bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal microcirculation alterations in rheumatoid arthritis patients compared to healty volunteers and their correlation to the disease activity and duration of disease
Authors: Assaf Abdelrahman , Günthner Roman , Braunisch Matthias , Bachmann Quirin , Kotliar Konstantin , Schmaderer Christoph , Moog Philipp
Published: January 2024

Aims/Purpose: Patients with rheumatoid arthritis (RA) have a high risk of developing cardiovascular diseases due to endothelial dysfunction, which is a risk factor for cardiovascular events. The retinal Vessel Analyzer (RVA, IMEDOS Systems) can capture retinal vessels non‐invasively in real‐time and analyse their dynamic responses to stimuli.

Methods: In order to assess the structural and functional changes in the retinal microvasculature, a non‐invasive Retinal Vessels Analyzer (RVA) was used to study 44 patients with RA (mean age 57.4 ± 13.2 years) and compare them to a control group of 44 age‐matched healthy individuals. The RVA was used to measure various parameters, including the Central Retinal Artery Equivalent (CRAE), Central Retinal Vein Equivalent (CRVE), and Arterio‐Venous Ratio (AVR), as well as the response of the retinal vessels to flickering light. After a 50 s baseline, rectangular shape, monochromatic flickering light (530–600 nm) of 12.5 Hz for 20 s was applied three times. The dilation of retinal vessels after flicker light stimulation was analysed.

Results: The results of the study showed that patients with RA had significantly higher CRVE and lower AVR compared to the control group (p = 0.04 and p = 0.01, respectively), indicating structural changes in the retinal microvasculature. The patients with RA also had a significantly stronger arterial dilation response to flickering light compared to the control group (n = 43), indicating functional changes in the retinal microvasculature. In patients with moderate to high disease activity according to the Disease Activity Score (DAS‐28 > 3.2) (n = 9), there was a negative significant correlation between the maximum arterial diameter (aMAX) and interleukin‐6 (IL‐6).

Conclusions: These findings suggest that RVA can be a useful tool for detecting structural and functional changes in the retinal microvasculature of patients with RA and that the disease activity and inflammation in RA may be related to these changes. However, the study notes that a larger cohort with a wider range of disease activity is needed to fully understand the effect of chronic inflammatory diseases on endothelial function.
Difference in lesion reactivation between pure type 2 and mixed type 1 and 2 macular neovascularization and its influence on long‐term treatment outcomes
Authors: Kim Chulgu
Published: January 2024

Aims/Purpose: To compare lesion reactivation and treatment outcomes between pure type 2 and mixed type 1 and 2 macular neovascularization (MNV) treated with anti‐vascular endothelial growth factor (VEGF).

Methods: This retrospective study included 155 patients diagnosed with Type 2 MNV. After the initial loading injections, as‐needed retreatment was provided. The difference in first lesion reactivation after the initial treatment was evaluated between pure Type 2 MNV (pure type 2 group, n = 37) and mixed Type 1 and 2 MNV (mixed group, n = 118). The degree of change in the best‐corrected visual acuity (BCVA) was also compared between the two groups.

Results: The mean follow‐up period was 32.7 ± 13.7 months. Lesion reactivation differed significantly between the Type 2 (60.0%) and mixed (84.5%) (p = 0.004) groups. The degree of visual change during the follow‐up period also differed significantly between the pure Type 2 (mean 2.8 lines of improvement) and mixed (mean 0.2 lines of deterioration) (p = 0.008) groups. In multivariate analysis, lesion type (p = 0.012) and baseline visual acuity (p = 0.002) were significantly associated with ≥2 lines of visual improvement.

Conclusions: Lesion reactivation and treatment outcomes differed between pure Type 2 and mixed Type 1 and 2 MNV. These results suggested the need for different treatment strategies for these two MNV subtypes.
Biometric risk factors for central serous chorioretinopathy
Authors: Gawęcki Maciej , Grzybowski Andrzej
Published: January 2024

Aims/Purpose: The goal of the present study was to find the biometric parameters associated with the incidence of CSCR.

Methods: The study included 66 eyes of 60 consecutive patients that were diagnosed with acute or chronic CSCR between 01.01.2021 and 30.06.2021. Six patients had a binocular disease. All patients had axial length and retinal parameters measured with the spectral domain optical coherence tomography (SD‐OCT) as well as refraction error tested after cycloplegia. Results of the affected eyes were compared with the healthy fellow eyes (39 eyes) and control group (75 eyes) and correlated to the duration of the disease.

Results: No significant differences were revealed between axial length of the affected eyes, healthy fellow eyes and controls (23.31 ± 1.06 vs. 23.59 ± 1.20 vs. 23.33 ± 1.19). Distribution of refraction errors was similar in the three analysed groups. Hypermetropic shift was noted in the affected eyes versus controls (p = 0.030); however, no difference was noted in the refraction error between the healthy fellow CSCR eyes and controls (p = 0.418). Both acute and chronic CSCR cases, as well as their fellow eyes, demonstrated significantly greater choroidal thickness compared to healthy individuals (p < 0.001). Longer disease duration was correlated with significant deficit in macular volume and average central retinal thickness (p < 0.05).

