Ocular Immunology and Inflammation最新文献

Purpose: To estimate the incidence of Optic Neuritis (ON) in Colombia using data from the national health registry between January 1, 2015, and December 31, 2020.

Methods: A population-based study was conducted using the Integrated Social Protection Information System from the Colombian Ministry of Health and the International Classification of Diseases-10 code for ON to estimate the incidence of ON from 2015 to 2020. We also evaluated the impact of the COVID-19 lockdown on the epidemiology of the disease in 2020. Finally, a standardized morbidity rate map was created to assess a country's ON geographic distribution.

Results: From 2015 to 2019, 2,463 new cases of ON were reported. The overall 5-year incidence rate was 1.56 cases per 100,000 inhabitants per year, 66% of the patients were females. The peak of presentation in males was the quinquennium of 50-54 years, and in females, it was 45-49 years. In 2020, coinciding with the COVID-19 pandemic, there was a reduction in the incidence of ON by approximately 0.15 cases per 100,000 inhabitants. The regions with a high number of cases and an increasing risk of new cases were Bogotá, Antioquia, and Valle del Cauca.

Conclusions: The incidence of ON in Colombia is lower compared to countries in the northern hemisphere, with women under 50 years being predominantly affected. The onset of the COVID-19 pandemic corresponded with a reduction in identifying new ON cases. This underscores governments' need to implement effective diagnostic strategies in the future.

Purpose: To study the positivity rate of conjunctival realtime polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Design: Systematic review and diagnostic accuracy meta-analysis.

Methods: MEDLINE and EMBASE were queried using medical subject headings terms. Diagnostic accuracy meta-analyses and forest plots were obtained using the RevMan software.

Results: After deduplication, appraisal of abstract titles and full-text analysis of 1441 articles, 42 articles with 3351 COVID-19 patients were included in this review. Of these, 412 conjunctival swabs/Schirmer paper strips tested positive for SARS-CoV-2 by RT-PCR. The pooled sensitivity of the RT-PCR tests across the 24 studies with laboratory-confirmed COVID-19 patients was 10.3%.

Conclusions: Only 1 in 10 RT-PCR tests performed on conjunctival swabs were positive for SARS-CoV-2. Although this suggests that SARS-CoV-2 is likely present and detectable in the conjunctiva, this detection method has low diagnostic potential.

Purpose: To evaluate the efficacy of systemic tumor necrosis factor-alpha inhibitors (TNFi) in the treatment of non-infectious uveitis (NIU).

Methods: This Swiss multicenter retrospective cohort study included patients with NIU requiring TNFi during the period from 2001 to 2018. Risk factors for the occurrence of new complications were identified using Cox regression analysis and hazard ratios (HR).

Results: Seventy-one patients (126 eyes; mean age 40.6 ± 14.4 years, mean duration of uveitis 46.0 ± 61.8 months) were followed for 40.2 ± 17.3 months after addition of TNFi. Under TNFi, visual acuity improved from 0.2 ± 0.3 to 0.1 ± 0.3 logMAR (p < 0.001). The portion of patients under systemic corticosteroids decreased from 81.7% to 25.4% (p < 0.001), while that for conventional synthetic disease-modifying anti-rheumatic drugs insignificantly decreased from 63.4% to 50.7% (p > 0.05). In 80.2% of eyes, complications were present at baseline with epiretinal gliosis (39.7%), cataract (41.3%) and macular edema (ME; 27.8%) being the most common. New complications under TNFi were encountered in 49.2% of eyes, also including recurrence (5 eyes) or new onset of ME (14 eyes). The need for switching of TNFi was associated with further complications (HR 3.78, p = 0.012).

Conclusion: Although the efficacy and tolerability of TNFi in a real-life setting are favorable, treatment is often initiated late, i.e., after many eyes have already developed complications. Even with TNFi, new complications, particularly ME, cannot be completely avoided. Further research is needed to assess the impact of earlier initiation of TNFi therapy.

Purpose: To report an uncommon, isolated presentation of bilateral choroidal detachments in a patient diagnosed with P-ANCA-associated vasculitis and to highlight the importance of an inflammatory work-up in such cases.

Methods: Case report.

