Ocular Gene Therapy in a Patient with Dystrophic Epidermolysis Bullosa.

Dystrophic epidermolysis bullosa is a rare genetic disease caused by damaging variants in COL7A1, which encodes type VII collagen. Blistering and scarring of the ocular surface develop, potentially leading to blindness. Beremagene geperpavec (B-VEC) is a replication-deficient herpes simplex virus type 1-based gene therapy engineered to deliver functional human type VII collagen. Here, we report the case of a patient with cicatrizing conjunctivitis in both eyes caused by dystrophic epidermolysis bullosa who received ophthalmic administration of B-VEC, which was associated with improved visual acuity after surgery.

A randomized, double-blind, placebo-controlled trial with mannan-conjugated birch pollen allergoids.

BACKGROUND: There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan-conjugated birch pollen allergoids for the short-course treatment of birch pollen-induced allergic rhinoconjunctivitis. METHODS: For this prospective, randomized, double-blind, placebo-controlled, dose-finding study, 246 birch pollen-allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan-conjugated birch pollen allergoids at five pre-seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti-allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed. RESULTS: The highest dose of mannan-conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose-dependent manner (3.6- and 4.5-fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to -70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II). CONCLUSION: All doses of mannan-conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation.

Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis and comorbid allergies.

BACKGROUND: Abrocitinib efficacy by comorbidity status in patients with moderate-to-severe atopic dermatitis (AD) has not been previously assessed. This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with AD and allergic comorbidities. METHODS: Data were pooled from patients who received abrocitinib 200 mg, 100 mg, or placebo in phase 2b (NCT02780167) and phase 3 (NCT03349060, NCT03575871) monotherapy trials. Patients with and without allergic comorbidities (allergic asthma, rhinitis, conjunctivitis, or food allergy) were evaluated for Investigator's Global Assessment (IGA) response (clear [0] or almost clear [1]), ≥75% improvement in the Eczema Area and Severity Index (EASI-75), ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4), and Dermatology Life Quality Index (DLQI) response (<2 with baseline score ≥2). Other outcomes were Patient-Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD), and treatment-emergent adverse events (TEAEs). RESULTS: Of 942 patients, 498 (53%) reported at least one allergic comorbidity (asthma only, 33%; conjunctivitis only or rhinitis only or both, 17%; food allergies only, 15%; >1 allergic comorbidity, 34%). Regardless of comorbidity status, from Week 2 to Week 12, higher percentages of patients treated with either abrocitinib dose achieved IGA 0/1, EASI-75, PP-NRS4, or DLQI 0/1 versus placebo-treated patients. Changes from baseline in POEM, SCORAD, and PSAAD were greater with abrocitinib than with placebo in patients with and without allergic comorbidities. Most TEAEs were mild or moderate. CONCLUSIONS: Efficacy and safety data support abrocitinib use to manage AD in patients with or without allergic comorbidities.

Developing a model for aqueous deficient dry eye secondary to periglandular cicatrizing conjunctivitis.

PURPOSE: The current study used various techniques to develop a rabbit animal model of lacrimal gland damage caused by scarring conjunctivitis in the periglandular area. METHODS: Left eyes of New Zealand white rabbits were injected with 0.1 ml of 1M NaOH subconjunctivally around superior and inferior lacrimal gland orifices (Group 1, n = 4), touched with 1M NaOH for 100 s to the superior and inferior fornices with conjunctival denuding (Group 2; n = 4), and electrocauterization to the ductal opening area (Group 3; n = 4). The ocular surface staining, Schirmer I, lacrimal gland, and conjunctival changes were observed at baseline,1, 4, 8, and 12 weeks. The degree of glandular inflammation, conjunctival fibrosis (Masson Trichrome), and goblet cell density (PAS) were also assessed. RESULTS: At 12 weeks, the lacrimal glands of group 1 rabbits with periglandular injection showed severe inflammation with mean four foci/10HPF and a significant mean reduction in the Schirmer values by 7.6 mm (P = 0.007). Lacrimal glands had diffuse acinar atrophy, loss of myoepithelial cells, and ductular dilatation. The overlying conjunctiva showed fibrosis, goblet cell loss, and corneal vascularization in the inferotemporal quadrant. No lacrimal gland or ocular surface changes were observed in groups 2 and 3 at 12 weeks, except for localized subconjunctival fibrosis. CONCLUSION: Periglandular injection of 0.1 ml of 1M NaOH induced extensive lacrimal gland damage with reduced secretion and scarring in the subconjunctival plane compared to direct cauterization or direct NaOH contact to the ductal orifices of the rabbit lacrimal gland.

