Intermediate-term impact on corneal endothelial cells and efficacy of Preserflo MicroShunt implantation in patients with open-angle glaucoma - a prospective study over two years.

INTRODUCTION: Preserflo MicroShunt is a novel microinvasive bleb forming device for the treatment of primary open-angle glaucoma. The intermediate- and long-term success and the impact of this procedure on corneal endothelial cell density remain to be investigated. METHODS: In this prospective observational study, 62 eyes of 55 glaucoma patients (mean age ± SD: 67.0 ± 15.0 years) receiving a Preserflo MicroShunt were included. Corneal endothelial cell density, intraocular pressure and best corrected visual acuity were assessed preoperatively and at 3, 6, 9, 12, 18 and 24 months postoperatively. Success rates, bleb revision rates and complications were analysed. Complete success was defined as an intraocular pressure reduction of ≥ 20% and achieving a target pressure of ≤ 18, ≤ 15 or ≤ 12 mmHg without antiglaucoma medication. Qualified success indicated that the criteria were reached with or without medication. RESULTS: Corneal endothelial cells showed no significant decline over 24 months (p > 0.05). Intraocular pressure showed a substantial reduction postoperatively (p < 0.001), decreasing from 29.6 ± 8,3 mmHg to 13.0 ± 4.3 mmHg after 24 months (p < 0.001). Complete and qualified success with a target pressure ≤ 15 mmHg was achieved in 52.9% and 54.6% of cases after 24 months, respectively. Best corrected visual acuity did not change after 24 months. CONCLUSION: Preserflo MicroShunt had no negative side effects on corneal endothelial cells and showed favourable success rates after 2 years in patients with open-angle glaucoma.

A COMPARATIVE ANALYSIS OF TRAUMATIC RETINAL DETACHMENT AFTER OPEN AND CLOSED GLOBE INJURIES IN CHILDREN.

PURPOSE: Pediatric traumatic retinal detachment (RD) resulting from open globe injuries (OGIs) or closed globe injuries (CGIs) presents unique challenges due to complexity often resulting in lifelong sequelae. This study compares pediatric traumatic RD outcomes and prognostic factors following OGI and CGI. METHODS: A retrospective analysis reviewed 47 cases of pediatric traumatic RD in children (age <18 years), who underwent RD surgery between 2002 and 2021. Among them, 25 cases were caused by CGI and 22 cases by OGI. Demographics, RD characteristics, surgical procedures, and anatomical and functional results were assessed. Predictive factors for visual outcomes were investigated. RESULTS: In the CGI group, mean (±SD) age was 11 years ± 4 years, and 10 years ± 5 years in the OGI group. Closed globe injury traumatic RD had significantly better preoperative (CGI: logarithm of the minimum angle of resolution 1.39 ± 0.19 (mean ± standard error); OGI: logarithm of the minimum angle of resolution 2.12 ± 0.20) and follow-up (CGI: logarithm of the minimum angle of resolution 0.94 ± 0.19; OGI: logarithm of the minimum angle of resolution 1.85 ± 0.20) best-corrected visual acuity (BCVA) ( P < 0.05). Initial BCVA improvement was observed in CGI only. In multivariable analysis, prognostic factors for favorable BCVA outcomes included higher preoperative BCVA, older age, and absence of proliferative vitreoretinopathy ( P < 0.05). CONCLUSION: Visual prognosis for pediatric traumatic RD remains limited, favoring CGI cases compared with OGI. Baseline BCVA emerged as a major determinant of final visual acuity. Tailored management approaches can optimize treatment results.

Comparing the quality of ChatGPT- and physician-generated responses to patients' dermatology questions in the electronic medical record.

