Neuroretinal and microvascular retinal features in dementia with Lewy body assessed by optical coherence tomography angiography.

OBJECTIVE: To explore retinal changes in patients with Dementia with Lewy Bodies (DLB) using Spectral Domain-Optical Coherence Tomography (SD-OCT) and Optical Coherence Tomography Angiography (OCTA), aiming to identify potential biomarkers for diagnosis and monitoring. METHODS: A cross-sectional study analyzed 15 DLB patients and 18 matched controls. Participants underwent physical, neurological, neuropsychological, and ophthalmological evaluations, including SD-OCT and OCTA. Logistic regression, adjusted for age, sex, and inter-eye correlation, was employed to identify retinal alterations in patients affected by DLB. RESULTS: OCTA revealed that DLB is associated with reduced superficial and deep vessel densities (SVD and DVD) in the macula (p < 0.01), as well as decreased peripapillary vessel density (ppVD, p < 0.01). SD-OCT parameters showed correlations with DLB, including reduced central macular thickness (CMT, p < 0.001) and thinning of the ganglion cell layer-inner plexiform layer (GCL-IPL, p < 0.01). Logistic regression (R²=0.26) identified reduced ppVD as a significant predictor of DLB (p = 0.030). CONCLUSIONS: Impairments in retinal capillaries, especially lower ppVD, might mirror cerebral hypoperfusion in DLB, potentially due to reduced Vascular Endothelial Growth Factor (VEGF) levels and increased α-synuclein. Further investigations are warranted to confirm the causal relationship between these observations, disease severity, and progression, as well as their potential role as biomarkers for DLB.

Proliferative Vitreoretinopathy in Retinal Detachment: Perspectives on Building a Digital Twin Model Using Nintedanib.

Proliferative vitreoretinopathy (PVR) is a pathological process characterized by the formation of fibrotic membranes that contract and lead to recurrent retinal detachment. Pars plana vitrectomy (PPV) is the primary treatment, but recurrence rates remain high, as surgery does not address the underlying molecular mechanisms driving fibrosis. Despite several proposed pharmacological interventions, no approved therapies exist, partly due to challenges in conducting preclinical and in vivo studies for ethical and safety reasons. This review explores the potential of computational models and Digital Twins, which are increasingly gaining attention in medicine. These tools could enable the development of progressively complex PVR models, from basic simulations to patient-specific Digital Twins. Nintedanib, a tyrosine kinase inhibitor targeting PDGFR, VEGFR, and FGFR, is presented as a prototype for computational models to simulate its effects on fibrotic pathways in virtual patient cohorts. Although still in its early stages, the integration of computational models and Digital Twins offers promising avenues for improving PVR management through more personalized therapeutic strategies.

Beta-Amyloid Peptide in Tears: An Early Diagnostic Marker of Alzheimer's Disease Correlated with Choroidal Thickness.

We aimed to evaluate the diagnostic role of Alzheimer's disease (AD) biomarkers in tears as well as their association with retinal and choroidal microstructures. In a cross-sectional study, 35 subjects (age 71.7 ± 6.9 years) were included: 11 with prodromal AD (MCI), 10 with mild-to-moderate AD, and 14 healthy controls. The diagnosis of AD and MCI was confirmed according to a complete neuropsychological evaluation and PET or MRI imaging. After tear sample collection, ß-amyloid peptide Aß1-42 concentration was analyzed using ELISA, whereas C-terminal fragments of the amyloid precursor protein (APP-CTF) and phosphorylated tau (p-tau) were assessed by Western blot. Retinal layers and choroidal thickness (CT) were acquired by spectral-domain optical coherence tomography (SD-OCT). Aß1-42 levels in tears were able to detect both MCI and AD patients with a specificity of 93% and a sensitivity of 81% (AUC = 0.91). Tear levels of Aß1-42 were lower, both in the MCI (p < 0.01) and in the AD group (p < 0.001) when compared to healthy controls. Further, Aß1-42 was correlated with psychometric scores (p < 0.001) and CT (p < 0.01). CT was thinner in the affected patients (p = 0.035). No differences were observed for APP-CTF and p-tau relative abundance in tears. Testing Aß1-42 levels in tears seems to be a minimally invasive, cost-saving method for early detection and diagnosis of AD.

