Exploring the Ocular Surface Microbiome and Tear Proteome in Glaucoma.

Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only modifiable risk factor to target the disease. Several associations between the gut microbiome and glaucoma, including the IOP, have been suggested. There is growing evidence that interactions between microbes on the ocular surface, termed the ocular surface microbiome (OSM), and tear proteins, collectively called the tear proteome, may also play a role in ocular diseases such as glaucoma. This study aimed to find characteristic features of the OSM and tear proteins in patients with glaucoma. The whole-metagenome shotgun sequencing of 32 conjunctival swabs identified Actinobacteria, Firmicutes, and Proteobacteria as the dominant phyla in the cohort. The species Corynebacterium mastitidis was only found in healthy controls, and their conjunctival microbiomes may be enriched in genes of the phospholipase pathway compared to glaucoma patients. Despite these minor differences in the OSM, patients showed an enrichment of many tear proteins associated with the immune system compared to controls. In contrast to the OSM, this emphasizes the role of the proteome, with a potential involvement of immunological processes in glaucoma. These findings may contribute to the design of new therapeutic approaches targeting glaucoma and other associated diseases.

Comprehensive automatic processing and analysis of adaptive optics flood illumination retinal images on healthy subjects.

This work presents a novel fully automated method for retinal analysis in images acquired with a flood illuminated adaptive optics retinal camera (AO-FIO). The proposed processing pipeline consists of several steps: First, we register single AO-FIO images in a montage image capturing a larger retinal area. The registration is performed by combination of phase correlation and the scale-invariant feature transform method. A set of 200 AO-FIO images from 10 healthy subjects (10 images from left eye and 10 images from right eye) is processed into 20 montage images and mutually aligned according to the automatically detected fovea center. As a second step, the photoreceptors in the montage images are detected using a method based on regional maxima localization, where the detector parameters were determined with Bayesian optimization according to manually labeled photoreceptors by three evaluators. The detection assessment, based on Dice coefficient, ranges from 0.72 to 0.8. In the next step, the corresponding density maps are generated for each of the montage images. As a final step, representative averaged photoreceptor density maps are created for the left and right eye and thus enabling comprehensive analysis across the montage images and a straightforward comparison with available histological data and other published studies. Our proposed method and software thus enable us to generate AO-based photoreceptor density maps for all measured locations fully automatically, and thus it is suitable for large studies, as those are in pressing need for automated approaches. In addition, the application MATADOR (MATlab ADaptive Optics Retinal Image Analysis) that implements the described pipeline and the dataset with photoreceptor labels are made publicly available.

Descemet membrane endothelial keratoplasty (DMEK): clinical results of precut versus surgeon-cut grafts.

PURPOSE: This study aims to investigate possible differences in clinical outcomes between precut and surgeon-cut grafts for Descemet membrane endothelial keratoplasty (DMEK). METHODS: 142 consecutive patients who underwent DMEK were included in the study. 44 patients received precut tissues, and 98 patients received surgeon-cut tissues. Precut grafts were allocated to the patient by the German Society for Tissue Transplantation if available. We compared the outcomes of both groups for changes in visual acuity, central corneal thickness, endothelial cell density, re-bubbling rate, and graft failure rate. RESULTS: Patients who received precut tissues experienced similar increase in visual acuity (median change 0.4 logMAR) and decrease of corneal swelling (median change 132 µm) compared with those who received surgeon-cut tissues (median VA change 0.3 logMAR, p = 0.55, CCT change 118 µm, p = 0.63). There was no statistical difference in endothelial cell density (1436 vs. 1569 cells/mm2, p = 0.37), re-bubbling (32% vs. 35%, p = 0.85), and graft failure rate (5% vs. 1%, p = 0.23). No primary graft failure occurred in the group of precut grafts. CONCLUSION: Both methods lead to comparable results for visual acuity, corneal deswelling, endothelial cell density, and re-bubbling rate. A previously described higher graft failure rate for precut tissues could not be confirmed in our study. Thus, we do not see medical reasons against the use of precut tissues. There are several advantages of precut DMEK tissues over surgeon-cut tissues, especially the prevention of graft loss during preparation in the operating theater.

