Evaluating the effect of rapamycin treatment in Alzheimer's disease and aging using in vivo imaging: the ERAP phase IIa clinical study protocol.

BACKGROUND: Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and preclinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer's disease have shown beneficial effects of rapamycin, including preventing or reversing cognitive deficits, reducing amyloid oligomers and tauopathies and normalizing synaptic plasticity and cerebral glucose uptake. The "Evaluating Rapamycin Treatment in Alzheimer's Disease using Positron Emission Tomography" (ERAP) trial aims to test if these results translate to humans through evaluating the change in cerebral glucose uptake following six months of rapamycin treatment in participants with early-stage Alzheimer's disease. METHODS: ERAP is a six-month-long, single-arm, open-label, phase IIa biomarker-driven study evaluating if the drug rapamycin can be repurposed to treat Alzheimer's disease. Fifteen patients will be included and treated with a weekly dose of 7 mg rapamycin for six months. The primary endpoint will be change in cerebral glucose uptake, measured using [18F]FDG positron emission tomography. Secondary endpoints include changes in cognitive measures, markers in cerebrospinal fluid as well as cerebral blood flow measured using magnetic resonance imaging. As exploratory outcomes, the study will assess change in multiple age-related pathological processes, such as periodontal inflammation, retinal degeneration, bone mineral density loss, atherosclerosis and decreased cardiac function. DISCUSSION: The ERAP study is a clinical trial using in vivo imaging biomarkers to assess the repurposing of rapamycin for the treatment of Alzheimer's disease. If successful, the study would provide a strong rationale for large-scale evaluation of mTOR-inhibitors as a potential disease-modifying treatment in Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06022068, date of registration 2023-08-30.

The relationship between retinal structure and visual function in non-immuno-compromised people living with HIV without retinitis on antiretroviral therapy.

BACKGROUND: This study sought to establish the association between retinal morphology, visual function and linear parameters of cerebral atrophy in non-immunocompromised people living with HIV (NIPLHIV). METHODS: Sixty participants (30 NIPLHIV, 30 controls), aged 18-45 years, were sourced from an outpatient clinic in South Africa. NIPLHIV on antiretroviral therapy (ART) had elevated CD4 counts and low viral loads. Macula thickness and volume measurements were obtained using the Spectralis optical coherence tomographer. Contrast sensitivity (CS), colour vision and visual-evoked potentials (VEP) were also obtained. Linear parameters of cerebral atrophy (Sylvian fissure ratio, SFR) and bicaudate nucleus ratio (BCR) were all acquired from computed tomography (CT) scans. Associations between retinal thickness and volume and visual function were established by principal component factor analysis. RESULTS: CS scores were indirectly associated with the Inner Nuclear Layer (INL)-ETDRS thickness and volume subfields (co-efficient = -0.07; p = 0.02 and -0.11; p = 0.001), respectively. F100 total error scores (TES) were directly associated with the thicknesses of Ganglion Cell Layer-ETDRS subfields (co-efficient = 6.06; p = 0.04) but indirectly associated with INL-ETDRS subfields (co-efficient = -5.49; p = 0.04). F100-TES were indirectly associated with volumes of RNFL (Retinal Nerve Fibre Layer)-ETDRS subfields (co-efficient = -5.54; p = 0.02) and inner retina -ETDRS subfields (co-efficient = -6.70; p = 0.02). P100 latency was directly associated with RNFL-ETDRS subfield thickness (co-efficient = 2.90; p = 0.02) and volumes of outer retina subfields (co-efficient = 2.72; p = 0.04). CS scores were directly associated with SFR (co-efficient = -0.04; p = 0.01). F100-TES were directly associated with BCR (co-efficient = 0.003; p = 0.004) and SFR (co-efficient = 0.002; p = 0.02). P100 latency was indirectly associated with BCR (co-efficient = -0.001; p = 0.03). CONCLUSION: The recognition of associations may be the first step in the proposal to develop a framework for the surveillance of vision in patients with NIPLHIV. We recommend a study of the sample population to track the stability of these observations before general recommendations for clinical care.

