The enigma of sclera-specific autoimmunity in scleritis.

Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value.

Differences in presentation between paediatric- and adult-onset primary Sjögren's syndrome patients.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a rare disease in paediatric patients. Presenting symptoms differ from those in adult patients. The aim of this study was to evaluate presenting symptoms, classification criteria and clinical assessments, including salivary gland ultrasonography (SGUS), at disease onset in paediatric and adult patients with pSS. METHODS: Data of 23 paediatric- and 33 adult-onset patients with pSS were obtained from our standardised multidisciplinary REpSULT and RESULT cohorts, respectively. Clinical, patient-reported, serological, functional, biopsy and SGUS parameters were compared. RESULTS: In paediatric-onset pSS (pedSS) patients, recurrent parotid gland swelling (91% vs. 49%, p<0.001) and fever (30% vs. 3%, p=0.006) were more often present than in adult-onset patients. In contrast, sicca symptoms of mouth (52% vs. 79%, p=0.046) and eyes (26% vs. 73%, p<0.001) were less common in pedSS patients. In paediatric patients, the entry criteria of the ACR/EULAR classification were most often met due to activity in the glandular domain of the ESSDAI. When applying the ACR/EULAR classification criteria, only 78% of pedSS fulfilled these criteria compared to 100% of adult patients. Abnormal glandular function tests had a greater contribution to fulfilling the criteria in adults, while the biopsy had a greater contribution in paediatric patients. Anti-SSA/Ro serology had similar contribution for both cohorts. SGUS Hocevar score was significantly higher in paediatric compared to adult patients (median 25 vs. 18, p=0.004). CONCLUSION: PedSS has a different presentation than adult-onset pSS. Recurrent parotid gland swelling in paediatric patients should alert clinicians to the potential presence of pSS.

PREDICTIVE VALUE OF OPTICAL COHERENCE TOMOGRAPHIC FEATURES IN THE BEVACIZUMAB AND RANIBIZUMAB IN PATIENTS WITH DIABETIC MACULAR EDEMA (BRDME) STUDY.

PURPOSE: To establish the predictive value of specific optical coherence tomography retinal features on visual outcomes and retinal thickness during anti-vascular endothelial growth factor treatment in patients with diabetic macular edema. METHODS: Post hoc analysis of compound data of a prospective, 6-month, multicenter, randomized controlled trial of 119 patients with diabetic macular edema receiving either intravitreal bevacizumab or ranibizumab were analyzed to assess the associations between baseline retinal morphologic parameters and change in best-corrected visual acuity and central subfield thickness. Based on the study protocol of the core study, best-corrected visual acuity and central subfield thickness were obtained before each mandatory monthly injection during 6 months. RESULTS: The presence of serous retinal detachment at baseline was associated with significant improvement in best-corrected visual acuity letter score at Month 3 and Month 6 (P < 0.001 and P = 0.01, respectively). In addition, the presence of disorganization of retinal inner layers was associated with lower best-corrected visual acuity letter score at Month 3 and Month 6 (P < 0.05 and P = 0.01, respectively). CONCLUSION: This study found that serous retinal detachment and disorganization of retinal inner layers were associated with different treatment responses to anti-vascular endothelial growth factor therapy in patients with diabetic macular edema.

FACTORS ASSOCIATED WITH PENTOSIDINE ACCUMULATION IN THE HUMAN VITREOUS.

PURPOSE: To explore factors associated with pentosidine accumulation in the human vitreous. METHODS: Vitreous samples were obtained during trans pars plana vitrectomy for macular hole or rhegmatogenous retinal detachment. Patient characteristics included age, gender, and diabetes mellitus. Ocular characteristics included pseudophakia, posterior vitreous detachment, and presence of intraocular fibrosis (epiretinal membrane, proliferative vitreoretinopathy, or both). Pentosidine concentration as a measure of accumulation of advanced glycation end products was determined by high performance liquid chromatography. RESULTS: Pentosidine concentrations were measured in 222 vitrectomy samples (118 female and 104 male patients [median age 66 years], treated for macular hole [n = 105] or rhegmatogenous retinal detachment [n = 117]). Pentosidine was found to accumulate significantly with age (P < 0.001). After correction for age, a multivariable linear regression model revealed significantly higher pentosidine values in eyes with intraocular fibrosis (P = 0.001), in phakic as compared with pseudophakic eyes (P = 0.02), and in the absence of a complete posterior vitreous detachment (P = 0.018). The authors found no association with diabetes mellitus or gender. CONCLUSION: This study confirmed an age-related pentosidine accumulation in the vitreous and found new factors relating to pentosidine levels. Findings support the hypothesis of enzyme-induced vitreous liquefaction and the hypothesis of pentosidine as a pro-fibrotic factor.

