bluuebunny/crossref_metadata_2025 huggingface dataset:
Convolutional neural networks for detection and classification of corneal pathologies on scheimpflug imaging
Authors: Hartmann Lennart , Armin Wolf , Christian Wertheimer
Published: January 2025

Aims/Purpose: Corneal tomography is a standard imaging modality for the assessment of corneal pathologies, but can sometimes be difficult for non‐specialist ophthalmologists to interpret. Convolutional neural networks as a means of deep learning are used in many clinical areas due to their ability to extract information from multidimensional data sets, especially images. The present retrospective, monocentric study was conducted to assess the use of a convolutional neural network in the detection and classification of corneal pathologies on tomography.

Methods: This is a retrospective monocentric study at a tertiary university‐based clinical centre. After a strict quality control, 13567 tomography records (from OCULUS Pentacam) were included. Raw data as well as anterior curvature and elevation data were exported. The raw data was then displayed using a self‐developed non‐linear heat map. Two corneal specialists used a self‐developed labelling tool for annotating the records into the following categories: Normal, regular astigmatism, irregular astigmatism, keratoconus, other ectasia, refractive surgery, pterygium and error. After the labelling process, the dataset was divided into a training set, a validation set and a test set.

Results: The training and the validation sets were used to train the network. Accuracy of the detection and classification within the test set was then measured. The accuracy of detection and classification of corneal pathologies by the neural network was 87%. This was accomplished by a combination of a learning rate of 0.001, a batch size of 16 and 500 epochs.

Conclusions: Here we show that training a convolutional neural network with images may help clinicians to detect and classify different corneal pathologies.
Ocular pain correlates with substance P levels in tears of healthy subjects
Authors: Palombella Silvia , Suanno Giuseppe , Pederzolli Matteo , Bartolomeo Nicolò , Tilaro Gianluca , Fonteyne Philippe , Massimo De Micheli , Bandello Francesco , Ferrari Giulio
Published: January 2025

Aims/Purpose: to quantify the level of the neuropeptide substance P (SP) in the tear fluid and correlate it with measures of ocular pain, corneal sensitivity, and conjunctival hyperemia in healthy subjects.

Methods: we enrolled 18 healthy patients (age range: 19–31 y/o) that were randomly divided into two groups: the first received the topical anesthetic oxybuprocaine (A+); the second one did not (A−). Subsequently, mild corneal nerve stimulation was applied with a hypertonic solution to both groups. Before and after the stimulation tear fluid was collected from all volunteers. We then measured SP levels with the ELISA test and correlated those with clinical parameters acquired before and after stimulation. Visual analogue scale (VAS) and ocular surface disease index (OSDI) questionnaires were used to assess ocular pain and discomfort, respectively. Moreover, corneal sensitivity and conjunctival hyperemia were measured with Cochet‐Bonnet esthesiometer and the Efron scale, respectively.

Results: in the A+ group, the application of the anesthetic statistically decreased the release of SP in the tear fluid after corneal stimulation (p < 0.01). On the contrary, SP levels in group A‐ tear were not modified by the corneal stimulation. As expected, the A+ group experienced lower ocular pain (p < 0.001), discomfort (p < 0.05), hyperemia (p < 0.01), as well as reduced corneal sensitivity (p < 0.0001) after the corneal stimulation compared to group A−. Remarkably, the SP levels positively correlated with corneal sensitivity (r = 0.6671, p < 0.01) and pain (r = 0.4979, p < 0.05). Moreover, a positive trend was observed between SP and ocular surface inflammation (p = 0.058).

Conclusions: our data demonstrated that the inhibition of corneal nerves decreased the SP release in tears together with inflammation and ocular pain. Therefore, SP levels in tears could be used as an objective marker to quantify pain and inflammation of the ocular surface.
In vivo implantation of the grosso shape‐memory implant for corneal shape and strength restoration
Authors: Xeroudaki Maria , Lepore Emiliano , Grosso Edoardo , Moustardas Petros , Mansutti Letizia , González Laura , Del Saz Ana Nolla , Lagali Neil
Published: January 2025

Aims: The GROSSO® implant is an ophthalmic medical device designed to reshape the ectatic cornea. The primary aim of this study is to assess for the first time the surgical implantation and safety of the device in vivo in a preclinical study done in rabbits.

Methods: A 9‐9.5mm diameter circular corneal pocket located at 2/3 of the minimum corneal thickness was created by femtosecond laser in the right eye only. In 8 control eyes the pocket was manually separated while in the GROSSO® group with 12 eyes, the implant was manually inserted through the access cut while being folded with a 6‐0 vicryl suture. After insertion in the intrastromal pocket, the suture was cut and the device was atraumatically unfolded inside the pocket. Intraocular pressure, tomography, biomechanics, in vivo confocal microscopy (IVCM) were evaluated before operation and postoperatively at 1 week and 1,2,3 and 6 months. Haze and neovascularization scoring was used to assess the inflammatory reaction to the implant.

Results: All surgeries were successfully completed but with a variable eccentric ablation due to the applanation which is designed in the femtolaser for the human cornea. Haze and neovascularisation did not differ between groups, with haze returning to preoperative levels at 3 months. Neovessels were detected in 5 GROSSO® and 2 control eyes at 1 month and were located outside or in the periphery of the implant and then they were treated with topical steroids resulting in vessel regression. The GROSSO® implantation did not alter the intraocular pressure or central corneal thickness compared to controls. Biomechanical strength of GROSSO® group increased relative to controls and preoperative levels, and IVCM showed minimal inflammation around the implants. The GROSSO® group had lower keratometry values at 1 month that remained stable to 6 months, while controls experienced changing keratometry up to 6 months.

