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Purpose: Retinal ischemia/reperfusion (I/R) injury is a common cause of visual impairment and blindness for which there remain limited treatment options. Nucleoside reverse transcriptase inhibitors...

Lipid peroxidation from oxidative stress is considered a major contributor to age-related macular degeneration (AMD). The retina is abundant with circulating low-density lipoproteins (LDL), which are taken up by LDL receptor (LDLR) in the RPE and Müller cells. The purpose of this study is to investigate the role of LDLR in the NaIO3-induced model of dry AMD. Confluent primary human RPE (hRPE) and LDLR-silenced ARPE-19 cells were stressed with 150 µM tert-butyl hydroperoxide (tBH) and caspase 3/7 activation was determined. WT and Ldlr−/− mice were administered NaIO3 (20 mg/kg) intravenously. On day 7, fundus imaging, OCT, ERG, and retinal thickness were measured. Histology, TUNEL, cleaved caspase 3 and lipid accumulation were assessed. Treatment of hRPE with tBH markedly decreased LDLR expression. Caspase 3/7 activation was significantly increased in LDLR-silenced ARPE-19 cells treated with tBH. In Ldlr−/− mice, NaIO3 administration resulted in significant (a) retinal thinning, (b) compromised photoreceptor function, (c) increased percentage of cleaved caspase 3 positive and apoptotic cells, and (d) increased lipid droplet accumulation in the RPE, Bruch membrane, choroid, and sclera, compared to WT mice. Our findings imply that LDLR loss leads to lipid accumulation and impaired retinal function, which may contribute to the development of AMD.

Multifaceted and divergent manifestations across tissues and cell types have curtailed advances in deciphering the cellular events that accompany advanced age and contribute to morbidities and mortalities. Increase in human lifespan during the past century has heightened awareness of the need to prevent age-associated frailty of neuronal and sensory systems to allow a healthy and productive life. In this review, we discuss molecular and physiological attributes of aging of the retina, with a goal of understanding age-related impairment of visual function. We highlight the epigenome–metabolism nexus and proteostasis as key contributors to retinal aging and discuss lifestyle changes as potential modulators of retinal function. Finally, we deliberate promising intervention strategies for promoting healthy aging of the retina for improved vision.

Microperimetry, or fundus-tracked perimetry, is a precise static-automated perimetric technique to assess central retinal function. As visual acuity only deteriorates at a late disease stage in RPGR-related retinitis pigmentosa (RP), alternative markers for disease progression are of great utility. Microperimetry assessment has been of critical value as an outcome measure in a recently reported phase I/II gene therapy trial for RPGR-related RP, both in terms of detecting safety and efficacy signals. Here, we performed a review of the literature. We describe the principles of microperimetry before outlining specific parameters that may be useful as outcome measures in clinical trial settings. The current state of structure-function correlations between short-wavelength autofluorescence, optical coherence tomography and adaptive optics in RPGR-related retinitis pigmentosa are also summarized.

Purpose Using a quick electroretinography (ERG) protocol for rapid assessment of the retinal function of wild giant pandas (Ailuropoda melanoleuca) performed in field conditions to demonstrate the range of ERG recordings in giant pandas of unknown retinal status. Animals studied Nine free range giant pandas. Procedure All the giant pandas were anesthetized using an intramuscular dexMTZ injection, which is a combination of dexmedetomidine and tiletamine-zolazepam. After 20 mins of dark adaptation, scotopic ERGs were obtained by using three flash intensities: -25 dB (0.0087 cd·s/m2 ), 0 dB (2.75 cd·s/m2 ), and +5 dB (8.7 cd·s/m2 ). Next, photopic ERGs were acquired using a single flash protocol with a flash intensity of 3.0 cd·s/m2 after 10 minutes of light adaptation. Results In scotopic ERG at 0.0087 cd·s/m2 , mean b-wave amplitude and peak time were 82.26 µV (SD ± 16.65 and 95% CI 68.33-96.18) and 66.97 ms (SD ± 10.86 and 95% CI 57.90-76.05), respectively. This flash intensity was below a-wave threshold and resulted in b waves with greater peak times compared to those with higher intensities. At 2.75 cd·s/m2 , the mean a-wave amplitude and peak time were 53.95 µV (SD ± 11.63 and 95% CI 44.23-63.67) and 16.13 ms (SD ± 2.62 and 95% CI 13.94-18.31), and mean b-wave amplitude and peak time were 119.57 µV (SD ± 15.54 and 95% CI 106.57-132.56) and 32.00 ms (SD ± 6.47 and 95% CI 26.59-37.41). At 8.7 cd·s/m2 , the mean a-wave amplitude and peak time were 58.85 µV (SD ± 14.90 and 95% CI 46.39-71.31) and 15.59 ms (SD ± 2.63 and 95% CI 13.40-17.79), and the mean b-wave amplitude and peak time were 132.97 µV (SD ± 22.11 and 95% CI 114.48-151.46) and 32.66 ms (SD ± 6.87 and 95% CI 26.91-38.40). In photopic ERG at 2.75 cd·s/m2 , the mean a-wave amplitude and peak time were 62.08 µV (SD ± 16.61 and 95% CI 48.19-75.97) and 16.28 ms (SD ± 0.90 and 95% CI 15.53-17.03), and the mean b-wave amplitude and peak time were 214.93 µV (SD ± 70.41 and 95% CI 156.07-273.80) and 33.09 ms (SD ± 1.27 and 95% CI 32.03-34.15). Conclusion Using a portable ERG system with a brief ERG protocol to perform electroretinographies in wild giant pandas is a practical, useful, and reliable method for the rapid assessment of their retinal function.

