The Effect of Self-Reported Visual Impairment and Sleep on Cognitive Decline: Results of the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Visual impairment could worsen sleep/wake disorders and cognitive decline. OBJECTIVE: To examine interrelations among self-reported visual impairment, sleep, and cognitive decline in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Miami-site. METHOD: HCHS/SOL Miami-site participants ages 45-74 years (n = 665) at Visit-1, who returned for cognitive test 7-years later (SOL-INCA). Participants completed the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ), validated sleep questionnaires and test for obstructive sleep apnea (OSA) at Visit-1. We obtained verbal episodic learning and memory, verbal fluency, processing speed, and executive functioning at Visit-1 and at SOL-INCA. Processing speed/executive functioning were added to SOL-INCA. We examined global cognition and change using a regression-based reliable change index, adjusting for the time lapse between Visit-1 and SOL-INCA. We used regression models to test whether 1) persons with OSA, self-reported sleep duration, insomnia, and sleepiness have an increased risk for visual impairment, 2a) visual impairment is associated with worse cognitive function and/or decline, and 2b) sleep disorders attenuate these associations. RESULT: Sleepiness (ß= 0.04; p < 0.01) and insomnia (ß= 0.04; p < 0.001) were cross-sectionally associated with visual impairment, adjusting for sociodemographic characteristics, behavioral factors, acculturation, and health conditions. Visual impairment was associated with lower global cognitive function at Visit-1 (ß= -0.16; p < 0.001) and on average 7-years later (ß= -0.18; p < 0.001). Visual impairment was also associated with a change in verbal fluency (ß= -0.17; p < 0.01). OSA, self-reported sleep duration, insomnia, and sleepiness did not attenuate any of the associations. CONCLUSION: Self-reported visual impairment was independently associated with worse cognitive function and decline.

Bi-nasal sectors of ganglion cells complex and visual evoked potential amplitudes as biomarkers in pituitary macroadenoma management.

The study aimed to evaluate the retinal ganglion cell structure using optical coherence tomography and the visual pathway function employing visual evoked potentials in the diagnosis and monitoring of patients with pituitary macroadenoma. A descriptive, cross-sectional, and longitudinal study (3 and 12 months follow-up) was conducted on forty-two patients. Thirty-five age-matched healthy controls were used in the cross-sectional one. Full neuro-ophthalmological evaluation (structural and functional) was carried out including global and segmented retinal nerve fiber layer/ganglion cell complex analysis and amplitude and latency of P100 component in the electrophysiology. Statistical data analysis was conducted with R version 3.6.3 and Python version 3.8. Associations were evaluated using Spearman's correlations. Amplitude sensitivities were 0.999, and bi-nasal sectors of ganglion cell complex thickness specificities were 0.999. This structural parameter had the highest diagnostic value (area under curve = 0.923). Significant associations were found between bi-nasal sectors with amplitude at 12' (rho > 0.7, p < 0.01) and median deviation of the visual field (rho > 0.5, p < 0.01) at 3 months. Pre-surgical values of bi-nasal sectors and amplitude can predict post-surgically median deviation and amplitude (Oz, 12') at 3 months with r 2 > 0.5. Bi-nasal sectors of ganglion cell complex and visual evoked potentials P100 amplitude are efficient biomarkers of visual pathway damage for pituitary macroadenoma patients' management. Pre-surgical values of the bi-nasal sector and visual evoked potentials' amplitude could help to predict the restoration of parvocellular pathway traffic after decompression.

Visual Acuity, Retinal Morphology, and Patients' Perceptions after Voretigene Neparovec-rzyl Therapy for RPE65-Associated Retinal Disease.

