bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal pigment epithelial (RPE) tears after serous pigment epithelial detachment (PED) in wet AMD: A retrospective study of 23 patients
Authors: Skalicky Nicolas , Cedro Luca , Katja Hatz
Published: December 2022

Purpose: Age‐related macular degeneration (AMD) is one of the main causes for vision impairment. Pigment epithelial detachment (PED) is a common finding, which in its serous form is associated with wet AMD. PED can lead to retinal pigment epithelial (RPE) tears, which are associated with a further loss in vision. One known risk factor for RPE ruptures is the use of anti‐VEGF injections in patients with persisting PED. The aim of our study was to identify morphological parameters in the SD‐OCT that could present risk factors for RPE tears. Furthermore, this study aims at helping to predict functional and morphological outcomes for patients with RPE tears associated with PED in AMD.

Methods: All patients in the database of Vista Augenklinik Binningen, Switzerland, diagnosed with RPE tears in SD‐OCT were included. Patients who presented with RPE tears at their first consultation were excluded from the study. Both morphological factors in imaging (SD‐OCT, FAF), as well as the history of anti‐VEGF injections prior and after the RPE tears occurred, were retrospectively analysed.

Results: 23 eyes of 23 patients (57% females) were included. At the time of the RPE tear, the mean age was 81.9 ± 13.1 years (range: 70–95 years, median: 83 years). Mean follow‐up time was 28.7 ± 31 months (range: 1–52 months) after the rupture. The mean height of PED was 324.5 μm (range: 24‐837 μm) at the first consultation. In 6 out of 7 patients (86%) with initial PED height > 526 μm, an RPE rupture occurred between the first and second consultation. 4 out of those 6 patients (67%) had received their first anti‐VEGF injection. Only 2 out of the other 16 patients (12%) with PED ≤375 μm had a rupture between the first and second consultation. The mean PED height in the last OCT imaging before rupture was 563 ± 486.55 μm (range: 121‐1039 μm). 8 patients (35%) had received exactly one anti‐VEGF injection before the rupture (mean height before rupture: 580,5 μm), another 8 patients (35%) received more than one injection (range: 2–55, mean height before rupture: 589,1 μm) and 7 patients (30%) did not receive anti‐VEGF injections (mean height before rupture: 513.1 μm).

Conclusions: The risk of RPE tears should be considered when treating patients with PED in wet AMD. Further studies with larger sample sizes should be encouraged in addition to the existing scores.
Toxic conjunctivitis due to cosmetics: Description of the pathology and evaluation of topical treatment with unpreserved hydrocortisone 3.35 mg/ml and ketotifen 0.25 mg/ml
Authors: Mokka Agni , Boboridis Konstadinos G.
Published: December 2022

Purpose: To describe the frequently misdiagnosed condition of toxic conjunctivitis due to facial cosmetics' use and to evaluate the effectiveness of our topical anti‐inflammatory treatment.

Methods: Over a one‐year period (2021) we recorded 28 patients (26 females and 2 males) with toxic conjunctivitis due to the use of facial cosmetic creams. The clinical presentation involves burning sensation, epiphora, redness and edema of palpebral conjunctiva with follicular response, edema of punctum and contact dermatitis of the medial lid skin. We advised cessation of facial creams and administered artificial tears with HA, topical unpreserved hydrocortisone 3.35 mg/ml (4 times daily for 2 weeks) and ketotifen 0.25 mg/ml (twice daily for 4 weeks). Follow up was in 2 and 4 weeks.

Results: All patients had symptoms for over 2 months and received more than 3 different treatments. In 4 weeks, 23/28 (82%) patients had full recovery, whereas 5/28 (18%) although improved required reaffirming of cosmetic cessation and continued topical ketotifen for two more weeks until complete resolution of symptoms.

Conclusions: Toxic conjunctivitis due to facial creams is a frequent condition, especially in women, and is often misdiagnosed as allergic conjunctivitis. Cessation of facial creams for the duration of the treatment is mandatory. Topical treatment with HA artificial tears, topical unpreserved hydrocortisone 3.35 mg/ml and ketotifen 0.25 mg/ml offers highly effective anti‐inflammatory action with no increase in intraocular pressure or other side effects.
Aflibercept as a treatment for neovascular membrane associated with choroidal osteoma
Authors: Perea Juan Antonio Sánchez , Menargues Manuel Almarcha , Abellán Maria Victoria Navarro , López Carmen Miquel
Published: December 2022

Purpose: To assess the importance of treating the patient with choroidal osteoma‐associated neovascular membrane by administering anti‐angiogenic (anti‐VEGF) drugs.

Methods:: We present a descriptive study (case report). We have performed a multimodal imaging study of a patient with an inferior temporal peripapillary choroidal osteoma. The best corrected visual acuity (BCVA) was taken in a patient diagnosed with a choroidal osteoma after magnetic resonance imaging (MRI) and ultrasound. The patient presented with a decrease in visual acuity and a study using optical coherence tomography angiography (OCTA) revealed a type II neovascular membrane affecting the temporal area of the choroidal osteoma. Optical coherence tomography (OCT) revealed a neurosensory detachment.

