Retraction Note: Autoantibodies detection in patients affected by autoimmune retinopathies.

The article "Autoantibodies detection in patients affected by autoimmune retinopathies", by M.R. Ceccarini, M.C. Medori, K. Dhuli, S. Tezzele, G. Bonetti, C. Micheletti, P.E. Maltese, S. Cecchin, K. Donato, L. Colombo, L. Rossetti, G. Staurenghi, A.P. Salvetti, M. Oldani, L. Ziccardi, D. Marangoni, G. Iarossi, B. Falsini, G. Placidi, F. D'Esposito, F. Viola, M. Nassisi, G. Leone, L. Cimino, L. De Simone, V. Mastrofilippo, T. Beccari, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63-DOI: 10.26355/eurrev_202312_34690-PMID: 38112948 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: -       Issues with ethical approval -       Undeclared conflict of interest In light of concerns regarding the potential manipulation of Supplementary Figure 2, the journal's inquiry has been unable to conclusively determine whether the alterations noted on PubPeer constitute figure manipulation. The investigation yielded divergent evaluations. However, given the aforementioned concerns, the Editor in Chief doubts the integrity of the findings presented and thus, has opted to retract the article. The authors disagree with this retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34690.

Autoantibodies detection in patients affected by autoimmune retinopathies.

OBJECTIVE: Autoimmune retinopathies (ARs) encompass a spectrum of immune diseases that are characterized by the presence of autoantibodies against retinal proteins in the bloodstream. These autoantibodies (AAbs) lead to a progressive and sometimes rapid loss of vision. ARs commonly affect subjects over 50 years of age, but also rare cases of kids under 3 years of age have been reported. PATIENTS AND METHODS: In this study, 47 unrelated Caucasian patients were enrolled. All subjects showed negative cancer diagnoses and negative results in their genetic screenings. We studied 8 confirmed retinal antigens using Western blotting analysis, with α-enolase followed by carbonic anhydrase II being the two most frequently found in the patients' sera. RESULTS: Nineteen patients were positive (40.4%), thirteen uncertain (27.7%), and fifteen were negative (31.9%). Their gender did not correlate with the presence of AAbs (p=0.409). CONCLUSIONS: AAbs are responsible for retinal degeneration in some cases, while in others, they contribute to exacerbating the progression of the disease; however, their detection is crucial to reaching a better diagnosis and developing more effective treatments for these conditions. Moreover, finding good biomarkers is important not only for AR monitoring and prognosis, but also for helping with early cancer diagnosis.

Photopic negative response of the human ERG: losses associated with glaucomatous damage.

PURPOSE: To evaluate in glaucomatous eyes the photopic electroretinogram (ERG) negative response (PhNR), a component that follows the b-wave peak and is thought to be correlated with inner retinal activity. METHODS: Eleven patients with open-angle glaucoma (OAG) and moderate field loss (Humphrey 30-2 [Humphrey Instruments, San Leandro, CA] mean deviation < or = -6 dB), eight with ocular hypertension (OHT), and eight age-matched normal subjects were tested. Optic discs of patients and control subjects were evaluated by confocal scanning laser ophthalmoscopy. ERGs were recorded to long-duration stimuli (250 msec) of photopic luminance (78 candelas [cd] /m2), presented in the macular region (12 degrees x 12 degrees field size) on a steady, adapting background. Amplitudes of the a-wave and b-wave and the PhNR were measured. Pattern reversal ERGs to 30-minute checkerboards were also recorded from patients and control subjects. RESULTS: Compared with control subjects, patients with OAG showed reduced PhNR (average reduction: 62%, P < 0.01), but normal a- and b-wave amplitudes. In patients with OHT, PhNR and a- and b-wave amplitudes did not differ from control values. In individual patients with OAG, PhNR amplitudes were correlated positively with pattern ERG amplitudes (r = 0.80; P < 0.01) and central (12 degrees) perimetric mean deviations (r = 0.68; P < 0.05) and negatively with cup-to-disc area ratios (r = -0.79; P < 0.01) and cup shape measures (r = -0.78; P < 0.01). CONCLUSIONS: Similar to that found in monkeys with experimentally induced glaucoma, the PhNR is selectively altered in human glaucoma. The correlation between PhNR losses and clinical parameter abnormalities suggests that this component depends on inner retina integrity and may be of clinical value for detecting glaucomatous damage.

Retinal sensitivity to flicker modulation: reduced by early age-related maculopathy.

