bluuebunny/crossref_metadata_2025 huggingface dataset:
PAUL device implantation in paediatric glaucoma patients with LTBP2 mutation: Case reports
Authors: Diafa Aspasia , Mourgela Anna , Papadopoulou Margarita , Atzamoglou Spyros , Adamopoulou Aspasia , Smarlamaki Rafaela , Kappou Christina , Paizi Nefeli Ioanna , Zisimopoulos Athanasios , Terzidou Chrysa , Kouri Agathi
Published: January 2024

Purpose: Latent‐transforming growth factor beta‐binding protein 2 (LTBP2) is a fibrillin‐related extracellular matrix protein. The protein is expressed in the ciliary body, and mutations in its gene lead to primary paediatric glaucoma due to anterior segment dysgenesis. These mutations in the Greek area appear almost exclusively in Roma families. In this work, we present the surgical treatment of two patients with PAUL® device implantation, and their preoperative and postoperative course.

Methods: Case Reports.

Results: Case 1: A 2‐month‐old female patient, the fifth child of a Roma family with an older sister with paediatric glaucoma, presented to the Ophthalmology clinic of our hospital with microspherophakia and megalocornea, a phenotype compatible with a mutation of the LTBP2 gene. She underwent a phakectomy for lens dislocation in both eyes. At the age of 2.5 years, she was diagnosed with hypertony and started topical treatment. After two years of treatment escalation and unsuccessful management of intraocular pressure, at the age of 4.5 years it was decided to implant a PAUL® glaucoma implant in her left eye. Case 2: An 8‐month‐old male patient, child of a Roma family, similarly presented with microspherophakia and megalocornea as well as hypertony. In addition to topical treatment, he underwent peripheral iridectomies and phakectomies in both eyes. After years of treatment escalation and unsuccessful management of intraocular pressure, at the age of 6.5 years it was decided to implant a PAUL® glaucoma implant in his left eye. We describe the surgical procedures as well as their postoperative course.

Conclusions: Regular monitoring of intraocular pressure is recommended in children with megalocornea, microspherophakia and/or ectopia lentis. Genetic testing of the LTBP2 gene is recommended in these patients. It is important to raise awareness in the ophthalmological community regarding the recognition of this phenotype in children of Roma families. The PAUL® device is one of the options for treating drug‐resistant paediatric glaucoma.
A series of acute corneal edema and residual subepithelial haze after bilateral selective laser trabeculoplasty
Authors: Vandewalle Evelien , Vincent Walgrave , Jeffrey Nijs , Alix Somers , Sophie Lemmens
Published: January 2024

Purpose: To report 3 cases of corneal edema and subepithelial haze soon after bilateral selective laser trabeculoplasty.

Methods: Selective laser trabeculoplasty was performed for the treatment of open‐angle glaucoma on 3 female, middle aged patients who subsequently developed corneal stromal haze within 24 to 48 h after the procedure.

Results: The patients were treated with topical steroids for several weeks. Due to uncontrolled intraocular pressure, one patient underwent a trabeculectomy. The corneal edema resolved. However, all three patients were left with a hyperopic shift.

Conclusions: Corneal edema and subepithelial haze after selective laser trabeculoplasty is an extremely rare event. Although certain causes are postulated to play a role in this complication, it is not yet understood what may predispose a patient to corneal changes as a result of this laser procedure.
Neuroprotective effects of GLP‐1 receptor agonists and their potential in retinal diseases
Authors: Mouhammad Zaynab Ahmad , von Spreckelsen Alexander , Bermudez Mariana Yolotzin Garcia , Vohra Rupali , Williams Pete , Kolko Miriam
Published: January 2024

Aims/Purpose: Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone naturally released in response to a meal and therapeutically used in the treatment of diabetes. GLP‐1 receptor agonists, including semaglutide (SEM), have shown to promote neuronal survival in animal models of stroke, Alzheimer's and Parkinson's disease including retinal diseases such as age‐related macular degeneration (AMD), diabetic retinopathy, retinal ischemia, glaucoma and retinitis pigmentosa. The purpose of this study is to identify a neuroprotective effect of SEM.

Methods: Retinal explants were treated with 50 nM SEM and incubated for 30 min, 4, 8 and 24 h. Tissue survival was measured through colorimetric lactate dehydrogenase (LDH) viability assays. Specific RGC survival was determined through immunohistochemical (IHC) staining. Energy metabolism was assessed through stable isotope labeling (13C) and gas chromatography–mass spectrometry (GC–MS). Mitochondrial function was assessed using Seahorse analysis.

Results: Ex vivo treatment with 50 nM SEM increased retinal tissue survival by 55.9% compared to control. IHC and Seahorse analyses revealed no significant differences between control and treatment with SEM in retinal explants and wholemounts. Minor effects on glucose metabolism were observed, in general showing improved metabolism in retinal explants. Significantly increased 13C labeling was observed in the TCA cycle intermediates citrate and α‐Ketoglutarate (KG) after 30 min incubation with 50 nM SEM (Citrate; Control: 10.8% vs. SEM: 23.93% and α‐KG; Control: 9.45% vs. SEM: 19.25%, presented as molecular carbon labeling).

