Neuroplasticity of visual brain network induced by hypoxia.

The effects of hypoxia on brain function remain largely unknown. This study aimed to clarify this issue by visual-stimulated functional magnetic resonance imaging design. Twenty-three college students with a 30-d high-altitude exposure were tested before, 1 week and 3 months after returning to sea level. Brain functional magnetic resonance imaging and retinal electroretinogram were acquired. One week after returning to sea level, decreased blood oxygenation level dependent in the right lingual gyrus accompanied with increased blood oxygenation level dependent in the frontal cortex and insular cortex, and decreased amplitude of electroretinogram a-wave in right eye; moreover, the bilateral lingual gyri showed increased functional connectivity within the dorsal visual stream pathway, and the blood oxygenation level dependent signals in the right lingual gyrus showed positive correlation with right retinal electroretinogram a-wave. Three months after returning to sea level, the blood oxygenation level dependent signals recovered to normal level, while intensively increased blood oxygenation level dependent signals in a broad of brain regions and decreased retinal electroretinogram were also existed. In conclusion, hypoxic exposure has long-term effects on visual cortex, and the impaired retinal electroretinogram may contribute to it. The increased functional connectivity of dorsal stream may compensate for the decreased function of retinal photoreceptor cells to maintain normal visual function.

Remyelination-oriented clemastine treatment attenuates neuropathies of optic nerve and retina in glaucoma.

As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells (RGCs). It is widely accepted that the level of intraocular pressure (IOP) is a major risk factor in human glaucoma, and reduction of IOP level is the principally most well-known method to prevent cell death of RGCs. However, clinical studies show that lowering IOP fails to prevent RGC degeneration in the progression of glaucoma. Thus, a comprehensive understanding of glaucoma pathological process is required for developing new therapeutic strategies. In this study, we provide functional and histological evidence showing that optic nerve defects occurred before retina damage in an ocular hypertension glaucoma mouse model, in which oligodendroglial lineage cells were responsible for the subsequent neuropathology. By treatment with clemastine, an Food and Drug Administration (FDA)-approved first-generation antihistamine medicine, we demonstrate that the optic nerve and retina damages were attenuated via promoting oligodendrocyte precursor cell (OPC) differentiation and enhancing remyelination. Taken together, our results reveal the timeline of the optic neuropathies in glaucoma and highlight the potential role of oligodendroglial lineage cells playing in its treatment. Clemastine may be used in future clinical applications for demyelination-associated glaucoma.

Silencing of ocular transthyretin, a gene responsible for hereditary transthyretin amyloidosis, by intravitreal injection of an siRNA conjugate into rabbit eyes.

The first small interfering RNA (siRNA) therapeutic received approval for hereditary transthyretin (ATTRv) amyloidosis, and the patients' lifespan extension by specific inhibition of hepatic synthesis of transthyretin (TTR) is expected. However, ocular amyloidosis in these patients has been a crucial issue. This study aims to evaluate the efficacy and safety of intravitreal TTR siRNA conjugate injection into rabbit eyes. Rabbit (r) TTR siRNA is a screened TTR siRNA conjugate from 53 candidates. The intraocular pressure (IOP) immediately after injection was high despite the 65.9 % decrease of aqueous humor TTR protein levels in the rTTR siRNA group compared with those in the Control siRNA group 2 weeks after the 50 µL siRNA injection. The IOP spike was milder after the 30 µL siRNA injection, and aqueous humor TTR levels decreased by ∼50 % in the rTTR siRNA group, which is consistent with the mRNA levels in the retina. The parameters of dark-adapted, light-adapted, and light-adapted 30 Hz electroretinogram and the thickness of each retinal layer in histological analysis demonstrated no significant differences between the groups. In conclusion, we developed TTR siRNA conjugates for rabbit eyes, and the results indicate that intravitreal TTR siRNA conjugate injection could be a therapeutic option for ocular amyloidosis caused by ATTRv amyloidosis.

