Uveitis Research Articles

Assessment of quality of life, psychosocial, and epidemiological aspects in patients diagnosed with tuberculous uveitis.

To assess the quality of life in patients diagnosed as having tuberculous uveitis and its association with sociodemographic, clinical, and psychosocial aspects. By conducting standardized interviews, clinical and demographic data were collected using a measure developed in this study. This measure was applied in addition to other measures, namely SF-12, Hospital Anxiety and Depression Scale, and NEI-VFQ-39, which were used to assess health-related quality of life, anxiety and depression symptoms, and visual functioning. The study included 34 patients [mean age: 46.5 ± 15.1 years, female patients: 21 (61.8%)]. The mean of the VFQ-39 score was 74.5 ± 16.6 and that of SF-12 physical and mental component scores were 45.8 ± 10.1 and 51.6 ± 7.5, respectively, for the health-related quality of life. Anxiety symptoms were the most prevalent compared with depression symptoms and were found in 35.3% of the participants. Tuberculous uveitis affects several scales of quality of life, thereby affecting a population economically active with a social, psychological, and economic burden.

Rituximab in the Treatment of Non-Infectious Uveitis: A Review.

Non-infectious uveitis (NIU) is an immune-mediated disorder manifesting as ocular pain, redness, floaters, and photophobia, and is a leading cause of preventable blindness. Managing NIU presents considerable challenges due to the condition's resistance to high-dose corticosteroids and various immunotherapies. This review assesses the efficacy and safety of rituximab (RTX) in the treatment of NIU, based on individual case reports and small-scale studies. A cohort of 78 patients (20 males, 58 females), with a mean onset age of 32.3 years (range 8-72), was analyzed. Juvenile idiopathic arthritis (JIA) was the most frequently associated comorbidity, affecting 28 patients, while anterior uveitis was the predominant subtype, observed in 26 of 47 cases. Prior to RTX therapy, patients had been treated with an average of 1.7 conventional immunosuppressive agents (range 0-5) and 1.1 biologics (range 0-4). RTX was introduced following the failure of high-dose corticosteroids, immunosuppressive drugs, and biologics to control the uveitis. The median time from diagnosis to RTX initiation was 7.7 years (range 0.25-21). Post-RTX, 44.2% of patients experienced improvement in visual acuity, 79.5% achieved resolution of ocular inflammation, and 8.9% showed partial improvement. Additionally, 81.1% were able to reduce their corticosteroid dosage. Overall, 88.6% (69 out of 78) demonstrated a positive response to RTX treatment. These findings indicate that RTX may serve as an effective therapeutic option for NIU unresponsive to steroids and multiple immunotherapies. It may also warrant consideration as a potential first-line treatment in certain cases.

Orbital Inflammation after Zoledronate Infusion

Zoledronate, a bisphosphonate, is commonly used as an annual intravenous infusion, primarily in the treatment of osteoporosis. Ocular adverse effects have been documented and orbital inflammation is one of the most severe. It may clinically manifest by eyelid edema, conjunctival congestion, chemosis, restricted ocular motility, pain, diplopia, and reduced vision. It usually has asymmetric involvement and rarely associated with anterior uveitis, scleritis, episcleritis or conjunctivitis. Prompt treatment is likely to have favorable outcomes. Though, the treatment of choice remains systemic corticosteroids, we highlight a case who developed orbital inflammation after Zoledronate-infusion and improved after topical corticosteroids administration.

Orbital Doppler ultrasonography evaluation in patients with ankylosing spondylitis: A prospective study.

