Microbiome and Retinal Vascular Diseases.

The gut microbiome consists of more than a thousand different microbes and their associated genes and microbial metabolites. It influences various host metabolic pathways and is therefore important for homeostasis. In recent years, its influence on health and disease has been extensively researched. Dysbiosis, or imbalance in the gut microbiome, is associated with several diseases. Consequent chronic inflammation may lead to or promote inflammatory bowel disease, obesity, diabetes mellitus, atherosclerosis, alcoholic and non-alcoholic liver disease, cirrhosis, hepatocellular carcinoma, and other diseases. The pathogenesis of the three most common retinal vascular diseases, diabetic retinopathy, retinal vein occlusion, and retinal artery occlusion, may also be influenced by an altered microbiome and associated risk factors such as diabetes mellitus, atherosclerosis, hypertension, and obesity. Direct cause-effect relationships remain less well understood. A potential prevention or treatment modality for these diseases could be targeting and modulating the individual's gut microbiome.

The Human Ocular Surface Microbiome and Its Associations with the Tear Proteome in Dry Eye Disease.

Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are limited. There is growing evidence that complex interactions between the ocular surface microbiome (OSM) and tear fluid constituents, potentially leading to inflammatory processes, are associated with ocular surface diseases such as DED. In this study, we aimed to find unique compositional and functional features of the OSM associated with human and microbial tear proteins in patients with DED. Applying whole-metagenome shotgun sequencing of forty lid and conjunctival swabs, we identified 229 taxa, with Actinobacteria and Proteobacteria being the most abundant phyla and Propionibacterium acnes the dominating species in the cohort. When DED patients were compared to controls, the species Corynebacterium tuberculostearicum was more abundant in conjunctival samples, whereas the family Propionibacteriaceae was more abundant in lid samples. Functional analysis showed that genes of L-lysine biosynthesis, tetrapyrrole biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis, and the super pathway of L-threonine biosynthesis were enriched in conjunctival samples of controls. The relative abundances of Acinetobacter johnsonii correlated with seven human tear proteins, including mucin-16. The three most abundant microbial tear proteins were the chaperone protein DnaK, the arsenical resistance protein ArsH, and helicase. Compositional and functional features of the OSM and the tear proteome are altered in patients with DED. Ultimately, this may help to design novel interventional therapeutics to target DED.

FLUORESCENCE LIFETIME IMAGING OPHTHALMOSCOPY AS PREDICTOR OF LONG-TERM FUNCTIONAL OUTCOME IN MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To assess whether macular fluorescence lifetimes may serve as a predictor for long-term outcomes in macula-off rhegmatogenous retinal detachment. METHODS: A single-center observational study was conducted. Patients with pseudophakic macula-off rhegmatogenous retinal detachment were included and evaluated 1 and 6 months after successful reattachment surgery. Fluorescence lifetime imaging ophthalmoscopy lifetimes in the central Early Treatment Diabetic Retinopathy Study grid subfield, in two distinct channels (short spectral channel and long spectral channel) were analyzed. Best-corrected visual acuity optical coherence tomography of the macula and fluorescence lifetimes were measured at month 1 and month 6. RESULTS: Nineteen patients were analyzed. Lifetimes of the previously detached retinas were prolonged compared with the healthy fellow eyes. Short lifetimes at month 1 were associated with better best-corrected visual acuity improvement (short spectral channel: r2 = 0.27, P < 0.05, long spectral channel: r2 = 0.23, P < 0.05) and with good final best-corrected visual acuity (short spectral channel: r2 = 0.43, P < 0.01, long spectral channel: r2 = 0.25, P < 0.05). Lifetimes were prolonged in some cases of outer retinal damage in optical coherence tomography scans. CONCLUSION: Fluorescence lifetime imaging ophthalmoscopy might serve as a prediction tool for functional recovery in pseudophakic macula-off rhegmatogenous retinal detachment. Retinal fluorescence lifetimes could give insight in molecular processes after rhegmatogenous retinal detachment.

Ciliary body length revisited by anterior segment optical coherence tomography: implications for safe access to the pars plana for intravitreal injections.

