Electroretinographic Evaluations of Eyes With Endophthalmitis.

Purpose: To determine the physiological status of the retina of eyes with endophthalmitis by examining the electroretinograms (ERGs) recorded with a portable recording system and to determine whether the pretreatment ERG findings were correlated with the best-corrected visual acuity (BCVA) after the treatment. Methods: We examined the medical records of 118 eyes of 108 patients who were diagnosed and treated for infectious endophthalmitis at Saitama Medical University Hospital, Japan, between January 2015 to November 2022. Of these, we studied the 25 eyes of 21 patients who had been evaluated by electroretinography. In bilateral cases, one eye was analyzed. The eyes were classified into those with postoperative endophthalmitis (group S, n = 12) and those with endogenous endophthalmitis (group E, n = 9). Photopic and flicker ERGs were recorded with the RETeval system. The pretreatment clinical factors studied were the ERG components that might be correlated with the post-treatment BCVA. Results: Eyes in Group E with larger amplitude flicker ERGs (P = 0.0053, ρ = -0.8333) had better BCVA after treatment. In Group S, eyes with larger amplitude flicker ERGs (P = 0.0086, ρ = -0.7173), photopic a-waves (P = 0.0323, ρ = 0.6177), and photopic b-waves (P = 0.0055, ρ = -0.7443) had better BCVA after treatment. Conclusions: Simple and rapid ERG evaluations under light-adapted condition are helpful in evaluating the pretreatment retinal function and to determine the visual prognosis in eyes with endophthalmitis. Translational Relevance: Simple and non-time-consuming ERG evaluations are helpful in evaluating the retinal function in eyes with endophthalmitis and predicting the visual prognosis.

ElectroRetinoGraphy toward an exploration of the therapeutic potential of antidepressants in patients with major depressive disorder: A scoping review of the literature.

Major Depressive Disorder (MDD) is characterized by at least one major depressive episode. It requires medical attention typically involving the prescription of antidepressants. Remission in MDD patients is often difficult to achieve because of the limited effectiveness of these drugs. Nowadays, numerous patients undergo various antidepressant treatments, with subjective changes in their personal experiences being regularly monitored. Therefore, it is essential to find clinical and objective tools that offer a more tailored approach to antidepressant selection. The neurochemistry of the retina being similar to the brain, one promising approach would be to use ElectroRetinoGraphy (ERG) measurements on MDD patients requiring antidepressant treatment. Thus, the aim of this scoping review is to highlight effects of different classes of antidepressants on retinal function evaluated by full-field ERG (ffERG), Pattern ERG (PERG) and multifocal ERG (mfERG) waveforms in MDD patients. These ERG measurements could serve as pivotal indicators in defining patient profiles, facilitating a more objective and personalized approach to therapeutic interventions, thereby advancing precision psychiatry.

Oscillatory potential findings in patients with acute ischaemic central retinal vein occlusion.

AIMS: To explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO). METHODS: 11 patients (11 eyes) with ischaemic CRVO and 32 patients (32 eyes) with non-ischaemic CRVO who presented with first-episode unilateral CRVO within 1 month of symptom onset and with no previous intervention were examined by the International Society for Clinical Electrophysiology of Vision standard ERG. RESULTS: A significant amplitude decline and peak time delay in light-adapted (LA) 3 ERG and LA 30 Hz flicker ERG (p<0.05 for all) was found in the ischaemic CRVO eyes, compared with the non-ischaemic CRVO eyes. The b/a amplitude ratio of dark-adapted (DA) 3 ERG, DA 10 ERG and LA 3 ERG was significantly different between the ischaemic and non-ischaemic groups (p<0.05 for all). Regarding oscillatory potentials (OPs), the amplitudes of OP1, OP2 and OP3 as well as the sum of DA 3 OP1-4 amplitudes (∑OPs) showed significant changes (p<0.01 for all) between two groups. No peak time delay of OPs was found between the ischaemic and non-ischaemic CRVO eyes. CONCLUSION: The amplitude of DA 0.01 ERG, components of LA 3 ERG and LA 30 Hz flicker ERG, and the b/a amplitude ratio could be among the most sensitive indicators in patients with acute ischaemic CRVO. The amplitudes of OP1, OP2, OP3 and ∑OPs in the CRVO eyes were reduced to 40% of the control values, showing that this quantitative method is reliable for detecting ischaemic retinal diseases, even in early stage.

