Background/Aims Neurofilament light chain (NfL) levels in cerebrospinal fluid and serum are reliable indicators for neuroaxonal damage in a broad spectrum of neurodegenerative diseases. Herein, we investigate NfL levels in serum and anterior chamber fluid of patients with glaucoma. Methods Patients scheduled for routine glaucoma or cataract surgery were recruited for this study. Retinal nerve fibre layer thickness was measured by optical coherence tomography (OCT, Heidelberg Spectralis). NfL levels in serum and in anterior chamber fluid were analysed with Simoa SR-X Analyzer (Quanterix; NFLIGHT, Lexington, Massachusetts, USA). T-test was used for parametric data and Mann-Whitney-U test for nonparametric data. Spearman’s rank-order correlation was used to investigate correlations. P values<0.05 were considered as statistically significant. Results Sixty patients with glaucoma and 58 controls were enrolled. Serum NfL concentration of patients with glaucoma was similar to serum NfL concentration in controls (median (IQR); 22.7 (18.9) pg/mL vs 22.5 (24.0) pg/mL; p=0.763). A positive correlation of serum NfL with age was observed in both patients with glaucoma (r=0.77; p<0.001) and in the control group (r=0.82, p<0.001). In the anterior chamber fluid, the NfL concentration was substantially increased in patients with glaucoma compared with controls (20.7 (101.3) pg/mL vs 3.1 (2.9) pg/mL; p<0.001). Furthermore, we found a positive correlation of anterior chamber fluid NfL with preoperative intraocular pressure (r=0.39, p=0.003) and with retinal nerve fibre layer thickness (r=0.58, p<0.001). Conclusion NfL levels in anterior chamber fluid are elevated in patients with glaucoma and correlate with intraocular pressure and retinal nerve fibre layer thickness. The presented data strongly support anterior chamber fluid NfL as a new marker for glaucoma.

In this report, we evaluated the role of iron in sodium iodate (NaIO₃)-induced model of age-related macular degeneration (AMD) in ARPE-19 cells in-vitro, and mouse models in-vivo. ARPE-19 cells, a human retinal pigmented epithelial cell line, were exposed to 10 mM of NaIO₃ for 24 h, and the expression and localization of major iron modulating proteins was evaluated by Western blotting (WB) and immunostaining. Synthesis and maturation of cathepsin-D (cat-D), a lysosomal enzyme, was evaluated by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) and WB respectively. For in-vivo studies, C57BL/6 mice were injected with 40 mg/kg mouse body weight of NaIO₃ intraperitoneally, and their retina was evaluated after 3 weeks as above. We observed that NaIO₃ induced a 10-fold increase in ferritin in ARPE-19 cells, which co-localized with LC3II, an autophagosomal marker, and LAMP-1, a lysosomal marker. A similar increase in ferritin was noted in retinal lysates and retinal sections of NaIO₃-injected mice by WB and immunostaining. Impaired synthesis and maturation of cat-D was also noted. Accumulated ferritin was loaded with iron, and released from retinal pigmented epithelial (RPE) cells in Perls’ and LAMP-1 positive vesicles. These observations suggest that NaIO₃ impairs lysosomal degradation of ferritin by decreasing the transcription and maturation of cat-D in RPE-19 cells. Iron-loaded ferritin accumulates in lysosomes and is released in lysosome membrane-enclosed vesicles in the extracellular milieu. Accumulation of ferritin in RPE-19 cells and fusion of ferritin-containing vesicles with adjacent photoreceptor cells is likely to create iron overload, compromising their viability. Moreover, reduced activity of cat-D is likely to promote the accumulation of other cellular debris in lysosomal vesicles, contributing to AMD-like pathology.

Purpose. Interleukin 6 (IL-6) plays a crucial role in both adaptive and innate immunity. The rs1800795 gene polymorphism of IL-6 is associated with various autoimmune diseases, like multiple sclerosis.Methods. 134 patients with HLAB27 positive iridocyclitis, 84 patients with intermediate uveitis, 132 controls, and 65 HLAB27 positive controls were recruited for the present case-control study. Main outcome measures were genotype distribution and allelic frequencies determined by polymerase chain reaction.Results. The frequency of carriers of the minor allele for rs1800795 was significantly higher in patients with intermediate uveitis compared to controls (p=0.04; OR: 1.46; CI: 1.02–2.11). Frequencies of the minor allele for rs1800795 did not differ significantly in patients with HLAB27 associated uveitis when compared to controls (p>0.05).Conclusion. These findings further deepen our understanding of the commonality between multiple sclerosis and intermediate uveitis. Given the functionality of the investigated polymorphism, new pathophysiological insights are gained that help to evaluate possible therapeutic targets.

