bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrobulbar haemorrhage and globe perforation after botulinum toxin injection into the medial rectus
Authors: Artola Ines , Antón Maria Teresa Cedazo , Sanchez Manuel Morales , Pernas Sergio , Hernandez Eduardo Conesa , Carretero Manuel Moriche 
Published: January 2024

Aims/Purpose: The aim of this communication is to show a recent case of both retrobulbar haemorrhage (RH) and probable globe perforation (GP) after botulinum toxin (BT) injection in the medial rectus of the right eye.Methods: We selected a recent case seen at our hospital. A 5u BT injection was performed under topical anaesthesia and guiding electromiography into the medial rectus due to a VI cranial nerve palsy. 2 min later the patient claimed intense pain and we evidenced a sudden growing periocular oedema and progressing exophthalmos. Retrobulbar haemorrhage was diagnosed and immediate canthotomy and cantholisys were performed, with consequent haemorrhage drainage. In the 24 h follow‐up visit, our patient claimed blurry vision and floaters. VA RE was 0.3 (before BT 0.7). Important corneal oedema and 3–4 + tyndall was observed. In the funduscopic exploration severe hemovitreous was observed; and an ocular ecography was performed, which showed no signs of retinal disruption. As vitreous started clearing and VA and floaters improved, observational treatment was decided. When we became able to see the retina with detail a possible perforation hole was seen in the infero‐medial quadrant, with no signs of traction or retinal elevation.Results: 3 months later, VA was 0.8 e° 1. Funduscopy showed an applied retina, with only a few persistent fibrine remainders in the inferior quadrant. Good‐coloured optic disc, with physiologic excavation and no signs of atrophy.Conclusions: Eventhough RH and GP are quite rare complications after BT infection, we should always take them into consideration. We also wanted to highlight these complications treatment.
RH: Immediate canthotomy and cantholysis must be performed
GP: close observation must be followed in order not to miss a retinal detachment.

Plus, to avoid them we should be careful to perform the right technique and to use the electromiograph to guide us into the muscle.
Optic nerve disorders and reduced visual acuity in children. Differential diagnosis
Authors: Díaz‐Barreda Mª. Dolores , Boned‐Murillo Ana , Fernández‐Espinosa Guisela , Sopeña María , Álvarez Marta Arias , Pinilla Isabel 
Published: January 2024

Aims/Purpose: Low visual acuity (VA) in children requires meticulous investigation in search of possible organic causes. Once an alteration in the optic nerve (ON) has been detected, differential diagnosis is essential due to the different prognosis and management of each entity.Methods: We report the case of a 10‐year‐old black girl who went to the ophthalmologist for decreased VA in the left eye (LE) with no other history, signs or symptoms. On examination she had VA in the right eye (RE) 1 (Snellen decimal scale) and 0.1 LE. No torticollis or stereopsis, exotropia and convergence deficit in the LE. Normal fundus of eye (FE) RE; LE papilla larger and pale, centred staphylomatous excavation with central whitish area, vessels emanating from the periphery of the ON and alteration of the surrounding pigmentation, peripheral retina hypopigmented. Optical coherence tomography (OCT) of macula was normal; of the ON was very altered. Ultrasound showed protrusion of the LE “bottleneck” disc.Results: In view of the suspicion of Morning Glory Syndrome (MGS), magnetic resonance imaging (MRI) and angio‐MRI were requested to rule out alterations in the central nervous system (CNS), especially vascular malformations. After explaining the findings and poor visual prognosis we opted for occlusions in the RE, improving VA to 0.2 OI. We consulted paediatrics, genetic testing and close follow‐up, paying special attention to the retina due to the association with choroidal neovascularisation (CNV) and retinal detachment (RD).Conclusions: The characteristics of MGS can be confused with other pathologies, especially ON coloboma. Peripapillary staphyloma, ON dysplasia or aplasia, advanced glaucoma, Aicardi's disease and Papillorenal disease must be ruled out. Once diagnosed, possible systemic associations must be studied due to their potential severity and follow‐up is essential, as a high percentage will present ophthalmological complications.
Visual field loss patterns in dominant and recessive optic atrophy based on OPA1 archetypes
Authors: Cascavilla Maria Lucia , Coutinho Catarina , Battista Marco , Zanchetta Ferdinando , Galzignato Alice , Lari Giorgio , Albertini Stefano , Brotto Luigi , Nucci Paolo , Fioresi Rita , Bandello Francesco , Barboni Piero 
Published: January 2024