Conclusions: The present study reveals that treatment with semaglutide has no toxic effect on retinal tissue and potentially has a neuroprotective effect. However, further studies are needed to fully understand the therapeutic potential of GLP‐1 receptor agonists in retinal diseases.
Biomechanical analysis of Corvis tonometry parameters in patients with hypotony after glaucoma filtering surgery
Authors: El Jarroudi Rachid Bouchikh , Arenas Jordi Loscos , Romero Pau Romera , García Jessica Botella
Published: January 2024

Aims/Purpose: Postoperative hypotony is a common complication of glaucoma filtering surgery, particularly with adjunctive use of antimetabolites, such as mitomycin C and 5‐fluorouracil. Precautions may be taken intraoperatively and postoperatively to decrease the likelihood of hypotony. Sometimes, despite these measures, the low‐pressure syndrome still can occur, the management of which can be difficult. The cornea has a complex biomechanical structure that determines its response under stress conditions and there are so many studies related with glaucoma and corneal biomechanical properties. However, in the best of our knowledge, there are no reports concerning the corneal parameters in patients with hypotony. This study aimed to investigate the possible correlation of hypotony risk after a filtering surgery with different corneal parameters obtained by Corvis.

Methods: A retrospective case control study of 30 eyes with chronic hypotony (IOP ≤6 mmHg for more than a month) after glaucoma filtering surgery at the Hospital Universitari Germans Trias i Pujol. In all patients, the IOP (represented in mmHg) and following parameters were obtained using the Corvis device: deformation amplitude ratio (DA), Ambrósio's relational thickness (ARTh), stiffness parameter at first applanation (SPA1), Integrated radius (IR), Stress strain index (SSI) and pachymetry (represented in μm).

Results: The results will be represented as the value in eyes with hypotony after glaucoma filtering surgery (cases) vs the healthy eye (control). IOP 4.4 ± 1.8 vs 18.1 ± 7.7. Pachymetry 527 ± 53.4 vs 549.1 ± 94. SPA1 65.2 ± 19.1 vs 111 ± 17.1 in controls (p < 0.05). ARTh 495 ± 170 vs 523 ± 222. IR 10.9 ± 2.67 vs 8.4 ± 1.36 (p < 0.05). DA 5.6 ± 0.7 vs 5 ± 0.5 (p < 0.05). SSI 1.3 ± 1.4 vs 1.6 ± 1.4.

Conclusions: SP‐A1 value decreased while the IOP decreased, suggesting that the lower corneal stiffness could increase the percentage of hypotony due to the different ocular biomechanical properties in these eyes, so therefore, it could be considered a risk marker for hypotonia in patients who are going to undergo glaucoma filtering surgery.
Isolated versus combined XEN‐implant surgery
Authors: Abellán Maria Victoria Navarro , González Luis Eloy Pérez , Perea Juan Antonio Sánchez , Menargues Manuel Almarcha , López Carmen Miquel , de los Reyes Retamero Sánchez María , Medina José Javier García
Published: January 2024

Aims/Purpose: A minimally invasive surgical technique in glaucoma surgery is XEN implant. It allows direct evacuation of aqueous humour from anterior chamber to subconjunctival space. It is indicated in mild or moderate primary open angle glaucoma in patients with treatment with 2 or more active ingredients and good conjunctival status. The objective is to evaluate the effectiveness and safety of XEN implant isolated versus combined cataract surgery.

Methods: Single‐centre retrospective observational study, conducted between 2018 and 2023. Follow‐up of 1 year in a sample of 44 eyes operated with XEN implant, 15 with isolated implant and 29 combined surgeries with cataract. Quantitative variables are expressed as mean ± standard deviation. Comparison between variables was performed using Student's t‐test after testing for normality of distribution using the Shapiro–wilk test.

Results: Combined cataract surgery with respect to XEN implant placement showed no significant difference in visual acuity improvement, nor in the decrease in post‐surgical hypotensive treatment and intraocular pressure, except in the first month in favour of isolated surgery (p > 0.02). Follow‐up with visual field and optical coherence tomography showed no significant differences, suggesting that there was no progression of glaucoma with both techniques. There were no intraoperative complications. Needling manoeuvre was performed in 60% of patients with isolated XEN compared to 30% with combined surgery. Good safety profile. Other studies find no significant differences in the postoperative success rate between combined surgery or not with phacoemulsification, nor differences in outcomes in phakic versus pseudophakic patients.

Conclusions: The XEN implant is effective and safe in terms of IOP lowering and the number of hypotensive drops. There are no significant differences in IOP lowering or in the number of drugs to be administered between the XEN implant alone and combined cataract surgery.
Tear‐borne interleukin 1‐beta and transforming growth factor‐beta and its relationship with clinical parameters in neophytes contact lens wearers
Authors: Pereira Eduardo Insua , Lira Madalena , Sampaio Ana Paula
Published: January 2024

Aims/Purpose: To determine the presence of Interleukin 1‐beta (IL1‐β) and Transforming growth factor‐beta (TGF‐β) in the tears of neophytes contact lens wearers; and investigate the relationship between their concentration, tear stability, and ocular physiology findings.

Methods: In this clinical trial, 12 neophytes (5 males, 24.0 ± 5.0 years) were dispensed with delefilcon A contact lenses. Physiological responses (bulbar and limbal hyperemia), non‐invasive tear break‐up times, and tear sample collections were obtained in the morning (before lens insertion; 9–10 a.m.) and afternoon (before lens removal; 7–8 p.m.) of the same day. The tear samples were assayed for IL1‐β and TGF‐β concentrations using Enzyme‐Linked Immunoabsorbent Assay kits. A parallel control group of 11 individuals (6 males, 25.0 ± 5.0) was also assessed to determine the levels of the biomarkers in the tears of non‐contact lens wearers.

