Acta Ophthalmologica最新文献

Mitochondria are vital organelles especially in metabolically active retinal pigment epithelium (RPE) cells but in age-related macular degeneration, they are also a source of factors that increase the cell stress. It is well known that excessive amount of reactive oxygen species (ROS) activate NLRP3, a pattern-recognition receptor capable of forming inflammasomes. Inflammasomes are intracellular protein complexes that can result in the activation of two pro-inflammatory cytokines, IL-1beta and/or IL-18, and promote pyroptotic cell death. We have recently shown that mitochondrial DNA (mtDNA), released to the cytosol upon mitochondrial damage, serves also as an activator for inflammasome pathway in human RPE cells. Its receptor is AIM2 that is specialized to respond to double-stranded DNA. Danger signals from dysfunctional mitochondria can activate both inflammasome types in same cells and thereby further enhance the inflammatory response. Collectively, recent data suggest that aged and dysfunctional mitochondria are a major risk factor that contribute to retinal inflammation by promoting the activation of different types of inflammasomes in human RPE cells.

Purpose: To identify topographic determinants of the anterior chamber angle in a sample of patients with keratoconus.

Methods: Two hundred patients who visited a tertiary eye hospital and were diagnosed with keratoconus, were recruited for this study. First, complete ocular examinations were performed for all patients, including measurement of uncorrected distance visual acuity, objective and subjective refraction, and slit-lamp biomicroscopy. Then, all study participants underwent corneal imaging by the Pentacam rotating Scheimpflug imaging system. The keratoconus was diagnosed based on distorted keratometric mires, scissoring of retinoscopic reflex, abnormal corneal topography (inferior-superior asymmetry, focal or inferior steepening, or a bow-tie pattern with skewed radial axes > 21°) consistent with keratoconus as well as the presence of at least one keratoconus biomicroscopic sign.

Results: The mean age of study participants was 32.40± 8.52 years (15-60 years) and 69.5% of them were male. No statistically significant difference was found in the anterior chamber angle between males and females (p-value = 0.447). There was a statistically significant inverse correlation between anterior chamber angle and age (r = -0.262, p-value < 0.001). The mean anterior chamber angle was significantly different among different groups of cone morphology; patients with nipple cone had the lowest mean anterior chamber angle (p-value = 0.001). Moreover, there was a statistically significant difference in the mean anterior chamber angle among different groups of cone location; the lowest mean anterior chamber angle belonged to patients with central cones (p < 0.001). Anterior and posterior Q-values were significantly directly correlated with anterior chamber angle (anterior Q: r = 0.122, p-value = 0.014, posterior Q: r = 0.192, p-value < 0.001).

Conclusions: Keratoconus patients with nipple and central cones and more negative Q-values were more prone to anterior chamber angle narrowing. It is recommended that the risk of angle closure be taken into account in this group of patients for diagnostic and treatment procedures.

Aims/Purpose: To evaluate the evolution and various clinical presentations of pseudoxanthoma elasticum in three family members.

Methods: Continuous follow-up was conducted in the outpatient ophthalmology clinics at our hospital. Clinical characteristics, including the presence of exudation, neovascular membranes, angioid streaks, and posterior pole atrophy, were documented and analyzed through detailed ophthalmological examinations and imaging tests. Visual acuity was assessed, and autofluorescence imaging was performed. Additionally, optical coherence tomography (OCT) and OCT angiography (OCT-A) were utilized to obtain high-resolution images of the retina and its blood flow.

Results: One daughter presented with exudation accompanied by a neovascular membrane, which was treated with intravitreal anti-VEGF injections. The other daughter maintains good vision and shows angioid streaks in the fundus without macular involvement. The mother is in an advanced stage of the disease, with significant retinoschisis and posterior pole atrophy.

Conclusions: This case study highlights the variability in the presentation and progression of pseudoxanthoma elasticum within the same family. Continuous and personalized follow- up is crucial for the appropriate management and early detection of complications in PXE patients.

Aims/Purpose: To shed light on optic neuritis as a potential ocular complication of Varicella-Zoster virus (VZV) infection.

Methods: Presentation of a clinical case.