BACKGROUND: ChatGPT is a free artificial intelligence (AI)-based natural language processing tool that generates complex responses to inputs from users. OBJECTIVES: To determine whether ChatGPT is able to generate high-quality responses to patient-submitted questions in the patient portal. METHODS: Patient-submitted questions and the corresponding responses from their dermatology physician were extracted from the electronic medical record for analysis. The questions were input into ChatGPT (version 3.5) and the outputs extracted for analysis, with manual removal of verbiage pertaining to ChatGPT's inability to provide medical advice. Ten blinded reviewers (seven physicians and three nonphysicians) rated and selected their preference in terms of 'overall quality', 'readability', 'accuracy', 'thoroughness' and 'level of empathy' of the physician- and ChatGPT-generated responses. RESULTS: Thirty-one messages and responses were analysed. Physician-generated responses were vastly preferred over the ChatGPT -responses by the physician and nonphysician reviewers and received significantly higher ratings for 'readability' and 'level of empathy'. CONCLUSIONS: The results of this study suggest that physician-generated responses to patients' portal messages are still preferred over ChatGPT, but generative AI tools may be helpful in generating the first drafts of responses and providing information on education resources for patients.

Comparative glycoproteomics of stem cells identifies new players in ricin toxicity.

Glycosylation, the covalent attachment of carbohydrate structures onto proteins, is the most abundant post-translational modification. Over 50% of human proteins are glycosylated, which alters their activities in diverse fundamental biological processes. Despite the importance of glycosylation in biology, the identification and functional validation of complex glycoproteins has remained largely unexplored. Here we develop a novel quantitative approach to identify intact glycopeptides from comparative proteomic data sets, allowing us not only to infer complex glycan structures but also to directly map them to sites within the associated proteins at the proteome scale. We apply this method to human and mouse embryonic stem cells to illuminate the stem cell glycoproteome. This analysis nearly doubles the number of experimentally confirmed glycoproteins, identifies previously unknown glycosylation sites and multiple glycosylated stemness factors, and uncovers evolutionarily conserved as well as species-specific glycoproteins in embryonic stem cells. The specificity of our method is confirmed using sister stem cells carrying repairable mutations in enzymes required for fucosylation, Fut9 and Slc35c1. Ablation of fucosylation confers resistance to the bioweapon ricin, and we discover proteins that carry a fucosylation-dependent sugar code for ricin toxicity. Mutations disrupting a subset of these proteins render cells ricin resistant, revealing new players that orchestrate ricin toxicity. Our comparative glycoproteomics platform, SugarQb, enables genome-wide insights into protein glycosylation and glycan modifications in complex biological systems.

Effect of elevated irrigation bottle height during cataract surgery on corneal endothelial cells in porcine eyes.

BACKGROUND: Cataract surgery induces corneal endothelial cell loss (ECL). This study investigates the relationship between bottle height (BH) and ECL induced due to irrigation and aspiration (I/A) in cataract surgery and quantifies protective effects of intraoperatively used ophthalmic viscoelastic substances. METHODS: Intermittent I/A without phacoemulsification was performed in porcine eyes for 10 min with varying BHs of 100 cm (BH100), 125 cm (BH125), 150 cm (BH150) or no treatment (control, no I/A). Additionally, in one group a dispersive ophthalmic viscoelastic substance was injected into the anterior eye chamber before treatment with I/A at a BH of 150 cm (BH150 + V). After exposure of the corneal endothelium to I/A, the corneas were prepared to split corneal buttons on day 0 and cultivated for 15 days. Endothelial cell density (ECD) was analyzed blinded on days 1, 8 and 15. RESULTS: Relative ECL significantly correlated with irrigation BH (control (n = 13): -9.69 ± 6.03% (average ± standard deviation); BH100 (n = 12): -9.69 ± 4.81%-p = 1.000; BH125 (n = 14): -19.44 ± 7.30% - p < 0.001; BH150 (n = 13): -21.99 ± 6.70%-p < 0.001). I/A-induced ECL was significantly decreased by the injection of ophthalmic viscoelastic, as BH150 + V (n = 14; -10.92 ± 4.09%-p = 1.000) showed a cell loss comparable to the control group. CONCLUSIONS: ECL is altered by I/A BH and reduced when viscoelastic substances are used.

[Optical coherence tomography in the differential diagnostics of important neuro-ophthalmological disease patterns]. / Die optische Kohärenztomographie in der Differenzialdiagnostik wichtiger neuroophthalmologischer Krankheitsbilder.