Altered Functional Responses of the Retina in B6 Albino Tyrc/c Mice.

Purpose: Mammals with albinism present low visual discrimination ability and different proportions of certain retinal cell subtypes. As the spatial resolution of the retina depends on the visual field sampling by retinal ganglion cells (RGCs) based on the convergence of upstream cell inputs, it could be affected in albinism and thus modify the RGC function. Methods: We used the Tyrc/c line, a mouse model of oculocutaneous albinism type 1 (OCA1), carrying a tyrosinase mutation, and previously characterized by a total absence of pigment and severe visual deficits. To assess their retinal function, we recorded the light responses of hundreds of RGCs ex vivo using multi-electrode array (MEA). We estimated the receptive field (RF)-center diameter of Tyr+/c and Tyrc/c RGCs using a checkerboard stimulation before simultaneously stimulating the center and surround of RGC RFs with full-field flashes. Results: Following checkerboard stimulation, the RF-center diameters of RGCs were indistinguishable between Tyrc/c and Tyr+/c retinas. Nevertheless, RGCs from Tyrc/c retinas presented more OFF responses to full-field flashes than RGCs from Tyr+/c retinas. Unlike Tyr+/c retinas, very few OFF-center RGCs switched polarity to ON or ON-OFF responses after full-field flashes in Tyrc/c retinas, suggesting a different surround suppression in these retinas. Conclusions: The retinal output signal is affected in Tyrc/c retinas, despite intact RF-center diameters of their RGCs. Adaptive mechanisms during development are probably responsible for this change in RGC responses, related to the absence of ocular pigments.

Short communication: Maintained visual performance in birds under high altitude hypoxia.

Birds are highly dependent on their vision for orientation and navigation. The avian eye differs from the mammalian eye as the retina is avascular, leaving the inner, highly metabolically active layers with a very long diffusion distance to the oxygen supply. During flight at high altitudes, birds face a decrease in environmental oxygen partial pressure, which leads to a decrease in arterial oxygen levels. Since oxygen perfusion to the retina is already limited in birds, we hypothesize that visual function is impaired by low oxygen availability. However, the visual performance of birds exposed to hypoxia has not been evaluated before. Here, we assess the optomotor response (OMR) in zebra finches under simulated high-altitude hypoxia (10%) and show that the OMR is largely maintained under hypoxia with only a modest reduction in OMR, demonstrating that birds can largely maintain visual function at high altitudes. The method of our study does not provide insight into the mechanisms involved, but our findings suggest that birds have evolved physiological mechanisms for retinal function at low tissue oxygen levels.

Establishment and comprehensive characterization of a novel dark-reared zebrafish model for myopia studies.

Myopia is predicted to impact approximately 5 billion people by 2050, necessitating mechanistic understanding of its development. Myopia results from dysregulated genetic mechanisms of emmetropization, caused by over-exposure to aberrant visual environments; however, these genetic mechanisms remain unclear. Recent human genome-wide association studies have identified a range of novel myopia-risk genes. To facilitate large-scale in vivo mechanistic examination of gene-environment interactions, this study aims to establish a myopia model platform that allows efficient environmental and genetic manipulations. We established an environmental zebrafish myopia model by dark-rearing. Ocular biometrics including relative ocular refraction were quantified using optical coherence tomography images. Spatial vision was assessed using optomotor response (OMR). Retinal function was analyzed via electroretinography (ERG). Myopia-associated molecular contents or distributions were examined using RT-qPCR or immunohistochemistry. Our model produces robust phenotypic changes, showing myopia after 2 weeks of dark-rearing, which were recoverable within 2 weeks after returning animals to normal lighting. 2-week dark-reared zebrafish have reduced spatial-frequency tuning function. ERG showed reduced photoreceptor and bipolar cell function (a- and b-waves) after only 2 days of dark-rearing, which worsened after 2 weeks of dark-rearing. We also found dark-rearing-induced changes to expression of myopia-risk genes, including egr1, vegfaa, vegfab, rbp3, gjd2a and gjd2b, inner retinal distribution of EFEMP1, TIMP2 and MMP2, as well as transiently reduced PSD95 density in the inner plexiform layer. Coupled with the gene editing tools available for zebrafish, our environmental myopia model provides an excellent platform for large-scale investigation of gene-environment interactions in myopia development.