Aims/Purpose: Identification and quantification of visual field loss patterns of dominant optic atrophy forms (ACO2 and AFG3L2 mutations) and recessive optic atrophy form (WFS1 mutation, Wolfram Syndrome, WS) based on machine learning‐obtained archetypes for OPA1‐Dominant Optic Atrophy (DOA).Methods: Five patients affected by hereditary optic neuropathies carrying ACO2 gene mutations, 5 with AFG3L2 mutations, and 20 with WFS1 mutations were enrolled. Visual field (VF) tests performed by SITA standard 30–2 or 24–2 Humphrey VF analyzer (Carl Zeiss Meditec, Dublin, CA, USA) were collected for these patients. The VFs of these rare mutations (30% WFS1, 10% ACO2 and 3% AFG3L2 [1]) were decomposed and quantified according to the archetypes (AT) obtained in the unsupervised machine learning model developed for the OPA1 mutation.Results: The archetype analysis (AA)‐model developed for the DOA‐OPA1 mutation is composed of twelve ATs, with the central, the ceco‐central, and the para‐central as the most significant ones. For WS patients, the VF‐decomposition was mostly made up of ATs resembling more severe abnormalities, while for the ACO2 and AFG3L2‐affected patients the most important ATs were similar to the OPA1 cases.Conclusions: The developed AA‐model based on OPA1‐DOA affected patients enabled the decomposition of VFs of more rare optic atrophy mutations. The association of weights to the different ATs for patient‐specific VFs showed to be a possible option to identify and quantify the most important patterns of visual field loss in such particular cases of autosomal dominant or recessive optic neuropathies. A pattern‐specific visual field loss might strengthen the differential diagnosis between OPA1 and other mutations and support future clinical and therapeutic trials.References1. Rocatcher A, Desquiret‐Dumas V, Charif M, et al. The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands. Brain 2023; 146(2): 455–460. doi: 10.1093/brain/awac395
Peripapillary retinal layer thickness is associated with retinal oxygen saturation in newly diagnosed patients with multiple sclerosis
Authors: Nes Dragana , Berg‐Hansen Pål , de Rodez Benavent Sigrid A. , Høgestøl Einar A. , Beyer Mona K. , Rinker Daniel A. , Veiby Nina , Karabeg Mia , Petrovski Beáta Éva , Celius Elisabeth G. , Harbo Hanne F. , Petrovski Goran 
Published: January 2024

Aims/Purpose: Structural and physiological abnormalities have been reported in the retina of people with multiple sclerosis (pwMS). We aimed to investigate whether change in the peripapillary retinal nerve fibre layer (RNFL) thickness is associated with difference in retinal oxygen (O2) saturation in newly diagnosed pwMS.Methods: Retinal oxygen saturation was measured using imaging by spectrophotometric non‐invasive retinal oximeter. RNFL thickness was acquired by RS‐3000 NIDEK OCT. Twenty‐five newly diagnosed pwMS were included. The measurements were performed primarily on the right eye; 25 healthy individuals (HCs) were age‐ and gender‐ matched with the pwMS. Arterio‐venular difference (A‐V diff) was calculated from the mean arteriolar and venular O2 saturation values based on measurements obtained from all vessels. Data were analysed by Spearman correlation.Results: There was a significant positive correlation between RNFL and A‐V diff in pwMS (p = 0.0014; rho = 0.4949), and no significant difference in the O2 saturation in retinal venules and arterioles in pwMS (mean: 60.0% and 93.7%; p = 0.5980) compared to HCs (mean: 59.3% and 91.5%; p = 0.8934), respectively.Conclusions: Our findings indicate that early in MS, changes in RNFL and A‐V diff are detectable, before patients develop any apparent/severe disease. We recommend inclusion of the peripapillary RNFL and A‐V diff in MS monitoring and research.
Changes in colour perception in Alzheimer's disease continuum
Authors: Elvira‐Hurtado Lorena , López‐Cuenca Inés , De Hoz Rosa , Salas Mario , Sanchez‐Puebla Lidia , Matamoros José A. , Fernández‐Albarral José A. , Salazar Juan Jose , Mestú Fernando , Gil Pedro , Ramirez Jose Manuel , Salobrar‐Garcia Elena 
Published: January 2024