Melanopsin-mediated amplification of cone signals in the human visual cortex.

The ambient daylight variation is coded by melanopsin photoreceptors and their luxotonic activity increases towards midday when colour temperatures are cooler, and irradiances are higher. Although melanopsin and cone photoresponses can be mediated via separate pathways, the connectivity of melanopsin cells across all levels of the retina enables them to modify cone signals. The downstream effects of melanopsin-cone interactions on human vision are however, incompletely understood. Here, we determined how the change in daytime melanopsin activation affects the human cone pathway signals in the visual cortex. A 5-primary silent-substitution method was developed to evaluate the dependence of cone-mediated signals on melanopsin activation by spectrally tuning the lights and stabilizing the rhodopsin activation under a constant cone photometric luminance. The retinal (white noise electroretinogram) and cortical responses (visual evoked potential) were simultaneously recorded with the photoreceptor-directed lights in 10 observers. By increasing the melanopsin activation, a reverse response pattern was observed with cone signals being supressed in the retina by 27% (p = 0.03) and subsequently amplified by 16% (p = 0.01) as they reach the cortex. We infer that melanopsin activity can amplify cone signals at sites distal to retinal bipolar cells to cause a decrease in the psychophysical Weber fraction for cone vision.

Impaired Dopamine Signaling in Early Diabetic Retina: Insights from D1R and D4R Agonist Effects on Whole Retina Responses.

The retina has low dopamine levels early in diabetes. To determine how low dopamine levels affected dopamine signaling, the effects of dopamine receptor agonists and mRNA localization were measured after 6 weeks of diabetes. Whole retina ex vivo electroretinogram (ERG) recordings were used to analyze how dopamine type 1 receptor (D1R) and type 4 (D4R) agonists change the light-evoked retinal responses of non-diabetic and 6-week diabetic (STZ injected) mouse retinas. Fluorescence in situ hybridization was utilized to analyze D4R and D1R mRNA locations and expression levels. D4R activation reduced A- and B-wave ERG amplitudes and increased B-wave implicit time and rise-time in the non-diabetic group without a corresponding change in the diabetic group. D1R activation increased B-wave rise-time and oscillatory potential peak time in the non-diabetic group also with no change in the diabetic group. The lack of responsivity to D1R or D4R agonists shows an impairment of dopamine signaling in the diabetic retina. D4R mRNA was found primarily in the outer nuclear layer where photoreceptor cell bodies reside. D1R mRNA was found in the inner nuclear layer and ganglion cell layer that contain bipolar, amacrine, horizontal and ganglion cells. There was no change in D4R or D1R mRNA expression between the non-diabetic and diabetic retinas. This suggests that the significant dopamine signaling changes observed were not from lower receptor expression levels but could be due to changes in dopamine receptor activity or protein levels. These studies show that changes in retinal dopamine signaling could be an important mechanism of diabetic retinal dysfunction.

Reduced contrast sensitivity, pattern electroretinogram ratio, and diminished a-wave amplitude in patients with major depressive disorder.

The electroretinogram (ERG), a non-invasive electrophysiological tool used in ophthalmology, is increasingly applied to investigate neural correlates of depression. The present study aimed to reconsider previous findings in major depressive disorder (MDD) reporting (1) a diminished contrast sensitivity and (2) a reduced patten ERG (PERG) amplitude ratio, and additionally, to assess (3) the photopic negative response (PhNR) from the flash ERG (fERG), with the RETeval® device, a more practical option for clinical routine use. We examined 30 patients with a MDD and 42 healthy controls (HC), assessing individual contrast sensitivity thresholds with an optotype-based contrast test. Moreover, we compared the PERG ratio, an established method for early glaucoma detection, between both groups. The handheld ERG device was used to measure amplitudes and peak times of the fERG components including a-wave, b-wave and PhNR in both MDD patients and HCs. MDD patients exhibited diminished contrast sensitivity together with a reduced PERG ratio, compared to HC. With the handheld ERG device, we found reduced a-wave amplitudes in MDD, whereas no significant differences were observed in the fERG b-wave or PhNR between patients and controls. The reduced contrast sensitivity and PERG ratio in MDD patients supports the hypothesis that depression is associated with altered visual processing. The findings underscore the PERG's potential as a possible objective marker for depression. The reduced a-wave amplitude recorded with the RETeval® system in MDD patients might open new avenues for using handheld ERG devices as simplified approaches for advancing depression research compared to the PERG.

