Ocular involvement in adult and paediatric patients with monogenic autoinflammatory diseases: a Spanish multicentre retrospective study.

OBJECTIVES: Ophthalmologic involvement in monogenic autoinflammatory diseases has been explored mainly in paediatric patients. The aim of this study is to characterise ophthalmologic manifestations, therapeutic management and visual outcomes in a Spanish (UVESAI) cohort of adult/paediatric patients with monogenic autoinflammatory diseases. METHODS: Multicentre and retrospective study of patients with monogenic autoinflammatory diseases and ocular involvement. Eye manifestations, structural complications, treatments used and visual outcomes were analysed, and compared with previous studies. RESULTS: Forty-six patients (44/2 adults/children; 21/25 adult/paediatric-onset) with monogenic autoinflammatory diseases [cryopyrin associated periodic syndromes (n=13/28.3%), mainly Muckle-Wells syndrome (MWS) (n=11/24%); familial Mediterranean fever (FMF) (n=12/26%); TNF receptor-associated periodic syndrome (TRAPS); (n=9/20%); Blau syndrome (n=8/17%); hyperimmunoglobulin D syndrome (HIDS) (n=2/4.3%), deficiency of adenosine deaminase-2 and NLRC4-Autoinflammatory disease] (one each) were included. Conjunctivitis (n=26/56.5%) and uveitis (n=23/50%) were the most frequent ocular manifestations. Twelve (26.1%) patients developed structural complications, being cataracts (n=11/24%) and posterior synechiae (n=10/22%) the most frequent. Conjunctivitis predominated in TRAPS, FMF, MWS and HIDS (mainly in adults), and uveitis, in Blau syndrome. Seven (8%) eyes (all with uveitis) presented with impaired visual acuity. Local and systemic treatment led to good visual outcomes in most patients. Compared with previous studies mainly including paediatric patients, less severe ocular involvement was observed in our adult/paediatric cohort. CONCLUSIONS: Conjunctivitis was the most common ocular manifestation in our TRAPS, FMF, MWS and HIDS patients, and uveitis predominated in Blau syndrome. Severe eye complications and poor visual prognosis were associated with uveitis. Adults with monogenic autoinflammatory diseases seem to exhibit a less severe ophthalmologic presentation than paediatric patients.

Diagnosis of Immunoglobulin G4-related disease in a child with ligneous conjunctivitis: a novel mutation in plasminogen gene and plasminogen activator inhibitor-1 polymorphism.

OBJECTIVES: Ligneous conjunctivitis (LC) is a chronic conjunctivitis characterized by recurrent, firm, fibrin-rich, woody pseudomembranes on the palpebral conjunctiva. It is an ultrarare autosomal recessive disease associated with congenital plasminogen (PLG) deficiency due to mutations in the PLG gene (6q26). Immunoglobulin G4-related disease (IgG4-RD) is an idiopathic, systemic fibroinflammatory disease characterized by elevated serum IgG4 concentration and tissue infiltration of IgG4-positive plasma cells leading to organ enlargement, fibrosis and damage. CASE REPORT: A 7-year-old girl with LC was hospitalized for recurrent pancreatitis and diagnosed as IgG4-RD. PLG activity level was 15% (normal range 55-145%). Co-segregation analysis indicated that the patient was homozygous for the c. NG_016200.1(NM_000301.5):c.1465 T>C mutation in PLG gene. c. NG_016200.1(NM_000301.5):c.1465 T>C PLG variant was found to be heterozygous by NGS analysis in both parents. She also had plasminogen activator inhibitor - 1 (PAI-1) NG_013213.1(NM_000602.5):c.-816A>G (4G/4G) homozygous polymorphism and a heterozygote NG_001333.2 (NM_002769.5):c.292_293insC mutation in the serine protease 1 (PRSS-1) gene. However, heterozygous PRSS-1NG_001333.2 (NM_002769.5):c.292_293insC variant was found in the mother of the patient. All detected variants are currently considered as a variant of uncertain (or unknown) significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) classification. Oral steroid, oral azathioprine, topical fresh frozen plasma, topical heparin, topical steroid and topical cyclosporine were given. After 3 years of follow-up, IgG4-RD is under partial remission and no pseudomembranes. CONCLUSION: She is the second case had both LC and IgG4-RD. We identified a NG_016200.1(NM_000301.5):c.1465 T>C novel homozygous mutation in PLG gene and a PAI-1 NG_016200.1(NM_000301.5):c.1465 T>C (4G/4G) homozygous polymorphism, which has been reported as a risk factor for thrombotic events.

