Ocular Immunology and Inflammation最新文献

Objectives: We aimed to establish the degree of consensus among clinicians on descriptors of KP morphology.

Methods: A web-based exercise in which respondents associated KP descriptors, as identified through a scoping review of the published literature, to images from different disorders. Inter-observer agreement was assessed using the Krippendorff kappa alpha metric.

Results: Of the 76 descriptive terms identified by the scoping review, the most used included "mutton-fat" (n = 93 articles, 36%), "fine/dust" (n = 76, 29%), "stellate" (n = 40, 15%), "large" (n = 33, 12%), and "medium" (n = 33, 12%). The survey of specialists (n = 26) identified inter-observer agreement for these descriptors to be poor ("stellate," kappa: 0.15, 95% confidence interval 0.13-0.17), limited ("medium": 0.27, 95% CI 0.25-0.29; "dust/fine": 0.36, 95% CI 0.34-0.37), or moderate ("mutton fat": 0.40, 95% CI 0.36-0.43; "large": 0.43, 95% CI 0.39-0.46).

Conclusion: The clinical utility of KP morphology as an indicator of disease classification is limited by low inter-observer agreement.

Purpose: To describe the frequency of uveitis recurrences in patients with non-infectious uveitis treated with the biosimilar infliximab-dyyb.

Design: Retrospective case series.

Methods: Records of uveitis patients treated with the biosimilar infliximab-dyyb between 2016 and 2022 at two institutions were reviewed. Data extracted included patient demographics, diagnosis, previous originator infliximab use, additional immunosuppression medications, infliximab-dyyb use, reason for switch, disease activity, and follow-up time.

Results: A total of 14 patients were identified. Seven patients were switched from originator infliximab to a biosimilar for nonmedical/non-ocular reasons (insurance prompted the switch). One patient was started directly on infliximab-dyyb due to active joint disease despite well-controlled uveitis. None of these eight patients developed inflammation after the switch. Six patients were started directly on infliximab-dyyb due to poorly controlled uveitis. Of these, five patients achieved disease quiescence during follow-up. The mean dose of originator was 1.79 mg/kg/week, with a median dosing schedule of 4 weeks prior to therapy with infliximab-dyyb. The mean final infliximab-dyyb dosage was 1.81 mg/kg/week, with a median dosing schedule of 4 weeks.

Conclusion: Infliximab-dyyb appears to be efficacious in achieving and maintaining uveitis control.

Introduction: Ocular syphilis is a rare but potentially sight-threatening manifestation of infection with the spirochete Treponema pallidum subspecies pallidum. Molecular strain typing of clinical specimens obtained from patients with syphilis can provide useful epidemiological and clinical information. In this study, we assess the utility of non-ocular clinical samples in strain typing for patients with diagnosed ocular syphilis.

Methods: We collected samples of excess blood, serum, and cerebrospinal fluid (CSF) from 6 patients with ocular syphilis treated in 2013-2016. DNA was extracted, purified, and then analyzed using an enhanced molecular typing method including sequence analysis of tp0548, number of repeats in the arp gene, and restriction fragment length polymorphism of the tpr gene.

Results: Molecular strain typing based on tp0548 gene sequence analysis revealed two cases of type F and two cases of type G in 3 of 6 (50%) cases with CSF samples, 1 of which was obtained after starting antibiotics. In a patient with 2 distinct episodes, the same tp0548 type (type G) was identified in both episodes using different sample types (CSF, whole blood). Serum samples were available in 6 cases, but none were successfully typed with any of the methods. Amplification of the tpr and arp genes was unsuccessful in all cases. Overall, strain types were identified in 4 of the 7 episodes.

Conclusion: Treponema pallidum strain types F and G were detected in CSF or whole blood in 4 of 7 episodes in this series. We demonstrate moderate sensitivity of strain typing in ocular syphilis using non-ocular clinical specimens.

Purpose: To describe features of a syphilitic vascularized iris mass on multimodal imaging and its resolution after penicillin treatment.

Methods: Observational case report and literature review of syphilitic iris masses.

Results: A 43-year-old woman presented with a unilateral vascularized tan iris mass in the setting of bilateral panuveitis that occurred along with bilateral papillitis, cystoid macular edema and retinal vasculitis. Laboratory work-up confirmed a diagnosis of syphilis. Ultrasound biomicroscopy (UBM) of the iris mass showed parapupillary hyperechoic full-thickness iris stromal thickening with small intrinsic circular lumens without cyst or ciliary body extension, while the anterior segment optical coherence tomography (AS-OCT) demonstrated a hyperreflective mass with deep iris extension and partial hyporeflective rim. Following treatment, the mass fully resolved without residual sequela. A review of literature identified 11 additional cases of syphilitic iris masses in the English literature from 1915 to present. Their presentations and clinical courses were reviewed herein.

Conclusions: This report characterizes a syphilitic iris mass on slit-lamp photography, iris fluorescein angiography, UBM and AS-OCT; depicts key characteristics of syphilitic iris masses; and highlights the need for close inspection of the iris mass as an uncommon sign of ocular syphilis.

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 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 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: 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.