Visual Outcomes of Traumatic Lens Dislocations and Subluxations Managed by Pars Plana Vitrectomy and Lensectomy.

AIM: The aim of this study was to evaluate the visual outcome of lens dislocation and subluxation managed by pars plana vitrectomy (PPV) and lensectomy in patients with open (OGIs) or closed globe injuries (CGIs). METHODS: Medical records of 70 consecutive patients treated by PPV and lensectomy over a period of 11 years (1 January 2010-31 December 2020) were retrospectively reviewed. We collected demographic data, best corrected visual acuity (BCVA) using a Snellen Chart pre- and postoperatively, associated ocular injuries and treatment strategy. Visual outcome was evaluated according to the final BCVA which was defined as poor <0.1 or good ≥0.1. RESULTS: The mean age was 57.9 ± 17.6 years. CGIs were present in 49 (70.0%) cases and open OGIs in 21 (30.0%) cases. The dislocation mechanism was zonular lysis in 59 cases (84.3%) and capsular rupture in 11 cases (15.7%). The intraocular lens implant (IOL) was sutured to the sclera in 51 (72.9%) cases or positioned in the capsular bag or in the sulcus in 3 (4.3%) cases and 1 (1.4%) case, respectively, whereas 15 (21.4%) patients remained aphakic. A good BCVA ≥ 0.1 was achieved in 45.71% of the eyes. The presence of retinal detachment (RD) (p = 0.014), iridodonesis (p = 0.011) and initial BCVA (p = 0.000) achieved statistical significance in predicting visual outcome. After treatment, 45.71% of patients achieved a final BCVA ≥ 0.1. CONCLUSION: RD, iridodonesis and initial BCVA were risk factors for poor visual outcome in our series.

The Predictive Capabilities of Artificial Intelligence-Based OCT Analysis for Age-Related Macular Degeneration Progression-A Systematic Review.

The era of artificial intelligence (AI) has revolutionized our daily lives and AI has become a powerful force that is gradually transforming the field of medicine. Ophthalmology sits at the forefront of this transformation thanks to the effortless acquisition of an abundance of imaging modalities. There has been tremendous work in the field of AI for retinal diseases, with age-related macular degeneration being at the top of the most studied conditions. The purpose of the current systematic review was to identify and evaluate, in terms of strengths and limitations, the articles that apply AI to optical coherence tomography (OCT) images in order to predict the future evolution of age-related macular degeneration (AMD) during its natural history and after treatment in terms of OCT morphological structure and visual function. After a thorough search through seven databases up to 1 January 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 1800 records were identified. After screening, 48 articles were selected for full-text retrieval and 19 articles were finally included. From these 19 articles, 4 articles concentrated on predicting the anti-VEGF requirement in neovascular AMD (nAMD), 4 articles focused on predicting anti-VEGF efficacy in nAMD patients, 3 articles predicted the conversion from early or intermediate AMD (iAMD) to nAMD, 1 article predicted the conversion from iAMD to geographic atrophy (GA), 1 article predicted the conversion from iAMD to both nAMD and GA, 3 articles predicted the future growth of GA and 3 articles predicted the future outcome for visual acuity (VA) after anti-VEGF treatment in nAMD patients. Since using AI methods to predict future changes in AMD is only in its initial phase, a systematic review provides the opportunity of setting the context of previous work in this area and can present a starting point for future research.

Macular hole Delphi consensus statement (MHOST).

PURPOSE: To derive a Delphi method-based consensus for the surgical management of Full Thickness Macular Hole (FTMH) and Lamellar Macular Hole (LMH). METHODS: 37 expert VR surgeons from 21 mainly European countries participated in Delphi method-based questionnaire for diagnosis and treatment of FTMHs and LMHs. RESULTS: A total of 36 items were rated in round 1 by 37 participants, of which 10 items achieved consensus: intraoperative verification of PVD; clinical superiority of OCT-based FTMH classification; practical ineffectiveness of ocriplasmin; circular 360° ILM peeling for small macular holes; use of regular surgical technique for the size of the hole in concomitant retinal detachment; performing complete vitrectomy; SF6 gas as preferred tamponade; cataract surgery if crystalline lens is mildly/moderately opaque; removal of both ILM and LHEP in LMH surgery. In round 2, 18 items with moderate consensus (45-70% agreement) in round 1 were rated by 35 participants. Final consensus was reached in 35% of questions related to both diagnosis and surgical procedures. CONCLUSIONS: This Delphi study provides valuable information about the consensus/disagreement on different scenarios encountered during FTMH and LMH management as a guide tosurgical decision-making. High rate of disagreement and/or variable approaches still exist for treating such relatively common conditions.