Ligneous conjunctivitis mimicking preseptal cellulitis in a 3-month-old infant.

BACKGROUND: Ligneous conjunctivitis is a very rare form of pseudomembranous conjunctivitis with few published cases in literature. We aim to describe the ocular findings and treatment in an infant with ligneous conjunctivitis resembling preseptal cellulitis on presentation. MATERIALS AND METHODS: Case report of a 3-month-old girl who was referred to a tertiary centre for ophthalmic assessment due to progressive eyelid oedema with no response to initiated topical and systemic antibiotics. Ethical approval has been achieved from the local ethics committee of the Ghent University Hospital and informed consent has been obtained from the parents of the child. RESULTS: Examination under general anaesthesia showed multiple, wood-like fibrinous pseudomembranes, originating from the conjunctiva, consistent with ligneous conjunctivitis. After careful removal of the coagulated exudate covering the cornea, a central corneal epithelial defect was evident without stromal infiltration. Histopathologic examination confirmed the predominance of fibrin within the pseudomembranes. Plasminogen activity was below the normal range. Genetic analysis did not identify a pathogenic variant in the PLG gene. The corneal epithelium re-epithelialised during the following days and the conjunctival lesions gradually subsided over the ensuing weeks whilst continuing heparin-containing artificial tears. CONCLUSION: A high level of suspicion is warranted in atypical cases of preseptal cellulitis which show no response to antibiotic treatment. Particularly in young children, examination under general anesthesia is warranted to allow diagnosis of rare causes of secondary eyelid oedema. We report an infant with unilateral ligneous conjunctivitis who responded well to topical, commercially-available heparin-containing artificial tears treatment. This approach is an effective and easy first-line treatment option in this condition, particularly in milder phenotypes.

Severe dysplasminogenemia due to homozygous PLG Ala620Thr variant in a Korean woman without a history of venous thromboembolism: A case report and literature review.

RATIONALE: Plasminogen plays an important role in fibrinolysis and is encoded by the PLG gene. The missense variant PLG Ala620Thr is the major cause of dysplasminogenemia in East Asian countries, including Korea. Although dysplasminogenemia was first reported in a Japanese patient with recurrent venous thromboembolism (VTE), subsequent studies have not demonstrated any clear association between the PLG Ala620Thr variant and the risk of VTE. To the best of our knowledge, this is the first report of a homozygous PLG Ala620Thr variant case from Korea. PATIENT CONCERNS: Here, we report a Korean family with PLG Ala620Thr mutation. The proband was a 34-year-old man who presented with multiple thrombotic arterial embolism and cardiac myxoma. INTERVENTIONS: Laboratory workup, including coagulation profile and PLG gene sequencing, was carried out for the affected family. DIAGNOSIS AND OUTCOME: The proband carried a heterozygous PLG Ala620Thr variant with decreased plasminogen activity of 65%. His 53-year-old mother, who had no reported history of VTE, was homozygous for the PLG Ala620Thr variant with decreased plasminogen activity of just 25%. Decreased plasminogen activity indicates dysplasminogenemia. LESSONS: We believe that this clinically silent homozygous case supports the previous findings that isolated PLG Ala620Thr variant does not confer a significant risk of VTE.

A large deletion in the Plasminogen gene is associated with ligneous membranitis in a Maltese dog.