Results: Patients wore lenses for an average of 7:20 [6,9] h. Bulbar and limbal hyperemia increased throughout the day (p < 0.001). Tear break‐up times were lower in the afternoon compared to the morning assessment (4.7 ± 2.0 Vs. 12.2 ± 8.8 seconds; p < 0.001). The IL1‐β levels were higher in neophytes compared to controls (3.2 ± 4.7 Vs. 0.1 ± 0.1 ρg/ml; p = 0.05) but only in the afternoon. A significant correlation was found between IL1‐β concentration, bulbar (r = 0.405, p = 0.008), and limbal hyperemia (r = 0.499, p = 0.027) in the morning period. No substantial changes were reported for TGF‐β.

Conclusions: The use of contact lenses might alter the IL1‐β regulatory mechanisms and disturb ocular surface homeostasis. However, more clinical evidence is needed to understand this phenomenon.
Exogenous endophthalmitis caused by Citrobacter Koseri
Authors: Prades Gemma Ortega , Sanmillán Héctor Carot , Pérez‐Torregrosa Vicente‐Tomás , Fabra Yolanda Cifre , Del Río Noemí Ruiz , Samper Antonio‐Miguel Duch
Published: January 2024

Aims/Purpose: To present a case of exogenous endophthalmitis caused by Citrobacter Koseri.

Methods: We present a 66‐year‐old man that works in an animal laboratory exercising their care, who came to the emergency department due to sudden loss of vision in his left eye. Using indirect ophthalmoscopy, we observed a dense hemovitreous that prevented visualization of the posterior structures. An ocular ultrasound was performed in which suggestive signs of retinal detachment are intuited, so we decided to perform an exploratory vitrectomy. During exploratory vitrectomy via pars plana, a dense fibrinoid vitreous was observed, with a tear at XIIh of more than 1 h in diameter. The vitrectomy was completed successfully after suturing the sclerotomies.

Results: The postoperative period evolved adequately, but 3 days later, the patient presented to the emergency room with pain and severe ocular inflammation. On physical examination, he presented intense conjunctival hyperemia, signs of corneal melting, and increased ocular tone. Endophthalmitis was diagnosed and treatment was started with reinforced intravitreal and eye drops antibiotics and anti‐inflammatories. 24 h later, the patient went back with an extrusion of the lens that was sent to microbiological study. On physical examination, we observed corneal melting that produced complete corneal perforation with extrusion of purulent and vitreous material and an urgent evisceration was performed. Two days later, the microbiological samples confirmed the Citrobacter Koseri microorganism.

Conclusions: Cases of exogenous endophthalmitis caused by Citrobacter are limited in the literature. In this case, exposed suture material and the epidemiological history of the patient were suspected as the source of infection. Despite early diagnosis and intensive treatment, the clinical course of Citrobacter endophthalmitis is very aggressive and has a poor visual prognosis. In our case it ended with evisceration.
HAP1 cell utilization for accurate interpretation of germline BAP1 variants
Authors: Repo Pauliina , Turunen Joni , Kivelä Tero
Published: January 2024

Aims/Purpose: Pathogenic germline variants in BRCA1‐Associated Protein 1 (BAP1) gene cause a rare, dominant, life‐threatening tumour predisposition syndrome (BAP1‐TPDS). It increases risk for atypical cutaneous Spitz tumours and for several index cancers: uveal melanoma, malignant mesothelioma, cutaneous melanoma, clear cell renal cell carcinoma, and basal cell carcinoma. Because about 50% of variants in the public database CLINVAR are of unknown significance (VUS) and accurate interpretation of variants is crucial for screening cancer in carriers, improved tools for genomic BAP1 variant interpretation are needed. We aimed to create a mammalian cell based tool for this purpose.

Methods: Four pathogenic BAP1 variants (c.67 + 1G > T, c.281A > G, c.680G > A, and c.1780_1781insT) and one VUS (c.1526C > T) were edited into the genome of near haploid HAP1 cells with CRISPR‐Cas9 and assayed for BAP1 expression and cell fitness. Proliferation and cell adhesion was quantified using xCelligence real‐time cell analysis system.

Results: BAP1 loss reduces growth of HAP1 cells, which we exploited as phenotypic readout for pathogenicity of inserted variants. Three BAP1‐TPDS history‐associated variants c.67 + 1G > T, c.281A > G, and c.1780_1781insT reduced HAP1 adhesion and proliferation roughly by 70–80% whereas the c.680G > A missense variant, identified in a patient with UM without BAP1‐TPDS family history, reduced proliferation by 50%. VUS c.1526C > T behaved similarly to wild type.

Conclusions: Qualitatively, the results of our in vitro tool for BAP1 variant interpretation agree with previous studies, validating the tool. The validated system has potential for scaling up for simultaneous analysis of multiple variants. Quantitatively, it might have potential for predicting higher or lower risk in family members.
Operator stress in ophthalmology: Impact on the result and management
Authors: Hammoumi Zineb , Daghouj Ghizlane , Ayad Rima , Otsasso Mathilde , Elmaaloum Loubna , Allali Bouchra , El Kettani Asmaa
Published: January 2024

Aims/Purpose: Our work aims to show the impact of the stress of the operator in ophthalmology on the quality of surgery, the daily life of the surgeon and the management capacity.

