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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.

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.

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.

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.

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.]

Impaired dark adaptation (DA), a defect in the ability to adjust to dimly lit settings, is a universal hallmark of aging. However, the mechanisms responsible for impaired DA are poorly understood. Vitamin A byproducts, such as vitamin A dimers, are small molecules that form in the retina during the vitamin A cycle. We show that later in life, in the human eye, these byproducts reach levels commensurate with those of vitamin A. In mice, selectively inhibiting the formation of these byproducts, with the investigational drug C20D3-vitamin A, results in faster DA. In contrast, acutely increasing these ocular byproducts through exogenous delivery leads to slower DA, with otherwise preserved retinal function and morphology. Our findings reveal that vitamin A cycle byproducts alone are sufficient to cause delays in DA and suggest that they may contribute to universal age-related DA impairment. Our data further indicate that the age-related decline in DA may be tractable to pharmacological intervention by C20D3-vitamin A.

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...

We aimed to establish a highly sensitive method for measuring visual function using spatial-sweep steady-state pattern electroretinography (swpPERG). Overall, 35 eyes of 35 healthy adults (18 men; mean age, 32.3 years) were examined using swpPERG, and the data were recorded using spatial-patterned and contrast-reversed stimuli of size 1 (thickest) to 6. Data were converted into frequency-domain using a Fourier transform and expressed by signal-to-noise ratio (SNR). The number of participants who showed SNR ≥ 1 was significantly lesser at stimulus sizes 5 and 6 compared with those at greater stimulus sizes. Among the data with SNR ≥ 1, SNRs were negatively correlated with age at stimulus size 5 (r = −0.500, P = 0.029), and positively correlated with macular volume evaluated by optical coherence tomography (OCT) within a 6-mm circle diameter from the fovea of the retinal nerve fibre layer at size 4 (r = 0.409, P = 0.025) and of the ganglion cell layer at size 5 (r = 0.567, P = 0.011). We found that SNRs of swpPERG, recorded using the EvokeDx system, were correlated with age and macular morphology in participants without diagnosed eye diseases. The system detected subtle differences in retinal function, which may help in early disease diagnosis and visual evaluation in neuroprotective interventions in the future.

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).

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.

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

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.

Background: The acute physiological changes induced by focal retinal photocoagulation (PC) have been largely unexplored. Methods: This was a case-series study. We recorded multifocal electroretinograms (mfERGs) just before PC, and mfERGs were also recorded 5&prime, 15&prime, one hour, 24 h, and one week after the PCs. Transient changes of mfERGs were analyzed in eyes which underwent PCs to treat diabetic macular edema. The mfERGs recorded from the predominantly irradiated area and that from non-irradiated areas were analyzed separately. Results: Fifteen eyes of 15 patients were included in this study. The mfERGs elicited from non-irradiated areas did not change after PC, but the mfERGs elicited from the irradiated area changed with time, the amplitude was larger at 60&prime, than that before (p &lt, 0.05) and at 5&prime, after PC (p &lt, 0.01) and significantly smaller at 24 h and 1 week than that before and at 60&prime, after the PC (p &lt, 0.01). The implicit time was significantly prolonged after PC. mfERG on irradiated area with the severe diabetic change was less altered after PCs. Conclusions: The transient increase in the amplitude at 60&prime, likely resulted from a biological amplification of partially damaged cells adjacent to the PC spots. The mfERGs manifested the dynamic alterations of the retinal function following PCs.

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 (

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.

Most animal models of glaucoma rely on induction of ocular hypertension (OHT), yet such models can suffer from high IOPs leading to undesirable retinal ischemia. Thus, animals with IOPs exceeding a threshold (e.g. > 60 mmHg) are often excluded from studies. However, due to the intermittent nature of IOP measurements, this approach may fail to detect ischemia. Conversely, it may also inappropriately eliminate animals with IOP spikes that do not induce ischemic damage. It is known that acute ischemia selectively impairs inner retinal function, which results in a reduced b-wave amplitude. Here, we explore the potential of using electroretinography (ERG) to detect ischemic damage in OHT eyes. 74 Brown Norway rats received a unilateral injection of magnetic microbeads to induce OHT, while contralateral eyes served as controls. IOP was measured every 2–3 days for 14 days after microbead injection. Retinal function was evaluated using dark-adapted bright flash ERG (2.1 log cd•s/m2) prior to, and at 7 and 14 days after, injection. We investigated two criteria for excluding animals: (IOP Criterion) a single IOP measurement > 60 mmHg; or (ERG Criterion) a b-wave amplitude below the 99.5% confidence interval for naive eyes. 49 of 74 rats passed both criteria, 7 of 74 failed both, and 18 passed one criterion but not the other. We suggest that ERG testing can detect unwelcome ischemic damage in animal models of OHT. Since brief IOP spikes do not necessarily lead to ischemic retinal damage, and because extended periods of elevated IOP can be missed, such ERG-based criteria may provide more objective and robust exclusion criteria in future glaucoma studies.