Efficacy and safety of intratonsillar immunotherapy for allergic rhinitis: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative treatment for IgE-mediated allergies. Therefore, exploring innovative allergen-specific immunotherapy routes is necessary. OBJECTIVE: To explore the efficacy and safety of the intratonsillar injection of house dust mite (HDM) extract in patients with HDM-induced allergic rhinitis (AR). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 80 patients with HDM-induced AR were randomized to receive 6 intratonsillar injections with HDM extract or placebo in 3 months. The total nasal symptom score (TNSS), visual analogue scale of nasal symptoms, combined symptom and medication score, mini rhinoconjunctivitis quality of life questionnaire, and serum allergen-specific IgG4 to Dermatophagoides pteronyssinus were all monitored at baseline and 3 months, 6 months, and 12 months after the treatment was finished. The intent-to-treat and per-protocol set (PPS) are both analyzed. RESULTS: The primary end points TNSS and ΔTNSS were improved significantly at 3 months after the patients with AR finished a 3-month 6-injection intratonsillar immunotherapy compared with those in the placebo treatment in both intent-to-treat and PPS. Results of visual analogue scale, combined symptom and medication score, and mini rhinoconjunctivitis quality of life questionnaire were also improved significantly at 3 months after the treatment in PPS. However, the improvement effect of intratonsillar immunotherapy at 6 and 12 months was limited and uncertain based on the data. The increase of serum Der p IgG4 in the active group was significantly higher than that in the placebo group at 3, 6, and 12 months after the treatment was finished. Adverse events were monitored, and no systemic adverse reactions were observed. CONCLUSION: The clinical trial revealed that intratonsillar injection with HDM extract was safe and effective in patients with AR. Optimizing the protocol and allergen formulations is expected to increase and maintain the efficacy of this novel approach. TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier: ChiCTR-TRC-13003600.

Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry.

BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. METHODS: Data were extracted from the prospective, multicenter BioDay registry (October 2017-2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. RESULTS: In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.

Residential exposure to mold, dampness, and indoor air pollution and risk of respiratory tract infections: a study among children ages 11 and 12 in the Danish National Birth Cohort.

BACKGROUND: The burden of respiratory tract infections (RTIs) is high in childhood. Several residential exposures may affect relative rates. OBJECTIVES: To determine risk of RTIs in children ages 11 and 12 by residential exposures. METHODS: We included children in the Danish National Birth Cohort (DNBC) at ages 11 and 12. We estimated incidence risk ratios (IRR) and 95% confidence intervals (CI) for counts of RTIs within the last year by exposure to mold/dampness, gas stove usage, summer and winter candle-burning, fireplace usage, cats and dogs indoors, and farmhouse living. We also estimated IRR and 95% CI for RTIs for predicted scores of four extracted factors ('owned house', 'mold and dampness', 'candles', and 'density') from exploratory factor analyses (EFA). RESULTS: We included 42 720 children with complete data. Mold/dampness was associated with all RTIs (common cold: IRRadj 1.09[1.07, 1.12]; influenza: IRRadj 1.10 [1.05, 1.15]; tonsillitis: IRRadj 1.19 [1.10, 1.28]; conjunctivitis: IRRadj 1.16 [1.02, 1.32]; and doctor-diagnosed pneumonia: IRRadj 1.05 [0.90, 1.21]), as was the EFA factor 'mold/dampness' for several outcomes. Gas stove usage was associated with conjunctivitis (IRRadj 1.25 [1.05, 1.49]) and with doctor-diagnosed pneumonia (IRRadj 1.14 [0.93, 1.39]). Candle-burning during summer, but not winter, was associated with several RTIs, for tonsillitis in a dose-dependent fashion (increasing weekly frequencies vs. none: [IRRadj 1.06 [0.98, 1.14], IRRadj 1.16 [1.04, 1.30], IRRadj 1.23 [1.06, 1.43], IRRadj 1.29 [1.00, 1.67], and IRRadj 1.41 [1.12, 1.78]). CONCLUSION: Residential exposures, in particular to mold and dampness and to a lesser degree to indoor combustion sources, are related to the occurrence of RTIs in children.