PURPOSE: To evaluate retinal, cone-mediated flicker sensitivity (CFS) in age-related maculopathy (ARM) by quantifying response gain and threshold of the focal electroretinogram (FERG) to flicker modulation. METHODS: Nineteen patients with ARM (visual acuity > or =20/30) and 11 age-matched control subjects were examined. Twelve patients had less than 20 soft drusen in the macular region and no hyper-/hypopigmentation (early lesion), whereas seven had more than 20 soft drusen and/or focal hyper-/hypopigmentation (advanced lesion). Macular (18 degree ) FERGs were elicited by a sinusoidally flickering (41 Hz) uniform field (on a light-adapting background) whose modulation depth was varied between 16.5% and 94%. Amplitude and phase of the response's fundamental harmonic were measured. RESULTS: In both control subjects and patients with ARM, log FERG amplitude increased with log stimulus modulation depth with a straight line (power law) relation. However, the slope (or gain) of the function was, on average, steeper in control subjects than in patients with either early or advanced lesions. Mean FERG threshold, estimated from the value of the log modulation depth that yielded a criterion response, did not differ between control subjects and patients with early lesions but was increased (0.35 log units) compared with control subjects in those with advanced lesions. In both patient groups, but not in control subjects, mean FERG phase tended to delay with decreasing stimulus modulation depth. CONCLUSIONS: Retinal CFS losses can be detected in ARM by evaluating the FERG as a function of flicker modulation depth. Reduced response gain and phase delays, with normal thresholds, are associated with early lesions. Increased response thresholds, in addition to gain and phase abnormalities, may reflect more advanced lesions. Evaluating CFS by FERG may directly document different stages of macular dysfunction in ARM.

The fundamental and second harmonic of the photopic flicker electroretinogram: temporal frequency-dependent abnormalities in retinitis pigmentosa.

OBJECTIVES: The flicker electroretinogram (FERG) consists mainly of a linear (fundamental, 1F) and a non linear (second harmonic, 2F) component. Previous results indicate that 2F originates more proximally in the retina than 1F, and that retinitis pigmentosa (RP) may affect 2F to a greater extent than 1F. The aim of this study was to evaluate FERG 1F and 2F abnormalities in RP as a function of the stimulus temporal frequency (TF). METHODS: Twelve patients with typical RP and 10 age-matched controls were examined. FERGs were recorded in response to uniform fields (18 degrees) presented in the macula on a light-adapting background. Stimuli were flickered sinusoidally at different, closely spaced TFs between 3.7 and 52 Hz. Amplitudes and phases of the Fourier analysed 1F and 2F components were measured. Components' apparent latencies were estimated from the rate at which phase lagged with TF. RESULTS: When compared to controls, mean 1F amplitudes of patients were reduced at both low (3.7-12.6 Hz) and high (14-52 Hz) TFs, with greatest losses (0.5 log units) around the peaks (3.7 and 41 Hz) of the normal TF function. Mean 2F amplitudes were reduced mainly at low TFs, with greatest losses (0.5 log units) at 5-8 Hz. On average, the shape of the 2F, but not 1F amplitude versus TF function, differed between patients and controls, showing a selective attenuation at low TFs. Mean 1F apparent latencies were delayed at both low and high TFs, with greater delays at low (85 ms) than at high (33 ms) TFs. Mean 2F apparent latencies were delayed only at low TFs (58 ms). CONCLUSIONS: In RP, 1F and 2F phase delays as well as 2F amplitude losses are dependent on TF, suggesting that FERG generators' subpopulations in both distal and proximal retina are differentially affected. Analysis of the FERG TF response is potentially useful to characterize cone system dysfunction in different genetic subtypes of RP.

Correlation of pattern electroretinogram with optic disc cup shape in ocular hypertension.

PURPOSE: To evaluate the correlation of pattern electroretinogram (PERG), an index of inner retinal function, with confocal scanning laser (CSLO) optic disc structural parameters in ocular hypertension (OHT). METHODS: Thirty-four patients with OHT, normal white-on-white (Humphrey 30-2) perimetry, and normal clinical optic discs were examined with PERG and CSLO disc analysis. Two groups of normal subjects (n = 38 and 18, for PERG and CSLO, respectively) and a group of 12 patients with early open-angle glaucoma (EOAG) were also tested. Pattern electroretinogram amplitudes were measured in response to sinusoidal gratings of variable spatial frequency (0.58-5.8 cycles/degree), modulated in counter-phase at 7.5 Hz. Morphometric optic disc parameters were obtained by the Heidelberg Retina Tomograph (HRT), either globally or from predefined disc sectors. In addition to standard parameters, the cup shape measure, an index of depth variation and steepness of the cup walls, was determined. RESULTS: In individual OHT patients, PERG amplitudes at 2.6 cycles/degree were negatively correlated with cup shape measures (r = -0.43, P < 0.01) obtained from analysis of the inferotemporal (IT) sector. No significant correlations were found for the other parameters. On average, the cup shape measures derived from IT sector or global analysis were significantly (P < 0.01) worse, and closer to the measures of EOAG patients, in OHT patients with abnormal PERG compared with those with normal PERGs. The cup shape measure displayed a low sensitivity (20%) and a high specificity (100%) in predicting PERG abnormalities in individual OHT patients. CONCLUSIONS: The results indicate that in OHT there is a significant although weak correlation between PERG amplitude and the shape of the optic disc cup, suggesting a parallel involvement of both function and morphology. Combined PERG and optic disc cup structural analysis is of potential diagnostic value to detect early damage to optic nerve head in individual OHT patients.