Advanced ImageJ Analysis in Degenerative Acquired Vitelliform Lesions Using Techniques Based on Optical Coherence Tomography.

Acquired vitelliform lesions (AVLs) are associated with a large spectrum of retinal diseases, among which is age-related macular degeneration (AMD). The purpose of this study was to characterize AVLs' evolution in AMD patients using optical coherence tomography (OCT) technology and ImageJ software. We measured AVLs' size and density and followed their impacts over surrounding retinal layers. Average retinal pigment epithelium (RPE) thickness in the central 1 mm quadrant (45.89 ± 27.84 µm vs. 15.57 ± 1.40 µm) was significantly increased, as opposed to the outer nuclear layer (ONL) thickness, which was decreased (77.94 ± 18.30 µm vs. 88.64 ± 7.65 µm) in the vitelliform group compared to the control group. We found a continuous external limiting membrane (ELM) in 55.5% of the eyes compared to a continuous ellipsoid zone (EZ) in 22.2% of the eyes in the vitelliform group. The difference between the mean AVLs' volume at baseline compared to the last visit for the nine eyes with ophthalmologic follow-up was not statistically significant (p = 0.725). The median follow-up duration was 11 months (range 5-56 months). Seven eyes (43.75%) were treated with intravitreal anti-vascular endothelium growth factor (anti-VEGF) agent injections, in which we noted a 6.43 ± 9 letter decrease in the best-corrected visual acuity (BCVA). The increased RPE thickness could suggest hyperplasia contrary to the decreased ONL, which could mirror the impact of the vitelliform lesion on photoreceptors (PR). Eyes that received anti-VEGF injections did not show signs of improvement regarding BCVA.

Artificial Intelligence for Personalised Ophthalmology Residency Training.

Residency training in medicine lays the foundation for future medical doctors. In real-world settings, training centers face challenges in trying to create balanced residency programs, with cases encountered by residents not always being fairly distributed among them. In recent years, there has been a tremendous advancement in developing artificial intelligence (AI)-based algorithms with human expert guidance for medical imaging segmentation, classification, and prediction. In this paper, we turned our attention from training machines to letting them train us and developed an AI framework for personalised case-based ophthalmology residency training. The framework is built on two components: (1) a deep learning (DL) model and (2) an expert-system-powered case allocation algorithm. The DL model is trained on publicly available datasets by means of contrastive learning and can classify retinal diseases from color fundus photographs (CFPs). Patients visiting the retina clinic will have a CFP performed and afterward, the image will be interpreted by the DL model, which will give a presumptive diagnosis. This diagnosis is then passed to a case allocation algorithm which selects the resident who would most benefit from the specific case, based on their case history and performance. At the end of each case, the attending expert physician assesses the resident's performance based on standardised examination files, and the results are immediately updated in their portfolio. Our approach provides a structure for future precision medical education in ophthalmology.

Visual Outcomes and Prognostic Factors of Traumatic Endophthalmitis Treated by Pars Plana Vitrectomy: 11 Years Retrospective Analysis.

Aim: To evaluate the visual outcome of traumatic endophthalmitis and describe the risk factors associated with poor visual acuity and retinal detachment (RD) development over an 11-year period. Methods: Medical records of 34 patients with traumatic endophthalmitis who underwent PPV over a period of 11 years (1 January 2010−31 December 2020) were reviewed. We extracted details regarding demographic data, initial and final best corrected visual acuity (BCVA) using a standard Snellen chart, wound and IOFB characteristics, ocular associated lesions, and treatment. The outcome was evaluated according to the final BCVA which was defined as poor < 0.1 or good ≥ 0.1 Results: Endophthalmitis rate was 29.8% in open globe injuries. The mean age was 43.6 ± 16.5 years and the majority of patients were males (32 out of 34, 94.1%). All patients received systemic (moxifloxacin) and intravitreal antibiotherapy. We performed pars plana vitrectomy (PPV) in all cases. Poor visual outcome was associated with wound size ≥ 3 mm (p = 0.02), the association of IOFB (p = 0.016), and the development of RD (p = 0.00). The presence of IOFB (p = 0.01) and wound size ≥ 3 mm (p = 0.01) were statistically associated with RD development. After treatment, 47.05% of patients achieved final BCVA ≥ 0.1. Conclusion: Wound size ≥ 3 mm, IOFB and RD were risk factors for poor visual outcomes in traumatic endophthalmitis.