Idiopathic epiretinal membrane.

BACKGROUND: Idiopathic epiretinal membrane (iERM) is a fibrocellular membrane that proliferates on the inner surface of the retina at the macular area. Membrane contraction is an important sight-threatening event and is due to fibrotic remodeling. METHODS: Analysis of the current literature regarding the epidemiology, clinical features, and pathogenesis of iERM and fibrotic tissue contraction. RESULTS: Epidemiologic studies report a relationship between iERM prevalence, increasing age, and posterior vitreous detachment. Clinically, iERM progresses through different stages characterized by an increased thickness and wrinkling of the membrane. Pathophysiologically, iERM formation is a fibrotic process in which myofibroblast formation and the deposition of newly formed collagens play key roles. Anomalous posterior vitreous detachment may be a key event initiating the formation of iERM. The age-related accumulation of advanced glycation end products may contribute to anomalous posterior vitreous detachment formation and may also influence the mechanical properties of the iERM. CONCLUSION: Remodeling of the extracellular matrix at the vitreoretinal interface by aging and fibrotic changes, plays a significant role in the pathogenesis of iERM. A better understanding of molecular mechanisms underlying this process may eventually lead to the development of effective and nonsurgical approaches to treat and prevent vitreoretinal fibrotic diseases.

Glial cells and collagens in epiretinal membranes associated with idiopathic macular holes.

PURPOSE: To investigate the identity of collagens and cellular components in the epiretinal membrane (ERM) associated with full-thickness idiopathic macular hole and their clinical relevance. METHODS: Pars plana vitrectomy with the peeling of internal limiting membrane and ERM was performed by 2 surgeons in 40 eyes with idiopathic macular holes. The clinical data were reviewed and the surgical specimens were processed for flat-mount and immunohistochemical analysis. RESULTS: Epiretinal membrane is a GFAP-positive gliotic and fibrotic scar which contains newly formed Type I, III, and V collagens. Type VI collagen was not observed. Colocalization studies found cells coexpressing GFAP/CRALBP, GFAP/α-SMA, and α-SMA/CRALBP, which are consistent with transdifferentiation of Müller cells into fibroblasts and myofibroblasts. The clinically significant ERMs can be divided into two groups according to the amount of cells in ERM: sparse cellular proliferation and dense cellular proliferation. The latter group is associated with a higher chance of surgical difficulty during internal limiting membrane peeling (P = 0.006). Preoperative and postoperative visual function were not affected by the density of the cellular proliferation. CONCLUSION: Retinal glial cells, probably transdifferentiated Müller cells, are involved in the formation of full-thickness macular hole-associated ERMs by a gliotic and fibrotic process. Such ERMs contain newly formed Type I, III, and V collagen depositions. The cell density of ERM affects its biomechanical properties and determines the difficulty of ERM peeling.

The incidence of rhegmatogenous retinal detachment in The Netherlands.

OBJECTIVE: To estimate the incidence and characteristics of rhegmatogenous retinal detachment (RRD) in The Netherlands in 2009. DESIGN: Retrospective, observational case series. PARTICIPANTS: All patients with RRD in the Dutch population in 2009. METHODS: By reviewing surgical logs, cases of primary RRD repair in 2009 were identified. Exclusion criteria included RRD before 2009 and exudative, tractional, or traumatic retinal detachments. Patient demographics, date of surgery, and lens status were documented. Incidence of RRD and 95% confidence intervals (CIs) were calculated based on the Poisson distribution. Age distribution, male-to-female ratio, and proportion of RRD patients with prior cataract extraction (CE) were determined. A Student t test was used to examine differences in the incidence of RRD between groups. MAIN OUTCOME MEASURES: Annual RRD incidence in the population and per gender-adjusted age category and proportion of RRD patients with prior CE. RESULTS: The annual RRD incidence was 18.2 per 100 000 people (95% CI, 11.4-18.8), with a peak incidence of 52.5 per 100 000 people (95% CI, 29.4-56.8) between 55 and 59 years of age. The Bilateral RRD rate was 1.67%. Macula-off presentation occurred in 54.5% of all RRD patients. Prior CE was noted in 33.5% of RRD eyes. The male-to-female ratio was 1.3:1, and RRD incidence was statistically significantly more frequent in males (P<0.0001). CONCLUSIONS: Rhegmatogenous retinal detachment is predominantly a disease of the population older than 50 years, and males are more susceptible to RRD. The annual RRD incidence is highly dependent on demographic characteristics.

