Acta Ophthalmologica最新文献

Purpose: We report the case of plateau iris syndrome (PIS) in a middle-aged woman, controlled by medical treatment.

Methods: Case report

Results: A 37-year-old woman, presented to our department with paroxysmal periorbital pain and progressive decline in VA in the left eye.Best corrected VA was 10/10 in both eyes.Anterior chamber(AC) was peripherally shallowed,but normal in the center bilaterally.Intra ocular pressure (IOP) was normal in OD and 38 in OS. C/d ratio was 0.3 in OD,0.4 in OS.On gonioscopy,angle was occludable in OD.In OS,it revealed convex iris,closed angle/360°,opening by indentation with double hump sign.Visual field showed no abnormalities. Bilateral laser peripheral iridotomy (LPI) was performed.Angle depth improved only in OD.The diagnosis of IPS was made.An UBM made revealed a lens volt (LV)measuring 1.11mm with an occludable angle in the OD.In the OS, LV was elevated 1.20mm, the angle was closed with peripheral anterior synechiae.Iridoplasty wasn't done.We discussed the phacoemulsification but as the patient was controlled by medical treatment and hadn't cataract, we opted to treat medically with regular controls.

Conclusions: Although PIS represents a diagnostic trap,based on a cautious anamnesis and a thorough gonioscopy,the accurate diagnosis can be made.Treatment may be challenging in some cases with many considerations.

Aims/Purpose: Corneal storage in organ culture (OC) at 31-34°C is the reference method in Europe. In France, eye banks have traditionally used CorneaMax/CorneaJet media (Eurobio, Les Ulis, France) for several decades. Recently, Tissue-C/Carry-C media (Alchimia-Moria, Antony, France) became available. This study aims at comparing the quality of corneas stored in these two media.

Methods: Eye banks in Saint Etienne and Rouen participated in the study. In Rouen, two experiments were conducted. The first included 18 pairs of corneas, with endothelial cell density (ECD) measured by routine eye bank methods on days -10 and -30 of OC, and 4 days after deswelling. In the second experiment, the protocol for Tissue-C was modified by renewing the medium on day-10. ECD was measured on days -10 and -22 of OC, and 4 days after deswelling. The ECD of 10 pairs of corneas was measured on days -4 and -28 at the Eye Bank of Saint-Etienne. After 2 days of deswelling, the viable ECD was assessed using Hoechst-Calcein-AM staining. Corneal thickness was also measured.

Results: In the first experiment in Rouen, ECD was higher in CorneaMax on day-30 (2202 ± 403 vs 2004 ± 434 cells/mm², p = 0.008) compared to Tissue-C, and higher in CorneaJet after 4 days of deswelling (2088 ± 399 vs 1852 ± 419 cells/mm², p = 0.019) compared to Carry-C. In the second experiment in Rouen, with the medium renewal for Tissue-C and reduced OC duration, the ECD difference disappeared. In Saint Etienne, with medium renewal for Tissue-C during OC, no significant difference in ECD was found during OC. However, the viable ECD of corneas deswelled in CorneaJet was significantly higher than in Carry-C (1647 ± 324 vs 1436 ± 235 cells/mm², p = 0.018).

Conclusions: CorneaMax recommends renewing the medium after the first ECD count, while Tissue-C does not. When following these instructions, CorneaMax showed better ECD results than Tissue-C. However, when the medium for Tissue-C was also renewed during OC, the ECD difference during OC disappeared. The viable ECD indicated that CorneaJet, a deswelling medium was superior to Carry-C. This could be related to the greater thickness of corneas in Tissue-C during OC.

A diverse array of examples wherein genetic diseases presents with clinical manifestations resembling uveitis will be presented. Through compelling case studies and in-depth analysis, we will shed light on how retinal dystrophies can mimic uveitis in their clinical presentation and the key features that can help us in the differential diagnosis of these conditions.

Aims/Purpose: In response to the global shortage of corneas, alternatives such as cell injection therapy and tissue-engineered endothelial keratoplasty (TEEK) have emerged, both relying on the mass production of primary cultured corneal endothelial cells (CECs). Cryopreservation of corneas (the primary cell culture source), cultured CECs (in vitro), and TEEK grafts (final products) is crucial to facilitate their industrialization and clinical application. While corneal cryopreservation has long been a challenge, advancements in cryoprotectants warrant a renewed investigation. This study aims to assess various cryopreservation methods for CECs n the three different states.