PURPOSE: To investigate the dependence of the ciliary body length (CBL) on the axial length (AL) and to draw conclusions on implications regarding safe pars plana access for intravitreal injections and vitreoretinal surgery. METHODS: A total of 200 individuals (mean age 42 years, SD ± 15.4) were enrolled in the study. Objective refraction and AL were obtained. Spherical equivalent (SE) was calculated. Anterior segment optical coherence tomography (ASOCT) was used to image and measure the CBL. RESULTS: The mean SE was - 1.64 diopters (SD ± 3.15, range - 14.5 to + 9 diopters) and the mean AL was 24.19 mm (SD ± 1.65, range 19.8-32.2 mm). There was a significant correlation between SE and AL (r2 = 0.62, p < 0.0001). Mean CBL correlated significantly with age (r2 = 0.11, p < 0.0001), AL (r2 = 0.23, p < 0.0001) and SE (r2 = 0.25, p < 0.0001). The mean CBL was 3351 µm (SD ± 459, range 2184-4451 µm). Three separate groups were defined by their AL with a normal AL group (AL 22.5 to 25 mm), a short AL group (AL < 22.5 mm) and a long AL group (AL > 25 mm). The mean CBL in the normal AL group was 3311 µm (SD ± 427), in the short AL group 2936 µm (SD ± 335) and in the long AL group 3715 µm (SD ± 365), and differed significantly (p < 0.0001) when compared. CONCLUSION: For interventions requiring pars plana access (as an intravitreal injection or vitreoretinal surgery), an incision distance of 3.5-4.0 mm posterior to the limbus is recommended. In our research, however, a difference of 0.77 mm in mean CBL between the group with short AL and the group with long AL is demonstrated, implying that the mean CBL in very short and very long eyes differs significantly. These findings suggest that the AL should be taken into account for pars plana access and that it would be advisable to prefer the shorter or longer recommended distance (3.5 and 4.0 mm, respectively) from the limbus, which correlates with the AL. If AL is > 25 mm, a distance of 4.0 mm from the limbus should be chosen; and if AL is < 22.5 mm, a distance of 3.5 mm seems adequate. TRIAL REGISTRATION NUMBER AND DATE: NCT00564291, 27 Nov 2007.

IMAGING ARTIFACTS IN FLUORESCENCE LIFETIME IMAGING OPHTHALMOSCOPY.

PURPOSE: To investigate and quantify the influence of imaging artifacts on retinal fluorescence lifetime (FLIO) values and to provide helpful hints and tricks to avoid imaging artifacts and to improve FLIO image acquisition quality. METHODS: A systematic analysis of potential parameters influencing FLIO quality and/or fluorescence lifetime values was performed in a prospective systematic experimental imaging study in five eyes of five healthy subjects. For image acquisition, a fluorescence lifetime imaging ophthalmoscope (Heidelberg Engineering) was used. Quantitative analysis of FLIO lifetime changes due to imaging artifacts was performed. RESULTS: Imaging artifacts with significant influence on fluorescence lifetimes included too short image acquisition time, insufficient illumination, ocular surface problems, and image defocus. Prior use of systemic or topical fluorescein makes analysis of retinal fluorescence lifetimes impossible. CONCLUSION: Awareness of possible sources of imaging artifacts is important for FLIO image acquisition and analysis. Therefore, standardized imaging and analysis procedure in FLIO is crucial for high-quality image acquisition and the possibility for systematic quantitative fluorescence lifetime analysis.

LONGITUDINAL FOVEAL FLUORESCENCE LIFETIME CHARACTERISTICS IN GEOGRAPHIC ATROPHY USING FLUORESCENCE LIFETIME IMAGING OPHTHALMOSCOPY.

PURPOSE: Short foveal fluorescence lifetimes (fFLT) in geographic atrophy are typically found in eyes with foveal sparing (FS) but may also occur in eyes without FS. We investigated whether short fFLT could serve as a functional biomarker for disease progression in geographic atrophy. METHODS: Thirty three eyes were followed over the course of 4 to 6 years. Foveal sparing was assessed using fluorescence lifetime imaging ophthalmoscopy, optical coherence tomography, fundus Autofluorescence, and macular pigment optical density. RESULTS: Eyes with FS exhibited shorter fFLT compared with eyes without FS. Short fFLT (<600 ps) were measured in all eyes with FS and half of the eyes without FS. Eyes with FS showed a bigger increase in fFLT per year (+39/+30 ps (short spectral channel/long spectral channel) in FS versus +29/+22 ps (short spectral channel/long spectral channel) in non FS). The best-corrected distance visual acuity correlated significantly with fFLT (P = 0.018 and P = 0.005 for short spectral channel/long spectral channel). Macular pigment optical density measurements correlated significantly with fFLT but not in all spectral channels (P ranging from 0.018 to 0.077). CONCLUSION: In geographic atrophy, shorter fFLT are associated with FS but they can also be observed in eyes without FS. Our longitudinal data suggest that shorter fFLT features in eyes with loss of FS represent an earlier stage of disease and may be more prone to loss of the visual acuity.