Our aim in this study is to compare patients with ankylosing spondylitis (AS), a rheumatologic disease that can cause eye involvement and the normal population in terms of orbital Doppler findings, which is an inexpensive and easily applicable method that can be used in early diagnosis and follow-up. The study was planned prospectively. The data of patients with AS were compared to those of age- and gender-matched healthy volunteers. A total of 42 participants, 23 (54.8%) males and 19 (45.2%) females, with a mean age of 42.4±12.6 years were included in the study. In addition to demographic information, such as age and gender, the diameter, peak systolic velocity, end-diastolic velocity, mean velocity, resistive index, pulsatility index, and blood flow volumes of the central retinal artery of the left eye were measured using spectral Doppler ultrasonography. According to the comparison of the patients with and without AS according to orbital Doppler ultrasonography findings, the mean velocity, resistive index, and volume measurements of the patients with AS were significantly higher than those without AS (p=0.028, p=0.039, and p=0.038, respectively). However, in the subgroup analysis of the AS group, the Doppler findings did not significantly differ between the patients with and without anterior uveitis. In the patient group with AS, independent of anterior uveitis (AU), there was a difference in Doppler parameters and therefore in ophthalmic vasculature. In patients with AS, orbital vascularity changes can be detected with orbital Doppler US before clinical signs appear.

Ocular thermography – A novel tool to suspect and monitor posterior scleritis

We report two cases of posterior scleritis (PS) where ocular thermography was used to monitor ocular surface temperature (OST). Case 1 was a known case of recurrent non-granulomatous anterior uveitis presented with pain in the left eye (OS). A relapse of anterior uveitis was suspected, but slit-lamp biomicroscopy was normal. Thermography showed increased temperature in OS, and B-scan confirmed PS in OS. Case 2, a known case of PS, during follow-up visits, was found to have increased OST in OS on two occasions, but no inflammation was detected clinically. Within the next 2 weeks, the patient returned with relapse on both occasions.

Brolucizumab and other anti‐VEGF induced intraocular inflammation

Anti‐vascular endothelial growth factor (VEGF) agents, such as bevacizumab, ranibizumab, and aflibercept, are widely used in the treatment of various retinal diseases. Recently, brolucizumab, a novel anti‐VEGF agent, has been introduced in the market for the treatment of neovascular age‐related macular degeneration. However, the use of some anti‐VEGF agents has been associated with an increased risk of intraocular inflammation.In particular, brolucizumab has been reported to be associated with a higher incidence of intraocular inflammation compared to other anti‐VEGF agents. The inflammation can manifest as anterior uveitis, vitritis, or even occlusive retinal vasculitis, and lead to severe and permanent visual loss in some cases. Although the exact mechanism of this phenomenon is not fully understood, it is believed to be related to the immune response triggered by the injection of foreign proteins into the eye.The clinical presentation of intraocular inflammation can range from mild symptoms, such as ocular discomfort and blurry vision, to severe visual loss. Prompt and appropriate management of intraocular inflammation is crucial to preserve vision in patients receiving anti‐VEGF agents. Early detection of inflammation and prompt initiation of anti‐inflammatory treatment can prevent further damage to the eye.In cases of mild to moderate inflammation, close monitoring and topical or systemic anti‐inflammatory medication may be sufficient to control the inflammation and prevent visual deterioration. Cessation of the causative anti‐VEGF treatment may be necessary to prevent further exacerbation of the inflammation. In such cases, the patient may need to be switched to an alternative treatment option for their underlying condition.Overall, clinicians should maintain a high level of vigilance for the development of intraocular inflammation in patients receiving anti‐VEGF therapy. Close monitoring, early detection, and appropriate management of inflammation can help preserve vision and minimize the potential complications associated with these agents.