Methods: This is a work including 147 residents in the various ophthalmology departments of Morocco as well as 90 young ophthalmologists. Using a Googleforms form.

Results: The age of ophthalmic surgeons varies between 25 and 38 years old, with a female predominance since they represent 59.3%. 237 responded to the questionnaire including 147 resident doctors in different cities of Morocco from the 1st to the 5th year and 90 young ophthalmologists. The type of intervention performed is pterygium surgery in 85.2% of cases, cataract in 81.5%, appendages in 33.3%. The number of patients operated is greater than 100 in 24.1% of cases, between 20 and 50 in 20.4%, between 10 and 20 in 20.4%... According to the operators, cataract surgery is the most stressful act in 79.2% of cases, followed by retina surgery in 22.6% of cases. Monophthalmic subjects represent the type of patient who stress surgeons the most in 75.5% of cases. The feeling before the act is predominated by stress in 50% of cases, excitability in 31.5%, and neutrality in 20.4%. During the operation, stress predominates in 53.7% of cases. For stress management before the operation 31.5% have a personal ritual and 25.9% try relaxation. During an intraoperative complication, 77.8% manage calmly. After surgery, 59.3% feel satisfaction, 44.4% doubt and 13% have insomnia. This psychological stress impacts 55.6% of the daily lives of surgeons. For daily stress management, 46.3% resort to sports activities, 22.2% to meditation and 9.3% to sophrology. 53.7% think of developing new strategies to manage stress.

Conclusions: Mental health is an essential element in everyone's life that allows us to realize our potential, to face the normal difficulties of life, to work successfully and productively. Stress management for the ophthalmic surgeon remains essential in his daily life and to carry out his interventions.
Orbital pleomorphic sarcoma: A case report
Authors: Mesa Sara Mesa , Borrero Cristina Gonzalez , Hoyos Carolina Ceballos , Usuga Juan Cadavid
Published: January 2024

Aims/Purpose: To report a case involving an undifferentiated pleomorphic sarcoma localized in the orbit.

Methods: Case report and literature review.

Results: Undifferentiated pleomorphic sarcomas (UPS) are one of the least common types within all malignant sarcomas, with their incidence reaching 5–10% of the cases. Within this group of UPS, tumours involving the head and neck have an even lower incidence (approximately 3 to 5%). We report the case of an 86 year old male with a history of cardiovascular disease, presenting with a painless lesion in his right eye. The orbit CT reported a soft tissue lesion in contact with the right ocular globe, lacrimal gland and extraconal fat. At examination the patient registered best corrected visual acuity right eye (OD) no light perception right eye and left eye (OS) 20/50. At slit lamp examination OD is not evaluable due to corneal compromise. OS anterior segment and posterior pole with no alterations. Immunohistochemistry was negative for P40, desmine, CD34, SOX‐10 and cytokeratin cocktail. S100 had weak and patchy staining. These results led to a giant cell pleomorphic sarcoma diagnosis, histological grade 3. The patient underwent urgent orbital exenteration, with an adequate postsurgical evolution and oncology follow up.

Conclusions: The diagnosis of an UPS is based on exclusion, due to their heterogeneous nature, with histological characteristics that overlap with other malignant mesenchymal neoplasms, mainly with metastatic sarcomatoid carcinoma and melanoma. These tumours are characterized by their rapid growth and potential for metastasis, especially in the lungs. Treatment includes surgical resection, sometimes combined with adjuvant chemotherapy. Strict periodic checkups are essential, since local recurrence is frequent (between 19 to 31%), with most cases occurring within the first 24 months.
Intravitreal application of stem cells and their products does not ameliorate experimental autoimmune uveitis
Authors: Skrlova Eva , Uherkova Eva , Palacka Katerina , Hermankova Barbora , Holan Vladimir , Heissigerová Jarmila
Published: January 2024

Aims/Purpose: Stem cell therapy has demonstrated potential therapeutic benefits in various medical disciplines. This study evaluated therapeutic effects of mesenchymal stem cells (MSCs) or their by‐products on intraocular inflammation in experimental autoimmune uveitis (EAU) model.

Methods: EAU was induced in C57BL/6J mouse strain through administration of IRBP, Freund's adjuvant and pertussis toxin. Conditioned medium was procured through cultivation of MSCs in serum‐free medium, while MSC supernatant was obtained via MSC centrifugation and membrane removal. Either conditioned medium or MSC supernatant was intravitreally administered unilaterally, typically on day 14 post‐EAU induction. Ocular fundus of mice was documented regularly. Experiments were generally concluded on day 28, with eyes processed for FACS and PCR analysis. Infiltration of retina by inflammatory cells (F4/80, CD11c, CD45, CD80, CD86, CD206) and gene expression of pro‐inflammatory factors (Gfap, Iba‐1, IL‐1, iNOS) were quantified.

Results: Across all experiments, clinical grading, FACS, and PCR analysis indicated exacerbation of intraocular inflammation. Post‐intravitreal administration of MSC by‐products into eyes with EAU, increased infiltration of retina by inflammatory cells and upregulation in gene expression of pro‐inflammatory factors were observed. These findings were corroborated in vitro, where co‐culturing of retina with EAU in presence of MSCs or their supernatant did not significantly reduce gene expression of pro‐inflammatory factors. Upsurge in pro‐inflammatory factors was also noted in control experiments on healthy eyes post‐intravitreal injection of no substance, serum‐free medium, PBS, or conditioned medium.