Results: We present the case of a 70-year-old woman, who arrived at the Emergency Room complaining of a bilateral acute loss of visual acuity. She had received treatment on several occasions for a recurring zoster involving the left V2 territory, the last episode being one month before her visit. She had a visual acuity of 0.3 on her right eye, and 0.6 on her left eye. Pupil examination evidenced a relative afferent pupillary defect (RAPD) on her right eye. Dyschromatopsia was documented by red desaturation and Ishihara tests. Fundus examination displayed an asymmetrical bilateral papillitis, predominant in her right eye. This finding was confirmed by an Optic Coherence Tomography (OCT). A cranial CT scan and a general blood analysis were performed, and both returned normal results. The patient was admitted to the Hospital to start treatment with intravenous steroids. Additional tests were performed, including blood serological tests, a temporal artery Doppler ultrasound, a cranial MRI, and a lumbar puncture. Blood serological tests showed positive high titles of IgG VZV, and came back negative for IgM VZV. Lastly, the polymerase chain reaction (PCR) test on the CSF sample turned out positive for VZV, shedding light on the diagnosis. Steroids were suspended and the patient was started on intravenous Acyclovir. Clinical evolution was favorable, and her visual acuity on the 2-month follow-up visit had climbed up to 0.6 on her right eye and 0.7 on her left eye.

Conclusions: This case illustrates the relevance of ruling out infectious causes of optic neuritis, specifically VZV, in patients in which other causes are less likely, those who present a bad evolution on inflammatory treatment, or who have a recent episode of VZV infection. MRI demyelination is a frequent finding in both demyelinating and infectious diseases, therefore not ruling out the latter. Positive blood serology indicates previous contact with VZV, but has little sensibility for detecting an active infection. All these reasons justify the need to select patient who may benefit of a lumbar puncture, as an early diagnosis radically changes the therapeutical approach.

Aims/Purpose: To compare measurements of circumpapillary Retinal Nerve Fiber Layer Thickness (cpRNFLT) and Pigment epithelium central limit Inner limit of the retina Minimal Distance (PIMD), respectively, between healthy and glaucoma eyes with regard to angular distribution of the measurements in the frontal plane and the variation coefficients for measurements of cpRNFLT-2π and PIMD-2π.

Methods: 17 eyes without ocular pathology and 7 with glaucoma, each from a different subject, were included. In each eye, the ONH was captured in 3 iterated volumes at one occasion with the OCT-Triton (Topcon, Japan). In each volume, the nerve fiber layer thickness was resolved in 12 frontal plane clock hrs as cpRNFLT with the Topcon software, and as PIMD with an automatic custom-made software. Finally, the 12 clock hrs were averaged and the inter-volume errors were determined with ANOVA for comparison of variation coefficients (CV:s) between cpRNFLT-2π and PIMD-2π.

Results: PIMD-2π was approximately 3 times higher than cpRNFLT-2π in the healthy eyes and 2.5 times higher in the glaucoma eyes. In both groups, PIMD peaked superiorly and inferiorly, slightly shifted nasally, and cpRNFLT peaked superiorly and inferiorly, slightly shifted temporally. The CV for iterated measurements at the same occasion was slightly higher for PIMD-2π than for cpRNFLT-2π in the healthy eyes, and of the same order for PIMD-2π and cpRNFLT-2π in the glaucoma eyes.

Conclusions: PIMD-2π and cpRNFLT-2π were lower in glaucoma- than in healthy eyes, probably due to less ganglion cell axons. PIMD-2π was generally 2.5-3 times higher than cpRNFLT-2π. The CV:s were on the order of 1.5-2.5 x10^-2 for both healthy- and glaucoma eyes and both quantities measured. Thus, averages of 3 volumes at each occasion is sufficient for comparison of measurements among occasions within subjects.

Aims/Purpose: To study the influence of strain on the expression of specific proteins in human keratocytes and its consequential effects on keratocyte intracellular redox homeostasis and behavior.

Methods: Strain was applied to human keratocytes using the Flexcell® Tension Systems. Proteomics and western blot were used to identify proteins regulated in response to strain. Immunofluorescence (IF) staining and live-cell imaging were employed to monitor reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨM). Expression of oxidative stress-related protein, and its influence on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation and keratocyte proliferation and migration, were assessed by western blot, IF staining and bromodeoxyuridine (BrdU) assay. Mouse injury models and keratocytes from keratoconus patients were used to assess how strain (intraocular pressure, IOP) influences downstream protein in vivo.