There are many disease patterns that are treated jointly by neurologists and ophthalmologists, for which optical coherence tomography (OCT) is of important differential diagnostic significance. In this context neurologists are mainly confronted by two patient collectives: patients with an acute ischemic event, who present with an acute but painless monocular visual deterioration (for central retinal artery occlusion) or with a monocular visual field defect (for arterial branch occlusion or anterior ischemic optic neuropathy). The second collective is patients without ophthalmological symptoms but with conspicuous optic nerve findings (papilledema or optic disc drusen). In this overview article both patient collectives are considered separately. In addition, the most important OCT findings for optic neuritis are presented. Before the disease patterns are described in detail, the normal OCT findings and the diagnostic possibilities of OCT are explained.

The histone chaperone CAF-1 safeguards somatic cell identity.

Cellular differentiation involves profound remodelling of chromatic landscapes, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNA interference (RNAi) screens targeting chromatin factors during transcription-factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPS cells). Subunits of the chromatin assembly factor-1 (CAF-1) complex, including Chaf1a and Chaf1b, emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Optimal modulation of both CAF-1 and transcription factor levels increased reprogramming efficiency by several orders of magnitude and facilitated iPS cell formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 to be a novel regulator of somatic cell identity during transcription-factor-induced cell-fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting.

Localized bullous pemphigoid after knee replacement surgery.

Bullous pemphigoid (BP) most commonly presents as widespread, itchy, tense blisters in older patients. Localized bullous pemphigoid is a less common form of BP that can be more difficult to diagnose because of its similarity to more common conditions such as allergic contact dermatitis or bullous cellulitis. Prompt recognition of localized BP is important so that appropriate treatment can be started. We present a 57-year-old woman who presented with pruritic tense bullae overlying the surgical scar from a knee replacement 6 months prior on her anterior right knee. This case illustrates the potential for localized BP to be triggered by surgical procedures.

Cerebral organoids model human brain development and microcephaly.

The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.

Staining of endothelial cells does not change the result of cell density.

To determine the corneal endothelial cell density human donor corneas are usually placed in hypotonic balanced salt solution for unstained cell counting. Experimental studies often stain the corneal endothelium to highlight cells and cell borders and simplify counting. However, staining normally terminates the experiments. Up to date, there is no publication comparing endothelial cell counts before and after staining. This study compared the counting results of unstained (hypotonic balanced salt solution) and stained (trypan blue & alizarin red S) assessment of the corneal endothelial cell density. No evidence for significantly differing cell counts was found between unstained and stained analysis of the corneal endothelial cell density. Therefore, we consider unstained counting non-inferior to stained counting.

Establishment of a porcine corneal endothelial organ culture model for research purposes.

Human corneas usually are not available for research, as they are used for transplantation only. At the same time, scientific studies on cultured human endothelial cells can produce misleading results due to inevitable dedifferentiation. Therefore, an organ-culture model of porcine corneas-displaying endothelial cell death rates comparable to those of cultured human corneas-would be very desirable. Fresh pig eyes were prepared under sterile conditions to obtain corneoscleral buttons, corneal buttons and so called "split corneal buttons" (new preparation method) and cultivated for 15 days. Morphology of the endothelial cell layer was observed by light microscopy on day 1, 8 and 15. On day 15 staining with trypan blue and alizarin red S was performed. Photographs were evaluated in a randomized, blinded manner. Here, the morphology of the corneal endothelium and the number of endothelial cells per mm2 were analyzed. After 15 days of cultivation the endothelial cell layer was maintained only in corneal buttons and split corneal buttons. Alizarin red S stained areas and the existence of polymorphisms like rosette figures and reformation figures were significantly less frequent in split corneal buttons than in corneal buttons. Loss of endothelial cells was significantly greater in corneal buttons [575 ± 25/250 cells/mm2 (median ± 25%/75%-quantile); 14.8%] than in split corneal buttons [417 ± 138/179 cells/mm2 (median ± 25%/75%-quantile); 10.2%]. The new preparation method of split corneal buttons allows the cultivation of porcine corneas for 2 weeks with cell death rates comparable to those of the corresponding human tissue in cornea banks without the need to add de-swelling additives to the media. This is therefore a simple and highly reliable method model to be applied in intervention studies on corneal endothelial cells in their natural compound.