The Integrity of Retinal Morphology in Non-immunocompromised People Living with HIV on Antiretroviral Therapy.

SIGNIFICANCE: Non-immunocompromised people living with HIV (NIPLHIV) share a similar immunocompetence to non-HIV (HIV) people with an elevated cluster of differentiation 4 (CD4) count in the era of antiretroviral therapy (ART). This has reduced the incidence of HIV retinopathy, thus raising the question of the integrity of the retinal morphology in NIPLHIV with longer life expectancy. PURPOSE: The study assessed the retinal thickness and volume of NIPLHIV without retinitis on ART and attempted to find associations with linear parameters of cerebral atrophy. METHODS: The study was conducted at a public hospital in South Africa. All people living with HIV were on ART with CD4 counts above 350 cells/mm3 and viral loads less than 10,000 copies/mL. The Heidelberg Spectralis ocular coherence tomographer assessed the retinal thickness and volume for comparison between 30 NIPLHIV and 30 HIV-negative participants. A subset of the HIV group obtained a computed tomography scan to determine the bicaudate ratio and the sylvian fissure ratio to assess cerebral atrophy. Independent t tests were performed to identify differences in retinal thickness and volume. Multivariate linear regressions measured associations between retinal thickness and volume with cerebral atrophy. RESULTS: The NIPLHIV group had a thicker mean global temporal subfields at Early Treatment Diabetic Retinopathy Study (ETDRS) 3 mm (P = .047) and ETDRS 6 mm (P = .03). The mean global temporal subfield volume at ETDRS 3 mm was also increased in the NIPLHIV group (P = .02). Nasal macula retinal nerve fiber layer thickness and the inferior inner nuclear layer macula volume were directly related to the bicaudate ratio, whereas the volumes at the outer retinal layer subfields of the macula were inversely related to sylvian fissure ratio in NIPLHIV. CONCLUSIONS: Macula thickness and volumetric differences do exist in NIPLHIV. Practitioners should keep NIPLHIV under retinal morphometric surveillance because they live longer. Associations of cerebral atrophy with retinal morphology may be used to monitor cerebral atrophy in NIPLIV on ART.

Agreement and Repeatability of Two Biometers to Measure Anterior Segment Components: Refractive Error Effect.

BACKGROUND To assess the repeatability and agreement between a new high-resolution optical coherence tomographer (OCT) and a Scheimpflug topographer. MATERIAL AND METHODS Sixty phakic and healthy participants were measured in this study, and one eye per participant was analyzed. Depending on their refractive error, each participant was allocated into a myopic, hyperopic, or emmetropic group. The Cirrus HD-OCT 5000 (Carl Zeiss Meditec, Jena, Germany), and the Sirius Scheimpflug topographer (Costruzione Strumenti Oftalmici, Florence, Italy) were used to take all measurements. RESULTS The repeatability of these instruments to measure the anterior chamber depth, angle-to-angle, thinnest pachymetry, and both nasal and temporal angles was smaller than 0.15 mm, 0.40 mm, 10 µm, and 10 degrees, respectively. However, the repeatability of the Scheimpflug instrument to measure the apex pachymetry was about 15 µm, and for the OCT, it was about 4 µm for all groups. On average, the Sirius Scheimpflug instrument measured shallower anterior chamber depth (about 0.10 mm), shorter angle-to-angle (about 0.5 mm), thinner corneas (approximately 10 µm), and narrower angles (around 5 degrees) for all refractive groups. CONCLUSIONS The repeatability of the Cirrus OCT and Sirius Scheimpflug instrument was good and independent of the refractive error. Nevertheless, to judge whether these instruments could be used interchangeable, clinical criteria are needed.

Power Profiles and In Vitro Optical Quality of Scleral Contact Lenses: Effect of the Aperture and Power.

