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published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63-DOI: 10.26355/eurrev_202312_34690-PMID: 38112948 has been retracted by the Editor in Chief for the following reasons.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 This article has been retracted.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.

Combined OCT distance and FBG force sensing cannulation needle for retinal vein cannulation: in vivo animal validation.

PURPOSE: Retinal vein cannulation is an experimental procedure during which a clot-dissolving drug is injected into an obstructed retinal vein. However, due to the fragility and minute size of retinal veins, such procedure is considered too risky to perform manually. With the aid of surgical robots, key limiting factors such as: unwanted eye rotations, hand tremor and instrument immobilization can be tackled. However, local instrument anatomy distance and force estimation remain unresolved issues. A reliable, real-time local interaction estimation between instrument tip and the retina could be a solution. This paper reports on the development of a combined force and distance sensing cannulation needle, and its experimental validation during in vivo animal trials. METHODS: Two prototypes are reported, relying on force and distance measurements based on FBG and OCT A-scan fibres, respectively. Both instruments provide an 80 [Formula: see text] needle tip and have outer shaft diameters of 0.6 and 2.3 mm, respectively. RESULTS: Both prototypes were characterized and experimentally validated ex vivo. Then, paired with a previously developed surgical robot, in vivo experimental validation was performed. The first prototype successfully demonstrated the feasibility of using a combined force and distance sensing instrument in an in vivo setting. CONCLUSION: The results demonstrate the feasibility of deploying a combined sensing instrument in an in vivo setting. The performed study provides a foundation for further work on real-time local modelling of the surgical scene. This paper provides initial insights; however, additional processing remains necessary.

Clinical features and long-term progression of reticular pseudodrusen in age-related macular degeneration: findings from a multicenter cohort.

PurposeTo determine whether reticular pseudodrusen (RPD) confer a long-term increased risk of progression to late age-related macular degeneration (AMD) in the fellow eye of patients with unilateral wet-AMD.Patients and methodsThis was a multicenter, combined prospective and retrospective, longitudinal, observational, study. Patients with wet-AMD in one eye were recruited from two centers and evaluated on the risk of progression to late-AMD in the second eye (study eye). A minimum follow-up of 5 years was required, unless progression occurred first. Baseline retinal profile of patients was evaluated using multimodal imaging. Baseline images were graded by two separate centers.ResultsWe recruited 88 patients (48 female) with a mean age of 75.6±7.1 years and mean follow-up of 65.7±20.9 months. Baseline prevalence of RPD was 58% (n=51). There was no statistically significant association of RPD with increased age (P=0.29) or sex distribution (P=0.39). The most sensitive image modality for RPD was IR (93%), followed by FAF (92%), OCT (74%, RF (33%) and CFP (29%). After 5 years, 54.50% (n=48) of the study eyes progressed to late-AMD. Of those, 81.25% (n=39) developed CNV and 18.75% (n=9) geographic atrophy. After correcting for age and sex, the presence of RPD was significantly associated with development of late-stage AMD (OR=2.55, P=0.03).ConclusionA multimodal approach is mandatory for RPD detection. RPD are highly prevalent in the fellow eyes of patients with unilateral neovascular AMD. Presence of RPD is associated with increased long-term risk of progression, highlighting the importance of comprehensive multimodal retinal imaging and careful monitoring of at-risk patients.

Determinants of visual acuity outcomes in eyes with neovascular AMD treated with anti-VEGF agents: an instrumental variable analysis of the AURA study.

PurposeTo identify the strongest variable(s) linked with the number of ranibizumab injections and outcomes in AURA, and to identify ways to improve outcomes using this association.MethodsAURA was a large observational study that monitored visual acuity over a 2-year period in patients with neovascular age-related macular degeneration (AMD) who received ranibizumab injections. Baseline characteristics, resource use, and outcomes were analyzed using an instrumental variable approach and regression analysis.ResultsData were analyzed from 2227 patients enrolled in AURA. Optical coherence tomography (OCT) and ophthalmoscopy were the most common diagnostic tests used, and this combination was the strongest instrumental variable. Use of OCT and ophthalmoscopy affected the number of injections given and resulted in an increase in visual acuity gains from baseline of 17.6 letters in year 1 and 2.5 letters in year 2. Regression models using the instrumental variable (OCT and ophthalmoscopy combined) showed that ≥5.1 (95% CI: 3.3-11.4) ranibizumab injections were needed to maintain visual acuity from baseline to year 1 and ≥8.3 (95% CI: 5.3-18.8) injections were needed to maintain visual acuity from year 1 to year 2. To gain ≥15 letters, ≥7.9 (95% CI: 5.1-17.5) ranibizumab injections would be needed in year 1 and ≥16.1 (95% CI: 10.3-36.4) injections would be needed over 2 years.ConclusionsThese findings highlight the role that regular monitoring plays in guiding neovascular AMD therapy and they showed that the number of ranibizumab injections needed to maintain visual acuity is higher than that administered in AURA.