Cocaine Abuse as an Immunological Trigger in a Case Diagnosed with Eales Disease.

Background: Eales disease is a clinical syndrome affecting the mid-peripheral retina with an idiopathic occlusive vasculitis and possible subsequent retinal neovascularization. The disease can develop into visually threatening complications. Case Presentation: We report the case of a 40-year-old Caucasian male with a history of cocaine abuse who presented with blurred vision in the left eye (LE). Fundus examination showed vitreous hemorrhages, peripheral sheathing of venous blood vessels, areas of retinal neovascularization in the LE, and peripheral occlusive phlebitis in the right eye. The full serologic panel was negative except for the heterozygous mutation of factor V Leiden. Clinical and biochemical parameters suggested a diagnosis of Eales disease. Therapy with dexamethasone, 1 mg per kg per day, tapered down slowly over 4 months, and peripheral laser photocoagulation allowed a regression of clinical signs and symptoms. Conclusion: This case shows an uncommon presentation of Eales disease associated with cocaine abuse. Both cocaine abuse and a thrombophilic pattern, as cofactors, might have sensitized the retinal microcirculation on the pathogenetic route to this retinal pathology. Furthermore, in view of this hypothesis, a thorough ocular and general medical history investigating drug abuse and coagulation disorders is recommended for ophthalmologists in such cases.

Correlation between Morphological Characteristics of Macular Edema and Visual Acuity in Young Patients with Idiopathic Intermediate Uveitis.

Background and Objectives: Macular edema (ME) is a common complication of intermediate uveitis (IU). It is often responsible for a decrease in visual acuity (VA). Three distinct patterns of macular edema have been described in intermediate uveitis, namely, cystoid macular edema (CME), diffuse macular edema (DME), and serous retinal detachment (SRD). The current study aims to describe the characteristics of macular edema in young patients with idiopathic intermediate uveitis and to correlate its features with VA using spectral domain optical coherence tomography (SD-OCT). Materials and Methods: A total of 27 eyes from 18 patients with idiopathic IU complicated by ME were included in this retrospective study. All patients underwent SD-OCT; data were gathered at the onset of ME. Best-corrected VA (BCVA) was correlated with the morphological features of ME. Results: BCVA was negatively correlated with Ellipsoid Zone (EZ) disruption (p = 0.00021), cystoid pattern (p = 0.00021), central subfield thickness (CST) (p < 0.001), and serous retinal detachment (0.037). Conclusions: In ME secondary to idiopathic IU, VA negatively correlates with Ellipsoid Zone disruption and increases in CST. Moreover, vision is influenced by the presence of cysts in the inner nuclear and outer nuclear layers and by the neuroepithelium detachment.

COMPARISON BETWEEN SCLERAL BUCKLING AND VITRECTOMY IN THE ONSET OF CYSTOID MACULAR EDEMA AND EPIRETINAL MEMBRANE AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To investigate the incidence and risk factors for the main complications in patients with rhegmatogenous retinal detachment treated with scleral buckling (SB) or pars plana vitrectomy (PPV). METHODS: A retrospective, comparative, observational study was conducted. The medical records of 107 patients with primary rhegmatogenous retinal detachment who were managed with SB (n = 57) or PPV (n = 50) were reviewed. Scleral buckling was performed using scleral encircling solid silicone band and circumferential solid silicone exoplant to support the break. Pars plana vitrectomy was combined with phacoemulsification in phakic eyes and with scleral encircling in inferior detachments. Follow-ups, including spectral-domain optical coherence tomography examination, were scheduled at 1, 3, and 12 months after surgery. Propensity score matching was used to adjust for potential preoperative selection bias. RESULTS: The overall incidence of postoperative cystoid macular edema (CME) and epiretinal membrane was 14.95% and 30.84%, respectively. Compared with SB, CME was more frequent in the PPV (P = 0.021) and in the PPV pseudophakic eyes (P = 0.027). Postoperative CME was an early, predominantly transient complication and regressed in 67% of SB and in 77% of PPV eyes within 12 months after surgery. No differences were observed regarding epiretinal membrane development. Except for the surgical technique, no preoperative factors associated with CME were identified. A correlation between epiretinal membrane and patients' age was found (P = 0.028). CONCLUSION: The incidence of CME after rhegmatogenous retinal detachment repair was higher in patients who underwent PPV, either alone or combined with phacoemulsification, than in those treated with SB. Epiretinal membrane development was correlated to older age, regardless of the surgical procedure.