Comparison of 55° Wide-Field Spectral Domain Optical Coherence Tomography and Conventional 30° Optical Coherence Tomography for the Assessment of Diabetic Macular Edema.

PURPOSE: To compare conventional 30° spectral domain optical coherence tomography (SD-OCT) with 55° wide-field SD-OCT for the assessment of diabetic macular edema (DME). METHODS: This study included 50 DME patients. Both 55° and 30° SD-OCT was conducted. Two readers evaluated scans according to a standardized grading protocol. Intergrader agreement as well as agreement between 30° and 55° SD-OCT were assessed. RESULTS: Intergrader agreement (κ) was strong and ranged from 0.79 to 1.0. Perfect interdevice agreement (κ = 1.0) was found for the detection of intra- and subretinal fluid. Excellent agreement (κ ≥ 0.9) was found for the presence of epiretinal membrane (κ = 0.92) and cotton-wool spots (κ = 0.92). A strong agreement was found for the presence of hard exudates (κ = 0.89) and microaneurysms (κ = 0.81). A moderate correlation was found for ellipsoid zone integrity (κ = 0.69) and configuration of the vitreomacular interface (VMI) (κ = 0.69). A weak agreement was found for retinal pigment epithelium atrophy (κ = 0.51) and external limiting membrane integrity (κ = 0.35). CONCLUSION: Wide-field OCT imaging may be beneficial for evaluating DME, particularly for assessing the VMI and the integrity of hyperreflective bands.

[Virtual reality perimetry and home perimetry]. / "Virtual reality perimetry" und "home perimetry".

In this article virtual reality (VR)-based procedures for home perimetry (HP) are described and an overview is given of which procedures can already be used today.

Functional and Morphological Outcomes after Trabeculectomy and Deep Sclerectomy-Results from a Monocentric Registry Study.

The aim of this study was to compare the effectiveness of trabeculectomy (TE) and deep sclerectomy (DS) in lowering intraocular pressure (IOP) and thereby preserving visual field and peripapillary retinal nerve fiber layer (RNFL) tissue in primary open-angle glaucoma (POAG) cases. IOP, number of IOP-lowering medications, visual acuity, mean defect of standard automated perimetry, and mean peripapillary RNFL thickness were retrospectively collected and followed up for 3 years after surgery. TE was performed in 104 eyes and DS in 183 eyes. Age, gender, laterality, IOP, number of medications, visual acuity, perimetry mean defect, and peripapillary RNFL thickness were equally distributed at baseline. Mean IOP decreased from 23.8 ± 1.4 mmHg and 23.1 ± 0.4 mmHg to 13.4 ± 0.6 mmHg (p < 0.001) and 15.4 ± 0.7 mmHg (p = 0.001) in the TE and DS groups, respectively. Mean defect remained stable (TE: -11.5 ± 0.9 dB to -12.0 ± 1.1 (p = 0.090); DS: -10.5 ± 0.9 dB to -11.0 ± 1.0 dB (p = 0.302)), while mean peripapillary RNFL thickness showed further deterioration during follow-up (TE group: 64.4 ± 2.1 µm to 59.7 ± 3.5 µm (p < 0.001); DS group: 64.9 ± 1.9 µm to 58.4 ± 2.1 µm (p < 0.001)). Both TE and DS were comparably effective concerning postoperative reduction in IOP and medication. However, glaucoma disease further progressed during follow-up.

Fluorescence lifetime imaging ophthalmoscopy and the influence of oral lutein/zeaxanthin supplementation on macular pigment (FLOS) - A pilot study.

BACKGROUND & AIMS: Oral lutein (L) and zeaxanthin (Z) supplementation enhances macular pigment optical density (MPOD) and plays a protective role in the development of age-related macular degeneration (AMD). Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a novel in vivo retinal imaging method that has been shown to correlate to classical MPOD measurements and might contribute to a metabolic mapping of the retina in the future. Our aim was to show that oral supplementation of L and Z affects the FLIO signal in a positive way in patients with AMD. METHODS: This was a prospective, single center, open label cohort study. Patients with early and intermediate AMD received oral L and Z supplementation during three months, and were observed for another three months after therapy termination. All visits included measurements of clinical parameters, serum L and Z concentration, MPOD measurements using heterochromatic flicker photometry, dual wavelength autofluorescence imaging, and FLIO. Correlation analysis between FLIO and MPOD were performed. RESULTS: Twenty-one patients completed the follow up period. Serum L and Z concentrations significantly increased during supplementation (mean difference 244.8 ng/ml; 95% CI: 81.26-419.9, and 77.1 ng/ml; 95% CI: 5.3-52.0, respectively). Mean MPOD units significantly increased (mean difference 0.06; 95% CI: 0.02-0.09; at 0.5°, 202; 95% CI: 58-345; at 2°, 1033; 95% CI: 288-1668; at 9° of eccentricity, respectively) after three months of supplementation with macular xanthophylls, which included L and Z. Median FLIO lifetimes in the foveal center significantly decreased from 277.3 ps (interquartile range 230.2-339.1) to 261.0 ps (interquartile range 231.4-334.4, p = 0.027). All parameters returned to near-normal values after termination of the nutritional supplementation. A significant negative correlation was found between FLIO and MPOD (r2 = 0.57, p < 0.0001). CONCLUSIONS: FLIO is able to detect subtle changes in MPOD after L and Z supplementation in patients with early and intermediate AMD. Our findings confirm the previous described negative correlation between FLIO and MPOD. Macular xanthophylls seem to contribute to short foveal lifetimes. This study is registered at ClinicalTrials.gov (identifier number NCT04761341).