OBJECTIVE: To assess the power profile and in vitro optical quality of scleral contact lenses with different powers as a function of the optical aperture. METHODS: The mini and semiscleral contact lenses (Procornea) were measured for five powers per design. The NIMO TR-1504 (Lambda-X) was used to assess the power profile and Zernike coefficients of each contact lens. Ten measurements per lens were taken at 3- and 6-mm apertures. Furthermore, the optical quality of each lens was described in Zernike coefficients, modulation transfer function, and point spread function (PSF). A convolution of each lens PSF with an eye-chart image was also computed. RESULTS: The optical power fluctuated less than 0.5 diopters (D) along the optical zone of each lens. However, the optical power obtained for some lenses did not match with its corresponding nominal one, the maximum difference being 0.5 D. In optical quality, small differences were obtained among all lenses within the same design. Although significant differences were obtained among lenses (P<0.05), these showed small impact in the image quality of each convolution. CONCLUSIONS: Insignificant power fluctuations were obtained along the optical zone measured for each scleral lens. Additionally, the optical quality of both lenses has showed to be independent of the lens power within the same aperture.

The accommodative process in children with cerebral palsy: different strategies to obtain clear vision at short distance.

AIM: Accommodation is the ability of the eye to change focus in order to maintain a sharp image of objects at various distances. The accommodative process is largely unknown in children and requires new assessment techniques. The aim of the study was to investigate this process in children with and without cerebral palsy (CP). METHOD: In a descriptive case-control study, children with CP (n=15; nine females, six males; median age 14y) and 21 typically developing children (11 females, 10 males; median age 12y) underwent standard ophthalmological examination and examination by the PowerRefractor. Six of the children had spastic bilateral CP, five had spastic unilateral CP, and four had dyskinetic CP. The children's Gross Motor Function Classification System (GMFCS) levels were as follows: level I, seven children; level II, two children; level III, three children; and level IV, three children. The PowerRefractor measures accommodation in response to minus lens stimuli. Continuous measurements of refraction/accommodation, eye position, and pupil size are obtained. The Kruskal-Wallis analysis of variance (ANOVA) and Mann-Whitney U test were used for between-group analysis (α=0.05), and Friedman ANOVA was used for within-group analysis. RESULTS: The stimuli-response gain (input/output) was approximately 80% in typical children inducing a focusing error (0.2-0.5D) increasing with minus lens power. Children with CP accommodated significantly less (gain: ~30%; p<0.001), inducing a larger focusing error (1.1-1.7D) increasing with minus lens power. The accommodative response was slower and more variable in children with CP. The pupil response did not mirror the accommodative response. INTERPRETATION: Children with CP exhibit problems in generating an appropriate accommodative response. This can affect everyday living and reading skills.

Prophylactic nicotinamide treatment protects from rotenone-induced neurodegeneration by increasing mitochondrial content and volume.

Leber's hereditary optic neuropathy (LHON) is driven by mtDNA mutations affecting Complex I presenting as progressive retinal ganglion cell dysfunction usually in the absence of extra-ophthalmic symptoms. There are no long-term neuroprotective agents for LHON. Oral nicotinamide provides a robust neuroprotective effect against mitochondrial and metabolic dysfunction in other retinal injuries. We explored the potential for nicotinamide to protect mitochondria in LHON by modelling the disease in mice through intravitreal injection of the Complex I inhibitor rotenone. Using MitoV mice expressing a mitochondrial-tagged YFP in retinal ganglion cells we assessed mitochondrial morphology through super-resolution imaging and digital reconstruction. Rotenone induced Complex I inhibition resulted in retinal ganglion cell wide mitochondrial loss and fragmentation. This was prevented by oral nicotinamide treatment. Mitochondrial ultrastructure was quantified by transition electron microscopy, demonstrating a loss of cristae density following rotenone injection, which was also prevented by nicotinamide treatment. These results demonstrate that nicotinamide protects mitochondria during Complex I dysfunction. Nicotinamide has the potential to be a useful treatment strategy for LHON to limit retinal ganglion cell degeneration.

Intravitreal MPTP drives retinal ganglion cell loss with oral nicotinamide treatment providing robust neuroprotection.