Keratitis fugax Hereditaria caused by a pathogenic variant in NLRP3

Keratitis fugax hereditaria (KFH, MIM 148200) is an autosomal dominant periodic corneal autoinflammation caused by a single pathogenic variant c.61G>C (rs200154873) in the NLRP3 gene. NLRP3 protein is a key component of the NLRP3 inflammasome, which activation leads to the secretion of IL‐1 beta and IL‐18 leading to inflammation. KFH is characterized by periodic unilateral attacks causing pain, redness, and reduced vision. Repeated attacks lead to permanently reduced visual acuity in a subset of the patients. Currently, we have examined 94 individuals with KFH from 26 families. Age of onset varied from 6 to 20 years (median, 11). During the acute attack symptoms were eye pain, photophobia, conjunctival injection, and foreign body sensation. Half of the patients (48%, n = 45) developed corneal oval opacities. KFH was most often misdiagnosed as anterior uveitis (26%, n = 24), conjunctivitis (13%, n = 12), recurrent erosion (11%, n = 10), and herpetic keratitis (10%, n = 9). Geographically, KFH is most prevalent in Finland and Sweden according to allele frequencies in gnomAD, 0.014% in Finland and 0.011% in Sweden. Patient‐derived peripheral blood mononuclear cells are more prone to secrete IL‐1β after NLRP3 inflammasome stimulation, confirming that the c.61G>C is a gain‐of‐function variant. Furthermore, prednisolone is a potent drug to reduce IL‐1β secretion in the cell culture. We recommend prednisolone for the treatment of acute attack, and for permanently reduced vision due to corneal opacities and thinning, scleral contact lenses are the first‐line treatment. KFH is underrecognized and misdiagnosed corneal disease and should be recognized at least in the Scandinavian population.

Immunotherapy induced uveitis

Uveitis can affect all layers of the eye and may be due to various etiologies: autoimmune, infectious, iatrogenic or masquerade syndrome. Recently, a new iatrogenic uveitis entity has been associated with cancer immunotherapy (CIT).Immune checkpoint inhibitors and targeted therapies including BRAF and MEK inhibitors are increasingly used for treatment of metastatic malignancies. There is currently 10 immune checkpoint inhibitors (ICPIs) targeting one of three ligands, leading to T‐cell activation for attack against malignant cells. These ligands include cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4, ipilimumab), programmed death protein 1 (PD‐1, pembrolizumab, nivolumab), and programmed death ligand‐1 (PD‐L1, atezolizumab, avelumab, durvalumab).ICPIs overcome T‐cell inhibition and increases the activity of immune system and the loss of immune homeostasis, which can lead to autoimmune/inflammatory side effects, termed immune‐related adverse events (IRAEs). IRAEs can include ophthalmic manifestations as uveitis, which can very between anterior uveitis, intermediate uveitis, and panuveitis, but also some cases of ocular surface disorders, optic neuropathy and orbitopathy.The aim of my presentation is therefore to describe ICPI‐induced ocular IRAEs, more specifically the uveitis, detailing the anatomical specificities, potential risk factors, workup, and the management through an adapted treatment, and outcome, in relation to the outcome of the underlying tumour.

Ophtalmologic, Serologic and Therapeutic Aspects of Ocular Toxoplasmosis Toxoplasmose Oculaire: Aspects Ophtalmologiques, Sérologiques et Thérapeutiques

Ocular toxoplasmosis (OT) is the most frequent cause of inflammation of the posterior segment of the eye due to infectious causes. It can occur in congenital toxoplasmosis, in the immunocom promised and, more rarely, in the immuno competent. It is a critical disease, as it can lead to blindness. The aim of our study was to investigate the clinical, serological, and therapeutic features of TO. Methods: A bicentric retrospective study was conducted at the Parasitology-Mycology laboratories of two Tunisian Hospitals(2017-2021), involving toxoplasma serologies performed on 175 patients in the context of exploration for uveitis and on six babies with congenital toxoplasmosis. As screening technique, we used was electrochemilum inescence (Cobas® e411) and Enzyme Linked Filtration Assay (mini-Vidas®). If IgM and/or IgG were positive, and depending on ophthalmo logical signs, we added a comparative Western Blot (WB) of serum and aqueous humor. Results Serological results were: – no immunity in 71 patients, rejecting OT – long-standing immunity in 103 patients, 15 of whom underwent comparative WB tests, four of which were positive- recent primary infection in one case with a positive WB. Thus, five cases of OT were confirmed(Three panuveitis and two anterior uveitis). Their respective ages were 14, 25, 33, 43 and 50 years old.Ophthalmological follow-up of five babies during the first year of life (one lost at six months) revealed chorioretinitis in one baby only. Conclusion Ocular involvement may represent a late revelation of unrecognized congenital toxoplasmosis. Its occurrence in immuno competent is not exceptional, but remains underestimated, as aqueous humor puncture is not systematically performed due to its invasive nature.