Visual outcome, treatment results, and prognostic factors in patients with scleritis.

PURPOSE: To analyze the visual outcome, systemic associations, effectiveness of treatment, and predicting features of 104 scleritis patients. DESIGN: Retrospective case series. PARTICIPANTS: One hundred four patients treated for scleritis at the University Medical Centers of Groningen and Utrecht, The Netherlands. METHODS: The clinical records of 104 patients diagnosed with scleritis between 1992 and 2011 at the University Medical Centers of Groningen (n = 64) and of Utrecht (n = 40) were analyzed retrospectively. MAIN OUTCOME MEASURES: Loss of visual acuity, ocular complications, related systemic disease, type of treatment, time to treatment success, and predictive features. RESULTS: Mean age ± standard deviation (SD) was 51.5 ± 13.6 years, and 63 (60.6 %) patients were female. Mean follow-up ± SD was 38.2 ± 33.8 months. A loss of more than 2 lines of Snellen acuity was observed in 23 patients, 3 of whom had a final visual acuity of no light perception. In general, patients with necrotizing scleritis (n = 15) had a poorer outcome. Ocular complications were observed in 88 (84.6%) patients. Underlying systemic disease was identified in 34 (32.7%) patients. Steroid-sparing immunosuppressive medication was used in 47 patients, 36 of whom were treated with methotrexate (MTX). This treatment was successful in 17 (47.2%) patients over the course of a mean ± SD of 103.7 ± 83.7 weeks. Mycophenolate mofetil was the treatment in 10 patients, and in 5 of these patients, treatment success was achieved in a mean ± SD of 65.3 ± 37.4 weeks. Treatment with tumor necrosis factor α (TNF-α) antagonists led to treatment success in a mean ± SD of 32.6 ± 21.8 weeks in 5 of the 11 treated patients. Patients with loss of visual acuity or those treated with steroid-sparing immunosuppressive drugs more often had an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation. CONCLUSIONS: Scleritis is a severe ocular inflammatory disease often associated with ocular complications. In this population, roughly half of the patients were treated with systemic immunosuppressive medication. Mycophenolate mofetil and TNF-α antagonists can be used in case of MTX failure. Tumor necrosis factor α antagonists seemed to be more effective than MTX. Within this group, an underlying associated disease, bilateral scleritis, and a longer duration of symptoms at presentation were predictive features for a more severe disease course.

Literature-related discovery techniques applied to ocular disease: a vitreous restoration example.

PURPOSE OF REVIEW: Literature-related discovery and innovation (LRDI) is a text mining approach for bridging unconnected disciplines to hypothesize radical discovery. Application to medical problems involves identifying key disease symptoms, and identifying causes and treatments for those symptoms from throughout the biomedical literature. LRDI has not been applied to vitreoretinal ophthalmological problems previously. This review illustrates the use of LRDI for potential restoration of degenerated vitreous. RECENT FINDINGS: Vitreous restoration literature is very small; much research is aimed at vitreous composition and degradation, improving vitrectomy, and pharmacological vitreolysis. LRDI has the potential to find ways to slow, halt, or reverse the degradation through systemic improvement and myriad local treatments, some not ordinarily used by the ophthalmology community. SUMMARY: The many potential discoveries and innovations were generated within a larger context, namely that timely healing required cause removal, healing obstacle removal, and healing acceleration (focused treatments) in an integrated manner. Although many potential causes, healing obstacles, and healing accelerations were identified strictly from the premier published literature, causes and obstacles that may have been operable but were not found in the literature were also postulated, as were gaps in the research that covered these potential causes and obstacles and unresearched treatments as well.

Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis.

PURPOSE: To identify factors associated with glaucoma surgery in pediatric uveitis. METHODS: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. RESULTS: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP > 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. CONCLUSION: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.

The genetics and disease mechanisms of rhegmatogenous retinal detachment.

Rhegmatogenous retinal detachment (RRD) is a sight threatening condition that warrants immediate surgical intervention. To date, 29 genes have been associated with monogenic disorders involving RRD. In addition, RRD can occur as a multifactorial disease through a combined effect of multiple genetic variants and non-genetic risk factors. In this review, we provide a comprehensive overview of the spectrum of hereditary disorders involving RRD. We discuss genotype-phenotype correlations of these monogenic disorders, and describe genetic variants associated with RRD through multifactorial inheritance. Furthermore, we evaluate our current understanding of the molecular disease mechanisms of RRD-associated genetic variants on collagen proteins, proteoglycan versican, and the TGF-ß pathway. Finally, we review the role of genetics in patient management and prevention of RRD. We provide recommendations for genetic testing and prophylaxis of at-risk patients, and hypothesize on novel therapeutic approaches beyond surgical intervention.

Goniotomy for Non-Infectious Uveitic Glaucoma in Children.

Secondary glaucoma is still a blinding complication in childhood uveitis, for which most commonly used surgical interventions (trabeculectomy or glaucoma drainage implant) involve multiple re-interventions and/or complications postoperatively. The goniotomy procedure has never been investigated in the current era, in which patients with pediatric uveitis receive biologics as immunosuppressive therapy for a prolonged period, with potential implications for the outcome. The purpose of the study is to evaluate the efficacy and safety of a goniotomy procedure in pediatric non-infectious uveitis in a retrospective, multicenter case series. The primary outcomes were the postoperative intraocular pressure (IOP), number of IOP-lowering medications, and success rate. Postoperative success was defined as 6 ≤ IOP ≤ 21 mmHg, without major complications or re-interventions. Fifteen eyes of ten children were included. Median age of the included patients at goniotomy was 7 years; median follow-up was 59 months. Median (interquartile range) IOP before surgery was 30 (26-34) mmHg with 4 (3-4) IOP-lowering medications. At 1, 2, and 5 years after goniotomy, median IOP was 15, 14, and 15 mmHg with 2 (0-2), 1 (0-2), and 0 (0-2) medications, respectively (p < 0.001 postoperatively versus preoperatively for all timepoints). Success rate was 100%, 93%, and 80% after 1, 2, and 5 years, respectively. There were no significant changes in visual acuity and uveitis activity or its treatment, and there were no major complications. Our results show that the goniotomy is an effective and safe surgery for children with uveitic glaucoma.

Association of Risk Variants in the CFH Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis.

Importance: Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients. Objective: To identify the genes and pathways associated with idiopathic MFC. Design, Setting, and Participants: This was a case-control genome-wide association study (GWAS) and protein study of blood plasma samples conducted from March 2006 to February 2022. This was a multicenter study involving 6 Dutch universities. Participants were grouped into 2 cohorts: cohort 1 consisted of Dutch patients with idiopathic MFC and controls, and cohort 2 consisted of patients with MFC and controls. Plasma samples from patients with idiopathic MFC who had not received treatment were subjected to targeted proteomics. Idiopathic MFC was diagnosed according to the Standardization of Uveitis Nomenclature (SUN) Working Group guidelines for punctate inner choroidopathy and multifocal choroiditis with panuveitis. Data were analyzed from July 2021 to October 2022. Main outcomes and measures: Genetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients. Results: This study included a total of 4437 participants in cohort 1 (170 [3.8%] Dutch patients with idiopathic MFC and 4267 [96.2%] controls; mean [SD] age, 55 [18] years; 2443 female [55%]) and 1344 participants in cohort 2 (52 [3.9%] patients with MFC and 1292 [96.1%] controls; 737 male [55%]). The primary GWAS association mapped to the CFH gene with genome-wide significance (lead variant the A allele of rs7535263; odds ratio [OR], 0.52; 95% CI, 0.41-0.64; P = 9.3 × 10-9). There was no genome-wide significant association with classical human leukocyte antigen (HLA) alleles (lead classical allele, HLA-A*31:01; P = .002). The association with rs7535263 showed consistent direction of effect in an independent cohort of 52 cases and 1292 control samples (combined meta-analysis OR, 0.58; 95% CI, 0.38-0.77; P = 3.0 × 10-8). In proteomic analysis of 87 patients, the risk allele G of rs7535263 in the CFH gene was strongly associated with increased plasma concentrations of factor H-related (FHR) proteins (eg, FHR-2, likelihood ratio test, adjusted P = 1.1 × 10-3) and proteins involved in platelet activation and the complement cascade. Conclusions and relevance: Results suggest that CFH gene variants increase systemic concentrations of key factors of the complement and coagulation cascades, thereby conferring susceptibility to idiopathic MFC. These findings suggest that the complement and coagulation pathways may be key targets for the treatment of idiopathic MFC.