Partial rescue of the full-field electroretinogram in patients with RPE65-related retinal dystrophy following gene augmentation therapy with voretigene neparvovec-rzyl.

PURPOSE: To present a series of patients with RPE65-related retinal dystrophy showing a partial rescue of the full-field electroretinogram (ERG) following gene replacement therapy with voretigene neparovec-rzyl (Luxturna®). METHODS: This retrospective chart review examined 17 patients treated with voretigene neparovec-rzyl (VN) at the Casey Eye Institute (2018-2022). The last pre-operative ERG and all available post-operative ERGs were analyzed to identify subjects with functional rescue. Measurements of amplitudes and implicit times were compared to data from age-matched controls and the attenuation relative to the lower limit of normal (LLN) was calculated. For comparison with other functional exams, the last pre-operative and all post-treatment best-corrected visual acuity (BCVA) data, visual field (VF) tests and full-field threshold stimulus tests (FST) were also described. RESULTS: Of patients who underwent ERGs, most had unrecordable ERGs that did not change after treatment. However, we identified three patients, treated bilaterally, who demonstrated partial rescue of the full-field ERG in both eyes which was sustained during the course of the study. CONCLUSIONS: This is the largest series of patients treated with VN showing a partial rescue of the ERG. This is also the first report of bilateral ERG rescue, as well as the first description of ERG recovery occurring in non-pediatric subjects. Full-field ERG could be used in combination with other psychophysical tests and imaging modalities to detect and deepen our understanding of the response to this gene therapy approach.

Sensitivity and specificity of the uniform field electroretinogram in glaucoma detection in comparison to the pattern electroretinogram.

PURPOSE: To determine the ability of the photopic negative response (PhNR) of the uniform field electroretinogram (UF-ERG) to identify early glaucomatous changes in comparison to the checkerboard and bar stimuli of the pattern electroretinogram (PERG). METHODS: Forty-nine glaucoma patients were classified into two groups: glaucoma-suspect (23 eyes) and early to moderate glaucoma (30 eyes), based on their clinical examination and the results of standard automated perimetry. Thirty patients (30 eyes) with intraocular pressures (IOP) of 21 mmHg or less, with no history of reported high IOP, were included as controls. PERG and UF-ERG recordings were obtained on a Diagnosys D-341 Attaché-Envoy System. Visual field testing was done only for glaucoma-suspect and glaucoma patients. RESULTS: All three tests (PERG bar stimulus, PERG checkerboard stimulus and PhNR) displayed significantly prolonged peak times for glaucoma and glaucoma-suspect patients, with delays ranging from 7.8 to 14.8%, depending on the test. The PERG bar stimulus also showed a significantly lower N95 amplitude for both glaucoma groups (with reductions of 26.0% and 33.0% for glaucoma-suspect and glaucoma groups, respectively). The PERG checkerboard N95 amplitude component had high sensitivity for detecting glaucoma patients but a low specificity (97% and 37%, respectively; AUC = 0.61). Overall, the PhNR peak time showed the highest sensitivity and specificity (77% and 90%, respectively; AUC = 0.87). CONCLUSIONS: PERG bar stimuli and the PhNR of the UF-ERG can be used in the clinical setting to detect glaucoma-related changes in glaucoma-suspect and glaucoma patients. However, our data confirm that the PhNR peak time has the best combined sensitivity and specificity.