Visual outcomes and prognostic factors following 23G vitrectomy for vitreous hemorrhage in eyes with proliferative diabetic retinopathy.

PURPOSE: We aimed to evaluate the factors influencing the visual gain following pars plana vitrectomy for vitreous hemorrhage in patients with proliferative diabetic retinopathy. METHODS: A retrospective study was conducted on 172 eyes of 143 consecutive patients with diabetes mellitus between January 2012 and January 2018. Demographic data, ophthalmological findings, surgery details, and visual outcomes were gathered after consulting the patients' records. The main outcome measured was the improvement of best corrected visual acuity and the secondary outcomes measured were rebleeding and complications. RESULTS: Best corrected visual acuity improved in 103 eyes (59.88%), worsened in 45 eyes (26.16%), and remained unchanged in 24 eyes (13.95%). Type 2 diabetes mellitus was significantly associated with better final best corrected visual acuity (p=0.0244). Previous treatment by pan-retinal laser photocoagulation or intravitreal bevacizumab determined better final best corrected visual acuity, but not significantly (p>0.05). Preoperative rubeosis iridis and neovascular glaucoma did not influence the outcomes. The lack of fibrovascular proliferation requiring dissection was a significant factor for better final best corrected visual acuity (p=0.0006). Rebleeding occurred in 37.1% of the eyes and it was not influenced by the antiplatelet drugs (p>0.05). Postoperative neovascular glaucoma was a negative prognostic factor (p=0.0037). CONCLUSION: The final best corrected visual acuity was influenced positively by type 2 diabetes mellitus and the absence of preoperative extensive fibrovascular proliferation and negatively by postoperative neovascular glaucoma.

Optical Coherence Tomography Measurements in Type 1 Diabetic Subjects with Low and Moderate Daily Physical Activity.

Background: Physical activity is nowadays recognized as a protective factor against cardiovascular conditions, being cost-effective and easy to implement. Through its positive effects on hemodynamic and oxidative stress, different intensities in daily physical activity could influence diabetic macular edema (DME) in type 1 Diabetes Mellitus (DM). Methods: With the help of a spectral domain optical coherence tomography (OCT) device, we studied the macular thickness and ETDRS map parameters in type 1 DM patients who were classified into two groups: low and moderate intensity routine physical activity status, using the international physical activity questionnaire (IPAQ). All subjects received comparable anti-VEGF treatment. Results: Having a long disease evolution, patients with type 1 DM (T1DM) with moderate physical activity displayed better OCT measurements in specific retinal sectors than their counterparts with low physical activity. Variables such as age and body mass index (BMI) can influence the level of physical activity in T1DM patients. Conclusions: This study showed a lower prevalence of DME in T1DM subjects with moderate physical activity levels, revealing lower values for ETDRS OCT parameters in specific retinal sectors. The macular volumes (mm3) were significantly lower in the right eye for this group of subjects. Abbreviations: BMI = body mass index, CMT = central macular thickness, DM = diabetes mellitus, DME = diabetic macular edema, DR = diabetic retinopathy, FT = foveal thickness, II = inferior inner thickness, IO = inferior outer thickness, IPAQ = international physical activity questionnaire, LE = left eye, OCT = optical coherence tomography, MMT = maximal macular thickness, mMT = minimal macular thickness, MV = macular volume, NI = nasal inner thickness, NO = nasal outer thickness, QoL = quality of life, RE = right eye, SI = superior inner thickness, SO = superior outer thickness, T1DM = type 1 diabetes mellitus, T2DM = type 2 diabetes mellitus, TI = temporal inner thickness, TO = temporal outer thickness.

Diabetic Macular Edema Optical Coherence Tomography Biomarkers Detected with EfficientNetV2B1 and ConvNeXt.