Neurodegenerative diseases have common underlying pathological mechanisms including progressive neuronal dysfunction, axonal and dendritic retraction, and mitochondrial dysfunction resulting in neuronal death. The retina is often affected in common neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Studies have demonstrated that the retina in patients with Parkinson's disease undergoes changes that parallel the dysfunction in the brain. These changes classically include decreased levels of dopamine, accumulation of alpha-synuclein in the brain and retina, and death of dopaminergic nigral neurons and retinal amacrine cells leading to gross neuronal loss. Exploring this disease's retinal phenotype and vision-related symptoms is an important window for elucidating its pathophysiology and progression, and identifying novel ways to diagnose and treat Parkinson's disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly used to model Parkinson's disease in animal models. MPTP is a neurotoxin converted to its toxic form by astrocytes, transported to neurons through the dopamine transporter, where it causes mitochondrial Complex I inhibition and neuron degeneration. Systemic administration of MPTP induces retinal changes in different animal models. In this study, we assessed the effects of MPTP on the retina directly via intravitreal injection in mice (5 mg/mL and 50 mg/mL to 7, 14 and 21 days post-injection). MPTP treatment induced the reduction of retinal ganglion cells-a sensitive neuron in the retina-at all time points investigated. This occurred without a concomitant loss of dopaminergic amacrine cells or neuroinflammation at any of the time points or concentrations tested. The observed neurodegeneration which initially affected retinal ganglion cells indicated that this method of MPTP administration could yield a fast and straightforward model of retinal ganglion cell neurodegeneration. To assess whether this model could be amenable to neuroprotection, mice were treated orally with nicotinamide (a nicotinamide adenine dinucleotide precursor) which has been demonstrated to be neuroprotective in several retinal ganglion cell injury models. Nicotinamide was strongly protective following intravitreal MPTP administration, further supporting intravitreal MPTP use as a model of retinal ganglion cell injury. As such, this model could be utilized for testing neuroprotective treatments in the context of Parkinson's disease and retinal ganglion cell injury.

Visual and optical performance and quality of life after implantation of posterior chamber phakic intraocular lens.

PURPOSE: To evaluate visual, optical, and quality of life (QoL) outcomes and intercorrelations after bilateral implantation of posterior chamber phakic intraocular lenses. METHODS: Twenty eyes with high to moderate myopia of 10 patients that underwent PRL implantation (Phakic Refractive Lens, Carl Zeiss Meditec AG) were examined. Refraction, visual acuity, photopic and low mesopic contrast sensitivity (CS) with and without glare, ocular aberrations, as well as QoL outcomes (National Eye Institute Refractive Error Quality of Life Instrument-42, NEI RQL-42) were evaluated at 12 months postoperatively. RESULTS: Significant improvement in uncorrected (UDVA) and best-corrected distance (CDVA) visual acuities were found postoperatively (p < 0.01), with significant reduction in spherical equivalent (p < 0.01). Low mesopic CS without glare was significantly better than measurements with glare for 1.5, 3, and 6 cycles/degree (p < 0.01). No significant correlations between higher order root mean square (RMS) with CDVA (r = -0.26, p = 0.27) and CS (r ≤ 0.45, p ≥ 0.05) were found. Postoperative binocular photopic CS for 12 cycles/degree and 18 cycles/degree correlated significantly with several RQL-42 scales. Glare index correlated significantly with CS measures and scotopic pupil size (r = -0.551, p = 0.04), but not with higher order RMS (r = -0.02, p = 0.94). Postoperative higher order RMS, postoperative primary coma and postoperative spherical aberration was significant higher for 5-mm pupil diameter (p < 0.01) compared with controls. CONCLUSIONS: Correction of moderate to high myopia by means of PRL implantation had a positive impact on CS and QoL. The aberrometric increase induced by the surgery does not seem to limit CS and QoL. However, perception of glare is still a relevant disturbance in some cases possibly related to the limitation of the optical zone of the PRL.