Effect of eccentric fixation on the steady-state pattern electroretinogram.

PURPOSE: The steady-state pattern electroretinogram (ssPERG) is used to assess retinal ganglion cell function in a variety of research contexts and diagnostic applications. In certain groups of patients or study participants, stable central fixation of the stimulus is not guaranteed. The present study aimed at assessing the effects of misfixation on the ssPERG response to checkerboard reversal stimuli. METHODS: Using two check sizes (0.8° and 15°), we compared ssPERG responses for several amounts of fixation deviation, ranging from 0° to 19° horizontally and from 0° to 14° diagonally. The stimulus area extended to 15° eccentricity, stimulus reversal rate was 15/s. RESULTS: Up to around 7° eccentricity, there was no sizable effect of fixation deviation under most conditions. Effects were somewhat larger for nasal than for temporal deviation, in particular for small checks. Diagonal deviation was associated with a response to luminance onset/offset at 7.5 Hz (subharmonic of the reversal rate), most prominently when the interior of a large check was fixated. CONCLUSION: Generally, moderate inaccuracies of fixation do not have a sizable effect on ssPERG amplitude. However, with large checks, the luminance response has to be considered.

Electroretinographic oscillatory potentials in Leber hereditary optic neuropathy.

PURPOSE: Leber hereditary optic neuropathy (LHON) affects retinal ganglion cells causing severe vision loss. Pattern electroretinogram and photopic negative response (PhNR) of the light-adapted (LA) full-field electroretinogram (ERG) are typically affected in LHON. In the present study, we evaluated dark-adapted (DA) and LA oscillatory potentials (OPs) of the flash ERG in genetically characterized LHON patients to dissociate slow from fast components of the response. METHODS: Seven adult patients (mean age = 28.4 ± 5.6) in whom genetic diagnosis confirmed LHON with mtDNA or nuclear DNAJC30 (arLHON) pathogenic variants were compared to 12 healthy volunteers (mean age = 35.0 ± 12.1). Full-field ERGs were recorded from both eyes. Offline digital filters at 50, 75 and 100 Hz low cutoff frequencies were applied to isolate high-frequency components from the original ERG signals. RESULTS: ERG a-waves and b-waves were comparable between LHON patients and controls, while PhNR was significantly reduced (p = 0.009) in LHON patients compared to controls, as expected. OPs derived from DA signals (75 Hz low cutoff frequency) showed reduced peak amplitude for OP2 (p = 0.019). LA OP differences between LHON and controls became significant (OP2: p = 0.047, OP3: p = 0.039 and OP4: p = 0.013) when the 100 Hz low-cutoff frequency filter was applied. CONCLUSIONS: Reduced OPs in LHON patients may represent disturbed neuronal interactions in the inner retina with preserved photoreceptoral (a-wave) to bipolar cell (b-wave) activation. Reduced DA OP2 and high-cutoff LA OP alterations may be further explored as functional measures to characterize LHON status and progression.

Slope between positive and negative ERG components in patients with open-angle glaucoma.

PURPOSE: To evaluate ERG morphology, in particular the slope between P50 and N95 components of the PERG, as well as between the b-wave and the photopic negative response (PhNR) of the light-adapted (LA) ERG in patients with retinal ganglion cell (RGC) dysfunction due to open-angle glaucoma. METHODS: The PERG and LA-ERG traces of 16 glaucoma patients and 21 age-similar controls were retrospectively analysed. The ERG signal between the peak of the positive component (P50 and b-wave) towards the negative component (N95 and PhNR) was described by a linear regression y = a + bx, where the parameter b indicated the steepness of the P50-N95 and b-PhNR slope. RESULTS: The P50-N95 slope was less steep in glaucoma patients (-0.079 ± 0.034 vs. -0.166 ± 0.050 in controls, p < 0.001), while the b-PhNR slope was not affected (-4.2 ± 2.1 vs. -4.4 ± 1.2, p = NS). The P50-N95 slope showed strong correlation with PhNR and N95 amplitude (r = -0.68 and -0.92, respectively; p < 0.001), while the b-PhNR slope correlated only with b-wave amplitude (r = -0.66, p < 0.001). CONCLUSIONS: The P50-N95 slope is a sensitive indicator of RGC dysfunction in patients with open-angle glaucoma. A similar component of LA-ERG, the b-PhNR slope, is less affected by glaucomatous RGC dysfunction and probably originates from similar retinal mechanisms as the b-wave.