Genetic polymorphisms and retinal vein occlusion in an Italian population.

In this study, we assessed the prevalence of polymorphisms in genes involved in hyperhomocysteinemia or hemostasis to shed light on their role, if any, in retinal vein occlusion (RVO). We recruited 37 Italian patients (17 men and 20 women) with a diagnosis of central or branch RVO based on fundus examination and retinal fluorescein angiography, as well as 45 healthy controls. Risk factors and family history of RVO of all subjects were recorded. The distributions of polymorphisms in patients and controls were evaluated using the χ(2) test and OR. We confirmed an increased risk in subjects with dyslipidemia (high density lipoprotein <59 mg/dL: 17.8% of controls, 43.2% of patients, P = 0.0002; low density lipoprotein >130 mg/dL: 26.7% controls, 54.1% patients, P = 0.0002), arterial hypertension (60% controls, 75.7% patients, P = 0.023), and high body mass index (28.9% controls, 70.3% patients, P < 0.0001, and excluded involvement of the selected polymorphisms in RVO. Overall, the tested polymorphisms did not appear to be useful for assessing predisposition or for the diagnosis and prognosis of RVO.

Clinical and molecular genetic study of 12 Italian families with autosomal recessive Stargardt disease.

Stargardt disease was diagnosed in 12 patients from 12 families using complete ophthalmologic examination, fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography. DNA was extracted for polymerase chain reaction (PCR) and direct DNA sequencing (ABCA4 gene). Genetic counseling and eye examination were offered to 16 additional family members. Various patterns of presentation were observed in patients with clinical diagnoses of Stargardt disease. The genetic study identified 2 mutations in 75% of families (9/12); a second mutation could not be found in the remaining 25% of families (3/12). The most frequent mutation was G1961E, found in 17% of families (2/12). This finding is similar to that of a previous analysis report of an Italian patient series. Four new mutations were also identified: Tyr1858Asp, Leu1195fsX1196, p.Tyr850Cys, and p.Thr959Ala. Our results suggest that PCR and direct DNA sequencing are the most appropriate techniques for the analysis of the ABCA4 gene. However, this method requires supplementation with specific PCR analysis to diagnose large deletions. The study of the families identified healthy carriers and affected subjects in presymptomatic stages and was also useful for evaluating the risk of transmission to progeny. Combined ophthalmologic and genetic evaluation enabled better clinical management of these families.

Intravitreal pegaptanib sodium for choroidal neovascularisation secondary to age-related macular degeneration: Pan-European experience.

PURPOSE: To evaluate visual outcomes in patients with neovascular age-related macular degeneration (NV-AMD) who were treated with pegaptanib sodium in European clinical ophthalmology practices. METHODS: Thirteen centres in eight European countries participated in this retrospective study. Medical records for patients with any angiographic subtype of subfoveal choroidal neovascularisation secondary to NV-AMD with visual acuities (study eye) of 20/40-20/320 treated with 0.3 mg pegaptanib as first-line treatment and with at least 24 weeks of follow-up were identified. Anonymised data reflecting at least 24 and up to 54 weeks of follow-up were recorded. Primary end points were visual acuity outcomes at weeks 24 and 54 compared with those reported at week 54 in the vascular endothelial growth factor (VEGF) Inhibition Study in Ocular Neovascularisation (VISION) trial. RESULTS: In all, 253 patients were followed for at least 24 weeks; 62 patients completed 54 weeks of follow-up. A mean of 4.4 (SD, 1.8) pegaptanib injections were administered through 24 weeks. Compared with the VISION trial, the European experience showed that >90% of patients in the current cohort lost <15 letters from baseline at both time points compared with 70% in the VISION trial at 54 weeks. Pegaptanib was well tolerated with no reported cases of endophthalmitis, traumatic cataract, or iatrogenic retinal detachment. CONCLUSIONS: Pegaptanib was found to stabilise vision in a greater percentage of patients and produced greater overall visual improvement in this group of treatment-naive patients with NV-AMD compared with outcomes reported in the VISION trial; however, interpretation of these results should be tempered given the differences in design between this retrospective study and the prospective controlled trial.

In-vivo diffusing-wave-spectroscopy measurements of the ocular fundus.