Are inflammation-related diseases risk factors for primary acquired nasolacrimal duct obstruction? A large scale, national case-control study.

PURPOSE: To evaluate the incidence and risk factors for inflammatory conditions among patients with primary acquired nasolacrimal duct obstruction (PANDO). METHODS: A retrospective case-control study was conducted among patients of Clalit Health Services (CHS) in Israel from 2001 to 2022. For each case, three controls were matched among all CHS patients according to year of birth, sex, and ethnicity. Differences in demographic characteristics, ocular surface, eyelid, upper airway, and systemic diseases were assessed between the groups, and odds ratios (OR) were calculated. RESULTS: A total of 60,726 patients diagnosed with PANDO were included. The average age of PANDO patients was 63 ± 18 years, 63% were female. Significant associations were found between PANDO and various ocular surface and eyelid conditions, including chronic conjunctivitis (OR 2.96, 95% CI [2.73-3.20]), vernal keratoconjunctivitis (OR 2.89, 95% CI [2.45-3.29]), and blepharitis (OR 2.75, 95% CI [2.68-2.83]). There was a significant association with various upper airway conditions, including rhinitis (OR 1.62, 95% CI [1.58-1.66]), chronic sinusitis (OR 1.71, 95% CI [1.62-1.80]), and deviated nasal septum (OR 1.76, 95% CI [1.69-1.84]). Association was also observed with systemic conditions, including asthma (OR 1.34, 95% CI [1.27-1.41]) and atopic dermatitis (OR 1.36, 95% CI [1.32-1.41]). CONCLUSION: Ocular surface, eyelid, upper airway, and systemic inflammatory-related diseases were found to be associated with PANDO, supporting the theory that inflammation has a prominent role in the pathophysiology of PANDO.

Temozolomide-associated blepharoconjunctivitis: a case report.

BACKGROUND: Temozolomide (TMZ) is an effective oral alkylating agent used in treating glioblastoma multiforme (GBM) and high-grade gliomas. It works by introducing methyl groups into DNA, inhibiting cell division. A case of blepharoconjunctivitis linked to the administration of TMZ is detailed in this report. CASE PRESENTATION: We present a case of a 58-year-old African-American man diagnosed with GBM. Following adjuvant TMZ treatment, he developed blepharoconjunctivitis, characterized by eyelid and conjunctival inflammation. Symptoms included eyelid swelling, crusting, and conjunctival discharge, which were promptly resolved with topical steroid cream and eye drops. CONCLUSIONS: Reports specifically linking TMZ to blepharoconjunctivitis are limited. The exact mechanism remains unclear but may involve inflammation extending from blepharitis to the conjunctiva. Healthcare providers must recognize and manage ophthalmic complications promptly. This case report highlights blepharoconjunctivitis associated with TMZ use in a GBM patient. While TMZ is an effective treatment, ophthalmic side effects can occur.

Sublingual immunotherapy tablets in monosensitized and polysensitized adults with allergic rhinoconjunctivitis.