Focal electroretinograms and fundus appearance in nonexudative age-related macular degeneration. Quantitative relationship between retinal morphology and function.

BACKGROUND: The aim of this study was to evaluate the focal electroretinogram (FERG), an objective indicator of outer retinal function, in nonexudative age-related macular degeneration (NE-AMD), and to compare FERG results with morphological lesions assessed by stereoscopic fundus photographs and fluorescein angiograms. METHODS: Twenty-five patients (25 eyes) with bilateral NE-AMD (visual acuity of the study eyes > or = 0.4) as well as 10 age- and sex-matched control subjects (10 eyes) were evaluated. FERGs were recorded from the macular region (9 degrees) in response to sinusoidal stimuli flickered at 32 Hz. Amplitude and phase angle of the Fourier-analyzed FERG fundamental component were measured. Fundus lesions were graded from color slides according to the Wisconsin age-related maculopathy grading system . Fluorescein angiograms were evaluated by an image analysis technique to compute the area with pathological hyperfluorescence (associated with drusen and/or retinal pigment epithelial atrophy) within the macular (approximately 9 degrees x 9 degrees) region. RESULTS: Compared to control eyes, NE-AMD eyes had a reduction in the mean FERG amplitude (57% loss, P<0.001) with no phase changes. Amplitudes of individual affected eyes were negatively correlated with either the Wisconsin grading score (r = -0.63, P < 0.001) or the percentage area of pathological hyperfluorescence (r = -0.70, P<0.01). Eyes with minimal NE-AMD lesions (Wisconsin score < or = 6) and normal acuity had a lower mean amplitude (47% loss, P < 0.05) than that of control eyes. CONCLUSIONS: The results indicate that, in NE-AMD, the FERG is altered in parallel with the extent and severity of fundus lesions. However, a functional impairment of outer macular layers, which is detected by FERG losses, could precede morphological changes typical of more advanced disease.

The first and second harmonics of the macular flicker electroretinogram: differential effects of retinal diseases.

We evaluated the effects of retinal diseases on the macular electroretinogram first and second harmonic components, which are dominated by outer and inner retinal activity, respectively. Macular electroretinograms in response to a uniform field (9 degrees x 9 degrees) flickering sinusoidally at either 32 or 8 Hz (peak frequencies of the first and second harmonics, respectively) were recorded in 14 patients with maculopathies involving photoreceptors (e.g., age-related macular degeneration), in 16 patients with postreceptoral macular diseases (e.g., branch occlusion of central retinal artery), and in 38 normal controls. Amplitude and phase of the first and second harmonic response components were evaluated by Fourier analysis. When compared to controls, patients with photoreceptor diseases had reduction in both first and second harmonic mean amplitudes and second harmonic phase delay; patients with postreceptoral diseases had normal first harmonic components but reduced and delayed second harmonic components. A discriminant analysis, by using first and second harmonic values, correctly classified 13 of 14 patients with photoreceptor diseases and 14 of 16 patients with postreceptoral disorders. These results indicate that combined evaluation of the macular electroretinogram first and second harmonic components is a useful test for identifying the site(s) of retinal dysfunction in patients with macular diseases.

Postreceptoral contribution to macular dysfunction in retinitis pigmentosa.

PURPOSE: To understand the sites of macular dysfunction in retinitis pigmentosa by evaluating focal electroretinogram (FERG) fundamental and second harmonic components, which are dominated by the activity of the outer and inner retina, respectively. METHODS: FERGs were recorded in response to a uniform field (9 degrees x 9 degrees) flickered sinusoidally at either 8 Hz or 32 Hz. The fundamental components of the responses to both the 8-Hz and 32-Hz stimuli and the second harmonic of the response to the 8-Hz stimulus were measured in their amplitudes and phases. Normal subjects (n = 17), as well as patients with typical retinitis pigmentosa (n = 22), cone dystrophy (CD, n = 7) and X-linked congenital retinoschisis (XLR, n = 5) served as subjects. The fundamental (32-Hz)-second harmonic (8 Hz) amplitude ratio was taken as an index of the relative function of outer-inner layers of the macula. RESULTS: Compared to controls, patients with retinitis pigmentosa showed losses of both FERG fundamental and second harmonic and an increase of the fundamental-second harmonic ratio. Patients with CD also showed losses of both fundamental and second harmonic, but the fundamental-second harmonic ratio was normal. Patients with XLR had a selective loss of the second harmonic, resulting in an increased fundamental-second harmonic ratio. On average, the fundamental-second harmonic ratio of patients with retinitis pigmentosa tended to increase with age. CONCLUSIONS: The results suggest that in retinitis pigmentosa, both receptoral and postreceptoral sites contribute to macular dysfunction. This differs from CD and XLR, where losses appear more selective for the outer and the inner retina. Postreceptoral losses in retinitis pigmentosa may become larger with increasing age.