We present what is to our knowledge the first observation of a diffusing-wave-spectroscopy signal recorded in-vivo on the ocular fundus. A modified ophthalmic microscope was developed which can acquire diffusing-wave-spectroscopy signal from the eye fundus. The diffusing-wave-spectroscopy signal was recorded in-vivo on a rabbit eye during transpupillary thermotherapy. Experimental results show the ability of the system to detect motion of the scattering sites in the ocular fundus layers during laser thermal heating.

Evolving European guidance on the medical management of neovascular age related macular degeneration.

BACKGROUND: Until recently, only two options were available for the treatment of choroidal neovascularisation (CNV) associated with age related macular degeneration (AMD)-thermal laser photocoagulation and photodynamic therapy with verteporfin (PDT-V). However, new treatments for CNV are in development, and data from phase III clinical trials of some of these pharmacological interventions are now available. In light of these new data, expert guidance is required to enable retina specialists with expertise in the management of AMD to select and use the most appropriate therapies for the treatment of neovascular AMD. METHODS: Consensus from a round table of European retina specialists was obtained based on best available scientific data. Data rated at evidence levels 1 and 2 were evaluated for laser photocoagulation, PDT-V, pegaptanib sodium, and ranibizumab. Other treatments discussed are anecortave acetate, triamcinolone acetonide, bevacizumab, rostaporfin (SnET2), squalamine, and transpupillary thermotherapy. RESULTS: PDT-V is currently recommended for subfoveal lesions with predominantly classic CNV, or with occult with no classic CNV with evidence of recent disease progression and a lesion size

Combining photodynamic therapy and feeder vessel photocoagulation: a pilot study.

Patients receiving photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis AG), a new treatment for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and pathologic myopia, should be scheduled for follow-up every 12 weeks (+/-2 weeks) after the initial treatment. However, important data from clinical practice and from small series studies suggest that this period between treatment may be too long for some patients. In this pilot study we explore the safety and the possibility of improving the extent and duration of PDT benefit using feeder vessel treatment (FVT). This study suggests that the combination of verteporfin therapy and FVT is a safe procedure; it also suggests a possibility for prolonging the effect of verteporfin therapy.

Laser treatment of feeder vessels in subfoveal choroidal neovascular membranes: a revisitation using dynamic indocyanine green angiography.

OBJECTIVE: This study aimed to determine whether the indocyanine green angiography (ICGA)-guided laser treatment of feeder vessels (FVs) may be useful in the management of the subfoveal choroidal neovascular membranes (CNVM) in patients with age-related macular degeneration (ARMD). DESIGN: Noncomparative case series. PARTICIPANTS: The authors considered a series of 15 patients with subfoveal CNVM in whom feeder vessels could be clearly detected by means of dynamic ICGA but not necessarily with fluorescein angiography (FA). On the basis of the indications of the pilot study, the authors also studied a second series of 16 patients with FVs smaller than 85 microm. INTERVENTION: Treatment of FV using argon green laser was performed. The ICGA was performed immediately after treatment, after 2, 7, 30 days, and then every 3 months, to assess FV closure. If an FV appeared to be still patent, it was immediately retreated and the follow-up was started again. The follow-up time ranged from 23 to 34 months for the pilot study and from 4 to 12 months for the second series. MAIN OUTCOME MEASURES: The obliteration of the membrane and change in visual acuity from baseline were measured. The effect on the treatment of the number and width of the FVs, and the size and location of the membrane, also was evaluated. RESULTS: In the pilot study, the CNVM was obliterated after the first treatment in only one patient, five patients needed more than one treatment, and obliteration failed in nine patients (40% success rate). The rate of success was affected by the width and number of the FVs. The success rate in the second series of 16 patients was higher (75%). CONCLUSIONS: The success of the laser treatment of FVs depends on their width, length, and number. Dynamic ICGA, which detects smaller FVs and makes it possible to control the laser effect and initiate immediate retreatment in the case of incomplete FV closure, should be considered mandatory for this type of treatment; a comparable success rate would have been unlikely using the other currently available methods of treating subfoveal CNVMs.

Deep retinal vascular anomalous complexes in advanced age-related macular degeneration.