Conclusions: The GROSSO® medical device can be safely implanted in the corneal stroma with laser‐assisted surgery. Postoperative inflammation was present in both treatment groups and minimal and could be treated with topical steroids. There were no changes in intraocular pressure or corneal thickness in the GROSSO® group and implanted corneas became flatter and biomechanically stronger thanks to the presence of the GROSSO® medical device.
Can the choice of artificial tears harm patients? A narrative review with learnings from the nordic guidelines
Authors: Mikha Katrine , Rasmussen Christian , Ahrensberg Simone , Freiberg Josefine , Heegaard Steffen , Kolko Miriam
Published: January 2025

Purpose: To provide an overview of artificial tears marketed in the Nordic countries: Denmark, Sweden, Norway and Finland. Furthermore, this review aims to highlight the different preservatives and other constituents found in artificial tears of the Nordic market, focusing on adverse effects.

Methods: Artificial tears appearing in the Nordic Guidelines of “Dry Eye Disease” 2022 edition were included and tables listing their components were created. Based on the preservatives and other constituents found in the artificial tears on the Nordic market, a literature search was conducted to investigate differences and potential adverse effects. Included articles were (i) studies performed on humans in vivo or in vitro human models, (ii) published between 2000‐2023 and (iii) studies focusing on effects, preservatives, toxicity, other constituents, and preservative‐free artificial tears.

Results: A total of 66 artificial tears were found on the Nordic market based on the Nordic Guidelines. A large proportion (27 out of 66) of the artificial tears contains preservatives. Ten of these are preserved with benzalkonium chloride (BAK) or cetrimide. After a thorough systematic literature search, 87 articles met the inclusion criteria. A substantial amount of evidence has been found for the toxic effects of BAK and phosphate buffer solutions. There is no evidence of toxic effects of lubricants, osmoprotectants and lipids.

Conclusions: The findings of this review highlight the paradoxical fact that many treatments for ocular surface diseases contain toxic preservatives contributing to a possible worse condition. In particular, long‐time toxic effects of BAK may contribute to disease progression.
Tear proteomics for the understanding of corneal biomechanical weakness in offspring of keratoconus patients
Authors: López‐López Maite , Alvite‐Piñeiro Tania , Pastoriza Yaiza , Lema Isabel , Regueiro Uxía
Published: January 2025

Aim: To analyze the tear proteome of offspring of keratoconus patients (O‐KC) to elucidate the molecular mechanisms involved in corneal weakening in high‐risk individuals.

Methods: 80 O‐KC young participants matched with 42 control subjects without KC family history were involved in this case‐control study. Corvis® ST and Pentacam® HR were used for the biomechanical and tomographic assessment. O‐KC eyes were classified as low, moderate, and high risk of KC development (O‐KC‐LR, O‐KC‐MR, and O‐KC‐HR) based on the corneal biomechanical behavior. Tear fluid was extracted using Schirmer strips, and the proteomic profile was analyzed using micro–liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS). SWATH‐MS method was used for protein quantification. Relationship and molecular characteristics of the proteins with differential expression between groups were explored using in silico tools. SPSS was used for statistical analysis.

Results: Biomechanical analysis showed that 18% of O‐KC eyes had moderate risk of KC development [O‐KC‐MR], and 11% biomechanical alterations compatible with high‐risk for ectasia development [O‐KC‐HR]. Of the total proteins quantified, 15 were dysregulated (p < 0.005) in the O‐KC samples, even in those cases without detectable alterations in corneal biomechanical properties [O‐KC‐LR]. Bioinformatic analysis linked dysregulated proteins with oxidative stress, cell adhesion, and cytoskeleton organization processes, as well as with major mechanotransduction paths such as RhoA, mTOR, or E‐cadherin/N‐cadherin signaling. LCN‐1, LF, CAPN1 and SOD1 showed high specificity and sensitivity for detecting biomechanical alterations and for discriminating between controls and O‐KC groups.

Conclusions: Our findings support the increased risk of the O‐KC with nearly a third of O‐KC eyes showing signs of corneal weakening that could lead to ectasia development and revealed new promising biomarkers for early detection of KC‐risk.
Management of a case of stromal herpetic keratitis
Authors: Cervilla Javier José Bermúdez , Mallen Victor , Biescas Andrés , Rius Nuria , Ila Carmen , Monleón Claudia Hernández‐Barahona , Navarro Damián García , Santana Carlos , Munuera Inés , Funes Elisa
Published: January 2025

Aims/Purpose: To present a case study of stromal herpetic keratitis (SHK) and emphasize the importance of accurate differential diagnosis and appropriate therapeutic approaches in primary care settings.

Methods: A detailed anamnesis and ocular examination were conducted, including fluorescein staining to identify dendritic corneal ulcers indicative of herpetic keratitis (HK). The patient was followed closely with a combination of antiviral and corticosteroid therapy.

Results: A 20‐year‐old woman presented with 72 hours of left eye redness, pain, tearing, and vision loss. No traumatic history was reported, but a recent herpetic lesion on the upper lip was noted. Clinical examination revealed significant conjunctival hyperemia and a characteristic dendritic lesion on the cornea. Detailed examination with a slit lamp showed a central dendritic ulcer stained with fluorescein and peripheral infected cells stained with rose Bengal, alongside a focal stromal inflammation. These findings confirmed the diagnosis of SHK. Follow‐up revealed resolution of the stromal inflammation and closure of the dendritic epithelial defect.