Effects of 2 Hz flickering light on refractive state, fundus imaging and visual function of C57BL/6 mice.

In this study, we investigated the effects of flickering light on refractive development of mice and the changes of fundus structure and function during this process. C57BL/6 mice were randomly divided into control group and flickering light-induced myopia (FLM) group. Mice in the control group were fed under normal lighting. FLM group mice were fed under lighting with a duty cycle of 50% and flash frequency of 2 Hz. Refractive status, axial length (AL), corneal radius of curvature (CRC), and electroretinogram signals were measured in all animals before treatment and at 2 and 4 weeks after treatment. Retinal thickness (RT), choroidal thickness (ChT) and choroidal blood perfusion (ChBP) were measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). After 4 weeks of flickering light stimulation, the mice became myopia, the AL increased, but the CRC remained constant. The induction of myopia reduced the implicit time and amplitude of a-wave and b-wave in electroretinogram, which affects the function of retina. Full-layer retinal thickness, ChT and ChBP decreased at both 2 and 4 weeks after flickering light induction. The superficial and middle layers of the retina were significantly thinner, while the deep layer was only slightly thinner without statistical significance. Calculated by the concentric circle algorithm, the decrease of choroidal blood perfusion in FLM was mainly concentrated in the concentric circle area with the optic disc as the center radius of 150-450 µm. In conclusion, the present study shows that flickering light can successfully induce myopia in C57BL/6 mice, affect the electrophysiological activity of retina, and cause changes in fundus tissue structure and blood flow.

Retinal Sensitivity in Macular Subfields and Their Association with Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration.

INTRODUCTION: The objective of this study was to evaluate retinal sensitivity in subfields and its association with the novel quantitative contrast sensitivity function (qCSF) in patients with early age-related macular degeneration (eAMD), in patients with intermediate AMD (iAMD), and in healthy controls. METHODS: In this prospective longitudinal study, retinal sensitivity of a customized 24-point grid was assessed by microperimetry Macular Integrity Assessment (MAIA, CenterVue, Padova, Italy) and divided into different subfields. The Multiple Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA, USA) was used for qCSF testing. Linear models were used to test the association of functional metrics with variables of interest. RESULTS: 92 study eyes from 92 participants were analyzed (13 eAMD, 31 iAMD, and 48 controls). Microperimetry subfield comparison showed significant differences (p < 0.0001) in the control group between superior and inferior hemifield as well as between central and peripheral subfields. For eAMD, significant differences were found between central and peripheral subfields (p < 0.001) and specific subfields (p < 0.05) and finally for iAMD between specific quadrants (p < 0.05) and specific squares (p < 0.05). Significant associations of retinal sensitivity with qCSF metrics were found for the area underneath the logarithmic contrast sensitivity function, contrast acuity and for the contrast sensitivity at specific spatial frequencies. CONCLUSIONS: This study showed significant differences in the evaluated retinal sensitivity subfields, providing localized natural history data for retinal sensitivity in healthy controls and patients with eAMD and iAMD.

Exploring autism via the retina: Comparative insights in children with autism spectrum disorder and typical development.