ISCEV standard for clinical pattern electroretinography (2024 update).

The pattern electroretinogram (PERG) is a localized retinal response evoked by a contrast-reversing pattern, usually a black and white checkerboard, which provides information about macular and retinal ganglion cell function. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV; www.iscev.org ) presents an updated and revised Standard for clinical PERG testing. This replaces the 2013 and all earlier versions. Minimum protocols for basic PERG stimuli, recording methods and reporting are specified, to promote consistency of methods for diagnosis and monitoring purposes, while responding to evolving clinical practices and technology. The main changes in the updated ISCEV Standard for clinical PERG include expanded guidance about large stimulus fields, stimulus parameters for simultaneous PERG and pattern visual evoked potential recording, baseline drift correction, and use of consistent ambient room lighting. These changes aim to provide a clinically relevant document about current practice which will facilitate good quality recordings and inter-laboratory comparisons.

Clinical course of two siblings with potassium voltage-gated channel modifier subfamily V member 2 (KCNV2)-associated retinopathy.

BACKGROUND: KCNV2-associated retinopathy causes a phenotype reported as "cone dystrophy with nyctalopia and supernormal rod responses (CDSRR; OMIM# 610356)," featuring pathognomonic findings on electroretinography (ERG). Here, we report the clinical courses of two siblings with CDSRR. CASE REPORTS: Patient 1: A 3-year-old boy with intermittent exophoria was referred to our hospital. The patient's decimal best-corrected visual acuity (BCVA) at age 6 was 0.7 and 0.7 in the right and left eyes, respectively. Photophobia and night blindness were also observed. Because the ERG showed a delayed and supernormal b-wave with a "squaring (trough-flattened)" a-wave in the DA-30 ERG, and CDSRR was diagnosed. The patient's vision gradually worsened, and faint bilateral bull's eye maculopathy was observed at the age of 27 years, although the fundi were initially unremarkable. Genetic examination revealed a homozygous missense variant, c.529T > C (p.Cys177Arg), in the KCNV2 gene. Patient 2: The second patient was Patient 1's younger sister, who was brought to our hospital at 3 years of age. The patient presented with exotropia, mild nystagmus, photophobia, night blindness, and color vision abnormalities. The patients' decimal BCVA at age 13 was 0.6 and 0.4 in the right and left eyes, respectively, and BCVA gradually decreased until the age of 24 years. The fundi were unremarkable. The siblings had similar ERG findings and the same homozygous missense variant in the KCNV2 gene. CONCLUSIONS: The siblings had clinical findings typical of CDSRR. High-intense flash ERG is recommended for identifying pathognomonic "squaring" a-waves in patients with CDSRR.

Rod-sparing in a bardet-biedl syndrome patient with mutations in the ARL6 gene.