Results: The expression of protein Cytochrome P450 1B1 (CYP1B1) and Aldehyde Dehydrogenase 3 Family Member A1 (ALDH3A1) was significantly upregulated in strained keratocytes. Increased CYP1B1 effectively suppressed H₂O₂-induced ROS production and mitigated the dissipation of ΔΨM. ALDH3A1 expression was negatively related to ROS accumulation. When the expression of ALDH3A1 was knocked down, NF-κB nuclear translocation was promoted, ultimately resulting in increased keratocyte proliferation and migration. Mice and keratoconus patients with increased corneal strain also showed elevated ALDH3A1.

Conclusions: Corneal strain significantly upregulates the expression of CYP1B1 and ALDH3A1. Increased CYP1B1 helps maintain keratocyte intracellular redox homeostasis and subsequently regulates keratocyte proliferation and migration via ALDH3A1.

Aims/Purpose: In a randomized trial of dry eye disease (DED) associated with meibomian gland dysfunction (MGD), patients received either perfluorohexyloctane eye drops (n = 156) or sodium chloride (NaCl) solution (n = 156) four times daily. The trial showed that perfluorohexyloctane significantly improved DED signs and symptoms with rapid efficacy and satisfactory safety compared to NaCl. This post hoc analysis evaluated efficacy in subgroups based on signs and symptoms, specifically discordant signs and symptoms.

Methods: Patients were grouped according to median changes in total corneal fluorescein staining (tCFS), eye dryness score (EDS), and ocular surface disease index (OSDI) between baseline and day 57 after treatment. Responses at day 57 were defined as: tCFS Response, decrease of ≥ 3 points from baseline; EDS Response, reduction of ≥ 30% from baseline; OSDI Response, reduction of ≥ 30% from baseline.

Results: In the tCFS ≤ 6 & EDS ≥ 60 group, the tCFS & EDS Response was 52.7% (29 patients) with perfluorohexyloctane vs. 28.4% (19) with NaCl (OR 95% CI: 2.82, 1.33–5.96, p = 0.0068). In the tCFS > 6 & EDS ≥ 60 group, the tCFS & EDS Response was 72.1% (31) vs. 36.6% (15) (OR 95% CI: 4.48, 1.78–11.25, p = 0.0014). In the tCFS ≤ 6 & OSDI ≥ 60 group, the tCFS & OSDI Response was 61.4% (27) vs. 28.2% (11) (OR 95% CI: 4.58, 1.79–11.74, p = 0.0015). In the tCFS > 6 & OSDI < 60 group, the tCFS & OSDI Response was 72.2% (26) vs. 42.9% (15) (OR 95% CI: 3.47, 1.29–9.33, p = 0.0138).

Conclusions: The post hoc analysis showed that perfluorohexyloctane eye drops significantly improved DED symptoms and signs in subgroups where symptoms and signs were discordant, such as those with tCFS ≤ 6 & EDS ≥ 60, tCFS ≤ 6 & OSDI ≥ 60, and tCFS > 6 & OSDI < 60, as well as in cases where both symptoms and signs were more severe, such as tCFS > 6 & EDS ≥ 60.

Purpose: Fuchs endothelial corneal dystrophy (FEDC) is by far the most common corneal endothelial diseases in Western countries, and 50% of keratoplasties are carried out to treat endothelial diseases. New treatments are also emerging (Descemetorhexis only, rock-inhibitors, mTor-inhibitors, FGF-1). It will therefore soon be vital to be able to determine the stage of each patient in a simple and reliable way, in order to personalize treatment. Visual acuity, retroillumination, specular microscopy and thickness mapping are the 4 pillars of the examination. However, current retro-illumination images are of insufficient quality. Aim: to present the first series of FECD observed using new-generation retroillumination.

Methods: We developed a prototype retroilluminator by modifying a slit lamp with the aim of obtaining high-resolution images, without parasitic reflection and without dazzling the patient. We then prospectively photographed 200 FECD patients. The images were then classified by 3 independent observers according to the modified Krachmer classification, which is the most widely used in the literature: it distinguishes patients according to the number of Guttae, the size of the area of confluent Guttae and the presence of oedema.

Results: The prototype produced clear, glare-free images in over 95% of cases. Persistent reflections were observed exclusively in pseudophakic patients. The high resolution made it possible to observe all the Guttae and to challenge Krachmer's grade 2 classification (more than 12 non-confluent drops), which included a major diversity of patients, some of whom had thousands of non-confluent Guttae. We also highlighted for the first time to our knowledge 2 new elements: the high frequency of radial alignment of Guttae, often over 360°, and the presence of Guttae in the periphery of the endothelium, suggesting that a cell migration anomaly is involved.