Hyperreflective Dots on OCT as a Predictor of Treatment Outcome in Diabetic Macular Edema: A Systematic Review.

TOPIC: This review aims to evaluate the role of hyperreflective dots (HRDs), detected using OCT, as a predictor of the treatment outcome in patients with diabetic macular edema (DME). CLINICAL RELEVANCE: The treatment of DME is possible, but its results are often unsatisfactory. Thus, it is important to develop biomarkers that can help to predict the treatment response to optimize the treatment's effect for individual patients. METHODS: PubMed, Embase, Web of science, and Cochrane library were searched (final search date on May 5, 2021). Participants were patients diagnosed with DME and provided with treatment. The predictor was HRDs, detected using OCT, before treatment. The outcomes were best-corrected visual acuity (BCVA) and central macular thickness (CMT), detected using OCT, after treatment. Two reviewers independently screened the titles and abstracts as well as full text. The refined Quality in Prognosis Studies tool was used to assess the risk of bias for each included study. Because of the clinical heterogeneity of the studies, a meta-analysis was not performed. RESULTS: Thirty-six studies were included. The Quality in Prognosis Studies assessment showed that most studies had a low or moderate risk of bias in 6 domains. Six studies could not find any correlation between baseline HRDs (either the presence or absence of HRDs [n = 1] or baseline HRD number [n = 5]) and outcome (BCVA or CMT), whereas 12 studies found a significant correlation between these variables. Eight studies reported that baseline HRDs could predict a poor visual outcome (n = 4 on prescence or abscence of HRD and n = 4 on HRD number), and 4 studies (n = 1 on prescence or abscence of HRD and n = 3 on HRD number) found that HRDs were predictive of visual improvement. Fifteen out of 17 studies found that the HRD number decreased after treatment. CONCLUSION: Based on the current literature, the HRD numbers decrease with treatment, but it is not clear whether HRDs predict the treatment outcome in patients with DME. Future investigations with more uniform approaches are needed to confirm the nature of this biomarker and its effect on DME treatment outcome.

Uveitic glaucoma in children: a systematic review on surgical outcomes.

PURPOSE: To compare the outcomes and complications of different surgical interventions for secondary glaucoma in pediatric uveitis. METHODS: Systematic review following the PRISMA standards. Main inclusion criteria were surgery for secondary glaucoma in pediatric uveitis at a mean age of 16 years or below, a mean follow-up period of at least 1 year after surgery, and at least 10 eyes per surgical intervention per study. We used the GRADE approach to assess study quality. Primary outcomes were intraocular pressure (IOP) and number of IOP lowering medications before and after surgery. Secondary outcomes were success rate and complications. RESULTS: Fourteen studies fulfilled the inclusion criteria, in which one (n = 11) or more (n = 3) surgical interventions were described, comprising in total six different procedures. According to the GRADE criteria, the quality of the studies was low to very low, in particular because of the small size and the applied study designs. All surgical interventions provided a significant decrease in IOP and number of IOP lowering medications. The success rates during follow-up varied widely, with the lowest rates of success after cyclophotocoagulation. The most frequently reported complications were ocular hypertension, hypotony, and hyphema, with an indication for a reoperation in more than one-third of the cases. Permanent vision loss was infrequently seen and was attributed to prolonged hypotony. CONCLUSIONS: The described surgical interventions are able to prevent blindness by lowering a medically uncontrolled IOP to an acceptable level. Therefore, there is a crucial role for surgical intervention in these children. Based on the present studies, no preferences can be made. Given the reported complications, more research with larger sample sizes and direct comparisons is needed to determine the most successful glaucoma treatment in children with uveitis.