Conclusions: No improvement in EAU was observed following application of MSC products, both in vivo and in vitro. Instead, inflammation was more severe. Trauma induced by intravitreal application itself significantly influenced outcome.

Financial support: GA UK 309621, SVV UK 260631.
Role of corneal sensory nerves in tearing and blinking
Authors: Acosta M. Carmen
Published: January 2024

The cornea is innervated trigeminal neurons classified in three different functional types: polymodal nociceptor, mechano‐nociceptor and cold thermoreceptor neurons. Corneal sensory nerves are responsible of the conscious sensations evoked by corneal stimulation, and are also involved in the trophic maintenance of the tissue. Besides, corneal nerve activity is also involved in the regulation of the protective functions of the ocular surface such as tearing and blinking.

Regulation of reflex and basal tearing is integrated at the brainstem and, in both cases, under the influence of the sensory inflow provided by several types of corneal sensory nerves. While reflex tearing is induced selectively by the stimulation of corneal polymodal nociceptors, basal tearing rate depends on the spontaneous activity of cold thermoreceptors. Thus, when cold thermoreceptors are silenced by environmental warming, basal tearing is compromised.

Voluntary, reflex and spontaneous (basal) blinking present differences in their characteristics and regulation mechanisms. Voluntary blinking depends on the direct instructions generated at the brain cortex, acting over the motor neurons located at the facial nucleus. Reflex blinking is integrated at the brainstem, being induced by the stimulation of the cornea and periocular skin, and even by loud sounds. Spontaneous blinking is claimed to be controlled by a CNS centre that established a blinking pattern. This pattern is modified under different conditions such as cognitive activity, being for example reduced during visual attentional tasks in order not to lose relevant visual information. When the activity of corneal cold thermoreceptors is abolished or reduced by ocular instillation of local anaesthetics, the frequency and characteristics of the spontaneous blinking is not modified. However, when the activity of cold thermoreceptors is increased for prolonged periods (for instance after topical instillation of F6H8 drops, which reduces the ocular surface temperature), blinking pattern become more regular and an increased number of blinks of larger the amplitude and shorter duration are induced. This increased blinking frequency produced when the activity of cold thermoreceptors is increased is sufficient to even counteract the reduction of blinking frequency induced during visual tasks performance. The increase in blink frequency driven by corneal cold thermoreceptors' activation may constitute a protective mechanism to prevent excessive desiccation of the ocular surface.

(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)
Finding ophthalmic risk and evaluating the value of eye exams and their predictive reliability ‐ A cohort to risk stratify the glaucoma population
Authors: Kolko Miriam
Published: January 2024

Project FOREVER is a comprehensive database of clinical eye data collected in 100 optician stores across Denmark. All participants are answering a questionnaire on eye health. The aims of Project FOREVER are to 1) identify risk factors and predictors of visual disability, 2) identify risk factors and predictors of systemic conditions to prevent life‐threatening diseases, and 3) validate the current eye health check in optician shops to optimize the collaboration between optometrists and ophthalmologists. The method by which we have started and how we implement Project FOREVER will be summarized. Moreover, some initial results will be presented and discussed.
Optical coherence tomography ‐ Additional contrast mechanisms, future trends, and cutting‐edge technological developments
Authors: Irsch Kristina
Published: January 2024

In ophthalmology, structural OCT measurements are now used routinely in the clinic to help with the diagnosis and management of anterior‐segment and retinal disorders. More recently, the development of additional or complementary contrast mechanisms, as well as novel approaches targeted at enhancing resolution, have opened up new opportunities for ophthalmic OCT applications. For example, different algorithms have been proposed to contrast the retinal and choroidal vasculature and analyse blood flow, which extend clinical spectral‐domain OCT (SD‐OCT) from structural to functional imaging capabilities. Such OCT‐based angiography (OCT‐A) relies on sequential capture of SD‐OCT images at the same tissue region and the subsequent analysis of temporal variations in the OCT signal. OCT‐A algorithms differ in this analysis, specifically in how they create contrast between flow and static tissue (i.e. how they distinguish vascular from other structures). Common is the assumption that the change in the OCT signal over time is mainly due to the motion of backscattering particles, such as erythrocytes. With so‐called polarization‐sensitive OCT (PS‐OCT), polarized light has also been employed to create tissue‐specific contrast. PS‐OCT has shown great potential for functional and quantitative imaging and exploits the fact that various tissues, particularly birefringent structures in the cornea and retina (e.g. corneal collagen fibrils and the retinal nerve fibre layer), can change the state of polarization of incident light. Other technological developments have focused on enhancing OCT's resolution. Note that while OCT enables high‐resolution cross‐sectional views (where the axial resolution is determined by the spectral bandwidth of the light source), it has a limited lateral or en‐face resolution. Integrating adaptive optics (AO) is one method to improve the lateral resolution of retinal OCT. This lecture will discuss recent technological advances and cutting‐edge developments, leading to additional contrast mechanisms and functional extensions (e.g. OCT‐A, PS‐OCT) or improved lateral resolution (e.g. AO‐OCT).
How I am working as a reviewer?
Authors: Grzybowski Andrzej
Published: January 2024