Analyzing the impact of glaucoma on the macular architecture using spectral-domain optical coherence tomography.

PURPOSE: Using spectral domain optical coherence tomography (SD-OCT) the retina can be segmented automatically to visualize all retinal layers. In glaucoma chronically elevated intraocular pressure leads to a decline of retinal ganglion cells (RGC) which changes retinal architecture. The goal of these analyses was to gain insight into the changes induced by glaucoma within all macular layers using SD-OCT within a closely circumscribed glaucoma cohort. MATERIALS AND METHODS: SD-OCT measurements with automated retinal layer segmentation were performed in both eyes of primary open-angle glaucoma patients with a defined monocular absolute visual field scotoma in the central 10° of the visual field and in an age-matched healthy control group. Thickness of single retinal layers and entire retina were compared with special attention to the localization of the visual field scotoma in the glaucomatous eyes. RESULTS: 30 eyes of 15 glaucoma patients and 15 eyes of 15 healthy controls were included in this study. Statistical significant thickness differences were detected in the control group between superior and inferior retina for the retinal nerve fiber layer (RNFL), the outer plexiform layer (OPL) and the outer nuclear layer (ONL). In the glaucoma group thickness differences between worse and less affected eyes in the RNFL, the ganglion cell layer (GCL) and the inner plexiform layers (INL) were found. Comparison between healthy and diseased eyes revealed significant thickness differences in the RNFL, GCL, IPL and total retinal thickness but not the outer retinal layers. CONCLUSION: Comparison between SD-OCT measurements of the macula between healthy and glaucomatous eyes in a closely circumscribed disease stage showed a pronounced disease impact on the inner but not the outer retina. These results provide evidence that GCL and IPL thickness seem to be good measures to discriminate between affected and unaffected eyes in testing for glaucoma.

Laser peripheral iridotomy changes anterior chamber architecture.

PURPOSE: The pressure gradient between anterior and posterior chamber in acute angle closure (AAC) and primary angle closure suspects is balanced by a sufficient laser peripheral iridotomy (LPI). The anterior chamber changes induced by LPI in patients with unilateral AAC were examined and compared to healthy eyes to define threshold values, which may help to discriminate between healthy and diseased eyes. METHODS: Using Scheimpflug photography, anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA), and central corneal thickness (CCT) were measured before and after LPI in both eyes of unilateral AAC cases. These measurements were compared to a group of healthy control eyes to determine threshold values for ACD, ACV, and ACA. RESULTS: The ACD, ACV, and ACA increased significantly in the 25 AAC eyes after LPI. The ACD, ACV, ACA, and CCT values in the AAC eyes obtained before LPI were compared to a control group of 59 healthy eyes with wide open chamber angles. The cutoff values revealed by receiver operating characteristic analysis were 2.1 mm for ACD, 90.5 mm2 for ACV, and 27.25° for ACA. CONCLUSIONS: Our results confirm the significant changes of the anterior segments architecture induced by LPI in AAC eyes. The found threshold values for ACD, ACV, and ACA may help in daily clinical routine to discriminate between healthy eyes and those in need for a prophylactic LPI.

Intraocular Pressure and Trabecular Meshwork Outflow Facility After Descemet Stripping Endothelial Keratoplasty.