Conclusions: The case underscores the critical need for accurate diagnosis of HK subtypes, as SHK requires specific treatment with topical corticosteroids in addition to antiviral therapy. Clinical guidelines indicate that the benefits of corticosteroid use in SHK outweigh the risks, though close monitoring is essential to mitigate adverse effects such as increased intraocular pressure and cataract formation. This case highlights the importance of prompt specialist referral when primary care practitioners encounter complex ocular presentations, ensuring timely and appropriate management to prevent irreversible vision loss.

References

Guidelines for Ocular Herpes Management.

SECOIR Monography: Update on Corneal Infections. Chapters 7 and 11.
Ocular bee sting with retained stinger
Authors: Iatissam  , Bentouhami Mohamed Reda , Hidan Younes , Mchachi Adil , Benhmidoune Laila , Rachid Rayad
Published: January 2025

Aims/Purpose: Ocular bee stings are a rare but can lead to severe inflammatory complications. Some cases have been described, but stinger retention is exceptional. We report the case of a young patient with a limbal bee sting, with stinger retention.

Methods: A male 19‐year‐old, presented a painful red eye following an accidental bee sting. Examination found a visual acuity of 20/20, conjunctival hyperaemia, a clear cornea, calm anterior chamber, and a perilimbal foreign body, which corresponded to the bee stinger.

We performed a conjunctival peritomy and removed the stinger using McPherson forceps under topical anesthesia. The sclera being intact, we sutured the conjunctiva and prescribed antibiotiotics and steroid drops. Evolution was marked with improvement and disappearance of symptoms.

Results: Bee sting wounds can penetrate tissues like a harpoon, complicating the stinger's removal, along with possible sequelae: mechanical like corneal abrasion or intrastromal retention, and toxic effects. The venom contains phospholipase A2 and mellitin, leading to membrane lysis and pain, as well as apamin, which causes mast cells degranulation and histamine release. It can cause conjunctivitis, corneal infiltrates, cataract, uveitis, hyphema, lens subluxation, retinal lesions, optic neuropathy or choroidal detachment.

Conclusions: Ocular bee stings are rare and can induce severe inflammation. Extraction of the stinger and topical antibiotic associated with steroids are the treatment of choice, in addition to close monitoring of possible complications.

References

Gudiseva H, Uddaraju M, Pradhan S, Das M, Mascarenhas J, Srinivasan M, Prajna NV. Ocular manifestations of isolated corneal bee sting injury, management strategies, and clinical outcomes. Indian J Ophthalmol. 2018 Feb; 66(2): 262‐268.

Chilibeck, C., Wang, N., & Murphy, C. (2021). Making a bee‐line for the eye: a limbal sting and retained honey bee. Clinical and Experimental Optometry, 104(4), 538–540.
New deep AI‐based algorithm to assess quality of primary corneal endothelial cell cultures
Authors: Maurin Corantin , Guillaume Bonnet , Yann Gavet , Inès Aouimeur , Louise Parveau , He Zhiguo , Philippe Gain , Thuret Gilles
Published: January 2025

Aims/Purpose: The development of cell therapies to treat corneal endothelial pathologies requires characterizing the cells during the cell culture process. The endothelial cell density (ECD) and morphometry are essential parameters for identifying cultures with sufficient phenotype and yield. However, they are difficult to measure on cells in culture using conventional image analysis tools. Aims: (1) To develop an AI‐based automatic cell segmentation method for reliable ECD and morphology measurement. (2) To select new morphometry parameters. (3) To classify endothelial cell cultures by quality.

Methods: Experiments were conducted on primary cultures of human corneal endothelial cells (hCECs) after immunofluorescent labeling against NCAM revealing lateral membranes. Cultures from donors < 30 years old (high ECD and regular mosaic) were compared with cultures form older donors comprising senescent cells and cells in endothelial‐mesenchymal transition. Images were acquired with an epifluorescence microscope. We compared two AI segmentation models, a custom model and the published Cellpose model1,2. Models were trained with manually labeled images and tested on separate images. Standard image analysis methods in Python measured cell number, morphology, comparing reference and AI‐generated images3. Additional metrics were developed to qualify endothelial cell culture and correlated with known metrics. K‐Means and other classifications were tested to classify cell culture quality.

Results: Cellpose outperformed the custom model in segmentation accuracy (mean relative error ± SD respectively: 0.054 ± 0.020 vs 0.0499 ± 0.0136). New reliable morphological measurements were defined, enabling classification of endothelial cell culture clusters based on quality. Coronal CV (coefficient of variation) was developed to complement classical CV used to characterize clinical endothelial cell.

Conclusions: AI segmentation of hCEC in culture significantly improves quality measurement during bioengineering, facilitating rapid analysis and classification of cell batches, thereby enhancing quality assessment and success rates for cell‐based endothelial therapy.

References

Stringer et al (2020).

Pachitariu et al (2022).

Gavet et al (2012).
Changes in the accommodative microfluctuations with different viewing conditions and stimuli targets
Authors: Dominguez‐Vicent Alberto , Selin Paulina , Venkataraman Abinaya
Published: January 2025

Aims/Purpose: To investigate how accommodative microfluctuations change with varying viewing conditions and stimulus targets, including different viewing distances, spatial frequencies, contrasts, and with negative contrast polarity.

Methods: Powerref3 was used to measure the AMFs. Four stimulus targets consisting of five letter words were presented on an Ipad: low contrast (LC) 10%, negative contrast polarity (NC), and two high contrast 100% in different sizes. Each stimulus corresponded to a visual acuity of 6/12, the high contrast target was additionally displayed at 6/36. The targets were presented at 40 cm and 4 m. 11 participants with no ocular pathologies or binocular or accommodative disorders were measured. The 6/12 target was used as a baseline reference for comparisons against the other stimuli targets in the analysis. The different components of the AMFs, the high (1.0‐2.3 Hz), mid (0.61–0.99 Hz) and low (0‐0.6 Hz) were analysed. The root mean square (RMS) accommodation values and accommodative response were also analysed.

