bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of S‐allyl L‐cysteine on retinal ischaemia: The role of MCP‐1 and PKM2
Authors: Chao Windsor Wen‐Jin , Chao Hsiao‐Ming
Published: January 2024

Aims/Purpose: Retinal ischaemia plays an important role in vision threatening retinal ischaemic disorders, such as central/branch RAO, nvAMD and normal tension glaucoma. The aim of this study was to determine the effects of S‐allyl L‐cysteine (SAC) and its underlying mechanism.

Methods: Porcine RPE (pRPE) cells were extracted from adult pig eyes and maintained in DMEM containing 10% FBS, 100 U/mL penicillin and 100 mg/mL streptomycin in a humidified atmosphere of 95% air and 5% CO2 at 37°C. Cell viability was evaluated by via a haemocytometre under an optical microscope. H2O2 (500 μM) was added for 24 h to stimulate an oxidative stress and SAC or vehicle was added to some groups of the cultured pRPE cells 15 min before adding H2O2.

Besides, high intraocular pressure (HIOP)‐induced retinal ischaemia was established by raising IOP to 120 mmHg for 60 min in a Wistar rat eye. This ischaemic insult is followed by 7 days of reperfusion. Whether and how ‘SAC’ is able to prevent retinal ischaemic injury were assessed by electrophysiology, fluorogold‐labeling and ELISA/western blot.

Results: H2O2 (500 μM) stimulated free radical formation in cultured pRPE cells and significantly reduced the cell viability. This harmful effect was dose‐dependently (25/50 μM) and significantly (100 μM) ameliorated by pretreatment with SAC. Moreover, post‐administration of mega‐dose SAC (I/R + SAC 9 μg/kg/day ≈ 0.18 mg/0.2 Kg rat) counteracted the ischaemia‐induced decrease in the ERG b‐wave and reduction in the RGC cell number in the rat retina. This study supports an antioxidative role for SAC. Through the ELISA/western blot, SAC (100 μM) appears to protect against H2O2‐induced oxidative stress via the downregulation of ischaemia‐related factor PKM2 and inflammatory biomarker MCP‐1.

Conclusions: SAC might protect against retinal ischaemia by antioxidation, anti‐ischaemia and anti‐inflammation (downregulating PKM2 and MCP‐1).

References

1. Chao, et al. S‐Allyl L‐Cysteine Protects the Retina against Kainate Excitotoxicity in the Rat. The Am J Chin Med, 42:693–708, 2014.

2. Chao, et al. Fortified S‐Allyl L‐Cysteine: Animal Safety, Effect on Retinal Ischemia, and Role of Wnt in the Underlying Therapeutic Mechanism. Evid Based Complement Alternat Med, 2020:1–12, 2020.
Optimizing criterion to reduce the variability between observers in the delimitation of the foveal avascular zone in diabetic patients
Authors: Fernández‐Espinosa Guisela , Ruíz‐Tabuenca Carlos , Orduna‐Hospital Elvira , Arcas‐Carbonell María , Sánchez‐Cano Ana , Pinilla Isabel , Salgado‐Remacha Francisco J.
Published: January 2024

Aims/Purpose: To reduce the variability when performing manual segmentation of the foveal avascular zone (FAZ) on retinal optical coherence tomography angiography (OCTA) images, and to find a new accurate FAZ delimitation criterion.

Methods: Seventy‐three eyes from healthy subjects, 40 eyes from Type 1 diabetes mellitus (DM1) patients without diabetic retinopathy (DR) and 54 eyes from Type 2 diabetes mellitus (DM2) patients with moderate DR and without diabetic macular oedema (DME) were evaluated using OCTA. A manual FAZ segmentation was performed by different observers of each OCTA image of the superficial (SCP) and deep capillary plexuses (DCP). After comparing the results, a new criterion was established to reduce the variability in the segmentations. The FAZ area and circularity were also studied.

Results: The novel criterion produces smaller areas (closer to the real FAZ), as well as a diminution of the standard deviation values, with a factor of 0.5, with lower variability than the different criteria of the explorers in both plexuses for the three groups. This was particularly notorious for the DM2 group with damaged retinas, where it was very difficult to define the FAZ limits. The acircularity values were also slightly reduced with the final criterion in all groups. In the DM2 group a significant reduction in the acircularity mean value of both plexuses was obtained. Looking for a relationship between the FAZ area and the acircularity, we found slightly higher values of acircularity for smaller FAZ areas. The number of extremal values was much higher for the initial method, and when the DCP was evaluated.

Conclusions: The implementation of a new criterion for FAZ segmentation produced more consistent results with less variability among observers.
Long‐term response to idebenone treatment in a patient with advanced Leber hereditary optic neuropathy
Authors: Kabanarou Stamatina , Sgourou Chrysoula , Bitzanakis Nikolaos , Bontzos Georgios , Gkizis Ilias , Xirou Vasiliki , Xirou Tina
Published: January 2024

Aims/Purpose: To present a case with advanced LHON and its response to 2‐year‐treatment with idebenone, which was prescribed 13 years after the onset of the disease.

Methods: A 40‐year‐old Caucasian male patient with a history of bilateral painless visual loss since the age of 28 was examined at our Ophthalmology department. His brother had also suffered similar visual loss. At presentation ETDRS best corrected visual acuity (BCVA) was counting fingers (CF) in both eyes (BE). Fundoscopy revealed pale optic discs bilaterally. Visual fields (30‐2) showed central scotomas in BE. During OCT/OCTA imaging of the optic disc RNFL and GCC thickness were decreased bilaterally. In electrophysiological assessment with flash visual evoked potentials a reduction in amplitude was recorded in BE but with normal latency. Full‐field ERG was within normal limits in BE. At the genetic test, a mitochondrial point mutation m. 3460 G>A at MT‐ND1 gene was detected, which was compatible with LHON. The patient was prescribed 300 mg idebenone per os three times/day for 24 months. Follow‐up visits were scheduled at 6, 12, 18 and 24 months.