Peer review is designed to evaluate the validity, quality and often the originality of articles for publication. Its aim is to provide the integrity of science by filtering out invalid or poor‐quality submissions. Moreover, the process of peer review adds value to the article by helping to improve that work. 90% of researchers feel that peer review improves the quality of their published paper. Peer reviewing is a critical, and constructive evaluation of submission, particularly including analysis of the paper structure and presentation, methodology strength and clarity; and originality of the study. There are some benefits related with reviewing. It makes a person better writer and better author of future scientific pieces. It helps to think critically about own research and become a better researcher. It is often a sign and proof of the reputation within the field. High‐quality reviews are noticed and appreciated by the editors, who often will invite reviewer to be more involved in editorial work, as an author of editorials or editorial board member. Very often journals invite new editorial members only with some previous history of reviewing for the journal. Reviewers also have often access to emerging ideas and trends much earlier than others.
Introduction to dynamic retinal vessel analyses
Authors: Kotliar K. E. , Lanzl I. M.
Published: January 2024

Retinal vessels possess the same structure and function as cerebral vessels and reflect the status of the central microcirculation. In the pre‐, post‐ and capillary areas, the behaviour of retinal vessels does influence blood flow and flow‐related metabolism through changes in arterial and venous diameter. In dynamic retinal vessel analysis, the function and structure of retinal vessels are subjected to a non‐invasive functional and structural examination over a period before, during and after a specific vascular stimulation. The use of several methodological modalities together with their relevant quantitative biomarkers represents a promising approach for the evaluation of ocular and systemic diseases of vascular origin as well as cerebro‐ or cardiovascular morbidity and mortality. Dynamic retinal vessel analysis has been employed in cross‐sectional and interventional clinical studies in ophthalmology and interdisciplinary in other branches of the medicine including cardiology, neurology, neurosurgery, nephrology, diabetology, hypertensiology, gynaecology and others. The paper aims to give a brief overview in the technology and the methodology of dynamic retinal vessel analysis.
Glaucoma or not glaucoma? ‐ How to navigate problematic cases?
Authors: Smedowski Adrian
Published: January 2024

Optic neuropathies refer to a group of eye conditions that involve acute or chronic damage to the optic nerve, which is responsible for transmitting visual information from the eye to the brain. The optic nerve is made up of millions of nerve fibres that can be affected by a variety of primary or secondary insults, leading to progressive neurodegeneration of optic nerve axons, being projections of retinal ganglion cells. The most common optic neuropathies that we should consider in differential diagnosis represent glaucoma, ischemic, inflammatory, toxic, hereditary, traumatic, and compressive optic neuropathies.

Although the visual field test is one of the most basic and oldest diagnostic method in ophthalmology, it represents a sophisticated test that allows to differentiate ongoing pathology, based on features of observed scotomas. The specific features include localization, steepness, relativity and symmetry of visual field defects. By combining those features with clinical anamnesis, imaging techniques and electrophysiological data, properly used visual fields can be a powerful tool to provide patients and other medical specialists with further direction of diagnostic process and treatment. This course aims to provide a series of cases‐based analysis of different visual field results, to establish certain universal rules and to provide useful tips, how to diagnose difficult glaucoma cases using perimetry and how to rule out non‐glaucomatous neuropathies, allowing to speed up and to properly direct the diagnostic process.
Does the Eyesi direct ophthalmoscope increase interest in ophthalmology?
Authors: Flockerzi Elias , Deuchler Svenja , Abdin Alaa Din , Flockerzi Veronika , Löw Ursula , Flockerzi Fidelis , Koch Frank , Seitz Berthold
Published: January 2024

Purpose: This study based on direct ophthalmoscopy (DO) teaching in medical curricula aimed to integrate both classic and simulator‐based DO techniques into the teaching of medical students.

Methods: 110 medical students received a multiple‐choice questionnaire (four theory questions, six fundus photographs) prior to simulator‐based (EyeSi® Direct, Haag‐Streit Simulation, Germany) and classic DO training (Heine BETA®200, Heine Optotechnik GmbH, Germany). Simulator‐based DO training was performed in groups of up to eight students.

Thereafter, they underwent an objective standardized clinical examination containing questions about (1) pupil dilation, (2) mydriasis contraindication, (3) ophthalmoscope adjustment and a practical test checking whether (1) optic nerve head, (2) macula, (3–6) upper/lower vessel arcade nasally versus temporally were identified correctly. Subsequently, classic DO was performed mutually and they reported the funduscopic structures they had recognized. Finally, the questionnaire was repeated 1 week later in combination with an evaluation of simulator‐based versus classic DO.

Results: Students improved from an average of 4.0 ± 1.5/10 before to 8.8 ± 1.5/10 correctly answered questions after training (p < 0.0001, Wilcoxon matched‐pairs test). 87|34|61 students named pupil dilating time mydriasis contraindication and adjusted the ophthalmoscope correctly. They successfully identified the optic nerve head (n(simulator)|n(classic) DO: 110|68, p < 0.0001, Fisher's exact test), the macula (93|22, p < 0.0001), the upper (98|75, p = 0.0002) and lower temporal vessel arcade (101|91, p = 0.0672), the upper (84|56, p = 0.0001) and lower nasal vessel arcade (87|48, p < 0.0001). They wished for more simulator‐based training, indicated a higher interest in ophthalmology after training and stated an improvement of their ophthalmoscopy skills.