Results: No significant difference in RMS or any of the frequency components were found for the various stimulus targets, including spatial frequency, contrast or negative contrast polarity, when compared to the reference 6/12 target. When comparing the RMS values for each stimulus condition between distances, a significant increase was seen at near for 6/12 (p = 0.027), 6/36 (p < 0.001) and LC (p = 0.002), but not for NC (p = 0.465). No significant difference in accommodative response was found between the different stimulus conditions (p = 0.427).

Conclusions: The findings suggest that AMFs are not significantly affected by the various stimuli targets presented in this study. However, the viewing distance significantly affected the AMFs, with increased AMFs at near.
Bilateral aqueous misdirection following cataract surgery: A case report
Authors: Tahhan Owais
Published: January 2025

Aims/Purpose: The purpose of the case‐report is to explore the aetiology, prevention and management where there is inadequate literature on the topic of BAM. This allows reflection on the case, its respective learning points and opportunities for future research into the prevention and screening of people with risk factors for BAM.

Methods: We present a case of an 85‐year‐old female with a history of bilateral cataract surgery, who presented with blurry vision, pain, photophobia, and elevated intraocular pressure (IOP). Detailed clinical examinations, including visual acuity assessment, IOP measurement, slit‐lamp examination, and gonioscopy were performed. Management strategies, including medical therapy and surgical intervention, are discussed.

Results: Upon presentation, the patient exhibited features consistent with BAM, including shallow anterior chambers, mid‐dilated pupils, and elevated IOPs. Immediate medical management with intravenous acetazolamide, topical pressure‐lowering agents, and cycloplegics was initiated. Subsequently, anterior vitrectomy was performed in both eyes, leading to the resolution of symptoms, deepening of anterior chambers, and normalization of IOPs at 6 weeks postoperatively.

Conclusions: Bilateral aqueous misdirection is a rare but potentially blinding complication following cataract surgery. Prompt recognition and aggressive management, including medical therapy and surgical intervention, are crucial for achieving favourable outcomes and preserving visual function. Clinicians should maintain a high index of suspicion for BAM in postoperative patients presenting with unexplained elevated IOP and shallowing of anterior chambers, facilitating timely diagnosis and intervention.

We present a case of BAM which has high educational value in its rarity. We investigate the evidence‐based risk‐factors and aetiology that apply in this case and discuss novel approaches to conservative and surgical management. Based on the literature some high‐risk cases would potentially benefit from taking preventative measures to reduce the incidence of BAM.
Effect of the spherical aberration in intraocular lenses on visual quality
Authors: Cervantes Dayan Flores , Ramírez Emilio Dorronzoro , Arevalo Vanesa Gerena , Paciencia Alfredo Morales , Haddi Inas Baoud Ould , Arias Cristina Bonnin , Sánchez Vanesa Blázquez
Published: January 2025

Aims/Purpose: To analyze the effect of corneal spherical aberrations (z40) on the selection of extended range intraocular lenses to optimize patients’ visual quality.

Methods: This is an observational, prospective, and cross‐sectional study. The sample consists of 30 patients with bilateral implantation of the study's intraocular lenses (IOLs): AcrySof® IQ Vivity™ (Alcon Laboratories, Inc, Fort Worth TX) with 22 eyes and Luxsmart® (Bausch & Lomb) with 38 eyes respectively. Each IOL has a manufacturer‐specified asphericity value, and the analysis of spherical aberrations was conducted with Pentacam HR® (Oculus Optikgeräte GmbH, Germany).

Photopic visual acuity (VA) – monocular and binocular (for distant, intermediate, and near vision) – was measured using the ETDRS test and evaluated one‐month post‐surgery. A p‐value of < 0.05 was considered the criterion for statistical significance, and the correlation was performed with Spearman's test.

Results: The average pupil diameter of the sample was 2.64 ± 0.39 mm, with a maximum value of 4.2 mm and a minimum of 1.90 mm. All patients experienced an improvement in postoperative VA under photopic conditions, regardless of the implanted IOL. The distant VA for the Vivity® lens was ‐0.05 LogMar and for Luxsmart® it was 0.01 LogMar; the near VA for Vivity® was 0.1 LogMar while for Luxsmart® it was 0.3 LogMar, and the intermediate VA for both lenses was 0.15 LogMar. No correlation was observed between Z40 parameters and VA

Conclusions: The IOL models studied, Vivity® and Luxsmart® provide optimal distance VA, although the Vivity® lens showed better results at all distances.
Isolated corneal intraepithelial neoplasia: An unheard variety
Authors: Carles‐Cerban Luis Maria , Moraña‐Borrageiros Maria Noelia , Alvarez‐Novoa‐Rodriguez‐Cadarso Andrea , Alvarez‐Rodriguez Roberto , De‐Rojas‐Silva Victoria
Published: January 2025

Aims/Purpose: The purpose of this clinical case is to present the symptoms, as well as biomicroscopical, tomographical and histological findings of the isolated corneal intraepithelial neoplasia, a very rare variety of ocular surface squamous neoplasia.

Methods: We present the case of a 78‐year‐old woman with foreign body sensation in her right eye for four months. The cornea presented, apart from crocodile shagreen, a white patch in the temporal‐inferior quadrant, separate from the limbus. This lesion showed punctate staining and contained a thin line of normal aspect. The optical coherence tomography (OCT) showed hyperreflective and thickened epithelium with sudden transition to normal cornea.

