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Objectives Salivary gland lymphocytic infiltrates are a hallmark of primary SS (pSS), but traditional biopsy techniques hold several disadvantages. Ultrasound-guided core needle (US-guided CN) parotid gland biopsy is minimally invasive and reliable for diagnosis of lymphoma in pSS. This proof-of-concept study aimed to explore this technique in the diagnostic work-up of pSS and is the first to address its value in a consecutive cohort independently of the presence of salivary gland swelling. Methods Combined incisional and US-guided CN parotid biopsy was performed in 20 patients with suspected or confirmed pSS from the Belgian Sjögren’s Syndrome Transition Trial (BeSSTT). Surface area and presence of a focus score (FS) of at least one, germinal centres and lymphoepithelial lesions were recorded. Results Salivary gland tissue was interpretable in 19 patients. Fourteen patients had ≥4 mm2 salivary gland tissue by both techniques, in four US-guided CN biopsies salivary gland tissue was Conclusions US-guided CN biopsy of the parotid gland is at least equivalent to incisional biopsy of the parotid gland in the diagnostic work-up of pSS.

Background Traboulsi syndrome is a very rare, syndromic form of ectopia lentis that is potentially sight-threatening at a young age. It is characterized by typical facial, skeletal and ocular signs. Materials and methods Two siblings, born to consanguineous parents, with a clinical phenotype consistent with Traboulsi syndrome, underwent extensive ophthalmic imaging and exome-based genetic testing. Both were treated with unilateral clear lens extraction via a limbal approach. Results Two siblings, one male and one female, presented with systemic and ocular features consistent with Traboulsi syndrome. Lens subluxation was present in all 4fouraffected eyes, and spontaneous subconjunctival bleb formation was detected in one eye. This eye also showed evidence of keratoconus-related corneal thinning. The clinical diagnosis of Traboulsi syndrome was confirmed molecularly. A homozygous, novel, pathogenic nonsense variant was identified in exon 25 of the ASPH gene: c.2181_2183dup, p.(Val727_Trp728insTer). Excellent visual outcomes following clear lens extraction and postoperative rigid gas-permeable contact lens fitting were obtained. Conclusions We expanded the genetic spectrum of Traboulsi syndrome with a novel frameshift variant in the ASPH gene. We showed that lensectomy followed by gas-permeable contact lenses is an efficient therapeutic approach to treat lens subluxation in Traboulsi syndrome. However, lifelong follow-up is crucial to avoid (late) postoperative complications.

Background: Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant retinal dystrophy related to C1QTNF5 gene variants.Materials and methods: Twenty-six patients (21–81 years) with L-O...

Autoantibody detection is an essential step in pSS diagnosis. However, the value of separate anti-Ro52, anti-Ro60 and anti-SSB/La detection in pSS diagnosis and phenotyping has not been extensively studied. This study aimed to explore disease characteristics of anti-SSA/Ro positive, suspected and definite pSS patients, in relation to serological profiles based on anti-Ro52, anti-Ro60 and anti-SSB/La reactivity.Of 187 anti-SSA/Ro positive patients included in the Belgian Sjögren's Syndrome Transition Trial (BeSSTT), 155 were considered definite pSS patients, due to fulfilment of the 2016 ACR-EULAR classification criteria, and 32 suspected, due to reactivity against SSA/Ro without presence of other criteria. None of the patients met any of the ACR-EULAR exclusion criteria for pSS. Patients were grouped based on the presence of anti-Ro52, anti-Ro60 and anti-SSB/La antibodies.Mono-reactivity against Ro60 or Ro52, double reactivity against Ro52/Ro60 and triple reactivity against Ro52/Ro60 and SSB was detected in respectively 30, 23, 70 and 60 patients. Mono-anti-Ro60 positive patients showed the least pSS features. Mono-anti-Ro52 positive patients reported a significantly higher dryness burden (p=0.016) and tended toward more salivary gland ultrasound (SGUS) abnormalities (p=0.054) than mono-anti-Ro60 positives. Double positive patients showed similar characteristics as mono-anti-Ro52 positive patients, whereas triple positive patients showed lowest unstimulated salivary flow rates (p=0.002) and Schirmer tests (p=0.002), highest ocular staining scores (p0.001), most positive labial salivary gland biopsies (p=0.039), most laboratory abnormalities compatible with B-cell hyperactivity and highest SGUS scores (p0.001) compared to other patient groups.These data indicate that separate detection of anti-Ro52, anti-Ro60 and anti-SSB/La reactivity is not only relevant towards pSS diagnosis, but markedly aids in patient stratification and evaluation of disease burden. Our results suggest a stepwise model in which mono-reactivity against Ro60 displayed the least objective and subjective glandular pSS features, whereas glandular abnormalities and signs of B-cell hyperactivity were most present in patients showing triple reactivity against Ro60, Ro52 and SSB/La.