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

Background: In retinitis pigmentosa (RP), inherited rod death is followed by cone loss and blindness. Why cones die is still a matter of consideration. Here, we investigate the pathogenic role of the sympathetic transmission in the rd10 mouse model of RP. Methods: Retinal levels of beta adrenergic receptor (BAR) 2 and norepinephrine (NE) were measured. After administration of the BAR1/2 blocker propranolol or the hypoxia-inducible factor (HIF)-1 activator dimethyloxalylglycine (DMOG), retinal levels of HIF-1&alpha, BAR2 or proteins involved in BAR2 desensitization were also measured. In DMOG treated mice, expression and localization of BAR2, inflammatory markers and cone arrestin were determined. Finally, rd10 mice were subjected to electroretinogram (ERG) analysis to assess rod and cone function. Results: In the rd10 retina, BAR2 overexpression and NE accumulation were found, with BAR2 immunoreactivity localized to M&uuml, ller cells. BAR2 overexpression was likely due to desensitization defects. Upregulated levels of BAR2 were drastically reduced by propranolol that also restored desensitization defects. Due to the low level of HIF-1 consequent to the hyperoxic environment in the rd10 retina, we hypothesized a link between HIF-1 and BAR2. HIF-1&alpha, stabilization with DMOG resulted in i. increased HIF-1&alpha, accumulation, ii. decreased BAR2 levels, iii. restored desensitization processes, iv. reduced expression of inflammatory markers and v. increased cone survival without improved retinal function. Conclusions: Our results support a pathogenic role of the sympathetic system in RP that might help to understand why rd10 mice show a positive response to BAR blockers.

Purpose Intravitreal injections of antivascular endothelial growth factor agents are widely performed, and subsequent intraocular pressure increase may cause retinal nerve fiber damage. This study aimed to determine the effects of paracentesis before intravitreal injection of an antivascular endothelial growth factor on electroretinograms. Methods This was a retrospective observational study in a university hospital. Twenty-five eyes of 25 patients who underwent intravitreal injections of antivascular endothelial growth factor agents were selected for evaluation. Intraocular pressures and electroretinograms were recorded before surgery (baseline), after anterior chamber paracentesis, and after intravitreal injection. The amplitudes and latencies of the a- and b-waves, photopic negative response, and oscillatory potential were measured. Changes in each component of the electroretinograms, intraocular pressure, and relationships between these two factors were investigated. The preoperative and postoperative ocular perfusion pressure was calculated based on blood pressure. Results The amplitudes of the b-waves were significantly smaller after intravitreal injection than at baseline (P = 0.02), while no significant change was found in the other components during surgery. There were no significant changes in the latencies of any component during surgery. The intraocular pressure was significantly lower (P < 0.001) after anterior chamber paracentesis (6.8 ± 4.3 mm Hg) compared to baseline (24.1 ± 8.1 mm Hg) or after intravitreal injection (17.1 ± 9.6 mm Hg; P < 0.001). Conclusions Performing anterior chamber paracentesis before an intravitreal injection can prevent the intraocular pressure elevation and thus minimize the electrophysiological retinal dysfunction. Translational Relevance Anterior chamber paracentesis before an intravitreal injection mitigates the adverse effects on retinal function.

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...