Autism spectrum disorder (ASD) is a widely recognized neurodevelopmental disorder, yet the identification of reliable imaging biomarkers for its early diagnosis remains a challenge. Considering the specific manifestations of ASD in the eyes and the interconnectivity between the brain and the eyes, this study investigates ASD through the lens of retinal analysis. We specifically examined differences in the macular region of the retina using optical coherence tomography (OCT)/optical coherence tomography angiography (OCTA) images between children diagnosed with ASD and those with typical development (TD). Our findings present potential novel characteristics of ASD: the thickness of the ellipsoid zone (EZ) with cone photoreceptors was significantly increased in ASD; the large-caliber arteriovenous of the inner retina was significantly reduced in ASD; these changes in the EZ and arteriovenous were more significant in the left eye than in the right eye. These observations of photoreceptor alterations, vascular function changes, and lateralization phenomena in ASD warrant further investigation, and we hope that this work can advance interdisciplinary understanding of ASD.

Neuroretinal Alterations in Schizophrenia and Bipolar Disorder: An Updated Meta-analysis.

Schizophrenia (SZ) and bipolar disorder (BD) are characterized by major symptomatic, cognitive, and neuroanatomical changes. Recent studies have used optical coherence tomography (OCT) to investigate retinal changes in SZ and BD, but their unique and shared changes require further evaluation. Articles were identified using PubMed and Google Scholar. 39 studies met the inclusion criteria. Diagnostic groups were proband (SZ/BD combined), SZ, BD, and healthy control (HC) eyes. Meta-analyses utilized fixed and random effects models when appropriate, and publication bias was corrected using trim-and-fill analysis ("meta" package in R). Results are reported as standardized mean differences with 95% CIs. Data from 3145 patient eyes (1956 SZ, 1189 BD) and 3135 HC eyes were included. Studies identified thinning of the peripapillary retinal nerve fiber layer (pRNFL, overall and in 2 subregions), m-Retina (overall and all subregions), mGCL-IPL, mIPL, and mRPE in SZ patients. BD showed thinning of the pRNFL (overall and in each subregion), pGCC, and macular Retina (in 5 subregions), but no changes in thickness or volume for the total retina. Neither SZ nor BD patients demonstrated significant changes in the fovea, mRNFL, mGCL, mGCC, mINL, mOPL, mONL, or choroid thicknesses. Moderating effects of age, illness duration, and smoking on retinal structures were identified. This meta-analysis builds upon previous literature in this field by incorporating recent OCT studies and examining both peripapillary and macular retinal regions with respect to psychotic disorders. Overall, this meta-analysis demonstrated both peripapillary and macular structural retinal abnormalities in people with SZ or BD compared with HCs.

Evaluation of ophthalmic vascular and neuroretinal alterations in fibromyalgia syndrome: a cross-sectional comparative study.

INTRODUCTION: Fibromyalgia syndrome (FMS) is a prevalent rheumatic disorder, and its pathogenesis includes genetic, neuroendocrine, and autonomic abnormalities, which may impact ocular structures. The aim was to conduct a comparative analysis of the ophthalmic vasculature and the retinal nerve fiber layer (RNFL) thickness between FMS and control groups using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: This cross-sectional comparative study included 43 FMS patients and 40 healthy controls recruited from a tertiary education and research hospital between January 2024 and May 2024. All patients satisfied the 2016 American College of Rheumatology criteria for FMS and consented. OCT and OCTA were used to assess the RNFL thickness and the retinal microvasculature structure. The Fibromyalgia Impact Questionnaire (FIQ) was performed to evaluate disease severity. RESULTS: The study found significantly higher total retinal parafoveal thickness and foveal density in FMS patients (p = 0.017 and p = 0.044, respectively). Nevertheless, there were no significant differences among the groups concerning total retinal foveal thickness, foveal avascular zone characteristics, superficial and deep capillary plexus densities, choriocapillaris flow area, and outer retinal flow area values (p > 0.05). The RNFL thickness in all quadrants did not reveal significant differences between the groups (p > 0.05). Furthermore, there was no significant correlation between FIQ scores and OCTA parameters or RNFL thickness values (p > 0.05). CONCLUSION: The study revealed slight differences in retinal parafoveal thickness and foveal density in FMS patients, but no substantial vascular or neurodegenerative alterations were observed compared to healthy controls. These data indicate that FMS may not substantially affect ocular structures, contrary to earlier hypotheses.