Aims/Purpose: The progression of Alzheimer's disease (AD) manifests from a preclinical stage, characterized by asymptomatic pathological alterations, to an advanced stage of AD accompanied by cognitive impairment. The aim of this study was to explore visual function along the entire AD continuum, from individuals with a high genetic predisposition to those in the moderate phase of the disease.Methods: All participants underwent a visual examination and had to be visually healthy to be included. The study contained five groups: controls (n = 53), individuals with a positive family history of AD (HF+) (n = 13), mild cognitive impairment (MCI) (n = 23), mild AD (n = 25) and moderate AD (n = 21). The study analysed the results of errors in colour perception.Results: A significant increase in the total number of errors was observed between the control group and the moderate AD group. And also when comparing the FH+ group with the MCI group, the mild AD group and the moderate AD group. Significant differences were found on the tritan axis between the control group and the mild AD group, as well as in the moderate AD group. Significant differences were observed between the FH+ group and the mild AD group, as well as in the moderate AD group. A significant increase in the number of errors on the deutan axis was observed between the control group and both the mild and moderate AD groups. In addition, a statistically significant increase was observed when comparing the FH+ group with the moderate AD group. The test correlated with the MMSE score and also showed good predictive value when memory impairment was present.Conclusions: Understanding the importance of changes in colour perception in AD continuum can aid in the early detection and treatment of AD, potentially improving patient outcomes and facilitating targeted interventions.
Natural course of clinically isolated optic neuritis: implications for trial design
Authors: Küchlin Sebastian , Ihorst Gabriele , Heinrich Sven , Marquez Pablo , Albrecht Philipp , Hug Martin , Diem Ricarda , Lagrèze Wolf 
Published: January 2024

Aims/Purpose: To characterize disease‐induced changes in the first six months after acute optic neuritis and to aid the design of future neuroprotection trials.Methods: Treatment‐independent analysis of the TONE trial cohort (NCT01962571), including 103 patients with acute optic neuritis and baseline high contrast visual acuity <0.5 dec. We analysed study visits at baseline and weeks 1, 4, 16 and 26 with mixed effects linear piece‐wise models to describe the dynamics of low contrast letter acuity, contrast sensitivity, visual fields, visually evoked potentials and macular and peripapillary retinal layer thicknesses. Sample size estimates are based on a two‐sided t‐test with α=0.05, power 80%, and treatment effects equal to 50% of the mean diseased induced change.Results: After baseline visual loss, there was improvement of visual function with thinning of inner and swelling of outer retinal layers. Clinical trials could reduce their required size by more than half when using macular ganglion cell and inner plexiform layer thinning (33 patients/group) over peripapillary retinal nerve fibre layer thinning (79/group) as the primary outcome. Similarly, trials of functional neuroprotection could reduce their size by more than 40% when employing the inter‐eye delta of 2.5% low‐contrast letter acuity (109/group) over the affected eye's value alone (189/group) as their outcome. The respective associations to vision‐related quality of life (NEI‐VFQ overall score) were similar (Pearson's |r| = 0.08 vs. 0.15 and 0.38 vs. 0.39). Because inner retinal layer thicknesses remained stable after four months but functional improvements continued up to month six, trials should follow up accordingly.Conclusions: The negative results of the TONE trial make its participants one of the best‐characterized and largest cohorts of acute optic neuritis. Our data show that future trials may benefit from substantial efficiency gains.
Archetypal analysis for dominant optic atrophy visual field loss
Authors: Coutinho Catarina , Zanchetta Ferdinando , Galzignato Alice , Battista Marco , Lari Giorgio , Albertini Stefano , Borrelli Enrico , Savini Giacomo , Cascavilla Maria Lucia , Bandello Francesco , Fioresi Rita , Barboni Piero 
Published: January 2024

Aims/Purpose: Identification of the characteristic visual field loss patterns of dominant optic atrophy (DOA) employing the Archetypal Analysis (AA) machine learning algorithm and further relation with patient‐specific parameters.Methods: For 64 patients affected by molecularly confirmed DOA with OPA1 heterozygous mutation, binocular visual field (VF) tests performed by SITA standard 30–2 or 24–2 Humphrey VF analyser (Carl Zeiss Meditec, Dublin, CA, USA) were collected. For patients that had multiple VF tests, several VFs were collected to enlarge the dataset. Resorting to Python 3.8 (Anaconda) an AA model was developed to determine and quantify the DOA underlying patterns of visual loss. After a careful analysis involving different linear and non‐linear machine Learning models and algorithms, the different archetypes (AT) were related to parameters such as age and visual acuity.Results: Considering 229 VF test, employing the AA, twelve archetypes were detected for the characterization and quantification of visual loss in DOA. Central, ceco‐central, and para‐central ATs revealed to be the most significant ones, matching the common characteristic scotomas for DOA patients, followed by quadrantanopia, altitudinal, and nasal step ATs.Younger patients were related to less severe visual loss representative ATs, while patients with lower visual acuity were related to more severe visual loss representative ATs.Conclusions: Archetypal analysis shows to be a potential powerful tool to support clinicians in the identification of DOA patients by identifying and quantifying visual loss patterns characteristic of this disease. Relation with other patient‐specific parameters might strengthen the differential DOA diagnosis.
Intravitreal injection of Noggin ameliorates retinal degeneration in a mouse model of retinitis pigmentosa
Authors: Fernandez‐Bueno Ivan , Font Carlos , Martin Abey , Martin Mark , Helm Courtney , Tsai E‐Jine , Xu Mei , George‐Weinstein Mindy , Bravo‐Nuevo Arturo 
Published: January 2024