(1) Background: Diabetes mellitus (DM) is a growing challenge, both for patients and physicians, in order to control the impact on health and prevent complications. Millions of patients with diabetes require medical attention, which generates problems regarding the limited time for screening but also addressability difficulties for consultation and management. As a result, screening programs for vision-threatening complications due to DM have to be more efficient in the future in order to cope with such a great healthcare burden. Diabetic macular edema (DME) is a severe complication of DM that can be prevented if it is timely screened with the help of optical coherence tomography (OCT) devices. Newly developing state-of-the-art artificial intelligence (AI) algorithms can assist physicians in analyzing large datasets and flag potential risks. By using AI algorithms in order to process OCT images of large populations, the screening capacity and speed can be increased so that patients can be timely treated. This quick response gives the physicians a chance to intervene and prevent disability. (2) Methods: This study evaluated ConvNeXt and EfficientNet architectures in correctly identifying DME patterns on real-life OCT images for screening purposes. (3) Results: Firstly, we obtained models that differentiate between diabetic retinopathy (DR) and healthy scans with an accuracy of 0.98. Secondly, we obtained a model that can indicate the presence of edema, detachment of the subfoveolar neurosensory retina, and hyperreflective foci (HF) without using pixel level annotation. Lastly, we analyzed the extent to which the pretrained weights on natural images "understand" OCT scans. (4) Conclusions: Pretrained networks such as ConvNeXt or EfficientNet correctly identify features relevant to the differentiation between healthy retinas and DR, even though they were pretrained on natural images. Another important aspect of our research is that the differentiation between biomarkers and their localization can be obtained even without pixel-level annotation. The "three biomarkers model" is able to identify obvious subfoveal neurosensory detachments, retinal edema, and hyperreflective foci, as well as very small subfoveal detachments. In conclusion, our study points out the possible usefulness of AI-assisted diagnosis of DME for lowering healthcare costs, increasing the quality of life of patients with diabetes, and reducing the waiting time until an appropriate ophthalmological consultation and treatment can be performed.

An overview of the visual dysfunctions in Parkinson's disease - Update from a prospective study in Transylvania.

Being a highly prevalent neurodegenerative disorder worldwide, Parkinson's disease (PD) shows its complexity not only in the variability of its pathology, but also in the complex constellation of its clinical picture. PD does not affect only the nervous system; instead, it is today recognized as having both motor and non-motor features. The purpose of this article is to report up-to-date information of an ongoing study, which correlates the motor features of Parkinson's disease (PD) with the visual disturbances (non-motor features) related to this disease. Abbreviations: PD = Parkinson's disease, HY = Hoehn-Yahr scale, MMSE = Mini-Mental state exam, UPDRS = Unified Parkinson's disease rating scale, RE = right eye, LE = left eye.

Outcomes and Prognostic Factors Following Pars Plana Vitrectomy for Intraocular Foreign Bodies-11-Year Retrospective Analysis in a Tertiary Care Center.

Aim: To evaluate the visual outcome of penetrating ocular injuries with a retained intraocular foreign body (IOFB) managed by pars plana vitrectomy (PPV) and to describe the risk factors associated with poor visual acuity and retinal detachment (RD) development. Methods: Medical records of 56 patients with IOFB that were removed by PPV over a period of 11 years (1 January 2010−31 December 2020) were reviewed. We extracted the demographic data, initial and final best corrected visual acuity (BCVA) using standard Snellen chart, IOFB characteristics, complications and surgical details. Outcome was evaluated according to the final BCVA: poor <0.1, good 0.1−<0.5 or excellent ≥0.5. Results: The mean age was 36.1 ± 14.1 (range, 16−71) years and the majority of patients were males (55 out of 56, 98.2%). IOFB was retinal in 27 (48.2%) cases and intravitreal in 29 cases (51.8%). IOFB size was ≤3mm in 26 (46.4%) cases and >3mm in 30 (53.6%) cases. Preoperative RD was identified in 12 (21.4%) cases and endophthalmitis in 17 cases (30.4%). IOFBs larger than 3 mm and retinal location were associated with RD development. Poor visual outcome was associated with initial BCVA, retinal location, RD and endophthalmitis. Conclusion: Initial BCVA, retinal foreign body, RD and endophthalmitis were risk factors for poor visual outcome.

Predicting Visual Acuity in Patients Treated for AMD.