The electroretinogram (ERG) is a powerful approach for investigating visual function in zebrafish ocular disease models. However, complexity, cost, and a literature gap present as significant barriers for the introduction of this technology to new zebrafish laboratories. Here, we introduce a simplified and effective method to obtain zebrafish ERGs. In-house assembled recording electrodes and a custom 3D-printed platform were used to gather high-quality and consistent ERG data from zebrafish at 3 developmental timepoints—larval, juvenile, and adult. Fish were tested under both scotopic (dark-adapted) and photopic (light-adapted) conditions to differentiate between the rod and cone systems, respectively. Robust ERG waveforms across all developmental timepoints were obtained using the methodology presented here. We observed an overall increase in signal amplitude as development progressed, reflecting maturation of the zebrafish retina. Oscillatory potentials could also be isolated from the generated waveforms. This simplified approach to the zebrafish ERG can generate waveforms comparable to the existing approaches and helps reduce barriers for zebrafish laboratories studying ocular development and disease.

Photoreceptor transplantation can rescue the retinal function of late-stage rd1 mice. Many studies have used synaptic markers to suggest that there are synaptic connections after transplantation, but how donor and host cells are connected remains unknown. Many molecules are needed for triad ribbon synapse formation in wild-type mice. Among them, pikachurin is an important extracellular matrix protein that bridges the pre- and postsynaptic components. To investigate the mechanism of the synaptic connection between donor photoreceptor and host retina, we studied the expression of pikachurin in late-stage rd1 mice before and after transplantation. The results showed that the full-length form of pikachurin could still be detected in the degenerated retina. After photoreceptors were transplanted to the subretinal space of rd1 or wild-type mice, pikachurin was detected in the cytoplasm of most donor photoreceptor cells. Pikachurin puncta may represent the cleaved form of the protein and may indicate synapse generation, but it was barely observed in the donor mass of wild-type mice (3.83 ± 3.17 puncta per 100 donor cells). In contrast, pikachurin puncta could be found in the graft of the rd1 mouse retina, but the number was low (21.35 ± 9.48 puncta per 100 donor cells). In addition, 54.12 ± 8.45% of bassoon puncta were paired with pikachurin puncta and 45.5 ± 6.33% were not, indicating that there were fewer pikachurin puncta than bassoon. These results suggest that pikachurin is involved in only a portion of the synaptic connection between the donor photoreceptor and host retina.

Purpose was to study how ultraviolet (UV) light (365 nm) applied in low doses (1200 J·m -2 ), corresponding to the regimens of spectrofluorimetric analysis of the limbus and lens area, to the anterior eye chamber, affects bioelectric activity of the retina. Material and methods. A group of 25 volunteers (12 men and 13 women aged 21.0 ± 1.3 years) with no signs of ophthalmological or somatic pathology underwent spectrofluorimetric assessment of the limbus and lens area, followed by an evaluation of retina electrogenesis state. Results. We revealed no changes in the electric activity of the retina during the whole period of observation. The amplitude of A-wave varied from 75.2 mcV to 86.2 mcV both before and after the spectrofluorimetric examination. There were no significant changes in b-wave characteristics at any periods of investigation; b/a index did not demonstrate any difference from the baseline level. Conclusion. UV radiation (365 nm) of the anterior eye chamber in doses not exceeding those permitted by the SANPIN 5804-91 standard has no effect on the retinal function, should be considered safe, and can be used in future studies.

X-linked retinoschisis (XLRS) is an inherited retinal condition that leads to schisis of the retina. In the past, treatment trials for XLRS have generally used OCT monitoring of the schitic cavities as the primary structural outcome measure and best corrected visual acuity as the primary functional outcome. Here, we report two cases of genetically confirmed XLRS with marked fluctuations in OCT morphology in the absence of treatment. Given this demonstration of spontaneous fluctuation in retinal structure on OCT in XLRS we suggest that alternative measures of retinal function should be used in future therapeutic trials in XLRS.

The aim of this study was to determine whether primary open-angle glaucoma (POAG) is associated with changes in fixation stability parameters assessed by microperimetry (MP) and whether the severity of glaucoma is related to a deterioration in these indicators. This study analyzed fixation stability using MP macular analyzer integrity assessment (MAIA) in patients with mild and moderate/severe POAG and healthy controls. The resulting fixation indices were correlated with parameters used to assess retinal function with MP and standard automated perimetry (SAP) and retinal structure with optical coherence tomography (OCT) and OCT angiography (OCTA). We enrolled 54 eyes in the POAG groups (32 eyes with mild POAG and 22 eyes with moderate/severe POAG) and 24 eyes in the healthy group. It was shown that fixation stability in POAG eyes deteriorated with increasing disease severity, and significant differences in bivariate contour ellipse area (BCEA) including 95% of fixation points were observed among groups (p = 0.042). Quantitative analysis of structural and functional retinal parameters also showed significant deterioration with the progression of glaucoma (p < 0.001). Correlations among fixation parameters and abnormalities in the retinal structure and function were confirmed. We concluded that POAG is associated with disturbances in the fixation pattern, which worsen as the disease progresses and can be effectively assessed by performing a MP test.

PURPOSE To assess the impact of neurodegenerative morphologic alterations due to macular telangiectasia type 2 (MacTel) on microperimetry (MP) and multifocal electroretinography (mfERG). METHODS Thirty-five eyes of 18 patients with MacTel were examined using spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), mfERG and MP. Software was used to match SD-OCT B-scans with the corresponding retinal sensitivity map and multifocal electroretinograms (mfERGs), thus enabling direct structure/function correlation. RESULTS Loss of the ellipsoid zone (EZ) had the strongest negative association with retinal sensitivity (16.77 dB versus 4.58 dB, adj. p

BACKGROUND AND OBJECTIVES: To characterize the clinical and ellipsoid zone (EZ) integrity outcomes in surgical intervention for symptomatic vitreomacular traction (VMT), and to evaluate the utility of intraoperative optical coherence tomography (OCT) during VMT surgery. PATIENTS AND METHODS: This was a post-hoc analysis of eyes in the DISCOVER study undergoing pars plana vitrectomy (PPV) with intraoperative OCT for VMT-related macular disease. Data were collected prospectively on feasibility and utility of intraoperative OCT, with follow-up lasting 12 months. RESULTS: Forty-three eyes of 41 patients were included and mean visual acuity improved from 20/96 to 20/45 ( P < .001). Intraoperative OCT provided information that impacted surgical decision-making in eight patients (18.6%). EZ integrity metrics significantly improved from baseline to 12 months and directly correlated with functional outcomes ( P < .001). CONCLUSIONS: Retinal function and morphology improved significantly following PPV for VMT. Intraoperative OCT provided surgeon-perceived valuable information in select cases. Further research is needed to determine whether this information impacts overall surgical outcomes. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:544–550.]