Results: At 6‐ and 12‐month follow‐up visits visual acuity, fundoscopic findings and OCT‐RNFL imaging remained unchanged. However, the patient reported subjective visual improvement bilaterally, with greater improvement in the visual field of the left eye. At 18 months following initiation of treatment an improvement of the visual field was documented in BE. No change of the GCC thickness was noted. At 2‐year follow‐up his condition remained improved.

Conclusions: Delayed treatment with idebenone in advanced LHON can lead to subjective visual improvement. Moreover, an improvement in visual fields can also be documented even after 18 to 24 months of the initiation of the treatment.
Telemedicine‐based eye screening program in Castilla and León: A reading centre‐assisted model
Authors: Lope Pablo Arlanzón , Espinilla Óscar García , Díez Andrea Novo , Recio Inmaculada Yepes , de la Iglesia Rodríguez Purificación , Gálvez María Isabel López , Jimeno José Carlos Pastor
Published: January 2024

Aims/Purpose: Diabetes Mellitus is a disease with increased prevalence in the world with an estimation of 8 to 10% of the European population affected. Diabetic retinopathy (DR) is its main ocular complication (affecting up to 20% of diabetics) and the main cause of vision loss in European working population. DR screening via telemedicine is fully accepted as a powerful tool to maintain the standards of care. Castilla and León is an extensive autonomous community in Spain and developed a telemedicine eye screening program based on reading centre (RC) support. The purpose of this work was to analyse the results achieved by the program in the period 2018–2022.

Methods: Program is currently active in two provinces and scheduled to be extended to all. It consists of 8 non mydriatic fundus cameras used by certified photographers acquiring images according to the JVN protocol under mydriasis. The images are analysed remotely at IOBA RC by a certified optometrist, or an ophthalmologist in case of suspicion of pathology.

Results: Globally, 22 430 examinations (179 440 pictures) have been performed since the beginning. Only 8.7% of examinations were not valuable, mainly due to media opacities. Of gradable examinations 70% showed no signs of pathology and 13.2% showed any level of DR. Only 1.3% had sight‐threatening DR and were referred to secondary care (hospital). In addition, 8.1% showed other pathology but RD and 33 patients were referred (AMD, vascular occlusions, etc.). The range of recruitment referred of global diabetic census is 54.2%–21.51% despite the impact of the pandemic. Our goal is to reach 70% of census.

Conclusions: RC assisted telemedicine is a successful model for DR screening. It allows for the identification of sight‐threatening RD, other prevalent eye pathology and its referral for treatment, thus maintaining the standards of care for the diabetic population contributing to reducing the care burden of hospitals and the health system sustainability.
Detection of subretinal and intraretinal fluids in optopol SD‐OCT using transfer learning
Authors: Assaf Abdelrahman , Orabi Mohamad , Loktyushin Alexander , Aydin Sökmen , Lanzl Ines
Published: January 2024

Aims/Purpose: The detection of subretinal fluid (SRF) and intraretinal fluid (IRF) in optical coherence tomography (OCT) images plays a crucial role in the diagnosis and treatment of certain eye diseases. In this study, we investigated the performance of a Transfer Learning artificial intelligence (AI) technique, which we used to perform the model adaptation from the domain of Heidelberg OCT images to Optopol devices.

Methods: A data set of 133 Optopol OCT images. 69 images indicating subretinal or intraretinal fluid and 64 fluid‐free images, were analysed. The AI algorithm that was initially trained on OCT images from Heidelberg device was fine‐tuned to perform the biomarker segmentation in Optopol (Revo NX, SOCT Copernicus REVO, REVO FC) OCT images. Manual assessments by the medical experts were used to evaluate the algorithm's performance.

Results: Our findings demonstrate the promising performance of the domain‐adapted model. in detecting SRF and IRF, when initially trained on OCT images from a different device. The algorithm achieved an accuracy of 80% while classifying the presence versus absence of the fluids on the balanced test data set.

Conclusions: The study demonstrates a successful application of a transfer learning technique for detection of subretinal and intraretinal fluids in OCT images acquired with the Optopol devices, indicating its potential for enhancing eye diagnostics. Further studies utilizing larger data sets, further biomarkers and diverse OCT devices are warranted to validate the algorithm's robustness and generalizability.
Retinal thickness as sensitivity as biomarkers of neurodegeneration in moderate diabetic retinopathy
Authors: Boned‐Murillo Ana , Fernández‐Espinosa Guisela , Hospital Elvira Orduna , Diaz Maria Dolores , cano Ana Sánchez , Pinilla Maria Sopeña , Bielsa Sofia , Lozano Isabel Pinilla
Published: January 2024

Aims/Purpose: To analyse total retinal thickness (RT) and inner retinal layers (IRL) in Type 2 diabetes mellitus (DM2) patients, measured with swept source OCT (SS‐OCT), and retinal sensibility with microperimetry.

Methods: A total of 54 DM2 subjects with moderate diabetic retinopathy (DR) with no signs of diabetic macular oedema (DME) and 73 age‐matched healthy individuals were assessed by SS‐OCT to quantify retinal thickness in the nine macular areas of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Retinal sensibility was measured by microperimetry with MAIA.

Results: Mean ages were 64.06 ± 11.98 years for the DM2 group and 60.79 ± 8.62 years for the control group. DM2 patients presented lower visual acuity (p < 0.001), RT was significantly higher in the outer temporal area (260.70 ± 19.22 μm in the control group vs. 271.90 ± 37.61 μm in the DM2 group, with p = 0.01), and retinal nerve fibre layer (RNFL) was significantly lower in the outer nasal area (50.38 ± 8.20 μm vs. 45.17 ± 11.25 μm, p = 0.005). Ganglion cells and inner plexiform layers (GCL+) in the parafoveal areas were thinner in DM2 and RT, GCL+ and GCL+ with RNFL (GCL++) significantly diminished with age in the outer ring. A positive correlation between LDL‐C and RNFL and a negative correlation between HDL‐C levels and inner temporal and central RNFL thickness were detected. The central and inner nasal areas presented a negative correlation between RNFL (p = 0.015) and MAIA (p = 0.008), while the outer inferior area showed a positive correlation (p = 0.025).

