost/timolol (13.83, SD = 2.54) was significantly lower than of bimatoprost (16.16, SD = 3.28; P < 0.0001) at week 8. Also, the change in mean IOP values was significantly higher in the latanoprost/timolol group at 10:00 am (P = 0.013) and 12:00 pm (P = 0.01), but not at 8:00 am (P = ns). During the water-drinking test, there was no significant difference in IOP increase (absolute and percentage) between groups; however, there was a significant decrease in mean heart rate in the latanoprost/timolol group. Finally, no significant changes in blood pressure and lung spirometry were observed in either groups. CONCLUSIONS: The fixed combination of latanoprost/timolol was significantly superior to bimatoprost alone in reducing IOP in patients with POAG or OHT. Further studies with large sample sizes should be taken to support the superior efficacy of latanoprost/timolol, as well as to better assess its profile of side effects.

Nerve fiber layer in glaucomatous hemifield loss: a case-control study with time- and spectral-domain optical coherence tomography / Camada de fibras nervosas na perda de hemicampo glaucomatoso: um estudo caso-controle com tomografia de coerência óptica time- e spectral-domain

PURPOSE: To evaluate the retinal nerve fiber layer measurements with time-domain (TD) and spectral-domain (SD) optical coherence tomography (OCT), and to test the diagnostic ability of both technologies in glaucomatous patients with asymmetric visual hemifield loss. METHODS: 36 patients with primary open-angle glaucoma with visual field loss in one hemifield (affected) and absent loss in the other (non-affected), and 36 age-matched healthy controls had the study eye imaged with Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, California, USA) and 3 D OCT-1000 (Topcon, Tokyo, Japan). Peripapillary retinal nerve fiber layer measurements and normative classification were recorded. Total deviation values were averaged in each hemifield (hemifield mean deviation) for each subject. Visual field and retinal nerve fiber layer "asymmetry indexes" were calculated as the ratio between affected versus non-affected hemifields and corresponding hemiretinas. RESULTS: Retinal nerve fiber layer measurements in non-affected hemifields (mean [SD] 87.0 [17.1] µm and 84.3 [20.2] µm, for TD and SD-OCT, respectively) were thinner than in controls (119.0 [12.2] µm and 117.0 [17.7] µm, P<0.001). The optical coherence tomography normative database classified 42% and 67% of hemiretinas corresponding to non-affected hemifields as abnormal in TD and SD-OCT, respectively (P=0.01). Retinal nerve fiber layer measurements were consistently thicker with TD compared to SD-OCT. Retinal nerve fiber layer thickness asymmetry index was similar in TD (0.76 [0.17]) and SD-OCT (0.79 [0.12]) and significantly greater than the visual field asymmetry index (0.36 [0.20], P<0.001). CONCLUSIONS: Normal hemifields of glaucoma patients had thinner retinal nerve fiber layer than healthy eyes, as measured by TD and SD-OCT. Retinal nerve fiber layer measurements were thicker with TD than SD-OCT. SD-OCT detected abnormal retinal nerve fiber layer thickness more often than TD-OCT.

OBJETIVO: Avaliar as medidas da camada de fibras nervosas da retina com a tomografia de coerência óptica (OCT) "time domain" (TD) e "spectral domain" (SD), e testar a habilidade diagnóstica de ambas as tecnologias em pacientes com perda assimétrica glaucomatosa de hemicampo visual. MÉTODOS: Trinta e seis pacientes com glaucoma primário de ângulo aberto com perda de campo visual em um hemicampo (acometido) e ausência de perda no hemicampo oposto (não-acometido), e 36 controles pareados por idade tiveram o olho de estudo examinado com Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, California, USA) e 3 D OCT-1000 (Topcon, Tokyo, Japan). As medidas de espessura da camada de fibras nervosas da retina peripapilar e classificação normativa fornecida pelos aparelhos foram registrados para análise. A média aritmética dos valores do gráfico de desvio total em cada hemicampo foi calculada para cada indivíduo. "Índices de assimetria" para campo visual e camada de fibras nervosas da retina foram calculados como a razão entre hemicampos acometido e não-acometido e hemirretinas correspondentes, respectivamente. RESULTADOS: As medidas da camada de fibras nervosas da retina em hemicampos não-acometidos (média [SD] 87.0 [17.1] µm e 84.3 [20.2] µm, para TD e SD-OCT, respectivamente) foram menores do que em controles (119.0 [12.2] µm e 117.0 [17.7] µm, P<0.001). O banco de dados normativo classificou como alterado 42% e 67% das hemirretinas correspondentes a hemicampos não-acometidos com TD e SD-OCT, respectivamente (P=0.01). As medidas da camada de fibras nervosas da retina foram consistentemente mais espessas com TD comparados com SD-OCT. Índices de assimetria da camada de fibras nervosas da retina foram semelhantes entre TD (0.76 [0.17]) e SD-OCT (0.79 [0.12]) e significantemente maiores do que o índice de assimetria do campo visual (0.36 [0.20], P<0.001). CONCLUSÃO: Os hemicampos normais de pacientes com glaucoma apresentaram camada de fibras nervosas da retina mais fina do que olhos saudáveis. As medidas da camada de fibras nervosas da retina foram mais espessas com TD do que com SD-OCT, que por sua vez detectou anormalidades na espessura da camada de fibras nervosas da retina mais frequentemente do que o TD-OCT.