Results: Serial OCT evaluation revealed a neovascular membrane with associated neurosensory detachment, which was treated with intravitreal injections of Aflibercept, resulting in an MAVC of 0.1 to an MAVC of 0.7 after 2 months. On OCTA we observed disruption of the retinal pigment epithelium. Treatment with monthly injections is required for the first 3 months, with bimonthly treatment for a further 6 months. At present the MAVC is 0.6 and no further injections are required for the time being.

Conclusions: Serial multimodality imaging is very useful in the follow‐up of patients with choroidal tumours. It allows us to observe associated complications such as the neovascular membrane that we found in the context of a patient with a choroidal osteoma, a benign bone tumour that mainly affects young women without associated diseases. Despite being benign, it can cause irreversible loss of vision either due to the tumour affecting the macular area or due to complications such as choroidal neovascularisation, which occurs in one third of cases.
Fish‐eye disease: Ocular characteristics in anterior‐segment optical coherence tomography of a patient with lecithin‐cholesterol acyltransferase deficiency
Authors: El Bakkali Ismael Bakkali , Arias Pablo Cisneros , Rivasés Guillermo Pérez , Moscarda Eva Josefina Núñez , de Rivas Marta Orejudo , Fernández Miguel Castillo , Martínez Marta Suñer , Puyuelo Francisco Javier Ascaso , Sayas María Ángeles Del Buey
Published: December 2022

Purpose: We describe a case of Fish‐Eye Disease (FED) in which the clinical features and visual function were investigated using anterior‐segment optical coherence tomography (AS‐OCT).

Methods: A 38‐year‐old Spanish man with a known history of dyslipidemia came to our Hospital referring mild blurred vision and whitening of both eyes. Visual acuity was 1.00 (decimal). Slit‐lamp examination showed bilateral, peripheral yellowish‐white corneal opacities, causing corneal clouding. An AS‐OCT was then performed, showing homogeneously hyper‐reflective corneal stroma. On systemic examination, the patient had low plasma high‐density lipoprotein cholesterol levels.

Results: Both slit‐lamp examination and AS‐OCT imaging revealed a corneal opacification compatible with FED, a clinical feature secondary to a lecithin‐cholesterol acyltransferase (LCAT) deficiency. The patient was sent to genetic counselling to study the mutation, which was later found to be positive for LCAT gene.

Conclusions: Although it is not a common genetic disorder, FED should be included in the differential diagnosis of corneal clouding. The findings from this case suggest that a complete eye examination, both with slit‐lamp and AS‐OCT, can be useful for an early FED diagnosis despite good visual acuity.
Morphological changes of eye tissues after the influence of high‐frequency electric current welding with suprachoroidal approach to induce chorio‐retinal adhesion
Authors: Saoud Omar , Sergiienko Andrii , Korol Anatoliy , Umanets Mykola , Petrovski Goran , Rehak Matus , Lytvynchuk Lyubomyr
Published: December 2022

Purpose: to evaluate the morphological changes in eye tissue after the influence of high‐frequency electric current welding (HFECW) with suprachoroidal approach in rabbit's eyes in order to induce chorio‐retinal adhesion as an alternative treatment for retinal tears.

Methods: 54 adult rabbits were used. The study complied to the ARVO statement for use of animals in ophthalmic and visual research. In the treated group, the retina was coagulated 7–10 mm from the limbus through a U‐shaped scleral incision with suprachoroidal approach using 23‐gauge tip and modified HFECW generator EK‐300 M1 (E.O. Paton Electric Welding Institute, Kyiv, Ukraine) with parameters: 66 kHz HFECW, three modes of 10–12 Volts (V), 12–14 V and 14–16 V. The eyes were then enucleated after 1 hour and 3‐, 7‐, 14‐ and 30‐days. Tissue changes were analysed using haematoxylin–eosin staining and light microscopy, and compared to the control eyes.

Results: In all treated eyes the monopolar HFECW induced an increased tissue adhesion in the area of electrode application, which strengthened with time. The retina responded by apparent destruction of rods, cones, loss of bipolar, amacrine, horizontal and ganglion cells, development of cysts and migration of RPEs. The choroid showed damage and migration of melanocytes. By 30 days, a ​​tissue thinning with partial cell regeneration and connective tissue degeneration were apparent. Amplification of the voltage from 10 to 16 V caused a shift from active exudation without significant tissue damage to acute retinal necrosis, respectively. The nearby lying retinal layers and vitreous remained intact.

Conclusions: Application of HFECW with suprachoroidal approach induced chorio‐retinal adhesion in 1 hour after the treatment, which strengthened within first weeks after the surgery. Implementation of HFECW as an alternative method to treat retinal tears in eyes with retinal detachment could reduce the need for endotamponade and the risks of its possible complications.
Evaluation of choroidal thickness in AMD: A 10‐year follow‐up study
Authors: Moleiro Ana Filipa , Rodrigues Rita , Carneiro Ângela , Falcão Manuel
Published: December 2022

Purpose: To evaluate choroidal thickness (CT) progression in patients with Age‐related macular degeneration (AMD) according to different phenotypes.

Methods: Retrospective review of patients followed on AMD outpatient clinic from our hospital. Subfoveal CT was measured recurring to cross‐sectional spectral‐domain optical coherence tomography (SD‐OCT) images. Annual measurements were performed for each patient. Demographics, visual acuity and number of intra‐vitreal treatments were also collected.