Purpose: To determine the therapeutic efficacy of intravitreal injections of Noggin in a rodent model of retinitis pigmentosa (RP). Noggin is expressed by Myo/Nog cells which are critical for eye morphogenesis and have been shown to be both neuroprotective and a source of contractile myofibroblasts in ocular diseases. Noggin is a bone morphogenic protein (BMP) inhibitor. BMPs play important roles in eye development but the strength of this signalling pathway must be carefully regulated. Furthermore, BMP levels increase in the central nervous system under stress and injury.Methods: Male and female C3H/HEJ mice (n = 30) exhibiting Pde6b gene mutation, considered a model of RP, were divided into 3 experimental groups (n = 10 each). At week 2.5 post birth, mice received either a bilateral, single intravitreal injection (1 μL) of phosphate buffer saline (PBS; Control 1), mouse serum albumin (MSA; Control 2), or human recombinant Noggin (25 ng; Treatment). At weeks 3 and 5, electroretinograms (ERGs) were performed to assess retinal function, and mice were sacrificed. Then, eyes were enucleated, fixed, frozen, cryosectioned, and immunolabelled to evaluate apoptosis (TUNEL), Myo/Nog cells (BAI1), and neuroretinal thickness.Results: Apoptosis was significantly decreased in the Noggin treated group compared to controls (PBS and MSA) at both time points. Noggin treatment also resulted in increased thickness of the neuroretina. The number of Noggin producing Myo/Nog cells was higher in the retinas of all the control groups compared to the Noggin‐injected group. ERGs showed significant improvement of the A‐ and B‐waves in Noggin injected mice when compared to control groups at 3‐ and 5‐weeks post‐birth.Conclusions: Intravitreal injection of Noggin in a RP rodent model improved retinal function and decreased apoptosis and retinal thinning. Myo/Nog cells increase in number in response to stress and injury. The decrease in the number of Myo/Nog cells in response to Noggin treatment further supports the conclusion that this BMP inhibitor reduced tissue damage. These results suggest that inhibition of BMP signalling may be a therapeutic approach to reducing retinal degeneration in RP.
A 15 month follow‐up study characterizing the progression of retinal pathology and visual loss in CLN3 ex7/8 mice
Authors: Torsti Tommi , Toropainen Elisa , Tamminen Toni , Kauppinen Anu , Kaarniranta Kai , Forsberg Markus M. 
Published: January 2024

Aims/Purpose: Juvenile form of neuronal ceroid lipofuscinosis is a is a rare neurological disease that manifests in childhood, by progressive visual dysfunction. The progression and timeline of the retinal degeneration in the eye has not been comprehensively characterized. We performed a 15‐month follow‐up study aiming to reveal the progression of retinal pathology in CLN3 ex7/8 mice modelling juvenile neuronal ceroid lipofuscinosis.Methods: ERG, OCT, and fundus imaging was performed in CLN3 ex7/8 mice every three months at 3, 6, 9, 12 and 15 months. Scotopic electroretinography was performed with Espion ERG using silver electrodes. Mice were kept overnight in dark room before testing. Eyes were exposed to flashes of light periodically increasing in intensity (0,0001–1 Cd × s/m2). Responses to multiple flashes were averaged to obtain a single waveform at each intensity. OCT and fundus images were captured with the Phoenix MICRON® Image‐Guided OCT.Results: In scotopic ERG responses lower amplitudes of a‐ and b‐wave were observed CLN3 ex7/8 mice compared to WT mice at all time points. A progressive, almost 2‐fold decrease of b‐wave amplitude (at 0.03 Cd × s/m2) was seen in CLN3 ex7/8 mice between 3 and 15 months, compared to WT. Most notable decline of b‐wave amplitude (~70% of the decrease, at 0.03 Cd × s/m2) was seen from age of 6 to 12 months. A‐wave amplitudes in CLN3 ex7/8 mice were consistently lower but not progressively reduced when compared to WT mice. The accumulation of drusen was observed in the fundus images of CLN3 ex7/8 mice. In OCT images we observed signs of retinal outer segment atrophy. These effects were not observed in WT animals to the same degree.Conclusions: We observed age‐dependent retinal outer segment atrophy with drusen‐like deposit accumulation visually with OCT and fundus imaging in CLN3 ex7/8 mice, and the results correlate well with ERG results. According to the progressive decline of b‐wave amplitude, the decrease of vision seems to be most prominent between the ages of 6 and 12 months. This result indicates progressive loss of function in inner retinal neurons. The present results reveal the progression of the pathology in CLN3 ex7/8 mice as well as the time window for testing novel disease‐modifying interventions in CLN3 ex7/8 mice.
A pilot study for decellularizing human and porcine cornea for future use in corneal regeneration
Authors: Josifovska Natasha , Niemi Essi M. , Scholz Hanne , Petrovski Goran 
Published: January 2024