Involvement of ocular surface in graft-versus-host disease: An update from immunopathogenesis to treatment.

Graft-versus-host disease is a common complication of hematopoietic stem cell transplantation and the ocular surface is a main target of inflammatory reaction.

Long-term ocular biometric variations after scleral buckling surgery in macula-on rhegmatogenous retinal detachment.

BACKGROUND: Myopic shift and biometric ocular changes have been previously observed after scleral buckling (SB) surgery in rhegmatogenous retinal detachment (RRD), but long term-term outcomes had not yet been explored. The purpose of present study is to evaluate long term ocular biometric changes in patients with primary macula-on RRD treated with SB. METHODS: In this retrospective, observational study, we reviewed the medical records of patients undergoing SB surgery for macula-on RRD. Ocular biometry was performed before and at the most recent visit after surgery. Axial length (AXL), anterior chamber depth (ACD), anterior corneal astigmatism and spherical equivalent in treated eyes were compared before and after surgery as well as with those of fellow eyes. RESULTS: Thirty-four eyes of 17 patients with a mean age of 57.0 ± 8.9 years were included. The mean follow-up duration was 50.9 ± 21.9 months (median 53.0; range 12 to 82 months). A significant postoperative AXL increase of 0.83 mm and a concomitant myopic shift of 1.35 diopters was observed in the operated eyes (p <  0.0001). The preoperative AXL was the only predictive factor of AXL change after surgery (B = 0.152, 95% CI 0.059 to 0.245, ß = 0.668, P = 0.003). Compared to fellow eyes, a postoperative ACD shallowing of 0.1 mm was found in operated eyes (p <  0.05), while there were no long-term changes of anterior corneal astigmatism. CONCLUSIONS: We show that the preoperative AXL is the only predictive factor of AXL increase after SB surgery. Scleral encircling induces a concomitant long-term shallowing of the AC, therefore fourth generation intraocular lens (IOL) power calculation formulae should be used for patients requiring cataract surgery after SB.

High myopic patients with and without foveoschisis: morphological and functional characteristics.

PURPOSE: Myopic foveoschisis (MF) is characterized by the splitting of the retinal layers in the fovea of patients with high myopia (HM). MF may progress into foveal detachment or macular hole formation with consequent loss of central vision. The aim of this study is to investigate morphological and functional changes of the macular region in myopic subjects with and without foveoschisis. DESIGN: Observational, cross-sectional, comparative study. METHODS: Forty-eight patients with HM and 24 healthy controls were evaluated by spectral domain-optical coherence tomography (SD-OCT), multifocal electroretinography (mfERG) and microperimetry (MP-1) tests to assess macular thickness, functionality and sensitivity values, respectively. The results of the diagnostic examinations were compared between three groups: HM patients with MF (N = 24), HM patients without MF (N = 24) and control group (CG) (N = 24). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). One-way analysis of variance (ANOVA) followed by Tukey's post hoc test was used to analyze differences between groups unless specified; p values < 0.05 were considered as statistically significant. Gender distribution was compared by the Chi square test. RESULTS: The statistical analysis with one-way ANOVA followed by Tukey's post hoc test showed a significant increase in macular thickness in HM patients with MF when compared to both HM patients without MF and CG. Morphological changes were associated with functional impairment as demonstrated by the significant decrease in amplitude of the P1 wave and MP-1 sensitivity (p < 0.05), according to the anatomical landmarks. CONCLUSIONS: This study showed that the morphological changes observed in the central retina of HM patients with MF are associated with functional alterations. High-tech diagnostic tests such as SD-OCT, mfERG and MP-1 could be useful for management in complications of MF.

Self-sealing posterior scleral perforation in airgun ocular trauma, surgical tip: a case report.