Imprinted expression in cystic embryoid bodies shows an embryonic and not an extra-embryonic pattern.

A large subset of mammalian imprinted genes show extra-embryonic lineage (EXEL) specific imprinted expression that is restricted to placental trophectoderm lineages and to visceral yolk sac endoderm (ysE). Isolated ysE provides a homogenous in vivo model of a mid-gestation extra-embryonic tissue to examine the mechanism of EXEL-specific imprinted gene silencing, but an in vitro model of ysE to facilitate more rapid and cost-effective experiments is not available. Reports indicate that ES cells differentiated into cystic embryoid bodies (EBs) contain ysE, so here we investigate if cystic EBs model ysE imprinted expression. The imprinted expression pattern of cystic EBs is shown to resemble fetal liver and not ysE. To investigate the reason for this we characterized the methylome and transcriptome of cystic EBs in comparison to fetal liver and ysE, by whole genome bisulphite sequencing and RNA-seq. Cystic EBs show a fetal liver pattern of global hypermethylation and low expression of repeats, while ysE shows global hypomethylation and high expression of IAPEz retroviral repeats, as reported for placenta. Transcriptome analysis confirmed that cystic EBs are more similar to fetal liver than ysE and express markers of early embryonic endoderm. Genome-wide analysis shows that ysE shares epigenetic and repeat expression features with placenta. Contrary to previous reports, we show that cystic EBs do not contain ysE, but are more similar to the embryonic endoderm of fetal liver. This explains why cystic EBs reproduce the imprinted expression seen in the embryo but not that seen in the ysE.

XEN45 gel stent in the treatment of pigmentary glaucoma: A two-year follow-up.

PURPOSE: To investigate safety and efficacy of the XEN gel stent in patients with pigmentary glaucoma (PG). METHODS: A retrospective analysis of 26 eyes of 19 patients with PG undergoing XEN gel stent implantation was performed. Best-corrected visual acuity, intraocular pressure (IOP), and number of antiglaucoma medications were analyzed preoperatively, and at 2 weeks and 3, 6, 12, and 24 months after surgery. Success, needling, and complications were analyzed. Complete success was defined as an IOP reduction of >20% and achieving a target IOP of ≤18, ≤15, or ≤12 mmHg without antiglaucoma medication. Qualified success was indicated if the IOP target was reached with or without medication. RESULTS: Mean IOP decreased significantly from 27.6 ± 14.3 (standard deviation, SD) mmHg to 14.3 ± 4.6 mmHg after one year (p < 0.001) and 15.1 ± 2.7 mmHg (p < 0.001) after two years. The median number of hypotensive drugs declined significantly from 4 (range: 3-5) to 0 (0-2) and 0 (0-3) after one and two years, respectively. After two years, complete success with an IOP of ≤18 mmHg and ≤15 mmHg was achieved in 73.1% and 61.5%, respectively. Half of the eyes required needling after a median time of 8 months (0.5-34 months). No sight-threatening complications were observed. CONCLUSION: The XEN gel stent is a safe and effective surgical treatment option for PG. Needling is an important part of the procedure and should be communicated preoperatively to the patients.

Two-Year Results of XEN Gel Stent Implantation for Pseudoexfoliative Glaucoma in Phakic versus Pseudophakic Eyes.

