OBJECTIVE: To compare the incidence of noninfectious uveitis in skin melanoma or lung cancer patients who received BRAF inhibitors with that in those who received immune checkpoint inhibitors (ICIs) or conventional cytotoxic chemotherapy.
METHODS: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration.
RESULTS: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < .001 and 95% CI 2.81-11.47, P < .001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = .001 and 95% CI 1.76-141.00, P = .014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = .046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis.
CONCLUSIONS: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration.

BACKGROUND: Despite HLA-B27-associated uveitis is one of the most frequent etiologies of uveitis worldwide, there are scarce studies on the clinical spectrum of this disease and the implications of therapeutic strategies used in the Latin-American population, with none conducted in Colombia. Thus, this study aimed to describe the clinical characteristics of a cohort of patients with positive HLA-B27-associated uveitis in Colombia and evaluate the impact of systemic treatment on the recurrence rate.
METHODS: We retrospectively reviewed 490 clinical charts of patients with uveitis, searching for those with positive HLA-B27-associated uveitis over eight years in a referral center in Bogotá, Colombia. We used descriptive statistics to summarize demographic and clinical characteristics and conducted a Chi-square test, Fisher Exact test, Spearman correlation, and Mann-Whitney test to assess associations between treatment strategies and the recurrences rate.
RESULTS: We analyzed 39 patients (59% females) with positive HLA-B27-associated uveitis, with a median age at the first consultation of 44.5 years (Range: 2-80) and a mean follow-up time of 86.4 weeks (1.65 years). Most patients had unilateral uveitis (53.8%) and an anterior anatomical diagnosis (76.6%); two had anterior chamber fibrinous reaction, and only one had hypopyon. Most patients did not show associated systemic symptoms (66.7%). Topical corticosteroids, NSAIDs, methotrexate, mydriatics, and adalimumab were the most used treatments. The most common complications included cataracts, posterior synechiae, and macular edema. We identified that the rate of recurrences decreases over time (r = -0.6361, P = 0.002571), and this decrease seems to be associated with the initiation of disease-modifying antirheumatic drugs (DMARDs) in chronic and recurrent cases.
CONCLUSIONS: The clinical spectrum of HLA-B27-associated uveitis in Colombian patients is distinct from other latitudes. Notably, we found a female predominance, older age at presentation, higher frequency of bilateral and vitreous involvement, and lower frequency of concomitant systemic diseases. Additionally, our results suggest that DMARDs such as methotrexate and biologic agents are good therapeutic options to avoid recurrences in chronic and recurrent cases.

Analyse and describe the anatomical and etiological classification, clinical and epidemiological characteristics and most frequent symptoms of uveitis cases in our population.
Descriptive, retrospective observational study of uveitis cases treated in the Ophthalmology Department of Virgen del Rocío University Hospital in 2021. The demographic and clinical characteristics were studied.
A total of 109cases of uveitis were studied, 46 men and 63 women, with a mean age of 45.43±16.11 years. The most frequent symptoms were pain (74.31%), hyperemia (73.39%) and blurred vision (65.14%). The most frequent anatomical classification was anterior (55.96%), followed by panuveitis (18.35%), posterior (12.84%) and intermediate uveitis (7.34%). Regarding etiology, most uveitis were idiopathic (42.99%), followed by non-infectious (38.32%) and finally infectious (18.69%).
In southern España, the characteristics of uveitis are similar to other studies in Western countries.

BACKGROUND: There is a substantial unmet need for effective therapies to treat patients with refractory dry eye disease (DED). The goal of this open-label pilot study was to investigate the efficacy and safety of repository corticotropin injection (RCI; Acthar® Gel; Mallinckrodt Pharmaceuticals) in subjects with DED, most of whom did not experience adequate response to standard-of-care therapies.
METHODS: Adults with moderate or severe-acute DED received 80 U of subcutaneous RCI twice weekly for 12 weeks. Primary efficacy outcomes were improvements in corneal fluorescein staining of superficial punctate keratitis (SPK) lesions and Symptom Assessment in Dry Eye (SANDE) scores. Secondary outcomes included changes in Schirmer\'s test scores, conjunctival lissamine green staining, erythema, intraocular pressure (IOP), and best corrected visual acuity (BCVA). Adverse events (AEs) were assessed continuously throughout the study.
RESULTS: Fifteen subjects received at least 1 dose of RCI, and 12 subjects completed the study. Compared to baseline (day 1), significantly fewer fluorescein-stained SPK lesions were detected at day 14 (p = 0.0250) and day 84 (p = 0.0240) after RCI treatment. Mean SANDE scores progressively declined from 62.0 at baseline to 46.9 at day 84. Erythema (p = 0.0046), conjunctival lissamine green staining of SPK lesions (p = 0.0317), and IOP (p = 0.0052) were all significantly improved after 12 weeks of RCI therapy. Schirmer\'s test scores and BCVA showed no significant changes throughout the study. No ocular AEs or deaths occurred, and no new safety signals were identified for RCI.
CONCLUSIONS: These results suggest that RCI may be a safe and effective treatment for moderate and severe DED.
BACKGROUND: ClinicalTrials.gov identifier: NCT03287635.