To the Editor: Full-field electroretinography (ffERG) assesses global retinal function based on measured electrical responses to standardized light stimuli under scotopic and photopic conditions. D...

Electroretinography (ERG) is a commonly used technique to study retinal function in both clinical and research ophthalmology. ERG responses can be divided into component waveforms, analysis of which can provide insight into the health and function of different types and populations of retinal cells. In dogs, ERG has been used in the characterization of normal retinal function, as well as the diagnosis of retinal diseases and measuring effects of treatment. While many components of the recorded waveform are similar across species, dogs have several notable features that should be differentiated from the responses in humans and other animals. Additionally, modifications of standard protocols, such as changing flash frequency and stimulus color, and mathematical models of ERG waveforms have been used in studies of human retinal function but have been infrequently applied to visual electrophysiology in dogs. This review provides an overview of the origins and applications of ERG in addition to potential avenues for further characterization of responses in the dog.

Purpose To evaluate changes in electroretinogram (ERG) response over the course of multiple sessions of panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PRP). Methods A prospective cohort study of 11 patients with PDR who required PRP was conducted. PRP was completed over three sessions. Each patient had five ERGs done: baseline, 1 week after each PRP session, and 6 weeks after the last session of PRP. Dark-adapted 0.01 ERG, Dark-adapted 3 ERG, Dark-adapted 10 ERG, Light- adapted 3 ERG, and Light-adapted 30 Hz flicker ERG were done. The mean change in a- and b-wave amplitudes as well as implicit times compared to baseline was analyzed. Results A significant reduction in peak amplitudes of both a- and b-waves and delay in latencies were observed in all responses (p Conclusion ERG findings following PRP show reduced retinal function after each session which partially recovers by 6 weeks after the completion of therapy. Clinicians should be mindful of these changes when planning the treatment course for patients with PDR.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum procedure for testing generalized retinal function but encourages more extensive testing. This extended protocol describes a method of assessing the function of the short-wavelength-sensitive cone (S-cone) retinal pathway, using a short-wavelength flash superimposed on a background that saturates the rods and adapts the L/M-cones to elicit a response, known as the S-cone ERG. Stimulus parameters such as the strength and luminance of the flash and background, respectively, and their spectral and temporal characteristics are specified. As a complement to the ISCEV standard, testing the S-cone ERG enables further characterization of light-adapted retinal function and may refine diagnosis of some retinal disorders. Typical applications are described including use in the diagnosis of rod monochromacy and S-cone monochromacy, identification and investigation of cone On-bipolar cell dysfunction and use of the technique to confirm the diagnosis of enhanced S-cone syndrome.

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal. Ocular toxoplasmosis is an infection in the eye caused by the parasite Toxoplasma Gondii. A common retinal finding in its inactive stages is pigmented retinochoroidal scarring. The retinal function in the affected area assumingly reflects the amount of retinal involvement. In this manuscript, we report the case of a 48-year-old woman who has a long-standing large retinochoroidal scar in the temporal posterior pole of her left eye. She had not experienced any visual symptoms, and no re-current infections had occurred as far as she knew. She had a scotoma in her nasal visual field that her optometrist detected by a coincidence when she was in her twenties. The corresponding visual field defect is smaller and less deep than what may be expected from the structural appearance of the scar. The reported case demonstrates that the visual function may be preserved in the visual field corresponding to a retinochoroidal scarred area due to toxoplasmosis, in spite of loss of structures in the outer retinal layers as seen with optical coherence tomography(OCT).

It has been known for over a century that the basic organization of the retina is conserved across vertebrates. It has been equally clear that retinal cells can be classified into numerous types, but only recently have methods been devised to explore this diversity in unbiased, scalable, and comprehensive ways. Advances in high-throughput single-cell RNA-sequencing (scRNA-seq) have played a pivotal role in this effort. In this article, we outline the experimental and computational components of scRNA-seq and review studies that have used them to generate retinal atlases of cell types in several vertebrate species. These atlases have enabled studies of retinal development, responses of retinal cells to injury, expression patterns of genes implicated in retinal disease, and the evolution of cell types. Recently, the inquiry has expanded to include the entire eye and visual centers in the brain. These studies have enhanced our understanding of retinal function and dysfunction and provided tools and insights for exploring neural diversity throughout the brain. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Background Developing easy-to-access biomarkers is crucial in Major Depressive Disorder. The retina has already been suggested as relevant. However, there is a need for a global and local assessment of whole retinal function using a reproducible, standardized protocol allowing for comparison across studies. Our aim is to assess whole retinal function in patients with actual unipolar Major Depressive Episode (MDE) using pattern, flash and multifocal electroretinogram (ERG) according to the International Society for Clinical Electrophysiology of Vision standardized protocols. Methods We assessed retinal function in 14 males and females with MDE, diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders, and in age- and sex-matched healthy controls. Results Comparing the patients with the controls, we observed the following using multifocal ERG: a significant increase in N1 peak time in ring 3 and a decrease in P1 amplitude in ring 2; using pattern ERG: a significant increase in P50 peak time; using flash ERG: a decrease in a- and b-wave peak time and an increase in the b-wave amplitude in dark-adapted 3.0, a decrease in a- and b-wave peak time and an increase in both wave amplitudes in light-adapted 3.0, and a decrease in the b-wave peak time in light-adapted flicker. Limitations Sample size. Contribution of pharmacological treatments to the outcomes cannot be formally excluded. Conclusions Patients with MDE exhibit delayed signaling in the central retina and hyperreactivity to light in the periphery. Central retinal function may be a marker of psychomotor retardation and cognitive impairment in MDE.