Conclusions: Innovative retroillumination images challenge Krachmer's classification by providing exceptional precision. They will make it easier to distinguish between sub-groups of patients with different visual repercussions and evolutionary profiles. Easy to use, this new device should help to improve both our understanding of FECD and its routine management.

Aims/Purpose: Dry eye syndrome (DES) is a multifactorial pathology of the ocular surface, characterized by disruption of tear film homeostasis. Although prevalent, distinct clinical biomarkers associated with the impairment of the lacrimal (LG) and meibomian glands (MG) that exacerbate the progression of DES are still largely lacking. This study was conducted to identify potential DES markers for precise clinical diagnosis.

Methods: Subjects underwent a battery of clinical examinations including the basic secretory test via Schirmer I to evaluate the functional impairment of the LG that leads to aqueous-deficient DES (DRYaq). Meanwhile, tear break-up time (TBUT) test was used to evaluate the impairment status of the MG, which leads to evaporative DES (DRYlip). Next, the tear samples (N = 307) were analyzed individually employing mass spectrometry-based proteomics, followed by in-depth statistical and bioinformatics analyses.

Results: A total of 47 proteins, largely secreted by the LG and annotated to antibacterial response (p = 5.0 × 10^-9) were found to be significantly (p < 0.01) decreased in abundance with the progression of DRYaq, namely LTF (r = -0.79), PROL1 (r = -0.64) and AZGP1 (r = -0.58). On the contrary, as many as 360 proteins were found to be significantly increased in abundance with the progression of DRYaq, namely SFN (r = +0.68), ORM2 (r = +0.67) and TXN (r = +0.66). These proteins are annotated to various biological functions, especially inflammatory response (p = 3.0 × 10^-17), apoptosis (p = 2.1 × 10^-29) and synthesis of reactive oxygen species (p = 3.7 × 10^-29). Only 26 proteins were found to be significantly expressed with the progression of DRYlip, namely ACTN2 (r = -0.33) and ARG1 (r = +0.48). These proteins are exclusively annotated to anti-inflammatory response (p = 8.1 × 10^-5), citrulline biosynthesis (p = 4.5 × 10^-3) and IL-15 signaling (p = 2.5 × 10^-4).

Conclusions: For the first time, our study analyzed the proteome of the largest number of individual tear samples in a clinical setting. Importantly, we identified progressive changes in the expression of specific protein markers correlated to the functionality of the LG and MG that could be potentially leveraged for future development of improved clinical diagnosis and targeted therapeutic interventions to ameliorate DES in a personalized manner.

Aims/Purpose: Retinal oxygen extraction has been found to be altered in several ocular and systemic diseases, such as diabetic retinopathy, glaucoma or neurodegenerative diseases. However, measurement techniques for the assessment of retinal oxygen extraction are limited because most of them are based on time-consuming and custom-built devices. In the present pilot study, we assessed retinal oxygen extraction during systemic hypoxia with a combination of two commercially available devices: Laser-Speckle Flowgraphy (LSFG) and retinal oximetry.

Methods: Retinal blood flow and retinal oxygen saturation were measured in each vessel around the optic nerve head at the same position. Arterial and venous oxygen content was estimated from the measured retinal oxygen saturation parameters and the difference between these two parameters was calculated (cO₂,_DIFF). By using mean vessel flow rate (MV) for retinal blood flow and cO₂,_DIFF, retinal oxygen extraction was determined. For each healthy study participant, baseline measurement and measurement during inhalation of 88% nitrogen in 12% oxygen were performed.

Results: Ten (10) healthy subjects (4 females, 6 males) with a mean age of 27 ± 3 years were included in this study. During systemic hypoxia, a significant decrease in arterial oxygen content occurred (p = 0.046) while venous oxygen content did not change, leading to a decrease in cO₂,_DIFF. As expected, this was accompanied by a significant increase in MV (p = 0.014). No change in retinal oxygen extraction was observed (46 ± 8 a.u. at baseline vs. 46 ± 5 a.u. during hypoxia, p = 0.997).

Conclusions: Breathing of 88% nitrogen in 12% oxygen caused a significant decrease in retinal arterial oxygen content. This was compensated by an increase in retinal blood flow in order to keep retinal oxygen extraction constant. This was physiologically expected, and these findings are consistent with the literature. Therefore, the presented approach for measurement of retinal oxygen extraction appears to be feasible.