Subjective satisfaction in long-term orthokeratology patients.

PURPOSE: To evaluate the subjective satisfaction in visual stability, night vision complains, and light distortion phenomena, and also the number of hours and days per week of lens wear, in patients with myopia undergoing orthokeratology (OK) treatment for at least 1 year. METHODS: A visual analog scale (VAS) questionnaire containing 18 items was administered to 44 patients, 29 women and 15 men (mean age, 24.39 ± 9.11 years), with a baseline spherical equivalent refractive error of -2.40 ± 0.94 diopters and astigmatism up to -0.5 diopters. Average treatment period by the time of data collection was 19 ± 7 months. Patients rated their satisfaction with the correction, with complaints of visual distortion being graded on a scale of 0 to 10, where 0 indicated no discomfort at all. RESULTS: More than 50% of patients skipped lens wear at least 1 night per week. The most common wearing pattern was 6-8 hours a day for 72.7% with 54.5% of patients wearing lenses every 2-3 nights only. Subjective vision scores after lens removal was 9.1 ± 1.1 after having worn the lenses and 8.1 ± 1.4 after skipping lens wear for 1 night. Subjective vision scores before lens insertion at the end of the day was 6.9 ± 2.0 and 5.8 ± 2.4, respectively. The number of hours until noticeable blur reduced with increased level of baseline myopia (r = 0.396; P < 0.001). CONCLUSION: Orthokeratology patients show an irregular wearing pattern after 1 year of treatment that has significant effects on the subjective visual performance over the next day of skipping lens wear. Light distortion under low-light conditions seems to be a transient complication of the treatment and most of the patients report an improvement after the first weeks of treatment.

The integrity of psychophysical visual function in non-immunocompromised PLHIV (NIPLHIV) without retinitis on antiretroviral therapy (ART).

Purpose: The present study investigated the integrity of contrast sensitivity (CS), colour vision, and pattern evoked vision potentials (VEP) in non-immunocompromised people living with HIV (NIPLHIV) without retinitis. Methods: All participants were visually asymptomatic and no history of ocular disorders, with CD4 counts above 350 cells/mm3, low viral loads and on ART. Thirty NIPLHIV and 30 age-matched HIV negative control groups underwent F100 hue colour assessment, Pelli-Robson contrast sensitivity assessment and pattern-reversal VEP. Results: The median F100 total error scores for NIPLHIV and controls was 33 (IQR: 28;41) and 28 (IQR: 26;48.50) respectively, this was statistically different (p= 0.020). The median P100 amplitude for NIPLHIV was 5.75 µV (IQR: 4.4;8.85) and 4.05 µV (IQR: 3.2;5.8) for controls, this was statistically different (p=0.045). The mean LogCS score 1.83±0.14 and the median P100 peak latency was 105.45 msec (IQR: 102.98;108.98) for NIPLHIV. Higher CD4+ counts were significantly associated with having higher F100 total error scores (OR=0.995; p=0.018), lower P100 amplitudes (OR=1.007; p=0.010) and higher P100 latencies (OR=0.994; p=0.011). Conclusion: Contrast sensitivity function, colour vision, and VEP were uncompromised in NIPLHIV. Associations between CD4 counts with F100 total error scores and P100 latency may aid in the surveillance of vision of NIPLHIV.

The prognostic implication of visual acuity at the time of uveal melanoma diagnosis.