On suspicion of corneal intraepithelial neoplasia, excisional biopsy was indicated, with Shields's non‐touch technique, 2 mm surgical margins and absolute‐alcohol application on the limbus.

Furthermore, a review of the past 25 years literature has been performed, using the following key words: corneal intraepithelial neoplasia; ocular surface squamous neoplasia.

Results: The histological result showed a corneal intraepithelial neoplasia with non‐assessable margins. One week after surgery, the defect had already been replaced by normal epithelium, and we added two cycles of co‐adjuvant topical mitomycin C (0.04%). Two years after surgery, the patient is asymptomatic and with no signs of recurrence.

Regarding the review, only 10 cases of isolated corneal intraepithelial neoplasia have been described in the past 25 years. No references of crocodile shagreen concurrence have been found, whereas there is some consensus of surgery as main treatment and OCT as useful diagnostic tool.

Conclusions: Isolated corneal intraepithelial neoplasia should always be included in differential diagnosis when it comes to a thickened and atypical lesion in the cornea. In this context, OCT can be useful, whereas final diagnosis and treatment should include excisional biopsy.
Submacular hemorrhage displacement with subretinal rtPA and air injection
Authors: Rego‐Lorca Daniela , Crespí‐Vilimelis Jaume , Loscos‐Giménez Irene , López‐de‐Eguileta Alicia , Díaz‐Cascajosa Jesús , Vela‐Segarra José Ignacio
Published: January 2025

Aims/Purpose: submacular hemorrhage (SMH) is a well‐known cause of severe vision loss. Surgical treatment aims displacement of the blood away from the fovea to prevent macular photoreceptor damage. Different surgical techniques have been described for this purpose, but, until date, the best approach remains a matter of debate. Injection of subretinal rtPA and air was first described in 2013 reporting encouraging results. We describe our experience with this surgical technique.

Methods: consecutive case series including patients with SMH managed with PPV and subretinal injection of rtPA and air. SMH was graded as small, large, extensive, or massive. SMH displacement was assessed one week after surgery.

Results: 36 eyes of 36 patients were evaluated. Etiologies of SMH included age‐related macular degeneration (83.3%), macroaneurysm rupture (8.3%), ocular traumatism (5.6%) and Terson syndrome (2.8%). Average time between diagnosis and surgical intervention was 6.1 days. Hemorrhage size was classified as small in 8 patients (22.2%), large in 8 patients (22.2%), extensive in 16 patients (44.4%) and massive in 4 patients (11.1%). Sub‐RPE hemorrhage was noticed in 21 patients (58.3%). One week after surgery, SMH displacement was achieved in 33 patients (91.7%). Visual acuity improved in 28 patients (77.8%), remained stable in 4 patients (11.1%) and worsened in 4 patients (11.1%). Postoperative complications included vitreous hemorrhage (11.1%), macular hole (5.6%), and retinal detachment (5.6%).

Conclusions: subretinal injection of air and rtPA is an effective technique for SMH displacement, facilitating rapid blood migration and, thus, reducing retinal deterioration and enabling greater visual recovery.

References

Martel JN, Mahmoud TH. Subretinal pneumatic displacement of subretinal hemorrhage. JAMA Ophthalmol. 2013; 131: 1632–5.
High myopia and atrophy complication: Multimodal study and prospects
Authors: Gonzalez Corinne
Published: January 2025

Aims/Purpose: This multimodal study of High Myopia with Atrophy areas, patchy atrophies of retina to analyze retina layers structure, focusing on outer retinal layers, particularly photoreceptor and Retinal pigment epithelium layers, their evolution, their impact on visual fonction. So the prospects of High Myopia's Atrophy complications.

Methods: A total of 84 eyes from 44 patients, with High Myopia. Multimodal study includes mainly OCT, notably OCT en Face (Spectralis HRA‐OCT, spectral domain OCT), combined with Autofluorescence, IR imaging, Fluorescein (FA) and Infracyanine (ICG) angiography (SLO Spectralis HRA‐OCT) (mainly when suspicion of subretinal neovascular complication). ETDRS visual acuity (VA), complete ophthalmic examination with Fundus exam were added. Follow‐up was done every year during 8 years.

Results: VA remain stable in 42% cases, impaired in 58% cases. Multimodal analyze highlight 15% stable, 85% Atrophy area increase, (patchy atrophies: 74% cases, peripapillary atrophy: 26% cases). Development of Atrophy include: increase of width, surface, perimeter of atrophic areas, thinning, fragmentation of retinal layers, particularly photoreceptor and retinal pigment epithelium layers. Combined Neovascular complication occurred in 27% cases (series of 3 IVT of Anti VEGF were done when neovascular activity was confirmed). Visual function condition depends on Topography of Atrophy, Atrophic areas, patchy atrophies too, Morphology of Atrophy, Atrophic areas, patchy atrophies too (width and length), their Evolution, and Macular Sparing. Atrophy complication of High Myopia leads to ask involvement of collagen, fibroelastic tissues physiopathology, genetic factors, way of life, key role of Age Macular Degeneration in High Myopia Elderly eyes. Those are the Prospects.