Background: Most patients with allergic rhinitis/conjunctivitis (AR/C) are sensitized to more than one allergen. An ongoing question is the efficacy of single-allergen immunotherapy in patients who are polysensitized. Objective: To evaluate the efficacy and safety of grass, ragweed, tree, and house-dust mite (HDM) sublingual immunotherapy (SLIT) tablets in adults with AR/C who are mono- or polysensitized. Methods: Data from adults (ages ≥ 18 years) with AR/C who participated in phase III double-blind, placebo controlled field trials (four grass, two ragweed, two HDM, one tree) were included in the post hoc analyses. Efficacy was assessed by the total combined score (TCS) (sum of AR/C daily symptom and medication scores) during the entire pollen season for grass and tree trials, and peak pollen season for ragweed trials versus placebo. Efficacy for the HDM SLIT-tablet was assessed by the total combined rhinitis score (TCRS) (sum of rhinitis daily symptom and medication scores) during the last 8 weeks of treatment versus placebo. Results: For the grass SLIT-tablet, TCS improved by 20% (mean difference 1.33 [95% confidence interval {CI}, 0.44-2.22]) in the subjects who were monosensitized (n = 442) and 20% (mean difference 1.28 [95% CI, 0.90-1.67]) in the subjects who were polysensitized (n = 1857). For the ragweed SLIT-tablet, TCS improved by 19% (mean difference 1.72 [95% CI, -0.20 to 3.63]) in the subjects who were monosensitized (n = 115) and 27% (mean difference 2.27 [95% CI, 1.28-3.27]) in the subjects who were polysensitized (n = 528). For the tree SLIT-tablet, TCS improved by 54% (mean difference 4.65 [95% CI, 2.48-6.82]) in the subjects who were monosensitized (n = 138) and 34% (mean difference 2.51 [95% CI, 1.34-3.69]) in the subjects who were polysensitized (n = 437). For the HDM SLIT-tablet, TCRS improved by 20% (mean difference 1.24 [95% CI, 0.48-1.99]) in the subjects who were monosensitized (n = 468) and 17% (mean difference 0.85 [95% CI, 0.43-1.28]) in the subjects who were polysensitized (n = 1294). The overall safety profile was not qualitatively different between the subjects who were monosensitized and the subjects who were polysensitized. Conclusion: Grass, ragweed, tree, or HDM SLIT-tablet treatment is effective for the specific allergen in question in adults with AR/C and who are monosensitized or polysensitized. Targeting one relevant allergen with SLIT-tablets induces a clinical effect for that allergen in patients who were polysensitized.

Use of Large Language Models to Assess the Likelihood of Epidemics From the Content of Tweets: Infodemiology Study.

BACKGROUND: Previous work suggests that Google searches could be useful in identifying conjunctivitis epidemics. Content-based assessment of social media content may provide additional value in serving as early indicators of conjunctivitis and other systemic infectious diseases. OBJECTIVE: We investigated whether large language models, specifically GPT-3.5 and GPT-4 (OpenAI), can provide probabilistic assessments of whether social media posts about conjunctivitis could indicate a regional outbreak. METHODS: A total of 12,194 conjunctivitis-related tweets were obtained using a targeted Boolean search in multiple languages from India, Guam (United States), Martinique (France), the Philippines, American Samoa (United States), Fiji, Costa Rica, Haiti, and the Bahamas, covering the time frame from January 1, 2012, to March 13, 2023. By providing these tweets via prompts to GPT-3.5 and GPT-4, we obtained probabilistic assessments that were validated by 2 human raters. We then calculated Pearson correlations of these time series with tweet volume and the occurrence of known outbreaks in these 9 locations, with time series bootstrap used to compute CIs. RESULTS: Probabilistic assessments derived from GPT-3.5 showed correlations of 0.60 (95% CI 0.47-0.70) and 0.53 (95% CI 0.40-0.65) with the 2 human raters, with higher results for GPT-4. The weekly averages of GPT-3.5 probabilities showed substantial correlations with weekly tweet volume for 44% (4/9) of the countries, with correlations ranging from 0.10 (95% CI 0.0-0.29) to 0.53 (95% CI 0.39-0.89), with larger correlations for GPT-4. More modest correlations were found for correlation with known epidemics, with substantial correlation only in American Samoa (0.40, 95% CI 0.16-0.81). CONCLUSIONS: These findings suggest that GPT prompting can efficiently assess the content of social media posts and indicate possible disease outbreaks to a degree of accuracy comparable to that of humans. Furthermore, we found that automated content analysis of tweets is related to tweet volume for conjunctivitis-related posts in some locations and to the occurrence of actual epidemics. Future work may improve the sensitivity and specificity of these methods for disease outbreak detection.