Salivary gland ultrasound (SGUS) is emerging as essential tool in primary Sjögren's Syndrome (pSS), but its link to symptom-based endotypes is unknown. Therefore, we explored SGUS outcomes in relation to endotypes in patients with definite and suspected pSS.Definite pSS patients (n = 171) fulfilling the 2016 ACR/EULAR classification criteria, and suspected pSS patients (n = 119), positive for at least one criterion, were included in the Belgian Sjögren's Syndrome Transition Trial (BeSSTT). Stratification into endotypes according to the Newcastle Sjögren's Stratification Tool resulted in low symptom burden (LSB), pain dominant with fatigue (PDF), dryness dominant with fatigue (DDF) and high symptom burden (HSB). SGUS was assessed with Hocevar score (0-48). The dataset was randomly divided into a discovery (n = 203) and replication (n = 87) cohort.SGUS had strong discriminative power for pSS classification (AUC=0.74), especially in DDF (AUC=0.89). In definite pSS, Hocevar scores in DDF were high compared to other endotypes (38 (20-44) versus 18 (9-33); p 0.001). Patients with highest SGUS-scores showed more sicca and laboratory abnormalities. Moreover, a subset of young, anti-SSA/Ro positive patients not fulfilling classification criteria showed clear SGUS abnormalities. Replication showed similar results.SGUS-scores were significantly higher in definite pSS with DDF endotype, providing the first evidence of imaging abnormalities in salivary glands matching distinct biological profiles ascribed to pSS endotypes. Additionally, a subset of patients with potential early disease was detected based on presence of anti-SSA antibodies and high SGUS-scores. These results underscore the role of SGUS as powerful tool both in pSS classification and stratification.

Vitreous opacities, which are collagen aggregates that form in the eye and cause vision impairment (eye floaters), are currently treated with invasive surgical intervention or high-energy laser photoablation. In this paper, the authors show that exposing gold nanoparticles or indocyanine green to low-energy laser pulses generates vapour nanobubbles that can disrupt collagen aggregates in the eyes of rabbit, suggesting a milder strategy for the treatment of eye floaters. In myopia, diabetes and ageing, fibrous vitreous liquefaction and degeneration is associated with the formation of opacities inside the vitreous body that cast shadows on the retina, appearing as 'floaters' to the patient. Vitreous opacities degrade contrast sensitivity function and can cause notable impairment in vision-related quality of life. Here we introduce 'nanobubble ablation' for safe destruction of vitreous opacities. Following intravitreal injection, hyaluronic acid-coated gold nanoparticles and indocyanine green, which is widely used as a dye in vitreoretinal surgery, spontaneously accumulate on collagenous vitreous opacities in the eyes of rabbits. Applying nanosecond laser pulses generates vapour nanobubbles that mechanically destroy the opacities in rabbit eyes and in patient specimens. Nanobubble ablation might offer a safe and efficient treatment to millions of patients suffering from debilitating vitreous opacities and paves the way for a highly safe use of pulsed lasers in the posterior segment of the eye.