The role of the N-Methyl-D-Aspartate Receptor (NMDAR) in the outer retina is unclear despite expression of the NMDAR-complex and its subunits in the outer retina. The flash-electroretinogram (fERG) offers a non-invasive measurement of the retinal field potentials of the outer retina that can serve to clarify NMDAR contribution to early retinal processing. The role of the NMDAR in retinal function was assessed using a genetic mouse model for NMDAR hypofunction (SR-/-), where the absence of the enzyme serine racemase (SR) results in an 85% reduction of retinal D-serine. NMDAR hypo- and hyperfunction in the retina results in alterations in the components of the fERG. The fERG was examined after application of exogenous D-serine to the eye in order to determine whether pre- and post-topical delivery of D-serine would alter the fERG in SR-/- mice and their littermate WT controls. Amplitude and implicit time of the low-frequency components, the a- and b-wave, were conducted. Reduced NMDAR function resulted in a statistically significantly delayed a-wave and reduced b-wave in SR-/- animals. The effect of NMDAR deprivation was more prominent in male SR-/- mice. A hyperfunction of the NMDAR, through exogenous topical delivery of 5 mM D-serine, in WT mice caused a significantly delayed a-wave implicit time and reduced b-wave amplitude. These changes were not observed in female WT mice. There were temporal delays in the a-wave and amplitude and a decrease in the b-wave amplitude and implicit time in both hypo- and NMDAR hyperfunctional male mice. These results suggest that NMDAR and D-serine are involved in the retinal field potentials of the outer retina that interact based on the animal's sex. This implicates the involvement of gonadal hormones and D-serine in retinal functional integrity.

Introduction This study aimed to evaluate whether treatment with fingolimod (FTY) may induce functional changes on the macular pre-ganglionic retinal elements in patients affected by relapsing–remitting multiple sclerosis (RR-MS) without optic neuritis (ON). Methods This case–control observational and retrospective study assessed multifocal electroretinogram (mfERG) responses from 35 healthy controls (mean age 43.58 ± 5.76 years), 41 patients with RR-MS without ON (mean age 40.64 ± 4.83 years, MS-noFTY group), and from 21 patients with RR-MS without ON (mean age 42.38 ± 12.34 years) and treated with fingolimod (Gilenya®, Novartis Europharm, 0.5 mg/day) (MS-FTY group). MfERG N1 and P1 implicit times (ITs), and N1–P1 response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0–5° (R1), 5–10° (R2), 10–15° (R3), 15–20° (R4), 20–25° (R5). We considered R1 and R2 as “central macular areas” and R3, R4 and R5 as “more eccentric retinal areas”. In the MS-FTY group, mfERG recordings were performed between 6 and 12 months (mean 7.2 ± 1.5 months) from the start of FTY. Results In the MS-FTY group, the mean values of mfERG N1 and P1 ITs and RADs detected in both central macular areas (R1 and R2) and in more eccentric retinal areas (R3, R4 and R5) were not significantly different (p > 0.01) with respect to those of control and MS-noFTY groups. Conclusions Our mfERG results suggest that the chronic use of FTY does not induce a dysfunction of pre-ganglionic retinal elements located in the 0–25° of central retina. Since FTY does not cause any retinal functional abnormality, we suggest that FTY treatment could not produce any toxic effect on pre-ganglionic retinal elements even in the absence of macular oedema.

Voltage-gated Ca2+ (Cav) channels play pivotal roles in regulating gene transcription, neuronal excitability, and neurotransmitter release. In order to meet the spatial and temporal demands of visual signaling, Cav channels exhibit unusual properties in the retina compared to their counterparts in other areas of the nervous system. Here, we review current concepts regarding the specific subtypes of Cav channels expressed in the retina, their intrinsic properties and forms of modulation, and how their dysregulation could lead to retinal disease.

Purpose: Retinal photoreceptors layer integrity is considered essential to visual function. We report a case of acute zonal occult outer retinopathy (AZOOR) complex disease (namely AIBSE: acute idiopathic blind spot enlargement) in which apparently a full anatomic regeneration is not needed for a complete functional recovery. Methods: Case report with multimodal imaging. Reports: Visual field recovery in the presence of photoreceptors layer disruption studied by means of Optical Coherence Tomography. Choroid and photoreceptors layer thickness thinned progressively during recovery. Conclusion: This case suggests that anatomical retinal integrity as shown by OCT does not always correspond to visual function. Our case highlights that a complete visual recovery can occur even when structural abnormalities are still observable.