Physical and Psychosocial Health in Pediatric Uveitis Patients.

BACKGROUND: To investigate the possible associations between childhood noninfectious uveitis and cardio-respiratory fitness, physical activity, health related quality of life and fatigue. METHODS: Cross-sectional analysis of 23 patients with noninfectious uveitis, aged 8-18 years. BMI, exercise capacity, muscle strength and physical activity were measured. Health-related quality of life and fatigue were assessed. The results were compared to standardized values for age matched healthy children. RESULTS: Twenty-three patients were included. Children with uveitis had a higher bodyweight and body mass index. Children with uveitis had lower cardio-respiratory fitness and they were less physically active, but they experienced a normal quality of life and normal fatigue. Parents of children with uveitis reported a lower quality of life and more fatigue for their children than parents of healthy children. CONCLUSION: Our study indicates that children with noninfectious uveitis are at risk of developing lower physical and psychosocial health.

Long-term abatacept treatment for 48 weeks in patients with primary Sjögren's syndrome: The open-label extension phase of the ASAP-III trial.

OBJECTIVE: To investigate treatment efficacy of long-term abatacept treatment in pSS patients. METHODS: The single-centre ASAP-III trial consisted of two phases: the randomised, double-blind, placebo-controlled phase (1:1 randomisation) from baseline to week 24, of which results have been published previously, and the open-label extension phase from week 24 to 48, in which all patients received abatacept. Main inclusion criteria were fulfilment of the AECG criteria, positive gland biopsy, disease duration ≤ 7 years and ESSDAI ≥ 5. Long-term treatment effects of abatacept on clinical, patient-reported, glandular and laboratory outcome measures were assessed in patients treated with abatacept from baseline to week 48. Furthermore, Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS) response (response on ≥3 of 5 items) was analysed. RESULTS: In patients on abatacept treatment for 48 weeks (n = 40), median ESSDAI improved from baseline 14.0 (IQR 9.0-16.8) to 4.0 (2.0-8.0) at week 48 (p < 0.001), with 50% of patients reaching low disease activity (ESSDAI < 5) at week 48. Median ESSPRI improved from 7.0 (IQR 5.4-7.7) to 5.0 (3.7-6.7) (p < 0.001). Significant improvement was also seen in dry eye and laboratory tests. Combining response at multiple clinically relevant items, 73% of patients were CRESS responders at week 48. Additional improvement was seen between week 24 and week 48 of abatacept treatment. CONCLUSION: In the open-label extension phase of the ASAP-III trial, improvement was seen up to 48 weeks of abatacept treatment in clinical, patient-reported, dry eye and laboratory outcomes. The majority of patients were CRESS responders at week 48.

Efficacy of low-dose methotrexate treatment in birdshot chorioretinopathy.

PURPOSE: To ascertain the effect of treatment with methotrexate (MTX) on the visual prognosis of birdshot chorioretinopathy (BSCR). METHODS: Retrospective case series of 76 consecutive patients with HLA-A29-positive BSCR, of whom 46 were followed for at least 5 years and 18 for longer than 10 years. A review of the medical records of 76 patients with BSCR. Treatment regimens were subdivided into the following groups: 1) No systemic immunomodulatory treatment; 2) Treatment with systemic corticosteroids; and 3) Treatments which comprised MTX. First, we calculated eye-years for the different therapeutic regimens and second, we subdivided the patients according to their initial treatment regimen and assessed visual outcomes. RESULTS: Mean visual acuity increased over time in the MTX-treated patients; remained unchanged in patients on systemic corticosteroids and decreased in the patients without systemic treatment (yearly change in LogMar -0.020, -0.034 and 0.028 with P = 0.034, P = 0.71 and P = 0.006 respectively). In the group treated initially with MTX, VA gradually increased in contrast to the remaining groups of patients (P = 0.003). CONCLUSION: In this series, treatment comprising MTX showed better visual outcomes than the untreated patients and corticosteroid-based treatment regimens.

Association of Rhegmatogenous Retinal Detachment Incidence With Myopia Prevalence in the Netherlands.

