Carsten Heinz

Purpose: Cataract surgery in patients with chronic anterior uveitis may be associated with increased risk for complications and poor outcomes. This study analyses visual outcome, uveitis course and complications after cataract surgery with intraocular lens (IOL) implantation in adolescents and adults with juvenile idiopathic arthritis (JIA)-associated or antinuclear antibodies (ANA)-positive uveitis. Methods: Data before and at 6 weeks, 1 and 2 years after surgery were retrospectively analysed according to Standardization of Uveitis Nomenclature (SUN) standards. Surgery was performed with small incisions, phacoemulsification and IOL implantation. Surgical technique was adapted to pre-existing uveitis-related morphological abnormalities. Predictors of visual outcome and vision-threatening complications at 2-year follow-up (FU) were analysed. Results: 93 surgeries of 83 patients (84% female; mean age 24.8±16.2 years) with JIA-associated (84%) or ANA-positive (16%) anterior uveitis were analysed. Preoperative treatment included topical steroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; 72.0%) or biological (b) DMARDs (65.6%). Besides cataract, uveitis-related complications (eg, fibrotic lens membrane, posterior synechiae and pupil contraction) were present in 95.7% before surgery. Best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) improved from 1.57±1.32 preoperatively to 0.42±0.83 at 2 years (p<0.001). Postoperative complications included posterior synechiae formation (30%), giant-cell deposits (35.7%), posterior capsule opacification (51.9%) and macular oedema (12.7%). Significant preoperative predictors of poor visual outcome included poor BCVA and high laser flare (LF) values, and those of postoperative ocular complications also included poor BCVA and a lack of systemic anti-inflammatory drug use (each, p<0.05). Conclusions: Beneficial outcomes can be achieved following cataract surgery with IOL implantation in adolescents and adults with JIA-associated or ANA-positive anterior uveitis. Important prerequisites include preoperative inactivity, appropriate surgical technique and sustained long-term uveitis inactivity with the use of DMARDs.

Background: Juvenile idiopathic arthritis-associated uveitis (JIAU) frequently follows a chronic and complicated course. Janus kinase inhibitors (JAKi) represent a promising new therapeutic option. Methods: Retrospective monocentric analysis of 20 children with chronic anterior JIAU treated with tofacitinib ( n = 18), baricitinib ( n = 1) or upadacitinib ( n = 1). Outcome measures: uveitis or arthritis inactivity at any time during follow-up, recurrences after achieving inactivity, sparing of medication, occurrence of new ocular complications, resolution of preexisting macular edema. Results: All patients had received methotrexate prior to baseline, and at least two biologics had been ineffective in 18/20 patients. Whilst receiving JAKi medication, uveitis was inactive in eight patients (anterior chamber cell count < 0.5+) at any time during follow-up (mean 9.2 ± 3.3 months), but uveitis relapsed in 6 of them subsequently. In 7 patients, treatment was terminated after ≤ 1 year due to inadequate response of ocular inflammation. During follow-up, new uveitis-related complications occurred in 7 patients (9 eyes), the most frequent were macular edema (8 eyes of 7 patients), and ocular hypertension (5 eyes of 3 patients). Reduction of concomitant systemic medication was possible in 3/14 patients. Any reduction of topical steroids during follow-up was possible in 24/30 eyes, and 23/30 eyes received a lower dose at the last follow-up than they did at baseline. Conclusions: Our data show limited effectiveness of JAKi treatment in patients with chronic DMARD-refractory JIAU. The number of patients in whom uveitis quiescence could be observed was low, as was the possibility for reduction of concomitant medication, and the relapse rate was high. Clinical trial number: Not applicable.