Conclusions: CSCR is a clinical entity that can occur in patients with every type of refraction error. Shorter axial length of the eyeball is not associated with higher prevalence of CSCR, however increased choroidal thickness is typical of that entity. Longer disease duration is correlated to the loss of retinal thickness and volume.
Visual and anatomical outcomes following intravitreal treatment of macular oedema secondary to retinal vein occlusion
Authors: Tasos Emmanuel , Sharma Pavel , Karia Janvi , Menem Dheyaedeen , Katzakis Michail , Minos Evangelos
Published: January 2024

Aims/Purpose: We sought to measure the visual and anatomical outcomes of patients treated for macular oedema secondary to retinal vein occlusion (RVO) with anti‐vascular endothelial growth factor (VEGF) medications or intravitreal steroids.

Methods: We retrospectively identified eyes with RVO in our Trust treated with anti‐VEGF injections or intravitreal steroids. Patient data such as age, gender and visual acuity (VA) were obtained from electronic patient records. Central retinal thickness (CRT) was measured via optical coherence tomography (OCT). Macular perfusion and ischaemia were assessed by fundus fluorescein angiography (FFA) on initiation of treatment. VA and CRT data were obtained for 24 months from starting treatment with anti‐VEGF injections or intravitreal steroids.

Results: 56 eyes (26 with branch RVO (BRVO), 22 with central RVO (CRVO) and 8 with hemi‐RVO (HRVO)) were identified and followed up for 24 months after starting anti‐VEGF treatment or intravitreal steroids. Mean change in VA at 24 months was +7.0 ± 16.3 letters among CRVO eyes and + 3.9 ± 21.3 letters among BRVO eyes, whereas for HRVO mean VA change was +20.3 ± 16.8 letters. Mean CRT decreased by 334.2 ± 163.5 μm in eyes with CRVO, 147.1 ± 193.1 μm in eyes with BRVO and 300.3 ± 118.6 μm in eyes with HRVO. Furthermore, we achieved VA stabilization or improvement in 91% of eyes treated under ‘optimal’ conditions, in line with the meta‐analysis of studies on RVO outcomes by Hunter & Williams (2022).

Conclusions: Current Trust protocols for intravitreal steroids and anti‐VEGF injections show good outcomes in RVO patients. Patients on treatment should be followed up regularly to minimize delays, while early treatment agent switches should be pursued if VA is dropping or macular oedema persists.

References

Hunter A, Williams M. Long‐term outcomes for patients treated for macular oedema secondary to retinal vein occlusion: a systematic review. BMJ Open Ophthalmol. 2022;7(1):e001010. doi:10.1136/bmjophth‐2022‐001010
Certification process in capturing retinographies in Castilla y Leon diabetic retinopathy screening program
Authors: Novo‐Diez Andrea , Arlanzón‐Lope Pablo , García‐Espinilla Óscar , Yepes‐Recio Inmaculada , De Iglesia‐Rodríguez Purificación , López‐Galvez María Isabel , Pastor José Carlos
Published: January 2024

Aims/Purpose: Certification processes are critical for tele‐ophthalmology and Reading Centers. In the diabetic retinopathy Castilla y Leon screening program capture is performed by nurses accredited in the three‐field protocol of the Joslin Vision Network (JVN). The purpose of this work was to evaluate the certification process including the times, difficulties and satisfaction degree.

Methods: Type II diabetics attend their primary care centre. Retinographies of both eyes under pharmacological mydriasis are acquired by nurses after inform consent. Images are sent, interpreted and categorized to the IOBA's Reading Center (University of Valladolid). Training consisted of an on‐site lecture, on‐line theory course (University patented) and on‐site practices. Trainees uploaded retinographies from 10 real patients to an online platform for evaluation. Certification required at least 5 correctly performed. The time and intents required to obtain the certification were analysed.

Results: 23 trainees from to 5 health areas were included. None of them had ever used a retinograph before. All of them successfully completed the program. The 21.74% of the trainees obtained their certification with the first 5 practices and completed the evaluation process in 1 day. 13.04% repeated 1 practice, 34.78% repeated 2, another 13.04% repeated 3 and 7.39% repeated 5. The certification process was completed after 17, 11, 20 and 8 days, respectively. Satisfaction of trainees with the theoretical lessons with a score of 8.67/10 and the practical training with a score of 9/10 was evaluated through an ad‐hoc survey.

Conclusions: Retinography capture certification was achieved between 1 and 20 days and the majority (69.52%) by repeating none to two practices. The trainees were highly satisfied with the theoretical and practical content of the course.
Porcine ex vivo retina model to study retinal neurodegenerative diseases: Potential role of mesenchymal stem cells
Authors: Pelusi Letizia , Ghelardoni Maddalena , Agnifili Luca , Cappellacci Ilaria , Allegretti Marcello , Hurst Jose , Schnichels Sven , Mastropasqua Leonardo , Bollini Sveva , Nubile Mario , Pandolfi Assunta , Mandatori Domitilla
Published: January 2024

Aims/Purpose: Retinal neurodegenerative diseases (RND) are associated with a progressive degeneration and death of retinal cells. Recently, mesenchymal stem cells (MSCs) showed a protective role against retinal cells degeneration and apoptosis. However, due to the complexity of such diseases, there is the need to develop in vitro or ex vivo models which allow the study of RND pathogenesis and better understand the regenerative role of MSCs. Therefore, the aim of our study was to use porcine retinas to establish a possible ex vivo model of spontaneous neuroretinal degeneration and employ this model to evaluate the efficacy of human amniotic fluid stem cells (hAFSCs) on retinal cells undergoing damage.