Objectives: To investigate whether phakia affects the outcome of XEN-45 gel stent implantation in the treatment of pseudoexfoliative glaucoma (PXG). Methods: A retrospective, comparative cohort study of 30 phakic and 55 pseudophakic PXG patients who received the XEN-45 gel stent at a tertiary centre. The primary outcome measure was two-year success defined as a ≥20% lowering of intraocular pressure (IOP) and a target IOP of 6-21 mmHg. Success was complete without and qualified irrespective of antiglaucoma medication use. Further glaucoma surgery other than needling was regarded as a failure. The secondary outcome measures included changes in IOP, revision and complication rates. Results: The complete two-year success rates were 70% and 59% in the phakic and pseudophakic groups, respectively (p = 0.75, log-rank test), and the qualified rates were 80% and 72%, respectively (p = 0.89). The median IOP reduction from baseline was 54% in phakic, and 46% in pseudophakic eyes. While needling rates were similar, the incidence of early incisional bleb revisions was significantly higher in the phakic eyes (13% vs. 0% within 3 months; p = 0.0098, chi-square). Increasing after a year, significantly more pseudophakic eyes failed due to secondary glaucoma surgery (16% vs. 0%; p = 0.0191). Conclusions: The XEN-45 gel stent offers equally effective IOP control for both phakic and pseudophakic patients. However, the onset of bleb revisions and the necessity for secondary glaucoma surgery differed significantly between the groups.

Incidence of central retinal artery occlusion peaks in winter season.

Introduction: Stroke incidence exhibits seasonal trends, with the highest occurrences observed during winter. This study investigates the incidence of central retinal artery occlusion (CRAO), a stroke equivalent of the retina, and explores its monthly and seasonal variations, as well as potential associations with weather and ambient air pollutants. Methods: A retrospective search of medical records spanning 15 years (January 2008-December 2022) was conducted at the University Eye Hospital Tübingen, Germany, focusing on diagnosed cases of CRAO. Incidences were evaluated on a monthly and seasonal basis (winter, spring, summer, fall). Weather data (temperature, precipitation, atmospheric pressure) and concentrations of ambient air pollutants [fine particulate matter (PM2.5), coarse particulate matter (PM10), nitrogen dioxide (NO2), and ozone (O3)], were analyzed for a potential association with CRAO incidence. Results: Out of 432 patients diagnosed with CRAO between 2008 and 2022, significantly varying incidences were observed monthly (p = 0.025) and seasonally (p = 0.008). The highest rates were recorded in February and winter, with the lowest rates in June and summer. Concentrations of NO2, PM2.5 and lower ambient air temperature (average, minimum, maximum) showed significant correlations with CRAO incidence. Discussion: This comprehensive 15-year analysis reveals a pronounced winter peak in CRAO incidence, with the lowest occurrences in summer. Potential associations between CRAO incidence and ambient air pollutants and temperature underscore the importance of considering seasonal trends and call for further investigations to elucidate contributing factors, potentially leading to targeted preventive strategies and public health interventions.

Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial.

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. AIMS: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. METHODS: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

[Optical coherence tomography in the differential diagnostics of important neuro-ophthalmological disease patterns]. / Die optische Kohärenztomographie in der Differenzialdiagnostik wichtiger neuroophthalmologischer Krankheitsbilder.

There are many disease patterns that are treated jointly by neurologists and ophthalmologists, for which optical coherence tomography (OCT) is of important differential diagnostic significance. In this context neurologists are mainly confronted by two patient collectives: patients with an acute ischemic event, who present with an acute but painless monocular visual deterioration (for central retinal artery occlusion) or with a monocular visual field defect (for arterial branch occlusion or anterior ischemic optic neuropathy). The second collective is patients without ophthalmological symptoms but with conspicuous optic nerve findings (papilledema or optic disc drusen). In this overview article both patient collectives are considered separately. In addition, the most important OCT findings for optic neuritis are presented. Before the disease patterns are described in detail, the normal OCT findings and the diagnostic possibilities of OCT are explained.

Inner Retinal Layer Hyperreflectivity Is an Early Biomarker for Acute Central Retinal Artery Occlusion.