Ligneous membranitis/conjunctivitis (LM, OMIM 217090) is a hereditary disorder caused by a congenital plasminogen (PLG) deficiency. In veterinary medicine, LM (OMIA 002020-9615) has rarely been reported in Golden Retrievers, Yorkshire Terriers, Doberman Pinschers and Scottish Terriers. In the latter breed, an A>T variation in an intron donor site of the PLG gene (PLG, c.1256+2T>A) has been found to be the sole causative molecular defect reported to date in dogs. Owing to the absence of plasmin enzymatic clearance which in turn depends on the lack of its proenzyme plasminogen, fibrin deposits tend to accumulate in viscous membranes on the eyes, triggering and sustaining an intense inflammatory response. A case of LM was diagnosed in a 7-month-old male Maltese dog. The dog was examined for severe recurrent conjunctivitis. A diagnosis of ligneous conjunctivitis was made by an ophthalmologist after a thorough eye examination and was confirmed by a complete lack of plasma activity of plasminogen. The main local signs were redness of the conjunctiva with persistent membranes having ligneous (wood-like) membranes on the eyes. The disease was associated with a complex rearrangement involving the plasminogen gene loci, causing the complete deletion of exon 1. This study provides a spontaneous animal model for LM associated with complete plasminogen deficiency and provides a method for detecting affected or carrier dogs.

Genotype Associations with the Different Phenotypes of Atopic Dermatitis in Children.

This study deals with detecting the associations of atopic dermatitis' (AD) phenotypes in children: alone or combined with seasonal allergic rhino-conjunctivitis (SARC) and/or perennial allergic rhinitis (PAR), and/or with bronchial asthma (BA) with single nucleotide polymorphisms (SNP) of filaggrin (FLG), thymic stromal lymphopoietin (TSLP) and orsomucoid-like-1 protein 3 (ORMDL3) genes. Male and female pediatric patients aged from 3 to 18 years old were recruited into the main (AD in different combinations with SARC, PAR, BA) and control groups (disorders of digestives system, neither clinical nor laboratory signs of atopy). Patients were genotyped for SNP of rs_7927894 FLG, rs_11466749 TSLP, rs_7216389 ORMDL3 variants. Statistically significant associations of the increased risk were detected of AD combined with SARC and/or PAR and AD combined with BA (possibly, SARC and/or PAR) with C/T rs_7927894 FLG and T/T rs_7216389 ORMDL3 genotypes. Genotype C/C rs_7927894 FLG significantly decreases the risk of AD combined with SARC and/or PAR by 2.56 fold. Several genotypes' associations had a trend to significance: C/C rs_7216389 ORMDL3 decreases and C/T rs_7216389 ORMDL3 increases the risk for developing AD alone phenotype; A/G rs_11466749 TSLP decreases the risk of AD combined with BA (possibly, SARC and/or PAR) phenotype development.

A Novel mRNA Modification Mutation in a Patient With Ligneous Conjunctivitis Coexisting With Heterozygous Familial Mediterranean Fever Mutation.

PURPOSE: To describe a novel mRNA mutation associated with ligneous conjunctivitis (LC) in a patient with heterozygous familial Mediterranean fever (FMF) mutation. METHODS: Case presentation of a patient with LC and heterozygous FMF mutation. The patient was evaluated for various genetically predisposed inflammatory diseases through whole exome sequencing. RESULTS: LC is a rare inflammatory ocular pathology presenting with recurrent conjunctivitis episodes with eosinophilic fibrin-rich pseudomembranes. FMF is an autoinflammatory disease presenting with recurrent episodes of fever, arthritis, and other inflammatory conditions. Various plasminogen (PLG) gene mutations have been identified in LC, whereas a variety of mutations in the Mediterranean fever (MEFV) gene have been identified in FMF patients. Based on the inflammatory nature of both pathologies, we aimed to evaluate and identify any potential common genetic pathway. We were not able to identify any mutation in PLG gene through whole gene sequencing; however, the patient was positive for heterozygous M680I FMF mutation, and we observed 22% of NM_000301.3:c.2130T>G (p.T710=) variant in mRNA isolated from affected tissue, which was not present in DNA sequence. CONCLUSIONS: To the best of our knowledge, this is the first case of LC caused by an mRNA mutation coexisting with another genetically predisposed autoinflammatory disease mutation.