Methods: To this end, neuroretinal explants were obtained from pig eyes and placed over the porous membrane of a transwell plate. To induce a time‐dependent spontaneous retinal degeneration, explants were cultured for 24, 48, 72, 96 h, 5 and 8 days. The damage grade was assessed with qRT‐PCR and immunohistochemistry analyses for GFAP and TUNEL‐assay. Then, the explants were co‐cultured with hAFSCs up to 8 days to evaluate their effect on retinal cells death via propidium iodide (PI) staining.

Results: Results demonstrated that the cultivation of retinal explants up to 8 days induced an increase in the gene expression of inflammatory (NF‐kB and TNF‐alpha), pro‐apoptotic (p21 and p53) and oxidative stress markers (NRF2). We also observed an increased expression of GFAP and CD11b, suggesting an activation of the microglia and up‐regulation of Müller cells. In addition, the cultivation time induced an increase in the number of apoptotic cells (TUNEL). However, interestingly, the cells death decreased after co‐cultivation with hAFSCs (PI staining).

Conclusions: In conclusion, our data demonstrate that the prolonged cultivation of porcine ex vivo retina can induce a time‐dependent spontaneous degeneration able to simulate a model of RND. Of note, the co‐culture preliminary data suggest a protective effects of hAFSCs on retinal cells death.
Retinal microglia and ganglion cells in a cuprizone (CPZ) induced mouse model of multiple sclerosis (MS)
Authors: Choi Soyoung , Nicholas Richard , Papadopoulos Dimitri , Cordeiro Maria Francesca
Published: January 2024

Aims/Purpose: Up to 90% of MS patients have ocular manifestations. Activated microglia (mg) are associated with age and diseases like MS. Mg change their activation states (ramified, hyper‐ramified, activated, amoeboid and rod) in response to stimuli, to exert either neuro‐protective or ‐toxic effects, leading to the rescue or loss of neurons. Here, we characterize retinal ganglion cell (RGC) densities and retinal mg morphotype proportions in eyes of a CPZ induced MS model and age‐matched controls.

Methods: Male C57 mice were fed CPZ (0.2%w/w) mixed chow for 4 months (m) until sacrificed at 6 m (6mCPZ) or 28 m (28mCPZ) old. Age‐matched controls (6mCtrl; 28mCtrl) were fed normal chow. Enucleated eyes were fixed in 4% PFA. Whole retinas were dissected, stained (RBPMS+RGCs; iba‐1+mg), mounted and imaged. A published retinal mg morphotyping algorithm and an automated RBPMS counting script were used. Two‐way ANOVA with paired analysis (PA) was used (mg n: 6mCtrl = 15; 6mCPZ = 7; 28mCtrl = 7; 28mCPZ = 10; and RGC n: 6mCtrl = 4; 6mCPZ = 3; 28mCtrl = 3; 28mCPZ = 4).

Results: There was a main effect of age for activated (p = 0.0282) and rod (p < 0.0001), and disease state for rod (p = 0.04) mg. PA showed higher activated mg in 28mCtrl versus 6mCtrl (p = 0.0485), and lower rod mg in 28mCtrl versus 6mCtrl (p = 0.0374) and in 28mCPZ versus 6mCPZ (p = 0.0007). There was a main effect of age (p = 0.0001) and disease state (p = 0.04) on RBPMS density. PA showed lower RGC density in 28mCtrl versus 6mCtrl (p = 0.0025) and in 28mCPZ versus 6mCPZ (p = 0.025).

Conclusions: Our results show that there is age‐related loss of rod mg and RGCs in healthy and CPZ groups, supporting reports that rod mg are involved in protecting less damaged neurons. Age‐related increased activated mg may cause RGC loss as transcription factors like TNFα, bind to RGC receptors, inducing apoptosis. Further transcriptomic analysis may clarify functional interpretations.
Diabetic retinopathy screening using a handheld non‐mydriatic camera
Authors: Iudakov Andrei , Kern Christoph , Lanzl Ines
Published: January 2024

Aims/Purpose: Our objective was to compare the diagnostic accuracy of diabetic retinopathy (DR) screening using a non‐mydriatic handheld digital camera as well as a stationary digital fundus non‐mydriatic camera to the standard fundus examination in medical mydriasis by an experienced observer.

Methods: The evaluation of images using a digital handheld non‐mydriatic camera in a clinical setting, coupled with pupil dilation for ungradable images, provides a valid method for identifying an advanced stage of DR requiring therapeutic measures. The hand held non mydriatic fundus camera could represent an alternative to the conventional screening in medical mydriasis in order to improve the access to DR screening in areas and populations with less access to the existinmedical infrastructure.

Results: The mean age of the 100 examined diabetic participants was 61.2 years (SD ± 9.08). The proportion of upgradable images in both types of non‐mydriatic imaging was 3% (1 eye – 2%, both eyes – 1%). When compared to the detection of any stage of DR, an advanced stage of DR showed higher diagnostic accuracy. The sensitivity for the advanced stage of DR was 13% for Reviewer 1 (positive predictive value [PPV] 5%) and 14% for Reviewer 2 (PPV 6%). The specificity was 94% for Reviewer 1 (negative predictive value [NPV] 96%) and 95% for Reviewer 2 (NPV 97%).

Conclusions: The evaluation of images using a digital handheld non‐mydriatic camera in a clinical setting, coupled with pupil dilation for ungradable images, provides a valid method for identifying an advanced stage of DR requiring therapeutic measures. The handheld non mydriatic fundus camera could represent an alternative to the conventional screening in medical mydriasis in order to improve the access to DR screening in areas and populations with less access to the existing medical infrastructure.