BACKGROUND: Intraorbital metallic foreign bodies have varied clinical presentations. Here, we report the unusual case of intraoperative evidence of spontaneously healed posterior scleral perforation in a severe ballistic trauma without previous instrumental signs of penetrating wound and complete visual restoration after surgery. CASE PRESENTATION: The patient was hit by several lead hunting pellets in the chest, abdomen, limbs, face and orbit. Computed Tomography (CT) images revealed the presence of a pellet within the orbitary cavity, close to the optic nerve, with no signs of penetrating ocular wound. While performing vitrectomy for severe vitreous hemorrhage, a point of strong adherence between a old hemorrhage and retinal surface was identified and managed conservatively, as it was attributed to trauma related-impact area. So, lead foreign body took an unusual trajectory impacting the globe and finally lodging back in the deep orbitary cavity, in absence of significant ocular injury and with visual prognosis preservation. CONCLUSIONS: Our findings provide further information on orbital injuries from airguns, a theme of growing popularity and concern. Intraoperative recognition of hardly removable old hemorrhagic clot as self-blockage site of posterior scleral penetrating trauma, allowed for surgical stabilization and minimal solicitation of the area to avoid inadvertent perforation.

VEGF inhibition alters neurotrophin signalling pathways and induces caspase-3 activation and autophagy in rabbit retina.

This study sought to evaluate the prospective role exerted by vascular endothelial growth factor (VEGF) in the modulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) signalling pathways in the rabbit retina. To reach this aim, the anti-VEGF agents aflibercept and ranibizumab were used as a pharmacological approach to evaluate the putative consequences elicited by VEGF inhibition on neurotrophin signalling. VEGF inhibition determined a marked imbalance in proneurotrophin expression, a significant reduction in TrkA and TrkB phosphorylation states and a decrease in the pan-neurotrophin receptor p75. Importantly, VEGF blockade also caused a strong increase in cleaved caspase-3, beclin-1 and lipidated LC3. The effects were more pronounced in the aflibercept group when compared with ranibizumab-treated rabbits, particularly 1 week after injection. This study demonstrates that VEGF exerts pivotal physiological roles in regulating NGF and BDNF pathways in the retina, as its inhibition by anti-VEGF agents deeply impacts neurotrophin homeostasis. These events are accompanied by a sustained induction of apoptotic and autophagic markers, suggesting that anti-VEGF-dependent impairments in neurotrophin signalling could be responsible for the activation of retinal cell death pathways.

In vivo antivascular endothelial growth factor treatment induces corneal endothelium apoptosis in rabbits through changes in p75NTR-proNGF pathway.

Intravitreal injection (IVT) of antivascular endothelial growth factor (anti-VEGF) agents is widely used for the treatment of retinal vascular diseases. Recently, the injection of anti-VEGF agents in the ocular anterior chamber has been proposed for the treatment of neovascular glaucoma and potential side effects on the corneal structures have been investigated with contrasting results. Increasing evidence has demonstrated that VEGF inhibition is associated with cellular apoptotic changes and that this effect may be mediated by alterations in nerve growth factor (NGF) pathway. In this study, we demonstrated that anterior chamber injection (IC), but not IVT injection of two different anti-VEGF agents, aflibercept and ranibizumab, affects rabbit corneal endothelium in terms of survival and apoptosis and is associated with changes in endothelial expression of NGF precursor (proNGF) and p75 neurotrophin receptor (p75NTR) receptor. We observed an increase in corneal endothelial cell incorporation of trypan blue and expression of cleaved-caspase 3 (c-Casp3), p75NTR, and RhoA after IC injection of both anti-VEGF drugs when compared with the vehicle. Our results showed that apoptosis induction by aflibercept was more pronounced when compared with that of ranibizumab. Aflibercept also mediated a significant increase in endothelial expression of proNGF when compared with the vehicle. In line with these data, IC administration of both anti-VEGF agents induced the activation of apoptotic signals in endothelial cells, including an increase in c-Casp3, decrease in Bad Ser 112 phosphorylation, and unbalance of AKT phosphorylation. These results demonstrated that administration of anti-VEGF in the anterior chamber of rabbit affects endothelial cell survival by inducing apoptosis through alteration of NGF pathway.

Attenuation of Choroidal Thickness in Patients With Alzheimer Disease: Evidence From an Italian Prospective Study.