To evaluate the postoperative visual function using a preoperative epiretinal membrane (ERM) classification based on the status of the inner layer structure. We assessed 62 eyes, one from each patient undergoing vitrectomy with internal limiting membrane (ILM) peeling for unilateral ERM. The inclusion criteria were as follows: (1) the presence of idiopathic ERM based on optical coherence tomography and a healthy contralateral eye, (2) successful surgery after 25- or 27-gauge transconjunctival 3-port pars plana vitrectomy with ILM peeling, and (3) a minimum follow-up period of 12 months. We included patients with preoperative ERM morphology with no disruption of the inner retinal layer in group A (37 eyes) and those with disruption in group B (25 eyes) and compared the visual acuity, central visual-field sensitivity (CVFS) measured using the Humphrey field analyzer 10–2 program, and detection rate of micro-scotoma (

The electroretinogram (ERG) has been employed for years to collect information about retinal function and pathology. The usefulness of this noninvasive test depends on our understanding of the cell sources that generate the ERG. Important contributors to the ERG are glial Müller cells (MCs), which are capable of generating substantial transretinal potentials in response to light-induced changes in extracellular K+ concentration ([K+]o). For instance, the MCs generate the slow PIII (sPIII) component of the ERG as a reaction to a photoreceptor-induced [K+]o decrease in the subretinal space. Similarly, an increase of [K+]o related to activity of postreceptor retinal neurons also produces transretinal glial currents, which can potentially influence the amplitude and shape of the b-wave, one of the most frequently analyzed ERG components. Although it is well documented that the majority of the b-wave originates from On-bipolar cells, some contribution from MCs was suggested many years ago and has never been experimentally rejected. In this work, detailed information about light-evoked [K+]o changes in the isolated mouse retina was collected and then analyzed with a relatively simple linear electrical model of MCs. The results demonstrate that the cornea-positive potential generated by MCs is too small to contribute noticeably to the b-wave. The analysis also explains why MCs produce the large cornea-negative sPIII subcomponent of the ERG, but no substantial cornea-positive potential.

Large animal model of optic nerve crush (ONC) plays an important role in translating novel therapeutic strategies developed in rodent model to clinical application. Due to the poor accessibility of the optic nerve (ON) in humans and large animals, lateral orbitotomy is needed to expose the retrobulbar ON. This study was to explore the effects of ONC and ON exposure with lateral orbitotomy (sham surgery) on the outer retinal function and structure in goats by using standard flash electroretinogram (FERG) and spectral-domain optical coherence tomography (SD-OCT). We found that ONC led to a transient reduction in FERG amplitudes at 1 week post injury (wpi), which recovered gradually over 2 months afterwards. Sham surgery alone also caused a similar pattern of amplitude reduction in FERG, although not as significantly as ONC did. Transient outer retinal thickening following ONC occurred at 4 wpi (when progressive thinning of the ganglion cell complex began), peaked at 8 wpi, then recovered gradually at 12 wpi. In contrast, outer retinal thickness remained unchanged statistically 3 months after sham surgery. Fundus fluorescein angiography showed that neither ONC nor ON exposure with lateral orbitotomy significantly caused any significant delay or absence of central retinal vascular filling. In summary, ONC with lateral orbitotomy affects outer retinal function and structure transiently.

Short wavelength automated perimetry (SWAP) is known for detecting the early reduction of retinal sensitivity (RS) in glaucoma. It’s application in retinal diseases have also been discussed previously. We investigated the difference in RS measured between standard white-on-white automated perimetry (WW) and blue-on-yellow SWAP in central serous chorioretinopathy (CSC). The overall RS (W-RS, S-RS) as well as the RS inside and outside of the serous retinal detachment (SRD) region were investigated in 26 eyes of 26 CSC patients using WW and SWAP. The central retinal thickness, central choroidal thickness, SRD area (SRDa), and SRD height at the fovea were measured using optic coherence tomography. RS inside the SRD region was lower than that of outside for both perimetries (both p

AIM: To assess the retinal function in patients with dense cataracts in resource poor settings in Kinshasa, DR Congo. METHODS: In a tertiary eye care center, the Purkinje entoptic test was performed as part of the ophthalmological examination in 98 eyes in patients with cataract, using a penlight. Totally 92 cataract patients including 86 patients suffered from unilateral and 6 from bilateral cataracts were included in the study. The investigator asked the patients about their perception of the vascular pattern most commonly described as a leafless or dead tree. Visual acuity≥6/60 was considered an indication of good visual function and visual acuity

Retinal photoreceptors are important in visual signaling for normal eye growth in animals. We used Gnat2 (cplf3/cplf3) (Gnat2(−/−)) mice, a genetic mouse model of cone dysfunction to investigate the influence of cone signaling in ocular refractive development and myopia susceptibility in mice. Refractive development under normal visual conditions was measured for Gnat2(−/−) and age-matched Gnat2(+/+) mice, every 2 weeks from 4 to 14 weeks of age. Weekly measurements were performed on a separate cohort of mice that underwent monocular form-deprivation (FD) in the right eye from 4 weeks of age using head-mounted diffusers. Refraction, corneal curvature, and ocular biometrics were obtained using photorefraction, keratometry and optical coherence tomography, respectively. Retinas from FD mice were harvested, and analyzed for dopamine (DA) and 3,4-dihydroxyphenylacetate (DOPAC) using high-performance liquid chromatography. Under normal visual conditions, Gnat2(+/+) and Gnat2(−/−) mice showed similar refractive error, axial length, and corneal radii across development (p>0.05), indicating no significant effects of the Gnat2 mutation on normal ocular refractive development in mice. Three weeks of FD produced a significantly greater myopic shift in Gnat2(−/−) mice compared to Gnat2(+/+) controls (−5.40 ± 1.33 D vs −2.28 ± 0.28 D, p=0.042). Neither the Gnat2 mutation nor FD altered retinal levels of DA or DOPAC. Our results indicate that cone pathways needed for high acuity vision in primates are not as critical for normal refractive development in mice, and that both rods and cones contribute to visual signalling pathways needed to respond to FD in mammalian eyes.