Results: One hundred and seventeen eyes from 87 patients (mean age 81.6 ± 6.6 years) were included. Intermediate AMD (group 1) was present in 14 eyes, exudative AMD (group 2) in 83 eyes, and atrophic AMD (group 3) in 14, while six eyes did not present any relevant pathology (group 4). Significant CT reduction was evident during the follow‐up of all the groups (p < 0.001, CT at beginning vs 5‐year follow‐up). No statistical differences in initial or 5‐years CT were noted between the groups (p = 0.123 and p = 0.126, respectively). After 5 years, CT presents a further significant annual reduction in AMD eyes (p < 0.001) while eyes without signs of AMD stabilize. The degree of choroidal thinning seems to vary between groups, especially during the 5 to 10 years follow‐up. At 10‐years follow‐up (N = 65), CT is statistically different among groups (p = 0.04) with atrophic AMD showing the lowest CT (mean CT 149.0 ± 38.0 μm, CT variation −42.7 ± 35.4 μm) and healthy eyes the lowest reduction (mean CT 313 ± 43.5 μm, CT variation −9.6 ± 9.2 μm). CT variation correlates with macular retinal thickness and the number of intravitreal injections in group 2 (p < 0.01). Visual acuity did not correlate with CT (p = 0.07) although thinner choroids present better visual acuities.

Conclusions: AMD eyes showed a significant choroidal thinning during the follow‐up, more marked in atrophic AMD. Macular retinal thickness seems to be a predictor of CT. Further studies, with a higher number of eyes are needed to validate our results.
Evaluation of risk factors for recurrence by anterior segment optical coherence tomography in pterygium surgery
Authors: González Marina Aguilar , Peris‐Martínez Cristina , Camps Isabel Pascual , Ontiveros Ana Hervás , Payá Emma Marín , Gregori Enrique España
Published: December 2022

Purpose: To study if there is an association between the values obtained by anterior segment optical coherence tomography (AS‐OCT) preoperatively and postoperatively to pterygium surgery using the technique of conjunctival autograft with biological glue and its risk of recurrence.

Methods: A prospective one‐year study was carried out in 50 patients with primary pterygium who underwent excision surgery and conjunctival autograft with biological glue. All of them received the same postoperative treatment. They were followed up in the same way by taking preoperative pterygium measurements and postoperative autograft measurements by AS‐OCT and the number of recurrences was recorded. To obtain the measurements, a line was drawn perpendicular to the ocular surface at the level of the scleral spur, and the intersection of this line with the ocular surface was taken as a reference point to measure the length and the thickness of the pterygium at limbus, center and head, and the thickness of the conjunctival autograft at 1 mm (epithelial, stromal and total), 2 mm (total) and 3 mm (total).

Results: The postoperatively autograft thickness AS‐OCT measurements were associated with pterygium recurrence after conjunctival autograft with biological glue surgery.

Conclusions: There are measurable factors by AS‐OCT that can be correlated with a higher rate of pterygium recurrence after surgery.
Effect of olfactory ensheathing glia clone TEG3 on neuroprotection, microglial activation and gene expression profile of allotransplanted retina with and without immunosuppression
Authors: Muñoz María Norte , Portela‐Lomba María , Sobrado‐Calvo Paloma , Di Pierdomenico Johnny , Vidal‐Sanz Manuel , Moreno‐Flores María Teresa , Agudo‐Barriuso Marta
Published: December 2022

Purpose: Olfactory ensheathing glia (OEG) is a macroglia from the embryonic ectoderm, with unique functions in guiding sensory axons from the olfactory mucosa (PNS) to the olfactory bulb (CNS). These properties, together with their high secretion of trophic factors, have made its use a field of study in axonal regeneration. However, their in vivo administration in the retina had never been tested, so we set out to evaluate their actions in the retina without injury and after an optic nerve crush (ONC) model. In addition, to simulate the clinical conditions of an allogeneic cell transplant, we evaluated how their properties were altered when combined with immunosuppressive treatment.

Methods: Wistar TEG3‐GFP+ cells were administered into the vitreous of SD female rats. Experimental groups: transplantation in intact retinas, in retinas just after ONC, and both with systemic immunosuppression. In some animals of each group, the retina was dissected for anatomical analysis and the total number of retinal ganglion cells (RGCs) was counted and the morphological activation of microglia was studied. The retinas of the remaining animals were dissected fresh for the study of gene expression by real‐time quantitative PCR. Animals injected with vehicles after ONC and intact animals without injury were used as controls. n = 3–8 animals/group/analysis.

Results: TEG3 neuroprotected RGCs after ONC at 7 days (18% more survival compared to vehicle group p < 0.05) but caused a large activation of microglia cells coupled with a 33% (p < 0.01) reduction of RGCs 21 after transplantation in intact retinas. Immunosuppression had no effect on neuroprotective properties but did recover some of the death observed at 21 days in intact retinas (up to a 17%, p < 0,05). Immunosuppression reduced the expression of pro‐inflammatory molecules (Tnf, Il6), macrogliosis markers (Gfap) and macrophage markers (Ptprc) in favour of anti‐inflammatory ones (Il10). However, markers of pyroptotic cell death (Casp4, Gsdmd) did not change after treatment, which would explain the elevated microglial activation and death observed at 21 days in intact and grafted retinas.