BACKGROUND: Visual outcomes after primary tumour treatment of uveal melanoma (UM) have been investigated repeatedly. This study evaluates the correlation between best-corrected visual acuity (BCVA) before treatment with clinicopathological factors and patient survival. SUBJECTS/METHODS: Pre-treatment BCVA was examined in relation to tumour dimensions and location, and survival in a retrospective cohort of 1809 patients who underwent plaque brachytherapy. BCVA was also correlated to tumour histological factors in a second cohort of 137 enucleated eyes. RESULTS: The mean BCVA of the tumour eye prior to plaque brachytherapy was LogMAR 0.42 (SD 0.46). Patients with low BCVA (LogMAR ≥ 1.00) did not differ in age (p = 0.19) and had similar frequency of ciliary body involvement (p = 0.99) but had tumours with greater apical thickness (p < 0.0001), greater diameter (p < 0.0001) and shorter distance to the optic disc and fovea (p < 0.0001). There were no significant relations between low BCVA and any of 13 examined tumour histological factors at a Bonferroni-corrected significance level (p > 0.004). Patients with low BCVA had greater incidence of UM-related mortality in competing risk analysis (p = 0.0019) and shorter overall survival (p < 0.0001). Low BCVA was also associated with increased hazard ratio (HR) for UM-related mortality in univariate analysis (HR 1.5, 95% confidence interval 1.2 to 1.9), but not in multivariate analysis with tumour size and location as covariates. CONCLUSIONS: UM patients with low BCVA before primary tumour treatment have a worse prognosis, likely related to increased tumour dimensions. Future studies should examine the prognostic significance of BCVA in relation to macula-involving retinal detachment and genetic factors.

Glial metabolic alterations during glaucoma pathogenesis.

Glaucoma is the leading cause of irreversible blindness. Current treatment options are limited and often only slow disease progression. Metabolic dysfunction has recently been recognized as a key early and persistent mechanism in glaucoma pathophysiology. Several intrinsic metabolic dysfunctions have been identified and treated in retinal ganglion cells to provide neuroprotection. Growing pre-clinical and clinical evidence has confirmed that metabolic alterations in glaucoma are widespread, occurring across visual system tissues, in ocular fluids, in blood/serum, and at the level of genomic and mitochondrial DNA. This suggests that metabolic dysfunction is not constrained to retinal ganglion cells and that metabolic alterations extrinsic to retinal ganglion cells may contribute to their metabolic compromise. Retinal ganglion cells are reliant on glial metabolic support under normal physiological conditions, but the implications of metabolic dysfunction in glia are underexplored. We highlight emerging evidence that has demonstrated metabolic alterations occurring within glia in glaucoma, and how this may affect neuro-glial metabolic coupling and the metabolic vulnerability of retinal ganglion cells. In other neurodegenerative diseases which share features with glaucoma, several other glial metabolic alterations have been identified, suggesting that similar mechanisms and therapeutic targets may exist in glaucoma.

Precision of a new SS-OCT biometer to measure anterior segment parameters and agreement with 3 instruments with different measurement principles.

PURPOSE: To evaluate the repeatability of a new swept source optical coherence tomography (SS-OCT) based biometer to measure anterior segment parameters, and to assess the agreement with three other imaging devices based on different measurements principles. SETTING: Unit of Eye and Vision, Department of Clinical Neuroscience, Karolinska Institutet, Sweden. DESIGN: Prospective, comparative case series. METHODS: 3 consecutive measuremetns were obtained in unoperated eyes with the Eyestar900 (SS-OCT), Lenstar 900, MS-39, and Sirius. The following anterior segment parameters were evaluated: central corneal thickness (CCT), corneal diameter (CD), aqueous depth (AQD), and corneal power metrics. The repeatability limit (Rlim), coefficient of variation (CoV), and a repeated measures Bland-Altman analysis were performed. RESULTS: 74 eyes of 74 participants were measured. The Rlims for CCT, CD, and AQD were lower than 10µm, 0.3mm, and 0.10mm for all devices, respectively. The corresponding CoVs for these parameters never exceeded 1.2%. The Rlim for the corneal power metrics never exceeded 0.60D for any of the instruments. Lenstar showed the best agreement with the MS-39 to measure CCT, CD, and AQD (limit of agreement interval, LoA: 15.54µm, 0.55mm, and 0.16mm, respectively). The mean difference for keratometry parameters was lower than 0.3D for all device comparisons, and the LoA interval ranged between 0.52D to 1.21D. CONCLUSIONS: The repeatability for measuring anterior segment parameters was good, and the agreement among all the instuments was good for CD and AQD measurements. However, for CCT and keratometer parameters, the instruments cannot be used interchangeably due to large LoA interval.