Electroretinographic changes in the inner and outer retinal layers before and after intravenous chemotherapy for retinoblastoma.

PURPOSE: To study the inner and outer retinal functions using a full-field electroretinogram (ERG) before and after intravenous chemotherapy (IVC) in children with retinoblastoma (RB). METHODS: Of the 11 eyes, seven had RB and four were normal. All children were examined under anesthesia using a handheld ERG machine with a standard protocol - light-adapted single-flash ERG (fERG), photopic single-flash 3.0- and 30-Hz flickers, and photopic negative response (PhNR) amplitudes at 72 ms (P72). The amplitudes and peak times were compared before and after IVC. RESULTS: Post-chemotherapy tumor regressed in all seven eyes. Of the seven eyes, the fERG peak time (a-wave) was delayed in two eyes (29%), whereas the b-wave was delayed in six eyes (86%). The fERG amplitude height for a- and b-waves decreased in five eyes (71%) and six eyes (86%), respectively. In addition, photopic flicker 30-Hz b-wave peak time delayed in five eyes (71%), whereas the b-wave amplitude height decreased in six eyes (86%). Simultaneously, the P72 amplitude height decreased in six eyes (86%), whereas the P-ratio increased in all seven eyes (100%). In comparison, the ERG responses improved in three of the four contralateral normal eyes. Overall, the cone function improved in two eyes (29%), whereas cone bipolar cell and retinal ganglion cell (RGC) function improved in one eye (14%) each. CONCLUSION: Comparison of light-adapted ERG changes before and after IVC showed reduced amplitudes and delayed peak times for both a and b waveforms, as well as reduced PhNR amplitude attributable to bipolar and RGC injury.

Correlation in retinal thickness and macular retina plus choroidal microcirculation in pediatric myopia.

To analyze the relationship in retinal thickness, macula retina and choroidal microcirculation in pediatric patients with myopia. Pediatric patients with high myopia (high myopia group, n = 30, 60 eyes) and pediatric patients with low to moderate myopia (low myopia group, n = 30, 60 eyes) admitted to our hospital from January 2021 to January 2022 were randomly selected as the study subjects. Retinal thickness, the blood density of retina, and the blood density of the choroid were collected in each area of the macula by taking optical coherence tomography (OCT) and OCT angiography (OCTA). Pearson correlation analysis was conducted to compare the results from the 2 groups. Outer retinal thickness showed a weak positive correlation with Superficial vascular complex flow density (SVD) and deep vascular complex flow density (DVD) (P < .05), but no significant correlation with choroidal capillary density (P > .05); inner retinal thickness showed a weak positive correlation with SVD and DVD (P < .05), but no significant correlation with choroidal capillary density (P > .05). In pediatric patients with myopia, there is a positive correlation between the blood flow density of macular retina and retinal thickness, and the retinal thickness will become thinner with increasing myopia.

Multicentric Longitudinal Prospective Study in a European Cohort of MYO7A Patients: Disease Course and Implications for Gene Therapy.

Purpose: We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene. Methods: Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed. Results: At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]). Conclusions: Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.

Characterizing Retinal Sensitivity and Structure in Congenital Stationary Night Blindness: A Combined Microperimetry and OCT Study.