Conclusions: TEG3 has a dual effect neurotoxic and neuroprotective in retina.
Cardiovascular risk factors and characterization of retinal drusen by OCT in subjects with genetic risk for the development of Alzheimer disease
Authors: Salobrar‐Garcia Elena , Sánchez‐Puebla Lidia , Gil‐Salgado Ines , Elvira‐Hurtado Lorena , Fernández‐Albarral José A. , Matamoros Jose A. , RAMIREZ Jose Manuel , Ramirez Ana I. , Ramirez‐Toraño Federico , Barabash Ana , SALAZAR Juan Jose , de Hoz Rosa
Published: December 2022

Purpose: The aim of this work is analyse and characterize retinal drusen in cognitively healthy subjects at high risk of developing Alzheimer's disease (AD) (having a family history (FH+) of AD and carrying ɛ4 allele for the ApoE gene) compared to control subjects.

Methods: Subjects are classified by their AD HF (HF‐ or HF+) and their ApoE ɛ4 allelic characterization (ApoE ɛ4‐ or ApoE ɛ4+) to analyse retinal drusen by OCT. Hypercholesterolemia (HCL), blood high pressure (HBP) and diabetes mellitus are also considered in this analysis. In addition, we analysed choroidal thickness by OCT.

Results: When we compared the drusen number between groups taking account the HCL, there was statistical significance between the FH‐ ApoE ɛ4‐ HCL+ group and (i) FH+ ApoE ɛ4‐ HCL+ and (ii) FH+ ApoE ɛ4+ HCL‐ groups. Considering HBP and comparing the drusen number between the study groups, we found statistically significant differences when comparing the FH‐ ApoE ɛ4‐ HBP‐ group and the FH+ ApoE ɛ4+ HBP+ group. We also found statistically significant differences in the number of drusen when comparing the FH‐ ApoE ɛ4‐ HBP+ group with: (i) FH+ ApoE ɛ4‐ HBP‐ group; and (ii) FH+ ApoE ɛ4+ HBP+ group).

Conclusions: In conclusion, there does not appear to be a relationship between AD HF or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared with patients without drusen, reaching statistical significance in the group of participants with an AD HF, without ApoE ɛ4, and with HCL. This thinning could trigger changes in choroidal perfusion that could give rise to the deposits that generate drusen.
Investigating the potential neuroprotective effect of semaglutide in the mouse retina
Authors: von Spreckelsen Alexander
Published: December 2022

Purpose: To investigate the potential locally mediated neuroprotective effect of the glucagon‐like peptide 1 receptor agonist, semaglutide, in the mouse retina, including an assessment of the underlying mechanisms of action.

Methods: The study was conducted using surgically isolated retinas from female C57BL/6jRj mice as ex vivo model system. Retinas were exposed to different concentrations (10–100 nM) of semaglutide for different exposure durations (2–48 h). Retinal explant viability was assessed employing the lactate dehydrogenase release assay. The number of retinal ganglion cells (RGCs) was quantified employing immunohistochemistry. The acute and intermediate effect of semaglutide on the ex vivo retinal glucose metabolism under euglycemic conditions was assessed through metabolic mapping employing [U‐13C]glucose, followed by relative analyte quantification employing gas chromatography–mass spectrometry. The influence of semaglutide on the retinal mitochondrial function was assessed by employing the Seahorse assay on isolated retinal mitochondria.

Results: Semaglutide exerted no effect on the retinal explant or RGC viability. Semaglutide may acutely potentiate the retinal ex vivo glucose metabolism/mitochondrial function indicated by statistically significant glucose hypermetabolism (increased 13C‐enrichment) of certain tricarboxylic acid intermediates (citrate and α‐ketoglutarate) relative to the control. Results on the effect of semaglutide on the mitochondrial function/oxygen consumption rate are not yet available.

Conclusions: Under the experimental conditions, semaglutide did not influence the retinal explant or RGC‐specific viability. Semaglutide may acutely potentiate the retinal ex vivo glucose metabolism by enhancing the mitochondrial function. Additional studies are needed for clarification.
What do we know about preservatives?
Authors: Tatham Andrew
Published: December 2022

Preservatives have played an important role in traditional topical ophthalmic medications. However, problems associated with preserved eye drops include ocular surface disease, poor tolerability and adherence, reduced quality of life, and increased risk of failure of glaucoma surgery. This presentation explores the evidence for and against the use of preservatives in glaucoma medications and explores whether preservative free drops should be first line for all. The cytotoxic effects of preservatives will be examined and practical advice provided on the management of iatrogenic ocular surface disease.
Generics pros and cons
Authors: Meier‐Gibbons Frances
Published: December 2022

Although generic drugs have been replacing branded drugs for many years, but it is only required since 1992 that they have the same active and inactive ingredients.

However, are generic drugs really the same as branded drugs? In systemically applied drugs, the amount of the active substance can be tested. In eye drops, however, we do not know the exact amount of the active substance which reaches the eye. Hence, the knowledge that the active substance is a small part of the whole drop and that the inactive parts may be changed in generic drugs lead to the conclusion that a generic eye drop may differ from the branded counterpart.

The advantages of generic drops are mainly the costs: A new generic drug needs only the proof of the therapeutic equivalence or the pharmacokinetic bioequivalence and a sufficient compatibility, therefore it is much cheaper to produce a new generic drug than a branded drug.

