Expression of Concern: Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma The Editor-in-Chief of Documenta Ophthalmologica is publishing an editorial expression of concern for the manuscript "Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma” by Li et al. (2019) [1].

Novel findings in enhanced S-cone syndrome: a case with macular retinal neovascularization and severe retinal vasculitis Abstract Purpose To describe a novel association of enhanced S-cone syndrome (ESCS) with macular retinal neovascularization and severe retinal vasculitis. Methods Clinical examination, spectral domain optical coherence tomography, fluorescein angiography, fundus autofluorescence, infrared reflectance and electroretinography were used to study a 25-year-old male with a history of night blindness from early childhood and recent accelerated visual loss in right eye. Results Pigmented lesions were observed along the arcades without peripheral retinal involvement. Intraretinal cystoid spaces, retinal neovascularization of posterior pole and severe peripheral and posterior retinal vasculitis were found on clinical examination and multimodal imaging. Based on characteristic clinical and electroretinographic findings, a diagnosis of ESCS was made. Conclusion This case highlights novel associations of retinal neovascularization and vasculitis with ESCS.

Using sellar region tumor’s size as a predictor of psychophysical and electrophysiological perimetric visual losses: a logistic regression approach Abstract Background Sellar region tumor growth represents an important cause of visual loss due to mechanical compression of the optic nerve apparatus. Many investigations have used non-invasive tools to evaluate the visual field consequences of this damage, and good associations have been reported between psychophysical and electrophysiological perimetries. Few reports have considered the tumor size as a predictor of visual field loss. Aims In the present study, we evaluated the association between the visual perimetry measured by Humphrey visual field analyzer and multifocal visual evoked cortical potential (mfVECP) and the tumor size. Methods Our sample was composed of 14 patients diagnosed with sellar tumors by magnetic resonance imaging. We accounted the number of sectors with negative visual responses for both methods. A simple logistic regression analysis was used to evaluate the association between the tumor dimensions and the visual field features Results Three patients had preserved visual fields, three patients showed hemianopic defects, and eight patients had generalized visual field losses at both evaluations. We observed that the three maximum diameters of the tumor and total tumor volume had different predictive abilities regarding the extent of visual field loss when using psychophysical and mfVECP data. The maximum craniocaudal diameter of the tumor was the better predictor of the psychophysical measurements, whereas for the mfVECP results, all tumor dimensions and volumes had similar values that predict visual field losses. Conclusion Tumor size as a predictor of visual loss has potential to assist in the clinical intervention and to prevent the irreversible visual impairment caused by tumors of the sellar region.

Two cases of unilateral cone-rod dysfunction with negative electroretinograms Abstract Purpose To report the findings in two patients with unilateral cone-rod dysfunction with the a-wave larger than the b-wave, i.e., negative-type, full-field electroretinogram (ERG). Methods Standard ophthalmological examinations were performed including the medical history, measurements of the best-corrected visual acuity and intraocular pressures, slit-lamp biomicroscopy, ophthalmoscopy, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and perimetry. ERG examinations were carried out with the ISCEV standard. Immunoblot analysis using the patient’s sera was performed to determine the presence of the recoverin1 antibody. Results The common findings in these two patients were: unilateral, male sex, sudden onset of photophobia or a reduction in the vision at an advanced age, preserved visual acuity, no complaint of night blindness, normal fundus appearance, negative-type dark-adapted 3.0 ERGs with reduced a-wave amplitudes, absent light-adapted 3.0 ERGs, and very reduced but recordable dark-adapted 0.01 ERGs. In addition, the multifocal ERGs in all areas except that in a hexagonal area within a 2.5° radius of the fovea were very reduced. Patients with similar findings have been reported earlier, but the subnormal a-wave of the dark-adapted 3.0 ERGs and extensive morphological alterations of the retina in the posterior pole in the OCT images were different from those of the reported patients. The OCT images showed an indistinct interdigitation zone and discontinuous ellipsoid zone. Anti-recoverin antibodies were not detected. Conclusions Negative ERGs with severely reduced cone and rod components suggest that both the cone and rod bipolar cell visual pathways may be disturbed. Slightly decreased a-wave suggests minor abnormality of photoreceptors. It is important to determine whether these patients represent a new clinical entity or a phenotypic variation of an already described retinal disorder.

