Acta Ophthalmologica最新文献

Aims/Purpose: To develop a novel classification of highly myopic eyes using artificial intelligence (AI) and investigate its relationship with contrast sensitivity function (CSF) and fundus features.

Methods: 616 highly myopic eyes of 616 patients were enrolled. CSF was measured using the quantitative CSF method. Myopic macular degeneration (MMD) was graded according to the International META-PM Classification. Thickness of the macula and peripapillary retinal nerve fiber layer (p-RNFL) were assessed by fundus photography and optical coherence tomography, respectively. Classification was performed by combining CSF and fundus features with principal component analysis and k-means clustering.

Results: With 83.35% total variance explained, highly myopic eyes were classified into 4 categories. The percentages of categories 1 to 4 were 14.9%, 37.5%, 36.2%, and 11.4%, respectively. CSF of the eyes in category 1 were the highest, followed by those in category 2 and then category 3, while the lowest was seen in category 4. Compared to those in category 1, eyes in category 2 presented higher percentage of MMD2 and thinner temporal p-RNFL. Eyes in categories 3 and 4 presented significantly higher percentage of MMD≥3, thinner nasal macular thickness and p-RNFL (p < 0.05). Multivariate regression showed category 4 had higher MMD grades, thinner macular and p-RNFL thickness compared to category 3.

Conclusions: We proposed an AI-based classification of highly myopic eyes by integrating features from both visual function and fundus. It might be an important tool to comprehensively evaluate highly myopic eyes.

Purpose: The gut microbiome is highly influential in diseases with inflammatory components. Multiple studies showed a link between the gut microbiome and age-related macular degeneration (AMD). However, no consistent taxa have been reported.

Methods: We included 1372 participants from the Rotterdam Study (RS). AMD features (e.g. [reticular pseudo-]drusen, retinal pigment epithelium degeneration, and hyperpigmentation) were graded by human graders on color fundus photographs. Next, areas of these features were automatically quantified by a deep learning segmentation model. Stages were determined according to the RS classification (preliminary = 239, early-intermediate = 75, late = 6). Propensity score matching was performed on age, sex and BMI. Multivariable associations with taxonomic and functional profiles were assessed using zero-adjusted models (MaAsLin2; Compound Poisson). p-values were false discovery rate-adjusted (q-values). Taxa associated (q < 0.25) with at least two out of seven AMD(-related) outcomes are reported.

Results: We observed no associations with alpha- or beta-diversity. Nineteen taxa were associated with AMD, of which 7 persisted after additional adjustment for dietary data. Eubacterium xylanophilum group, Lachnoclostridium, Faecalibacterium, Odoribacter splanchnicus and Parabacteroides distasonis were associated with an AMD phenotype. Parabacteroides and Akkermansia were inversely associated with an AMD phenotype. Moreover, 46 MetaCyc pathways were associated with AMD, of which 15 persisted after additional adjustment for dietary data. GLUCARDEG.PWY, PWY.5028, PWY.5347, PWY.5415, PWY.5532, PWY.5971, PWY.6969 and TCA were associated with an AMD phenotype. FOLSYN.PWY, LEU.DEG2.PWY, PANTO.PWY, PANTOSYN.PWY, PWY.6612, PWY0.1586 and PYRIDNUCSYN.PWY were inversely associated with an AMD phenotype.

Conclusions: Several gut microbiota were associated with an AMD phenotype. AMD pathophysiology might be linked to changes in gut-related metabolic pathways.

Aims/Purpose: Age-related macular degeneration (AMD), a degenerative disease causing irreversible central vision loss in the elderly, is characterized by dysregulation of the retinal pigment epithelium (RPE). During AMD, stressed RPE releases extracellular vesicles (EVs) carrying bioactive cargo, potentially disrupting the outer blood-retinal barrier (oBRB) and accelerating AMD progression. Mechanisms behind EV-induced oBRB disruption and their role in choroidal neovascularization (CNV) are unclear. Our study aims to assess how RPE-derived EVs under inflammatory conditions impact oBRB integrity and CNV in AMD.

Methods: We used highly polarized primary cultures of porcine RPE (pRPE), porcine eyecups with the RPE exposed, and human umbilical vein endothelial cells (HUVEC). RPE and HUVEC cells were treated with TNF, LPS, or EVs derived from inflamed RPE cells. Additionally, Balb/c mice were intravitreally injected with RPE-derived EVs.