The disadvantages are manifold: The drop can vary in the inactive substances and therefore in the tolerability. The shape of the bottle, the tip of the bottle and the size of the opening of the tip can vary, leading to a considerable difference in number of drops in one bottle.

Last but not least the patients may be sceptical about a generic drug, not knowing if it is as effective as the branded drug and having problems adapting to new shapes and colours of the bottles.

Generic drugs have taken over a big part of the anti‐glaucomatous drug market. However, we need to inform the patients that there may be substantial differences between generic and branded drugs and check the patients more often after changing their medication.
When to suspect mitochondrial disease and how to investigate it
Authors: La Morgia Chiara
Published: December 2022

Mitochondrial diseases are caused by both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) mutations and are characterized by heterogeneous clinical presentations due to the potential affection of each organ of the body, in particular those with high energy requirements.

The most common clinical presentations of mitochondrial defects are mitochondrial myopathy, central nervous system manifestations including cerebral, cerebellar, brainstem and spinal cord atrophy, white matter disease, stroke‐like episodes and epilepsy, peripheral neuropathy, optic atrophy, pigmentary retinopathy, sensorineural deafness, cardiomyopathy, diabetes and kidney disorders.

Thus, clinical diagnostic work‐out for mitochondrial disorders should include muscle biopsy, brain MRI with magnetic resonance spectroscopy, electromyography, electroencephalography, ophthalmological evaluation, audiometry, cardiac evaluation including echocardiogram, endocrinological and nephrological evaluation. Laboratory exams may include traditional markers as creatine kinase and lactic acid as well as more recent biomarkers such as GDF‐15 and FGF‐21.

Genetic testing includes both nuclear and mtDNA sequencing based on family history that can point towards a matrilinear or mendelian transmission of the genetic defect. Sporadic cases are also possible and this particularly apply to single mtDNA deletions and nuclear de‐novo mutations. Biochemical analysis of muscle biopsy is also important to evaluate the presence of single/multiple respiratory chain complexes defect.

The most common mitochondrial disorder due to mtDNA mutations is Leber's Hereditary Optic Neuropathy, followed by Mitochondrial Encephalopathy, Lactic Acidosis and Stroke‐like Episodes (MELAS), whereas among the nuclear genes OPA1 gene mutations are the most common cause of Dominant Optic Atrophy.

Reference

La Morgia C, Maresca A, Caporali L, Valentino ML, Carelli V. Mitochondrial diseases in adults. J Intern Med. 2020 Jun;287(6):592–608. doi: 10.1111/joim.13064. PMID: 32463135.
Chronic progressive external ophthalmoplegia
Authors: Karanjia Rustum
Published: December 2022

Chronic progressive external ophthalmoplegia (CPEO) is an array of genetic condition which causes progressive paralysis of the extraocular muscles and lid ptosis. CPEO can occur in isolation or in association with other systemic features (CPEO‐plus) including myopathy, dysarthria, ataxia, and parkinsonism. The condition can be part of a neurological syndrome such as Kern‐Sayre Syndrome (KSS), were pigmentary retinopathy, cerebellar ataxia, heart block and/or elevated CSF protein occur in addition to progressive external ophthalmoplegia.

The condition is caused by disfunction of oxidative phosphorylation and several genes in both the mitochondrial DNA and nuclear DNA have been demonstrated to cause CPEO. This results in a varied inheritance pattern, depending on the gene involved in the individual pedigree.

Clinically, most patients with CPEO develop a progressive symmetrical external ophthalmoplegia and thus do not typically experience diplopia. If diplopia is present, however, it can usually be managed by prism lenses although some patients do require surgical correction. This contrasts with the clinically significant ptosis, which typically requires surgical correction.

In this session we will review the clinical features and the genetic variants associated with CPEO along with the clinical management and pitfalls in caring for patient with CPEO.
How imaging can make the uveitis challenging cases easy
Authors: Koutsiouki Chrysa
Published: December 2022

Imaging plays a key role in the diagnosis, treatment and prognosis of uveitis. As uveitis case can be challenging especially the refractory ones the use of imaging is critical. Therefore on the already Gold standard Techniques (FFA / ICGA/OCT) new imaging modalities (wide filed imaging /FAF/ EDI/OCT‐A) are offering a better appreciation of the pathophysiologic mechanism involved, provide also non‐invasive methods to accurately diagnose differentiate, monitor the response to treatment or even demonstrate Biomarkers for disease activity. Thus significantly contributes to better visual and functional outcomes on the uveitis group patients.
Vitreoretinal complications of uveitis. The role of vitrectomy
Authors: Vakalis Athanasios
Published: December 2022

Vitrectomy plays an important role in both diagnosis and treatment of uveitis. With recent advances in techniques, instrumentation, laboratory testing and the advent of drug delivery systems, this role has recently expanded.

We explain the indications and techniques for vitreous and retinal biopsy, the clearing of media opacities, removal of inflammatory debris, dealing with structural complications such as CMO, ERM, hypotony and retinal detachment and the technique of inserting drug delivery systems. The Role of vitrectomy in controlling inflammation and reducing the need of medication as well as its potential complications is also discussed.
Alternatives to gonioscopy: Pros and cons
Authors: Rojanapongpun Prin
Published: December 2022

Gonioscopy is a not very attractive and well‐accepted examination, neither by the ophthalmologist, nor by the patient.