Purpose: To investigate inner retinal hyperreflectivity on optical coherence tomography (OCT) as a potential biomarker indicating acute central retinal artery occlusion (CRAO). Methods: A total of 56 patients at two university hospitals with acute CRAO (symptom onset ≤48 h) were included in this retrospective study. The optical intensity of the inner retinal layers was determined in both eyes and the relationship between symptom onset and inner retinal layer optical intensity in OCT scans compared to the unaffected fellow eye was analyzed. Several differential diagnoses [central retinal vein occlusion, anterior ischemic optic neuropathy, diabetic macular edema, and subretinal fibrosis/disciform scar (Junius-Kuhnt)] served as controls to validate optical intensity-based diagnosis of CRAO. Results: CRAO strongly correlated with an increased inner retinal layer hyperreflectivity in this cohort with acute CRAO with a time since symptom onset ranging from 1.1 to 48.0 h. Receiver operating characteristic (ROC) analysis showed an area under the curve of 0.99 to confirm CRAO with a true positive rate of 0.93 and a false positive rate of 0.02. No correlation between optical intensity and time since symptom onset was noticeable. None of the differential diagnoses did show an elevated optical intensity of the inner retinal layers as it was detectable in CRAO. Conclusion: OCT-based determination of inner retinal layer hyperreflectivity is a very promising biomarker for a prompt diagnosis of CRAO in an emergency setting. This may be of major interest to speed up the administration of a possible thrombolytic treatment.

[Acute diagnostics of central retinal artery occlusion and biomarkers of ischemia : Diagnostics with consequences?] / Akutdiagnostik des retinalen Zentralarterienverschlusses und Biomarker der Ischämie : Diagnostik mit Konsequenzen?

BACKGROUND: Acute central retinal artery occlusion (CRAO) represents an ophthalmological emergency with neurological implications, which must be immediately investigated and treated. Intravenous thrombolysis could improve the prognosis only within the first 4.5 h due to limited retinal tolerance to ischemia. Accordingly, ophthalmological acute diagnostics should be reduced to the minimum necessary followed by immediate referral to a clinic with neurovascular expertise. The typical anamnesis is well-suited for triaging and should be carried out ín a standardized way in order to determine the onset of symptoms as exactly as possible. In addition to pathognomic findings in fundoscopy, there are characteristic ischemia-related changes in optical coherence tomography (OCT), which document ischemia in the inner retina and under some circumstances can provide inferences for the onset of ischemia. OBJECTIVE: This review article summarizes the acute ophthalmological diagnostic management of acute CRAO with a focus on the typical OCT and transorbital ultrasound (TOUS) findings and discusses their potential use as ischemic biomarkers. CONCLUSION: Characteristic biomarkers make OCT an important diagnostic tool in the management of acute CRAO. Additional information can be obtained by TOUS. With an evidence-based treatment established in the future both tools could be used for indications for treatment and for estimating the prognosis.

Optical coherence tomography-based determination of ischaemia onset - the temporal dynamics of retinal thickness increase in acute central retinal artery occlusion.

PURPOSE: Acute central retinal artery occlusion (CRAO) induces ischaemic retinal oedema. The purpose of this study was to define sensitivity and specificity of optical coherence tomography (OCT) based retinal thickness analysis in determining ischaemia onset in CRAO. METHODS: The relative retinal thickness increase (RRTI) in comparison with the fellow eye was analysed retrospectively in OCT scans of 66 patients diagnosed with CRAO between January 2010 and December 2019 within 48 hr of ischaemia onset. The natural course of RRTI and the sensitivity and specificity of OCT-based determination of ischaemia onset in identifying CRAO within 4.5 hr using the RRTI were evaluated. RESULTS: Relative retinal thickness increase (RRTI) in acute CRAO follows a hyperbolic curve with a steep incline within the early phase after which it reaches a plateau. Optical coherence tomography (OCT)-based retinal thickness analysis in CRAO allows to differentiate patients with ischaemia onset within the past 4.5 hr or thereafter with a sensitivity of 100% and a specificity of 94.3%. CONCLUSION: Relative retinal thickness increase (RRTI) allows to identify CRAO patients that are eligible for a potentially beneficial reperfusion therapy within a therapeutic window of 4.5 hr with a high accuracy. Especially in patients with unknown ischaemia onset, this diagnostic tool could be of major importance in the future clinical management.