References

1. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B (2018) IDF diabetes atlas: global estimates of diabetes prevalence for 2017.
Popper and maculopathy
Authors: Sancho Ainhoa Mimendia , Maeso Alicia Traveset , Costales‐Mier Felipe , Bertomeu Pau Cid
Published: January 2024

Aims/Purpose: To describe a case of a patient with poppers maculopathy.

Methods: The ocular findings were evaluated with spectral optical coherence tomography and fundus imaging.

Results: A 23‐year‐old female presented with a history of central phosphenes and decreased vision after inhaling popper. Best‐corrected visual acuity (VA) was 0.9/1, the exploration of anterior segment was normal. Fundus examination revealed yellow lesion appearance at macula. Associated with a disruption of the presumed inner segment/outer segment junction (IS/0S) in the optical coherence tomography (OCT). After 1 month VA increased and OCT improved.

Conclusions: Popper's maculopathy is an emerging disease that cause structural and functional affection of the outer retinal architecture. If we have a patient with bilateral vision loss with irregularity of the ellipsoid zone at the fovea, he should be asked specifically about poppers abuse.
Associations of neurovascular dysfunction with inner retinal layer thickness in non‐proliferative diabetic retinopathy
Authors: Pemp Berthold , Palkovits Stefan , Sacu Stefan , Schmidl Doreen , Garhöfer Gerhard , Schmetterer Leopold , Schmidt‐Erfurth Ursula
Published: January 2024

Aims/Purpose: Neurovascular dysfunction and inner retinal layer thinning are among the earliest detectable retinal changes in diabetes, and both worsen during development and progression of diabetic retinopathy (DR). However, direct interactions between these features have not been investigated so far. Therefore, we aimed to analyse associations between the retinal functional hyperaemic response and thickness of the individual neuroretinal layers in eyes with non‐proliferative DR.

Methods: Thirty patients with Type 1 diabetes featuring mild (n = 15) or moderate (n = 15) non‐proliferative DR and 14 healthy subjects were included in this cross‐sectional study. Retinal vessel diameters were measured before and during illumination with flickering light using a dynamic vessel analyser. Individual retinal layer thickness in the macula was analysed from spectral domain optical coherence tomography.

Results: Flicker light‐induced vessel dilation was significantly reduced in diabetes patients compared to healthy controls (veins: 3.0% vs. 6.1%, p < 0.001; arteries: 1.3% vs. 5.1%, p = 0.005). Univariately, the response in retinal veins of diabetes patients correlated significantly with ganglion cell layer (GCL) thickness (r = 0.46, p = 0.010) and inner plexiform layer thickness (r = 0.40, p = 0.027), and negatively with haemoglobin A1c (HbA1c) levels (r = −0.41, p = 0.023) and age (r = −0.38, p = 0.037), but not with baseline diameters, glucose levels, or diabetes duration. In a multiple regression model only HbA1c (p = 0.027, β = −0.40) and GCL thickness (p = 0.030, β = 0.39) remained significantly associated with the vascular flicker light response.

Conclusions: The results indicate that thinner GCL and worse glycaemic control both contribute to reduced neurovascular coupling in patients with clinical signs of DR. Progression of neurovascular dysfunction in DR might be related to structural degeneration of the neurovascular complex in the inner retina.
Low vision rehabilitation program in patients with myopic macular degeneration: A case series
Authors: Fernandes Nádia , Pereira Débora , Carvalho Tiago , Lanca Carla
Published: January 2024

Aims/Purpose: Patients with pathologic myopia are at risk of developing myopic macular degeneration (MMD) that leads to vision loss and irreversible visual impairment. Working age and elderly populations are affected by loss of productivity and quality of life. Low vision services should offer specialized training programs to help patients to overcome the difficulties in daily living activities. The aim of this study was to describe the results of a low vision rehabilitation program (LVR) in patients with MMD.

Methods: Five patients (8 eyes) with MMD were included in the LVR at an ophthalmology clinic in Portugal. The LVR had a length of 8 weeks and was divided into two phases. The first phase included the use of prisms for image relocation (IR) with eccentric viewing exercises to stabilize the preferred retinal locus. At the second phase, training with low vision aids was performed. Best corrected visual acuity (BCVA) for distance and near, contrast sensitivity (CS), reading speed (RS) and face recognition were compared pre and post rehabilitation.

Results: Patients had MMD category 3 (patchy chorioretinal atrophy) and 4 (macular atrophy) in the best eye. Vision impairment varied between mild and severe. The IR prisms varied from 2 to 6 prism dioptres. Electronic devices were the most prescribed low vision aids. At the end of the LVR, the outcomes were good in all patients. BCVA increased by two to three lines, CS increased by two to four lines, RS increased by 40 to 60 words per minute and face recognition improved in all patients.

Conclusions: The LVR was beneficial, improving visual function and functional vision outcomes in all patients. LVR programs seem to be effective in patients with pathologic myopia. Longitudinal studies are necessary to ascertain the long‐term efficacy of LVR.