Conclusions: High Myopia with ATROPHY complication is a great question to better consider follow‐up protocol, screening, particularly of and when neovascular complication sometimes here with. Multimodal analysis enables better precision, discrimination in Atrophy assessment, evolution, so, issue to preserve visual function and allows to better manage the prospects.
Cytomegalovirus retinitis in a patient with human immunodeficiency virus: A clinical case study
Authors: Bestué Ana Pueyo , Ciubotaru Olga , Pueyo‐Bestué Ignacio , Fernández‐Velasco Diego , Mallén Victor , Bermúdez Javier , Biescas Andrés , Rius Núria , Ila Carmen , Hernández‐Barahona Claudia
Published: January 2025

Aims/Purpose: To present a clinical case of cytomegalovirus (CMV) retinitis in a patient with newly diagnosed HIV, highlighting the characteristic retinal appearance and treatment outcomes.

Methods: A 52‐year‐old male with no significant medical history presented with weight loss and persistent diarrhea. Initial evaluation revealed HIV infection at AIDS stage C3, with a high viral load (2,330,000 copies/mL) and severe immunosuppression (CD4 count = 10 cells/μL). Additional findings included pancolitis, atypical pulmonary infiltrates, and pancytopenia. Ophthalmologic examination was conducted due to reported visual disturbances.

Results: Ophthalmologic assessment revealed a visual acuity of 1.0 in both eyes and intraocular pressure of 10 mmHg. Fundoscopy and ultra‐wide field retinography identified lesions resembling a "cheese and tomato pizza" in the right eye, characterized by granular white‐yellow and white‐gray paravascular infiltrates, retinal opacification, and associated hemorrhages. Optical coherence tomography (OCT) showed foveal integrity but significant vitreous cellularity in the right eye and optic nerve edema.

The patient was treated with Valganciclovir 900 mg every 12 hours for CMV, alongside a combination antiretroviral therapy (ART) regimen of Bictegravir, Emtricitabine, and Tenofovir, plus Atovaquone due to cotrimoxazole intolerance. Follow‐up examinations indicated a gradual improvement in retinal lesions, with the right eye showing residual peripheral nasal lesions and the left eye remaining clear.

Conclusions: This case underscores the importance of early diagnosis and prompt initiation of antiviral and antiretroviral therapies in managing advanced opportunistic infections in HIV/AIDS patients. The "cheese and tomato pizza" analogy aids in the visual identification of CMV retinitis. Continuous monitoring and timely intervention are crucial for preserving vision and improving patient outcomes.

References

Basic and Clinical Science Course, Retina. American Academy of Ophthalmology. 2021

Diaz Llopis M. AIDS in Ophthalmology. Lecture 1996 Spanish Society of Ophthalmology (SEO)
Comparison of intravitreal PBS injection timepoints in the mouse oxygen‐induced retinopathy model
Authors: Lappeteläinen Birgitta , Jääskeläinen Niina , Tenhunen Anni , Ekolle Xavier , Vergun Olga , Haapaniemi Anne Mari , Kolehmainen Anni , Koponen Anna Mari , Partanen Päivi , Vähätupa Maria
Published: January 2025

Aims/Purpose: Intravitreally (IVT) administered phosphate‐buffered saline (PBS) is known to reduce neovascularization in the mouse oxygen‐induced retinopathy (mOIR) model, and often used as a vehicle control in preclinical efficacy studies. Here, the aim was to compare the effects of PBS on neovascularization and revascularization when administered at different timepoints. VEGF‐inhibitor aflibercept (Eylea®) was used as a reference control.

Methods: C57BL/6JRj male and female mice were exposed to 75 % oxygen from postnatal day 7 (P7) for 5 days. At P12 the mice were returned to normoxic conditions and IVT injected with PBS or aflibercept to the right eye at P12, P13, or P14 (n = 7‐9 eyes/group). Contralateral left eye was left untreated. Retinal flat mounts collected at P17 were stained with Isolectin B4, and microscopy images covering the whole retinal flat mount were analyzed for the size of neovascular (NV) and avascular (AVA) area using a proprietary AI‐based algorithm.

Results: NV or AVA area did not differ between PBS and aflibercept at P12. Aflibercept reduced neovascularization by 83 % at P13 (Mann‐Whitney test, p < 0.001) and by 65 % at P14 (unpaired t‐test, p < 0.01) when compared to PBS, while AVA was similar between groups. When compared to untreated eyes, PBS significantly reduced neovascularization at P12, and the size of AVA area at P12 and P13 (Mann‐Whitney test, p ≤ 0.001).

Conclusions: Our findings show significant anti‐angiogenic effect of PBS when injected at P12, suggesting that P12 is not an optimal timepoint for IVT treatment if PBS is used as a vehicle. PBS administered at P13 or P14 did not block neovascularization while it still was inhibited by aflibercept. Further studies are needed to explore if similar effect at P12 is seen with other vehicle or neutral antibody controls.
Serum RNA profile reflects fluid status and atrophic retinal changes in neovascular age‐related macular degeneration
Authors: Heloterä Hanna , Kostanek Joanna , Liukkonen Mikko , Siintamo Leea , Watala Cezary , Blasiak Janusz , Kaarniranta Kai
Published: January 2025

Aims/Purpose: The increasing prevalence of age‐related macular degeneration (AMD), a disease that can result in the loss of central vision, is an emerging problem worldwide due to aging societies. This creates a challenge for the healthcare system and understanding of the mechanisms of AMD pathogenesis will help in early, personalized, and efficient intervention. Current diagnostic methods rely on optical coherence tomography/angiography imaging, which identifies existing damages, but does not provide information on the mechanisms behind them. In this study, we analyzed mRNAs, lncRNA, and small ncRNAs profiles in the serum of nAMD patients and associated them with anatomical changes observed at the retinal level.

Methods: RNA‐Seq analysis of human serum samples from neovascular AMD and control patients.