Neuronal ceroid lipofuscinoses (CLN) are neurodegenerative disorders among the most frequent, inherited as an autosomal recessive trait. Affected patients can present with progressive decline in cognitive and motor functions, seizures, a shortened life span and visual deficiency. CLN2 is one of the rare CLN that benefits from treatment by cerliponase alpha an enzyme replacement therapy. Preliminary results on treated animal models have shown delayed neurological signs and prolonged life span. However, cerliponase alpha did not prevent vision loss or retinal degeneration in those animal models. Cerliponase alpha has currently been delivered to a few CLN2-affected patients. We report the case of one patient suffering from CLN2 treated with intracerebroventricular infusions of cerliponase alpha 300 mg every two weeks. Evolution of his retinal function was assessed by three successive flash-ERG and flash-VEP recordings throughout his treatment over a 4-year period. Before treatment at the age of 4 years 5 months, patient’s retinas were normal (normal fundi and normal flash-ERG). After 29 infusions at the age of 6 years 10 months, a-wave combined response was absent, while cone and flicker responses were normal. After 80 infusions at the age of 8 years 9 months, a-wave cone response was absent with b-wave peak time increased, and no combined response. Despite treatment, our patient’s retinas showed a progressive abnormal and inhomogeneous function. Rods function was altered first, then the scotopic system and afterward, the cones. This result differs from those recorded in animal models. The relative preservation of cone functioning for a while could not be unequivocally attributed to enzyme replacement therapy as we lack comparison with the evolution of flash-ERGs recorded in untreated subjects.

To evaluate the retinal function and the relative neural conduction along the visual pathway after treatment with citicoline in liposomal formulation (CLF) eye drops in patients with open angle glaucoma (OAG). Twelve OAG patients (mean age ± standard deviation 52.58 ± 11.39 years, intraocular pressure

Cdr1as is the abundant circular RNA (circRNA) in human and vertebrate retinas. However, the role of Cdr1as in the retina remains unknown. In this study, we aimed to generate a Cdr1as knockout (KO) mouse model and investigate the retinal consequences of Cdr1as loss of function. Through in situ hybridization (ISH), we demonstrated that Cdr1as is mainly expressed in the inner retina. Using CRISPR/Cas9 targeting Cdr1as, we successfully generated KO mice. We carried out ocular examinations in the KO mice until postnatal day 500. Compared with the age-matched wild-type (WT) siblings, the KO mice displayed increased b-wave amplitude of photopic electrophysiological response and reduced vision contrast sensitivity. Through small RNA profiling of the retinas, we determined that miR-7 was downregulated, while its target genes were upregulated. Taken together, our results demonstrated for the first time that Cdr1as ablation led to a mild retinal consequence in mice, indicating that Cdr1as abundance is not indispensable for retinal development and maintenance.

BackgroundIntravitreal injections of topotecan are used in the management of retinoblastoma with vitreous seeds. This study evaluated whether intravitreal topotecan was associated with retinal toxicity.MethodsRetrospective cohort study of patients with retinoblastoma who were treated with intravitreal topotecan at Memorial Sloan Kettering Cancer Center between December 2014 and May 2019. Electroretinogram (ERG) responses under anaesthesia were measured immediately before treatment with intravitreal topotecan and at the next visitor approximately one-month. Ocular toxicity was defined by a decrease in the ERG response at 30 Hz at follow-up.ResultsOcular toxicity was evaluated by ERG on 50 evaluable injections administered to 28 eyes. 22 (44.0%) injections were performed with concurrent intravitreal melphalan. The median time to ERG measurement following an injection was 27 days. By using a paired t-test, intravitreal topotecan combined with melphalan (n=22) at a dose of 25 μg or 30 μg was associated with a significant decrease in ERG amplitude at follow-up (p=0.046, 95% CI −20.4 μV to −0.2 μV). Among eyes that only received topotecan (n=28) at doses of 20 μg or 30 μg, there was not a significant difference in ERG amplitude measured (p=0.85, 95% CI −7.0 μV to 5.8 μV).ConclusionIntravitreal topotecan combined with intravitreal melphalan was associated with a decrease in ERG amplitude; there was not a significant decrease in ERG amplitude observed in patients who received topotecan alone. These findings suggest that intravitreal topotecan injections at doses of 20 μg or 30 μg are not associated with retinal toxicity in patients with retinoblastoma.

Introduction Schizophrenia patients often experience auditory hallucinations (AHs) and visual hallucinations (VHs). However, the degree and type of brain and retinal alterations associated with combined AHs and VHs in schizophrenia patients remain unknown. There is an urgent need for a study that investigates the trajectory of brain and retinal alterations in patients with first‐episode untreated schizophrenia accompanied by combined AHs and VHs (FUSCHAV). Methods FUSCHAV patients (n = 120), divided into four groups according to AH and VH symptom severity (severe AHs combined with severe VHs [FUSCHSASV, 20 patients]; middle‐to‐moderate AHs combined with severe VHs [FUSCHMASV, 23 patients]; severe AHs combined with middle‐to‐moderate VHs [FUSCHSAMV, 28 patients]; and middle‐to‐moderate AHs combined with middle‐to‐moderate VHs [FUSCHMAMV, 26 patients]), were compared to healthy controls (n = 30). Gray matter volume (GMV) was adopted for brain structural alteration assessment. Total retinal thickness was adopted as a measure of retinal thickness impairment. Results In the pilot study, the rate of GMV reduction showed an inverted U‐shaped pattern across the different FUSCHAV patient groups according to AH and VH severity. The degree of retinal impairment remained stable across the groups. More notably, in the secondary follow‐up study, we observed that, after 6 months of treatment with antipsychotic agents, all the GMV reduction‐related differences across the different patient groups disappeared, and both GMV and retinal thickness demonstrated a tendency to deteriorate. Conclusions These findings indicate the need for heightened alertness on brain and retinal impairments in patients with FUSCHAV. Further deteriorations induced by antipsychotic agent treatment should be monitored in clinical practice., (1) GMV reduction and gFCD increases in the frontal–parietal lobule of FUSCHAV patients demonstrate an inverted U‐shape pattern according to differences in AH and VH severity, indicating functional compensation correlated with volume reduction. (2) There appears to be reciprocal deterioration in auditory and visual disturbances among FUSCHAV patients as observed through both brain and retinal abberations. (3) Although brain alterations in FUSCHAV patients differ with degree of AH and VH severity, retinal impairment remains constant among FUSCHAV groups.