Background The retinal microcirculation has been studied in various diseases including multiple sclerosis (MS). However, inter-eye correlations and potential differences of the retinal blood flow velocity (BFV) remain largely unstudied but may be important in guiding eye selection as well as the design and interpretation of studies assessing or utilizing retinal BFV. The primary aim of this study was to determine inter-eye correlations in BFVs in healthy controls (HCs). Since prior studies raise the possibility of reduced BFV in MS eyes, a secondary aim was to compare retinal BFVs between MS eyes, grouped based on optic neuritis (ON) history and HC eyes. Methods Macular arteriole and venule BFVs were determined using a retinal function imager (RFI) in both eyes of 20 HCs. One eye from a total of 38 MS patients comprising 13 eyes with ON (MSON) and 25 eyes without ON (MSNON) history were similarly imaged with RFI. Results OD (right) and OS (left) BFVs were not significantly different in arterioles (OD: 3.95 ± 0.59 mm/s; OS: 4.08 ± 0.60 mm/s, P = 0.10) or venules (OD: 3.11 ± 0.46 mm/s; OS: 3.23 ± 0.52 mm/s, P = 0.06) in HCs. Very strong inter-eye correlations were also found between arteriolar (r = 0.84, P

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 : The RETeval system (LKC Technologies, Inc., Gaithersburg, MD, USA) is a hand-held device for recording electroretinogram (ERG) responses with skin electrodes, placed over the lower eyelid, close to the lid margin. Some subjects find this uncomfortable due to proximity to eyelashes. We explored the effect of changing electrode position in healthy subjects. Methods : Photopic flicker ERGs were recorded in 120 healthy twins as part of a wider study. For 48 subjects (Group 1), recording electrodes were placed in “comfortable” positions, even if this was 1-2 cm below the lid margin. For 72 subjects (Group 2), the lid margin position was used as recommended by the manufacturer. Photopic flicker and flash ERGs were recorded for an additional 5 healthy subjects in two consecutive recording sessions: in the test eye, the electrode was placed just below the lid margin in the first session, and 1.5 cm below in the second; in the fellow eye (control eye), the electrode was just below the lid margin throughout. Amplitudes and implicit times (test eye normalised to control eye) were compared for the two sessions. Pupils were undilated; stimuli were designed to deliver the same retinal illuminance as international standard stimuli. Results : For Group 1, mean (SD) flicker ERG amplitudes were 22.9 (13.1) and 22.4 (13.3) µV for right and left eye respectively. Implicit times were 25.8 (2.1) and 25.9 (1.1) ms. For subjects with consistent positioning at the lid margin, amplitudes were 35.3 (10.1) and 37.6 (17.3) µV; implicit times were 25.3 (1.1) and 26.1 (2.4) ms. Mean amplitudes were significantly lower for the first group (p 0.2). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly smaller when positioned 1.5 cm from the lid margin (p 0.6). Conclusions : Moving RETeval electrodes further from the lid margin significantly reduces response amplitudes, but does not significantly affect implicit times. The study highlights the importance of consistent electrode positioning. However, in research studies in which participants may find standard electrode positions uncomfortable, it may be feasible to alter the position if analysis is restricted to implicit time parameters. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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.

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.

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.

Introduction To prevent local reduction in retinal function caused by retained subretinal perfluorocarbon liquid (PFCL), it has been noted that removal of PFCL under the fovea should be considered, with a vitrectomy selected for such removal. Case Report A vitrectomy was performed for traumatic retinal detachment during which PFCL was temporarily used as an intraocular tamponade for retina flattening. Following surgery, subfoveal PFCL was retained beneath the retina. Two months later, a macular hole developed and visual acuity decreased to 20/100, for which a vitrectomy was planned as treatment. However, the macular hole spontaneously closed and visual acuity eventually recovered to 20/25. Conclusion Our findings indicate that PFCL retained underneath the retina in the macular region can cause a macular hole, though spontaneous discharge may subsequently occur, leading to resolution.

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.

In the present study, we investigated whether blue light emission diode (LED) light exposure affects the maternal behavior of mice. The brain function of the offspring mice, including short-term memory, locomotor activity, anxiety-like behavior, and depression-like behavior, was evaluated. Pregnant mice at day 11 were housed in the apparatus for exposure to blue LED light during the daytime. Nesting behavior and the survival of pups were observed until weaning. After weaning, the offspring mice were bred in normal light conditions until 12 weeks old, and then the Y-maze test, open field test, and tail suspension test were performed. Retinal functions were evaluated by electroretinogram and histological analysis. Blue LED light exposure during the daytime induced retinal damage, but did not affect behavior related to maternal care in maternal mice. In the offspring mice, blue LED light exposure during the daytime did not affect the retina or brain functions. These findings suggest that blue LED light during the daytime might not be a risk factor for disruption of the mother-infant relationship or offspring brain development in mice.