Test–retest repeatability of the pattern electroretinogram and flicker electroretinogram Abstract Purpose To evaluate the repeatability of the steady-state pattern electroretinogram (PERG) and full-field flicker electroretinogram (Flicker ERG) protocols, delivered by the office-based Neuro Optic Vision Assessment (NOVA)™ testing platform, in healthy subjects. Methods Healthy individuals underwent PERG (16° and 24°) and Flicker ERG [fixed luminance (FL) and multi-luminance (ML)] testing protocols. Test–retest repeatability of protocols was calculated using intra-class correlation coefficients (ICC). Reference values of the parameters of the aforementioned tests were also calculated. Results The ICCs for the PERG parameters ranged from 0.793 to 0.911 (p < 0.001). The ICCs for the Flicker ERG parameters ranged from 0.968 to 0.994 (p < 0.001). A linear regression analysis was applied to assess the impact of age on ERG responses. Age had a significant impact on all PERG parameters (16° or 24°). The phase response of the FL Flicker ERG significantly decreased with age (β = − 0.837, p ≤ 0.001). The FL Flicker ERG Magnitude was also impacted with a significant quadratic effect of age (β = − 0.0047, p = 0.0004). Similarly, the Phase Area Under the Curve (Phase AUC) of the ML Flicker ERG significantly declined with age (β = − 0.007, p = 0.009), and the impact on the Magnitude AUC was significant as well, with a negative quadratic age effect. Conclusions The PERG and Flicker ERG protocols, delivered by an office-based testing platform, were shown to have good-to-excellent test–retest repeatability when tests were performed in the same order and in immediate succession.

Late-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration Abstract Purpose To report the clinical and genetic characteristics of 6 cases with late-onset night blindness with peripheral flecks accompanied by progressive trickle-like macular degeneration. Methods Clinical and genetic data were collected from 6 independent patients who complained of night blindness in their fifth to eighth decade of life. The ophthalmological examinations included ophthalmoscopy, fundus autofluorescence (FAF), and full-field electroretinography (ERG). Whole exome sequencing with target gene analysis was performed to determine the causative genes and variants. Results All of the patients first complained of night blindness at the ages of 40–71 years. Funduscopic examinations demonstrated white or atrophic flecks scattered in the posterior pole and peripheral retina bilaterally. FAF showed patchy hypo-autofluorescence spots in the posterior pole similar to that of the trickling type of age-related macular degeneration (AMD). The region of abnormal FAF rapidly expanded with age, and one eye developed a choroidal neovascularization. The full-field scotopic ERGs with 20 min of dark adaptation were severely reduced or extinguished in all cases. There was partial recovery of the ERGs after 180 min of dark adaptation. The cone ERGs were reduced in all cases. Whole exome sequencing revealed no pathogenic variants of 301 retinal disease-associated genes. Conclusions The six cases had some common features with the flecked retina syndrome, familial drusen, and late-onset retinal degeneration although none had pathogenic variants causative for these disorders. These cases may represent a subset of severe trickling AMD or a new clinical entity of acquired pan-retinal visual cycle deficiency of unknown etiology.

A comparison of contrast sensitivity and sweep visual evoked potential (sVEP) acuity estimates in normal humans Abstract Purpose Several previous studies have demonstrated that for normal adult subjects the optotype acuity measured with charts is better than the acuity determined with the sweep visual evoked potential (sVEP) using gratings or checks. However, there is no difference in psychophysical measures of acuity with optotype or grating charts. Thus, it is unclear whether the acuity discrepancy between optotype charts and the sVEP result from the stimulus design or other methodological differences. The purpose of this experiment is to determine the relationship between acuities extrapolated from a contrast sensitivity function (CSF) that uses optotypes and the sVEP. Methods Normal subjects (N = 10) with acuity of 0.00 logMAR or better (ETDRS chart) were recruited for this study. Two commercially available systems were used to measure CSFs [i.e., the Beethoven System (Ryklin Software, NY) and the qCSF system (Adaptive Sensory Tech, CA)]. The stimuli for the Beethoven were sine wave gratings (0.75–18.50 cpd), and thresholds were determined with a 2-alternative forced choice (2-AFC) procedure combined with a staircase. The stimuli for the qCSF system were spatially filtered letters (10 possible letters, 10-AFC) with the letter sizes and contrasts determined by a Bayesian adaptive procedure. Visual acuity was determined by fitting the data with a double exponential equation and extrapolating the fit to a contrast sensitivity of one. The sVEP was obtained with the PowerDiva (Digital Instrumentation for Visual Assessment, version 3.5, CA). The stimuli were sine wave gratings (80% contrast, 3–36 cpd) counterphased at 7.5 Hz. The final acuity was the average of two estimates each derived from the average of 10 sweeps. Results The average logMAR chart (acuity converted to cpd), sVEP, Beethoven, and qCSF acuities were 36.6 ± 4.62 cpd (mean ± SD), 31.2 ± 4.59 cpd, 27.3 ± 7.38 cpd, and 27.6 ± 6.36 cpd, respectively. The logMAR chart acuity was significantly different from the other acuity estimates (all p values < 0.05). The sVEP, Beethoven, and qCSF acuities were not different from one another (all p values > 0.05). The Beethoven and the qCSF acuities had a good intraclass correlation coefficient (ICC = 0.85). Conclusions Similar to previous publications, the sVEP acuity estimate was less than the optotype chart acuity. The acuity determined with the sVEP and the CSFs with letter and grating stimuli were not statistically different, suggesting that the difference in acuity with the sVEP and optotype charts does not result from stimulus differences. Other methodological differences must account for the discrepancy in sVEP and optotype chart acuity.