Conclusions: Retinal sensitivity and macular RNFL thickness decrease in DM2 with moderate DR with no DME. Its correlation suggests the existence of diabetic retinal neurodegeneration.
Choroidal thickness after anti‐vascular endothelial growth factor in treatment‐naïve typical neovascular age‐related macular degeneration patients: A systematic review and meta‐analysis
Authors: Hoven Erlend , Michelet John‐Thomas , Vettore Mario , Lagali Neil
Published: January 2024

Aims/Purpose: To evaluate the effect of anti‐vascular endothelial growth factor (anti‐VEGF) on choroidal thickness (CT) in treatment‐naïve typical neovascular age‐related macular degeneration (AMD) patients during the loading phase.

Methods: A systematic literature search was conducted in CENTRAL, MEDLINE, EMBASE, Scopus, Web of Science, Clinical Trials, ICTRP and ISRCTN from inception to October 19, 2022. The protocol was registered with PROSPERO (CRD42022371192). We included both retrospective and prospective randomized controlled trials, cohort studies, case control and case series of typical neovascular AMD patients. Studies with polypoidal choroidal vasculopathy or unclear diagnoses and reports in other languages than English were excluded. Risk of bias was assessed using critical appraisal tools provided by Joanna Briggs Institute.

Results: 43 studies were included in the review. Meta‐analysis of all studies reporting sufficient data and simultaneously disregarding measurement technique, macular neovascularization (MNV) type and anti‐VEGF type, yielded a significant decrease of CT with anti‐VEGF treatment. To decrease bias, sub‐analyses for Type 1 and 2 MNV sorted by anti‐VEGF type found a significant effect for both aflibercept and ranibizumab, and the effect appears greater in the aflibercept group. For Type 3 MNV, the baseline CT was generally thinner and the decrease more modest.

Conclusions: Anti‐VEGF drugs decrease CT in typical neovascular AMD. There is a greater effect of aflibercept compared to ranibizumab. For bevacizumab and brolucizumab there are few studies, but available data show a tendency of greater effect in the latter. There are low numbers of randomized trials on the topic and publication bias might affect the results. More studies randomized to treatment of patients with a thin baseline choroid should be conducted.
Multimodal imaging study and clinical management in Coats' disease
Authors: Abellán Maria Victoria Navarro , Moreno Elisa Foulquié , Perea Juan Antonio Sánchez , Menargues Manuel Almarcha , López Carmen Miquel , Sánchez María De Los Reyes Retamero , Medina José Javier García
Published: January 2024

Aims/Purpose: Coats' disease is an idiopathic ocular condition characterized by retinal telangiectasia, aneurysms, and exudation, frequently affects unilateral eyes of young males. Rare pathology of difficult diagnosis and clinical management. Follow‐up by multimodal imaging of clinical improvement after correct treatment in Coats' Disease.

Methods: Morales Meseguer University Hospital, Murcia, Spain. Observational study using multimodal imaging of clinical cases in patients diagnosed with Coats' disease. Retrospective follow‐up during several visits between 2021–2023. Images taken with optical coherence tomography (OCT), fluorescein angiography (FA) and autofluorescence.

Results: Presentation two clinical cases. A 56‐year‐old female and a 28‐year‐old male diagnosed with Coats disease in right eye. Best corrected visual acuity (BVAC) of 0.6 and 0.5, respectively. Female had macular oedema (ME) with hard exudates in temporal arcade territory with areas of venous and arterial sheathing, macroaneurysm in inferior temporal arcade territory. Hypertrophy of the peripheral retinal pigment epithelium. OCT shows EM, subretinal fluid (SRF) and hyperreflective dots in middle layers. Male with a history of vitrectomy and phacoemulsification after regmatogenous and tractional retinal detachment secondary to the disease, presents pseudophakia, angular synechiae and iridotomies, vascular malformations, inferior haemorrhages, zone of temporal and nasal inferior exudation with FSR area, inferior tear pigmented with laser. OCT shows ME with FSR. Both cases, FA proves blood fluids levels and saccular aneurysms of arterial arterioles and venules. We note an improvement BVAC and EM with resolution of FSR on multimodal imaging study after intravitreal and focal laser treatment.

Conclusions: Multimodal imaging in the follow‐up of Coats' disease is essential to assess correct treatment. Treatment with focal laser and intravitreal therapy is safe and effective in control of Coats disease.
Sarcoidosis‐related uveitis: A case series study
Authors: Chafter Camilia , Maamouri Rym , Ammar Nadia Ben , Somai Mehdi , Boussema Fatma , Cheour Monia
Published: January 2024

Purpose: The aim of this study was to characterize the epidemiological and clinical characteristics of ocular involvement in patients with systemic sarcoidosis.

Methods: Retrospective case series study carried out at the Ophthalmology department of Habib Thameur University Hospital of Tunis between the 1st January 2022 and the 1st January 2023. Fifteen patients (30 eyes) were included. Based on the International Workshop on Ocular Sarcoidosis criteria, three patients had biopsy‐proven sarcoidosis; eight had presumed sarcoidosis and four had probable sarcoidosis. All patients had a complete ocular examination and systemic work‐up.

Results: The median age at presentation was 45 years (range: 29–66). The sex ratio was 1:13. Ocular involvement was the presenting symptom in 11 patients. Bilateral granulomatous uveitis was the presenting form in all patients. Panuveitis was the most common anatomic pattern (9), followed by anterior (3), anterior and intermediate (2) and intermediate (1) uveitis. Posterior segment involvement included multifocal choroiditis (3) retinal vasculitis (5) macular oedema (4) and optic nerve head granuloma (1). Systemic manifestations included bilateral hilar lymphadenopathy (8) eyelid granuloma (2) neurosarcoidosis (3) Peripheral facial nerve palsy (2).