The leading diagnostic tool in modern ophthalmology, Optical Coherence Tomography (OCT), is not yet able to establish the evolution of retinal diseases. Our task is to forecast the progression of retinal diseases by means of machine learning technologies. The aim is to help the ophthalmologist to determine when early treatment is needed in order to prevent severe vision impairment or even blindness. The acquired data are made up of sequences of visits from multiple patients with age-related macular degeneration (AMD), which, if not treated at the appropriate time, may result in irreversible blindness. The dataset contains 94 patients with AMD and there are 161 eyes included with more than one medical examination. We used various techniques from machine learning (linear regression, gradient boosting, random forest and extremely randomised trees, bidirectional recurrent neural network, LSTM network, GRU network) to handle technical challenges such as how to learn from small-sized time series, how to handle different time intervals between visits, and how to learn from different numbers of visits for each patient (1-5 visits). For predicting the visual acuity, we performed several experiments with different features. First, by considering only previous measured visual acuity, the best accuracy of 0.96 was obtained based on a linear regression. Second, by considering numerical OCT features such as previous thickness and volume values in all retinal zones, the LSTM network reached the highest score (R2=0.99). Third, by considering the fundus scan images represented as embeddings obtained from the convolutional autoencoder, the accuracy was increased for all algorithms. The best forecasting results for visual acuity depend on the number of visits and features used for predictions, i.e., 0.99 for LSTM based on three visits (monthly resampled series) based on numerical OCT values, fundus images, and previous visual acuities.

Interleaved Optical Coherence Tomography: Clinical and Laboratory Biomarkers in Patients with Diabetic Macular Edema.

(1) Background: The global burden of diabetes mellitus (DM) has been estimated to reach 600 million patients worldwide by 2040. Approximately 200 million people will develop diabetic retinopathy within this time frame. Diabetic macular edema (DME) is a severe, vision-threatening complication that can develop at any stage of diabetic retinopathy, and it represents the main cause of vision loss in patients with DM. Its harmful consequences on visual function could be prevented with timely recognition and treatment. (2) Methods: This study assessed the clinical (demographic characteristics, diabetic evolution, and systemic vascular complications); laboratory (glycated hemoglobin, metabolic parameters, capillary oxygen saturation, and renal function); ophthalmologic exam; and spectral-domain optical coherence tomography (SD-OCT) (macular volume, central macular thickness, maximal central thickness, minimal central thickness, foveal thickness, superior inner, inferior inner, nasal inner, temporal inner, inferior outer, superior outer, nasal outer, and temporal outer thicknesses, disruption of the ellipsoid zone, and disruption of the inner retinal layers (DRIL) parameters in three groups of individuals: healthy controls (HC), patients with DME and type 1 DM (T1DM-group A), and patients with DME and type 2 DM (T2DM-group B) to identify novel correlations between them that would open a path to new pathogenetic hypotheses and, implicitly, to the identification of new therapeutic methods, as part of a tailored treatment within the concept of precision medicine. (3) Results: The duration of DM was significantly longer in group A as compared with group B, as were the prevalence of smoking and systemic vascular complications. Capillary oxygen saturation and estimated glomerular filtration rates were significantly lower, and serum creatinine levels were significantly higher in group A as compared to group B. Regarding the OCT findings, DME had a predominantly eccentric pattern, and the right eye was more severely affected in both groups of patients. Significantly higher values were obtained in group B as compared to group A for the following OCT biomarkers: macular volume, central macular thickness, maximal central thickness, minimal central thickness, foveal thickness, superior inner, inferior inner, nasal inner, inferior outer and nasal outer thickness. The disruption of the ellipsoid zone was significantly more prevalent within group A, whereas the overall disruption of the retinal inner layers (DRIL) was identified significantly more frequently in group B. (4) Conclusions: Whereas systemic and laboratory biomarkers were more severely affected in patients with DME and T1DM, the OCT quantitative biomarkers revealed significantly higher values in patients with DME and T2DM.

SD-OCT Biomarkers and the Current Status of Artificial Intelligence in Predicting Progression from Intermediate to Advanced AMD.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the Western World. Optical coherence tomography (OCT) has revolutionized the diagnosis and follow-up of AMD patients. This review focuses on SD-OCT imaging biomarkers which were identified as predictors for progression in intermediate AMD to late AMD, either geographic atrophy (GA) or choroidal neovascularization (CNV). Structural OCT remains the most compelling modality to study AMD features related to the progression such as drusen characteristics, hyperreflective foci (HRF), reticular pseudo-drusen (RPD), sub-RPE hyper-reflective columns and their impact on retinal layers. Further on, we reviewed articles that attempted to integrate biomarkers that have already proven their involvement in intermediate AMD progression, in their models of artificial intelligence (AI). By combining structural biomarkers with genetic risk and lifestyle the predictive ability becomes more accurate.