Effects of triamcinolone acetonide (TA) combined with aminoguanidine (AG) on vascular endothelial function, vascular endothelial growth factor (VEGF) expression and retinal function in diabetic retinopathy (DR) patients were studied. A total of 100 patients with DR admitted to the Taizhou Second People's Hospital Affiliated to Yangzhou University from January 2016 to December 2018 were collected and randomly divided into observation group (n=50) and control group (n=50). The control group was only treated with TA (4 mg), while the observation group was additionally treated with AG (50 mg/kg). The therapeutic effect and adverse reactions were observed, and the changes in blood glucose (GLU), blood lipid, serum inflammatory cytokines and oxidative stress indexes before and after treatment were detected. Moreover, the serum VEGF level was examined, the central macular thickness (CMT), retinal neovascularization (RNV) leakage area and best corrected visual acuity (BCVA) of retinopathy were observed, and the vascular endothelial function indexes such as nitric oxide (NO), endothelin-1 (ET-1) and intercellular adhesion molecule-1 (ICAM-1) were detected. The therapeutic effect in the observation group was significantly better than that in control group (P

PURPOSE To evaluate the effect of ultraviolet A radiation on retinal function and structure after the corneal collagen crosslinking procedure. METHODS In the present prospective, single-center cohort study 17 eyes of 17 patients who underwent collagen crosslinking (Dresden protocol) for the treatment of corneal ectasia were examined preoperatively and at 2 and 6 weeks postoperatively with multifocal electroretinogram and optical coherence tomography. The P1 amplitude density (P1-AD) of the central retinal response was documented in 5 concentric rings, with ring 1 (R1) representing the foveal response and rings 2 to 5 (R2-R5) corresponding to successive annuli of stimulation. Visual acuity, corneal densitometry at the 0 to 2 mm zone and at the 2 to 6 mm annulus, and macular thickness (MT; central, 1 mm, 3 mm, and 5 mm zones) were recorded. RESULTS The preoperative values of P1-AD were R1 = 109.96 ± 28.96, R2 = 49.8 ± 14.46, R3 = 29.85 ± 8.9, R4 = 19.33 ± 6.3, and R5 = 16.39 ± 5.48 nV/deg. At 2 weeks, these values were R1 = 77.54 ± 24.47, R2 = 36.55 ± 12.53, R3 = 21.53 ± 7.71, R4 = 15.3 ± 6.13, and R5 = 13.32 ± 5.48, showing a significant reduction for R1-R4 (P ≤ 0.026). The 6-week P1-AD was R1 = 99.8 ± 31.23, R2 = 40.67 ± 16.39, R3 = 24.98 ± 7.13, R4 = 16.35 ± 4.84, and R5 = 13.76 ± 3.98, showing no significant differences compared with preoperative values (P ≥ 0.054). Corneal densitometry increased significantly at 2 weeks (P < 0.001) and remained increased at 6 weeks (P < 0.001), showing statistically insignificant correlations with 2-week P1-AD (P ≥ 0.553). The central MT increased (P = 0.787), whereas MT at 1 mm (P = 0.444), 3 mm (P = 0.039), and 5 mm (P < 0.001) zones decreased. CONCLUSIONS The return of P1-AD to preoperative (physiologic) values at 6 weeks confirms the safety standards of the duration and intensity of ultraviolet A radiation, as proposed by the Dresden protocol. However, temporary postoperative retinal dysfunction cannot be excluded.

Background A great body of evidence suggests that there are retinal functional and structural changes that occur in Alzheimer’s disease (AD). However, whether such changes are primary or secondary remains to be elucidated. We studied a range of retinal functional and structural parameters in association with AD- specific pathophysiological markers in the double transgenic APP/PS1 and control mice across age. Methods Electroretinogram (ERG) and optical coherence tomography (OCT) was performed in APP/PS1 and wild type (WT) control mice every 3 months from 3 to 12 months of age. For functional assessment, the a- and b-wave of the ERG, amplitude of oscillatory potentials (OP) and the positive scotopic threshold response (pSTR) were quantified at each time point. For structural assessment, the inner and outer retinal thickness was segmented and measured from OCT scans. Episodic memory was evaluated at 6, 9 and 12 months of age using the novel object recognition test. Amyloid beta (Aβ) distribution in the hippocampus and the retina were visualised at 3, 6 and 12 months of age. Inter- and intra- group analysis was performed to study rate of change for each parameter between the two groups. Results Inter-group analysis revealed a significant difference in b-wave and OPs of APP/PS1 compared to WT controls starting from 3 months (p p p Conclusions We observed an age-related decline in retinal functional and structural parameters in both APP/PS1 and WT controls, however, inter-group analysis revealed that inner retinal functional and structural decline is exacerbated in APP/PS1 mice, and that retinal functional changes precede structural changes in this strain. Further studies are required to confirm whether such phenomenon occurs in humans and if studying retinal functional changes can aid-in early assessment of AD.