Results: A 70-year-old male with a past medical history of autoimmune hepatitis presented with a sudden decrease in vision in both eyes. Over the course of the previous decade, he had experienced recurrent attacks of episcleritis, which were successfully managed with topical corticosteroid eye drops. The patient was diagnosed with bilateral detachments without accompanying scleritis or intraocular inflammation. Inflammatory markers revealed high P-ANCA and anti-MPO levels, confirming the diagnosis of P-ANCA-associated vasculitis. Treatment with systemic rituximab and corticosteroids led to the resolution of the choroidal detachment in both eyes. A 40-month follow-up confirmed the sustained resolution of the detachments.

Conclusion: Choroidal detachment without other extraocular/intraocular inflammation can be associated with P-ANCA-associated vasculitis, a previously under-reported link. It is important to consider an inflammatory work-up for patients presenting with choroidal detachment to rule out conditions like P-ANCA-associated vasculitis.

In pregnancy, a plethora of factors causes changes in maternal immunity. Uveitis flare-ups are more frequent in the first trimester and in undertreated patients. Management of non-infectious uveitis during pregnancy remains understudied. A bibliographic review to consolidate existing evidence was performed by a multidisciplinary group of Ophthalmologists, Gynaecologists and Rheumatologists. Our group recommends initial management with minimum-required doses of corticosteroids, preferably locally, to treat intraocular inflammation whilst ensuring good neonatal outcomes. If ineffective, clinicians should consider addition of Cyclosporine, Azathioprine or Certolizumab pegol, which are seemingly safe in pregnancy. Other therapies (such as Methotrexate, Mycophenolate Mofetil and alkylating agents) are teratogenic or have a detrimental effect on the foetus. Furthermore, careful multidisciplinary preconception discussions and close follow-up are recommended, monitoring for flare-ups and actively tapering medication doses, with a primary endpoint focused on protecting ocular tissues from inflammation, whilst giving minimal risk of poor pregnancy and foetal outcomes.

Purpose: To assess two cases of filamentary keratitis with elevated serum levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies without known rheumatoid arthritis (RA).

Methods: A retrospective chart review was conducted on cases with filamentary keratitis and elevated anti-CCP antibodies between January 2021 and January 2023. Patient demographics, clinical characteristics, and serological test results were reviewed.

Results: The first patient, a 77-year-old man, presented with foreign body sensation and eye redness. He reported mild dry mouth but no joint pain or known autoimmune disease, though he had a family history of RA. Schirmer test scores were 7 and 12 mm in the right and left eyes, with an ocular staining score (OSS) of 12 in each eye. His serum anti-CCP antibody level was >2,777 U. Over 3 years of follow-up, he showed no signs of RA development. The second patient, an 84-year-old man, presented with severe burning and light sensitivity but no dry mouth or joint pain. Schirmer test scores were 2 and 3 mm in the right and left eyes, with OSS of 9 and 5, respectively. His serum anti-CCP level was 1330 U. He developed inflammatory arthritis and was diagnosed with RA 16 months after initial presentation.

Conclusion: This report suggests that filamentary keratitis with elevated serum anti-CCP antibody levels may indicate early RA. These findings underscore the importance of anti-CCP testing in filamentary keratitis patients, even without typical RA symptoms. Further research is needed to explore the link between anti-CCP antibodies and ocular surface diseases in RA.

Purpose: This study aims to investigate the role of Interleukin-37 (IL-37) in mouse models of dry eye.

Methods: Two murine models of dry eye were employed in this investigation.   The evaluation of the anti-inflammatory impact of IL-37 (200 μl, 10 μg/ml) on dry eye mice involved intraperitoneal injections administered once daily for 7 days. Additionally, intraperitoneal injection of VO-Ohpic trihydrate (VO, 0.25 mg/kg) in dry eye mice was performed to investigate the role of PTEN in the IL-37 anti-inflammatory signaling pathway. Tear production was assessed using phenol red cotton thread, while corneal damage was examined through sodium fluorescein staining using a slit lamp. Histological alterations in the lacrimal gland were observed through H&E staining. PAS staining was used to assess conjunctival goblet cells. The levels of NFκB-P65, p-NFκB-P65, IL-1β, IL-6, TNF-α, CD3, AQP5, α-SMA and PTEN proteins were determined via Western blotting or immunofluorescence.

Results: Following IL-37 treatment, both dry eye models exhibited reduced corneal fluorescence staining scores and enhanced tear production. In lacrimal gland, the expression of p-NFκB-P65, IL-1β, IL-6, CD3 and TNF-α was diminished, while PTEN, AQP5, α-SMA expression increased after IL-37 treatment in both dry eye mice. However, the intraperitoneal injection of VO significantly attenuated the anti-inflammatory effect of IL-37 on dry eye mice.