Glaucoma has a significant impact on quality of life. Here, we aimed to evaluate the influence of a reduction in glaucoma medications on quality of life and patient satisfaction after phacoemulsification combined with the Xen gel stent. We carried out a cross-sectional survey of patients who underwent phacoemulsification with the Xen gel stent at the Medical University of Graz, Austria. Quality of life was assessed using the German version of the Glaucoma Symptoms Scale (GSS)—questionnaire. Patients were also asked whether the operation reduced glaucoma medications and to indicate their overall satisfaction from 1 (totally discontented) up to 10 (totally contented). Questionnaires of 80 patients were evaluated. A total of 36 patients (45.0%) reported a reduction in glaucoma medications. Three items of the GSS were significantly better in patients who needed fewer glaucoma medications after the operation (“hard to see in daylight”, 75.0 ± 31.1 vs. 57.7 ± 39.1, p = 0.035; “hard to see in dark places”, 81.1 ± 28.7 vs. 54.9 ± 41.2, p = 0.002; and “halos around lights”, 88.3 ± 25.9 vs. 68.8 ± 38.6, p = 0.002). Patient satisfaction was significantly higher when the procedure led to a reduction in glaucoma medication (8.3 ± 2.0 vs. 6.8 ± 3.1; p = 0.034). The reported quality of life and patient satisfaction were significantly better when phacoemulsification with the Xen gel stent reduced the number of glaucoma medications needed.

The genetic background for the concomitance of uveitis and other autoimmune diseases remains elusive. Here the role of two IL2RA gene variants (rs11594656 and rs12722495) was investigated in intermediate uveitis and HLAB27 acute anterior uveitis. One hundred fifty-nine patients with HLAB27 acute anterior uveitis, 85 patients with intermediate uveitis, 138 HLAB27 negative controls and 100 HLAB27 positive controls were recruited for this case-control study. Main outcome measures were genotype distribution and allelic frequencies determined by polymerase chain reaction. The frequencies of carriers of the minor allele at rs11594656 and rs12722495 were significantly different in patients with intermediate uveitis compared to HLAB27 positive and negative controls combined (p<0.05). For rs12722495 the minor G allele was protective (genotypic OR: 0.29 [0.12-0.69]), and for rs11594656 the minor A allele conferred risk (genotypic OR: 1.59 [1.09-2.32]). No significant differences in genotype distribution were found between patients with HLAB27 acute anterior uveitis and HLAB27 positive or negative control subjects. We found rs11594656 and rs12722495 to be associated with intermediate uveitis but not with HLAB27 acute anterior uveitis. The genetic heterogeneity found at the IL2RA locus could help explain patterns of concomitance with other autoimmune diseases.

Purpose: Numerous studies suggest that reactive oxygen species play a crucial role in the development of glaucoma. Since glaucoma patients exhibit posterior vitreous detachment earlier than controls, it has been suggested that reactive oxygen species—increased in glaucoma—also affect the vitreous. In the present study we evaluated the influence of open-angle glaucoma oxidative stress on the redox state of vitreous albumin. Methods: Albumin redox states of the vitreous and plasma were evaluated in 22 subjects—11 open-angle glaucoma patients and 11 controls—matched for age, gender, and vitreous state. According to the redox state of cysteine-34, albumin can be separated into: human mercaptalbumin (the thiol form), human nonmercaptalbumin1 (a reversible modification due to mild oxidation), and human nonmercaptalbumin2 (an irreversible modification due to severe oxidation). Results: Albumin of both, the open-angle glaucoma group and the control group, was more oxidized in the vitreous compared to plasma. Furthermore, significantly higher human nonmercaptalbumin1 fractions were found in the vitreous of open-angle glaucoma patients compared to controls. No significant differences were found in the plasma albumin fractions between the groups. Conclusion: Our results support the hypothesis that oxidative stress plays a crucial role in open-angle glaucoma and that reactive oxygen species in glaucomatous eyes may also affect the vitreous.