Therefore, it is logical, that there is an extensive research and development on the field of other options. These options, like Anterior Segment ‐OCT, Scheimpflug Camera, UBM and the “Gonioscope”, will be shown with their theoretical and practical advantages and disadvantages as well as their clinical use will be discussed and shown with pictures and movies.
Reading a standard automated perimetry printout
Authors: Jansonius Nomdo
Published: December 2022

Interpreting the results of standard automated perimetry (SAP) is not difficult but a systematic approach is pivotal. In this part of the course we address the following topics: Which test to choose in which situation? Is the test reliable? What are common artefacts and how do you recognize them? What do the various plots mean on the printout? What do the global indices mean? How do you differentiate a normal from an abnormal test? What abnormalities are typical of glaucoma? And what of other pathologies?
Recent aspects of riboflavin and UV‐a corneal crosslinking for keratoconus
Authors: Gkatzioufas Zisis
Published: December 2022

Corneal crosslinking (CXL) has been proven to inhibit the progression of keratoconus and corneal ectatic disease. Over the last years, new treatment protocols have emerged, aiming to increase efficacy and safety of the procedure. Nowadays, a plethora of different modalities are available, such as ‘epi‐on’ and ‘epi‐off’ procedures, ‘accelerated’ CXL, ‘pulsed’ CXL, ‘customized’ CXL, etc. At the same time, riboflavin solutions have also evolved in order to provide improved outcomes.

This talk will highlight the above mentioned innovations and evaluate their clinical relevance and importance, emphasizing on the ‘gold standard’ in CXL therapies, in an evidence‐based manner.
Intracorneal ring segments for KC and iatrogenic keratectasia
Authors: Daas Loay , Hamon L. , Flockerzi E. , Seitz B.
Published: December 2022

ICRS are polymethylmethacrylate (PMMA) implants developed to be inserted in the corneal stroma aiming to remodel the ectatic corneal curvature. In 2000, ICRS have been introduced for the implantation in KC treatment. Since then, several authors have demonstrated the efficacy of this surgical procedure for improving the refractive and topographic results of KC patients. Moreover, the method has been extended to a larger spectrum of corneal ectasia, such as pellucid marginal degeneration (PMD) and iatrogenic ectasia after laser in situ keratomileusis (LASIK). Our aim was to evaluate the functional results, i.e. how uncorrected and corrected distance visual acuity can be improved by implantation of ICRS. Progression of ectasia seems to be retarded. However, consistent follow‐up visits at close intervals are necessary to identify complications at an early stage. The complications after ICRS implantation are rare due to strict patient selection and modern surgical techniques.
Role of AS‐OCT in DALK and PKP for KC
Authors: Wylegala Edward
Published: December 2022

OCT has been a diagnostic device in corneal diseases for many years. Non‐contact examination enables obtaining morphological and morphometric data useful in clinical practice. For example, a patient with keratoconus is a diagnostic tool in surgical procedures such as keratoplasty, intracorneal ring implants, and corneal collagen cross‐linking (CXL). The presentation will show the practical aspects of using AS OCT diagnostics in patients with a cone qualified for deep lamellar keratoplasty and penetrating keratoplasty. The use of intraoperative OCT in surgical treatment supported by excimer and femtosecond lasers will also be presented.
Insights into corneal re‐vascularization and vascular remodelling in the eye
Authors: Lagali Neil
Published: December 2022

While corneal neovascularization is a well‐known, sight‐threatening condition presenting a risk for corneal transplant rejection and failure, corneal revascularization has received much less attention. Although ocular revascularization is well studied in the context of regrowth of choroidal vessels following regular anti‐angiogenic injections for age‐related macular degeneration, the corneal context is less well documented. Here, the differences between initial and subsequent episodes of corneal neovascularization are explored, as well as the underlying changes at the mechanistic, structural and biochemical levels, through basic studies in the murine cornea. Repeat neovascularization is found to be more aggressive than the vessel ingrowth in an initial phase, pointing towards a memory effect in the corneal tissue. Furthermore, these regrown vessels are more resistant to treatment than initial vessels, which can have implications for the long‐term treatment and rebound of corneal vessels and prognosis for graft survival. We also highlight several factors that may be driving this aggressive revascularization response, with an eye towards future interventions aimed at preventing revascularization following initial treatments for corneal neovascularization.
Nerves, vessels and inflammation at the ocular surface
Authors: Ferrari Giulio
Published: December 2022

Corneal nerves are essential in the maintenance of ocular surface homeostasis. The role of peripheral nerves in promoting the onset of corneal inflammation, instead, is only recently starting to emerge. The extremely dense sensory innervation, and complete absence of vessels, in the normal cornea, makes it an ideal target of neuroinflammation.

Previous work from us demonstrated that acute nerve disruption is followed by corneal neovascularization and inflammation. We hypothesized that neuropeptide Substance P is a key modulator of corneal neuroinflammation. Indeed, our data show that neuropeptide Substance P is a key promoter of inflammation and neovascularization in pre‐clinical models of corneal burns, neovascularization, stem cell deficiency and ocular graft versus host disease. Further, we demonstrate that this effect is mediated by the Neurokinin 1 receptor, which is the principal receptor for Substance P. Moreover, we show that highly prevalent human corneal diseases/trauma are associated with increased Substance P expression in the tear fluid. This has significant clinical implication because medications are available to selectively block Neurokinin 1 receptor. Indeed, topical application of Neurokinin 1 receptor antagonists inhibits leukocyte infiltration, and ameliorate multiple clinical signs of inflammation in animal models of ocular surface inflammation.