Conclusion: A standardized simulator‐based approach improves medical students' skills in ophthalmoscopy and arouses professional interest in ophthalmology.
Simulator approaches in otorhinolaryngology ‐ Looking beyond the ophthalmological horizon
Authors: Flockerzi Veronika , Schick Bernhard , Flockerzi Elias , Berndt Sabrina
Published: January 2024

Purpose: To improve medical students' learning of handheld otoscopy technique and findings based on a standardized simulator‐based procedure.

Methods: A group of 120 medical students received a questionnaire containing 10 multiple choice questions (four theory questions, six pathological eardrum findings) prior to simulator‐based training (Earsi otoscope, Haag‐Streit Simulation, Germany) and classic otolaryngology internship without separate otoscopy training. Simulator‐based practical training was performed in groups of four students for 90 min with 40 students (“simulator group”) in addition to the classic otolaryngology internship (“control group”). After training, the students in the simulator‐group underwent an objective standardized clinical examination. Items assessed were (1) use of the correct hand, (2) correct handling of the otoscope, (3) stabilization of the otoscope with a finger, (4) pulling pinna upwards and backwards, (5) correct insertion depth, (6) atraumatic performance, (7) time required for task completion and (8) percentage of the assessed eardrum surface (cut‐off <85%). In addition, students were asked to draw the pathology shown during the examination (myringosclerosis, a whitish scar on the tympanic membrane) on a provided tympanic membrane sketch. The drawing was classified as “correct” or “incorrect” by a person uninvolved in the course. A maximum of eight points could be achieved. Students evaluated the simulator‐based otoscopy training afterwards. At the end of the otolaryngology internship, the questionnaire was repeated 4 weeks after the simulator‐based otoscopy training.

Results: All participating students improved from an average of 4.5 ± 1.7/10 before otolaryngology internship to 6.4 ± 1.7/10 correctly answered questions after training. Looking at the two subgroups, it is noticeable that the students in the simulator group (7.1 ± 1.6/10) performed better than those without simulator‐based otoscopy training (6 ± 1.6/10). All students in the simulator group achieved good results in the objective standardized clinical examination (5.1 ± 1.4/8).

The participating students rated the simulator‐based training mostly as “very good“. The students wished for more simulator‐based training and indicated higher interest in otolaryngology after training. Furthermore, they stated an improvement of their otoscopy skills and understanding of eardrum findings.

Conclusion: A standardized simulator‐based approach improves medical students' skills in handheld otoscopy and arouses professional interest in otolaryngology.
Anti‐VEGF for wet AMD ‐ Which drug and how often?
Authors: Swiech Anna
Published: January 2024

Introduction of anti‐VEGF agents as a treatment option of neovascular AMD (ex AMD) in 2004 have brought dramatic progression in the treatment of that disease and until now it is a gold standard for ex AMD management. In that course we will present following subjects concerning ex AMD treatment with the use of anti‐VEGF drugs. We will present a variety of anti‐VEGF agents used now for ex AMD treatment: ranibizumab, aflibercept, brolucizumab, faricimab. We will discuss the differences between these drugs, in terms of efficacy and safety. Results from clinical trials and real life observations will be presented. Novel drug‐faricimab will be presented as bispecific antibody‐which inhibits both angiopoietin‐2 and VEGF‐A which possesses superior therapeutic action in reducing vascular leaking and inflammatory responses. The rules of different regiments of anti‐VEGF treatment will be discussed‐ fixed, PRN (pro re nata), TREX (treat and extend). We will discuss as well two important problems: When to switch to the other drug in ex AMD treatment and which were the results of the treatment of patients with ex AMD during the COVID‐19 pandemic. New therapeutic strategies in ex AMD will be presented as research in under way to develop novel anti‐VEGF agents with longer duration of action and to identify new methods of delivery with long‐ term release of anti‐VEGF medication as intraocular implants.
The implantable miniature telescope (IMT) new developments: The US and UK experience
Authors: Levy Marc H. , Keegan David , Neffendorf James E.
Published: January 2024

The Implantable Miniature Telescope (IMT) is a viable option for patients afflicted with decreased vision in both eyes (20/160 to 20/800) from the advanced form of dry age‐related macular degeneration. It has a 21‐year history of being both safe and effective. The IMT uses a Galilean telescope design that utilizes wide‐angle quartz micro‐optics when used in conjunction with the cornea to create a telephoto system that magnifies objects in view by 2.7X. This axial magnification allows central images to be projected onto healthy paramacular areas of the retina instead of the fovea alone, thereby reducing the central blind spot and allowing the patient to discern images that may have been previously unrecognizable or difficult to see. The IMT is both FDA approved and carries a CE mark. The FDA lowered the minimum age from 75 to 65 years of age, based on the 5‐year FDA data that showed slightly more visual improvement in younger patients than patients aged 75 years and older.