Purpose: To investigate the characteristics of microperimetry and optical coherence tomography (OCT) in congenital stationary night blindness (CSNB), as well as their structure-function association. Methods: This cross-sectional study included 32 eyes from 32 participants with CSNB, comprising 18 with complete CSNB and 14 with incomplete CSNB, along with 36 eyes from 36 CSNB-unaffected controls matched for age, sex, and spherical equivalent. Using MP-3 microperimetry, central retinal sensitivity was assessed within a 20° field, distributed across six concentric rings (0°, 2°, 4°, 6°, 8°, and 10°). OCT was used to analyze retinal and choroidal thickness. The study aimed to assess the overall and ring-wise retinal sensitivity, as well as choroidal and retinal thickness in CSNB and CSNB-unaffected controls, with a secondary focus on the relationship between retinal sensitivity and microstructural features on OCT. Results: In comparison with CSNB-unaffected subjects, the overall and ring-wise retinal sensitivity as well as choroidal thickness were reduced in patients with CSNB (P < 0.001). Moreover, the central sensitivity in incomplete CSNB group was lower than in complete CSNB group (25.72 ± 3.93 dB vs. 21.92 ± 4.10 dB; P < 0.001). The retinal thickness in the CSNB group was thinner outside the fovea compared with the CSNB-unaffected group. Multiple mixed regression analyses revealed that point-to-point retinal sensitivity was significantly correlated with BCVA (P = 0.002) and the corresponding retinal thickness (P = 0.004). Conclusions: Examination of retinal sensitivity and OCT revealed different spatial distribution profiles in CSNB and its subtypes. In CSNB eyes, retinal sensitivity on microperimetry was associated with retinal thickness on OCT.

Individual Prognostication of Disease Activity and Disability Worsening in Multiple Sclerosis With Retinal Layer Thickness z Scores.

BACKGROUND AND OBJECTIVES: Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted z scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS). METHODS: We established age-adjusted OCT reference data using generalized additive models for location, scale, and shape for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses, involving 910 and 423 healthy eyes, respectively. Next, we transformed the retinal layer thickness of PwMS from 3 published studies into age-adjusted z scores (pRNFL-z and GCIP-z) based on the reference data. Finally, we investigated the association of pRNFL-z or GCIP-z as predictors with future confirmed disability worsening (Expanded Disability Status Scale score increase) or disease activity (failing of the no evidence of disease activity [NEDA-3] criteria) as outcomes. Cox proportional hazards models or logistic regression analyses were applied according to the original studies. Optimal cutoffs were identified using the Akaike information criterion as well as location with the log-rank and likelihood-ratio tests. RESULTS: In the first cohort (n = 863), 172 PwMS (24%) had disability worsening over a median observational period of 2.0 (interquartile range [IQR]:1.0-3.0) years. Low pRNFL-z (≤-2.04) were associated with an increased risk of disability worsening (adjusted hazard ratio (aHR) [95% CI] = 2.08 [1.47-2.95], p = 3.82e-5). In the second cohort (n = 170), logistic regression analyses revealed that lower pRNFL-z showed a higher likelihood for disability accumulation at the two-year follow-up (reciprocal odds ratio [95% CI] = 1.51[1.06-2.15], p = 0.03). In the third cohort (n = 78), 46 PwMS (59%) did not maintain the NEDA-3 status over a median follow-up of 2.0 (IQR: 1.9-2.1) years. PwMS with low GCIP-z (≤-1.03) had a higher risk of showing disease activity (aHR [95% CI] = 2.14 [1.03-4.43], p = 0.04). Compared with raw values with arbitrary cutoffs, applying the z score approach with optimal cutoffs showed better performance in discrimination and calibration (higher Harrell's concordance index and lower integrated Brier score). DISCUSSION: In conclusion, our work demonstrated reference cohort-based z scores that account for age, a major driver for disease progression in MS, to be a promising approach for creating OCT-derived measures useable across devices and toward individualized prognostication.

Retinal blood flow association with age and weight in infants at risk for retinopathy of prematurity.