PURPOSE: Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder characterized by pleiotropism that affects multiple organ systems. The primary features of BBS include rod-cone dystrophy, renal anomalies, post axial polydactyly, and neurologic deficits. The clinical picture of BBS is extensively heterogenous, with inter and intra familial patients varying in levels of syndromic manifestations and severity of symptoms. METHODS: In this study we examined a monocular BBS patient who was compound heterozygous for mutations in the ARL6 (BBS3) gene. RESULTS: The patient reported visual complaints consistent with a clinical picture of cone or cone-rod dystrophy. Fundus imaging showed retinal mottling on color photos and a parafoveal hyperfluorescent ring on short wave autofluorescence (SW-AF). Full field electroretinogram (ffERG) revealed normal scotopic step tracings and diminished amplitudes in the photopic steps. CONCLUSION: This rod-sparing result was consistent with cone-dystrophy and is the first known case of a rod-sparing ffERG phenotype in a BBS patient with mutations in the ARL6 gene. This contributes to the existing phenotype and may potentially contribute to furthering our understanding of BBS pathophysiology.

Assessing the pattern electroretinogram as a proxy measure for dopamine in the context of iron deficiency.

OBJECTIVES: Animal studies have suggested that dietary iron deficiency (ID) negatively affects dopamine (DA) synthesis and re-uptake, which in turn negatively affects memory and cognition. This study was intended to assess whether the pattern electroretinogram (pattern ERG) could be used as an indirect measure of DA in college-age women with and without ID by determining the extent to which features of the ERG were sensitive to iron status and were related to other indirect measures of DA. METHODS: The pattern ERG was measured in 21 iron deficient non-anemic (IDNA) and 21 iron sufficient (IS) women, who also performed a contrast detection and probabilistic selection task, both with concurrent electroencephalography (EEG). Both spontaneous and task-related blink rates were also measured. RESULTS: The implicit times of the A- and B-waves were significantly longer for the IDNA than for the IS women. Both the amplitudes and implicit times of the A- and B-waves were significantly correlated with levels of serum ferritin (sFt). Only the amplitude of the A-wave was correlated with spontaneous blink rate. It was possible to accurately identify a woman's iron status solely on the basis of the implicit time of the B-wave. Finally, the implicit times of the ERG features mediated the relationship between iron levels and accuracy in the probabilistic selection task. CONCLUSIONS: Results suggest the utility of the pattern ERG in testing the hypothesis that iron deficiency affects DA levels in humans and that this may be one of the mechanisms by which iron deficiency negatively affects cognition.

Pattern electroretinogram, blue-yellow visual evoked potentials and the risk of developing visual field defects in glaucoma suspects: a longitudinal "survival" analysis with a very long follow-up.

PURPOSE: Estimating glaucoma suspects' risk for visual field defects helps to avoid under- and over-treatment. In this retrospective, longitudinal cohort study with a very long follow-up, we studied whether pattern electroretinograms (PERG) amplitudes and blue-on-yellow visual evoked potential (BY-VEP) latencies can predict visual field defects. METHODS: Participants of the Erlangen Glaucoma Study were examined with PERG and BY-VEP between 9/1991 and 8/2001. Stimuli were created using an optical bench with Maxwellian view and consisted of vertical gratings (0,88 cpd) in a 32° field for both PERG and BY-VEP. Patients were treated according to clinical standards and performed standard automated perimetry (SAP) annually. Retrospectively, patients with normal SAP at baseline were selected. Primary endpoint was conversion to perimetric glaucoma. Predictive value was modeled using Kaplan-Meier analyses and a multivariate cox proportional hazards model with the continuous variables PERG amplitude, BY-VEP peak time and SAP square-root of loss variance (sLV) after stratification for Jonas classification of the optic discs. RESULTS: Of 412 patients (288: Jonas 0, 103: I, and 21: II; baseline age: 20-60 years), 65 converted to perimetric glaucoma during follow-up (0.5-23.3 years; median 5.5 years). Optic disc classification was a strong risk factor for conversion (log rank p < 0.0001), and patients with more advanced changes progressed earlier. In the multivariate analysis (log rank p = 0.005), only PERG amplitude remained an independent risk factor after stratification for optic disc morphology (p = 0.021), with a ~ 30% higher risk per µV amplitude decrease. CONCLUSIONS: PERG helps to estimate glaucoma suspects' risk for visual field defects.