Results: Treatment with TNF or LPS reduced the transepithelial resistance (TER) of pRPE cells monolayer and disrupted the tight junction complexes. Although inflammatory stimuli reduced EVs release from the apical membrane of RPE cells, increased CD63 levels and MMPs levels and activity were found in EVs. Moreover, these EVs led to the disruption of the RPE monolayer. In the Matrigel assay of HUVEC, angiogenesis was induced by both TNF and LPS, and by RPE-derived EVs isolated after the LPS stimulus. At seven days following intravitreal injection, EVs induced outer retinal structural changes in the Balb/c mice.

Conclusions: Our study indicates that EVs released from RPE cells following an inflammatory insult contribute to the oBRB disruption and induce neovascularization, indicating that EVs may play a key role in the onset and progression of AMD.

Support: GOAP, Bayer; FCT, Portugal: 2020.04811.BD (to BM), PEst UIDB/04539/Base/2020 and UIDP/04539/Programatico/2020 through POCI-01-0145-FEDER-007440, CENTRO-01-0145-FEDER-000008: BRAINHEALTH2020

Aims/Purpose: The restoration of accommodation after cataract surgery remains to be one of the biggest challenges in ophthalmology. Numerous concepts for restoration of accommodation have failed due to a lack of objective accommodation measurement. The purpose of this study was to demonstrate the dynamic pseudophakic accommodation in patients with an accommodative AIOL by means of an objective accommodation measurement and to compare the data with a young phakic, a presbyopic and a monofocal pseudophakic person.

Methods: We included 3 patients in the study who had a Lumina AIOL implanted in both eyes. All patients had completed at least the 6 month follow-up. In addition, we included both eyes of 3 comparative persons with different status of the lens (phakic, presbyopic and pseudophakic). We used a binocular open-field videorefractor (PowerRef 3, Plusoptix GmbH, Germany) to measure the change of refraction, pupil diameter and ocular convergence while patients were asked to focus on an ETDRS chart. The ETDRS chart was then continuously moved from 6m distance to 33 cm distance while the patients were asked to focus on a single letter. The resulting curves were then compared to demonstrate the objective change in refraction.

Results: The data exhibit a continuous change of binocular refraction which follows the pupil constriction and decrease of pupil distance (convergence) in the young phakic person and the AIOL patients. The maximum accommodative change was up to 2.5 D in the AIOL patients and up to 3 D in the young phakic person for a stimulus distance of 33 cm. The presbyopic patient and the monofocal pseudophakic patient showed pupil constriction and convergence but the accommodative range was less pronounced with a maximum change of 1 D.

Conclusions: The PowerRef 3 allows for an objective proof of pseudophakic accommodation in patients with an AIOL. AIOL eyes show defined change of refractive power that can be maintained constant for the time of fixation to a near target compared to presbyopic and monofocal pseudophakic eyes that show only little modulation, which can be attributed to pseudo-accommodative effects.

Aims/Purpose: The purpose of this clinical case is to present the symptoms, as well as biomicroscopical, tomographical and histological findings of the isolated corneal intraepithelial neoplasia, a very rare variety of ocular surface squamous neoplasia.

Methods: We present the case of a 78-year-old woman with foreign body sensation in her right eye for four months. The cornea presented, apart from crocodile shagreen, a white patch in the temporal-inferior quadrant, separate from the limbus. This lesion showed punctate staining and contained a thin line of normal aspect. The optical coherence tomography (OCT) showed hyperreflective and thickened epithelium with sudden transition to normal cornea.

On suspicion of corneal intraepithelial neoplasia, excisional biopsy was indicated, with Shields's non-touch technique, 2 mm surgical margins and absolute-alcohol application on the limbus.

Furthermore, a review of the past 25 years literature has been performed, using the following key words: corneal intraepithelial neoplasia; ocular surface squamous neoplasia.

Results: The histological result showed a corneal intraepithelial neoplasia with non-assessable margins. One week after surgery, the defect had already been replaced by normal epithelium, and we added two cycles of co-adjuvant topical mitomycin C (0.04%). Two years after surgery, the patient is asymptomatic and with no signs of recurrence.

Regarding the review, only 10 cases of isolated corneal intraepithelial neoplasia have been described in the past 25 years. No references of crocodile shagreen concurrence have been found, whereas there is some consensus of surgery as main treatment and OCT as useful diagnostic tool.

