Uveitis and Other Ocular Complications Following COVID-19 Vaccination

Coronavirus disease 2019 (COVID-19) vaccines can cause transient local and systemic post-vaccination reactions. The aim of this study was to report uveitis and other ocular complications following COVID-19 vaccination. The study included 42 eyes of 34 patients (20 females, 14 males), with a mean age of 49.8 years (range 18–83 years). The cases reported were three herpetic keratitis, two anterior scleritis, five anterior uveitis (AU), three toxoplasma retinochoroiditis, two Vogt-Koyanagi-Harada (VKH) disease reactivations, two pars planitis, two retinal vasculitis, one bilateral panuveitis in new-onset Behçet’s disease, three multiple evanescent white dot syndromes (MEWDS), one acute macular neuroretinopathy (AMN), five retinal vein occlusions (RVO), one non-arteritic ischemic optic neuropathy (NAION), three activations of quiescent choroidal neovascularization (CNV) secondary to myopia or uveitis, and one central serous chorioretinopathy (CSCR). Mean time between vaccination and ocular complication onset was 9.4 days (range 1–30 days). Twenty-three cases occurred after Pfizer-BioNTech vaccination (BNT162b2 mRNA), 7 after Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19), 3 after ModernaTX vaccination (mRNA-1273), and 1 after Janssen Johnson & Johnson vaccine (Ad26.COV2). Uveitis and other ocular complications may develop after the administration of COVID-19 vaccine

Fattori di crescita e cellule staminali

La personalizzazione delle più moderne strategie di riabilitazione visiva è in grado di ottimizzare l’utilizzo del residuo visivo e/o delle capacità sensoriali non visive in un crescente numero di pazienti, realizzando un reale miglioramento della loro qualità di vita. Tuttavia, la maggior parte dei pazienti affetti da patologie oculari invalidanti o potenzialmente tali richiedono informazioni su possibili terapie in grado di farli tornare a vedere riferendosi, in particolare, alle cellule staminali ed a fattori di crescita quali, il fattore di crescita della cellula nervosa o Nerve Growth Factor (NGF) identificato da Rita Levi Montalcini negli Anni ‘50. I fattori di crescita sono proteine con molteplici funzioni di omeostasi tessutale tra cui la proliferazione, il differenziamento e la maturazione cellulare. Numerosi studi sperimentali sono in corso per valutare le potenzialità terapeutiche dei diversi fattori di crescita e per inquadrare il loro ruolo nella gestione dei pazienti con patologie disabilitanti le funzioni visive. Le cellule staminali sono cellule non mature e non specializzate, caratterizzate dalle capacità di auto-rinnovamento e di differenziamento eterogeneo (pluripotenza). L’auto-rinnovamento è la possibilità di compiere un numero illimitato di cicli replicativi mantenendo sempre il medesimo stadio differenziativo. La “potenza” è la capacità di generare una o più linee cellulari tramite il differenziamento. All'interno di quest’ultimo concetto è includibile anche quello di trans-differenziamento, cioè la capacità di una cellula staminale in fase di differenziamento di cambiare la propria linea cellulare modificando il suo programma di sviluppo. Il trans-differenziamento, evidenziato finora solo in animali da esperimento, permette a cellule staminali mesenchimali adulte o Mesenchimal Stem Cells (MSCs) di differenziarsi in cellule molto specifiche (come neuroni, cellule epiteliali, tipi cellulari ectodermici o endodermici) saltando da un cammino differenziativo ad un altro. Le tematiche riguardanti la “cura degli occhi” mediante fattori di crescita e cellule staminali devono essere affrontate in maniera del tutto diversa in relazione ai differenti tessuti oculari coinvolti dalla patologia causa di minorazione visiva. In base all’eterogenea derivazione embriogenetica delle diverse strutture oculari, sono distinguibili due principali ambiti applicativi: i. patologie del segmento anteriore, con particolare riferimento a quelle coinvolgenti le strutture corneali, quali l’epitelio (che origina dall’ectoderma), lo stroma (che origina dalla superficie anteriore della capsula di mesenchima indifferenziato che circonda il calice ottico) e l’endotelio (che origina da cellule della cresta neurale); ii. patologie del segmento posteriore, con particolare riferimento a quelle della retina / nervo ottico e dell’epitelio pigmentato retinico (EPR) che, rispettivamente, originano dalle pareti neuro-ectodermiche interna ed esterna dei calici ottici, derivanti dal tratto cefalico del tubo neurale come parti integranti del sistema nervoso centrale in formazione