Methods: Ten cryopreservation media and varying cooling rates (-2°C/min, -1°C/min, or -0.5°C/min) were first tested on cultured CECs. After thawing, cell survival rates were assessed using Trypan blue staining and an automated cell counter. Subsequently, the best conditions identified for cultured CECs were applied to native CECs adhered to their Descemet's membrane and CECs on TEEKs. Post-thawing viability was assessed using triple labeling with Hoechst, Ethidium, and Calcein-AM (Pipparelli et al. IOVS 2011).

Results: A gradual cooling rate of -1°C per minute and the cryopreservation medium CryoStor CS10 provided the best conditions for in vitro CECs, ensuring an average viability of 91 ± 1% post-cryopreservation. However, applying the same conditions to native CECs on corneas or CECs on TEEK grafts resulted in a viability of less than 80%. Upon thawing, CECs tended to detach easily from the DM or bio-engineered grafts, leading to significant areas without cells.

Conclusions: Cryopreservation is effective for in vitro cultured CECs but remains very challenging for CECs attached to the DM or TEEKs. The next step will be to address cell attachment issues during cryopreservation.

Neurodevelopmental visual disorders (NDVD) are complex conditions that frequently arise from failure of proper embryonic eye formation, thereby directly impacting on the functional organization of the visual areas of the brain and, indirectly, on that of other brain regions. As a consequence, NDVD are heterogeneous in nature with clinical features that often include defects other than the visual ones. Understanding how the eye forms and what does interfere with the acquisition of its characteristic cup shape is thus a prerequisite to understand how NDVD arise. I will discuss our recent studies analyzing the mechanisms that different vertebrate species uses to shape the eye primordium focusing on the role of the retina pigment epithelium (RPE). The vertebrate eye-primordium consists of a pseudostratified neuroepithelium, the optic vesicle, in which cells acquire neural retina or RPE fates. As these fates arise, the optic vesicle assumes a cup-shape, influenced by mechanical forces generated within the neural retina. Whether the RPE passively adapts to retinal changes or actively contributes to optic vesicle morphogenesis remained unexplored. We generated a zebrafish Tg(E1-bhlhe40:GFP) line to track RPE morphogenesis and interrogate its participation in optic vesicle folding. We have shown that, in virtual absence of proliferation, RPE cells stretch and flatten, thereby matching the retinal curvature and promoting optic vesicle folding. Localized interference with the RPE cytoskeleton disrupts tissue stretching and optic vesicle folding. This mechanism differs from that present in amniotes, in which proliferation drives RPE expansion with a much-reduced need of cell flattening. Thus, extreme RPE flattening and accelerated differentiation are efficient solutions adopted by fast-developing species to enable timely optic cup formation. Analysis of transcriptomic dynamics (RNA-seq) and chromatin accessibility (ATAC-seq) in segregating neural retina and RPE populations highlights an early recruitment of desmosomal genes in the flattening RPE, revealing Tead factors as upstream regulators. Investigation of GRNs dynamics uncovers an unexpected sequence of TF recruitment during RPE specification, which is conserved in human-derived organoids, despite mechanistic differences in their RPE expansion. Taking this information together we are now developing hiPSC-derived eye organoids carrying mutations in genes responsible for congenital eye malformations, such as microphthalmia or anophthalmia, to identify which are the morphogenetic events that fail, thereby originating NDVD.

Aniridia is a rare ocular disorder characterized by the hypoplasia or absence of the iris associated with severe visual loss. Two-thirds of cases are generated by mutations in the PAX6 gene and are frequently associated with severe aniridia-associated keratopathy (AAK), which is characterized by pain, persistent epitheliopathy, corneal neovascularization and progressive loss of limbal stem cell function. The pathophysiology of AAK is still unclear; however, leukocyte infiltration and nerve degeneration have been reported. Substance P (SP) is a neuropeptide secreted by nerve fibers, immune and epithelial cells in the cornea and exerts its pro-inflammatory functions by binding to neurokinin-1 receptor (NK1R), promoting nerve activation, leukocyte chemotaxis and extravasation, thus contributing to the inflammatory response. In this context, the modulation of NK1R activation could be used as an innovative therapy to control inflammation and pain associated with AAK.