Achromatopsia causes severely reduced visual acuity, photoaversion, and inability to discern colors due to cone photoreceptor dysfunction. In 2010, we reported on day-blindness in sheep caused by a...

To compare retinal function changes in eyes with proliferative diabetic retinopathy (PDR) after intravitreal ranibizumab (IVR), combined or not with conventional (ETDRS) or multispot laser panretinal (PASCAL) photocoagulation (PRP). This study included laser-naive PDR patients that required PRP. Eyes were randomly and prospectively assigned to receive IVR or IVR combined with PASCAL or EDTRS. PRP was performed at baseline in 1 (PASCAL) or 2 (ETDRS) sessions. In eyes with macular edema, macular short pulse grid laser was associated with IVR at baseline and IVR was repeated monthly or quarterly if neovascularization was detected on angiography. Comprehensive ophthalmological evaluations, including SD-OCT, were performed at baseline and every 4 weeks after treatment. Full-field electroretinography (ERG: extended ISCEV standard) was performed at baseline and at 12, 24 and 48 weeks. IVR = 13, PASCAL = 15 and ETDRS = 15 eyes finished 48-week follow-up. There was a statistically significant BCVA improvement of 0.1–0.3 logMAR in all groups, and fluorescein angiography leakage area (FLA) reduced in 56%, 73%, and 73% from baseline for ETDRS, IVR and PASCAL, respectively, up to 48 weeks without significant differences between groups (p > 0.05). A significant a- and b-wave amplitudes reduction was observed for dark- and light-adapted ERG for ETDRS and PASCAL, but only minor dark-adapted b-wave reduction was found for IVR, up to 48 weeks. As an example, at week 48, combined response b-wave amplitude reduced in 181.5 ± 31.4 µV, 128.0 ± 27.9 µV and 82.4 ± 15.2 µV for ETDRS, PASCAL and IVR (p

Although congenital stationary night blindness (CSNB) has been described in a Japanese beagle dog research colony, certain clinical correlates with human CSNB have not yet been described, nor has an estimate of frequency of the condition been made in inbred and outbred beagle populations. A beagle with CSNB obtained from a commercial research dog supplier in the USA and matched control dogs (n = 3) underwent examination, refraction, ocular imaging, assessment of visual navigation ability and detailed electroretinography (ERG). Retrospective review of ERGs in two independent groups of inbred (n = 15 and 537, respectively) and one group of outbred dogs (n = 36) was used to estimate CSNB frequency in these populations. In the affected dog, there were absent dark-adapted b-waves in response to dim-light flashes, severely reduced dark-adapted b-waves in response to bright-light flashes, and normal light-adapted b-waves with a-waves that had broadened troughs. Long-flash ERGs confirmed a markedly reduced b-wave with a preserved d-wave, consistent with cone ON-bipolar cell dysfunction. There was evidence of normal rod photoreceptor a-wave dark adaptation, and rapid light adaptation. In the wider beagle populations, five inbred beagles had a b/a wave ratio of

Purpose To establish whether there is cone contribution to retinal function and structure in chinchillas (Chinchilla lanigera), in view of the prevailing notion that this species possesses a pure rod retina. Methods Photopic electroretinography (ERG) responses to high-intensity flashes (10 and 25 cd*s/m2 ) were recorded unilaterally in six pigmented chinchillas following 10 minutes of light adaptation (30 cd/m2 ). Retinas of two animals were studied histologically, and immunohistochemistry (IHC) was conducted to detect the presence of short and medium/long wavelength cone photoreceptors. Results ERG recordings revealed photopic responses, albeit of low amplitudes. Histopathology demonstrated presumptive cone inner segments in the photoreceptor layer. Presence of cone photoreceptors was confirmed by IHC. Cone density was higher in the central retina, and red/green cones outnumbered blue cones. Conclusions Our results provide convincing evidence for the presence of functioning cone photoreceptors in the chinchilla retina, disproving the established belief that the species has a pure rod retina.

Electronic displays have become an integral part of life in the developed world since the revolution of mobile computing a decade ago. With the release of multiple consumer-grade virtual reality (VR) and augmented reality (AR) products in the past 2 years utilizing head-mounted displays (HMDs), as well as the development of low-cost, smartphone-based HMDs, the ability to intimately interact with electronic screens is greater than ever. VR/AR HMDs also place the display at much closer ocular proximity than traditional electronic devices while also isolating the user from the ambient environment to create a “closed” system between the user's eyes and the display. Whether the increased interaction with these devices places the user's retina at higher risk of damage is currently unclear. Herein, the authors review the discovery of photochemical damage of the retina from visible light as well as summarize relevant clinical and preclinical data regarding the influence of modern display devices on retinal health. Multiple preclinical studies have been performed with modern light-emitting diode technology demonstrating damage to the retina at modest exposure levels, particularly from blue-light wavelengths. Unfortunately, high-quality in-human studies are lacking, and the small clinical investigations performed to date have failed to keep pace with the rapid evolutions in display technology. Clinical investigations assessing the effect of HMDs on human retinal function are also yet to be performed. From the available data, modern consumer electronic displays do not appear to pose any acute risk to vision with average use; however, future studies with well-defined clinical outcomes and illuminance metrics are needed to better understand the long-term risks of cumulative exposure to electronic displays in general and with “closed” VR/AR HMDs in particular. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:346–354.]