Conclusions: Isolated corneal intraepithelial neoplasia should always be included in differential diagnosis when it comes to a thickened and atypical lesion in the cornea. In this context, OCT can be useful, whereas final diagnosis and treatment should include excisional biopsy.

Aims/Purpose: Electrical stimulation is not only a suitable method for researching the human nervous system but also for treating neuronal disorders. In ophthalmology, it is applied to patients suffering from various retinal diseases like retinitis pigmentosa. It is known that in the application of direct current stimulation (DCS), the polarity of the current determines the increase or decrease in neuronal activity and enables different therapeutic approaches. However, the polarisation-dependent effect of the current on the vascular processes in the retina has not yet been investigated. This study examined the effect of anodal and cathodal DCS on the temporal vessels of the inner retina.

Methods: The study was conducted on 24 healthy subjects (14w, 10m, mean age 25.5 ± 3.2yr) who were randomly assigned to either an anodal or a cathodal DCS group (symmetrical design). To test the effect of the DCS (800μA; ring-shaped electrode placed surrounding the eye, square electrode placed at the occiput) on vascular regulation, the DCS was combined with visual flicker stimulation using the Dynamic Vessel Analyzer (DVA, Imedos Systems GmbH; standard protocol). Exclusion criteria were ocular and systemic diseases. We investigated two primary vessel segments (superior temporal artery (STa) and vein (STv)) located between 0.5 and 2.0 disc diameters from the optic disc. For each subject the DVA was performed two times (first baseline DVA1, followed by a 20-minute DCS (different polarity depending on the group), and directly afterwards a second DVA2). For statistical analysis, the t-test for paired samples was used and Bonferroni corrected.

Results: The mean vascular responses (STa/STv) for the anodal DCS group were DVA1: 3.7 ± 1.7%/3.4 ± 1.6%; DVA2: 3.5 ± 1.3%/5.4 ± 3.2% and for the cathodal DCS group DVA1: 3.2 ± 2.0%/4.0 ± 2.6%; DVA2: 3.2 ± 1.4%/2.5 ± 1.3%. For the venous vascular response, we found a significant increase after anodal DCS (p = 0.019) and a significant decrease after cathodal DCS (p = 0.018).

Conclusions: We were able to successfully determine the effect of different DCS polarities on the retinal vascular system. We found significant effects on the veins. The absence of effects on the arteries indicates different regulatory pathways in the retina. This should be investigated by further selective stimulation.

Aims/Purpose: This study aims to investigate the intraday and day-to-day variability in the tear fluid proteome to better exploit its potential as a source of non-invasive biomarkers by assessing the consistency of tear protein abundance over time.

Methods: Tear protein composition was monitored in two individuals over three weeks. Tears were collected weekly, both in the morning and in the afternoon, by microcapillary tube sampling. Ultrahigh-resolution shotgun proteomics was used to analyze the tear fluid samples, providing a detailed profile of the tear proteome.

Results: The differential analysis of proteomics data provided a comprehensive overview of the tear fluid proteome. The majority of the identified proteins maintained consistent levels throughout the monitoring period. Specifically, only 25 proteins exhibited significant intraday variation, but no day-to-day fluctuation. These variations were observed in the morning and afternoon samples, indicating that while some proteins may be up- or downregulated within a day, the overall proteome remains largely stable.

The proteins that showed significant variation included those involved in immune response, protein synthesis, and cellular stress response. These findings suggest that while the tear proteome is generally stable, certain proteins may be sensitive to external factors or physiological changes occurring throughout the day.

Conclusions: The stability of the tear proteome indicates its viability for non-invasive diagnostic applications, making it a promising source of biomarkers for personalized medical approaches. The study underscores the need for further research into the temporal variability of tear proteins to fully harness their potential.

Aims/Purpose: Aberrant molecular changes are a major driver of age-related retinopathies. Furthermore, sexual dimorphism is a key variable in disease predilection, although it is not well defined in preclinical studies. Among the potential targets for mitigating age-related proteome modifications attributed to vision impairment, we recently unraveled the protective effects of soluble epoxide hydrolase (sEH/ Ephx2) inhibition in glaucoma. Here, we hypothesized that molecular responses of the aging retina are also sexually divergent in the Ephx2^-/- (KO) mice.