Based on the UK experience, the FDA initiated an independent study on pseudophakic patients to monocularly exchange a posterior chamber intraocular lens for the 2.7X IMT, but unfortunately recruitment was inadequate to derive useful data. An injectable form of the IMT (SING) is currently being investigated in the US and UK which shortens the surgical time, incision length and capsulorhexis requirements. As the incidence of advanced age‐related macular degeneration increases due to the development of geographic atrophy, the IMT should be strongly considered in patients who are visually symptomatic in order to gain an increase of daily living.
Genetic findings of individuals with inherited retinal diseases in Finland
Authors: Turunen Joni
Published: January 2024

Genetic research can benefit from population isolates like Finland, as they tend to have a high concentration of deleterious alleles on a small number of low‐frequency variants. To investigate gene findings from the patients with inherited retinal disorders (IRD) in Finland, retrospectively collected data from the patients with IRDs treated between January 1st of 2012, and December 31st of 2020 at the Department of Ophthalmology, Helsinki University Hospital. Of the 638 patients that underwent genetic testing, 79% received a likely genetic diagnosis (504/638). The genetic findings corresponded to autosomal recessive (AR) inheritance in 242 patients, X‐linked (XL) in 158, autosomal dominant (AD) in 94, and mitochondrial inheritance in 22 patients. The most common genetic diagnosis was X‐linked retinoschisis as 17% (84/504) harboured pathogenic variants in RS1. The most common retinitis pigmentosa genes with causative variants were CERKL (8.5%, 43/504), RPGR (5.8%, 24/504), and EYS (5%, 25/504). CERKL variant c.375C>G, p.(Cys125Trp) and EYS c.1155T>A, p.(Cys385Ter) are frequent founder mutations. The Stargardt disease is less common than in other Western countries, the pathogenic variants in the ABCA4 gene were found in 24 patients. Pathogenic variants were also found in CHM (26), and CLRN1 (16). The genetic landscape of IRDs in Finland differs from other Western countries due to its specific isolated population history. The high yield of genetic findings is possibly explained by the enriched founder mutations in the population. One‐fifth of the patients are lacking genetic diagnosis, which might be due to shortages in the testing methods, i.e., non‐coding variants and complex structural genomic variants are missing. To address this problem, we have been utilizing the whole genome and long‐read sequencing methods to uncover new pathogenic variants. In two families with IRDs, we have found large structural variants in the RP1 and PRPH2 genes using Nanopore long‐read sequencing. In the future, we try to utilize the advantages of the population isolate to find unknown genes causing IRDs.
Small extracellular vesicles derived from reactive microglia contribute to retinal neuroinflammation and neurodegeneration
Authors: Aires Inês Dinis , Boia Raquel , Ribeiro‐Rodrigues Teresa , Girão Henrique , Francisco Ambrósio António , Santiago Ana Raquel
Published: January 2024

Glaucoma is a leading cause of blindness worldwide and is characterized by progressive degeneration of retinal ganglion cells and damage to the optic nerve. Elevated intraocular pressure is a main risk factor. Moreover, chronic neuroinflammation plays an important role in glaucoma. Microglia become reactive when challenged with elevated pressure, releasing cytotoxic factors that contribute to retinal ganglion cell death. We have been reporting that controlling microglia‐mediated neuroinflammation in experimental glaucoma is sufficient to protect retinal ganglion cells from damage.

Small extracellular vesicles are constitutively released by most cells and are important vehicles of intercellular communication, conveying lipids, proteins and genetic material. Small extracellular vesicles derived from microglia exposed to elevated pressure trigger a pro‐inflammatory response in microglia, as determined by increased production of proinflammatory cytokines, microglia motility, phagocytosis, and proliferation. These small extracellular vesicles also increase cell death and impact the survival of retinal ganglion cells. The depletion of retinal microglia halt neuroinflammation induced by small extracellular vesicles isolated from microglia at elevated pressure, suggesting that microglial small extracellular vesicles preferentially interact with microglia. Small extracellular vesicles isolated from microglia challenged with elevated pressure are also enriched in proteins associated with inflammatory signalling and RNA processing and in miRNAs that modulate the NF‐kappaB pathway.

This route of communication between microglia involving small extracellular vesicles helps to clarify the pathological mechanisms in glaucoma and may open new perspectives for the development of therapies targeting microglia neuroinflammation.

Funding: FCT, Portugal (UID/NEU/04539/2019; UIDB/04539/2020; UIDP/04539/2020), COMPETE‐FEDER (FCOMP‐01‐0124‐FEDER‐028417; POCI‐01‐0145‐FEDER‐007440), Centro 2020 Regional Operational Programme (CENTRO‐01‐0145‐FEDER‐000008: BRAINHEALTH2020).
Corneal epithelial cell markers in congenital aniridia
Authors: Szentmáry Nóra , Amini Maryam , Suiwal Shweta , Fries Fabian N. , Nastaranpour Mahsa , Seitz Berthold , Li Zhen , Chai Ning , Ludwig Nicole , Stachon Tanja
Published: January 2024

Congenital aniridia is a rare panocular disease in which almost all structures of the eye are affected. The observed corneal abnormalities are called aniridia‐associated keratopathy (AAK). AAK is characterized by progressive limbal stem cell deficiency (LSCD), epithelial thinning and erosions, corneal ulceration, vascularization, inflammation and pannus formation. Although in some aspects AAK resembles other types of LSCD, through its specific genetic origin, alterations in corneal epithelial cell gene expression differ from other types of corneal diseases. Primary limbal epithelial cells of aniridia subjects lack expression of KRT3 and KRT12 mRNA and protein, and DSG1, ADH7, FABP5, CRABP2, SPINK7 and ALDH1A1 mRNA expression is decreased in these cells. However, miRNA 138‐5p expression is upregulated. This epithelial behaviour can also be mimicked using an siRNA based aniridia primary limbal epithelial cell model.