Results: In the present work, we showed the difference in the serum RNA profile between neovascular AMD (nAMD) patients and controls. Moreover, the RNA profile of nAMD patients corresponded with anatomical changes in the retinal fluid compartments and atrophic changes and was affected by intravitreal anti‐vascular endothelial growth factor treatment.

Conclusions: Therefore, serum could be used as a target for a liquid biopsy to explore anatomical changes in the eye during nAMD progression and treatment. This finding opens a new pathway in AMD studies, which are limited due to restricted access to live human target material and the limited value of animal models of human AMD.
Human versus artificial intelligence: Validation of a deep learning model for retinal layer and fluid segmentation in optical coherence tomography images from patients with age‐related macular degeneration
Authors: Santos‐Oliveira Joana , Miranda Mariana , Mendonça Ana Maria , Sousa Vânia , Melo Tânia , Carneiro Ângela
Published: January 2025

Aims/Purpose: Artificial intelligence (AI) models have received considerable attention in recent years for their ability to identify optical coherence tomography (OCT) biomarkers with clinical diagnostic potential and predict disease progression. This study aims to externally validate a deep learning (DL) algorithm by comparing its segmentation of retinal layers and fluid with a gold‐standard method for manually adjusting the automatic segmentation of the Heidelberg Spectralis HRA + OCT software Version 6.16.8.0.

Methods: A total of sixty OCT images of healthy subjects and patients with intermediate and exudative age‐related macular degeneration (AMD) were included. A quantitative analysis of the retinal thickness and fluid area was performed, and the discrepancy between these methods was investigated.

Results: The results showed a moderate‐to‐strong correlation between the metrics extracted by both software types, in all the groups, and an overall near‐perfect area overlap was observed, except for in the inner segment ellipsoid (ISE) layer. The DL system detected a significant difference in the outer retinal thickness across disease stages and accurately identified fluid in exudative cases. In more diseased eyes, there was significantly more disagreement between these methods.

Conclusions: This DL system appears to be a reliable method for accessing important OCT biomarkers in AMD. However, further accuracy testing should be conducted to confirm its validity in real‐world settings to ultimately aid ophthalmologists in OCT imaging management and guide timely treatment approaches.

References: Pawloff, M.; Gerendas, B.S.; Deak, G.; Bogunovic, H.; Gruber, A.; Schmidt‐Erfurth, U. Performance of retinal fluid monitoring in OCT imaging by automated deep learning versus human expert grading in neovascular AMD. Eye 2023, 37, 3793–3800.
Diagnosis of birdshot chorioretinopathy without typical funduscopy spots
Authors: Funes Elisa , Munuera Inés , Merino Jacobo Yañez , Sopeña‐Pinilla Maria , Ciobotaru Olga , Bestué Ana Pueyo , Pueyo‐Bestué Ignacio , Fernandez‐Velasco Diego , Mallen Victor , Bermudez Javier
Published: January 2025

Aims/Purpose: To present a case of birdshot chorioretinopathy (BCR) in a Spanish patient with HLA‐A29 positivity without characteristic “birdshot” spots on ophthalmoscopy.

Methods: A 53‐year‐old Spanish female presented at the ophthalmological emergency department of a tertiary hospital with complaints of blurred vision in the right eye for one week. The patient had a significant ocular history of anterior uveitis, one episode of macular edema in the left eye and cataract surgery in both eyes. Corrected visual acuity was 0.8 in the right eye (OD) and 0.9 in the left eye. Funduscopic examination demonstrated peripapillary atrophy, increased cellularity in the vitreous and atrophic lesions (suspicious of old foci of chorioretinitis) in the right eye and peripapillary atrophy and atrophic lesions. Late phase fluorescein (FA) showed perivascular and optic disc leakage in OD and hyperfluorescent lesions which corresponded to areas of atrophy in OI. Laboratory evaluations were positive for human leukocyte antigen – A29 (HLA‐A29). At this point, indocyanine green angiography (ICGA) was ordered which revealed hypocyanescent lesions throughout the choroid in both eyes that were centered on the optic disc, supporting the diagnosis of BCR.

Results: The patient started 45 mg of prednisone daily, followed by 3 pulses of intravenous methylprednisolone, which made the increase in vitreous cells in the right eye disappear. Prednisone was progressively decreased by 5 mg each week, until reaching 20 mg, at which time Methotrexate was started at 10 mg per week.

Conclusions: This case highlights the importance of ICGA in the diagnosis of BCR, even in the absence of characteristic spots on ophthalmoscopy. Proper diagnostic work‐up, including assessing HLA‐A29 positivity, is needed to manage atypical cases.
Retinal imaging biomarkers in assessing treatment response when switching from aflibercept to faricimab in resistant neovascular age‐related macular degeneration cases
Authors: Kabanarou Stamatina , Bitzanakis Nikolaos , Sgourou Chrysoula , Gkizis Ilias , Fragkiskos Petros , Xirou Tina
Published: January 2025

Aims/Purpose: To assess treatment response when switching from aflibercept to faricimab in neovascular age‐related macular degeneration cases (nAMD) using imaging biomarkers in optical coherence tomography (OCT) and OCT‐angiography (OCTA).

Methods: This is a retrospective study of nAMD patients attending our clinic who have switched from aflibercept to faricimab treatment. Data collected from patients’ medical and imaging records included: ETDRS best corrected visual acuity (BCVA), OCT and OCTA. During OCT imaging the following features were identified: Central Retinal Thickness (CRT), Pigment epithelial detachment (PED), subretinal fluid (SRF), intraretinal fluid (IRF), hypereflective foci (HF). Ιn OCTA imaging the CNV activity was assessed according to standard activity criteria (lacy‐wheel shape, widely anastomosed network etc). All the aforementioned biomarkers were evaluated for all included patients every month after the initiation of treatment with faricimab.