PURPOSE: Increased intraocular pressure (IOP) is a frequent complication after penetrating keratoplasty and can be due to reduced trabecular meshwork outflow facility. Descemet stripping endothelial keratoplasty (DSEK) is a lamellar technique for replacing pathologic corneal endothelium and may be associated with a lower risk of postoperative IOP rise. In a prospective clinical study we studied IOP and outflow facility before and after DSEK. METHODS: In 23 eyes of 23 patients before, 1 day, 6 weeks, and 3, 6, and 12 months after DSEK, IOP was measured using Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT). Trabecular meshwork outflow facility (C-value) was assessed by impression tonography with the Schioetz tonometer. Central corneal thickness was measured by Haag-Streit pachymetry. Best spectacle corrected visual acuity, ocular surface fluorescein staining, and corneal sensation were also recorded. RESULTS: Mean IOP showed a trend toward increase from preoperatively to 1 year postoperatively, which was not statistically significant (GAT: 13.5±3.3 to 15.3±4.7 mm Hg; DCT: 13.7±2.9 to 16.7±4.8 mm Hg; Schioetz: 12.4±2.8 to 15.3±2.9 mm Hg). Outflow facility increased significantly from 0.19±0.03 before to 0.29±0.05 mm/Δmm Hg/min at 1 year after DSEK (P=0.002). Best spectacle corrected visual acuity increased significantly from 0.98±0.48 to 0.36±0.17 logMAR (P=0.0004). Corneal sensitivity was unchanged and corneal staining significantly decreased from the preoperative to 1 year postoperative period (P=0.01). Mean central corneal thickness changed significantly from 650±59 to 621±73 µm (P=0.002). CONCLUSIONS: IOP as measured by GAT, DCT, and Schioetz tends to increase during the first year after DSEK in eyes without previous glaucoma, whereas trabecular meshwork outflow facility as measured by Schioetz tonography improves. These findings are likely to be due to a progressive increase of corneal rigidity affecting transcorneal pressure measurements of both IOP and trabecular meshwork outflow facility.

Corneal back surface radius after DSEK and DSAEK: a comparative single surgeon case control study.

The purpose of this study was to analyse and compare the visual and refractive results after DSEK with manual donor dissection and DSAEK with microkeratome-assisted donor dissection in a retrospective unmasked case control study. DSEK was performed in 15 eyes of 15 patients (74.9 ± 7.9 years; 4♂, 11♀). DSAEK was performed in 15 eyes of 15 patients (76.5 ± 6.6 years; 4♂, 11♀) using the Carriazo-Pendular-microkeratome and Schwindt artificial anterior chamber. The best corrected visual acuity (BCVA), corneal geometry assessed using Scheimpflug photography (SP) and anterior segment optical coherence tomography (AS-OCT) was regularly measured in 15 matched pairs receiving DSEK or DSAEK. Mean BCVA improved from 1.1 ± 0.5 to 0.5 ± 0.2 logMAR (p = 0.001) after DSEK and from 1.0 ± 0.5 to 0.2 ± 0.2 logMAR (p = 0.001) in the DSAEK-group. After 6 months, BCVA was significantly better in the DSAEK-group. Corneal refractive power decreased from 36.9 ± 1.5 to 35.9 ± 1.3 D (p = 0.01) in the DSEK-group and from 37.7 ± 1.6 to 36.4 ± 1.6 D (p = 0.01) in the DSAEK-group. The corneal back surface radius changed from 6.05 ± 1.6 to 5.82 ± 0.45 in the DSEK (p = 0.03) and from 6.72 ± 0.96 to 5.39 ± 0.33 in the DSAEK-group (p = 0.01). Mean central corneal thickness (CCT) measured by SP decreased from 741 ± 105 to 605 ± 63 µm (p = 0.26) after DSEK and from 700 ± 98 to 607 ± 88 µm (p = 0.01) after DSAEK. At no point in time during follow-up, mean CCT was significantly different in both groups. The ratio between central and peripheral transplant thickness decreased slightly from 0.65 ± 0.16 to 0.59 ± 0.16 after DSEK (p = 0.57) and from 0.52 ± 0.08 to 0.43 ± 0.14 after DSAEK (p = 0.17). The ratio difference between DSEK and DSAEK-groups was not statistically significant. The use of a pendular microkeratome for DSAEK results in faster visual rehabilitation but does not decrease the surgically induced change of cornea-based hyperopisation which is due to posterior corneal curvature.