Abnormalities of retinal function in type 2 diabetes mellitus patients without clinical diabetic retinopathy detected by multifocal electroretinogram.

OBJECTIVE: To study the changes of retinal function in type 2 diabetes mellitus(DM) patients without apparently diabetic retinopathy via multifocal electroretinogram. METHODS: Thirty-six type 2 DM patients (72 eyes) without visible diabetic retinopathy were selected as the experimental group, and thirty-five healthy subjects (70 eyes) were selected as the control group. All subjects were underwent multifocal electroretinogram (mf- ERG). RESULTS: Compared with the control group, the implicit time delay of the P1 wave in the first ring, third ring, fourth ring, and fifth ring of the experimental group was significant (t = -3.154, p = 0.004, t = -8.21, p = 0.000, t = -3.067, p = 0.004, t = -4.443, p = 0.000, respectively). The implicit time of the N1 wave in the fourth- and fifth-ring were also significantly delayed compared with the control group (t = -3.549, p = 0.001, t = 2.961, p = 0.005, respectively). Compared with the control group, the implicit time of the P1 wave and N1 wave in the temporal region of the experimental group were delayed (t = -2.148, p = 0.037, t = -2.834, p = 0.007, respectively). There were no significant difference between the experimental group and the control group of the temporal area in the amplitude density of P1 wave, N1 wave. There was no difference in the implicit time and amplitude density of the N1 and P1 waves in the nasal region between the experimental group and the control group. The multifocal electroretinogram complex parameters showed better specificity and sensitivity in the diagnosis of diabetic retinopathy. CONCLUSION: The multifocal electroretinogram can detect abnormal changes in the retina of type 2 DM patients without visible diabetic retinopathy. The multifocal electroretinogram complex parameter is a potential indicator for the early diagnosis of diabetic retinopathy.

Efficacy and safety of intravitreal injections of conbercept for the treatment of idiopathic choroidal neovascularization.

BACKGROUND: To determine the efficacy and safety of intravitreally injected conbercept, a vascular endothelial growth factor receptor fusion protein, for the treatment of idiopathic choroidal neovascularization (ICNV). METHODS: This retrospective study analyzed outcomes in 40 patients (40 eyes) with ICNV who received intravitreal injections of conbercept 0.5 mg (0.05 ml) and were followed up for at least 12 months. All patients underwent full ophthalmic examinations, including best-corrected vision acuity (BCVA), intraocular pressure (IOP), slit-lamp examination, color fundus photography, optical coherence tomography angiography, multifocal electroretinogram, and fundus fluorescence angiography, if necessary, at baseline and after 1, 3, 6, and 12 months. BCVA, macular central retinal thickness (CRT), IOP, CNV blood flow area, thickness of the CNV-pigment epithelial detachment complex, thickness of the retinal nerve fiber layer (RNFL), and the first positive peak (P1) amplitude density in ring 1 before and after treatment were compared. RESULTS: Mean baseline BCVA (logMAR), CRT, CNV blood flow area, and CNV-pigment epithelial detachment complex thickness were significantly lower 1, 3, 6, and 12 months after than before conbercept treatment (P < 0.05 each). IOP and baseline RNFL thickness were unaffected by conbercept treatment. P1 amplitude density was significantly higher 1, 3, 6, and 12 months after than before conbercept treatment (P < 0.05 each). None of the 40 eyes showed obvious ocular adverse reactions, such as endophthalmitis, glaucoma, cataract progression, and retinal detachment, and none of the patients experienced systemic adverse events, such as cardiovascular and cerebrovascular accidents. CONCLUSIONS: Intravitreal injection of conbercept is beneficial to eyes with ICNV, inducing the recovery of macular structure and function and improving BCVA, while not damaging the neuroretina. Intravitreal conbercept is safe and effective for the treatment of ICNV.