Novel homozygous mutation of plasminogen in ligneous conjunctivitis: a case report and literature review.

Background:Ligneous conjunctivitis (LC) is a rare disease characterized by the development of a wood-like pseudomembrane on the tarsal conjunctiva secondary to type I plasminogen deficiency. Here we reported on a Chinese patient with LC in a consanguineous family and performed a literature review of all reported mutations for this disease. Methods: A 13-month-old girl diagnosed with LC and her parents were included in this study. Hematoxylin and eosin staining was used to perform histopathology examination. The plasminogen activity was determined by chromogenic assay. Sanger sequencing was performed to screen the mutation site for the disease. In silico analysis was applied to predict the pathogenesis of the identified mutation. In addition, we reviewed the literatures on PLG mutations of LC. Results: Histopathology examination revealed the infiltration of inflammatory cells on membranous lesions. Plasma plasminogen activity was severely decreased in the patient and moderately decreased in her parents (patient: plasminogen activity, 2.50%; father: plasminogen activity, 41.02%; mother: plasminogen activity, 54.07%). Co-segregation analysis indicated that the patient was homozygous for the c.763 G > A (p.Glu255Lys) mutation in plasminogen gene (PLG). Bioinformatics analysis strongly suggested that the mutation was damaging for the disease. The model analysis indicated the mutation might cause abnormal spatial structure and low stability, thus affecting functional activity. A literature review of the LC mutations indicated a strong genetic heterogeneity of the disease. Conclusions: LC exhibited strong genetic heterogeneity, and our study identified a novel homozygous missense mutation of plasminogen (c.763 G > A, p.Glu255Lys) in one Chinese patient with LC.

RelB regulates basal and proinflammatory induction of conjunctival CCL2.

Purpose: This study investigated the involvement of NF-kB in regulating postoperative conjunctival inflammation.Methods: Experimental surgery was performed as described for the mouse model of conjunctival scarring. Expression of NF-κB in postoperative conjunctival tissues or conjunctival fibroblasts were assessed by real-time PCR, immunoblotting and immunofluorescence analyses. Downregulation of RelB was achieved using small interfering RNA. Cellular cytokine secretion was determined using multiplex cytokine assay.Results: RelB was the most highly induced member of the NF-kB family on day 2 post-surgery. Elevated RelB may be found associated with vimentin-positive cells and fibroblasts in vivo and in vitro. In conjunctival fibroblasts, RelB may be induced by TNF-α but not TGF-ß2 while its silencing caused selective induction of CCL2 secretion by both basal and TNF-α-stimulated fibroblasts.Conclusions: High RelB induction in the inflammatory phase and the selective modulation of CCL2 suggest a specific anti-inflammatory role for RelB in the postoperative conjunctiva.

Type 1 Plasminogen Deficiency With Pulmonary Involvement: Novel Treatment and Novel Mutation.

Type 1 plasminogen deficiency is a rare genetic disorder. Type 1 plasminogen deficiency is characterized by fibrin-rich pseudomembrane formation on mucosal surfaces, particularly the conjunctiva. Tracheobronchial tree involvement is a less common reported manifestation of type 1 plasminogen deficiency. Pseudomembranes in the tracheobronchial tree may result in respiratory compromise and ultimately fail if not recognized and treated. Currently, there is no specific replacement therapy approved for the treatment of congenital plasminogen deficiency. In the present paper, we report that type 1 plasminogen deficiency with novel frameshift mutation and pulmonary involvement was treated initially with systemic fresh frozen plasma followed by pulmonary lavage with fresh frozen plasma and tissue plasminogen activator.