Purpose: To effectively decellularize human and porcine corneas for future use in corneal regeneration by using an already established decellularization technique being efficient in decellularizing blood vessels.Methods: One human and 4 porcine corneas were decellularized by using various washing steps with 3‐[(3‐cholamidopropyl) dimethylammonio]‐1‐propanesulfonate (CHAPS) detergent, Benzonase, Ethylenediaminetetraacetic acid (EDTA), 5% Dextran or 5% D‐Mannitol. The quality of the decellularization process was assessed by quantitative and qualitative measurement of DNA content, glycosaminoglycans (GAGs), immunofluorescent staining for Collagen I, V and keratocan, and Transmission Electron Microscopy (TEM) to observe the structure of the collagen fibrils was used.Results: The decellularization process showed 99,94% and 99,52% DNA content reduction in the human and porcine corneas when using Dextran, respectively, while more DNA remained in the porcine corneas when D‐Mannitol was used. Similar pattern was observed in the preservation of GAGs, with the highest amount being found in the human cornea, and less in the porcine corneas. H&E and Immunofluorescent staining showed no presence of cell nuclei when compared to the control native corneas, while Alcian blue staining qualitatively confirmed the presence of GAGs. Collagen I, V and keratocan were still present in the decellularized corneas when compared to the native ones, while TEM microscopy further confirmed the similar patterns of the collagen fibrils in the decellularized‐, compared to the native‐ corneas.Conclusions: This pilot study showed that our decellularization method is effective in decellularizing human and porcine corneas, with very high amount of DNA being removed from the corneas, while the GAGs were preserved to an acceptable extent, and the structure and pattern of the collagen fibrils maintained.
Monomeric C‐reactive protein exacerbates choroidal neovascularization in vivo: Implications for age‐related macular degeneration
Authors: Fernandez‐Robredo Patricia , Hernandez Maria , Romero‐Vázquez Sara , Recalde Sergio , Bezunartea Jaione , Orduña Maite Moreno , Layana Alfredo García , Adàn Alfredo , Molins Blanca 
Published: January 2024

Aims/Purpose: Increased systemic levels of the acute phase reactant C‐reactive protein (CRP) have been linked to increased risk of age‐related macular degeneration (AMD). CRP undergoes conformational changes upon activation in inflammatory microenvironments between pentameric (pCRP) and monomeric forms (mCRP). CRP conformations present different phenotypes, as mCRP has more proinflammatory properties and has been shown to induce blood retinal barrier disruption in vitro. Thus, we aimed to evaluate the impact of CRP forms on choroidal neovascularization (CNV) in vivo.Methods: pCRP and mCRP forms were intravenously (iv) or intravitreally (ivt) injected in C57BL6/J mice (n = 12) previously subjected to CNV induction by laser and compared to controls. CNV lesions were monitored by fluorescein angiography and mice were euthanized 11 days after lesion induction. CNV areas were measured in lectin stained choroidal flatmounts. To evaluate the CRP dissociation, pCRP was coupled to a fluorescent molecule before injection. After tissue extraction mCRP was detected by immunofluorescence in posterior pole flatmounts.Results: Both pCRP and mCRP injected significantly increased CNV areas compared to control mice. Retinal severe edema was also observed close to the lesion in retinographies, and was more severe in intravitreally injected groups. Finally, pCRP was observed to dissociate into mCRP in intravitreally injected animals with pCRP.Conclusions: We confirmed that CRP increases CNV areas and severe edema in the retina, suggesting that CRP is activated in the CNV inflammatory environment. Additionally, the pCRP form dissociates in vivo into mCRP close to CNV damaged tissue, hypothesizing that mCRP is the CRP conformation that contributes to the exacerbation of the CNV process. Further studies are needed to investigate anti‐mCRP molecules as candidates for mono‐ or anti‐VEGF combined therapy for AMD treatments.