Anti-VEGF Therapy for Retinal Vein Occlusions

Retinal vein occlusion (RVO) is the second most common cause of visual loss in the Western World. RVO is usually classified into branch RVO (BRVO) and central RVO (CRVO) according to the anatomical site of the vascular occlusion. The pathogenesis of RVO is not yet fully understood, however an important event is the intraluminal thrombus formation, which is usually secondary to several conditions such as hypertension, hyperlipidemia, diabetes and thrombophilia. The blockage of venous circulation causes an elevation of intraluminal pressure in the capillaries, leading to hemorrhages and leakage of fluid within the retina, increase of interstitial pressure and a consequent reduction of retinal perfusion. Ischemia may develop resulting in secretion of vascular endothelial growth factor (VEGF) that causes further vascular leakage and retinal oedema. VEGF has therefore a leading role in RVO pathogenesis and symptoms. As a consequence use of anti-VEGF agents by intravitreal injections has become very common with the aim to improve the clinical outcomes in these patients. Currently 2 anti-VEGF agents (ranimizumab and aflibercept) have been FDA (Food and Drug Administration) and EMA (European Medicine Agency) approved for the treatment of RVO, while another VEGF inhibitor (bevacizumab) is often used "off-label" in clinical practice. Many treatment regimens have been suggested in the clinical trials with these drugs, as monthly injections or injections when needed, however the ideal regimen has not been defined yet. We conducted a systematic review searching MEDLINE for the following terms: retinal vein occlusion, ranibizumab, bevacizumab, aflibercept, vascular endothelial growth factor, macular oedema. Data were extracted by one author (AG and BE) and checked by a second (BPM, CC). Aim of this article was to review available data for each drug, focusing on their efficacy and safety trying to compare their advantages and limits.Retinal vein occlusion (RVO) is the second most common cause of visual loss in the Western World. RVO is usually classified into branch RVO (BRVO) and central RVO (CRVO) according to the anatomical site of the vascular occlusion. The pathogenesis of RVO is not yet fully understood, however an important event is the intraluminal thrombus formation, which is usually secondary to several conditions such as hypertension, hyperlipidemia, diabetes and thrombophilia. The blockage of venous circulation causes an elevation of intraluminal pressure in the capillaries, leading to hemorrhages and leakage of fluid within the retina, increase of interstitial pressure and a consequent reduction of retinal perfusion. Ischemia may develop resulting in secretion of vascular endothelial growth factor (VEGF) that causes further vascular leakage and retinal oedema. VEGF has therefore a leading role in RVO pathogenesis and symptoms. As a consequence use of anti-VEGF agents by intravitreal injections has become very common with the aim to improve the clinical outcomes in these patients. Currently 2 anti-VEGF agents (ranimizumab and aflibercept) have been FDA (Food and Drug Administration) and EMA (European Medicine Agency) approved for the treatment of RVO, while another VEGF inhibitor (bevacizumab) is often used “off-label” in clinical practice. Many treatment regimens have been suggested in the clinical trials with these drugs, as monthly injections or injections when needed, however the ideal regimen has not been defined yet. We conducted a systematic review searching MEDLINE for the following terms: retinal vein occlusion, ranibizumab, bevacizumab, aflibercept, vascular endothelial growth factor, macular oedema. Data were extracted by one author (AG and BE) and checked by a second (BPM, CC). Aim of this article was to review available data for each drug, focusing on their efficacy and safety trying to compare their advantages and limits

Optical Coherence Tomography in Inflammatory and Neoplastic Lesions Deforming the Choroidal Profile