Importance: The incidence of rhegmatogenous retinal detachment (RRD) is partly determined by its risk factors, such as age, sex, cataract surgery, and myopia. Changes in the prevalence of these risk factors could change RRD incidence in the population. Objective: To determine whether the incidence of RRD in the Netherlands has changed over recent years and whether this change is associated with an altered prevalence of RRD risk factors. Design, Setting, and Participants: This cohort study included data from all 14 vitreoretinal clinics in the Netherlands, as well as a large Dutch population-based cohort study. All patients who underwent surgical repair for a primary RRD in the Netherlands from January 1 to December 31, 2009, and January 1 to December 31, 2016, were analyzed, in addition to all participants in the population-based Rotterdam Study who were examined during these years. Analysis began February 2018 and ended November 2019. Exposures: RRD risk factors, including age, male sex, cataract extraction, and myopia. Main Outcomes and Measures: Age-specific RRD incidence rate in the Dutch population, as well as change in RRD incidence and risk factor prevalence between 2009 and 2016. Results: In 2016, 4447 persons (median [range] age, 61 [3-96] years) underwent surgery for a primary RRD within the Netherlands, resulting in an RRD incidence rate of 26.2 per 100 000 person-years (95% CI, 25.4-27.0). The overall RRD incidence rate had increased by 44% compared with similar data from 2009. The increase was observed in both phakic (1994 in 2009 to 2778 in 2016 [increase, 39%]) and pseudophakic eyes (1004 in 2009 to 1666 in 2016 [increase, 66%]), suggesting that cataract extraction could not solely account for the overall rise. Over the same period, the prevalence of mild, moderate, and severe myopia among persons aged 55 to 75 years had increased by 15.6% (881 of 4561 [19.3%] vs 826 of 3698 [22.3%]), 20.3% (440 of 4561 [9.6%] vs 429 of 3698 [11.6%]), and 26.9% (104 of 4561 [2.3%] vs 107 of 3698 [2.9%]), respectively, within the population-based Rotterdam Study. Conclusions and Relevance: In this study, an increase was observed in primary RRD incidence in the Netherlands over a 7-year period, which could not be explained by a different age distribution or cataract surgical rate. A simultaneous myopic shift in the Dutch population may be associated, warranting further population-based studies on RRD incidence and myopia prevalence.

Clinical Phenotyping of Primary Sjögren Syndrome Patients Using Salivary Gland Ultrasonography: Data From the RESULT Cohort.

OBJECTIVE: To investigate salivary gland ultrasound (SGUS) abnormalities in relation to clinical phenotype and patient characteristics, disease activity, and disease damage in patients with primary Sjögren syndrome (pSS). METHODS: Consecutive outpatients included in our REgistry of Sjögren Syndrome LongiTudinal (RESULT) cohort were selected. Patients with pSS who were included were classified according to the American College of Rheumatology/European League Against Rheumatism (EULAR) criteria and underwent full ultrasonographic examination (Hocevar score 0-48) at baseline. Total SGUS scores of ≥ 15 were considered positive. Patient characteristics, disease activity, and disease damage were compared between the different SGUS groups. RESULTS: In total, 172 of 186 patients with pSS were eligible, of whom 136 (79%) were SGUS positive. Compared with patients who were SGUS negative, SGUS-positive patients had significantly longer disease duration, higher EULAR Sjögren Syndrome Disease Activity Index, higher Sjögren Syndrome Disease Damage Index, and were more likely to have a positive parotid gland biopsy, anti-SSA/SSB antibodies, and abnormal unstimulated whole saliva (UWS) and ocular staining score (OSS), and higher levels of IgG and rheumatoid factor. Regarding patient-reported outcome measurements (PROM), patients who were SGUS positive scored significantly lower on the EULAR Sjögren Syndrome Patient-Reported Index for fatigue and pain, and more often found their disease state acceptable compared with patients who were SGUS negative. SGUS total score showed significant associations with various clinical and serological variables, and with PROM. Highest associations were found for UWS (ρ = -0.551) and OSS (ρ = 0.532). CONCLUSION: Patients who were SGUS positive show a distinct clinical phenotype in all aspects of the disease compared with patients who were SGUS negative: clinical, functional, serological, and PROM. SGUS could be a helpful tool in selecting patients for clinical trials and estimating treatment need.