These data have allowed us to initiate a clinical trial for compassionate use of neurokinin 1 receptor antagonists for the treatment of recalcitrant ocular surface inflammation.
Colour vision changes in patients with pressure differences across the lamina cribrosa
Authors: Barbur John , Wong Sui
Published: December 2022

The retinal nerve fibre layer (RNFL) thickness parameters describe the integrity of retinal ganglion cells (RGC) and their axons and can be affected in pathological processes involving the optic nerve. Glaucoma and papilledema are two conditions where RGCs and hence RNFL, are damaged due to the pressure differences across the lamina cribrosa. The latter separates the intraocular and intracranial pressure compartments. In glaucoma, the intraocular pressure (IOP) is elevated and in papilledema, the intracranial pressure is elevated. When intracranial pressure is managed, papilledema patients can recover without significant loss of RGC. Conversely irreversible RGC loss can occur in severe cases.

Subtle, functional changes that are often not detected clinically can remain following recovery. The detection of such changes require sensitive functional tests and a knowledge of normal age limits for the stimulus attribute investigated.

Results of preliminary studies designed to assess how colour vision and rod and cone mediated flicker sensitivity recover in papilledema will be reported for a number of patients. Following recovery, the results often reveal binocular summation effects, even when the differences between the two eyes remain significant. Patients classed clinically as fully recovered continue to show small differences between the two eyes, even when the measured binocular thresholds are within the expected age limits.

In summary, the preliminary findings from this investigation show how various attributes of vision are affected during the early stages of the disease and after treatment and recovery from late stage of severe papilledema with loss of RGCs.
Colour vision impairments in ophthalmological and neurological disorders
Authors: Castelo‐Branco Miguel
Published: December 2022

The value of colour vision assessment in the understanding of ophthalmological and neurological disorders impairments cannot be underestimated. Here we discuss impairment of parallel retinocortical pathways in early stages of Parkinson's disease. The debate on the relative contribution of retinal vs. cortical mechanisms is also addressed concerning Multiple Sclerosis and Alzheimer's Disease.

We discuss evidence on the hypothesis that the retina mirrors the brain in terms of pathology and in which neurological conditions this might apply. The converse situation of retrograde degeneration in the case of multiple sclerosis is also addressed.

Cortical changes secondary to retinal disease, such as glaucoma and diabetic retinopathy may also bias colour perception. Finally, we discuss the potential role of colour vision measures as disease related biomarkers that can be used for diagnostic, prognostic and treatment effects assessment.
Basics of artificial intelligence
Authors: Wong Damon
Published: December 2022

Artificial intelligence (AI) is increasingly being used in different fields, including ophthalmology. Recent studies have demonstrated that AI‐based techniques have started to approach near‐human levels of performance, and has led to much interest and excitement. Yet, excitement about AI has also been accompanied by sometimes unrealistic expectations. This talk will provide an overview on the basics of AI, including a brief history on its development and the different types of AI, including machine‐learning and deep‐learning. Fundamental principles of deep‐learning will be introduced, and key differences between traditional image processing techniques and deep‐learning will also be discussed, together with limitations and potential pitfalls of the technology. The talk will also provide a glimpse into recent and emerging trends in this rapidly evolving field.
Artificial intelligence for diabetic retinopathy screening
Authors: Grzybowski Andrzej
Published: December 2022

Diabetes constitutes a significant problem for global health and wellbeing. The number of people living with diabetes raised from 108 million in 1980 to 422 million in 2014. By 2035, 592 million people will have diabetes, with the largest rise in low‐ and middle‐income regions. Diabetic retinopathy (DR) is one of the major complications of diabetes, estimated to be the leading cause of blindness among working‐age adults globally. The increasing worldwide population, coupled with increasing prevalence of diabetes and increased incidence of diabetic retinopathy all lead to increasing number of patients with ocular complications of diabetes. Only a few countries were able to successfully establish and continue diabetic retinopathy screening on national level, most prominently – United Kingdom and Singapore. The NHS Diabetic Eye Screening Programme, a continuation of an English screening programme set up in 2006, reported in 2014 that DR is no longer the leading cause of certifiable blindness in England and Wales for the first time in 50 years. The advent of deep‐learning based DR detection revealed a significant improvement in the accuracy of the newly developed or improved systems. It requires a careful balance between sensitivity and specificity, imaging modality, gradeability of the images, all of which will need to be weighed against the potential cost. Deep learning DR detection has been found to be cost‐effective in developed countries, like Singapore and United Kingdom. However, the feasibility of implementing AI DR screening in countries without a robust teleophthalmology screening programme setup beforehand and other resource‐limited settings should still be evidenced. IDx‐DR is the first autonomous diagnostic software and one of the very first AI‐based software's in medicine to receive Federal Drug and Administration (FDA) approval. Eyeart was approved by FDA for the similar purpose in 2020. In European Union, there are more than 10 different AI‐based devices for DR screening registered, however in different classes, I and IIa. There are also significant shortcomings in current studies of AI in DR, including that great majority of them are sponsored or dependent on the respective algorithm's' company. Independent studies, particularly comparisons or studies establishing objective criteria through which the respective algorithms could be compared are rare.
AI‐based software for cardiovascular disease assessment
Authors: Arnould Louis
Published: December 2022