Ocular surface inflammation induces de novo expression of substance P in the trigeminal primary afferents with large cell bodies.

We evaluated the changes in substance P (SP)-expressing trigeminal neurons (TNs) innervating the cornea following ocular surface inflammation. Ocular surface inflammation was induced in Sprague-Dawley rats using 0.1% benzalkonium chloride (BAK). The corneal staining score, corneal epithelial apoptosis, conjunctival goblet cells, and density of corneal subbasal nerve plexus (SNP) were assessed, and the mRNA levels of SP, interleukin (IL)-1ß, IL-6, and tumour necrosis factor-α were measured in corneas and ipsilateral trigeminal ganglia (TG). SP-immunoreactivity (IR) was measured in corneal intraepithelial nerves and TNs. The cell size of corneal TNs in the TG was calculated. All parameters were observed immediately (BAK group), at 1 week (1 w group), and 2 months (2 m group) after 2 weeks of BAK application. BAK caused an increase in the corneal staining score and the number of apoptotic cells, loss of conjunctival goblet cells, reduced density of corneal SNP, and upregulated expression of SP and inflammatory cytokines in both the cornea and TG in the BAK group but those changes were not observed in the 2 m group. On the other hand, SP-IR% and mean cell size of corneal TNs increased significantly in the BAK, 1 w, and 2 m groups, compared to the control. Our data suggest that following ocular surface inflammation, large-sized corneal TNs which normally do not express SP, expressed it and this phenotype switching lasted even after the inflammation disappeared. Long-lasting phenotypic switch, as well as changes in the expression level of certain molecules should be addressed in future studies on the mechanism of corneal neuropathic pain.

Functional Fibrinolysis Assays Reveal Different Mechanisms underlying Plasminogen Dysfunction in Ligneous Conjunctivitis.

BACKGROUND: Ligneous conjunctivitis (LC) is a rare disorder associated with plasminogen deficiency characterized by chronic fibrin deposits in the eyelids. All patients with plasminogen deficiency do not develop LC, whose underlying mechanisms remain unknown. OBJECTIVE: We investigated whether fibrinolytic activity was correlated with phenotype and/or genotype in patients suffering from LC and their relatives. METHODS: Plasminogen activity/antigen levels and PLG mutations were determined in 10 patients with LC, 17 of their asymptomatic relatives, and 10 healthy individuals used as a control group. Plasma fibrinolytic activity was evaluated using three different assays: (1) tissue-plasminogen activator (t-PA) front lysis, (2) cell-based urokinase-dependent euglobulin clot lysis (ECLT) at the surface of corneal cells, and (3) urokinase-dependent plasminogen activation. RESULTS: Plasminogen activity varied from <10 to 40% in patients, 36 to 105% in relatives, and >80% in control healthy individuals. Homozygous K19E mutation was associated with normal antigenic plasminogen levels. In front-lysis experiments, all patients had a lower fibrinolysis rate as compared with their relatives and to control individuals. The cell-based ECLT and plasminogen activation assay demonstrated that urokinase-mediated fibrinolysis was not impaired in patients with homozygous K19E mutation compared with the other mutants. CONCLUSION: We confirm that plasminogen levels fail to predict LC occurrence. In these conditions, t-PA clot lysis front is useful to predict clinical outcome in plasminogen deficiency. Moreover, we provide evidence that occurrence of LC overlaps quantitative and qualitative plasminogen deficiencies. The homozygous K19E mutation is associated with isolated impaired t-PA-mediated fibrinolysis compared with other mutants.

An association analysis to identify genetic variants linked to asthma and rhino-conjunctivitis in a cohort of Sicilian children.

Asthma and rhino-conjunctivitis are common chronic diseases in childhood. In this cross-sectional study, we performed a gene association analysis with current asthma and rhino-conjunctivitis in a cohort of Sicilian children aged 10-15 years. Overall, our findings reveal the importance of different genetic variants at 4p14, 16p12.1, 17q12, 6p12.2 and 17q21.1, identifying possible candidate genes responsible for susceptibility to asthma and rhino-conjunctivitis.