Conclusions: Uveitis was the initial presentation of sarcoidosis in the majority of our subjects. Panuveitis was the most commonly encountered anatomic form. Our findings support the prominent role of the ocular examination in the early detection of sarcoidosis.
Characterization of a new fluorescence lifetime imaging ophthalmoscope
Authors: Nycz Julia , Link Dietmar , Klemm Matthias , Klee Sascha , Haueisen Jens
Published: January 2024

Aims/Purpose: Fluorescence lifetime imaging ophthalmoscopy (FLIO) allows in vivo measurement of autofluorescence intensity decays of endogenous fluorophores in the ocular fundus. So far, only devices from Heidelberg Engineering based on the Spectralis system have been used in FLIO research. Here, we present and characterize a new FLIO device based on the RETImap system from Roland Consult.

Methods: The device is based on a confocal scanning laser ophthalmoscope (35° field, 512 × 512 px). A ps diode laser (BDL‐SMN 473 nm, Becker & Hickl GmbH, Berlin, Germany) excites autofluorescence. The fluorescence photons are split into a short (498–560 nm, SSC) and a long (560–720 nm, LSC) spectral channel (one HPM‐100‐40 detector [Becker & Hickl GmbH] each) and are detected by time‐correlated single photon counting (SPC‐160, Becker & Hickl GmbH). We determined the maximum laser power (ILT2400, International Light Technologies, Inc. Peabody, MA, USA) and analysed the instrument's behaviour at three different laser power levels (150 μW, 200 μW and max.) in terms of laser spectrum (CAS140CT, Instrument Systems GmbH, Munich, Germany) and instrument response function (IRF). The IRF was determined using a 25 μM Eosin Y solution, mixed with a 5 M solution of potassium iodide, placed in a flat cuvette (110‐OS, Hellma GmbH & Co. KG, Müllheim, Germany) in front of the objective lens of the FLIO device. Fluorescence measurements of approximately 1‐min duration were performed three times for all three laser powers. The IRF and the full width at half maximum (FWHM) were calculated using FLIMX software (www.flimx.de).

Results: The max. laser power was 280 μW. The peak wavelengths of the laser spectra were 467.6 (150 μW), 467.9 (200 μW) and 468.0 nm (280 μW). IRF FWHM in SSC were 298.6 ± 1.1 ps (150 μW), 341.0 ± 2.5 ps (200 μW) and 347.5 ± 6.0 ps (280 μW). In LSC, the IRF FWHM were 290.4 ± 3.8 ps (150 μW), 344.0 ± 3.4 ps (200 μW) and 358.8 ± 1.3 ps (280 μW). Results are mean ± standard deviation.

Conclusions: A new fluorescence lifetime imaging ophthalmoscope has been characterized. The device offers a high laser power for fluorescence excitation, a large field of view, a high spatial resolution, and a sufficiently high time resolution. Thus, it is suitable for fluorescence lifetime studies.
Emergency treatment approaches for central retinal artery occlusion
Authors: Smiri Meryam , Nassim Haddoum Karim , Abdeldjalil Mansouri , Mohamed El Sanharawi
Published: January 2024

Aims/Purpose: Central retinal artery occlusion (CRAO), which can be likened to a stroke in the eye, is considered a critical condition requiring immediate attention. The aim of this case was to assess whether anterior chamber paracentesis has a notable impact on the ultimate visual acuity in eye experiencing acute CRAO.

Methods: We present the case of a 62‐year‐old man with no significant ophthalmological history, only hypertension under treatment. Presented to the emergency care within an hour after experiencing a sudden decrease in visual acuity in his left eye, whose visual prognosis improved after an urgent ocular chamber paracentesis.

Results: The ophthalmological examination revealed a visual acuity of 10/10 on the right (OD) and positive light perception/10 on his left eye (OS). The intraocular pressure was normal in both eyes. Slit lamp and fundus examination showed on OS a positive reflex afferent pupillary defect and a whitish appearance of the retina, with narrowed retinal blood vessels and a cherry red spot in the macula while all was normal on OD. In this case an anterior chamber paracentesis was conducted, involving the removal of 0.3 mL of aqueous fluid from the anterior chamber using a small (30 gauge) needle. By decreasing the intraocular pressure through medical means (acetazolamide 250 mg 1cp 3 times a day for 7 days) and performing the anterior chamber paracentesis, the aim is to optimize the conditions for promoting the movement of any potential embolus away from the central retina and along the vessel. After one week, significant improvement was observed. The visual acuity in the OS was measured at 9/10, and the intraocular pressure was 10 mmHg. Ophthalmoscopic examination revealed the disappearance of the previously observed whitish retina, with a granular appearance of the macula. Despite these positive changes, impairment in the visual field has been noted and still persistent even after six months of follow‐up.

Conclusions: Paracentesis, by reducing intraocular pressure, can enhance retinal arterial perfusion pressure, vasodilatation and the dislodgement of thrombi or emboli. Despite the prognosis often being poor, it is essential to take quick action and implement appropriate management strategies to prevent permanent vision loss.
Pre‐operative OCT in idiopathic epiretinal membrane surgery: The importance of biomarkers in predicting visual outcomes
Authors: Monteiro Catarina , da Costa Tomás Reis , Dias Maria Teixeira , Almeida Júlio , Ramalho Mário , Pires Graça , Teixeira Susana , Prieto Isabel
Published: January 2024

Aims/Purpose: To evaluate the influence of inner segment (IS)/outer segment (OS) junction integrity in the post‐operative visual outcomes in patients submitted to idiopathic epiretinal membrane surgery.