Stage specific glaucomatous changes of the macula recorded using spectral domain optical coherence tomography.

BACKGROUND: This study aimed to compare the thickness of different macular retinal layers in glaucomatous eyes and healthy controls, and evaluate the diagnostic performance of spectral domain optical coherence tomography (SD-OCT) parameters. METHODS: In this cross-sectional comparative study, 48 glaucomatous eyes and 44 healthy controls were included. The thickness of the total retina and all retinal layers were obtained using the Early Treatment Diagnostic Retinopathy Study (ETDRS) grid. The minimal and average values of outer and inner ETDRS-rings were calculated. The diagnostic performance for detection of glaucoma was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The thickness of the total retina, ganglion cell layer (GCL), and inner-plexiform layer (IPL) was significantly thinner in glaucomatous eyes in all sectors except the center (all p<0.05). The thickness of retinal nerve fiber layer (RNFL) was significantly thinner in the glaucoma group except in the center, nasal inner, and temporal outer sectors (all p<0.05). Layer thinning advanced with glaucoma severity. The minimal outer GCL thickness showed the highest AUC value for discrimination between glaucomatous eyes and healthy controls(0.955). The minimal outer IPL showed the highest AUC value for discriminating early-stage glaucomatous eyes from healthy controls (0.938). CONCLUSIONS: Glaucomatous eyes were found to have significant thinning in the macular region. GCL and IPL showed high ability to discriminate glaucomatous and early-stage glaucomatous eyes from controls. Applying the minimal value to the ETDRS grid has the potential to provide good diagnostic abilities in glaucoma screening.

PRESERFLO MicroShunt implantation versus trabeculectomy for primary open-angle glaucoma: a two-year follow-up study.

BACKGROUND: To compare the intermediate-term efficacy of PRESERFLO (PF) MicroShunt implantation with trabeculectomy (TE) in patients with primary open-angle glaucoma, focusing on longitudinal changes of functional and structural parameters. METHODS: This retrospective comparative study included 104 eyes of 104 patients who underwent TE and 83 eyes of 83 patients that underwent PF implantation between January 2019 and December 2020, with a minimum follow-up of two years. Baseline and postoperative intraocular pressure (IOP), number of IOP-lowering medications, visual field mean defect (MD) and peripapillary retinal nerve fibre layer (RNFL) thickness measured using optical coherence tomography were assessed and compared between groups. RESULTS: Baseline characteristics (age, sex, IOP, number of IOP-lowering medications, MD, RNFL thickness) were comparable between the two groups (all P > 0.05). During the two-year of follow-up, mean IOP decreased from 24.09 ± 1.15 mmHg and 21.67 ± 0.77 mmHg to 11.37 ± 1.13 mmHg (P < 0.001) and 15.50 ± 1.54 mmHg (P = 0.028), and the mean number of IOP-lowering medications decreased from 3.25 ± 0.14 and 3.51 ± 0.14 to 0.53 ± 0.14 (P < 0.001) and 1.06 ± 0.43 (P < 0.001) in the TE and PF groups, respectively. MD remained stable [- 11.54 ± 0.93 dB and - 11.17 ± 1.66 to - 10.67 ± 0.91 dB (P = 0.226) and - 10.40 ± 4.75 dB (P = 0.628) in the TE and PF groups, respectively] but RNFL thickness decreased continuously during follow-up [62.79 ± 1.94 µm and 62.62 ± 2.05 µm to 57.41 ± 1.81 µm (P < 0.001) and 60.22 ± 1.98 µm (P = 0.182) in the TE and PF groups, respectively]. CONCLUSION: PF implantation is comparably effective in the intermediate term in lowering IOP and reducing the use of IOP-lowering medications over a two-year follow-up period. Although visual field defects were stable, RNFL continued to decrease during postoperative follow-up.