The impact of lutein-loaded poly(lactic-co-glycolic acid) nanoparticles following topical application: An in vitro and in vivo study.

Antioxidant therapies are of interest in the prevention and management of ocular disorders such as cataracts. Although an active area of interest, topical therapy with antioxidants for the treatment of cataracts is complicated by multiple ocular anatomical barriers, product stability, and solubility. Entrapment and delivery of antioxidants with poly(lactic-co-glycolic acid) nanoparticles is a possible solution to these challenges, however, little is known regarding their effects in vitro or in vivo. Our first aim was to investigate the impact of blank and lutein loaded PLGA nanoparticles on viability and development of reactive oxygen species in lens epithelial cells in vitro. Photo-oxidative stress was induced by ultraviolet light exposure with cell viability and reactive oxygen species monitored. Next, an in vivo, selenite model was utilized to induce cataract formation in rodents. Eyes were treated topically with both free lutein and lutein loaded nanoparticles (LNP) at varying concentrations. Eyes were monitored for the development of anterior segment changes and cataract formation. The ability of nanodelivered lutein to reach the anterior segment of the eye was evaluated by liquid chromatography coupled to mass spectrometry of aqueous humor samples and liquid chromatography coupled to tandem mass spectrometry (targeted LC-MS/MS) of lenses. LNP had a minimal impact on the viability of lens epithelial cells during the short exposure timeframe (24 h) and at concentrations < 0.2 μg LNP/μl. A significant reduction in the development of reactive oxygen species was also noted. Animals treated with LNPs at an equivalent lutein concentration of 1,278 μg /mL showed the greatest reduction in cataract scores. Lutein delivery to the anterior segment was confirmed through evaluation of aqueous humor and lens sample evaluation. Topical treatment was not associated with the development of secondary keratitis or anterior uveitis when applied once daily for one week. LNPs may be an effective in the treatment of cataracts.

Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial)

IntroductionAdalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted...

Palpebral sarcoid nodules

ABSTRACT Herein, we report a case of systemic sarcoidosis confirmed by a eyelid biopsy in a 47-year-old North African female with a past medical history of a bilateral granulomatous anterior and intermediate uveitis. She presented to the ophthalmological department for bilateral palpebral painful discomfort. An examination revealed the presence of bilateral, rounded, well-limited, subcutaneous, nodular lesions on the upper and inferior lid. A cutaneous biopsy confirmed the presence of a non-caseating granulomatous inflammation. The diagnosis of a definite ocular sarcoidosis was made and she was treated with local steroid ointment associated to hydroxychloroquine. A skin examination of the patient with granulomatous uveitis cannot be stressed enough. A biopsy allows us to make the diagnosis and to treat the patients appropriately. Key words: Inflammation, Granulomatosis, Eye, Skin Biopsy

The relation of neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and mean platelet volume with idiopathic acute anterior uveitis

Objective In this study leukocyte, lymphocyte, neutrophil, platelet count, mean platelet volume (MPV), neutrophil/lymphocyte (NLR) ratio and platelet/lymphocyte ratio (PLR) were retrospectively evaluated in patients with idiopathic acute anterior uveitis. Materials and methods Medical records were retrospectively reviewed from March 2016 to February 2020. Fifty patients (25 men and 25 women) and as the control group, 50 healthy volunteers (25 males and 25 females) were included in this study. Blood samples of the patients were taken before starting treatment. A complete ophthalmological examination, including corrected visual acuity, tonometry, slit lamp and fundus examination, was performed in all patients. Gender, age, leukocyte, neutrophil, lymphocyte, platelet, MPV, PLR, and NLR values of the patients were recorded. Results In this study, a statistically significant difference was found in leukocyte ( p &lt; .001), neutrophil ( p &lt; .001), platelet ( p &lt; .001), NLR ( p &lt; .001) and PLR ( p &lt; .001) values. No significant difference was found between the two groups in terms of lymphocyte count ( p = .063) and in the MPV value ( p = .051). Leukocyte, neutrophil, platelet count, NLR, and PLR values were higher in the uveitis group compared to the control group. In the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) for NLR was 0.805, with a sensitivity of 56.0% and a specificity of 98.0%. The AUC for PLR was 0.657, with a sensitivity of 52.0% and a specificity of 98.0%. Conclusion In this retrospective study, leukocyte, neutrophil, platelet count, PLR, and NLR levels were significantly higher in patients with idiopathic acute anterior uveitis compared to the control group. These blood parameters are useful as diagnostic markers and can be used in early diagnosis.