Clinical, histopathological, and genetic aspects in one case of ligneous conjunctivitis.

Ligneous conjunctivitis is an uncommon and recurrent type of chronic conjunctivitis. A prevalent cause of this disease is a Plasminogen deficiency, resulting from recessive mutations in the human encoding plasminogen (PLG) gene. This deficiency affects the conjunctiva and also other mucous membranes. Only few hundred cases have been reported in the literature. Here we report a case of a 9-year-old boy with diagnosis of ligneous conjunctivitis. Histopathological examination in hematoxylin-eosin (HE) staining and sequencing of PLG gene were performed to confirm diagnosis. Histopathological findings confirmed the diagnosis of ligneous conjunctivitis. The patient is compound heterozygous for c.1026T>G (p.Val342Gly) and c.2384G>C (p.Arg795Pro) mutations in PLG gene. Both mutations have not been described previously, and the bioinformatic analysis strongly suggests that are causative of the disease. To the best of our knowledge, this is the first case report of a Chilean patient with ligneous conjunctivitis.

Treatment of plasminogen deficiency patients with fresh frozen plasma.

Congenital plasminogen (Plg) deficiency leads to the development of ligneous membranes on mucosal surfaces. Here, we report our experience with local and intravenous fresh frozen plasma (FFP). We retrospectively reviewed medical files of 17 patients and their eight first-degree relatives. Conjunctivitis was the main complaint. Thirteen patients were treated both with intravenous and conjunctival FFP. Venous thrombosis did not develop in any. Genetic evaluation revealed heterogeneous mutations as well as polymorphisms. Diagnosis and treatment of Plg deficiency is challenging; topical and intravenous FFP may be an alternative treatment.

The prevalence and clinical manifestation of hereditary thrombophilia in Korean patients with unprovoked venous thromboembolisms.

BACKGROUND: Hereditary thrombophilia (HT) is a genetic predisposition to thrombosis. Asian mutation spectrum of HT is different from Western ones. We investigated the incidence and clinical characteristics of HT in Korean patients with unprovoked venous thromboembolism (VTE). METHODS: Among 369 consecutive patients with thromboembolic event who underwent thrombophilia tests, we enrolled 222 patients diagnosed with unprovoked VTE. The presence of HT was confirmed by DNA sequencing of the genes that cause deficits in natural anticoagulants (NAs). Median follow-up duration was 40±38 months. RESULTS: Among the 222 patients with unprovoked VTE, 66 (29.7%) demonstrated decreased NA level, and 33 (14.9%) were finally confirmed to have HT in a genetic molecular test. Antithrombin III deficiency (6.3%) was most frequently detected, followed by protein C deficiency (5.4%), protein S deficiency (1.8%), and dysplasminogenemia (1.4%). The HT group was significantly younger (37 [32-50] vs. 52 [43-65] years; P < 0.001) and had a higher proportion of male (69.7% vs. 47%; P = 0.013), more previous VTE events (57.6% vs. 31.7%; P = 0.004), and a greater family history of VTE (43.8% vs. 1.9%; P < 0.001) than the non-HT group. Age <45 years and a family history of VTE were independent predictors for unprovoked VTE with HT (odds ratio, 9.435 [2.45-36.35]; P = 0.001 and 92.667 [14.95-574.29]; P < 0.001). CONCLUSIONS: About 15% of patients with unprovoked VTE had HT. A positive family history of VTE and age <45 years were independent predictors for unprovoked VTE caused by HT.

Plasminogen Tochigi mice exhibit phenotypes similar to wild-type mice under experimental thrombotic conditions.