Conjunctivitis: Diagnosis and Management.

Conjunctivitis caused by viruses, bacteria, or allergies is one of the most common eye conditions in primary care. There is no single sign or symptom that accurately differentiates viral from bacterial conjunctivitis. A comprehensive history and physical examination can guide diagnosis. Viral and allergic conjunctivitis are more common in adults and typically present with watery discharge. Supportive care options for viral conjunctivitis include artificial tears, cold compresses, and antihistamine eye drops. Strict personal hygiene, including frequent handwashing, is essential to decrease the risk of transmission. Topical antihistamines with mast cell-stabilizing activity are the treatment of choice for allergic conjunctivitis. Bacterial conjunctivitis is more common in children and typically presents as mucopurulent discharge with the eyelids matted shut. Delayed antibiotic prescribing has been found to have similar symptom control as immediate prescribing. Ophthalmology referral is indicated for conjunctivitis in a neonate or patients with severe pain, decreased vision, recent ocular surgery, vesicular rash on the eyelids or nose, history of rheumatologic disease, or immunocompromised state.

Progressive Necrotizing Ocular Surface Disease, Despite Immunosuppression.

A 60-year-old man was referred with 2 years of left conjunctivitis that persisted despite antibiotic and systemic corticosteroid therapy. The severity and extent of surface disease had increased slowly after prior dacryocystorhinostomy. Subsequent conjunctival biopsies demonstrated granulomas with patchy necrosis but no evidence of malignancy or organisms; systemic screening for sarcoidosis and tuberculosis was negative. A markedly thickened and inflamed left ocular surface was present on referral, with areas of conjunctival ischemia and patchy white slough on the tarsi. Further ocular surface biopsy did not reveal malignancy, and therefore mycobacterial infection was considered a possible cause. Mycobacterium tuberculosis was cultured, albeit only after repeated conjunctival swabs and biopsies. Appropriate treatment led to a very rapid resolution of ocular surface disease. Localized periocular tuberculosis is extremely rare outside developing nations, and its rarity may cause this differential diagnosis for persistent severe ocular surface disease to be overlooked in industrialized nations.

Bedside Leukocyte Esterase Testing to aid in Diagnosing Bacterial Conjunctivitis in Children.

BACKGROUND: Conjunctivitis is a frequent symptom in pediatric emergency departments; however, the etiology of conjunctivitis is difficult to clinically differentiate. OBJECTIVE: Our study objective was to evaluate the test performance characteristics of leukocyte esterase (LE) test strips in diagnosing bacterial conjunctivitis. METHODS: Patients aged from 3 months through 21 years presenting to an emergency department with symptoms of conjunctivitis were prospectively enrolled from September 2018 to March 2020. A swab of the affected eye was applied to the LE test strip and another swab was sent for culture processing. The primary outcome was the association between LE test results and eye culture results. RESULTS: We enrolled 189 patients. Overall, 117 eye cultures (62%) were positive. The sensitivity and specificity of LE testing was 96% (95% CI 90-98%) and 14% (95% CI 7-25%), respectively. Positive predictive value was 64% (95% CI 57-71%) and negative predictive value was 67% (95% CI 39-87%). CONCLUSIONS: The LE test strip had limited ability to differentiate bacterial conjunctivitis from other etiologies.

Nonhealing Surgical Wounds in a Patient with Plasminogen Deficiency Type 1 Successfully Treated with Intravenous Plasminogen: A Case Report.