OBJECTIVE: To explore the effect of patients' age, baseline visual acuity (VA), and intraoperative foveal detachment on outcomes of subretinal voretigene neparvovec-rzyl (Luxturna) therapy and to assess patients' perceptions of the treatment effect. DESIGN: Multicenter, retrospective, consecutive case series, and cross-sectional prospective survey. PARTICIPANTS: All 41 consecutive patients treated with voretigene neparvovec-rzyl after Food and Drug Administration approval at 3 institutions between January 2018 and May 2020. METHODS: A retrospective chart review of operative reports, clinical notes, ancillary testing, and complications, comparing data at baseline and at 1, 2 to 3, 6 to 9, and 10 to 15 months after subretinal surgery was conducted. A survey was administered to adult patients and parents of pediatric patients. MAIN OUTCOME MEASURES: Changes in best-corrected VA and retinal morphology and in patients' perceptions. RESULTS: Seventy-seven eyes of 41 patients (16 adults and 25 pediatric patients; age range, 2-44 years; mean follow-up, 10 months [range, 1 week to 18.5 months]) were analyzed. There was no statistically significant vision change for the adults, whereas there was a trend of improvement for pediatric patients, which reached statistical significance for some time points. The baseline VA did not affect the posttherapy VA (P = 0.23). The central foveal thickness decreased mildly in both pediatric patients and adults, without significant differences between the populations. The fovea was detached by voretigene neparvovec-rzyl in 62 (81%) eyes. The inner segment-outer segment junction remained unchanged in 91% of 54 eyes with gradable OCT, with or without foveal detachment. Thirty-two (78%) patients were reached for the survey an average of 1.15 ± 0.50 years (range, 0.31 to 2.31) after the surgery in the first eye. Improvement in night, day, or color vision was reported by 23 (72%), 22 (69%), and 18 (56%) patients, respectively. CONCLUSIONS: This study is limited by the large variability in follow-up time. There were no persistent statistically significant vision changes. A decrease in foveal thickness was noted in most eyes, but the long-term significance of this remains to be determined.

Multimodal Imaging Findings in Two Children With Microphthalmos.

Microphthalmos, also called microphthalmia, is a rare developmental disorder of the eye that can be caused by genetic or chromosomal abnormalities or environmental factors. The spectrum of clinical presentation includes nanophthalmia and posterior microphthalmia. It affects approximately one in 1,000 individuals, although there is insufficient literature regarding the clinical and different imaging modalities findings. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:444-446.].

Longitudinal changes in the macula and optic nerve in familial dysautonomia.

OBJECTIVE: Familial Dysautonomia (FD) disease, lacks a useful biomarker for clinical monitoring. In this longitudinal study we characterized the structural changes in the macula, peripapillary and the optic nerve head (ONH) regions in subjects with FD. METHODS: Data was consecutively collected from subjects attending the FD clinic between 2012 and 2019. All subjects were imaged with spectral-domain Optical Coherence Tomography (OCT). Global and sectoral measurements of mean retinal nerve fiber layer (RNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness, and ONH parameters of rim area, average cup-to-disc (C:D) ratio, and cup volume were used for the analysis. The best fit models (linear, quadratic and broken stick linear model) were used to describe the longitudinal change in each of the parameters. RESULTS: 91 subjects (149 eyes) with FD of ages 5-56 years were included in the analysis. The rate of change for average RNFL and average GCIPL thicknesses were significant before reaching a plateau at the age of 26.2 for RNFL and 24.8 for GCIPL (- 0.861 µm/year (95% CI - 1.026, - 0.693) and - 0.553 µm/year (95% CI - 0.645, - 0.461), respectively). Significant linear rate of progression was noted for all ONH parameters, except for a subset of subjects (24%), with no cupping that did not show progression in any of the ONH parameters. CONCLUSIONS: The rapidly declining RNFL and GCIPL can explain the progressive visual impairment previously reported in these subjects. Among all structural parameters, ONH parameters might be most suitable for longitudinal follow-up, in eyes with a measurable cup.

Investigating Vascular Complexity and Neurogenic Alterations in Sectoral Regions of the Retina in Patients With Cognitive Impairment.