Our main aim was to quantify the expression of NK1R and SP in the cornea of a PAX 6^+/− mouse model of AAK compared to unaffected animals at different ages. This model express PAX6 gene in heterozygosis and is characterized by iris hypoplasia, abnormal lens morphology, cataracts, corneal opacification, and incomplete separation of lens from the cornea, typical features associated with AAK patients. Corneal samples were collected from mice at different ages, that is 1 month old, 2 months old, 4 months old, and 7 months old, and immunohistochemistry was performed on cross-sections to quantify the expression of SP and NK1R. In the control samples, NK1R decreased over time albeit not significant. The expression level in the PAX6 ^+/− samples was comparable to controls at 1, 4, and 7 months old. However, the expression level of NK1R obtained from 2 months old mice was significantly higher compared not only to 1, 4 and 7 months old PAX6 ^+/− mice but also to all control groups (p < 0.001). The same trend was observed also for SP. Indeed, SP was significantly more expressed in the corneas of 2 months old mice compared to other time points and also to control groups (p < 0.01). These data confirm that the expression of SP goes together with the expression of NK1R during the development of healthy animals. Our data suggest that there may be a window of opportunity for the modulation of SP activity at 2 months of age. Future experiments will be performed in order to investigate the actual efficacy of NK1R blockade for the treatment of AAK.

In this talk, we will discuss who can benefit from simulation-based education, and how it is implemented in a "Best Practice" manner. We will also discuss the role of stake-holders. Real-life examples will be given.

Aims/Purpose: In the last decades, retinal alterations have been shown by OCT in Alzheimer's disease (AD), initially affecting the macular region in early AD, and subsequently progressing to the peripapillary retina, pointing out this tissue to be considered for diagnosis and follow-up in AD. This study aimed to investigate retinal changes in patients with mild cognitive impairment (MCI), an intermediate stage between normal aging and AD, to know if in this preclinical stage there are changes in the retina.

Methods: Sixteen healthy subjects and 16 MCI patients were included. All participants underwent comprehensive ophthalmic evaluation and macular OCT (SD-OCT, Heidelberg, Germany) to assess retinal structure. The thickness of each retinal layer in the macular area was measured using the OCT software, with manual verification and modification of segmentation if necessary. Thicknesses of retinal layers, including retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE), were analyzed. The inner and outer macular rings were evaluated according to the standard macular grid of the Early Treatment Diabetic Retinopathy Study (ETDRS). Statistical analysis was performed using two-way ANOVA with Tukey´s multiple comparison test.

Results: Individuals with MCI exhibited significant thinning in the OPL in the inner ring of the superior sector (p < 0.01), along with significant thickening in the ONL in the same area (p < 0.05) compared to controls. Additionally, a trend towards thinning in the inner retinal layers was observed in the MCI group.

Conclusions: While in the inner retinal layers it was shown a thinning, it is noteworthy that in the ONL it was shown a thickening. OCT holds promise as a non-invasive tool for MCI screening. Further research with larger sample sizes is warranted to validate and expand upon these findings.

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: Glaucoma, a leading cause of irreversible blindness globally, is often associated with elevated intraocular pressure (IOP). However, other risk factors may play a role, particular vascular related parameters. This investigation aimed to explore the association between glaucoma and dyslipidaemia (DL) in participants in a primary care screening pilot. NCT 05875090

Methods: analysis at screening visit comparing the odds of a positive referral between participants with and without DL. Secondary outcomes were medication with statins. Positive referral was defined by IOP≥24mmHg or AI≥0.73. Descriptive and bivariate analyses were used to compare the glaucoma proportions and IOP/AI means between groups. Significance was set at p < 0.05 with 95% confidence intervals (CI).

Results: Data from 839 participants (54% male, 62 ± 4 years) across 11 functional units were analysed. Many had low educational attainment (69%), diabetes (81,1%), hypertension (63,4%), and DL (66,2%). Among participants with DL, 7,38% had glaucoma positive outcome at screening. No difference in glaucoma odds was found between DL and non-DL patients (OR 0.782; CI 0.400-1.528), nor between DL patients medicated with statins compared to those non-medicated (OR 2.083; CI 0.597-7.276). Interestingly, DL may be associated with a positive referral due to high IOP (but not disc damage) when compared to non-DL subjects (OR 0.404; CI 0.155-1.055; p = 0.09), but further analyses with larger samples are needed.

Conclusions: Analysing the association between dyslipidaemia and glaucoma revealed a significant prevalence of DL, with 7,38% meeting positive referral criteria. While the study suggests a potential difference in glaucoma based on IOP between individuals with and without DL, this finding lacks statistical significance. Further analyses, including consideration of confounders and biases, are necessary for confirmation. Continued research and clinical observation are vital for a deeper understanding of this association.