Retinal vascular and neuronal degeneration are established pathological features of diabetic retinopathy. Data suggest that defects in the neuroglial network precede the clinically recognisable vascular lesions in the retina. Therefore, new treatments that target early-onset neurodegeneration would be expected to have great value in preventing the early stages of diabetic retinopathy. Here, we show that the nucleoside reverse transcriptase inhibitor lamivudine (3TC), a newly discovered P2rx7 inhibitor, can attenuate progression of both neuronal and vascular pathology in diabetic retinopathy. We found that the expression of P2rx7 was increased in the murine retina as early as one month following diabetes induction. Compared to non-diabetic controls, diabetic mice treated with 3TC were protected against the formation of acellular capillaries in the retina. This occurred concomitantly with a maintenance in neuroglial function, as shown by improved a- and b-wave amplitude, as well as oscillatory potentials. An improvement in the number of GABAergic amacrine cells and the synaptophysin-positive area was also observed in the inner retina of 3TC-treated diabetic mice. Our data suggest that 3TC has therapeutic potential since it can target both neuronal and vascular defects caused by diabetes.

Purpose To compare retinal function by using fundus-guided microperimetry (MP) and multifocal electroretinography (mfERG) for detecting hydroxychloroquine (HCQ) maculopathy. Methods Forty-six eyes of 25 patients referred to our clinical practice for HCQ maculopathy assessment and 3 groups of normal control subjects were evaluated by mfERG and MP. Macular structure was assessed using spectral-domain optical coherence tomography (SD-OCT). Ring ratios from the three innermost mERG rings were compared with average sensitivity of each MP ring at approximately equivalent distances from the fovea. HCQ toxicity was defined as an mfERG ring ratio or mean MP ring sensitivity >2 standard deviations below the normal mean. The sensitivity and specificity of MP to detect HCQ toxicity relative to mfERG were evaluated. Results MP rings MR2 and MR3 were positively correlated with corresponding mfERG ring ratios (r = 0.52, P = 0.002 and r = 0.56, P < 0.001 respectively). Ring 2 and ring 3 measures of MP and mfERG were significantly worse in HCQ eyes than controls (P < 0.001). The sensitivity of MP to detect toxicity for MR1 through MR3 ranged from 33% to 88%, whereas specificity ranged from 72% to 85%. Through rings 1 to 3, the frequency of abnormal function ranged from 20% to 48% for MP, 11% to 35% for mfERG, and 41% to 45% for SD-OCT. Conclusions The frequency of detection of HCQ toxicity with MP was greater than with mfERG. MP showed an overall good sensitivity and moderate specificity in detecting HCQ-induced functional deficits. Translational Relevance Results from this study may allow clinicians to improve screening accuracy for HCQ toxicity by using the alternative modality of MP.

Introduction: Central and paracentral retinal function is often compromised in various retinal diseases. In these conditions, microperimetry is an important tool for assessing retinal sensitivity values. As retinal diseases are prevalent among the elderly, cataract often coexists. This study investigates the effect of cataract surgery on retinal sensitivity in patients with cataract without retinal disease. Material and Methods: A total of 30 patients already scheduled for cataract surgery were enrolled and microperimetry and visual acuity evaluation was performed before and after cataract extraction. The patients were allocated to 1 of 3 study groups in accordance with the main cataract subtype: nuclear, cortical, or posterior subcapsular (PSC) cataract. Results: Visual acuity increased significantly after cataract surgery (from 0.34 to 0.00 logMar, p < 0.001, paired t test). Similarly, median retinal sensitivity increased significantly from 23 dB (IQR 21–25 dB) to 27 dB (IQR 25.75–28 dB) (p < 0.001, Wilcoxon test). The increase of retinal sensitivity after cataract surgery was highest in the PSC cataract group. Conclusion: This study showed an increase in retinal sensitivity values after cataract removal, especially in the PSC group. Therefore, coexisting cataract should be considered when interpreting microperimetry results.