Methods: Retinae were isolated from 160 young (3-5 months) and old (12-24 months) wild type (WT) and KO mice of both sexes. Samples were pooled (n = 5 mice/group/replicate) with 4 biological replicates per group and subjected to robust proteomic and bioinformatic analyses to elucidate the underlying mechanistic changes.

Results: We observed age- and sex-related body weight changes in mice of both sexes, with no significant differences between the WT and KO mice. Proteome profiling showed significant (p < 0.05) differential expression of proteins between the genders, with a significant involvement in the eIF2 and ferroptosis signaling pathways in both sexes. Remarkably, the female sex exhibited striking resilience against ferroptosis, while the male counterpart demonstrated profound activation of this pathway in both WT (p = 4.2×10^-4; z-score: 1.3) and KO mice (p = 4.2×10^-4; z-score: 2). Intriguingly, aged WT females were highly susceptible to retinal diseases (p = 9.6×10^-4) and neurodegeneration (p = 9.9×10^-4), but KO significantly regulated proteins related to synaptogenesis (p = 3.8×10^-2) and neurotransmission (p = 1.7×10^-2). In addition, KO significantly activated neuritogenesis (p = 5.4×10^-5) and cell-cell contact (p = 1.2×10^-3) in both sexes. It is noteworthy that a major upstream transcription regulator, X-box binding protein 1 (XBP1), which is responsible for maintaining protein homeostasis by ameliorating ER stress, was found only in aged male retinae (WT: p = 3.9×10^-4; KO: p = 8.1×10^-3).

Conclusions: Taken together, we showed for the first time a sex-related trend in the proteome of aging KO retina, which is crucial for understanding the pathomechanistic underpinnings of age-related retinal diseases and potential targeted intervention.

Proliferative diabetic retinopathy (PDR) poses as a significant threat to patient's vision if untreated or treated insufficiently. Panretinal photocoagulation (PRP) has long been a mainstay treatment for this condition. The advent of anti-VEGF therapy provided an additional option for the management of this condition. The aim of the presentation is to present the effects of anti VEGF treatment in PDR with special emphasis on the combination: PRP with anti-VEGF therapy. Results of treatment with these modalities, especially regression of neovascularization, together with the incidence of potential complications will be discussed. Additional aspects of such therapy, such as BCVA improvement and central retinal thickness reduction will also be presented. Potential indications for such treatment will be outlined as well as possible treatment schedules for such management.

Regulation of distinct molecular pathways in coordinately developing tissues drives eye development. This process involves factors in signaling, transcription, translation and post-transcriptional control that together determine the proteome of individual cells. Characterizing these regulatory events and their relationships with each other in distinct ocular tissues will lead to the derivation of gene regulatory networks (GRNs) for eye development, which in turn will allow building of the “developmental oculome” (Lachke, Maas (2010) Wiley Interdiscip Rev Syst Biol Med 2(3):305-323 doi: 10.1002/wsbm.59). Toward this goal, we generated and analyzed various omics datasets on developing eye tissues, performed functional characterization of key molecules, and developed a web resource called iSyTE (Anand, Lachke (2017) Exp Eye Res 156:22-33 PMC5026553; Kakrana et al (2018) Nucleic Acids Res 46(D1): D875-D885 doi: 10.1093/nar/gkx837; Lachke (2022) Exp Eye Res 214:108889 PMC8792301). To extract further insights from these omics data, it is necessary to analyze them in the context of experimentally verified data on the eye. These data can be used for training machine learning systems to develop models for eye development. The data used for training represents a an important factor in machine learning systems, i.e. the quality of these data is a key contributor that determines the robustness of the resulting models. There is a wealth of molecular functional (i.e. experimental evidence-based) data on the eye that has been generated by researchers worldwide over the past several decades. These individual regulatory data “nodes” (regulators and targets) – currently “static” in the literature with limited connectivity – hold rich potential to define detailed, and importantly, experimentally validated GRNs that can be used for training machine learning systems. As proof of principle, we have focused on ocular lens development and curated mechanistic data from individual gene perturbation evidences in the mouse from >100 original research articles. This has led to definition of thousands of experimentally validated relationships (edges) between key factors and their targets (nodes) in lens development. These resources serve as strong foundational data for training machine learning systems and represent the essential first step toward advancing our understanding of the natural computing governing eye development, and how its perturbation results in ocular developmental disorders.