Pigmented and albino rabbits are commonly used in visual research; however, the lack of pigment in the eyes may affect retinal responses. Here, we compare and describe the differences of retinal function between pigmented (English Butterfly) and albino (New Zealand) rabbits. Electroretinograms were recorded in pigmented and albino rabbits in the dark-adapted eye, in the light-adapted eye and for four temporal frequencies in the light-adapted eye. The implicit time and amplitude of the a- and b-waves were analyzed, as well as the amplitude and phase of the first harmonic component of the photopic flicker response. Albino rabbits presented significantly larger amplitudes for both a- and b-waves at all intensities and frequencies. The intensity–response function of the scotopic b-wave also showed that the albino retina is more sensitive than the pigmented retina and the larger flicker amplitudes found in the albino group also revealed post-receptoral changes specifically related to cone pathways. The larger amplitude of albino receptoral and post-receptoral activities might be attributed to greater availability of light due to scatter and reflection at the retinal layer, and as the differences in response amplitudes between the groups increase with flicker frequency, we suggest that ON bipolar cells recover faster in the albino group, suggesting that this might be a mechanism to explain the higher temporal resolution for albinos compared to the pigmented group.

Objective: This case report presents a patient with central retinal artery occlusion (CRAO) who was successfully treated with hyperbaric oxygen (HBO2) but subsequently suffered a recurrence of his visual loss. Methods: CRAO may be treated successfully with HBO2 if treatment is undertaken promptly after the onset of vision loss. The goal ofHBO2 therapy is to oxygenate the ischemic inner retinal layers via diffusion from the hyperoxygenated choroidal circulation until recanalization of the central retinal artery occurs. Results: A 71-year-old man presented with hand motion vision and fundus findings of CRAO in his left eye. Treatment with HBO2 was initiated approximately 9.5 hours after loss of vision. The patient experienced return of vision to a near-normal level during HBO2. His vision loss recurred, however, 15 minutes after the HBO2 session. There was a delay to follow-up HBO2 treatments, and the improvement of vision that resulted from these subsequent HBO2 sessions was much less than that experienced during his initial HBO2 treatment. Conclusions: Recovery of vision during initial HBO2 treatment indicated that this patient’s retina had not yet suffered irreversible ischemic damage at that point in time. CRAO patients with a good result from initial HBO2 treatment should be admitted to a stroke center and should have their visual status monitored hourly. Should vision loss recur, ag- gressive use of intermittent 100% normobaric and hyperbaric oxygen is indicated to preserve retinal function until central retinal artery recanalization occurs. An evidence-based management plan for such patients is presented.

Purpose To compare per-region macular sensitivity and delay from objective perimetry with Matrix perimetry and retinal thickness in mild diabetic macular edema (DMO). Methods Thirty-three patients with type 2 diabetes (T2D) aged 59.2 ± 10.5 years participated in a longitudinal study. Macular thickness, sensitivities and delays from the objectiveFIELD Analyzer (OFA), and Matrix perimeter sensitivities were mapped onto a common spatial layout to compute per-region correlations between structure/function measures. A generalized linear mixed-effects logistic regression model determined which variables contributed to clinical diagnosis of DMO. Results For OFA, the mean sensitivity differences compared with normal in patients with T2D were negative and the mean delay differences positive, indicating lowered sensitivities and prolonged delays, both increasing with diabetes duration. Shorter diabetes duration could produce either localized peripheral hypersensitivities or shorter delays. Functional change could occur when retinal thickness was stable. Peripheral macular thickness correlated with central and peripheral OFA sensitivity and delay, all P < 0.0012 in DMO and a median of P = 0.001 without DMO; this was not true for Matrix sensitivities. The logistic model determined that peripheral thickness, OFA sensitivity (P = 0.043), and time in the study (P = 0.001) contribute independently to the odds of DMO versus no DMO. Conclusions Mean sensitivities decreased and mean delays increased with duration of diabetes. Peripheral macular thickness correlated significantly with central and peripheral macular OFA sensitivity and delay. Peripheral macular thickness and functional measures may provide sensitive prognostic data. Translational Relevance Functional loss can precede structural change in DMO, so including such functional assessment for deciding on treatment may be beneficial.

This review summarizes the pathological features of diabetic retinopathy. The lesions occurring in the diabetic retina have been described over many decades using descriptive and experimental approaches based on clinical studies on patients, human post-mortem material, animal models and various in vitro systems. We have also accumulated a wealth of knowledge about basic molecular mechanisms and key pathogenic processes that drive these abnormalities in diabetic retina. Despite these advances, there are still limited therapeutic options for diabetic retinopathy with those currently available only addressing late-stage disease. With a particular focus on the earlier stages of diabetes, there is growing appreciation the complex neuronal, glial and microvascular abnormalities which progressively disrupt retinal function. This is especially true from the perspective of the neurovascular unit during health and disease. Based on a strong appreciation of cellular and molecular pathology that underpins diabetic retinopathy, further advances are anticipated as we drive towards development of efficacious therapeutic options that can address all stages of disease.

Psychiatry and neuroscience research need novel approaches to indirectly investigate brain function. As the retina is an anatomical and developmental extension of the central nervous system (CNS), changes in retinal function may reflect neurological dysfunctions in psychiatric disorders. The last and most integrated retinal relay before visual information transfer to the brain is the ganglion cell layer. Here, based on collected arguments, we argue that these cells offer a crucial site for indirectly investigating brain function. We describe the anatomical and physiological properties of these cells together with measurements of their functional properties named pattern electroretinogram (PERG). Based on ganglion cell dysfunctions measured with PERG in neurological disorders, we argue for the relevance of studying ganglion cell function in psychiatric research. We review studies that have evaluated ganglion cell function in psychiatric and addictive disorders and discuss how changes in PERG measurements could be functional markers of pathophysiological mechanisms of psychiatric disorders.

Computational models of the neural retina simulate the response of the retina to input light. In their most detailed form, the models yield neural output as a spatially varying pattern of spike trains which fully encode the incident dynamic image. In vivo, this retinal output is relayed to higher vision processing centers in the brain such as the lateral geniculate nucleus and the primary visual cortex in humans and primates. Neural retinal models assist not only in the understanding of normal and abnormal retinal function, but are useful for investigating retinal response to artificial stimuli such as electrical stimulation by a vision prostheses.