Electrophysiological findings in delayed discovery of a metallic intraocular foreign body in a child: case report Abstract Purpose To report a case of a child with strabismus and delayed discovery of a metallic intraocular foreign body with good recovery of visual acuity and stereopsis with 36-month follow-up. Methods A 4-year-old girl was evaluated due to exotropia of right eye initiated 9 months before with progressive worsening. Visual acuity was 1.00 logMAR (20/200) in the right eye and 0.00 logMAR (20/20) in the left eye. Anterior segment evidenced a small paracentral corneal leukoma, posterior synechia and mild lens opacity in the temporal quadrant only in the right eye. Fundus examination in the right eye identified the presence of an intraocular foreign body, with appearance of metallic components surrounded by retinal pigmented endothelial cells atrophy. Full-field electroretinography (ERG) showed reduced amplitudes and delayed implicit times for both rods and cones in the affected eye. All tests were normal in the fellow eye. Results Pars plana vitrectomy was promptly performed in the right eye, followed by phacoemulsification with intraocular lens implantation 4 months later due to worsening of the lens opacification. The full-field ERG was repeated after the surgical procedures. The ERG showed mild worsening of all responses in the right eye. After 36 months of follow-up, visual acuity was 0.20 logMAR (20/32) with improvement of the ocular misalignment and with 60 s of arc stereopsis with ERG responses unchanged. Conclusion In this young girl perforating ocular trauma with metallic material was lately diagnosed with strabismus as a sign of alert. Prompt surgical intervention and proper management were essential to provide reasonable visual function including some degree of stereopsis, even though retinal dysfunction characterized by ERG was persistent.

Multifocal electroretinogram in eyes with intravitreal silicone oil and changes following silicone oil removal Abstract Purpose To determine the effect of intravitreal silicone oil (SO) on multifocal electroretinogram (mfERG) and the changes in mfERG following SO removal. Methods Twelve eyes of 12 patients with SO in vitreous cavity with corrected distance visual acuity (CDVA) > 20/200 were prospectively enrolled as cases over a period from July 2016 to June 2018. The fellow normal eyes served as control. The eyes were evaluated with P1 and N1 wave amplitude and implicit time on mfERG at baseline, 1 and 4 weeks after SO removal. Results The mean age was 44.9 ± 18.9 (range 18–74) years. The indication for SO injection was retinal detachment (n = 9, three macula-on eyes, six macula-off eyes) and endophthalmitis (n = 3). The median (range) LogMAR CDVA at baseline was 0.54 (0.18–0.78) in cases and did not change post-SO removal (p = 0.29). There was a significant decrease in average P1 and N1 wave amplitude (p = 0.0001 and 0.0001, respectively) and delay in average P1 and N1 wave implicit time (p = 0.0002 and 0.021, respectively) in cases as compared to controls. The macular status and duration of SO tamponade did not have a significant correlation with mfERG parameters. There was a significant increase in average P1 and N1 wave amplitude (p = 0.009 and 0.003, respectively) at 1 week following SO removal but no change in average P1 and N1 wave implicit time (p = 0.41 and 0.37, respectively). Conclusion mfERG may be reliably performed for the assessment of macular function in SO-filled eyes. Intravitreal SO exerts an insulating effect on the density of the electric potentials.

ISCEV extended protocol for the S-cone ERG Abstract 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.