Methods: This was a retrospective observational study that included patients who underwent plana vitrectomy with internal limiting membrane (ILM) peeling between 2017 and 2022 our centre. All patients were submitted to a complete ophthalmological observation and high‐resolution (HR) spectral domain optical coherence tomography (SD‐OCT) (Spectralis® Heidelberg) scans centred on the fovea. Best corrected visual acuity (BCVA) and OCT morphology were evaluated pre‐operatively and at 1, 3, 6 and 12 months after the surgery. Our main outcome was to understand if there was a statistical correlation between the pre‐operative IS/OS junction integrity status and post‐operative BCVA gain.

Results: This retrospective study included 39 eyes from 39 patients (19 male and 20 female) with a mean age of 70.9 ± 7.8 years. Pre‐operatively, mean BCVA was 0.23 ± 0.12. Pre‐operative OCT scans revealed a mean central foveal thickness (CFT) of 549 ± 110 μm. BCVA showed a mean post‐operative improvement of 0.09 ± 0.14 at 1 month, 0.19 ± 0.17 at 3 months, 0.26 ± 0.21 at 6 months and 0.29 ± 0.23 at 12 months. There was a mean CFT reduction of 77 ± 87 μm, 129 ± 116 μm, 136 ± 121 μm and 160 ± 135 μm at 1, 3, 6 and 12 months post‐operatively. Regarding IS/OS junction status, 20 patients presented with an intact IS/OS junction and 19 patients with a disrupted or irregular junction. At 6 and 12 months post‐operatively, the correlation between visual acuity gain and IS/OS status was statistically very significant (p‐value = 0.008 and 0.002, respectively).

Conclusions: IS/OS junction status in pre‐operative OCT seems to be a strong predictor of visual outcomes in patients submitted to vitreoretinal surgery for idiopathic epiretinal membrane. This biomarker should be taken into account regarding the visual prognosis of these patients.
Research of branched retinal vein occlusion with arteriovenous crossing site
Authors: Noh Seung Yoon , Kim Taehwan , Kwon Yoonhyung
Published: January 2024

Aims/Purpose: The study was designed to analyse the incidence of branch retinal vein occlusion with characteristics of arteriovenous crossing.

Methods: Patients diagnosed with branch retinal vein occlusion from January 2012 to January 2017 were enrolled. We selected 117 patients with recognizable arteriovenous crossing on fundus photography. The control group consisted of 120 patients who had no eye disorders and normal fundus photography. To analyse the characteristics of BRVO arteriovenous crossing, the sites were compared with arteriovenous crossing sites in similar locations in the contralateral vascular arcade of the BRVO site. Second, the numbers of arteriovenous crossings and crossings in which the positions of an artery and a vein alternated in the main venous pathways were studied. Last, distances between arteriovenous crossings at the main venous pathway were analysed.

Results: Of branch retinal vein occlusion patients, 75.2% showed an artery anterior to the vein at arteriovenous crossing sites. In the control group, 61.5% of arteriovenous crossing sites showed artery anterior to the vein. The total number of arteriovenous crossing sites was not different from that of the contralateral arcade in the same eye, but the number of arteries anterior to veins was significantly different. The total number of arteriovenous crossing sites was statistically different from that of the control group of normal people. Distance between arteriovenous crossings were measured by the ImageJ program. Group A showed a 2.619 ± 0.859 DD (Disc Diameter) and group C was 3.505 ± 0.859 DD, a significant difference.

Conclusions: The study shows that arteriovenous crossing sites play an important role in branch retinal vein occlusion, and an artery anterior to a vein is more important at such crossing sites. Moreover, the distance between arteriovenous crossing sites can affect the incidence of BRVO.
Role of heparin‐binding mediators in the resistance to anti‐VEGF therapies in diabetic retinopathy
Authors: Rezzola Sara , Loda Alessandra , Mutti Greta , Romano Vito , Morescalchi Francesco , Tabellini Giovanna , Parolini Silvia , Semeraro Francesco
Published: January 2024

Aims/Purpose: Anti‐vascular endothelial growth factor (VEGF) drugs represent the standard of care for diabetic retinopathy (DR); however, lack of response occurs in approximately 50% of patients. Aim of our work is the identification of the mediators responsible for anti‐VEGF drug resistance.

Methods: Vitreous samples were collected from anti‐VEGF non‐responder (non‐RES) patients; non‐RES heat‐inactivated (HI) vitreous were used as control. To develop a new orthotopic model of DR, non‐RES or HI vitreous were injected intravitreally in mice and after 48 h retinas were explanted and analysed. The composition of non‐RES vitreous was assessed by an angio‐inflammatory protein array. The effect of the inhibition of the bioactive heparin‐binding mediators (HBMs) present in non‐RES vitreous was evaluated in the endothelial spheroid sprouting assay.

Results: Mouse orthotopic intravitreal injection of non‐RES vitreous upregulated the expression of pro‐angiogenic/pro‐inflammatory mediators; moreover, it induced alterations of retinal vessels, accumulation of inflammatory infiltrate, and activation of astrocyte gliosis. Notably, HI vitreous was ineffective, pointing to a proteinaceous nature of the non‐RES vitreal mediators acting on mouse retinae. In this context, the blockade of vitreal HBMs mediated by the biotechnological heparin‐like molecule K5‐N, OS (H) or by the pentapeptide Boc2, completely abrogated the activity of non‐RES samples. It is worth noticing that the potency of anti‐HBP compounds was significantly higher than the anti‐VEGF ranibizumab, which was partially effective only at the clinically relevant and saturating concentration of 10 μM, with no further improvement at a double dose.