References

1. Chen Y, Han X, Gordon I, Safi S, Lingham G, Evans J, Li J, He M, Keel S. A systematic review of clinical practice guidelines for myopic macular degeneration. Journal of Global Health 2022; 12. https://doi.org/10.7189/jogh.12.04026

2. Vingolo EM, Napolitano G, & Casillo L. Pathologic Myopia: Complications and Visual Rehabilitation. 2019. https://doi.org/10.5772/intechopen.85871
Digoxin‐induced retinal toxicity after acute kidney injury in a patient with dilated cardiomyopathy: A case report
Authors: Park Hyeyeon , Kim Minhee , Roh Young‐Jung
Published: January 2024

Aims/Purpose: We would like to report a case of digoxin‐induced retinal toxicity.

Methods: Observational case report. Clinical follow‐up was performed using optical coherence tomography and electroretinography.

Results: A 50‐year‐old female patient was referred to our clinic with symptoms of blurred vision and a whitening of the central visual field. She had no prior ophthalmic history but had underlying diseases including hypertension, hyperlipidaemia, dilated cardiomyopathy, systemic lupus erythematosus and chronic kidney disease. She had been admitted to the department of nephrology due to acute renal impairment, presenting with flank pain and oliguria. At the initial examination, her best‐corrected visual acuity was 0.5 in the right eye and 0.4 in the left eye. The Ishihara colour vision test revealed 3/17 and 1/17 in the right and left eye, respectively. Optical coherence tomography showed blurring and thickening of the ellipsoid zone in both eyes. Electroretinography demonstrated decreased cone cell function. She had been taking digoxin 0.125 mg for dilated cardiomyopathy for the past 2 years. Following the onset of acute renal impairment, her serum digoxin level was found to be 2.95 ng/mL, more than twice the normal range [0.6–1.2]. Suspecting digoxin intoxication, we consulted with her cardiologist and decided to discontinue digoxin. 3 weeks after discontinuing the medication, she reported improvement in the whitening of central visual field. Her best‐corrected visual acuity improved to 0.7 in the right eye and 0.6 in the left eye, and the Ishihara colour vision test showed 16/17 in both eyes. OCT demonstrated normalization of the ellipsoid zone thickness, and ERG showed ongoing recovery of cone cell function.

Conclusions: Digoxin toxicity is known to result in visual disturbances—including decreased visual acuity, blurry vision and central scotoma with altered colour perception—caused by direct dysfunction of photoreceptors. Symptoms are gradually recovered within days to months after discontinuation of the medication. When facing visual problems in a patient with comorbidities, it is important to elicit a complete history, with all drug and detailed complaints, and to include a drug adverse effect. If a drug intoxication was suspected, medical consultations should be obtained.
Local ischaemia morphology in diabetics differs from healthy controls
Authors: Hoffmann Simon , Kessler Lucy , Khoramnia Ramin , Nahm Werner
Published: January 2024

Aims/Purpose: To evaluate local macular ischaemia morphology additional to global metrics in diabetic macular ischaemia (DMI) patients and healthy controls.

Methods: The study was registered: DRKS‐ID DRKS00024399. Informed written consent was obtained from all participants. Seven DMI patients and seven patients after cataract surgery were included as healthy controls. 10 × 10° Heidelberg Spectralis OCT Angiography was recorded and divided to superficial/deep vascular complexes (SVC/DVC) following the inbuilt segmentation. Further processing was done in MATLAB R2022a. After binarization following Otsu's method for threshold determination, minimum distances to blood vessels were calculated for each pixel applying a sliding window. More than 30 μm distance to the next vessel was considered ischaemic. Morphology analysis of the resulting ischaemic lesions was conducted for SVC and DVC separately. The total ischaemic area; mean ischaemic area per lesion; area and circularity of the second largest ischaemic lesion—avoiding the foveal avascular zone—was extracted. Two‐sample Student t‐tests were performed testing differences of healthy controls and DMI patients in SVC and DVC for each of the four named metrics. Statistical significance was defined when p < 0.05.

Results: Analysing total ischaemic area, statistically significant differences were found for SVC and DVC data. Mean ischaemic area per lesion was significantly larger in DMI patients in SVC but not in DVC. The area of the largest ischaemic lesion avoiding FAZ was significantly larger in DMI patients in both SVC and DVC. Lesion circularity did not reveal significant differences.

Conclusions: Supplementing reported global nonperfusion differences, local nonperfusion morphology differs significantly between DMI patients and healthy controls. Findings need to be replicated in a larger trial in the future. Research on structure function correlation in areas of nonperfusion will shed light on clinical implications.
Nanoparticle‐based sustained drug delivery for the treatment of ocular neovascular diseases
Authors: Durak Saliha , Kutlu Ozlem , Cetinel Sibel
Published: January 2024

Aims/Purpose: Nanoparticles have shown great potential as a drug delivery system for the treatment of neovascular ocular diseases characterized by the growth of abnormal blood vessels in the retina. The current standard of therapy for neovascular ocular diseases involves administering monoclonal antibody‐based anti‐VEGF drugs via intravitreal injections on a periodic basis. The short half‐lives of these drugs necessitate frequent injections, which can limit the effectiveness of the treatments. Hence, there is a need to develop new approaches for enhanced bioavailability and sustained and long‐lasting delivery of anti‐VEGF drugs. The aim of this study was to utilize poly (glycerol sebacate) (PGS) nanoparticles to achieve an extended release of anti‐VEGF (anti‐vascular endothelial growth factor) drugs, with the objective of reducing the frequency of intravitreal injections required for treatment.

Methods: Double emulsion solvent evaporation method was utilized for the synthesis of PGS nanoparticles. Nanoparticle size and polydispersity index (PDI) were determined with dynamic light scattering method.