Background/Objectives: Optical coherence tomography (OCT) and OCT angiography (OCT-A) provide detailed measurements of retinal structure and vasculature; however, age-related differences in how these parameters correlate with one another remain poorly understood. We hypothesized that vascular–structural integration in the macula is more pronounced in adults than in children. Our aim was to characterize correlation patterns in pediatric and adult populations to inform the development of age-specific clinical interpretation guidelines. Methods: This prospective cross-sectional observational study enrolled 37 healthy children (age 1–17 years) and 28 healthy adults (age 18–65 years). Eyes with ocular or systemic conditions affecting the retina or prior intraocular surgery were excluded. Standardized OCT and OCT-A acquisition protocols provided structural and vascular measures. Univariable correlation analyses applied a stringent threshold (p < 0.001) to identify robust associations. Significant univariable results were entered into multivariable regression models adjusting for age, gender, intraocular pressure, and axial length. A Group-wise Linkage Proportion quantified the percentage of potential significant correlations among eight predefined anatomical parameter groups. Results: Ninety univariable correlations met p < 0.001. Fourteen correlations were shared across age groups, notably foveal avascular zone metrics and vessel density, showing very large negative correlations (r = −0.70 to −0.87). The pediatric cohort displayed 40 unique correlations, primarily linking optic nerve head flow indices to retinal nerve fiber layer thickness. Adults exhibited 36 unique correlations, dominated by macular vascular–thickness coupling concentrated in the parafoveal region. After multivariable adjustment, 52 of 90 associations remained significant. Adult-specific associations lost significance more frequently (58%) than pediatric-specific associations (43%), whereas correlations shared across both groups showed complete stability (100%). The Group-wise Linkage Proportion indicated pronounced macular vascular–structural coupling in adults (48.4%) versus near absence in children (1.2%). Conclusions: Retinal parameter correlation patterns show fundamental differences between pediatric and adult eyes. While optic nerve head-macular thickness relationships remain consistent across ages, adults exhibit mature, localized integration of macular vascular and structural parameters absent in children. These findings suggest that pediatric and adult OCT/OCT-A measurements may benefit from separate reference standards, although prospective validation is required before clinical implementation.

This in vitro study investigated the adhesion of human human monocytes / macrophages (MΦ) to poly(styrene-block-isobutylene-block-styrene) (SIBS)-based PreserFlo® MicroShunts, as macrophage interactions can significantly influence microimplant success. For this, purified human MΦ were cultured for 35 days on SIBS-based PreserFlo® MicroShunts and compared against control intraocular lens (IOL) materials (PMMA and hydrophilic acrylate). We found significantly higher MΦ adhesion on the PreserFlo® MicroShunts than on PMMA or hydrophilic acrylic IOLs (p < 0.05). These results indicate that the surface properties of the SIBS-based MicroShunt promote greater MΦ adhesion in vitro compared to commercial IOLs under the conditions tested. This differential adhesion could have implications for the long-term performance of the implant, particularly in uveitic eyes. While increased MΦ adhesion is a known component of the foreign body response, further functional analysis of the macrophage secretome and polarization state (M1 vs. M2) is required to confirm whether this leads to clinically significant fibrosis. Furthermore, in vivo studies are required to elucidate the specific impact of these interactions on long-term clinical performance in uveitic eyes.

Purpose: Clinical presentation of anterior uveitis affecting the iris is nearly identical in patients with juvenile idiopathic-associated uveitis (JIAU) and patients with antinuclear antibody-positive anterior uveitis (ANA-U). This study investigates whether the iris transcriptomes of patients with JIAU or ANA-U differ or reflect the clinical homogeneity. Methods: Iris biopsies were obtained from patients with JIAU (n = 31) or ANA-U (n = 9) during trabeculectomy, iridectomy, or complex cataract surgery. Frozen iris tissues were homogenized, the RNA was isolated and analyzed using a bulk RNA sequencing approach. Genes with a Benjamini–Hochberg false discovery rate (FDR) p ≤ 0.05 and a log₂ fold change (FC) of >1 or <−1 were defined as significantly differentially expressed genes (DEGs). Pathway enrichment analysis was subsequently performed to characterize these DEGs. Results: The JIAU group included nine male and 22 female patients (median age 10.2 [IQR 7.2, 13.7] years), while the ANA-U group consisted of one male and eight female patients (median age 10.2 years (IQR [6.1, 11.7]) years). No DEGs were identified when comparing the iris transcriptomes of JIAU and ANA-U directly. Subgroup analyses based on disease activity revealed 35 DEGs in ANA-U, one DEG in JIAU. Inter-group comparisons based on uveitis activity status yielded no DEGs. In the merged JIAU/ANA-U cohort, 28 DEGs were upregulated in the active vs. inactive uveitis. Regarding secondary glaucoma, 12 DEGs were identified in JIAU, and 15 DEGs were identified in the corresponding ANA-U subgroup. Inter-group comparisons based on glaucoma status yielded no DEGs. In the merged JIAU/ANA-U cohort, 20 DEGs were identified between patients with and without glaucoma. Conclusions: Our findings reveal only marginal differences in gene expression patterns in iris tissues from JIAU and ANA-U patients. These results suggest a high degree of similarity in the underlying inflammatory processes of both uveitis subsets.