Evidence is accumulating that cognitive function, and visual impairment may be related. In this pilot study, we investigated whether multifractal dimension and lacunarity analyses performed in sectoral regions of the retina may reveal changes in patients with cognitive impairment (CI) that may be masked in the study considering the whole retinal branching pattern. Prospective age-matched subjects (n = 69) with and with no CI and without the presence of any ophthalmic history were recruited (age > 55+ years). The Montreal Cognitive Assessment (MoCA) was used to measure CI, and full-field electroretinogram (ERG) was performed. Also, visual performance exams were conducted using the Rabin cone contrast test (CCT). Quantification of the retinal structure was performed in retinal fundus images [45 o field of view (FOV), optic disk centered] with excellent quality for all individuals [19 healthy controls (HC) and 20 patients with CI] after evaluating the inclusion and exclusion criteria in all study participants recruited (n = 69). The skeletonized vasculature network that comprised the whole branching pattern observable in the full 45° FOV was obtained for each image and divided into nine equal regions (superotemporal, superior, superonasal, macular, optic disk, nasal, inferotemporal, inferior, and inferonasal). The multifractal behavior was analyzed by calculating the generalized dimension Dq (Do, D1, and D2), the lacunarity parameter (Λ), and singularity spectrum f(α) in the nine sectoral skeletonized images as well as in the skeletons that comprised the whole branching pattern observable in the full 45° FOV. The analyses were performed using the ImageJ program together with the FracLac plug-in. Independent sample t-tests or Mann Whitney U test and Pearson correlation coefficient were used to find associations between all parameters in both groups. The effect size (Cohen's d) of the difference between both groups was also assessed. A p-value < 0.05 was considered statistically significant. Significant correlations between multifractal and Λ parameters with the MoCA and implicit time ERG-parameter were observed in the regional analysis. In contrast, no trend was found when considering the whole retinal branching pattern. Analysis of combined structural-functional parameters in sectoral regions of the retina, instead of individual retinal biomarkers, may provide a useful clinical marker of CI.

Spectrum of peripheral retinal ischemia in Wyburn-Mason syndrome.

PURPOSE: We report two cases of Wyburn-Mason syndrome that illustrate the spectrum of peripheral retinal ischemia seen in this condition. OBSERVATIONS: A 12-year-old female presented with a retinal arteriovenous malformation and sclerotic vessels associated with retinal ischemia on fluorescein angiography, as well as an ipsilateral ophthalmic arteriovenous malformation on magnetic resonance imaging. An 11-year-old male presented with retinal vascular engorgement and tortuosity along with a central retinal vein occlusion and secondary neovascularization. CONCLUSIONS AND IMPORTANCE: Retinal ischemia in Wyburn-Mason syndrome is heterogeneous and may be progressive, with secondary complications that result in neovascularization. Furthermore, it is necessary to recognize that this is a systemic condition that requires neurological evaluation.

Delayed Onset of Retinopathy of Prematurity Associated With Mitochondrial Dysfunction and Pearson Syndrome.

Retinopathy of prematurity (ROP) is a biphasic disease in which the first phase is characterized by high oxygen tension leading to vaso-obliteration in the retina. Pearson syndrome is a rare multisystem mitochondrial disease with a defect in cellular respiration. The authors describe a patient with Pearson syndrome and delayed onset of ROP at a postconceptual age of 42 weeks. The proposed mechanistic theory was the increased oxygen use associated with the metabolic impairments in Pearson syndrome counterbalancing the effects of supplemental oxygen during the vaso-obliterative stage of ROP. [J Pediatr Ophthalmol Strabismus. 2019;56:e60-e64.].

Ganglion Cell Complex Analysis as a Potential Indicator of Early Neuronal Loss in Idiopathic Intracranial Hypertension.

Reliable visual field testing is the gold standard in identifying future vision loss in patients with Idiopathic Intracranial hypertension (IIH). However, when field performance is unreliable, GCC analysis may be useful. We evaluated IIH patients over three visits: initial visit, follow-up visit and a third visit, almost 1 year later. We evaluated mean deviation (MD), GCC and RNFL at presentation and the second visit and compared it to the mean deviation (MD) on fields at the third visit. As early as the second visit, GCC loss correlated with visual field results seen at the third visit.

Investigating Multimodal Diagnostic Eye Biomarkers of Cognitive Impairment by Measuring Vascular and Neurogenic Changes in the Retina.