Repeatability of a fully automated swept-source optical coherence tomography biometer and agreement with a low coherence reflectometry biometer.

BACKGROUND: To evaluate the repeatability of a fully automated swept-source optical coherence tomography (SS-OCT) and its agreement with an optical low coherence reflectometry (OLCR) for several biometric parameters. METHODS: In this study, 74 eyes of 74 patients were measured using the Eyestar 900 SS-OCT and Lenstar LS 900 OLCR. Flat keratometry (K1) and steep keratometry (K2), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), and axial length (AL) were measured three times with each device. The repeatability was analyzed with the intrasubject standard deviation, coefficient of variability (CoV), and coefficient of repeatability (CoR) for each instrument. The agreement between the instruments was evaluated with Bland-Altman analysis. RESULTS: K1, K2 and CCT CoV values were < 0.2%, < 0.4% and < 0.55%, respectively. Higher CoV values were found for ACD and LT ranging from 0.56% to 1.74%. The lowest CoV values were found for the AL measurements (0.03% and 0.06% for the Eyestar 900 and the Lenstar LS 900, respectively). AL measurements provided the highest repeatability, measured with both CoV and CoR values, and the CCT was the parameter with the lowest repeatability. The CCT and LT measurements were statistically significant between the two biometers (P < 0.001). The interval of the limits of agreement was < 0.6 D for K1 and K2, 15.78 µm for CCT, 0.21 mm for ACD, 0.34 mm for LT, and 0.08 mm for AL. CONCLUSIONS: Both biometers provide repeatable measurements for the different parameters analyzed and can be used interchangeably.

Effect of six different autorefractor designs on the precision and accuracy of refractive error measurement.

PURPOSE: To evaluate the precision of objective refraction measurements with six different autorefractors that have different designs and measurement principles and to compare the objective refraction values with the subjective refraction. METHOD: Objective refraction of 55 participants was measured using six autorefractors with different designs. The instrument features mainly varied in terms of measurement principles, inbuilt fogging, open or closed view, and handheld or stationary designs. Two repeated measurements of objective refraction were performed with each autorefractor. The objective refractions from the six autorefractors were compared with the standard subjective refraction. The repeatability limit and Bland-Altman were used to describe the precision and accuracy of each autorefractor, respectively. The analysis was done using the spherical component of the refraction and the power-vector components, spherical equivalent (M), and cylindrical vectors. RESULTS: The repeatability of all autorefractors was within 1.00 and 0.35D for measuring the M and both cylindrical components, respectively. Inbuilt fogging was the common feature of the instruments that showed better repeatability. Compared to subjective refraction, the mean difference for sphere and M was below +0.50D, and it was close to zero for the cylindrical components. The instruments that had inbuilt fogging showed narrower limit of agreement. When combined with fogging, the open field refractors showed better precision and accuracy. CONCLUSIONS: The inbuilt fogging is the most important feature followed by the open view in determining the precision and accuracy of the autorefractor values.

Agreement of different OCT scan directions for individual retinal-layer thickness measurements in multiple sclerosis subjects with prior unilateral optic neuritis.

The similarities between horizontal and vertical Optical Coherence Tomography (OCT) scans for the individual retinal layer thickness measurements in the macula was evaluated. Two volumetric scans (B-scans oriented horizontally and vertically) were performed in 64 multiple sclerosis subjects with history of unilateral optic neuritis and 64 healthy controls. The agreement between the thickness measurements with horizontal and vertical OCT scans was evaluated in 3 groups of eyes: healthy controls, eyes with history of optic neuritis and the fellow eyes. The mean difference in individual layer thickness between the scans was smaller than the instrument's axial resolution in all 3 groups. The limit of agreement (LoA) varied among the different layers and sectors analyzed and this trend was similar in all the groups. For the inner retinal layers (retinal nerve fiber layer to inner nuclear layer), the inner macular sectors had a larger LoA compared to the corresponding outer sectors. In the outer plexiform and nuclear layers, the central and inner sectors (except inner temporal) had LoA larger than the other sectors and layers. The larger LoA seen for different layers and sectors suggests that the scan direction must be same for the follow-up OCT measurements and in clinical studies.