This prospective study evaluated the relationship between laser speckle contrast imaging (LSCI) ocular blood flow velocity (BFV) and five birth parameters: gestational age (GA), postmenstrual age (PMA) and chronological age (CA) at the time of measurement, birth weight (BW), and current weight (CW) in preterm neonates at risk for retinopathy of prematurity (ROP). 38 Neonates with BW < 2 kg, GA < 32 weeks, and PMA between 27 and 47 weeks underwent 91 LSCI sessions. Correlation tests and regression analysis were performed to quantify relationships between birth parameters and ocular BFV. Mean ocular BFV index in this cohort was 8.8 +/- 4.0 IU. BFV positively correlated with PMA (r = 0.3, p = 0.01), CA (r = 0.3, p = 0.005), and CW (r = 0.3, p = 0.02). BFV did not correlate with GA nor BW (r = - 0.2 and r = - 0.05, p > 0.05). Regression analysis with mixed models demonstrated that BFV increased by 1.2 for every kilogram of CW, by 0.34 for every week of CA, and by 0.36 for every week of PMA (p = 0.03, 0.004, 0.007, respectively). Our findings indicate that increased age and weight are associated with increased ocular BFV measured using LSCI in premature infants. Future studies investigating the associations between ocular BFV and ROP clinical severity must control for age and/or weight of the infant.

Effects of Optical Zone Variation of High-Addition Multifocal Contact Lenses on the Global Flash Multifocal Electroretinography.

OBJECTIVES: To evaluate the retinal response to myopic defocus after the wear of soft multifocal contact lenses with high addition through electroretinography. METHODS: Twenty-seven participants meeting inclusion criteria were enrolled. Tropicamide 1% drops (2) were instilled. Participants were then fitted with three different contact lenses: a single-vision spherical lens (SE +3.00 D), L1, serving as a control, and two soft multifocal lens designs (SE +3.00 D/add +10 D), one with a central distance zone of 4.0 mm (L2) and one with a central distance zone of 7.0 mm (L3). A global flash multifocal electroretinography was performed. Direct component (DC) amplitude, DC peak time, induced component (IC) amplitude, and IC peak time were recorded. Waveforms were grouped into five concentric areas, covering from 0° to 24° of retinal eccentricity. Differences of L2/L3 versus L1 were analyzed with t tests. Finally, correlations were calculated between the percentage of defocus in the pupil area versus the electroretinography results. RESULTS: Results show that the DC amplitude, caused mainly by photoreceptors and bipolar cells, is not influenced by the design of the lenses. The IC amplitude, however, is significantly decreased when the lens with a smaller optical zone (L2) is worn. This significant difference only concerns the ring 5, which corresponds to a retinal eccentricity of 15.7° to 24.0°. CONCLUSION: Soft multifocal lens designs influence the peripheral retinal reaction to defocus. A larger treatment zone seems to significantly impact the retinal response to defocus between 15.7° and 24.0° of eccentricity from the macula.

Alzheimer's disease pathophysiology in the Retina.

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid ß-protein (Aß) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aß deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.

Variability of relationship between inner-retinal structural changes and visual dysfunction in optic neuropathy.

Optical coherence tomography (OCT) displays the retinal nerve fiber layer (RNFL) or macular ganglion cell and inner plexiform layer (GCIPL) thickness below 1st percentile in red color. This finding generally indicates severe inner-retinal structural changes and suggests poor visual function. Nevertheless, some individuals show preserved visual function despite these circumstances. This study aimed to identify the correlation between best-corrected visual acuity (BCVA) and inner-retinal thickness based on OCT parameters in various optic neuropathy patients with extremely low RNFL/GCIPL thickness, and determine the limitation of OCT for predicting visual function in these patients. 131 patients were included in the study. The mean BCVA in logMAR was 0.55 ± 0.70 with a broad range from - 0.18 to 3.00. Among the OCT parameters, temporal GCIPL (r = - 0.412) and average GCIPL (r = - 0.366) exhibited the higher correlations with BCVA. Etiological comparisons of optic neuropathies revealed significantly lower BCVA in LHON (all p < 0.05). Idiopathic optic neuritis (ON) and MOGAD exhibited better and narrower BCVA distributions compared to the other optic neuropathies. OCT had limited utility in reflecting BCVA, notwithstanding significant inner-retinal thinning after optic nerve injuries. Caution is needed in interpreting OCT findings, especially as they relate to the etiology of optic neuropathy.