Purpose: Current pediatric ophthalmology practice relies on adult reference values for optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) interpretation due to limited age-appropriate normative data, potentially leading to diagnostic misclassification. Methods: We conducted a prospective, cross-sectional study comparing OCT and OCT-A parameters between 37 healthy Caucasian children (1–17 years) and 28 adults (19–65 years) using identical Zeiss CIRRUS protocols. Parameters included peripapillary retinal nerve fiber layer (RNFL), macular thickness, ganglion cell-inner plexiform layer (GCIPL), optic nerve head (ONH) perfusion, and macular vascular density. Results: Children exhibited significantly thinner parafoveal macular thickness compared to adults (251.67 ± 21.32 vs. 270.36 ± 17.02 μm; p < 0.001) while RNFL thickness remained comparable. OCT-A demonstrated higher ONH perfusion in children across multiple sectors (p < 0.001). Within the pediatric cohort, younger children (1–9 years) showed higher macular vessel and perfusion density than older children (10–17 years). All pediatric scans achieved excellent image quality with no exclusions. Conclusions: Clinically significant age-related differences in retinal structure and vasculature necessitate pediatric-specific reference ranges. The demonstrated technical feasibility supports routine OCT/OCT-A implementation in pediatric practice with age-appropriate interpretation guidelines.

Purpose: This study sets out to analyze the correlation of ET-1, a vasoactive peptide, along with various cytokines and vascular factors, with clinical parameters and OCT/OCT-A measurements in glaucoma participants. Methods: Eyes of participants with cataract (n = 30) or glaucoma (n = 87) were examined with optical coherence tomography (OCT) and OCT angiography (OCT-A). Aqueous humor (AqH) from the examined eye and plasma were sampled during cataract or glaucoma surgery and analyzed by means of ELISA and Luminex assay to determine their levels of ET-1 and 35 proteins deemed relevant for regulation of the AqH outflow pathway, ocular perfusion (OP), and glucose metabolism. Results: Glaucomatous eyes are characterized by reductions in RNFL thickness and OP, reflected by reduced vessel density. Furthermore, significantly elevated peripheral ET-1 levels were detected in participants with glaucoma. In addition, significantly elevated AqH levels of MMP-2, MMP-3, ET-1, sEMMPRIN, ZAG, sLOX-1, follistatin, cortisol, endostatin, sTIE-2, and PDGF-BB were detected in the glaucomatous eyes, with correlation to reduced VD for APN, C3a, MMP-3, resistin, sTIE-2, and ZAG. Multivariable analysis showed a correlation of AqH APN levels with the reduced VD in glaucomatous eyes. Conclusions: The peripheral ET-1 level and the intraocular levels of APN, C3a, MMP-3, resistin, sTIE-2, and ZAG are associated with impaired OP in glaucoma. Furthermore, elevated intraocular levels of MMP-3, ZAG, and APN were identified as biomarkers for impaired perfusion in glaucoma.

Uveitis diseases are generally rare and therefore often pose a significant challenge in treatment. In developed countries, non-infectious uveitis is one of the most common causes of severe functional impairment and even blindness. The current guidelines provide information on when and how to initiate treatment, but do not include recommendations on when and how to reduce or discontinue treatment. The Treatment Exit Options for Uveitis Register (TOFU) was initiated over five years ago, with the aim of improving the evidence for therapy reduction and termination. Over the past five years, the register has been established nationally with funding from the German Federal Ministry of Education and Research (BMBF), the Eye Foundation and industry partners and has since been expanded in individual European countries. The registry is under the auspices of the Uveitis Section of the German Ophthalmological Society (DOG). The analysis of baseline data from around 1000 patients shows that, in the prospectively documented patient population, intermediate uveitis is most common, followed by posterior uveitis, panuveitis and retinal vasculitis. The disease was bilateral in 75.9% of cases. The mean visual acuity was 0.22 ± 0.36 logMAR. Patients with panuveitis had the worst visual acuity, with 0.27 ± 0.39 logMAR. Severe visual impairment (> 1.0 logMAR) was observed in only 1% of patients at baseline. The continuation and European expansion will ensure the continuous generation of high-quality data in the coming years and thus help to develop recommendations on the end of therapy.

Fundus autofluorescence (FAF) is a prompt and non-invasive imaging modality helpful in detecting pathological abnormalities within the retina and the choroid. This narrative review and case series provides an overview on the current application of FAF in posterior and panuveitis. The literature was reviewed for articles on lesion characteristics on FAF of specific posterior and panuveitis entities as well as benefits and limitations of FAF for diagnosing and monitoring disease. FAF characteristics are described for non-infectious and infectious uveitis forms as well as masquerade syndromes. Dependent on the uveitis entity, FAF is of diagnostic value in detecting disease and following the clinical course. Currently available FAF modalities which differ in excitation wavelengths can provide different pathological insights depending on disease entity and activity. Further studies on the comparison of FAF modalities and their individual value for uveitis diagnosis and monitoring are warranted.