Purpose To report the first case of corneal graft rejection presumably associated with pembrolizumab immunotherapy. Methods Case report and literature review. Results An asymptomatic 85-year-old woman with a history of bilateral penetrating keratoplasty presented for a follow-up visit with bilateral diffuse keratic precipitates and subepithelial infiltrates. There were no anterior chamber cells. Bilateral subclinical corneal graft rejection was suspected. Three months previously, pembrolizumab immunotherapy was started for a metastatic urothelial cell tumor. Corneal graft rejection was managed with topical dexamethasone drops, which were tapered slowly. Pembrolizumab treatment was continued with careful ophthalmological follow-up. Unfortunately, recurrence of corneal graft rejection was observed 8 weeks after cessation of topical dexamethasone drops. After consulting the treating oncologist, pembrolizumab treatment was stopped to prevent recurrent corneal graft rejection. Conclusions We report the first case of corneal graft rejection presumably associated with pembrolizumab immunotherapy. Corneal graft rejection may be successfully managed with corticosteroid therapy. However, constant vigilance and follow-up are advised because of the risk of recurrence in case of continued pembrolizumab treatment. Given the subclinical presentation, baseline ophthalmological screening is advised in all corneal graft patients after initiating immune checkpoint inhibitor therapy.

Biologics, like peptides, proteins and nucleic acids, have proven to be promising drugs for the treatment of numerous diseases. However, besides the off label use of the monoclonal antibody bevacizumab for the treatment of corneal neovascularization, to date no other biologics for corneal diseases have reached the market. Indeed, delivering biologics in the eye remains a challenge, especially at the level of the cornea. While it appears to be a rather accessible tissue for the administration of drugs, the cornea in fact presents several anatomical barriers to delivery. In addition, also intracellular delivery barriers need to be overcome to achieve a promising therapeutic outcome with biologics. This review outlines efforts that have been reported to successfully deliver biologics into the cornea. Biochemical and physical methods for achieving delivery of biologics in the cornea are discussed, with a critical view on their efficacy in overcoming corneal barriers.

PURPOSE: Only recently Tintelnotia was described as a new genus in the Phaeosphaeriaceae family of fungi containing two species, T. opuntiae and T. destructans. Until now, T. destructans keratitis was associated with contact lens wear and ocular trauma. We present the first case of T. destructans keratomycosis presenting as a superinfection in herpetic keratitis. OBSERVATIONS: We present a case of a 53-year-old woman who presented with a unilateral keratitis since 3 weeks without history of trauma or contact lens wear, not responding to topical ofloxacin. Polymerase Chain Reaction (PCR) of the corneal ulcer was positive for Herpes Simplex Virus type 1 (HSV-1). Signs and symptoms progressively improved after starting topical and systemic antiviral therapy. Six weeks later however, our patient presented with a new white infiltrate in the previous herpetic epithelial defect. In vivo confocal microscopy showed fungal hyphae and culture from corneal scrapings identified a hyphomycete. Intensive antimycotic therapy could not prevent a corneal perforation 1 week later. Penetrating keratoplasty was performed with intracameral injection of amphotericin B. Culture of the corneal button and PCR and sequence analysis on the fungal isolate confirmed the diagnosis of T. destructans keratomycosis. Six months after penetrating keratoplasty, biomicroscopy showed a clear graft without recurrence of fungal activity. CONCLUSIONS AND IMPORTANCE: T. destructans is an emerging opportunistic pathogen causing severe keratomycosis. Despite intensive antimycotic therapy, rapid progression to corneal perforation can be seen. Early diagnosis using confocal microscopy, fungal culture and PCR can allow prompt initiation of treatment, which should be guided by in vitro susceptibility testing. ispartof: Am J Ophthalmol Case Rep vol:19 pages:100791- ispartof: location:United States status: Published online

Photodynamic and photothermal cell killing at the surface of tissues finds applications in medicine. However, a lack of control over heat dissipation following a treatment with light might damage surrounding tissues. A new strategy to kill cells at the surface of tissues is reported. Polymeric films are designed in which iron oxide nanoparticles are embedded as photosensitizers. Irradiation of the films with pulsed laser light generates water vapor bubbles at the surface of the films. It is found that "bubble-films" can kill cells in close proximity to the films due to mechanical forces which arise when the bubbles collapse. Local irradiation of bubble-films allows for spatial selective single cell killing. As nanosurgery becomes attractive in ophthalmology to remove superficial tumors, bubble-films are applied on the cornea and it is found that irradiation of the bubble-films allows spatial and selective killing of corneal cells. As i) the photosensitizer is embedded in the films, which reduces its uptake by cells and spreading into tissues and ii) the bubble-films can be removed from the tissue after laser treatment, while iii) a low laser fluence is sufficient to generate vapor bubbles, it is foreseen that bubble-films might become promising for safe resection of superficial tumors.