Application of remimazolam-0.6% sevoflurane anesthesia for flash visual evoked potential monitoring during pituitary adenoma resection: a non-inferiority randomized controlled trial.

BACKGROUND: Flash visual evoked potential (FVEP) is a critical method for monitoring intraoperative visual function during neurosurgery. A new benzodiazepine drug called remimazolam has recently been used for general anesthesia. However, the impact of remimazolam on FVEP remains unclear. Therefore, we aimed to investigate how remimazolam, in comparison to propofol, when combined with 0.6% sevoflurane anesthesia, affects the FVEP waveform during pituitary adenoma resection. METHODS: Overall, 36 patients undergoing pituitary adenoma resection under general anesthesia were randomly assigned to either the remimazolam group (Group R) or the propofol group (Group P) in a prospective, randomized, controlled, non-inferiority trial. For anesthesia induction, a bolus of 0.2 mg/kg remimazolam or 2 mg/kg propofol was intravenously infused for approximately one minute. The anesthesia was maintained by continuous infusion of either remimazolam (0.7-1.0 mg/kg/h) or propofol (4-6 mg/kg/h), in combination with 0.6% sevoflurane, aimed at sustaining the bispectral index (BIS) within the range of 40-60. The primary outcome was the N75-P100 amplitude of FVEP recorded at approximately 20 min after intubation (T0). 10% of the amplitude at T0 in group P was defined as the non-inferiority margin (δ). Confidence interval testing was used to evaluate the non-inferiority hypothesis. The secondary outcomes covered the P100 latency of FVEP, electroretinogram (ERG) b wave amplitude, demographic characteristics, hemodynamics, and occurrence of adverse events. RESULTS: The BIS index during anesthesia was comparable between the groups at the same measured time points (P > 0.05). The N75-P100 amplitude at T0 in group R was 7.64 ± 1.36 µV, while it was 6.96 ± 0.95 µV in group P (P = 0.09), with a mean difference of 0.68 µV (95% CI, -0.11 µV to 1.48 µV). The δ was set at 0.7 and the lower limit of the 95% CI exceeded the -δ. Both remimazolam and propofol had little effect on ERG b-wave amplitudes. At the designated time points, FVEP amplitude and P100 latency displayed no appreciable variation between the two groups (P > 0.05). Furthermore, there were no significant differences in the incidence of adverse events related to anesthesia, needle electrodes, or surgery between the two groups (P > 0.05). CONCLUSION: Our findings suggest that remimazolam-0.6% sevoflurane is non-inferior to propofol-0.6% sevoflurane for general anesthesia, based on the FVEP N75-P100 amplitude. The electrophysiological data obtained in both groups indicate that reproducible and stable FVEP and ERG waveforms can be acquired at set time points. Therefore, for reliable FVEP monitoring, remimazolam-0.6% sevoflurane appears to be a safe and effective protocol in general anesthesia. TRIALS REGISTRATION: This study was registered on chictr.org.cn (ChiCTR2200056803, 17/02/2022).

Amelioration of Photoreceptor Degeneration by Intravitreal Transplantation of Retinal Progenitor Cells in Rats.

Photoreceptor degeneration is a major cause of untreatable blindness worldwide and has recently been targeted by emerging technologies, including cell- and gene-based therapies. Cell types of neural lineage have shown promise for replacing either photoreceptors or retinal pigment epithelial cells following delivery to the subretinal space, while cells of bone marrow lineage have been tested for retinal trophic effects following delivery to the vitreous cavity. Here we explore an alternate approach in which cells from the immature neural retinal are delivered to the vitreous cavity with the goal of providing trophic support for degenerating photoreceptors. Rat and human retinal progenitor cells were transplanted to the vitreous of rats with a well-studied photoreceptor dystrophy, resulting in substantial anatomical preservation and functional rescue of vision. This work provides scientific proof-of-principle for a novel therapeutic approach to photoreceptor degeneration that is currently being evaluated in clinical trials.