Conclusions: Our data show that VEGF is only part of a complex machinery regulating angiogenesis, inflammation and oedema formation during DR and that drug resistance is due to the activation of compensatory mechanisms mediated by HBMs besides VEGF.
Functional and morphological characterization of ocular phenotype in C3H/HeOuJ (Pde6b‐rd1) mice
Authors: Tähtivaara Leena , Haapaniemi Anne Mari , Jääskeläinen Niina , Tenhunen Anni , Partanen Päivi , Koponen Anna Mari , Kolehmainen Anni , Ekolle Xavier , Kalesnykas Giedrius , Cerrada‐Gimenez Marc
Published: January 2024

Aims: C3H/HeOuJ mice (The Jackson Laboratory strain #000635) are homozygous for the retinal degeneration 1 mutation Pde6brd1 (rd1) causing severe visual deficits. The purpose of this study was to characterize the ocular phenotype of male and female mice with the rd1 mutation.

Methods: The ophthalmic phenotype of mixed sex rd1 and aged‐matched C57BL/6J wild type (WT) mice (6 females and 4 males for rd1 group, 6 females and 5 males for WT group) was assessed at 3 months of age. Retinal photoreceptor function was quantified using scotopic flash electroretinography (fERG) with six different light intensities: 0.003, 0.01, 0.1, 1, 3 and 10 cd.s/m2 (Celeris, Diagnosys LLC). Retinal morphology was evaluated with spectral domain optical coherence tomography (SD‐OCT) (Envisu R2200, Bioptigen Inc./Leica Microsystems). Retinal thickness was measured from SD‐OCT images using a proprietary convolutional neural network. Optomotor reflex (OMR) was measured as photopic visual acuity and contrast sensitivity at 0.019 and 0.06 cyc/° (OptoDrum Plus, Striatech GmbH). Data were analysed by unpaired t‐test or Mann–Whitney test.

Results: At 3 months of age, the rd1 mutation resulted in significant impairment of visual function in both male and female mice compared to age‐matched WT. fERG a and b‐wave amplitudes were decreased by 90% in both sexes (p < 0.001). The rd1 mice had only minimal visual acuity and contrast sensitivity assessed by OMR. Functional decline correlated with structural changes, notably the significant thinning of the retina (p < 0.001).

Conclusions: The Pde6brd1 mutation resulted in severe functional and structural changes at 3 months of age. The mice presented significantly decreased but detectable fERG amplitudes, however, they had no functional vision as assessed by OMR. Combining fERG and OMR offers longitudinal in‐life quantification of retinal circuitry and functional vision with great utility for evaluation of novel therapeutic approaches for regeneration of the visual system.
Clinical pattern and outcomes of acute retinal necrosis in a referral Center in Tunisia, North Africa: A 17‐year retrospective study
Authors: Mahjoub Anis , Abroug Nesrine , Oussama Ben Saidi , Hajer Loukil , Sana Khochtali , Khairallah Moncef
Published: January 2024

Aims/Purpose: To describe the pattern of acute retinal necrosis (ARN) in a referral centre in Tunisia, North Africa.

Methods: The charts of 22 patients diagnosed with ARN from January 2006 to January 2023 were retrospectively reviewed.

Results: The mean age at presentation was 39.2 (range, 12–70) years, sex ratio was 1.75. The mean diagnostic delay was 17.9 days (range 1–60). The mean visual acuity at presentation was 20/400. All patients presented with a mild to moderate anterior uveitis (100%) with granulomatous keratic precipitates in 18 eyes (81%) and ocular hypertension in 4 eyes (18%). Necrotizing retinitis involved >50% of the retina in 36.5%of eyes. Polymerase chain reaction on aqueous humour sample identified varicella zoster virus in 10 eyes (45%), herpes simplex virus‐1 in 4 eyes (18%) and was negative in 8 eyes (22%). All patients received intravenous acyclovir, followed by oral antivirals. Intravitreal injections of ganciclovir were administered in 12 eyes (54.5%). Follow‐up ranged from 1 month to 48 months. The mean final visual acuity was 20/200. Complications included retinal detachment (RD) (31.8%), macular oedema (18%), macular atrophy (22%), epimacular membrane (22%), cataract (27%), optic nerve atrophy (18%) and central retinal artery occlusion (4%). No patient developed bilateral ARN. Prophylactic laser was performed in 7 eyes (32%). RD was treated with pars plana vitrectomy and silicone oil injection in 7 eyes.

Conclusions: ARN syndrome in Tunisia is most commonly caused by VZV.
Changes in vascular density of optic nerve head in diabetic 1 patients with no retinopathy using optical coherence tomography angiography
Authors: Boned‐Murillo Ana , Fernández‐Espinosa Guisela , Hospital Elvira Orduna , Diaz Maria Dolores , Pinilla Maria Sopeña , Alvarez Marta Aria , Grasa Cristina Tomas , Lozano Isabel Pinilla
Published: January 2024

Aims/Purpose: To analyse optic nerve head (ONH) blood perfusion using optical coherence tomography angiography (OCTA) in Type 1 diabetes mellitus (DM12) patients without retinopathy and in healthy control eyes.

Methods: A total of 33 DM1 subjects without diabetic retinopathy (DR) and 24 age‐matched healthy individuals were assessed by OCTA to quantify radial peripapillary capillary (RPC) plexus density thickness in the four areas of the ETDRS grid.

Results: Mean ages were 50.64 ± 9.05 for the DM1 group and 53.17 ± 4.56 years for the control group, with no differences between groups (p = 0.22). Superior RPC value was 64.48 ± 4.37 versus 64.45 ± 6.13 (p = 0.98), temporal RPC value was 57.42 ± 7.04 versus 55.07 ± 5.03 (p = 0.21), nasal RPC value was 59.58 ± 5.03 versus 61.00 ± 4.74 (p = 0.31), and inferior RPC value was 64.57 ± 4.17 versus 62.86 ± 7.21 (p = 0.32), in the DM1 group and in the control group, respectively.