To report a case of unilateral cancer-associated retinopathy (CAR) with clinical, serological and electroretinogram (ERG) normalization after aggressive cancer treatment combined with steroids and rituximab. Work-up included extensive clinical and electrophysiological testing. Also, serological work-up for antiretinal antibodies and oncological screening was organized. A 45-year-old female presented with progressive photopsias, photophobia and relative central scotoma in the right eye since 6 weeks prior. BCVA was 1.0 in both eyes. Biomicroscopy, IOP and fundus exam were unremarkable. Also, colour vision, autofluorescence imaging, OCT and EOG were normal. Visual fields showed decreased central sensitivity in the right eye. ERG showed a unilateral, electronegative combined and ON-bipolar response. A diagnosis of CAR was suspected. After a diagnosis of an adenocarcinoma of the right ovary, radical ovariectomy and hysterectomy were performed, followed by adjuvant chemotherapy. A whole-body PET scan revealed no metastasis. Treatment with rituximab monoclonal antibodies in combination with corticosteroids was initiated. The patient tested positive for serum autoantibodies against TRPM1, a transient receptor potential cation channel expressed in ON-bipolar cells. During treatment, there was progressive improvement in symptoms and the ERG normalized. Serology confirmed complete clearance of autoantibodies. Although rare, unilateral CAR does occur and in cases with high clinical suspicion an oncological work-up is mandatory. Aggressive cancer treatment combined with steroids and rituximab can lead to normalization of the clinical and ERG phenotype, with clearing of antiretinal antibodies.

Purpose: Autosomal dominant retinitis pigmentosa (adRP) is characterized by an extensive genetic heterogeneity, implicating 27 genes, which account for 50 to 70% of cases. Here 86 Belgian probands with possible adRP underwent genetic testing to unravel the molecular basis and to assess the contribution of the genes underlying their condition. Methods: Mutation detection methods evolved over the past ten years, including mutation specific methods (APEX chip analysis), linkage analysis, gene panel analysis (Sanger sequencing, targeted next-generation sequencing or whole exome sequencing), high-resolution copy number screening (customized microarray-based comparative genomic hybridization). Identified variants were classified following American College of Medical Genetics and Genomics (ACMG) recommendations. Results: Molecular genetic screening revealed mutations in 48/86 cases (56%). In total, 17 novel pathogenic mutations were identified: four missense mutations in RHO, five frameshift mutations in RP1, six mutations in genes encoding spliceosome components (SNRNP200, PRPF8, and PRPF31), one frameshift mutation in PRPH2, and one frameshift mutation in TOPORS. The proportion of RHO mutations in our cohort (14%) is higher than reported in a French adRP population (10.3%), but lower than reported elsewhere (16.5±30%). The prevalence of RP1 mutations (10.5%) is comparable to other populations (3.5%-10%). The mutation frequency in genes encoding splicing factors is unexpectedly high (altogether 19.8%), with PRPF31 the second most prevalent mutated gene (10.5%). PRPH2 mutations were found in 4.7% of the Belgian cohort. Two families (2.3%) have the recurrent NR2E3 mutation p.(Gly56Arg). The prevalence of the recurrent PROM1 mutation p.(Arg373Cys) was higher than anticipated (3.5%). Conclusions: Overall, we identified mutations in 48 of 86 Belgian adRP cases (56%), with the highest prevalence in RHO (14%), RP1 (10.5%) and PRPF31 (10.5%). Finally, we expanded the molecular spectrum of PRPH2, PRPF8, RHO, RP1, SNRNP200, and TOPORS-Associated adRP by the identification of 17 novel mutations, SCOPUS: ar.j, info:eu-repo/semantics/published

Dear Editor,Since the outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic, the use of alcohol-based hand sanitizers (ABHS) has increased exponentially as one of the measures to prevent the...