ABSTRACT: Intravenous plasminogen replacement therapy for patients with plasminogen deficiency type 1 (hypoplasminogenemia) was recently approved for marketing in the US. In this case report, the authors describe a 33-year-old man with hypoplasminogenemia who developed nonhealing postsurgical wounds following trauma to his right hand despite receiving standard treatment for 4 months. The patient was enrolled in a compassionate-use protocol with intravenous plasminogen replacement therapy and experienced prompt resolution of surgical wounds. He was the first human patient to receive replacement therapy with plasminogen, human-tvmh in the US and first to demonstrate cutaneous wound healing in addition to resolution of ligneous lesions attributable to plasminogen deficiency type 1.

[Bacterial Conjunctivitis: Current Aspects of Diagnosis and Therapy]. / Bakterielle Konjunktivitis: Aktuelle Aspekte der Diagnostik und Therapie.

Bacterial conjunctivitis is a leading cause of infectious conjunctivitis in children and second most common cause in adults. Although often self-limiting, it can lead to complications like corneal scarring and systemic infections in high-risk groups including newborns and immunocompromised patients. Thus, prompt diagnosis and treatment are essential for these vulnerable populations. Common bacterial causes are Staphylococcus aureus and Streptococcus pneumoniae in adults and Haemophilus influenzae and Moraxella catarrhalis in children. Clinical features alone do not reliably identify the causative pathogen. Microbiological testing is necessary for persistent or severe cases. Topical antibiotics like azithromycin or fluorochinolones are usually prescribed. However, gonococcal and chlamydial conjunctivitis warrant systemic antibiotics due to their potential for severe complications. Increasing antibiotic resistance might even necessitate tailored therapy based on antibiotic susceptibility profiles. Screening and treating pregnant women is an effective prevention strategy by reducing perinatal transmission (especially of gonococcal and chlamydial infections). In summary, while often self-limiting, potential complications and rising antibiotic resistance underscore the importance of timely diagnosis and treatment of bacterial conjunctivitis. Preventive measures including maternal screening are crucial public health initiatives to curb the risks associated with this common eye infection.

Ocular manifestations of granulomatosis with polyangiitis: report from a tertiary eye care center.

PURPOSE: To report demographic characteristics and ophthalmological manifestations of patients with granulomatosis with polyangiitis (GPA) in a tertiary eye care center in Turkey. METHODS: Medical records of patients with GPA-related ocular manifestations evaluated between 2013 and 2023 were included. Demographic and clinical characteristics of the patients including nature of systemic involvement, ophthalmologic symptoms and signs, laboratory investigations and treatment modality were reviewed. RESULTS: Twelve eyes of 10 patients (5 female/5 male) were included. The mean age was 57.2 ± 12.2 (35-71) years. Five (50%) patients were already diagnosed with GPA. Ocular involvement was the first manifestation of GPA in 3 patients. The remaining 2 patients had simultaneous systemic and ocular symptoms at presentation. Conjunctival hyperemia (9 eyes) and pain (7 eyes) were the most frequent presenting symptoms followed by blurred vision (3 eyes). The frequencies of ocular manifestations were as follows:episcleritis (3 eyes), isolated peripheral ulcerative keratitis (PUK) (3 eyes), scleritis (3 eyes), simultaneous PUK and scleritis (2 eyes) and periorbital mass (1 eye). CONCLUSION: Ophthalmological manifestations can be the initial findings in GPA. Since GPA can affect different structures of the eye, it sometimes might be challenging for ophthalmologists. Therefore, it is crucial for ophthalmologists to be well-informed about GPA-related ocular findings and to have a high index of suspicion for GPA. Although PUK associated with scleritis is highly suggestive for GPA, isolated cases of PUK or scleritis can be seen in GPA. Therefore, it is important to adopt a multidisciplinary approach, consider GPA in differential diagnosis, and benefit from accurate diagnostic tests.

Actinic conjunctivitis and its relationship with prurigo in an indigenous population from the Highlands of Chiapas, Mexico.