Conclusion: IL-37 emerges as an anti-inflammatory mediator within the lacrimal gland of dry eye mice, exerting its effects through the IL-37-PTEN-NFκB signaling pathway.

Purpose: Behçet's syndrome (BS) is a chronic inflammatory disease affecting the small and large vessels of the venous and arterial systems and is characterized by recurrent oral and genital ulcers. Uveitis represents the most typical ocular manifestation and completes the triple symptom complex originally described. Recognized treatments for Behçet's uveitis (BU) include systemic glucocorticoids and immunosuppressive agents. No study has reported on the use of upadacitinib for BS with panuveitis. Herein, we report the use of upadacitinib in two patients with BU suffering from macular edema and persistent inflammation, which was refractory to systemic glucocorticoids and immunosuppressive agents.

Methods: We retrospectively followed-up two cases, including an adolescent girl and a man in his thirties, with a 2- and 10-year history of BS, respectively.

Results: Upadacitinib successfully treated BU, leading to improved visual acuity, controlled intraocular inflammation, and the disappearance of macular edema in both patients. The patients in this study were either recalcitrant to or intolerant to conventional therapy and adalimumab. Only the female patient revealed a mildly abnormal blood picture and slight transaminitis after 6 months of upadacitinib administration. However, no serious adverse events were reported in either of the two patients during follow-up.

Conclusion: Upadacitinib can be considered an important future option for managing recurrent and recalcitrant cases of BU, especially in those with chronic ocular inflammation and macular edema, which are refractory to conventional therapies.

Purpose: To assess the diagnostic performance of two chatbots, ChatGPT and Glass, in uveitis diagnosis compared to renowned uveitis specialists, and evaluate clinicians' perception about utilizing artificial intelligence (AI) in ophthalmology practice.

Methods: Six cases were presented to uveitis experts, ChatGPT (version 3.5 and 4.0) and Glass 1.0, and diagnostic accuracy was analyzed. Additionally, a survey about the emotions, confidence in utilizing AI-based tools, and the likelihood of incorporating such tools in clinical practice was done.

Results: Uveitis experts accurately diagnosed all cases (100%), while ChatGPT achieved a diagnostic success rate of 66% and Glass 1.0 achieved 33%. Most attendees felt excited or optimistic about utilizing AI in ophthalmology practice. Older age and high level of education were positively correlated with increased inclination to adopt AI-based tools.

Conclusions: ChatGPT demonstrated promising diagnostic capabilities in uveitis cases and ophthalmologist showed enthusiasm for the integration of AI into clinical practice.

Purpose: To explore the role of the proinflammatory cytokine, macrophage migration inhibitory factor (MIF), in a murine model of dry eye disease (DED).

Methods: The role of MIF on DED was determined using genetically MIF deficient mice and pharmacological inhibition of MIF. DED was induced with 0.5 mg of scopolamine via subcutaneous injection in wild type (WT) and mice lacking MIF (Mif^-/-), three times a day for 21 days. DED signs, tear volume, ferning pattern and cytology impression were evaluated. Also, eye tissues were collected to determine transcripts of key inflammatory mediators and histopathological damage. In a second set of experiments, we neutralized MIF with ISO-1, an isozaxiline-derivative MIF tautomerase activity-inhibiting small molecule in WT mice, following an acute DED model for 10 days. ISO-1 was given starting on day 3 after DED induction and signs were evaluated, including a recovery phase in both experimental approaches.

Results: When compared to WT, Mif^-/- mice showed attenuated signs of DED like preserved mucin pattern and increased tear volume. Also, Mif^-/- mice maintained conjunctival epithelial cells and less corneal damage, associated with lower levels of TNFα and IL-1β. At recovery phase, Mif^-/- mice presented improved signs. Interestingly, in cornea and conjunctiva the absence of MIF selectively downregulated the transcription of inflammatory enzymes like inos and nox4 whereas displayed enhanced transcripts of il-4, il-13, tgfβ and cox2. Finally, pharmacological inhibition of MIF using ISO-1, replicated the above findings in the mouse model.

Conclusion: MIF is a central positive mediator of the inflammatory process in experimental DED, thus, targeting MIF could be used as a novel therapy in ocular surface inflammatory pathologies.