PURPOSE: The authors describe the clinical characteristics of a group of patients with age-related macular degeneration (AMD), deep retinal vascular anomalous complexes (RVACs), advanced Bruch membrane changes, and severe visual loss. Based on clinical evaluation and imaging studies, the authors hypothesize the cause of such retinal vascular formations. PATIENTS AND METHODS: The authors quantified an initial case series of 6 patients and expanded it to 11 patients (14 eyes) with AMD and RVACs diagnosed by fluorescein angiography or slit-lamp examination. Associated pigment epithelial detachments (PEDs) of 13 eyes are described. In addition to the clinical and fluorescein angiography descriptions, infrared imaging and indocyanine green angiography were used to characterize more recently described RVACs and fellow eyes. RESULTS: Each study eye had a clearly defined anastomosis connecting the retinal circulation to a vascular complex in the deep retina. The RVACs associated with PEDs assumed a more central location than did typical choroidal neovascularization associated with PEDs. In seven eyes with RVACs, there were clinically recognizable retinovascular findings: intraretinal hemorrhages, telangiectasia, or microaneurysms. Legal blindness occurred in 9 of 11 patients. CONCLUSION: These results indicate that retinovascular changes can be associated with nondisciform AMD. The authors speculate that neurodegenerative changes and hypoxia may lead to such changes, the RVAC being a more advanced finding. Closure of an RVAC with photocoagulation is difficult, perhaps because of its higher blood flow. The visual outcome is poor, not only because of the advanced state of the underlying AMD, but also because of the exudative nature of the RVAC.

In vivo measurement of lipofuscin in Stargardt's disease--Fundus flavimaculatus.

PURPOSE: Several histopathologic studies have concluded that Stargardt's disease (Fundus flavimaculatus) is associated with abnormally high levels of lipofuscin-like material in the retinal pigment epithelium. The purpose of this study was to determine whether this material has the same fluorescence characteristics as lipofuscin in vivo and whether noninvasive measurements identify a significant elevation in this material. METHODS: Five patients with autosomal recessive Stargardt's disease were included in this study, as were 45 healthy controls. All patients had the angiographic dark choroid sign. The intensity and emission spectra of lipofuscin fluorescence were measured by noninvasive fundus spectrophotometry at 7 degrees temporal to the fovea. RESULTS: The fluorescence intensities in the five patients with Stargardt's disease were significantly higher (P < 0.0001) than those observed in normal subjects of the same age. The emission spectra in the patients are similar in shape to those measured in normals, but flecks appear to shift the spectra toward shorter wavelengths. CONCLUSIONS: The spectral characteristics of the fluorophore observed in patients with Stargardt's disease are consistent with those of retinal pigment epithelial lipofuscin. These patients have abnormally high levels of lipofuscin, confirming previous histopathologic observations. Noninvasive retinal pigment epithelial lipofuscin measurements may be a useful adjunct in the diagnosis of Stargardt's disease.-F. flavimaculatus.

In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics.

PURPOSE: To characterize the intrinsic fluorescence (autofluorescence) of the human ocular fundus with regard to its excitation and emission spectra, age relationship, retinal location, and topography, and to identify the dominant fluorophore among the fundus layers. METHODS: Using a novel fundus spectrophotometer, fluorescence measurements were made at 7 degrees temporal to the fovea and at the fovea in 30 normal subjects and in 3 selected patients. Topographic measurements were made in 3 subjects. Ex vivo measurements of fluorescence of human retinal pigment epithelium (RPE) were obtained and compared to in vivo data. RESULTS: Fundus fluorescence reveals a broad band of emission between 500 and 750 nm, a maximum of approximately 630 nm, and optimal excitation of approximately 510 nm. Exhibiting a significant increase with age, this fluorescence is highest at 7 degrees to 15 degrees from the fovea, shows a well-defined foveal minimum, and decreases toward the periphery. In vivo fluorescence spectra are consistent with those obtained ex vivo on human RPE. Measurements with short wavelength excitation are strongly influenced by ocular media absorption and reveal an additional minor fluorophore in the fovea. CONCLUSIONS: Spectral characteristics, correlation with age, topographic distribution, and retinal location between the choriocapillaris and the photoreceptors suggest that the dominant fundus fluorophore is RPE lipofuscin. The minor fluorophore is probably in the neurosensory retina but has not been identified.

Arteriovenous crossing as a risk factor in branch retinal vein occlusion.

To evaluate the importance of the position of the artery anterior to the vein in the arteriovenous crossing to the pathogenesis of first- and second-order branch retinal vein occlusion, we studied the fluorescein angiograms of 65 patients with branch retinal vein occlusion (65 eyes). The corresponding crossing in the opposite arcade (superior or inferior) served as the control. In a statistically significant percentage of crossings, the arteries were anterior to the veins in second-order branches (odds ratio, 6.66; 95% confidence interval, 1.98 to 32.33; chi 2, 12.56; P = .000394). However, their position was not found to be important in the pathogenesis of first-order occlusions (odds ratio, 1.3; 95% confidence interval, 0.23 to 9.01; chi 2, 0.14; P = .708281). These results suggest that some differences may exist in the risk factors for branch retinal vein occlusion depending on the site of the occlusion.