PURPOSE: Actinic conjunctivitis (AC), along with cheilitis (AChe), is part of the clinical spectrum of actinic prurigo (AP), a rare photo dermatosis that affects high-risk populations. We analyzed the clinical manifestations and onset of actinic conjunctivitis (AC), and its relationship with prurigo (AP) in a susceptible population. METHODS: This prospective observational cohort study was performed on Indigenous populations from the highlands of Chiapas, Mexico. Thorough dermatological and ophthalmological examinations were performed in patients attending a primary health care center. The clinical features, labor and environmental factors, onset timing, and clinical staging of AC and AP were analyzed. RESULTS: Of the 2913 patients studied, 54 patients (108 eyes) (1.8%) had AC, and 14 patients (25.9%) had AP. The mean age at diagnosis was 36.18 ± 18.52 years (6-70 years). The mean residential altitude was 1884 ± 434.2 m above sea level. Mean self-reported sun exposure was 5.14 ± 3.1 h a day (0.5-12 h). A total of 90.7% reported exposure to biomass fuels during cooking, and 50% to farm animals. AC was the sole manifestation in 70% of the cases. All patients had nasal and temporal photo-exposed conjunctiva. Among the eyes, 12.9% were classified as stage-1, 64.8% as stage-2, and 22.2% stage-3. A total of 83.3% of the patients had hyperpigmented lesions, and 35.1% had evaporative dry eye disease. CONCLUSIONS: AC may be the initial or sole manifestation of AP. Most AC cases (87%) were initially observed at the advanced stages of the disease. Although solar exposure was not associated with late AC stages, a positive association was found with farm animal exposure. Evaporative dry eye associated with meibomian gland dysfunction has not been previously reported in patients with AC.

[Conjunctival fungal infection mimicking a recurrent conjunctival mass: a case report].

A 40-year-old man presented with recurrent ocular surface masses in his left eye persisting for over a year. Despite undergoing resection of the conjunctival mass and receiving anti-inflammatory treatment at another hospital, the mass reappeared within a week post-surgery. Over the past 6 months, the mass gradually increased in size, accompanied by a decline in vision. Following conjunctival mass excision combined with amniotic membrane transplantation at Beijing Tongren Hospital, Capital Medical University, histopathological examination revealed a fungal infection of the conjunctiva, resulting in a diagnosis of fungal conjunctivitis and conjunctival granuloma in the left eye. The patient received systemic antifungal medications and local therapy, resulting in a stable condition with no recurrence of the mass.

Plasminogen: an enigmatic zymogen.

Plasminogen is an abundant plasma protein that exists in various zymogenic forms. Plasmin, the proteolytically active form of plasminogen, is known for its essential role in fibrinolysis. To date, therapeutic targeting of the fibrinolytic system has been for 2 purposes: to promote plasmin generation for thromboembolic conditions or to stop plasmin to reduce bleeding. However, plasmin and plasminogen serve other important functions, some of which are unrelated to fibrin removal. Indeed, for >40 years, the antifibrinolytic agent tranexamic acid has been administered for its serendipitously discovered skin-whitening properties. Plasmin also plays an important role in the removal of misfolded/aggregated proteins and can trigger other enzymatic cascades, including complement. In addition, plasminogen, via binding to one of its dozen cell surface receptors, can modulate cell behavior and further influence immune and inflammatory processes. Plasminogen administration itself has been reported to improve thrombolysis and to accelerate wound repair. Although many of these more recent findings have been derived from in vitro or animal studies, the use of antifibrinolytic agents to reduce bleeding in humans has revealed additional clinically relevant consequences, particularly in relation to reducing infection risk that is independent of its hemostatic effects. The finding that many viruses harness the host plasminogen to aid infectivity has suggested that antifibrinolytic agents may have antiviral benefits. Here, we review the broadening role of the plasminogen-activating system in physiology and pathophysiology and how manipulation of this system may be harnessed for benefits unrelated to its conventional application in thrombosis and hemostasis.