Precision and Agreement of Individual and Simultaneous Macular and Optic Disc Volumetric Measurements With Spectral Domain Optical Coherence Tomography.

Purpose: To evaluate the precision of individual and combined macula and optic disc volumetric analysis, and the agreement between these two scan modes with spectral domain optical coherence tomography (OCT). Methods: Macular and optic disc volumetric measurements were performed with individual and combined scan protocols in one eye of 75 healthy subjects. Three repeated measurements were performed with each protocol. From the macular area, retinal thickness in nine different sectors and ganglion cell complex thickness in eight different sectors were analyzed from both scan modes. From the optic disc area, the peripapillary retinal nerve fiber layer (pRNFL) thickness in 12 clock sectors and the optic disc parameters were evaluated. For all the parameters, repeatability limit and agreement analysis were performed. Results: For the retinal thickness measurements in macula, the combined scan had two to three times larger repeatability limit than the individual scan for all the sectors except the central sector, where the repeatability limit was five times larger. The limits of agreement intervals were lower than 20 µm for all sectors, except the central. The ganglion cell complex measurements also had larger repeatability limits for the combined scans, and the limits of agreement intervals were <10 µm for all sectors. For the pRNFL thickness, the repeatability values were distributed like a vertically elongated ellipse for both scans, but still the repeatability was better for individual scan compared to the combined scan. The shortest and widest interval are obtained for sectors 9 (9 µm) and 12 (40 µm), respectively. The repeatability limit was <0.15 units for all disc parameters with both scan modes. Conclusion: The individual macula and optic disc scans had better repeatability than the combined scan mode, and the two scan modes cannot be used interchangeability due to the wide limits of agreement.

Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction.

Nicotinamide adenine dinucleotide (NAD) is a REDOX cofactor and metabolite essential for neuronal survival. Glaucoma is a common neurodegenerative disease in which neuronal levels of NAD decline. We assess the effects of nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron in glaucoma) in normal physiological conditions and across a range of glaucoma relevant insults including mitochondrial stress and axon degenerative insults. We demonstrate retinal ganglion cell somal, axonal, and dendritic neuroprotection by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We performed metabolomics enriched for small molecular weight metabolites for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption, including consistent changes to α-ketoglutaric acid, creatine/creatinine, homocysteine, and glycerophosphocholine. This metabolic disruption is prevented by nicotinamide. Nicotinamide provides further neuroprotective effects by increasing oxidative phosphorylation, buffering and preventing metabolic stress, and increasing mitochondrial size and motility whilst simultaneously dampening action potential firing frequency. These data support continued determination of the utility of long-term nicotinamide treatment as a neuroprotective therapy for human glaucoma.

Visual fatigue during control room work in process industries.

BACKGROUND: Working in front of computer screens is visually demanding and related to adverse eye symptoms. Occurrence of glare further increases visual fatigue. OBJECTIVE: This paper presents results from an examination of visual ergonomics in control room environments at two Swedish process industries. METHODS: Visual conditions were examined and evaluated in nine control rooms and eighteen process operators answered questions about their perceived workload and visual experiences. RESULTS: When working in the control rooms, the mental workload was rated significantly higher by the participants, compared to experienced performance. The operators further experienced significantly higher visual fatigue and blurred vision compared to double vision and sore eyes. Visual demands were increased in conditions where contrast glare was present, as well as frequent changes of focusing distances, and low contrast between background and characters in computer screens. CONCLUSIONS: Suboptimal visual working conditions in the control rooms contributes to increased visual demands on the operators. Presence of glare is leading to visual fatigue and an unnecessary high mental load. The findings support the relevance of considering principles of general and visual ergonomics when designing and organizing work in control rooms. Workstation design should also be flexible to allow for individual and contextual adjustments.