OBJECTIVE: To estimate the frequency of first-time ocular events in patients treated with immune checkpoint inhibitors (ICI).
METHODS: Patients with cancer in 2011-2018 in Denmark were included and followed. The outcomes were first-time ophthalmologist consultation and ocular inflammation. One-year absolute risks of outcomes and hazard ratios were estimated.
RESULTS: 112,289 patients with cancer were included, and 2195 were treated with ICI. One year after the first ICI treatment, 6% of the patients with cancer, 5% and 8% of the lung cancer (LC) and malignant cutaneous melanoma (MM) patients, respectively, had a first-time ophthalmologist consultation. The risk of ocular inflammation was 1% (95% confidence interval (CI) 0.4-1.2). Among patients with MM, ICI was associated with ocular inflammation in women (HR 12.6 (95% CI 5.83-27.31) and men (4.87 (95% CI 1.79-13.29)). Comparing patients with and without ICI treatment, the risk of first-time ophthalmologist consultation was increased in patients with LC (HR 1.74 (95% CI 1.29-2.34) and MM (HR 3.21 (95% CI 2.31-4.44).
CONCLUSIONS: The one-year risks of first-time ophthalmologist consultation and ocular inflammation were 6% and 1%, respectively, in patients treated with ICI. In patients with LC and MM, the risk was increased in patients with ICI compared with patients without ICI.

This study explored systemic immune changes in 11 subjects with X-linked retinoschisis (XLRS) in a phase I/IIa adeno-associated virus 8 (AAV8)-RS1 gene therapy trial (ClinicalTrials.gov: NCT02317887). Immune cell proportions and serum analytes were compared to 12 healthy male controls. At pre-dosing baseline the mean CD4/CD8 ratio of XLRS subjects was elevated. CD11c+ myeloid dendritic cells (DCs) and the serum epidermal growth factor (EGF) level were decreased, while CD123+ plasmacytoid DCs and serum interferon (IFN)-γ and tumor necrosis factor (TNF)-α were increased, indicating that the XLRS baseline immune status differs from that of controls. XLRS samples 14 days after AAV8-RS1 administration were compared with the XLRS baseline. Frequency of CD11b+CD11c+ DCc was decreased in 8 of 11 XLRS subjects across all vector doses (1e9-3e11 vector genomes [vg]/eye). CD8+human leukocyte antigen-DR isotype (HLA-DR)+ cytotoxic T cells and CD68+CD80+ macrophages were upregulated in 10 of 11 XLRS subjects, along with increased serum granzyme B in 8 of 11 XLRS subjects and elevated IFN-γ in 9 of 11 XLRS subjects. The six XLRS subjects with ocular inflammation after vector application gave a modestly positive correlation of inflammation score to their respective baseline CD4/CD8 ratios. This exploratory study indicates that XLRS subjects may exhibit a proinflammatory, baseline immune phenotype, and that intravitreal dosing with AAV8-RS1 leads to systemic immune activation with an increase of activated lymphocytes, macrophages, and proinflammatory cytokines.

Adalimumab (ADA), a fully human monoclonal tumor necrosis factor (TNF)-α antibody, is one of the most widely used biologics in the treatment of inflammatory diseases. However, ADA can exacerbate infectious conditions, induce paradoxical reactions such as inflammation, and cause neoplasia. Human T-cell leukemia virus type 1 (HTLV-1) is an infectious agent that induces inflammation and neoplastic infiltration in the eye. To date, numerous HTLV-1 carriers have been treated with adalimumab to suppress inflammation out of necessity, when standard anti-inflammatory drugs such as steroids and immunosuppressive agents have proven inadequate to control the inflammation. Here, we clarify the safety of adalimumab for the eye under HTLV-1 infectious conditions in vitro. We used the adult retinal pigment epithelial cell line (ARPE)-19 cell line as ocular resident cells, and used MT2 and TL-Om1 as HTLV-1-infected cells. ARPE-19 and MT2/TL-Om1 were co-cultured, and then adalimumab was administered. Production of cytokines and chemokines, TNF-α receptor (TNF-R), HTLV-1 proviral load (PVL), and apoptosis were measured to assess the effects of adalimumab. Contact between ARPE-19 and MT2/TL-Om1 produced inflammatory cytokines such as TNF, interleukin (IL)-6, IL-8 and IL-10, and transduced chemokines such as interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), monokine induced by interferon-γ (MIG), and regulated on activation, normal T cell expressed and secreted (RANTES). No inflammatory cytokines and chemokines were exacerbated by adalimumab. Expression of TNF-R on ARPE-19 and MT2/TL-Om1 cells, HTLV-1 PVLs of MT2/TL-Om1 cells, and cell growth rate and apoptotic rate of ARPE-19 were unaffected by adalimumab. In conclusion, adalimumab does not appear to exacerbate HTLV-1-associated inflammatory conditions in the eye or increase PVL in HTLV-1-infected T cells. These data suggest that adalimumab could be used safely for the eye under HTLV-1 infectious conditions from the perspective of in vitro assessment.