Clinical pattern and outcomes of acute retinal necrosis in a referral Center in Tunisia, North Africa: A 17‐year retrospective study

Aims/Purpose: To describe the pattern of acute retinal necrosis (ARN) in a referral centre in Tunisia, North Africa.Methods: The charts of 22 patients diagnosed with ARN from January 2006 to January 2023 were retrospectively reviewed.Results: The mean age at presentation was 39.2 (range, 12–70) years, sex ratio was 1.75. The mean diagnostic delay was 17.9 days (range 1–60). The mean visual acuity at presentation was 20/400. All patients presented with a mild to moderate anterior uveitis (100%) with granulomatous keratic precipitates in 18 eyes (81%) and ocular hypertension in 4 eyes (18%). Necrotizing retinitis involved &gt;50% of the retina in 36.5%of eyes. Polymerase chain reaction on aqueous humour sample identified varicella zoster virus in 10 eyes (45%), herpes simplex virus‐1 in 4 eyes (18%) and was negative in 8 eyes (22%). All patients received intravenous acyclovir, followed by oral antivirals. Intravitreal injections of ganciclovir were administered in 12 eyes (54.5%). Follow‐up ranged from 1 month to 48 months. The mean final visual acuity was 20/200. Complications included retinal detachment (RD) (31.8%), macular oedema (18%), macular atrophy (22%), epimacular membrane (22%), cataract (27%), optic nerve atrophy (18%) and central retinal artery occlusion (4%). No patient developed bilateral ARN. Prophylactic laser was performed in 7 eyes (32%). RD was treated with pars plana vitrectomy and silicone oil injection in 7 eyes.Conclusions: ARN syndrome in Tunisia is most commonly caused by VZV.

Use of Anterior Chamber Paracentesis for Diagnosis in Viral Anterior Uveitis

In ophthalmic practices in the Intelligent Research in Sight (IRIS) Registry, 1.6% of eyes with viral anterior uveitis underwent anterior chamber paracentesis. When performed, anterior chamber paracentesis was associated with a change in diagnosis in 42% of cases.

Cytomegalovirus detected by qPCR in iris and ciliary body of immunocompetent corneal donors

BackgroundCytomegalovirus (CMV) can cause a wide panel of ocular infections. The involvement of CMV as a cause of anterior uveitis in the immunocompetent patient is recent and remains poorly understood. ObjectiveTo investigate the presence of CMV in anterior uveal tissues of immunocompetent corneal donors. Study DesignWe collected aqueous humor, iris, and ciliary body from both eyes of 25 donors died at the Limoges University Hospital between January 2020 and July 2021. CMV serology was determined for all patients from post-mortem blood sample. Ocular tissues were split in 2 fragments for qPCR and 2 for histological analysis. CMV genomes copies were quantified by Multiplex qPCR after DNA extraction. Results16 of 25 patients (64%) displayed positive CMV serology, with a median age of 67 years. Viremia was positive in 3 of 16 (19%) CMV-positive patients. No CMV DNA copies were found from the aqueous humor samples. CMV DNA was detected in iris and ciliary body of 28 of 32 eyes of seropositive donors, and 5 of 18 eyes of seronegative donors. The median viral copy number [IQR] was 2.41 × 102 [8.91 × 101 - 1.01 × 103] copies/1 × 106 cells in the CMV-positive group and 0.00 [0.00 - 3.54 × 102] copies/1 × 106 cells in the CMV-negative group (p<0.001). Histology and immunohistochemistry did not reveal any CMV lesions from any sample. ConclusionCMV DNA was found in iris and ciliary body of immunocompetent seropositive patients, but also, although less frequently, from seronegative donors. These results highlight mechanisms of infection, latency and reactivation of CMV in ocular tissues.