The Influence of Cataract on Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO).

Purpose: To investigate the influence of lens opacifications on fluorescence lifetime imaging ophthalmoscopy (FLIO). Methods: Forty-seven eyes of 45 patients were included. Mean fluorescence lifetimes (Tm) were recorded with a fluorescence lifetime imaging ophthalmoscope in a short spectral channel (SSC) and a long spectral channel (LSC). Retinal and lens autofluorescence lifetimes were measured in subjects before and after cataract surgery. Lens opacification was graded using the Lens Opacities Classification System III (LOCS III) classification. Results: The retinal Tm decreased significantly after cataract surgery in both spectral channels (SSC: -53%, P < 0.0001; LSC: -26%, P = 0.0041). The lens Tm differed significantly between the crystalline and the artificial lens in both spectral channels (P < 0.0001). The "nuclear opacity" and "nuclear color" score of the LOCS III classification correlated significantly with the mean Tm difference in both spectral channels (P < 0.0001). Conclusions: Lens opacification results in significantly longer retinal Tm. Therefore the lens status has to be considered when performing cross-sectional fluorescence lifetime analysis. Cataract-formation and cataract-surgery needs to be considered when conducting longitudinal studies. Grading of nuclear opacity following the LOCS III classification provides an approximate conversion formula for the mean change of lifetimes, which can be helpful in the interpretation of data in patients with lens opacities. Translational Relevance: FLIO is significantly influenced by lens opacities. Using a lens opacity grading scheme and measuring fluorescence lifetimes before and after cataract surgery, an approximative conversion formula can be calculated, which enables the comparison of lifetimes after cataract surgery or over the course of time.

Understanding the Interactions Between the Ocular Surface Microbiome and the Tear Proteome.

Purpose: The purpose of this study was to explore the interplay between the ocular surface microbiome and the tear proteome in humans in order to better understand the pathogenesis of ocular surface-associated diseases. Methods: Twenty eyes from 20 participants were included in the study. The ocular surface microbiome was sequenced by whole-metagenome shotgun sequencing using lid and conjunctival swabs. Furthermore, the tear proteome was identified using chromatography tandem mass spectrometry. After compositional and functional profiling of the metagenome and functional characterization of the proteome by gene ontology, association studies between the ocular microbiome and tear proteome were assessed. Results: Two hundred twenty-nine taxa were identified with Actinobacteria and Proteobacteria being the most abundant phyla with significantly more Propionibacterium acnes and Staphylococcus epidermidis in lid compared to conjunctival swabs. The lid metagenomes were enriched in genes of the glycolysis lll and adenosine nucleotides de novo and L-isoleucine biosynthesis. Correlations between the phylum Firmicutes and fatty acid metabolism, between the genus Agrobacterium as well as vitamin B1 synthesis and antimicrobial activity, and between biosynthesis of heme, L-arginine, as well as L-citrulline and human vision were detected. Conclusions: The ocular surface microbiome was found to be associated with the tear proteome with a role in human immune defense. This study has a potential impact on the development of treatment strategies for ocular surface-associated diseases.

Gravitational pseudoaccommodation in patients with aphakic iris-claw intraocular lenses.

PURPOSE: To assess whether iris-claw intraocular lenses (IOLs) undergo gravitation-dependent changes in position and refraction. SETTING: Tertiary referral center, Bern, Switzerland. DESIGN: Observational case study. METHODS: Patients with a history of pars plana vitrectomy and IOL exchange with implantation of an aphakic iris-claw IOL (Artisan) were included in this study. Objective refraction was obtained with a handheld autorefractometer, and the IOL position was measured by ultrasound biomicroscopy with the patient prone, sitting, and supine. RESULTS: Twenty-one eyes of 19 patients with retropupilary IOLs (13) or prepupillary IOLs (8) were included. The mean spherical equivalent (SE) in the sitting position was -0.81 diopter (D) ± 0.95 (SD), and the mean distance from the endothelium to the anterior edge of the IOL was 3.35 ± 0.72 mm. The mean SE in the supine position was -0.61 ± 1.28 D, whereas the mean SE in the prone position was -1.34 ± 1.17 D (P = .0030). The IOL position changed from 3.50 mm in the supine position to 3.06 mm in the prone position (P < .0001). CONCLUSIONS: The aphakic iris-claw IOL was subject to significant movement related to gravity. The change in the refractive effect suggests that there is a degree of pseudoaccommodation caused by the forward shift of the aphakic IOL in the face-down position. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.