Conclusions: DM1 patients presented lower values in all areas except I compared to healthy individuals, with no significant differences. Larger cohort studies need to support RPC density as a possible biomarker in detecting eyes with DR.
Lamotrigine‐associated macular phototoxicity in Asperger syndrome
Authors: Haddar Selim , Braham Imene Zhioua , Mrad Syrine Ben , Hachicha Ines , Erraies Khalil , Boukari Mejdi , Zhioua Raja Gmar
Published: January 2024

Purpose: Asperger's syndrome is a neurodevelopmental disorder that falls within the autism spectrum disorder family. Comorbid conditions such as depression and anxiety are commonly associated, and lamotrigine is often prescribed off‐label for treatment. It has the capacity to absorb ultraviolet (UV) light and generate free oxygen radicals, which can potentially cause cellular damage. In this case report, we present multimodal imaging findings in a patient diagnosed with solar maculopathy.

Methods: A young patient was referred to our department for bilateral visual decline and central scotoma. The patient was examined with multimodal imaging including fundus photography, fundus autofluorescence (FAF), swept‐source optical coherence tomography (SS‐OCT) and multifocal electroretinogram.

Results: A 25‐year‐old patient with Asperger's syndrome treated with lamotrigine was referred to our department for bilateral visual decline and central scotoma. Best corrected visual acuity (BCVA) was 0.40 in both eyes. Dilated fundus examination revealed a bilateral yellow foveal lesion. Fundus autofluorescence (FAF) imaging showed foveal hyperautofluorescence. SS‐OCT in the macular region of both eyes showed a disruption of the ellipsoid zone and the external limiting membrane. Upon further questioning, the patient disclosed history of repeatedly gazing at the sun. The diagnosis of solar maculopathy associated with lamotrigine was established.

Conclusion: This is the second report of lamotrigine associated retinal phototoxicity. Lamotrigine, recognized as a photosensitizer, may induce a photochemical response, with retinal phototoxicity. Caution must be exercised to educate patients about the importance of not gazing directly at the sun, as it van cause irreversible retinal impairment.
Endophthalmitis after cataract surgery
Authors: Choi Moon Jeong
Published: January 2024

Aims/Purpose: Retrospective review in 164 patients with endophthalmitis after cataract surgery, and intended to figure out the factors which affect clinical features, bacteria identification and final visual acuity (VA).

Methods: We followed the guideline of EVS for operative treatment. In the case of initial LP, vitrectomy was conducted. HM or better, either IOAI (intraocular antibiotics injection, 1.0 mg/0.1 mL of vancomycin and 2.25 mg/0.1 mL of ceftazidime) or vitrectomy was optionally conducted. After initial treatment, we conducted reintervention within 48 h where the decrease of vitreous opacity and hypopyon, and pain relief did not show up. We obtained A/C fluid and vitreous specimen for figure out the bacteria identification.

Results: 25 patients had initial VA below LP, the cases of HM were 86 and 53 patients had better than FC. 81 patients were observed where it took 3 days until the symptoms of post‐operative endophthalmitis occurred. Where final VA improved by 0.5 or better, the case that vitrectomy was conducted with early treatment was not statistically much different from the case of sole IOAI. The influential factors in final VA was where it took more than 3 days for endophthalmitis to occur after cataract surgery, initial VA was HM or better, and the result of bacteria identification was Gram(+) and those 3 cases affected the positive outcomes.

Conclusions: Good initial VA means the diagnosis of endophthalmitis was relatively prompt. It can be said that intraocular tissues were less damaged, the virulent would be infected by less bacteria and then those affect positive prognosis. In addition, endophthalmitis diagnosed 3 days later after surgery, prognosis was good. It seems that this is because damage of intraocular tissues occurs slowly as pathogenicity did not progress quickly with light clinical features where it is infected by weak bacteria. And it can be considered that the period until post‐operative endophthalmitis occurs affects prognosis.
Ruthenium brachytherapie and sandwich therapy for medium sized uveal melanomas
Authors: Do Ha‐Vy , Czapla Celine , Vogel Heike , Hildebrandt Guido , Guthoff Rudolf , Fuchsluger Thomas , Brockmann Claudia
Published: January 2024

Aims/Purpose: Brachytherapy using ruthenium is an established procedure for the treatment of uveal melanomas, the most common malignant primary intraocular tumour in adults. The supplementary use of transpupillary thermotherapy (TTT) with brachytherapy is known as sandwich therapy. Due to the rarity of uveal melanomas, long‐term outcome of large cohorts treated by ruthenium brachytherapy with and without TTT is of special clinical and scientific interest.

Methods: Based on a retrospective longitudinal study, patients with uveal melanoma who received treatment using ruthenium brachytherapy at the Department of Ophthalmology from 1994 to 2021, were analysed. The evaluation includes tumour height, visual acuity, radiation data, side effects, local recurrence, bulbus preservation and occurrence of metastasis.

Results: Overall, 150 patients with medium sized uveal melanoma (tumour height >3.0 and ≤7.0 mm) who received ruthenium brachytherapy were included. The mean age of patients at diagnosis was 63.5 ± 12.9 years (median 65), the proportion of women was 60.0%. Tumours were located centrally in 48.7% of cases; ciliary body involvement was seen in 4%. Additive transpupillary thermotherapy (TTT) was performed in 70.7% of cases as part of a sandwich therapy. After therapy and a mean follow‐up of 68.0 ± 58.3 years tumours height was significantly reduced from 4.5 ± 1.1 to 1.4 ± 1.6 mm (p < 0.001). Visual acuity showed deterioration from 0.25 ± 0.43 to 1.0 ± 0.85 logMAR (p < 0.001) due to the large proportion of centrally located tumours. In 29.9% of cases no side effects requiring therapy occurred. Within the remaining cases cataracta complicata (41.3%) and radiation retinopathy (30.0%) were observed. Local tumour control was achieved in 86.0% of patients, in 91.3% of cases the ocular globe was preserved. Metastatic free survival was seen in 86.4% of patients.