Circumpapillary Retinal Nerve Fiber Layer OCT Imaging in a Parkinson's Disease Cohort-A Multidisciplinary Approach in a Clinical Research Hospital.

(1) Background: The purpose of this paper is to report the data of the first study in a Clinical Research Hospital, in the Transylvania region, focusing on the Spectral Domain Optical Coherence Tomography (SD-OCT) measurements in the early stages of Parkinson's disease (PD), and to compare the results with age-matched healthy controls. (2) Methods: This study assessed the circumpapillary retinal nerve fiber layer (cpRNFL) SD-OCT measurements (Heidelberg Spectralis, Heidelberg Engineering, Germany) of two study groups: patients suffering from PD (Hoehn-Yahr stages 1-3) and healthy controls. Secondary objectives were to investigate the reported visual symptoms by evaluating the color vision, contrast sensitivity, and the central visual defects for macular disease using standardized charts. Subjects with prior history of ophthalmologic diseases, advanced stages of PD (Hoehn-Yahr stages 4-5), or with psychiatric conditions were not included in this study. The same team of neurologists and ophthalmologists evaluated all individuals in order to have comparable data and to eliminate inter-examiner differences. All subjects were recruited from the same Clinical Research Hospital in the Transylvania region, Romania. (3) Results: 72% of the PD patients (n = 17) in this study reported visual symptoms. In respect to the ophthalmologic chart evaluation for PD patients, the most frequent disturbances were identified in the Ishihara color perception testing (33%). The regression analysis showed significant results for the Ishihara testing in relation to the cpRNFL thinning in the temporal retinal sectors for both eyes. cpRNFL thinning was predominantly contralateral to the parkinsonism (p = 0.001). The temporal and global values of the cpRNFL were significantly lower in all PD patients < 70 years old, compared to the age-matched healthy controls. (4) Conclusions: Specific patterns of cpRNFL thinning were found in the PD subjects younger than 70 years. A multidisciplinary approach is essential for a complete evaluation of PD patients.

Complete oculomotor nerve palsy - first manifestation of gastric adenocarcinoma: clinical experience and literature review.

The diagnosis and management of the alteration of the normal function of the oculomotor nerve (third cranial nerve) varies depending on the characteristics of the paralysis, the age of the patient, and the associated symptoms and signs. Oculomotor nerve palsy may be caused by lesions located anywhere from the oculomotor nucleus to the termination of the third nerve in the extraocular muscles. Although there have been significant advances in neuroimaging to facilitate early diagnosis, the management of a patient presenting with isolated oculomotor palsy is still challenging. This review tackles the case of a 52-year-old patient, with a history of pulmonary tuberculosis (at the age of five), referred to the Department of Ophthalmology, St. Spiridon Emergency Clinical Hospital, Iasi, Romania. The patient had diplopia accompanied by right eyelid ptosis, symptoms that began suddenly 10 days before hospitalization. The clinical examination showed right eye grade II palpebral ptosis, exotropia with limitation of eyeball movements in adduction, supra-∕infraduction. Biomicroscopic examination of the anterior pole revealed the presence of anisocoria and light-near dissociation on the affected side. Numerous investigations were performed to identify the cause, starting with tumoral markers, which were within normal limits. Magnetic resonance angiography (MRA) was performed, and posterior communicating artery aneurysm was ruled out. The endocrinology examination and hormonal laboratory tests were also within normal parameters. Due to suspicions of generalized tuberculosis raised by the infectious disease doctor or presence of secondary lesions, thoraco-abdomino-pelvic computed tomography (CT) scan with contrast agent was done and its findings required gastroenterological exploration. After various explorations, the certainty diagnosis was set by histopathological examination, which revealed gastric adenocarcinoma.

The Future of Stem Cells and Their Derivates in the Treatment of Glaucoma. A Critical Point of View.