INTRODUCTION: To compare the 12-month choroidal thickness (CT) change between Alzheimer disease (AD) patients and normal subjects. METHODS: In this prospective, observational study, 39 patients with a diagnosis of mild to moderate AD and 39 age-matched control subjects were included. All the subjects underwent neuropsychological (Mini Mental State Examination, Alzheimer disease Assessment Scale-Cognitive Subscale, and the Clinical Dementia Rating Scale) and ophthalmological evaluation, including spectral domain optical coherence tomography, at baseline and after 12 months. CT was measured manually using the caliper tool of the optical coherence tomography device. RESULTS: After 12 months, AD patients had a greater reduction of CT than controls (P≤0.05, adjusted for baseline CT, age, sex, axial length, and smoking). DISCUSSION: CT in patients with AD showed a rate of thinning greater than what could be expected during the natural course of aging.

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders.

The tear film represents the interface between the eye and the environment. The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome. Despite having a multifactorial origin, the main risk factors are female gender and advanced age. Likewise, morphological changes in several glands and in the chemical composition of their secretions, such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors that maintain a steady ocular surface. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic inflammation that involves the ocular surface. DE syndrome is one of the most commonly encountered diseases in clinical practice, and many other causes related to daily life and the increase in average life expectancy will contribute to its onset. This review will consider the disorders of the ocular surface that give rise to such a widespread pathology. At the end, the most recent therapeutic options for the management of DE will be briefly discussed according to the specific underlying pathology.

Spectral domain optical coherence tomography and B-scan ultrasonography in the evaluation of retinal tears in acute, incomplete posterior vitreous detachment.

BACKGROUND: The purpose of this study was to evaluate the extension and traction effects of posterior vitreous detachment (PVD) complicated with retinal tears using spectral domain optical coherence tomography (OCT) and B-scan ultrasonography. METHODS: Complete ophthalmological examination, B-scan ultrasonography and spectral domain OCT were performed in patients with acute PVD and retinal tears. Vitreous detachment was classified as complete or incomplete, based on extent of posterior pole or peripheral vitreous detachment. Retinal tear location and persistent traction on the retinal flap was evaluated with B-scan ultrasonography and OCT. Categorical data were evaluated with Fisher's exact test. Statistical significance was considered as P < 0.05. RESULTS: Twenty-six eyes of 25 patients were assessed. Four eyes (15 %) presented complete PVD with detachment at the posterior pole and periphery. 22 eyes (85 %) presented incomplete PVD with detachment in the periphery. Twenty eyes presented retinal tears in the superior quadrants with respect to only 6 in the inferior quadrants (p = 0.006). There was a higher incidence of retinal tears in the pre with respect to post-equatorial areas (19 vs 7 eyes, p = 0.019). B-scan ultrasonography and OCT revealed persistent traction on the retinal tear flap in 19 and 15 eyes, respectively. CONCLUSIONS: In acute PVD, retinal tears are prevalently associated with peripheral vitreous detachment. The impact of complete or incomplete PVD can be of clinical value when evaluating patients with retinal tears.

Intravitreal anti-vascular endothelial growth factor for retinal angiomatous proliferation in treatment-naive eyes: long-term functional and anatomical results using a modified PrONTO-style regimen.

PURPOSE: To evaluate long-term outcome of intravitreal anti-vascular endothelial growth factor monotherapy in retinal angiomatous proliferation. METHODS: Twenty-one treatment-naive eyes were included in this prospective, interventional case series. Treatment was three monthly injections of bevacizumab and/or ranibizumab with a modified PrONTO-style regimen. Best-corrected visual acuity (BCVA) was evaluated. The influence of baseline BCVA and pretreatment pigment epithelial detachment on BCVA outcome or retreatment were assessed by Pearson correlation analysis. RESULTS: Results were evaluated at 2 years and 3 years for 21 and 13 eyes, respectively. Mean baseline BCVA improved significantly from 44.5 (± 11.0) (20/32) to 51.1 (± 9.7) (20/24) and 50.8 (± 10.4) letters (20/24) at 2 and 3 years, respectively (P = 0.02 and P = 0.049). Pigment epithelial detachment correlated negatively with BCVA outcome (r = -0.65, P = 0.002 and r = -0.67, P = 0.01 at 2 years and 3 years, respectively) and was significantly associated with retreatment (r = 0.62, P = 0.003 and r = 0.87, P < 0.0001 at 2 years and 3 years, respectively). Complete occlusion of the lesion was obtained in 71% and 69% of eyes at 2 years and 3 years, respectively, with a mean of 9.4 injections at 3 years. CONCLUSION: Intravitreal anti-vascular endothelial growth factor monotherapy was a valid option for retinal angiomatous proliferation. Stable or improved visual acuity was obtained in 95% and 100% of eyes at 2 years and 3 years, respectively.