The choroid is the main part of the uvea, the vascular layer of the eye that lies between the retina and the sclera. The high vascular component of the choroid makes this structure susceptible to inflammation in multisystemic diseases, as well as the most common site of metastasis in the eye. Therefore, the choroid is involved in many pathological conditions, from uveitis to intraocular tumors. Differentiating between inflammatory and neoplastic lesions deforming the choroidal profile can sometimes be challenging. In addition, scleral disorders can also deform the choroidal profile. Choroidal imaging includes ophthalmic ultrasonography, indocyanine green angiography, and optical coherence tomography (OCT). Recent advances in choroidal imaging techniques, such as enhanced depth imaging optical coherence tomography (EDI-OCT) and swept-source optical coherence tomography (SS-OCT), have facilitated an in-depth analysis of the choroid. The purpose of this review article is to report on and highlight the most common OCT findings to help in the differential diagnosis between inflammatory and neoplastic lesions deforming the choroidal profile

Uveitis and Other Ocular Complications Following COVID-19 Vaccination

Coronavirus disease 2019 (COVID-19) vaccines can cause transient local and systemic post-vaccination reactions. The aim of this study was to report uveitis and other ocular complications following COVID-19 vaccination. The study included 42 eyes of 34 patients (20 females, 14 males), with a mean age of 49.8 years (range 18–83 years). The cases reported were three herpetic keratitis, two anterior scleritis, five anterior uveitis (AU), three toxoplasma retinochoroiditis, two Vogt-Koyanagi-Harada (VKH) disease reactivations, two pars planitis, two retinal vasculitis, one bilateral panuveitis in new-onset Behçet’s disease, three multiple evanescent white dot syndromes (MEWDS), one acute macular neuroretinopathy (AMN), five retinal vein occlusions (RVO), one non-arteritic ischemic optic neuropathy (NAION), three activations of quiescent choroidal neovascularization (CNV) secondary to myopia or uveitis, and one central serous chorioretinopathy (CSCR). Mean time between vaccination and ocular complication onset was 9.4 days (range 1–30 days). Twenty-three cases occurred after Pfizer-BioNTech vaccination (BNT162b2 mRNA), 7 after Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19), 3 after ModernaTX vaccination (mRNA-1273), and 1 after Janssen Johnson & Johnson vaccine (Ad26.COV2). Uveitis and other ocular complications may develop after the administration of COVID-19 vaccine

Impact of methylenetetrahydrofolate reductase C677T polymorphism on the efficacy of photodynamic therapy in patients with neovascular age-related macular degeneration

The most severe visual impairments due to age-related macular degeneration (AMD) are frequently caused by the occurrence of choroidal neovascularization (CNV). Although photodynamic therapy with verteporfin (PDT-V) is currently a second-line treatment for neovascular AMD, it can be conveniently combined with drugs acting against vascular endothelial growth factor (anti-VEGF) to reduce the healthcare burden associated with the growing necessity of anti-VEGF intravitreal re-injection. Because the common 677 C > T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR-C677T; rs1801133) has been described as predictor of satisfactory short-term responsiveness of AMD-related CNV to PDT-V, we retrospectively examined the outcomes of 371 Caucasian patients treated with standardized, pro-re-nata, photodynamic regimen for 24 months. Responder (R) and non-responder (NR) patients were distinguished on the basis of the total number of scheduled PDT-V (TN-PDT-V) and change of best-corrected visual acuity (∆-BCVA). The risk for both TN-PDT-V and ∆-BCVA to pass from R to NR group was strongly correlated with CT and TT genotypes of MTHFR-C677T variant resulting, respectively, in odd ratios of 0.19 [95% CI, 0.12-0.32] and 0.09 [95% CI, 0.04-0.21] (P < 0.001), and odd ratios of 0.24 [95% CI, 0.15-0.39] and 0.03 [95% CI, 0.01-0.11] (P < 0.001). These pharmacogenetic findings indicate a rational basis to optimize the future clinical application of PDT-V during the combined treatments of AMD-related CNV, highlighting the role of thrombophilia to be aware of the efficacy profile of photodynamic therapy

Aqueous Humor Analysis in Overlapping Clinical Diagnosis of Cytomegalovirus and Rubella Virus Anterior Uveitis