Results: Nanoparticles were synthesized with a size of approximately 150 nm and PDI less than 0.3. The encapsulation efficiency of nanoparticles loaded with anti‐VEGF drugs was found to be 74%. The 30% drug release from nanoparticles in the first 2 months indicates that nanoparticles are a promising candidate for sustained drug release applications. Cell‐viability studies showed that anti‐VEGF drug‐loaded nanoparticles did not exhibit toxicity to ARPE‐19 cells, but they did exhibit anti‐angiogenesis properties by inhibiting the growth of HUVEC cells in a concentration‐dependent manner.

Conclusions: The development of new‐generation materials for the storage and preservation of anti‐VEGF drugs, as well as their enhancement with prolonged release, will considerably improve the efficacy of long‐term treatment strategies for ocular neovascular diseases.
Targeted retinal spectroscopy: Towards a localized assessment of biomarkers in the eye fundus
Authors: Akitegetse Cleophace , Lapointe Nicolas , Poirier Jasmine , Picard Maxime , Sauvageau Dominic
Published: January 2024

Aims/Purpose: The non‐invasive evaluation of biomarkers for the screening, diagnosis, and monitoring of ocular and neurological diseases is receiving increasing attention. Targeted retinal spectroscopy (TRS) enables simultaneous imaging and high‐quality spectral analysis from specific regions of the eye fundus. It offers valuable information on the structure, composition, and function of retinal tissues. This study demonstrates the capabilities of TRS and assesses its effectiveness in retinal oximetry.

Methods: The Zilia Ocular TRS platform was developed and evaluated. First, a reference target and a model eye were used to demonstrate the targeted spectral analysis. Then, Monte Carlo simulations were used to identify crucial TRS parameters—such as spectral range, resolution, noise, and tissue scattering—for retinal oximetry. Simultaneous imaging of the eye fundus and diffuse reflectance spectra acquisitions were performed in two targeted regions of the eye fundus of eight healthy subjects to determine blood oxygen saturation (StO2).

Results: Experiments performed with the reference target and model eye showed precise and distinct spectral signatures for each targeted region. Simulation results showed that highest StO2 accuracy was obtained with a spectral range between 530 nm and 585 nm, while a resolution below 4 nm compromised the accuracy. In addition, acquisition areas larger than blood vessels led to an underestimation of StO2, and a linear correlation was found between the additive noise level and the variability of StO2. In vivo oximetry measurements revealed significant differences in StO2 between the optic nerve head and the parafovea.

Conclusions: TRS opens up new possibilities for disease screening, diagnosis and monitoring, including assessing oximetry in glaucoma, diabetic retinopathy, age‐related macular degeneration, etc. To account for confounding factors, careful selection of acquisition parameters is crucial, as emphasized in this study.
Bruch's membrane and Brücke's muscle in the pars plana region
Authors: Panda‐Jonas Songhomitra , Jonas Jost , Jonas Rahul , Jonas Shefali
Published: January 2024

Aims/Purpose: To examine Bruch's membrane (BM) in association with the longitudinal part of the ciliary muscle (LPCM) in the pars plana region.

Methods: Using light microscopy, we histomorphometrically assessed BM and the LPCM in the pars plana region.

Results: The histomorphometric study included 51 eyes (51 patients; mean age: 60.8 ± 15.0 years; axial length: 26.0 ± 3.3 mm; range: 21.0–36.0 mm). The LPCM (total length: 4.60 ± 1.10 mm) ended 1.15 ± 0.56 mm anterior to the ora serrata. Within the pars plana region, the LPCM (length: 2.58 ± 0.98 mm) had direct contact with BM for 1.95 ± 0.99 mm (71.1 ± 18.4% of the BM undersurface), while a capillary layer was interposed between BM and the LPCM for 0.70 ± 0.40 mm (29.0 ± 18.4%). In the pars plana region free of LPCM close to the ora serrata, the percentage of BM covered by the capillary layer was higher than in the pars plana region containing the LPCM (63.0 ± 42.1% versus 29.0 ± 18.4%; p < 0.001). At the LPCM end, BM was in direct contact with collagenous tissue from the LPCM and was focally thickened as compared to BM (with an underlying capillary layer (9.5 ± 5.3 μm vs. 4.3 ± 1.2 μm; p < 0.001).

Conclusions: The direct contact of BM with the LPCM in the pars plana in association with focal BM thickening at the LPCM end suggests an insertion of LPCM on BM. Taking into account the biomechanical strength of BM, it may imply a functional unit of the LPCM with BM in the process of accommodation with a secondary movement of the posterior BM and tertiary thickening of the subfoveal choroidal space.
Paracentral acute middle maculopathy as the first sign of internal carotid artery dissection
Authors: Comes Marta , Rovira Elena Gracia , Fabra Yolanda Cifre , Parot Álvaro Andrés Ojeda , Sanmillán Héctor Carot , Mora José Miguel Vilaplana , Barrón Andrea Díaz , Duch‐Samper Antonio M.
Published: January 2024

Purpose: It is proposed to present a clinical case of a patient with a paracentral acute middle maculopathy (PAMM) as the first sign of presentation of severe internal carotid artery (ICA) dissection.

Methods: An initial basic ophthalmologic examination of the patient was performed, followed by an optical coherence tomography (OCT) and an OCT‐angiography (OCT‐A) of each eye. Finally, the patient was evaluated by a neurologist, performing a cerebral and supra‐aortic trunks (SAT) computed tomography (CT) angiography.