This review focuses on the clinical translation of preclinical studies, especially those that have used stem cells in the treatment of glaucoma, with an emphasis on optic nerve regeneration. The studies referred to in the review aim to treat optic nerve atrophy, while cell therapies targeting other sites in the eye, such as the trabecular meshwork, have not been addressed. Such complex and varied pathophysiological mechanisms that lead to glaucoma may explain the fact that although stem cells have a high capacity of neuronal regeneration, the treatments performed did not have the expected results and the promise offered by animal studies was not achieved. By analyzing the facts associated with failure, important lessons are to be learned: the type of stem cells that are used, the route of administration, the selection of patients eligible for these treatments, additional therapies that support stem cells transplantation and their mode of action, methods of avoiding the host's immune response. Many of these problems could be solved using exosomes (EV), but also miRNA, which allows more targeted approaches with minimal side effects.

Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma.

Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging (MRI), serum and cerebrospinal fluid (CSF) markers, and tumour stereotactic biopsy. Imaging techniques, such as susceptibility-weighted imaging (SWI), T2* (T2-star) gradient echo (GRE) or arterial spin labelling based perfusion-weighted MRI (ASL-PWI) facilitate the diagnosis. Germinomas are highly radiosensitive tumours, with survival rates >90% in the context of chemoradiotherapy. However, patients with resistant disease have limited therapeutic options and poor survival. The aim of this review is to highlight the genetic, epigenetic, and immunologic features, which could provide the basis for targeted therapy. Intracranial germinomas present genetic and epigenetic alterations (chromosomal aberrations, KIT, MAPK and PI3K pathways mutations, DNA hypomethylation, miRNA dysregulation) that may represent targets for therapy. Tyrosine kinase and mTOR inhibitors warrant further investigation in these cases. Immune markers, PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1), are expressed in germinomas, representing potential targets for immune checkpoint inhibitors. Resistant cases should benefit from a personalized management: genetic and immunological testing and enrolment in trials evaluating targeted therapies in intracranial germinomas.

Correlations between Retinal Arterial Morphometric Parameters and Neurodegeneration in Patients with Type 2 Diabetes Mellitus with No or Mild Diabetic Retinopathy.

Background and Objectives: In patients with diabetes mellitus (DM), the neural retina is starting to degenerate before the development of vascular lesions. Our purpose was to investigate the correlation between the retinal arterial morphometric parameters and structural neurodegeneration in patients with type 2 DM with no or mild diabetic retinopathy (DR). Materials and Methods: This is a prospective study including 53 eyes of patients with type 2 DM and 32 eyes of healthy controls. Based on SD-OCT (spectral domain-optical coherence tomography) images, using a micro-densitometry method, we measured the outer and luminal diameter of retinal arteries and calculated the AWT (arterial wall thickness), WLR (wall-to-lumen ratio), and WCSA (wall cross-sectional area). GCL (ganglion cell layer) and RNFL (retinal nerve fiber layer) thickness were analyzed in correlation with the retinal arterial morphometric parameters mentioned above. Results: GCL was thinner in the inner quadrants in the NDR (no DR) group compared to controls (p < 0.05). RAOD (retinal artery outer diameter), RALD (retinal artery lumen diameter), AWT, WLR, and WCSA were similar between groups. A regression model considering age, gender, duration of DM, and HbA1C was carried out. Central GCL thickness was correlated positively with RAOD (coefficient 0.360 per µm, p = 0.011), RALD (coefficient 0.283 per µm, p = 0.050), AWT (coefficient 0.304 per µm, p = 0.029), and WCSA (coefficient 3.90 per µm, p = 0.005). Duration of DM was positively correlated with WCSA (coefficient 0.311 per one year duration of diabetes, p = 0.043). Conclusions: Significant GCL thinning in the inner quadrants preceded the morphological retinal arterial morphometric changes, supporting the neurodegeneration as primary pathogenic mechanism in DR.

Malfunction of outer retinal barrier and choroid in the occurrence and progression of diabetic macular edema.

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy, affecting 1 in 15 patients with diabetes mellitus (DM). The disruption of the inner blood-retina barrier (BRB) has been largely investigated and attributed the primary role in the pathogenesis and progression in DME, but there is increasing evidence regarding the role of outer BRB, separating the RPE from the underlying choriocapillaris, in the occurrence and evolution of DME. The development of novel imaging technologies has led to major improvement in the field of in vivo structural analysis of the macula allowing us to delve deeper into the pathogenesis of DME and expanding our vision regarding this condition. In this review we gathered the results of studies that investigated specific outer BRB optical coherence tomography parameters in patients with DM with the aim to outline the current status of its role in the pathogenesis and progression of DME and identify new research pathways contributing to the advancement of knowledge in the understanding of this condition.