Results: 14 eyes of 14 patients were assessed, after a mean number of 2.4 injections. BCVA remained unchanged in 3 eyes and improved by a mean of 0.13 in the remaining cases. CRT was stable in 2 eyes and decreased by a mean of 100μm (range 21‐306) in 12. PED, SRF, IRF and HF were present in 13, 12, 9 and 7 eyes respectively, decreased in 7,9,5, and 1 eyes respectively and increased in 0,1,2 and 2 eyes respectively. In OCTA CNV showed less signs of activity in 3 patients and remained stable in the rest.

Conclusions: In our study most of nAMD cases resistant to aflibercept treatment after switching to faricimab treatment showed improvement in all OCT biomarkers apart from HF. Also, some of them showed less signs of activity in OCTA. BCVA improved in the majority of cases, although this improvement was compromised due to the chronicity of the disease. Switching from aflibercept to faricimab in resistant cases, can be a beneficial alternative as evidenced by positive changes in OCT/OCTA biomarkers.
Study of complement system C3 protein expression in glial cells during retinal neurodegeneration
Authors: Fernández‐Sánchez Laura , Ruiz‐Conca Mateo , Estalrich Marta , Tebar Estela , Tornero Lucia , Kutsyr Oksana , Cuenca Nicolas , Lax Pedro , Maneu Victoria
Published: January 2025

Aims/Purpose: Inherited retinal dystrophies (IRD) are retinal neurodegenerations that course with photoreceptor cell death and neuroinflammation. Microglia, astrocytes and Müller cells are the main glial cells involved in retinal neuroinflammation, but its role is still not fully understood. These cells show evidence of both beneficial and harmful effects. Two different phenotypes of microglia and astrocyte cells have been described in brain inflammation, neuroprotectant (M2 and A2, respectively), and neurotoxic (M1 and A1). The neurotoxic phenotype has been related to the activation of the complement system. In fact, the protein C3 has been identified as a marker of the neurotoxic phenotype in the brain. We aim to identify the different inflammatory profiles of glial cells involved in retinal inflammation present in neurodegenerative diseases.

Methods: We used two mice models of IRD for this study, a rd10 mice as a model of RP, and Prph2KI/KI mice, as a model of central areolar choroidal dystrophy (CACD). The C57Bl/6 mice were used as healthy controls. We used specific antibodies for labeling the three retinal glial cell types and the complement factor C3 for performing expression analysis by flow cytometry and immunohistochemistry, using samples at different stages of retinal degeneration in each animal model of study.

Results: Our results show that in retinal degeneration, the microglia, Müller cells and astrocytes display two different phenotypes according to C3 expression. The profile of C3 expression varies among glial cells as the degeneration progresses, possibly indicating a different contribution of each of them to the degenerative process. Interestingly, at least three different subpopulations of Müller cells were detected according to the expression of GFAP and C3 markers.

Conclusions: We identified different phenotypes of glial cells during the course of retinal neurodegeneration in two different mice models of inherited retinal dystrophies. These results can help to better understand both the function and role of these cells on neuroinflammation.
Dynamic retinal vessel analysis with flicker light stimulation: Higher stimulation frequencies lead to higher vascular responses
Authors: Link Dietmar , Freitag Stefanie , Klee Sascha
Published: January 2025

Aims/Purpose: Dynamic retinal vessel analysis (DVA) with flicker light is an established method of retinal vessel analysis. Stimulation is generally performed according to a standard protocol at 12.5 Hz. Technologically, a full‐field shutter is used, which is located in the illumination path. In 2002, Polak et al. investigated the flicker‐induced vascular response at different frequencies (2–64Hz). This showed that from frequencies > 4Hz, smaller responses tend to result. However, current developments in light stimulation are moving towards spatio‐temporal stimulators. We therefore used a spatial light modulator (SLM) in a DVA setup. In this work, we investigated vascular responses at a lower and higher stimulation frequency compared to 12.5Hz. The dilation maxima were determined and compared.

Methods: We studied 12 subjects (7w, 5m, 26.6 ± 3.7yr, 1 eye). We measured two primary vessels each: a superior temporal artery and a vein. All subjects were free of ocular and systemic diseases. A high‐power LED (515nm) and a transmissive liquid crystal display (Sony LCX017AL) were connected to a mydriatic fundus camera. The SLM was controlled via standard graphics card and a customized software. The field of view was set to 30°. Each subject was measured two times. One measurement was carried out at 3.75Hz and one at 30Hz flicker frequency, randomized among the subjects. As in Polak et al. (2002), measurements were taken with 60s baseline, 60s flicker stimulation. Decay measurement was 120s. The pause time between two measurements was 15min. The mean value and standard deviation were calculated for each stimulation frequency and vessel type. The differences were tested for normal distribution and either the paired t‐test or the Wilcoxon signed‐rank test was performed.

Results: All subjects were able to successfully complete the study (n = 12). Arteries showed a mean maximum dilatation of 2.8 ± 1.2% at 3.75Hz and 4.0 ± 1.6% at 30Hz (p = 0.023, Cohen's d = 0.765). Veins showed 2.8 ± 1.7% at 3.75Hz and 4.4 ± 2.5% at 30Hz (p = 0.005, Cohen's d = 1.015).

Conclusions: We successfully performed a study on the generation of different flicker frequencies using a transmissive liquid crystal display. The results are contrary to those of Polak et al. (2002). Other parameters need to be compared in further studies.