Impact of prostaglandin analogues on the likelihood of macular edema development in a model of autoimmune uveitis against the background of ophthalmotonus pressure

Impact of prostaglandin analogues on the likelihood of macular edema development in a model of autoimmune uveitis against the background of ophthalmotonus pressure

Intravitreal application of stem cells and their products does not ameliorate experimental autoimmune uveitis

Aims/Purpose: Stem cell therapy has demonstrated potential therapeutic benefits in various medical disciplines. This study evaluated therapeutic effects of mesenchymal stem cells (MSCs) or their by‐products on intraocular inflammation in experimental autoimmune uveitis (EAU) model.Methods: EAU was induced in C57BL/6J mouse strain through administration of IRBP, Freund's adjuvant and pertussis toxin. Conditioned medium was procured through cultivation of MSCs in serum‐free medium, while MSC supernatant was obtained via MSC centrifugation and membrane removal. Either conditioned medium or MSC supernatant was intravitreally administered unilaterally, typically on day 14 post‐EAU induction. Ocular fundus of mice was documented regularly. Experiments were generally concluded on day 28, with eyes processed for FACS and PCR analysis. Infiltration of retina by inflammatory cells (F4/80, CD11c, CD45, CD80, CD86, CD206) and gene expression of pro‐inflammatory factors (Gfap, Iba‐1, IL‐1, iNOS) were quantified.Results: Across all experiments, clinical grading, FACS, and PCR analysis indicated exacerbation of intraocular inflammation. Post‐intravitreal administration of MSC by‐products into eyes with EAU, increased infiltration of retina by inflammatory cells and upregulation in gene expression of pro‐inflammatory factors were observed. These findings were corroborated in vitro, where co‐culturing of retina with EAU in presence of MSCs or their supernatant did not significantly reduce gene expression of pro‐inflammatory factors. Upsurge in pro‐inflammatory factors was also noted in control experiments on healthy eyes post‐intravitreal injection of no substance, serum‐free medium, PBS, or conditioned medium.Conclusions: No improvement in EAU was observed following application of MSC products, both in vivo and in vitro. Instead, inflammation was more severe. Trauma induced by intravitreal application itself significantly influenced outcome.Financial support: GA UK 309621, SVV UK 260631.

PIM1 signaling in immunoinflammatory diseases: an emerging therapeutic target.

PIM1, the proviral integration site for Moloney murine leukemia virus, is a member of the serine/threonine protein kinase family. It is involved in many biological events, such as cell survival, cell cycle progression, cell proliferation, and cell migration, and has been widely studied in malignant diseases. However, recent studies have shown that PIM1 plays a prominent role in immunoinflammatory diseases, including autoimmune uveitis, inflammatory bowel disease, asthma, and rheumatoid arthritis. PIM1 can function in inflammatory signal transduction by phosphorylating multiple inflammatory protein substrates and mediating macrophage activation and T lymphocyte cell specification, thus participating in the development of multiple immunoinflammatory diseases. Moreover, the inhibition of PIM1 has been demonstrated to ameliorate certain immunoinflammatory disorders. Based on these studies, we suggest PIM1 as a potential therapeutic target for immunoinflammatory diseases and a valid candidate for future research. Herein, for the first time, we provide a detailed review that focuses on the roles of PIM1 in the pathogenesis of immunoinflammatory diseases.

Efficacy of Corticosteroids in the Treatment of Autoimmune Uveitis and its Effect on T Helper Cell and S100 Protein Levels in Peripheral Blood

Efficacy of Corticosteroids in the Treatment of Autoimmune Uveitis and its Effect on T Helper Cell and S100 Protein Levels in Peripheral Blood