Plasminogen (Plg) is a precursor of plasmin that degrades fibrin. A race-specific A620T mutation in Plg, also known as Plg-Tochigi, originally identified in a patient with recurrent venous thromboembolism, causes dysplasminogenemia with reduced plasmin activity. The Plg-A620T mutation is present in 3-4% of individuals in East Asian populations, and as many as 50,000 Japanese are estimated to be homozygous for the mutant 620T allele. In the present study, to understand the changes of thrombotic phenotypes in individuals with the mutant 620T allele, we generated knock-in mice carrying the homozygous Plg-A622T mutation (PlgT/T), an equivalent to the A620T mutation in human Plg. PlgT/T mice grew normally but showed severely reduced plasmin activity activated by urokinase, equivalent to ~8% of that in wild-type mice. In vitro fibrin clot lysis in plasma was significantly slower in PlgT/T mice than in wild-type mice. However, all experimental models of electrolytic deep vein thrombosis, tissue factor-induced pulmonary embolism, transient focal brain ischaemic stroke, or skin-wound healing showed largely similar phenotypes between PlgT/T mice and wild-type mice. Protein S-K196E mutation (Pros1E/E) is a race-specific genetic risk factor for venous thromboembolism. Coexistence in mice of PlgT/T and Pros1E/E did not affect pulmonary embolism symptoms, compared with those in Pros1E/E mice. Hence, the present study showed that the Plg-A622T mutation, which confers ~8% plasmin activity, does not increase the risk of thrombotic diseases in mice under experimental thrombotic conditions and does not modify the thrombotic phenotype observed in Pros1E/E mice. PlgT/T mice can be used to investigate the potential pathophysiological impact of the Plg-A620T mutation.

miRNAs that associate with conjunctival inflammation and ocular Chlamydia trachomatis infection do not predict progressive disease.

We previously showed that conjunctival miR-147b and miR-1285 were upregulated in Gambian adults with inflammatory scarring trachoma, and miR-155 and miR-184 expression was strongly associated with conjunctival inflammation and ocular Chlamydia trachomatis infection in children from Guinea-Bissau. We investigated whether the single or combined expression of miR-147b, miR-1285, miR-155 and miR-184 was able to identify individuals with increased risk of incident or progressive scarring trachoma. Conjunctival swab samples were collected from 506 children between the ages of 4 and 12 living in northern Tanzania. These 506 samples formed the baseline sample set of a 4-year longitudinal study. Chlamydia trachomatis infection was diagnosed by droplet digital PCR and expression of miR-155, miR-184, miR-1285 and miR-147b was tested by qPCR. Individuals were assessed for incidence and progression of conjunctival scarring by comparison of conjunctival photographs taken at baseline and 4 years later. miR-184 and miR-155 were strongly associated with inflammation and infection at baseline; however, no miR was associated with 4-year scarring incidence or progression. miR-184 expression was more strongly downregulated during inflammation in non-progressors relative to progressors, suggesting that a disequilibrium in the efficiency of wound healing is a significant determinant of progressive conjunctival fibrosis.

Ocular Manifestations of Inherited Phospholipase-Cγ2-Associated Antibody Deficiency and Immune Dysregulation.

PURPOSE: To report the ocular manifestations of phospholipase-Cγ2-associated antibody deficiency and immune dysregulation (PLAID). METHODS: Case report and literature review. RESULTS: A 21-year-old woman diagnosed with PLAID was referred for evaluation of repeated episodes of ocular inflammation resulting in bilateral peripheral corneal pannus with episcleritis and corneal scarring accompanied by systemic manifestations including epidermolysis bullosa and interstitial lung disease. Systemic immunosuppression with corticosteroids and interleukin-1 (IL-1) receptor antagonist (anakinra) was supplemented with topical anakinra to avoid systemic side effects, which resulted in partial improvement of the ocular symptoms. Oral prednisone was restarted to treat active lesions during bouts of inflammation. CONCLUSIONS: Ocular PLAID is a bilateral chronic or recurrent inflammatory disease of the ocular surface leading to severe and early cicatricial ocular surface and corneal involvement because of high IL-1 production. Management of PLAID may require both topical and systemic immunomodulatory treatments, potentially including targeted local anti-IL-1 therapy.