Previous studies have demonstrated that cognitive impairment (CI) is not limited to the brain but also affects the retina. In this pilot study, we investigated the correlation between the retinal vascular complexity and neurodegenerative changes in patients with CI using a low-cost multimodal approach. Quantification of the retinal structure and function were conducted for every subject (n = 69) using advanced retinal imaging, full-field electroretinogram (ERG) and visual performance exams. The retinal vascular parameters were calculated using the Singapore Institute Vessel Assessment software. The Montreal Cognitive Assessment was used to measure CI. Pearson product moment correlation was performed between variables. Of the 69 participants, 32 had CI (46%). We found significantly altered microvascular network in individuals with CI (larger venular-asymmetry factor: 0.7 ± 0.2) compared with controls (0.6 ± 0.2). The vascular fractal dimension was lower in individuals with CI (capacity, information and correlation dimensions: D0, D1, and D2 (mean ± SD): 1.57 ± 0.06; 1.56 ± 0.06; 1.55 ± 0.06; age 81 ± 6years) vs. controls (1.61 ± 0.03; 1.59 ± 0.03; 1.58 ± 0.03; age: 80 ± 7 years). Also, drusen-like regions in the peripheral retina along with pigment dispersion were noted in subjects with mild CI. Functional loss in color vision as well as smaller ERG amplitudes and larger peak times were observed in the subjects with CI. Pearson product moment correlation showed significant associations between the vascular parameters (artery-vein ratio, total length-diameter ratio, D0, D1, D2 and the implicit time (IT) of the flicker response but these associations were not significant in the partial correlations. This study illustrates that there are multimodal retinal markers that may be sensitive to CI decline, and adds to the evidence that there is a statistical trend pointing to the correlation between retinal neuronal dysfunction and microvasculature changes suggesting that retinal geometric vascular and functional parameters might be associated with physiological changes in the retina due to CI. We suspect our analysis of combined structural-functional parameters, instead of individual biomarkers, may provide a useful clinical marker of CI that could also provide increased sensitivity and specificity for the differential diagnosis of CI. However, because of our study sample was small, the full extent of clinical applicability of our approach is provocative and still to be determined.

REVERSIBLE NYCTALOPIA ASSOCIATED WITH VITAMIN A DEFICIENCY AFTER RESECTED MALIGNANT ILEAL CARCINOID AND PANCREATIC ADENOCARCINOMA.

PURPOSE: To describe the rapid time course of visual and electroretinographic recovery from vitamin A deficiency in a patient with a history of multiple resected abdominal tumors, including ileal carcinoid and pancreatic adenocarcinoma. METHODS: A 61-year-old white man with a history of resected malignant ileal carcinoid and Stage III pancreatic adenocarcinoma referred with complaints of 6 weeks of difficulty with night vision. RESULTS: Initial testing showed significantly reduced scotopic rod responses in both eyes and decreased vitamin A levels and a normal cancer-associated retinopathy laboratory panel. He had complete recovery of both his symptoms and full-field electroretinography within 5 days of starting intramuscular vitamin A. CONCLUSION: Vitamin A deficiency-related retinopathy after abdominal surgery may be an underreported complication. This case provides a unique clinical perspective in our patient with a history of ileal carcinoid and Stage III pancreatic adenocarcinoma and confirms that rapid symptomatic and electroretinographic recovery is possible with appropriate treatment.

Founder mutation in IKBKAP gene causes vestibular impairment in familial dysautonomia.

OBJECTIVE: To assess vestibular function in patients with familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy - caused by a mutation in the IKBKAP gene (c.2204 + 6 T>C) - and characterized by marked gait ataxia. METHODS: Cervical and vestibular evoked myogenic potentials (cVEMPs and oVEMPs) were recorded from the sternocleidomastoid (SCM) and extraocular muscles in 14 homozygous patients, 2 heterozygous patients, and 15 healthy controls during percussion of the forehead. RESULTS: cVEMP and oVEMP amplitudes were significantly lower, and peak latencies significantly delayed, in the FD patients. There were no differences in overall EMG during attempted maximal voluntary contractions of the SCM muscle, suggesting intact efferent function. The two heterozygotes with a minor haplotype missense (R696P) mutation in exon 19 of the IKBKAP gene had cVEMP responses less affected than the homozygous. CONCLUSIONS: The founder mutation in the IKBKAP gene affects the development of vestibular afferent pathways, leading to attenuated cVEMPs. SIGNIFICANCE: Vestibular abnormalities may contribute to the gait ataxia in FD.