Results: We present a 54‐year‐old patient who came to the emergency room complaining of central blurred vision in his left eye (OS) during 24 h. On ophthalmological examination, it is remarkable a visual acuity (VA) of counting fingers at 1 m in OS. Eye fundus (EF) of OS showed small oval whitish macular lesions. Macular OCT of OS revealed hyperreflective bands in the internal nuclear layer (INL) and OCT‐A showed areas with low flow at deep capillary plexus (DCP) and macular vascular density (MVD) parameters decreased compared to the right eye (OD). During the examination, the patient began to feel a slight loss of strength in his right hemibody with dizziness, so he was explored by a neurologist and a cerebral and SAT CT angiography was performed, which reported severe left ICA dissection with an area of hypoperfusion in the territory of the left middle cerebral artery, but without intracranial vascular occlusion. Since there was no image of occlusion and given the mild neurological symptoms, endovascular treatment was rejected and anticoagulation with enoxaparin was established. Two months later, VA of OS improved to 1, with no significant lesions in the EF. The OCT of OS showed a slight thinning of the INL and the OCT‐A revealed a greater flow in the DCP with better MVD values.

Conclusions: This entity should be considered in patients with visual disturbances. PAMM may be the first sign of ICA pathology.
Effect of systemic sclerosis on macular anatomy
Authors: Matallana Maravillas De Paco , Rodriguez Andrea Carolina Garcés , Cascon Miguel Martin , de los Reyes Retamero Sánchez María , López Carmen Miquel , Vellosillo Monica Del Río , Marin Maria Teresa Herranz , Garcia‐Medina Jose Javier
Published: January 2024

Aims/Purpose: Systemic sclerosis, also known as scleroderma, is a rare autoimmune disease that involves the hardening of the skin and also hinders the blood supply by occluding the small arteries and capillaries that carry blood to the tissues. Our aim was to compare the retinal thickness of different segmentations at the macula.

Methods: In this pilot study 22 eyes from subjects with systemic sclerosis were compared with 22 eyes from healthy subjects (controls). All participants underwent a complete ophthalmological study and optical coherence tomography (OCT) measurements (Spectralis, Heidelberg Engineering, Germany) including complete retina, inner and outer layers, intermediate retinal layers (inner nuclear layer + outer plexiform layer + outer nuclear layer) and ganglion cell complex thickness (macular retinal nerve fibre layer + ganglion cell layer + inner plexiform layer) at the macula using Early Treatment Diabetic Retinopathy Study (ETDRS) grid so foveal, parafoveal and perifoveal subfields were measured. The values of the thickness of each segmentation in relation to the thickness of the complete retina (considered layer segmentation thickness divided by complete retina thickness) were also compared.

Results: Best‐corrected visual acuity was lower in systemic sclerosis group but age, gender, spherical equivalent, intraocular pressure and axial length did not show any differences between both groups. Diffuse thinning in parafovea of complete retina, inner retina, outer retina, intermediate retina and ganglion cell complex was found in systemic sclerosis group. Fovea is also thinner in complete retina and intermediate retina in systemic sclerosis group. When considering the comparisons of the results in relation to complete retina thickness no differences were found between groups.

Conclusions: Systemic sclerosis induces the thinning specially in the parafovea of all the considered macular segmentations alike.
Retinal neurodegeneration induced by sodium iodate administration and visual cortex activity
Authors: Espitia Michael , Navarro Santiago Milla , de la Villa Pedro , Germain Francisco
Published: January 2024

Aims/Purpose: Recently investigations have shown that using sodium iodate (NaIO3) provides a promising animal model of retinal neurodegeneration. The aim of this research is to characterize the effects of this compound in the visual pathway.

Methods: First, a single dose of NaIO3 (65 mg/kg) was administered intraperitoneally to mice (C57BL/6J strain) with a knock‐out mutation for the Opn4 gene (Opn4−/−). Then, behavioural tests (light avoidance assay, optomotor test, pupillary light reflex) were performed until Day 28. Electrophysiological tests (electroretinogram, ERG; visual evoked potentials, VEP), were performed weekly until Day 42. Finally, the retina was analysed histologically by immunohistochemical methods on day 57th.

Results: First, the results of the behavioural test in the experimental group (NaIO3) reflected a progressive decrease in light sensitivity after 28 days, and a decrease in visual acuity and as well as a completely loss of the pupillary light reflex after 7 days since the administration. Second, the electrophysiological activity of retina and primary visual cortex (ERG, VEP) was significantly reduced in the treated group (NaIO3) with respect to the control group. Finally, histological analysis of the retina showed structural alterations in the outer segments of the photoreceptors of the treated animals (NaIO3).

Conclusions: This research demonstrates the appearance of alterations in the outer retina and a decrease in the response at the level of the visual cortex after NaIO3 administration, as expected. This confirms that NaIO3‐induced retinal neurodegeneration is effective in obtaining a promising experimental model that could be used in the study of diseases associated with the visual system and in the development of novel therapeutic strategies.
Lipid‐lowering therapy in the treatment of massive hard exudates in type 1 diabetes
Authors: Palarie Natalia , Natalia Palii , Tagadiuc Olga
Published: January 2024

Aims/Purpose: Today there is no approved medical therapy for hard macular exudates in diabetes and unfortunately this pathology often leads to significant visual loss. Purpose of our study was to assess whether long‐term lipid‐lowering therapy with fenofibrate could reduce the number and extension of massive macular exudates in Type 1 diabetes patients.