The healthcare burden of cardiovascular disease remains a priority. Understanding their underlying mechanisms and improving identification of people with higher systemic vascular risk profile with non‐invasive examinations seem to be crucial. In Ophthalmology, retinal imaging is simple, non‐invasive and it can provide in vivo insight of the retinal microcirculation. For more than 10 years, research teams have been working on software developed to allow automatic analysis of the retinal vascular network from different imaging technique (fundus photographs, oct‐angiography or adaptive optics…) and to provide a description of the geometric characteristics of its arterial and venous components. At the same time, research teams have explored the pathophysiological association between macro vascular and micro vascular alterations. Thus, retinal microcirculation could be considered as a witness of the systemic cardiovascular status. New approach with retinal images dataset and artificial intelligence algorithms recently strengthened the interest of retinal microvascular biomarker. Deep learning and machine learning algorithms provided very thorough description of the retinal vascular network. Moreover, they were able to assess strong associations between retinal features and calcium heart score or biological age for example. Thus, the interest of retinal biomarker in terms of screening, monitoring or prediction of cardiovascular disease is very promising.
In vivo confocal microscopy demonstrates longitudinal bilateral changes of corneal immune cells and nerves in herpetic keratitis
Authors: Hamrah Pedram
Published: December 2022

Purpose: To analyse bilateral corneal immune cell and nerve alterations in patients with unilateral herpes zoster ophthalmicus (HZO) by laser in vivo confocal microscopy (IVCM) and their correlation with corneal sensation and clinical findings.

Materials and methods: This is a prospective, cross‐sectional, controlled, single‐center study. Twenty‐four eyes of 24 HZO patients and their contralateral clinically unaffected eyes and normal controls (n = 24) were included. Laser IVCM (Heidelberg Retina Tomograph/Rostock Cornea Module), corneal esthesiometry (Cochet‐Bonnet) were performed. Changes in corneal dendritiform cell (DC) density and morphology, number and length of subbasal nerve fibres and their correlation to corneal sensation, pain, lesion location, disease duration, and number of episodes were analysed.

Results: HZO‐affected and contralateral eyes showed a significant increase in DC influx of the central cornea as compared to controls (147.4 ± 33.9, 120.1 ± 21.2, and 23.0 ± 3.6 cells/mm2; p < 0.0001). In HZO eyes DCs were larger in area (319.4 ± 59.8 μm2; p < 0.001) and number of dendrites (3.5 ± 0.4 n/cell; p = 0.01) as compared to controls (52.2 ± 11.7, and 2.3 ± 0.5). DC density and size showed moderate negative correlation with total nerve length (R = −0.43 and R = −0.57, respectively; all p < 0.001). A higher frequency of nerve beading and activated DCs close to nerve fibres were detected specifically in pain patients.

Conclusions: Chronic unilateral HZO causes significant bilateral increase in corneal DC density and decrease of the corneal subbasal nerves as compared to controls. Negative correlation was observed for DC density and size to nerve parameters, suggesting interplay between the immune and nervous systems. Patients with chronic pain also showed increased nerve beading and activated DCs.
Implication of Müller glia in glaucoma
Authors: Vecino Elena , Pereiro Xandra , Ruzafa Noelia
Published: December 2022

Glaucoma is a neurodegenerative disease and the leading cause of irreversible blindness in the world, whose main risk factor is increased intraocular pressure. When visual problems are first detected in patients with glaucoma, already half of the retinal ganglion cells (RGCs), the neurons that send visual information from the eye to the brain, have died principally in the peripheral retina. The timeframe of cell death is prolonged, lasting even decades after an initial diagnosis. Müller glia (MG) are the main macroglial cell in the retina, play prominent roles regulating normal and pathological physiology and react to neuronal injury in glaucoma. The change to a reactive phenotype of MG initiates signalling cascades that may serve a neuroprotective role, but may also proceed to promote damaging effects on RGCs. However, the underlying mechanisms and signalling pathways that specifically promote protective versus destructive roles of reactive glial cells are mostly unclear.

Our main hypothesis is that MGs exert an important role in the death of RGCs in glaucoma with the MGs in the periphery being the most sensitive to intraocular pressure, promoting the death of RGCs. Preventing MG response to elevated pressure, MG can neuroprotect RGCs in early stages of glaucoma.

We have proved in vitro, that in control condition MG secret neuroprotective factors, and under elevated pressure MG are the responsible for the RGCs death, being less sensitive to the elevated hydrostatic pressure (EHP) the MG present in the central retina. Moreover, stretch‐activated nonselective TRPV4 cation channels present in MG are differently activated by the pressure depending of their location within the retina. Proteomic analysis from the conditioned media (CM) of MG revealed different protein expression levels being more pronounced in the CM from MG from peripheral retina in EHP. Proteins identified correspond mainly to functions such as: apoptosis, oxidative stress, inflammation and angiogenesis.

We conclude that the different sensibility of the RGCs to pressure in glaucoma could be related with the different activation of the neighbours MG.