This pilot study investigated the in vivo therapeutic potential and tolerability of a multimodal ophthalmic formulation, topical eye drops (TED), for acute mustard gas keratopathy (MGK) using a rabbit model.
Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD]) received single sulfur mustard gas (SM) vapor injury, whereas contralateral eyes were left untreated or received TED for tolerabilty evaluation. Two rabbit eyes received no treatment and served as age-matched naive control. The four groups were: Naive (oculus sinister [OS] untreated eyes; n = 9); TED (OS treated only with TED BID for 3 days; n = 9); SM (OD exposed to SM vapor; n = 9); and SM+TED (OD exposed to SM+TED BID for 3 days; n = 9). Ocular examination in live rabbits were performed utilizing slit-lamp biomicroscopy, Fantes grading system, fluorescein staining, Schirmer\'s tests, pachymetry, and applanation tonometry. Cellular and molecular changes in rabbit corneas were assessed after humane euthanasia on day-3 and day-7 with histopathological and real-time polymerase chain reaction PCR techniques.
TED to rabbit eyes was found tolerable in vivo. SM-exposed eyes showed significant increase in Fantes scores, central corneal thickness (CCT), Schirmer\'s test, epithelium-stroma separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer\'s test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factor-TGF-β1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity.
The developed multimodal eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo.
TED is effective against MGK.

Dry eye syndrome is a common disease associated to eyes inflammation, irritation and tear film instability. The enzymatic complex of xanthine oxidoreductase (XOR) is involved in the generation of reactive oxygen species (ROS) and uric acid that, in the end, can cause reperfusion injuries, irritation and pathological conditions. Furthermore, in the eye, it has been proposed that oxygen free radicals might play a significant role in retinal ischemic damage. A new artificial drop formulation based on arabinogalactan and hyaluronic acid has been proposed in this article. The uric acid and the ROS formation have been monitored. The effect of the arabinogalactan, the hyaluronic acid and their mixture has been studied. The arabinogalactan entails a uric acid and ROS reduction of 27% and 38% respectively; no significant reduction of uric acid or ROS has been observed after the addition of hyaluronic acid alone. Notably the combination of arabinogalactan and hyaluronic acid involves the reduction of uric acid and ROS equal to 38% and 62%, namely. This study demonstrates that this artificial drop formulation can markedly reduce the uric acid and ROS formation in vitro; thus, the use of this formulation may contribute in the resolution of the dry eye syndrome.

Ocular tuberculosis is an extrapulmonary tuberculous infection and has varying manifestations which pose a huge challenge to diagnosis and treatment. The purpose of this study is to describe the various clinical manifestations of ocular inflammations due to tuberculosis and to assess the response to treatment following antituberculous therapy (ATT) and corticosteroids in these patients.
We performed a retrospective analysis of 29 patients with presumed ocular tuberculosis who were started on ATT and completed follow-up of at least 6 months after ATT was initiated. The data collected were: age at presentation, sex, laterality, presence or absence of pulmonary/extrapulmonary tuberculosis, history of exposure to tuberculosis, site of ocular involvement and duration of illness, visual acuity at presentation and at 6-month follow-up, and response to treatment.
Most of the patients were of economically productive age, between 21-60 years. This most common presentation in our study population was unilateral nongranulomatous anterior uveitis. In spite of the delay between symptom onset and start of therapy, favorable response was noted in 79.3% of patients at completion of 6 months of ATT. The various reasons for the delay in start of therapy were also evaluated.
In this case series, we presented the various ocular manifestations and the difficulties faced in the diagnosis of presumed ocular tuberculosis. Outcomes of ATT were favorable in most of our patients. Thus, the clinician should exercise a very high degree of suspicion and should not withhold a trial of ATT.