Choroidal Effusion with Exudative Retinal Detachment following Non Perforating YAG-Laser Peripheral Iridotomy: A Case Report.

AIM: To report a case of choroidal effusion and exudative retinal detachment following a non perforating Yttrium-Aluminium-Garnett (YAG)-laser iridotomy. DESIGN: Case report. METHODS: A 53-year-old woman complains of sudden onset of blurred vision in her left eye 15 days after the attempt of YAG-laser peripheral iridotomy. Clinical examination revealed 3+ flare and 1+ cells in the anterior chamber, 2+ vitreous cells, swollen optic nerve, ciliochoroidal effusion, and exudative retinal detachment involving macular area in the left eye. After starting treatment with prednisone 25 mg once daily, choroidal effusion and retinal detachment were managed successfully without any surgical approach. CONCLUSION: Serous choroidal and exudative retinal detachments are rare complications following YAG-laser procedure. In our case, this clinical presentation occurs after a non perforating iridotomy. In medical practice, exudative retinal detachment should be always considered after YAG-laser iridotomy.

Perspective role of Substance P in Amyotrophic Lateral Sclerosis: From neuronal vulnerability to neuroprotection.

The neuropeptide Substance P (SP) and its preferred Neurokinin1 Receptor (NK1R) are known to participate in the physiopathology of neurodegenerative diseases and mainly exert a neuroprotective role. In the present work, we have described the involvement of SP and NK1R in Amyotrophic Lateral Sclerosis (ALS). This was demonstrated by the detection of altered levels of SP in the brain, spinal cord and cerebrospinal fluid (CSF) of patients and preclinical models of ALS, and by its ability to inhibit excitotoxicity-induced neurodegeneration in ALS animal models. These data are supported by results indicating an excitatory effect of SP at the motor neuron (MN) level, which promotes locomotor activity. ALS patients are characterized by a differential susceptibility to MNs degeneration, since sphincters and extraocular muscles are classically spared. It is hypothesized that SP may play a role in the maintenance of the ocular system and the innervation of the pelvic floor by contributing directly or indirectly to the selective resistance of this subset of MNs.

Long-Term Functional Outcomes of Retinal Detachment Due to Acute Retinal Necrosis: A Case Series.

Objectives: To evaluate the long-term anatomical and functional prognosis of patients with retinal detachment (RD) secondary to acute retinal necrosis (ARN) treated with pars plana vitrectomy (PPV). Methods: This retrospective case series included 21 eyes from 21 patients with RD secondary to ARN. The study analyzed vitreous or aqueous biopsy results, the impact of antiviral therapy, time to retinal detachment, changes in visual acuity (VA), and anatomical and surgical outcomes. All cases underwent 23-gauge PPV with silicone oil tamponade, and an episcleral encircling band was used in 11 cases. All patients received systemic antiviral therapy at diagnosis. Results: Retinal reattachment was achieved in 91% of cases during follow-up, with an average follow-up period of 39.5 ± 36.8 months. The average time from ARN diagnosis to RD onset was 33.3 ± 27.5 days. VZV was detected in 10 eyes through PCR analysis. Significant differences in visual prognosis were found between macula-off and macula-on RD (p = 0.048). Eyes with optic nerve head inflammation had worse final VA (p = 0.010). No significant difference was observed between preoperative VA and VA at the end of follow-up (p = 0.665). Conclusions: VZV was the primary virus associated with ARN-related RD. Early involvement of the macula and optic nerve in retinitis negatively impacted the final visual prognosis.