Conclusions: Brachytherapy using ruthenium plaque with and without TTT represents a safe procedure in the treatment of uveal melanomas over the last three decades.
Enhanced choroidal thickness, total choroidal area and choroidal vascularity index from deep‐learning generated OCT images
Authors: Bellemo Valentina , Kumar Ankit , Wong Damon , Chua Jacqueline , Liu Xinyu , Xu Xinxing , Liu Yong , Schmetterer Leopold
Published: January 2024

Aims/Purpose: Our goal is to enhance the visualization of the choroid in clinical standard spectral‐domain OCT (SDOCT) scans using a deep‐learning (DL) approach that uses matching swept‐source OCT (SSOCT). We aim to improve the measurement of the sub‐foveal choroidal thickness (SFCT), total choroidal area (TCA), and choroidal vascularity index (CVI) in SDOCT images.

Methods: A total of 105 350 SDOCT and SSOCT B‐scan images (Zeiss Cirrus 5000 and Zeiss PlexElite) were used to develop the DL model. The data set included B‐scans from healthy (238 eye pairs from 155 patients) and glaucoma (192 eye pairs from 122 patients) subjects. The DL model learned deep anatomical features from SSOCT scans and generated enhanced SDOCT images. The peak signal‐to‐noise ratio (PSNR) and structural similarity index metric (SSIM) were used to assess the quality of generated images. In addition, we compared the anatomical parameters derived from the generated and ground‐truth SSOCT images, including SVCT, TCA and CVI values.

Results: We tested our method using 20 580 B‐scan image pairs from 84 eyes. The DL‐generated images effectively preserved the anatomical structure of the retina layers and improved the visualization of the choroid. The enhanced SDOCT images had higher image quality than the original SDOCT images, as demonstrated by the higher PSNR (31 dB vs. 18 dB) and SSIM values (3.4 times higher SSIM than the original SDOCT images). SVCT, TCA, and CVI measurements from the DL‐generated SDOCT images showed strong correlations with corresponding measurements using SSOCT with high Pearson's coefficients (0.93, 0.99, and 0.93), high intra‐class correlation indices (0.96, 0.99 and 0.96), and high coefficient of determination r2 values (0.85, 0.98 and 0.86).

Conclusions: Our DL model enhances the visibility of the choroid in images, surpassing the capabilities of standard clinical SDOCT images. As a result, accurate measurement of SVCT, TCA and CVI, which were previously limited due to imaging depth constraints of SDOCT, becomes possible. This technology opens up new possibilities for utilizing affordable SDOCT devices to study the choroid in healthy and pathological conditions.
Comparison in treatment effect according to the IPL treatment area in meibomian gland dysfunction patients
Authors: Min Ji Sang , Jun Ikhyun , Kim Tae‐im , Seo Kyoung Yul
Published: January 2024

Aims/Purpose: We investigated whether there is a difference in the treatment effect according to the intense pulsed light (IPL) treatment site of meibomian gland dysfunction (MGD) patients.

Methods: Patients who underwent 3 IPL treatment at 3‐week intervals were divided into groups A, B and C according to the treatment site (Group A, upper lid and lower lid; Group B, lower lid and lateral canthus; Group C, lower lid). Lid abnormality score (LAS), meibum expressibility (ME), meibum quality (MQ), lipid layer thickness (LLT), type I Schirmer test (ST), tear break‐up time (TBUT) test, and corneal staining scores (CFSs), and ocular surface disease index (OSDI) were obtained before the first and after the third IPL treatment.

Results: Of 136 patients (136 eyes) were recruits, 45 (45 eyes) in group A, 56 (56 eyes) in group B, and 36 (36 eyes) in group C were included. LAS, ME, MQ, TBUT, CFS, and OSDI were significantly improved in group A, B, and C. The difference value of LAS before and after IPL treatment in group A and B were significantly greater than that of group C.

Conclusions: Additional IPL treatment of upper lid and lateral canthus were considered to provide additional improvement in treating MGD patients.
Changes of the bulbar conjunctiva as the result of glaucoma medication treatment
Authors: Tetarchuk Vladyslav , Zhmud Tetiana
Published: January 2024

Aims/Purpose: To determine changes of the bulbar conjunctiva as the result of glaucoma medication treatment.

Methods: We used an impression cytology method which implies the application of a cellulose acetate filter to the ocular surface, twice in the same place, to remove superficial layers of the nasal quadrant conjunctiva epithelium. The strips were removed after a few seconds of exposure, transferred into a fixative solution, followed by histological staining and light microscopy examination. The presence of squamous metaplasia was assessed using Nelson's scale, based on cells' morphology, staining behaviour, integrity and nucleoplasmic ratio. The case study included the first group of patients suffering from POAG and DED (80) (mean age = 63.8 ± 6.7 years) which was divided into 4 subgroups: 1 ‐ patients (40), who suffer from glaucoma for less than 5 years; 2 (40) ‐ more than 5 years; subgroup a (40) ‐ with one drug instilled, b (40) ‐ 2 or more drugs instilled. The second group consisted of almost healthy patients (mean age = 67.9 ± 8.9 years) All of them underwent general ophthalmological examination.

Results: According to OSDI all glaucoma patients had dry eye symptoms (15 or more points). In subgroup 1 40% were diagnosed with Nelson I, 60% with Nelson II. In subgroup 2 15% had Nelson I, 55% had Nelson II and 30% had Nelson III. In subgroup a 20% of patients had Nelson I, 60% had Nelson II, and 20% were diagnosed with Nelson III. In subgroup b 30% had Nelson I, 60% had Nelson II, 10% of patients had Nelson III.

Conclusions: 80% of cases show changes that correspond to II‐III Nelson degrees according to Nelson classification. The severity of metaplasia correlated with the duration of eye drops therapy, but not with the amount of them. According to the results that we received, and the international data, it is recommended to choose drugs without preservatives and other potentially toxic components for the long‐term treatment of glaucoma.