Methods: There were 46 (92 eyes) Type 1 diabetes persons (18–42 years) with diabetic maculopathy and massive hard exudates included in this study. HbA1C ranging from 6% to 9%. The mean visual acuity was 0.3 ± 0.1. Patients were divided into two groups: main (22 person) and control (24 person). Exclusion criteria: patients on lipid‐lowering drugs, oral contraceptive pills, hormone replacement therapy, pregnant woman, familial hypercholesterolemia, hypothyroidism, chronic liver and kidney disease. All patients in the main group received fenofibrate 145 mg once a day for 8 months, patients in control group had conventional therapy. All patients had undergone standard ophthalmological examination, fundus photos and OCT scanning on presentation and during follow‐up visits. Patients were followed at 2, 6, 12 and 18 months after the start of the treatment.

Results: In the main group anatomic result expressed by the reduction of number and extension of hard exudates, decrease in central retinal thickness was achieved in 77% of patients (17 patients, 34 eyes). Central retinal thickness in the main group decreased from mean 392 mkm to 255 mkm ± 30 mkm. Good functional result was achieved in 64% of patients (28 eyes), where visual acuity increased from 0.3 to 0.5 ± 0.1. This effect was stable for the whole follow‐up period. In the control group 74% of patients had no anatomic neither functional changes. In 15% of patients mean visual acuity slightly improved from 0.3 to 0.4 ± 0.05 with decrease in central retinal thickness from mean 386 mkm to 320 mkm ± 30 mkm due to better compensation of the main disease. In 15% the number and extension of hard exudates increased with further vision deterioration. No fenofibrate side effects were noticed in either group.

Conclusions: Fenofibrate in Type 1 diabetic patients diminishes number of macular hard exudates, reduces macular oedema, improves visual acuity with stable effect over the time.
EYS mutation causes RPE dysfunction in a patient‐derived cellular model
Authors: de la Cerda Berta , Reyes Alvaro Plaza , Delagado Ana García , Sánchez Lourdes Valdés , Diaz‐Corrales Francisco
Published: January 2024

Aims/Purpose: Although EYS‐associated retinal disease is normally described as a photoreceptor dysfunction, the natural role of the EYS protein is not yet clearly defined and it may also affect the RPE, as has been previously shown for other genes causing retinal disease. We have studied the impact of EYS gene mutations on the maturation and function of an RPE cellular model obtained from a patient.

Methods: RPE was differentiated in vitro from a patient‐derived iPSC line and characterized. Morphological assessment of EYS‐RPE included light microscopy and electron microscopy. We studied gene expression by rt qPCR and transcriptomic analysis and cellular localization of the main RPE markers by immunofluorescence. For physiology, we tested the transepithelial resistance, phagocytic activity and secretion of PEDF and VEGF.

Results: Microscopic phenotyping of the EYS‐RPE shows areas where cells grow in several layers, different from the healthy RPE model that grows as a monostratified epithelium. Moreover, the ultrastructure shows a loose attachment between cells and a disorganized distribution of the organelles and vesicles compared to the polarized distribution inside a healthy RPE cell, among other differences. Regarding gene expression, several RPE markers are downregulated in the EYS‐RPE pointing to a general dysregulation of the RPE metabolism and differentiation. The immunofluorescence study correlates with the gene expression data. As expected from the previous information, the EYS‐RPE physiology is affected, including a diminished phagocytic capacity and altered secretion of PEDF and VEGF.

Conclusions: Our data indicate that EYS dysfunction is not only a photoreceptor disease but also affects RPE at many levels, from differentiation to impairing some of its key roles in the retina, which may contribute to retinal disease in EYS patients.
Alterations in glutamate and nitric oxide metabolism in the RdS mice
Authors: Almansa Inmaculada , Espuis Carla , Cantó Antolin , Martínez‐González Javier , Olivar Teresa , Hernández‐Rabaza Vicente , Sanz María Miranda
Published: January 2024

Aims/Purpose: Nitric oxide (NO) is an essential signalling molecule, with gaseous nature. NO is synthesized by the conversion of L‐arginine to L‐citrulline. This reaction is catalysed by the enzyme nitric oxide synthase (NOS). There are three NOS isoforms, but nNOS reflects most of the production of NO in the retina. Although NO is employed in the retina to maintain ocular function, it has also been related to different visual diseases. Increased levels of NO have been associated with ocular diseases involving increased glutamate concentrations, ischaemia, oxidative stress and inflammation (such as retinitis pigmentosa (RP)). The main purpose of this work was to determine glutamate retinal concentrations at different stages of the retinal degeneration that occurs in the rds mice and to study possible NO metabolism alterations.

Methods: Rds mice were treated in accordance with the ARVO statement for the use of animals in ophthalmic and vision research. Mice were sacrificed at different postnatal days (11, 17, 21 and 28). Retinal glutamate concentrations were determined by high pressure liquid chromatography (HPLC). The expression of different enzymes related with NO metabolism (nNOS, guanylate cyclase (GC) and arginase) was determined by histochemistry.

Results: Glutamate as well as nNOS was observed to be increased in the retina of rds mice mainly between the peak of rods and cones death. GC was observed to be decreased in the rds mice compared to control ones and no significant changes were observed in arginase expression when we compared rds and control mice.

Conclusions: There are alterations in the expression of glutamate, nNOS and GC in rds mice retina compared to control mice. RP is a disease with no effective treatment to date and NO metabolism may be a new target in RP treatment.