: Background and Objectives: A cross-sectional single-center study was conducted to investigate the etiology in hypertensive anterior uveitis whose clinical features are not fully distinctive from cytomegalovirus or from rubella virus and to demonstrate the possible coexistence of both these viruses in causing anterior uveitis. Materials and Methods: The clinical charts of a cohort of patients with hypertensive viral anterior uveitis of uncertain origin consecutively seen in a single center from 2019 to 2022 were retrospectively reviewed; data on the clinical features, aqueous polymerase chain reaction, and antibody response to cytomegalovirus and rubella virus were collected. Results: Forty-three eyes of as many subjects with viral anterior uveitis of uncertain origin were included. Thirty-two patients had an aqueous polymerase chain reaction or antibody index positive to cytomegalovirus only, while 11 cases had an aqueous antibody response to both cytomegalovirus and rubella virus. This latter overlapping group had a statistically significant higher rate of hypochromia and anterior vitritis (p-value: 0.02 and &lt; 0.001, respectively). Conclusions: The simultaneous presence of intraocular antibodies against cytomegalovirus and rubella virus could redefine the differential diagnosis of hypertensive viral anterior uveitis, demonstrating a possible “converged” immune pathway consisting in a variety of stimuli

Clinical Features and Prevalence of Spondyloarthritis in a Cohort of Italian Patients Presenting with Acute Nongranulomatous Anterior Uveitis

PURPOSE: To describe the clinical features of acute nongranulomatous anterior uveitis (NGAU) patients and to estimate the prevalence of concomitant spondyloarthritis (SpA). METHODS: Retrospective study of consecutive patients affected by NGAU referred to the Ocular Immunology Unit of the AUSL-IRCCS di Reggio Emilia, Italy, between January 2016 and January 2019. All patients underwent ophthalmic evaluation and blood test with HLA-B27 typing and were referred to a rheumatologist to identify any undiagnosed SpA. SpA was classified according to the Assessment of SpondyloArthritis international Society (ASAS) criteria in axial or peripheral SpA. Patients were divided into two groups: NGAU with associated SpA (SpA+) and NGAU without SpA (SpA-). Clinical and demographic features of the two groups, including sex, HLA-B27, family history of rheumatic disease, uveitis laterality, course, and severity of ocular inflammation, complications, and treatment, were compared. RESULTS: Ninety-nine patients with NGAU were enrolled, of whom 36 (36%) with a diagnosis of SpA: 14 with peripheral SpA and 22 with axial SpA. The prevalence of SpA was higher in HLA-B27-positive patients than in HLA-B27-negative patients (50% vs. 15%, p < 0.0001). The multivariate logistic regression (R(2) = 0.28) for SpA diagnosis identified as significant predictive factors: age at diagnosis (odds ratio [OR] = 0.95, 95% confidence interval [CI]: 0.91-0.99) and HLA-B27+ (OR = 5.32, 95% CI: 1.80-15.70). CONCLUSIONS: Our results confirmed the high prevalence of undiagnosed SpA in patients with NGAU, suggesting that, regardless of HLA-B27 status, in the presence of IBP and/or peripheral arthritis, patients with NGAU must be referred to the rheumatologist to allow earlier diagnosis

Cataract Surgery with Intraocular Lens Implantation in Juvenile Idiopathic Arthritis-Associated Uveitis: Outcomes in the Era of Biological Therapy

This study compared the outcomes of cataract surgery with intraocular lens (IOL) implantation in patients with juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis treated with antimetabolite drugs and systemic corticosteroids (Non-Biological Group) versus patients treated with antimetabolites and biological drugs (Biological Group). A cohort of patients with cataract in JIA-associated uveitis undergoing phacoemulsification with IOL implantation was retrospectively evaluated. The main outcome was a change in corrected distance visual acuity (CDVA) in the two groups. Ocular and systemic complications were also recorded. The data were collected preoperatively and at 1, 12, and 48 months after surgery. Thirty-two eyes of 24 children were included: 10 eyes in the Non-Biological Group and 22 eyes in the Biological Group. The mean CDVA improved from 1.19 +/- 0.72 logMAR preoperatively to 0.98 +/- 0.97 logMAR at 48 months (p = 0.45) in the Non-Biological Group and from 1.55 +/- 0.91 logMAR preoperatively to 0.57 +/- 0.83 logMAR at 48 months (p = 0.001) in the Biological Group. The postoperative complications, including synechiae, cyclitic membrane, IOL explantation, glaucoma, and macular edema, were not statistically different between the two groups. An immunosuppressive treatment with biological drugs can improve the visual outcome after cataract surgery in patients with JIA-associated uveitis, but it does not significantly reduce postoperative ocular complications